bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Functional Cross-Talk between Surface GABAA and Dopamine D5 Receptors
Authors: Maingret François , Groc Laurent
Published: May 2021

The γ-aminobutyric acid type A receptor (GABAAR) plays a major role in fast inhibitory synaptic transmission and is highly regulated by the neuromodulator dopamine. In this aspect, most of the attention has been focused on the classical intracellular signaling cascades following dopamine G-protein-coupled receptor activation. Interestingly, the GABAAR and dopamine D5 receptor (D5R) have been shown to physically interact in the hippocampus, but whether a functional cross-talk occurs is still debated. In the present study, we use a combination of imaging and single nanoparticle tracking in live hippocampal neurons to provide evidence that GABAARs and D5Rs form dynamic surface clusters. Disrupting the GABAAR–D5R interaction with a competing peptide leads to an increase in the diffusion coefficient and the explored area of both receptors, and a drop in immobile synaptic GABAARs. By means of patch-clamp recordings, we show that this fast lateral redistribution of surface GABAARs correlates with a robust depression in the evoked GABAergic currents. Strikingly, it also shifts in time the expression of long-term potentiation at glutamatergic synapses. Together, our data both set the plasma membrane as the primary stage of a functional interplay between GABAAR and D5R, and uncover a non-canonical role in regulating synaptic transmission.
Alpha-Helical Protein KfrC Acts as a Switch between the Lateral and Vertical Modes of Dissemination of Broad-Host-Range RA3 Plasmid from IncU (IncP-6) Incompatibility Group
Authors: Mitura Monika , Lewicka Ewa , Godziszewska Jolanta , Adamczyk Malgorzata , Jagura-Burdzy Grazyna
Published: May 2021

KfrC proteins are encoded by the conjugative broad-host-range plasmids that also encode alpha-helical filament-forming KfrA proteins as exemplified by the RA3 plasmid from the IncU incompatibility group. The RA3 variants impaired in kfrA, kfrC, or both affected the host’s growth and demonstrated the altered stability in a species-specific manner. In a search for partners of the alpha-helical KfrC protein, the host’s membrane proteins and four RA3-encoded proteins were found, including the filamentous KfrA protein, segrosome protein KorB, and the T4SS proteins, the coupling protein VirD4 and ATPase VirB4. The C-terminal, 112-residue dimerization domain of KfrC was involved in the interactions with KorB, the master player of the active partition, and VirD4, a key component of the conjugative transfer process. In Pseudomonas putida, but not in Escherichia coli, the lack of KfrC decreased the stability but improved the transfer ability. We showed that KfrC and KfrA were involved in the plasmid maintenance and conjugative transfer and that KfrC may play a species-dependent role of a switch between vertical and horizontal modes of RA3 spreading.
Size-Exclusion Chromatography Separation Reveals That Vesicular and Non-Vesicular Small RNA Profiles Differ in Cell Free Urine
Authors: Karttunen Jenni , Stewart Sarah E. , Kalmar Lajos , Grant Andrew J. , Karet Frankl Fiona E. , Williams Tim L.
Published: May 2021

Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases. We aimed to identify the optimal method for isolating small (<200 nm) EVs from human urine prior to small RNA analysis. EVs from filtered healthy volunteer urine were concentrated using three methods: ultracentrifugation (UC); a precipitation-based kit (PR); and ultrafiltration (UF). EVs were further purified by size-exclusion chromatography (SEC). EV preparations were analysed with transmission electron microscopy (TEM), Western blotting, nanoparticle tracking analysis (NTA) and an Agilent Bioanalyzer Small RNA kit. UF yielded the highest number of particles both before and after SEC. Small RNA analysis from UF-concentrated urine identified two major peaks at 10–40 nucleotides (nt) and 40–80 nt. In contrast, EV preparations obtained after UC, PR or SEC combined with any concentrating method, contained predominantly 40–80 nt sized small RNA. Protein fractions from UF+SEC contained small RNA of 10–40 nt in size (consistent with miRNAs). These data indicate that most of the microRNA-sized RNAs in filtered urine are not associated with small-sized EVs, and highlights the importance of removing non-vesicular proteins and RNA from urine EV preparations prior to small RNA analysis.
Genetic and Epigenomic Modifiers of Diabetic Neuropathy
Authors: Jankovic Milena , Novakovic Ivana , Nikolic Dejan , Mitrovic Maksic Jasmina , Brankovic Slavko , Petronic Ivana , Cirovic Dragana , Ducic Sinisa , Grajic Mirko , Bogicevic Dragana
Published: May 2021

Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.
The Sexually Dimorphic Adrenal Cortex: Implications for Adrenal Disease
Authors: Lyraki Rodanthi , Schedl Andreas
Published: May 2021

Many adrenocortical diseases are more prevalent in women than in men, but the reasons underlying this sex bias are still unknown. Recent studies involving gonadectomy and sex hormone replacement experiments in mice have shed some light onto the molecular basis of sexual dimorphism in the adrenal cortex. Indeed, it has been shown that gonadal hormones influence many aspects of adrenal physiology, ranging from stem cell-dependent tissue turnover to steroidogenesis and X-zone dynamics. This article reviews current knowledge on adrenal cortex sexual dimorphism and the potential mechanisms underlying sex hormone influence of adrenal homeostasis. Both topics are expected to contribute to personalized and novel therapeutic approaches in the future.
Photosynthetic Linear Electron Flow Drives CO2 Assimilation in Maize Leaves
Authors: Shimakawa Ginga , Miyake Chikahiro
Published: May 2021

Photosynthetic organisms commonly develop the strategy to keep the reaction center chlorophyll of photosystem I, P700, oxidized for preventing the generation of reactive oxygen species in excess light conditions. In photosynthesis of C4 plants, CO2 concentration is kept at higher levels around ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) by the cooperation of the mesophyll and bundle sheath cells, which enables them to assimilate CO2 at higher rates to survive under drought stress. However, the regulatory mechanism of photosynthetic electron transport for P700 oxidation is still poorly understood in C4 plants. Here, we assessed gas exchange, chlorophyll fluorescence, electrochromic shift, and near infrared absorbance in intact leaves of maize (a NADP-malic enzyme C4 subtype species) in comparison with mustard, a C3 plant. Instead of the alternative electron sink due to photorespiration in the C3 plant, photosynthetic linear electron flow was strongly suppressed between photosystems I and II, dependent on the difference of proton concentration across the thylakoid membrane (ΔpH) in response to the suppression of CO2 assimilation in maize. Linear relationships among CO2 assimilation rate, linear electron flow, P700 oxidation, ΔpH, and the oxidation rate of ferredoxin suggested that the increase of ΔpH for P700 oxidation was caused by the regulation of proton conductance of chloroplast ATP synthase but not by promoting cyclic electron flow. At the scale of intact leaves, the ratio of PSI to PSII was estimated almost 1:1 in both C3 and C4 plants. Overall, the photosynthetic electron transport was regulated for P700 oxidation in maize through the same strategies as in C3 plants only except for the capacity of photorespiration despite the structural and metabolic differences in photosynthesis between C3 and C4 plants.
Targeting RTK-PI3K-mTOR Axis in Gliomas: An Update
Authors: Colardo Mayra , Segatto Marco , Di Bartolomeo Sabrina
Published: May 2021

Gliomas are the most common and challenging malignancies of the central nervous system (CNS), due to their infiltrative nature, tendency to recurrence, and poor response to treatments. Indeed, despite the advances in neurosurgical techniques and in radiation therapy, the modest effects of therapy are still challenging. Moreover, tumor recurrence is associated with the onset of therapy resistance; it is therefore critical to identify effective and well-tolerated pharmacological approaches capable of inducing durable responses in the appropriate patient groups. Molecular alterations of the RTK/PI3K/Akt/mTOR signaling pathway are typical hallmarks of glioma, and several clinical trials targeting one or more players of this axis have been launched, showing disappointing results so far, due to the scarce BBB permeability of certain compounds or to the occurrence of resistance/tolerance mechanisms. However, as RTK/PI3K/mTOR is one of the pivotal pathways regulating cell growth and survival in cancer biology, targeting still remains a strong rationale for developing strategies against gliomas. Future rigorous clinical studies, aimed at addressing the tumor heterogeneity, the interaction with the microenvironment, as well as diverse posology adjustments, are needed—which might unravel the therapeutic efficacy and response prediction of an RTK/PI3K/mTOR-based approach.
Synthesis and Structural Characterization of Half-Sandwich Arene–Ruthenium(II) Complexes with Bis(imidazol-1-yl)methane, Imidazole and Benzimidazole
Authors: Matveevskaya Vladislava V. , Pavlov Dmitry I. , Samsonenko Denis G. , Ermakova Ekaterina A. , Klyushova Lyubov S. , Baykov Sergey V. , Boyarskiy Vadim P. , Potapov Andrei S.
Published: May 2021

Mono- and binuclear arene–ruthenium(II) complexes with imidazole-containing ligands were prepared by the reaction of the ligands (L1 = bis(imidazole-1-yl)methane; ImH = 1H-Imidazole; BImH = 1H-Benzimidazole) with [(p-cym)Ru(µ-Cl)2]2 dimers. When bis(imidazole-1-yl)methane reacted with [(p-cym)Ru(µ-Cl)2]2 in methanol, a binuclear complex of the type [Ru2(L1)2(p-cym)2Cl2]Cl2 (2) with cyclic structure was synthesized, whereas by using acetonitrile as a solvent under the same reaction conditions, an unexpected C–N bond cleavage was observed, and a complex of formula [Ru(ImH)2(p-cym)Cl]Cl (1) with coordinated imidazole molecules was obtained. Another type of arene–ruthenium complex [Ru(BImH)(p-cym)Cl2] (3) was obtained by the reaction of benzimidazole and [(p-cym)Ru(µ-Cl)2]2. All compounds were characterized by spectral (FT-IR, NMR 1H, 13C) and single-crystal X-ray diffraction methods; their catalytic activity in transfer hydrogenation and the cytotoxicity against MCF-7 and HepG2 cells were evaluated.
A New Complex Borohydride LiAl(BH4)2Cl2
Authors: Dolotko Oleksandr , Kobayashi Takeshi , Hlova Ihor Z. , Gupta Shalabh , Pecharsky Vitalij K.
Published: May 2021

A new mixed alkali metal–aluminum borohydride LiAl(BH4)2Cl2 has been prepared via mechanochemical synthesis from the 2LiBH4–AlCl3 mixture. Structural characterization, performed using a combination of X-ray powder diffraction and solid-state NMR methods, indicates that the LiAl(BH4)2Cl2 phase adopts a unique 3D framework and crystallizes in an orthorhombic structure with the space group C2221, a = 11.6709(6) Å, b = 8.4718(4) Å, c = 7.5114(3) Å. The material shows excellent dehydrogenation characteristics, where hydrogen evolution starts at Tons = 70 °C, releasing approximately 2 wt.% of nearly pure (99.8 vol.%) hydrogen and a very small amount (~0.2 vol.%) of diborane. When compared to halide-free mixed alkali metal–aluminum borohydrides, the presence of Al‒Cl bonding in the LiAl(BH4)2Cl2 structure likely prevents the formation of Al(BH4)3 upon decomposition, thus suppressing the formation of diborane.
Add Germany to the List—Adventive Population of Trissolcus japonicus (Ashmead) (Hymenoptera: Scelionidae) Emerges in Germany
Authors: Dieckhoff Christine , Wenz Sophie , Renninger Maura , Reißig Anne , Rauleder Helmut , Zebitz Claus P. W. , Reetz Jana , Zimmermann Olaf
Published: May 2021

The brown marmorated stink bug, Halyomorpha halys, is a polyphagous pest species of worldwide economic importance. Since the mid-1990s, it has invaded and become established in various countries outside its native Asian range. In the newly invaded areas, biological control by native natural enemies has been shown to be insufficient in the long-term control of this severe pest. Adventive populations of Trissolcus japonicus, an important biological control agent of H. halys in Asia, have been reported from North America and some European countries since the mid-2010s. This egg parasitoid species seems to follow in the wake of the establishment of H. halys populations outside their native Asian range. Here, we report the first discovery of an adventive population of T. japonicus in Germany. In 2020, adult T. japonicus were recovered from parasitized H. halys egg masses (naturally laid and sentinel egg masses) and collected in ruderal areas using an insect suction sampler. The arrival of T. japonicus in Germany, unintentional through pathways yet unknown, corroborates a northbound expansion of its range within Europe. Further field surveys will show the extent of its dispersal and establishment capacities within this new distribution area.
Multimodality Imaging of the Anatomy of the Aortic Root
Authors: Paiocchi Vera Lucia , Faletra Francesco F. , Ferrari Enrico , Schlossbauer Susanne Anna , Leo Laura Anna , Maisano Francesco
Published: May 2021

The aortic root has long been considered an inert unidirectional conduit between the left ventricle and the ascending aorta. In the classical definition, the aortic valve leaflets (similar to what is perceived for the atrioventricular valves) have also been considered inactive structures, and their motion was thought to be entirely passive—just driven by the fluctuations of ventricular–aortic gradients. It was not until the advent of aortic valve–sparing surgery and of transcatheter aortic valve implantation that the interest on the anatomy of the aortic root again took momentum. These new procedures require a systematic and thorough analysis of the fine anatomical details of the components of the so-called aortic valve apparatus. Although holding and dissecting cadaveric heart specimens remains an excellent method to appreciate the complex “three-dimensional” nature of the aortic root, nowadays, echocardiography, computed tomography, and cardiac magnetic resonance provide excellent images of cardiac anatomy both in two- and three-dimensional format. Indeed, modern imaging techniques depict the aortic root as it is properly situated within the thorax in an attitudinally correct cardiac orientation, showing a sort of “dynamic anatomy”, which admirably joins structure and function. Finally, they are extensively used before, during, and after percutaneous structural heart disease interventions. This review focuses on the anatomy of the aortic root as revealed by non-invasive imaging techniques.
Association of Immune Thrombocytopenia and Inflammatory Bowel Disease in Children
Authors: Guarina Angela , Barone Angelica , Tornesello Assunta , Marinoni Maddalena , Lassandro Giuseppe , Giordano Paola , Motta Milena , Spinelli Marco , Fontanili Ilaria , Giona Fiorina , Menna Francesco , Chiocca Elena , Fotzi Ilaria , Petrone Angelamaria , Graziano Francesco , Saracco Paola , Puccio Giuseppe , Citrano Michele , Russo Giovanna , Farruggia Piero
Published: May 2021

Background: The association between inflammatory bowel disease (IBD) and immune thrombocytopenia (ITP) is still uncertain. In this multicenter retrospective study, the coexistence of both diseases was investigated in children diagnosed from 1 January 2000 to 31 December 2019. Methods: Clinical characteristics of both IBD and ITP, onset of disorders, and patient’s response to treatment were collected through a structured form sent to 55 Italian pediatric referring centers for hematological disorders. Result: Centers responded to the survey and reported the coexistence of IBD and ITP in 14 children. The first diagnosis was ITP in 57.1% and IBD in 35.7% of patients: it was simultaneous in 7.1%. IBD was classified as ulcerative colitis (57.1%), Crohn disease (35.7%), and unclassified (7.1%). No therapy for IBD other than steroids had any effect on ITP course. Colectomy resulted in recovery from ITP in 1 of the 2 patients surgically treated. ITP was always mild but turned to be chronic in half of patients. Conclusions: In all patients, ITP was mild without any evident impact on IBD severity, but the incidence of chronic ITP seems to be higher than what is usually observed in the pediatric age group. Colectomy had unpredictable effects on ITP.
Long-Term Complications after Surgical or Medical Treatment of Predominantly Forefoot Diabetic Foot Osteomyelitis: 1 Year Follow Up
Authors: Tardáguila-García Aroa , García-Álvarez Yolanda , García-Morales Esther , López-Moral Mateo , Sanz-Corbalán Irene , Lázaro-Martínez José Luis
Published: May 2021

Aim: To compare long-term complications according to the treatment received for management of diabetic foot osteomyelitis (surgical or medical) at 1 year follow up. Design and Participants: A prospective observational study was conducted involving 116 patients with diabetic foot osteomyelitis. The patients received surgical or medical treatment based on the principles described in the literature. To register the development of a complication, both groups of treatments were followed-up 1 year after the ulcer had healed. Results: Ninety-six (82.8%) patients received surgical treatment and 20 (17.2%) medical treatment. No differences were found in the time to healing between both groups of treatment, 15.7 ± 9.2 weeks in the surgical group versus 16.4 ± 12.1 weeks in the medical group; p = 0.103. During follow up, 85 (73.3%) patients developed complications without differences between both groups, 68 (70.8%) in the surgical group versus 17 (85%) in the medical group (p = 0.193). The most common complication in both groups was re-ulceration. We did not observe significant differences comparing complication-free time survival between both treatments (p = 0.665). Conclusion: The onset of complications after healing in patients who suffered from diabetic foot osteomyelitis was not associated with the treatment received. Surgical and medical approaches to the management of diabetic foot osteomyelitis produced similar results in long-term follow up.
Evaluation of Clinical Factors Predictive of Diabetes Remission Following Bariatric Surgery
Authors: Mateo-Gavira Isabel , Sánchez-Toscano Esteban , Mayo-Ossorio Mª Ángeles , Pacheco-García José Manuel , Prada-Oliveira Jose Arturo , Vílchez-López Francisco Javier
Published: May 2021

Bariatric surgery is an effective treatment for achieving significant weight loss and improving metabolic comorbidities such as type 2 diabetes mellitus (T2DM). The aim of our study was to investigate clinical factors related to T2DM remission in obese patients who had undergone bariatric surgery. Methods: A cohort of patients with T2DM and a minimum of class II obesity undergoing bariatric surgery had their clinical and anthropometric variables assessed. The statistical evaluation included multivariate analyses of clinical factors predicting a T2DM remission two years post-surgery. Results: 83 patients were included (mean age 44.13 ± 10.38 years). Two years post-surgery, the percentage of excess weight lost was 63.43 ± 18.59%, and T2DM was resolved in 79.5% of the patients. T2DM remission was directly related to a high body mass index (BMI) (OR: 1.886; p = 0.022) and the absence of macro-vascular complications (OR: 34.667; p = 0.002), while it was inversely associated with T2DM with a duration longer than 5 years (OR: 0.022; p = 0.040) and baseline insulin treatment (OR: 0.001; p = 0.009). 15.6% of the patients presented early complications and 20.5% developed late complications. Conclusion: In our study sample, bariatric surgery proved to be an effective and safe technique for sustained medium-term weight loss and the resolution of T2DM. A higher baseline BMI, a shorter T2DM duration, non-insulin treatment, and the absence of macro-vascular complications are factors predictive of T2DM remission.
Genetic Risk and Phenotype Correlation of Primary Open-Angle Glaucoma Based on Rho-Kinase Gene Polymorphisms
Authors: Kim Yong-Woo , Bak Eunoo , Wy Seoyoung , Lee Seung-Chan , Kim Yu-Jeong , Kim Young-Kook , Park Ki-Ho , Jeoung Jin-Wook
Published: May 2021

Rho-associated coiled-coil kinase (ROCK) signaling can affect glaucoma risk by regulating trabecular meshwork outflow. We investigated the effect of ROCK gene polymorphism on the risks of primary open-angle glaucoma (POAG) and POAG-related phenotypes including intraocular pressure (IOP) in a Korean population. A total of 24 single-nucleotide polymorphisms (SNPs) from ROCK1 and ROCK2 were selected and genotyped for 363 POAG patients and 213 healthy controls. Among the 363 POAG patients, 282 were normal-tension glaucoma (NTG, baseline IOP ≤ 21 mmHg) and 81 were high-tension glaucoma (HTG, baseline IOP > 21 mmHg). The SNPs rs288979, rs1006881, rs35996865, rs10083915, and rs11873284 in ROCK1 (tagged to each other, r2 = 1) were nominally associated with risk of HTG (OR = 0.52, p = 0.045). However, there were no SNPs that were significantly associated with the risk of NTG. In the genotype-phenotype correlation analysis, the SNPs rs2230773 and rs3771106 in ROCK2 were significantly correlated with central corneal thickness (CCT)-adjusted IOP (p = 0.024) and axial length (AXL; p = 0.024), respectively. The present data implicated the role of ROCK in POAG development, and as such, can serve as a good reference for upcoming Rho/ROCK-pathway-related studies on POAG.
Preoperative Serum GDF-15, Endothelin-1 Levels, and Intraoperative Factors as Short-Term Operative Risks for Patients Undergoing Cardiovascular Surgery
Authors: Kato Takashi , Nakajima Toshiaki , Fukuda Taira , Shibasaki Ikuko , Hasegawa Takaaki , Ogata Koji , Ogawa Hironaga , Hirota Shotaro , Ohashi Hirotaka , Saito Shunsuke , Takei Yusuke , Tezuka Masahiro , Seki Masahiro , Kuwata Toshiyuki , Sakuma Masashi , Abe Shichiro , Toyoda Shigeru , Inoue Teruo , Fukuda Hirotsugu
Published: May 2021

Objectives: The Society of Thoracic Surgeons (STS) risk score is widely used for the risk assessment of cardiac surgery. Serum biomarkers such as growth differentiation factor-15 (GDF-15) and endothelin-1 (ET-1) are also used to evaluate risk. We investigated the relationships between preoperative serum GDF-15, ET-1 levels, and intraoperative factors and short-term operative risks including acute kidney injury (AKI) for patients undergoing cardiovascular surgery. Methods: In total, 145 patients were included in this study (92 males and 53 females, age 68.4 ± 13.2 years). The preoperative STS score was determined, and the serum GDF-15 and ET-1 levels were measured by ELISA. These were related to postoperative risks, including AKI, defined according to the Acute Kidney Injury Network (AKIN) classification criteria. Results: AKI developed in 23% of patients. The GDF-15 and ET-1 levels correlated with the STS score. The STS score and GDF-15 and ET-1 levels all correlated with preoperative eGFR, Alb, Hb, and BNP levels; perioperative data (urine output); ICU stay period; and postoperative admission days. Patients with AKI had longer circulatory pulmonary bypass (CPB) time, and male patients with AKI had higher ET-1 levels than those without AKI. In multivariable logistic regression analysis, the preoperative ET-1 level and CPB time were the independent determinants of AKI, even adjusted by age, sex, and BMI. The preoperative GDF-15 level, CPB time, and RCC transfusion were independent determinants of 30-day mortality plus morbidity. Conclusion: Preoperative GDF-15 and ET-1 levels as well as intraoperative factors such as CPB time may be helpful to identify short-term operative risks for patients undergoing cardiovascular surgery.
SARS-CoV-2—Morphology, Transmission and Diagnosis during Pandemic, Review with Element of Meta-Analysis
Authors: Grudlewska-Buda Katarzyna , Wiktorczyk-Kapischke Natalia , Wałecka-Zacharska Ewa , Kwiecińska-Piróg Joanna , Buszko Katarzyna , Leis Kamil , Juszczuk Klaudia , Gospodarek-Komkowska Eugenia , Skowron Krzysztof
Published: May 2021

The outbreak of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2). Thus far, the virus has killed over 2,782,112 people and infected over 126,842,694 in the world (state 27 March 2021), resulting in a pandemic for humans. Based on the present data, SARS-CoV-2 transmission from animals to humans cannot be excluded. If mutations allowing breaking of the species barrier and enhancing transmissibility occurred, next changes in the SARS-CoV-2 genome, leading to easier spreading and greater pathogenicity, could happen. The environment and saliva might play an important role in virus transmission. Therefore, there is a need for strict regimes in terms of personal hygiene, including hand washing and surface disinfection. The presence of viral RNA is not an equivalent of active viral infection. The positive result of the RT-PCR method may represent either viral residues or infectious virus particles. RNA-based tests should not be used in patients after the decline of disease symptoms to confirm convalescence. It has been proposed to use the test based on viral, sub-genomic mRNA, or serological methods to find the immune response to infection. Vertical transmission of SARS-CoV-2 is still a little-known issue. In our review, we have prepared a meta-analysis of the transmission of SARS-CoV-2 from mother to child depending on the type of delivery. Our study indicated that the transmission of the virus from mother to child is rare, and the infection rate is not higher in the case of natural childbirth, breastfeeding, or contact with the mother. We hope that this review and meta-analysis will help to systemize knowledge about SARS-CoV-2 with an emphasis on diagnostic implications and transmission routes, in particular, mother-to-child transmission.
Measurements of Bone Health after Thyroid-Stimulating Suppression Therapy in Postmenopausal Women with Differentiated Thyroid Carcinoma: Bone Mineral Density versus the Trabecular Bone Score
Authors: Chung Chae Won , Choi Hoon Sung , Kong Sung Hye , Park Young Joo , Park Do Joon , Ahn Hwa Young , Cho Sun Wook
Published: May 2021

Background: Thyroid-stimulating hormone (TSH) suppression therapy is an important treatment modality for differentiated thyroid carcinoma (DTC), but it increases fracture risk. The aim of this study was to evaluate changes in bone mineral density (BMD) and trabecular bone score (TBS) in postmenopausal DTC patients receiving TSH suppression therapy. Methods: A total of 410 postmenopausal DTC patients who underwent thyroidectomy and had at least two dual-energy X-ray absorptiometry measurements, including a preoperative measurement, were included. Patients who had osteoporosis medication for more than 1 year were classified as ‘patients with osteoporosis’. Results: In patients without osteoporosis, the change in %BMD was similar between TSH suppression (−) and (+) groups, while the decrease in %TBS was significantly greater in the TSH suppression (+) group than that of the TSH suppression (−) group. The relative risk of vertebral fracture was decreased by TBS changes but not by BMD changes. In patients with osteoporosis, both BMD and TBS showed significant increases in the TSH suppression (−) group but not in TSH suppression (+) group. At year 4, TBS was significantly lower in the TSH suppression (+) group than that in the TSH suppression (−) group, while BMD showed no difference between groups. Conclusions: TBS may better reflect bone health than BMD in postmenopausal DTC patients with TSH suppression therapy.
Risk of SARS-CoV-2 Infection in Previously Infected and Non-Infected Cohorts of Health Workers at High Risk of Exposure
Authors: Sánchez-Montalvá Adrián , Fernández-Naval Candela , Antón Andrés , Durà Xavier , Vimes Alba , Silgado Aroa , Velásquez-Orozco Fernando , Espinosa-Pereiro Juan , Salvador Fernando , Pumarola Tomás , Almirante Benito , Esperalba Juliana
Published: May 2021

The objective of this study is to assess the risk of newly acquired RNA detection-proven SARS-CoV-2 infection after previous SARS-CoV-2 infection. This is a prospective study conducted from March to September 2020 in Barcelona, Spain. Healthcare workers caring for SARS-CoV-2 infected patients were divided in two cohorts: (a) previously RNA-proven SARS-CoV-2 infected cohort with mild symptoms (IC) and (b) healthy cohort (HC). Weekly SARS-CoV-2 RNA detection assays from nasopharyngeal swabs were performed. Serology status was assessed at the beginning and at the end of the study. Twenty participants were included in each group. The median age was 30 (IQR 27–34.75) years, and 55% were female. The median time of follow up was 49 (IQR 49–51) days. Fifteen out of 246 (6%) nasopharyngeal swab samples were positive for SARS-CoV-2, all in the IC. The percentage of participants in the IC with a probable newly acquired SARS-CoV-2 RNA-proven infection was 20% (95% IC 5.7–43.6%) at the end of the 7-week follow up period. The incidence reinfection rate was 28.6 (95% IC 7.8–73.2) cases per 1000 person-week. Despite detectable IgG antibodies against SARS-CoV-2 participants highly exposed to SARS-CoV-2 may develop a newly acquired SARS-CoV-2 RNA detection episode during the first months after the initial infection.
The Phenolic Antioxidant 3,5-dihydroxy-4-methoxybenzyl Alcohol (DHMBA) Prevents Enterocyte Cell Death under Oxygen-Dissolving Cold Conditions through Polyphyletic Antioxidant Actions
Authors: Fukai Moto , Nakayabu Takuya , Ohtani Shintaro , Shibata Kengo , Shimada Shingo , Sakamoto Soudai , Fuda Hirotoshi , Furukawa Takayuki , Watanabe Mitsugu , Hui Shu-Ping , Chiba Hitoshi , Shimamura Tsuyoshi , Taketomi Akinobu
Published: May 2021

Cold preservation in University of Wisconsin (UW) solution is not enough to maintain the viability of the small intestine, due to the oxidative stress. The novel phenolic antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) has dual properties to reduce oxidative stress, radical scavenging, and antioxidant protein induction, in other cells. This study was designed to determine whether DHMBA reduces cold preservation injury of enterocytes, and to identify the effector site. Enterocytes were subjected to 48-h cold preservation under atmosphere in UW solution (±DHMBA), and then returned to normal culture to replicate reperfusion of the small intestine after cold preservation. At the end of cold preservation (ECP) and at 1, 3, 6, and 72 h after rewarming (R1h, R3h, R6h, and R72h), we evaluated cell function and the injury mechanism. The results showed that DHMBA protected mitochondrial function mainly during cold preservation, and suppressed cell death after rewarming, as shown by the MTT, ATP, mitochondrial membrane potential, LDH, and lipid peroxidation assays, together with enhanced survival signals (PI3K, Akt, p70S6K) and induction of antioxidant proteins (HO-1, NQO-1, TRX-1). We found that DHMBA mitigates the cold-induced injury of enterocytes by protecting the mitochondria through direct and indirect antioxidative activities.
The Role of Different Indexes of Adiposity and Body Composition for the Identification of Metabolic Syndrome in Women with Obesity
Authors: Radetti Giorgio , Fanolla Antonio , Grugni Graziano , Lupi Fiorenzo , Tamini Sofia , Cicolini Sabrina , Sartorio Alessandro
Published: May 2021

The aim of this study was to compare the accuracy of different indexes of adiposity and/or body composition in identifying the metabolic syndrome (MetS) in a group of 1528 Caucasian women with obesity: (age ± standard deviation (SD): 50.8 ± 14 years (range 18–83); body mass index (BMI) 43.3 ± 5.9 kg/m2 (30.7–72.9 kg/m2)). The following indexes were assessed in each subject: BMI, fat-free mass index (FFMI), fat mass index (FMI), tri-ponderal mass index (TMI), waist-to-height ratio (WtHR), and the body mass fat index (BMFI). Thereafter, a threshold value adjusted for age, which could identify MetS, was calculated for each index. A significant correlation was found among all indexes (p < 0.0001 for all). However, when the area under the curve (AUC) was compared, WtHR performed significantly better in the whole group and in the different age groups, apart from a lack of statistical difference between WtHR and BMFI in the 45–55 years age group. In conclusion, WtHR seems to be a fair index useful for identifying MetS in women with obesity. The use of thresholds appropriate for age can help further improve its accuracy, thus reinforcing the clinical evaluation for MetS screening.
Growth Factors Assessed during Kasai Procedure in Liver and Serum Are Not Predictive for the Postoperative Liver Deterioration in Infants with Biliary Atresia
Authors: Madadi-Sanjani Omid , Froemmel Stephanie , Falk Christine S. , Vieten Gertrud , Petersen Claus , Kuebler Joachim F. , Klemann Christian
Published: May 2021

Background: Biliary atresia (BA) is a neonatal cholangiopathy characterized by progressive destruction of the biliary system resulting in liver cirrhosis. Residual bile drainage can temporarily be achieved through Kasai portoenterostomy (KPE) and some children show long-term survival with their native liver. However, most children eventually require liver transplantation (LTX). As several growth factors (GF) and chemokines have been shown to promote fibrogenesis in the liver, we assessed whether GF are predictive for the course of disease. Material and Methods: Liver and sera samples were collected from 49 infants with BA during KPE. Levels of 13 different GF were measured by multiplex immunoassay. Patient outcomes were stratified into favorable (bilirubin < 20 µmol/L at 2-year follow-up) and unfavorable (LTX). GF levels were compared between groups by a t-test, correlation coefficients were calculated, and principal component analyses performed. Results: Twenty-two patients showed a favorable and 27 an unfavorable disease course. No relation of GF and outcome could be established. In both groups, high levels of SDF-1alpha/CXCL12 (1473.0 ± 497.5 pg/mL), FGF2 (301.2 ± 207.8 pg/mL), and VEGF-a (209.0 ± 146.4 pg/mL) levels were measured within the liver, followed (in descending order) by PDGF-bb, LIF, GM-CSF, BDNF, VEGF-d, beta-NGF, IL-7, SCF, PIGF-1, and EGF. Serum marker levels showed much higher mean variation compared to hepatic values and no correlation to the protein microenvironment in the liver. Conclusions: Our study demonstrates high amounts of GF in livers from infants with BA at KPE, but no correlation to the outcome or serum values could be established. Our data suggest that local or systemic GF levels are unsuitable for prediction of the disease course. Collectively, we conclude that in BA the degree of proliferative activity caused by GF is a dismissible factor for the further course of disease.
Influence of Substance Use Disorder on Treatment Retention of Adult-Attention-Deficit/Hyperactive Disorder Patients. A 5-Year Follow-Up Study
Authors: Pallucchini Alessandro , Carli Marco , Maremmani Angelo , Scarselli Marco , Perugi Giulio , Maremmani Icro
Published: May 2021

Attention-Deficit/Hyperactivity Disorder (ADHD) is the most widespread neurodevelopmental disorder, and it still persists into adulthood in 2–6% of the population. Psychiatric comorbidities are very common in adult ADHD (A-ADHD) patients; in particular, Substance Use Disorder (SUD) is found in 40% of these patients. Co-occurrence of ADHD and SUD is described as detrimental to clinical outcome by many authors, while only a few studies describe good clinical results in A-ADHD-SUD patients when they were treated for ADHD, both for the efficacy and the compliance of patients. In this study we tested to determine whether SUD can influence the treatment outcome of A-ADHD patients by correlating lifetime, past and current substance use in A-ADHD patients with their outcome (retention rate) during a 5-year follow-up of patients treated with stimulant and non-stimulant medications, using Kaplan–Meier survival analysis with overall and pairwise comparison. The association between demographic, symptomatological and clinical aspects with retention in treatment, adjusting for potential confounding factors, was summarized using Cox regression. After 5 years of observation, the cumulative treatment retention was 49.0%, 64.3% and 41.8% for A-ADHD patients without lifetime SUD (NSUD/A-ADHD), A-ADHD with past SUD (PSUD/A-ADHD) and A-ADHD with current SUD (CSUD/A-ADHD), respectively. Overall comparisons were not significant (Wilcoxon Rank-Sum (statistical) Test = 1.48; df = 2; p = 0.477). The lack of differences was confirmed by a Cox regression demonstrating that the ADHD diagnosis according to DIVA, gender, education, civil status, presence of psychiatric comorbidity, and psychiatric and ADHD familiarity; severity of symptomatological scales as evaluated by WHODAS, BPRS, BARRAT, DERS, HSRS, and ASRS did not influence treatment drop-out (χ2 22.30; df = 20 p = 0.324). Our A-ADHD-SUD patients have the same treatment retention rate as A-ADHD patients without SUD, so it seems that substance use comorbidity does not influence this clinical parameter.
3D X-ray Microscopy as a Tool for in Depth Analysis of the Interfacial Interaction between a Single Carbon Fiber and an Epoxy Matrix after Mechanical Loading
Authors: Vogtmann Julia , Klingler Andreas , Rief Thomas , Gurka Martin
Published: May 2021

The benefit of fiber-reinforced composites originates from the interaction between the fiber reinforcement and the matrix. This interplay controls many of its mechanical properties and is of utmost importance to enable its unique performance as a lightweight material. However, measuring the fiber−matrix interphase strength with micromechanical tests, like the Broutman test, is challenging, due to the many, often unknown boundary conditions. Therefore, this study uses state-of-the-art, high-resolution X-ray computed microtomography (XRM) as a tool to investigate post mortem the failure mechanisms of single carbon fibers within an epoxy matrix. This was conducted at the example of single carbon fiber Broutman test specimens. The capabilities of today’s XRM analysis were shown in comparison to classically obtained light microscopy. A simple finite element model was used to enhance the understanding of the observed fracture patterns. In total, this research reveals the possibilities and limitations of XRM to visualize and assess compression-induced single fiber fracture patterns. Furthermore, comparing two different matrix systems with each other illustrates that the failure mechanisms originate from differences in the fiber−matrix interphases. The carbon fiber seems to fail due to brittleness under compression stress. Observation of the fiber slippage and deformed small fracture pieces between the fragments suggests a nonzero stress state at the fragment ends after fiber failure. Even more, these results demonstrate the usefulness of XRM as an additional tool for the characterization of the fiber−matrix interphase.
Hiding in Fouling Communities: A Native Spider Crab Decorating with a Cryptogenic Bryozoan in a Mediterranean Marina
Authors: Tanduo Valentina , Virgili Riccardo , Osca David , Crocetta Fabio
Published: May 2021

Camouflage is the method by which animals conceal by blending in with the environment, and may be achieved by fixed or changing color, shape, texture, chemical secretions, and/or behavior [...]
The Use of News Information Published in Newspapers to Estimate the Impact of Coastal Storms at a Regional Scale
Authors: Sancho-García Amanda , Guillén Jorge , Gracia Vicente , Rodríguez-Gómez Ana Carlota , Rubio-Nicolás Belén
Published: May 2021

The evaluation of coastal damage caused by storms is not straightforward and different approaches can be applied. In this study, damage caused by extreme storms is evaluated at a regional scale based on news information published in regional newspapers. The data derived from the news are compared with hydrodynamic parameters to check the reliability of this methodology as a preliminary” fast approach” to evaluate storm damage and to identify hotspots along the coast. This methodology was applied to the two most extreme storms ever recorded along the Spanish Mediterranean coast, which occurred in January 2017 and January 2020, severely impacting the coast and causing significant community concerns. The news information from different media sources was processed and weighted to describe the resulting erosion, inundation, sand accumulation, and destruction of infrastructures. Moreover, an accuracy index for scoring the quality of the information was proposed. In spite of some limitations of the method, the resulting regional coastal hazard landscape of damage provides a rapid overview of the intensity and distribution of the damage and enables one to identify the location of potential hotspots for the analyzed extreme storm events. The results show that estimated damage intensity is better related to maximum wave energy than cumulative wave energy during a storm, and that beach characteristics should also be included for understanding the distribution of coastal damage.
Hydrodynamic Modelling for a Transportation System of Two Unmanned Underwater Vehicles: Semi-Empirical, Numerical and Experimental Analyses
Authors: Rehman Faheem Ur , Huang Luofeng , Anderlini Enrico , Thomas Giles
Published: May 2021

Underwater transportation is an essential approach for scientific exploration, maritime construction and military operations. Determining the hydrodynamic coefficients for a complex underwater transportation system comprising multiple vehicles is challenging. Here, the suitability of a quick and less costly semi-empirical approach to obtain the hydrodynamic coefficients for a complex transportation system comprising two Unmanned Underwater Vehicles (UUVs) is investigated, where the interaction effects between UUVs are assumed to be negligible. The drag results were verified by Computational Fluid Dynamics (CFD) analysis at the steady state. The semi-empirical results agree with CFD in heave and sway; however, they were overpredicted in surge due to ignoring the wake effects. Furthermore, experiments were performed for the validation of the time-domain motion simulations with semi-empirical and CFD results. The simulations which were performed with the CFD drags were close to the experiments. The semi-empirical approach could be relied on once a correction parameter is included to account for the interactive effect between multiple UUVs. Overall, this work makes a contribution by deriving a semi-empirical approach for the dynamic and controlling system of dual UUVs, with CFD and experiments applied to ascertain its accuracy and potential improvement.
Population Genomic Screening for Genetic Etiologies of Neurodevelopmental/Psychiatric Disorders Demonstrates Personal Utility and Positive Participant Responses
Authors: Wain Karen E. , Tolwinski Kasia , Palen Emily , Heidlebaugh Alexis R. , Holdren Karahlyn , Walsh Lauren Kasparson , Oetjens Matthew T. , Ledbetter David H. , Martin Christa Lese
Published: May 2021

Genomic variants that cause neurodevelopmental/psychiatric disorders (NPD) are relatively prevalent and highly penetrant. This study aimed to understand adults’ immediate responses to receiving NPD-related results to inform inclusion in population-based genomic screening programs. Nine recurrent, pathogenic copy number variants (CNVs) were identified from research exome data, clinically confirmed, and disclosed to adult participants of the Geisinger MyCode Community Health Initiative DiscovEHR cohort by experienced genetic counselors. A subset of in-person genetic counseling sessions (n = 27) were audio-recorded, transcribed, and coded using a grounded theory approach. Participant reactions were overwhelmingly positive and indicated that an NPD genetic etiology was highly valuable and personally useful. Participants frequently reported learning disabilities or other NPD that were not documented in their electronic health records and noted difficulties obtaining support for NPD needs. Most intended to share their genetic result with family members and health care providers and were interested in how their result could improve their healthcare. This study indicates that results from population-based NPD genomic screening can provide personal value for adults with NPD, were viewed positively by participants, and could improve clinical outcomes by informing symptom monitoring for NPD and co-morbidities, promoting improved health behaviors, and enhancing psychotherapeutic approaches.
Renin Feedback Is an Independent Predictor of Outcome in HFpEF
Authors: Binder Christina , Poglitsch Marko , Duca Franz , Rettl René , Dachs Theresa Marie , Dalos Daniel , Schrutka Lore , Seirer Benjamin , Ligios Luciana Camuz , Capelle Christophe , Eslam Roza Badr , Qin Hong , Hengstenberg Christian , Bonderman Diana
Published: May 2021

Drugs which interact with the renin angiotensin aldosterone system (RAAS) aim to reduce the negative effects of angiotensin (Ang) II. Treatment with these drugs anticipate a compensatory up-regulation of renin; however, it has been shown that there is a large variability in circulating plasma renin (PRA), even in patients with optimal medical therapy in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Our aim was to measure plasma renin activity (PRA-S), its response to RAAS inhibitor (RAASi) therapies and its effects on outcome in patients with HF with preserved ejection fraction (HFpEF). For this purpose, 150 HFpEF patients were included into a prospective single-center registry. Equilibrium (eq) angiotensin metabolites were measured from serum samples using mass spectroscopy. PRA-S (eqAng I + eqAng II) was calculated and compared in respect to the primary endpoint defined as all-cause death. PRA-S in patients with RAASi therapy was not significantly higher than in patients without RAASi (p = 0.262). Even after adjusting for confounding factors, PRA-S remained predictive for all-cause death in the multivariable model with a hazard ratio of 2.14 (95%CI 1.20–3.82, p = 0.010). We conclude that high PRA-S is associated with poor prognosis in patients with HFpEF, regardless of RAASi treatment, which could ultimately result in hyperactivated RAAS and consecutive negative effects on the cardiovascular and renal system, leading to poor outcome in patients with HFpEF.