bluuebunny/crossref_metadata_2025 huggingface dataset:
Women’s Expressed Motivational Factors for Participation in Aquarobics Classes
Authors: Currie Janet L.
Published: April 2022

Leisure provides a vehicle for women to develop friendships in later life, yet few studies have explored older women’s experiences of social and emotional connections with leisure. This article provides insights into the perceived benefits a group of older women state they gain from participation in aquarobics for leisure. The main themes to emerge from the focus group interview data (n = 19 women, x¯ age = 75 years), illustrating the key motivational factor for participation in the classes, included an individual desire to improve one’s overall fitness. Participants also expressed a strong sense of belonging from being able to socialize after the activity, and highly valued the welcoming atmosphere and feeling of comradery involved. The aquarobics instructor was noted as performing a very important role in ensuring delivery of an enjoyable class experience where participants experienced variety, had fun, and felt happy taking part. For this group of women, aquarobics forms a health promoting leisure context offering an important space for gaining subjective wellbeing, building social connectedness and resisting the dominant ideology of aging.
Pathophysiology of the Serotonin System in the Nervous System and Beyond
Authors: De Deurwaerdère Philippe , Di Giovanni Giuseppe
Published: April 2022

Serotonin (5-HT) is an attractive neurotransmitter system, in terms of physiology, physiopathology, and medicines [...]
Chronic Experimental Model of TNBS-Induced Colitis to Study Inflammatory Bowel Disease
Authors: Silva Inês , Solas João , Pinto Rui , Mateus Vanessa
Published: April 2022

Background: Inflammatory bowel disease (IBD) is a world healthcare problem. In order to evaluate the effect of new pharmacological approaches for IBD, we aim to develop and validate chronic trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Methods: Experimental colitis was induced by the rectal administration of multiple doses of TNBS in female CD-1 mice. The protocol was performed with six experimental groups, depending on the TNBS administration frequency, and two control groups (sham and ethanol groups). Results: The survival rate was 73.3% in the first three weeks and, from week 4 until the end of the experimental protocol, the mice’s survival remained unaltered at 70.9%. Fecal hemoglobin presented a progressive increase until week 4 (5.8 ± 0.3 µmol Hg/g feces, p < 0.0001) compared with the ethanol group, with no statistical differences to week 6. The highest level of tumor necrosis factor-α was observed on week 3; however, after week 4, a slight decrease in tumor necrosis factor-α concentration was verified, and the level was maintained until week 6 (71.3 ± 3.3 pg/mL and 72.7 ± 3.6 pg/mL, respectively). Conclusions: These findings allowed the verification of a stable pattern of clinical and inflammation signs after week 4, suggesting that the chronic model of TNBS-induced colitis develops in 4 weeks.
Reorganization of Parvalbumin Immunopositive Perisomatic Innervation of Principal Cells in Focal Cortical Dysplasia Type IIB in Human Epileptic Patients
Authors: Szekeres-Paraczky Cecília , Szocsics Péter , Erőss Loránd , Fabó Dániel , Mód László , Maglóczky Zsófia
Published: April 2022

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. As several studies have revealed, the abnormal functioning of the perisomatic inhibitory system may play a role in the onset of seizures. Therefore, we wanted to investigate whether changes of perisomatic inhibitory inputs are present in FCD. Thus, the input properties of abnormal giant- and control-like principal cells were examined in FCD type IIB patients. Surgical samples were compared to controls from the same cortical regions with short postmortem intervals. For the study, six subjects were selected/each group. The perisomatic inhibitory terminals were quantified in parvalbumin and neuronal nuclei double immunostained sections using a confocal fluorescent microscope. The perisomatic input of giant neurons was extremely abundant, whereas control-like cells of the same samples had sparse inputs. A comparison of pooled data shows that the number of parvalbumin-immunopositive perisomatic terminals contacting principal cells was significantly larger in epileptic cases. The analysis showed some heterogeneity among epileptic samples. However, five out of six cases had significantly increased perisomatic input. Parameters of the control cells were homogenous. The reorganization of the perisomatic inhibitory system may increase the probability of seizure activity and might be a general mechanism of abnormal network activity.
Myoglobin Interaction with Lactate Rapidly Releases Oxygen: Studies on Binding Thermodynamics, Spectroscopy, and Oxygen Kinetics
Authors: Adepu Kiran Kumar , Bhandari Dipendra , Anishkin Andriy , Adams Sean H. , Chintapalli Sree V.
Published: April 2022

Myoglobin (Mb)-mediated oxygen (O2) delivery and dissolved O2 in the cytosol are two major sources that support oxidative phosphorylation. During intense exercise, lactate (LAC) production is elevated in skeletal muscles as a consequence of insufficient intracellular O2 supply. The latter results in diminished mitochondrial oxidative metabolism and an increased reliance on nonoxidative pathways to generate ATP. Whether or not metabolites from these pathways impact Mb-O2 associations remains to be established. In the present study, we employed isothermal titration calorimetry, O2 kinetic studies, and UV-Vis spectroscopy to evaluate the LAC affinity toward Mb (oxy- and deoxy-Mb) and the effect of LAC on O2 release from oxy-Mb in varying pH conditions (pH 6.0–7.0). Our results show that LAC avidly binds to both oxy- and deoxy-Mb (only at acidic pH for the latter). Similarly, in the presence of LAC, increased release of O2 from oxy-Mb was detected. This suggests that with LAC binding to Mb, the structural conformation of the protein (near the heme center) might be altered, which concomitantly triggers the release of O2. Taken together, these novel findings support a mechanism where LAC acts as a regulator of O2 management in Mb-rich tissues and/or influences the putative signaling roles for oxy- and deoxy-Mb, especially under conditions of LAC accumulation and lactic acidosis.
Probiotics Enhance Bone Growth and Rescue BMP Inhibition: New Transgenic Zebrafish Lines to Study Bone Health
Authors: Sojan Jerry Maria , Raman Ratish , Muller Marc , Carnevali Oliana , Renn Jörg
Published: April 2022

Zebrafish larvae, especially gene-specific mutants and transgenic lines, are increasingly used to study vertebrate skeletal development and human pathologies such as osteoporosis, osteopetrosis and osteoarthritis. Probiotics have been recognized in recent years as a prophylactic treatment for various bone health issues in humans. Here, we present two new zebrafish transgenic lines containing the coding sequences for fluorescent proteins inserted into the endogenous genes for sp7 and col10a1a with larvae displaying fluorescence in developing osteoblasts and the bone extracellular matrix (mineralized or non-mineralized), respectively. Furthermore, we use these transgenic lines to show that exposure to two different probiotics, Bacillus subtilis and Lactococcus lactis, leads to an increase in osteoblast formation and bone matrix growth and mineralization. Gene expression analysis revealed the effect of the probiotics, particularly Bacillus subtilis, in modulating several skeletal development genes, such as runx2, sp7, spp1 and col10a1a, further supporting their ability to improve bone health. Bacillus subtilis was the more potent probiotic able to significantly reverse the inhibition of bone matrix formation when larvae were exposed to a BMP inhibitor (LDN212854).
Sclerostin: From Molecule to Clinical Biomarker
Authors: Omran Ahmed , Atanasova Diana , Landgren Filip , Magnusson Per
Published: April 2022

Sclerostin, a glycoprotein encoded by the SOST gene, is mainly produced by mature osteocytes and is a critical regulator of bone formation through its inhibitory effect on Wnt signaling. Osteocytes are differentiated osteoblasts that form a vast and highly complex communication network and orchestrate osteogenesis in response to both mechanical and hormonal cues. The three most commonly described pathways of SOST gene regulation are mechanotransduction, Wnt/β-catenin, and steroid signaling. Downregulation of SOST and thereby upregulation of local Wnt signaling is required for the osteogenic response to mechanical loading. This review covers recent findings concerning the identification of SOST, in vitro regulation of SOST gene expression, structural and functional properties of sclerostin, pathophysiology, biological variability, and recent assay developments for measuring circulating sclerostin. The three-dimensional structure of human sclerostin was generated with the AlphaFold Protein Structure Database applying a novel deep learning algorithm based on the amino acid sequence. The functional properties of the 3-loop conformation within the tertiary structure of sclerostin and molecular interaction with low-density lipoprotein receptor-related protein 6 (LRP6) are also reviewed. Second-generation immunoassays for intact/biointact sclerostin have recently been developed, which might overcome some of the reported methodological obstacles. Sclerostin assay standardization would be a long-term objective to overcome some of the problems with assay discrepancies. Besides the use of age- and sex-specific reference intervals for sclerostin, it is also pivotal to use assay-specific reference intervals since available immunoassays vary widely in their methodological characteristics.
Many Ways to Rome: Exercise, Cold Exposure and Diet—Do They All Affect BAT Activation and WAT Browning in the Same Manner?
Authors: Scheel Anna K. , Espelage Lena , Chadt Alexandra
Published: April 2022

The discovery of functional brown adipose tissue (BAT) in adult humans and the possibility to recruit beige cells with high thermogenic potential within white adipose tissue (WAT) depots opened the field for new strategies to combat obesity and its associated comorbidities. Exercise training as well as cold exposure and dietary components are associated with the enhanced accumulation of metabolically-active beige adipocytes and BAT activation. Both activated beige and brown adipocytes increase their metabolic rate by utilizing lipids to generate heat via non-shivering thermogenesis, which is dependent on uncoupling protein 1 (UCP1) in the inner mitochondrial membrane. Non-shivering thermogenesis elevates energy expenditure and promotes a negative energy balance, which may ameliorate metabolic complications of obesity and Type 2 Diabetes Mellitus (T2DM) such as insulin resistance (IR) in skeletal muscle and adipose tissue. Despite the recent advances in pharmacological approaches to reduce obesity and IR by inducing non-shivering thermogenesis in BAT and WAT, the administered pharmacological compounds are often associated with unwanted side effects. Therefore, lifestyle interventions such as exercise, cold exposure, and/or specified dietary regimens present promising anchor points for future disease prevention and treatment of obesity and T2DM. The exact mechanisms where exercise, cold exposure, dietary interventions, and pharmacological treatments converge or rather diverge in their specific impact on BAT activation or WAT browning are difficult to determine. In the past, many reviews have demonstrated the mechanistic principles of exercise- and/or cold-induced BAT activation and WAT browning. In this review, we aim to summarize not only the current state of knowledge on the various mechanistic principles of diverse external stimuli on BAT activation and WAT browning, but also present their translational potential in future clinical applications.
Characterization of the Skeletal Muscle Proteome in Undernourished Old Rats
Authors: Barbé Caroline , Salles Jérôme , Chambon Christophe , Giraudet Christophe , Sanchez Phelipe , Patrac Véronique , Denis Philippe , Boirie Yves , Walrand Stéphane , Gueugneau Marine
Published: April 2022

Aging is associated with a progressive loss of skeletal muscle mass and function termed sarcopenia. Various metabolic alterations that occur with aging also increase the risk of undernutrition, which can worsen age-related sarcopenia. However, the impact of undernutrition on aged skeletal muscle remains largely under-researched. To build a deeper understanding of the cellular and molecular mechanisms underlying age-related sarcopenia, we characterized the undernutrition-induced changes in the skeletal muscle proteome in old rats. For this study, 20-month-old male rats were fed 50% or 100% of their spontaneous intake for 12 weeks, and proteomic analysis was performed on both slow- and fast-twitch muscles. Proteomic profiling of undernourished aged skeletal muscle revealed that undernutrition has profound effects on muscle proteome independently of its effect on muscle mass. Undernutrition-induced changes in muscle proteome appear to be muscle-type-specific: slow-twitch muscle showed a broad pattern of differential expression in proteins important for energy metabolism, whereas fast-twitch muscle mainly showed changes in protein turnover between undernourished and control rats. This first proteomic analysis of undernourished aged skeletal muscle provides new molecular-level insight to explain phenotypic changes in undernourished aged muscle. We anticipate this work as a starting point to define new biomarkers associated with undernutrition-induced muscle loss in the elderly.
Resolving the Mechanism of Acoustic Plasmon Instability in Graphene Doped by Alkali Metals
Authors: Marušić Leonardo , Kalinić Ana , Radović Ivan , Jakovac Josip , Mišković Zoran L. , Despoja Vito
Published: April 2022

Graphene doped by alkali atoms (ACx) supports two heavily populated bands (π and σ) crossing the Fermi level, which enables the formation of two intense two-dimensional plasmons: the Dirac plasmon (DP) and the acoustic plasmon (AP). Although the mechanism of the formation of these plasmons in electrostatically biased graphene or at noble metal surfaces is well known, the mechanism of their formation in alkali-doped graphenes is still not completely understood. We shall demonstrate that two isoelectronic systems, KC8 and CsC8, support substantially different plasmonic spectra: the KC8 supports a sharp DP and a well-defined AP, while the CsC8 supports a broad DP and does not support an AP at all. We shall demonstrate that the AP in an ACx is not, as previously believed, just a consequence of the interplay of the π and σ intraband transitions, but a very subtle interplay between these transitions and the background screening, caused by the out-of-plane interband C(π)→A(σ) transitions.
Targeting Sirt1, AMPK, Nrf2, CK2, and Soluble Guanylate Cyclase with Nutraceuticals: A Practical Strategy for Preserving Bone Mass
Authors: McCarty Mark F. , Lewis Lujan Lidianys , Iloki Assanga Simon
Published: April 2022

There is a vast pre-clinical literature suggesting that certain nutraceuticals have the potential to aid the preservation of bone mass in the context of estrogen withdrawal, glucocorticoid treatment, chronic inflammation, or aging. In an effort to bring some logical clarity to these findings, the signaling pathways regulating osteoblast, osteocyte, and osteoclast induction, activity, and survival are briefly reviewed in the present study. The focus is placed on the following factors: the mechanisms that induce and activate the RUNX2 transcription factor, a key driver of osteoblast differentiation and function; the promotion of autophagy and prevention of apoptosis in osteoblasts/osteoclasts; and the induction and activation of NFATc1, which promotes the expression of many proteins required for osteoclast-mediated osteolysis. This analysis suggests that the activation of sirtuin 1 (Sirt1), AMP-activated protein kinase (AMPK), the Nrf2 transcription factor, and soluble guanylate cyclase (sGC) can be expected to aid the maintenance of bone mass, whereas the inhibition of the serine kinase CK2 should also be protective in this regard. Fortuitously, nutraceuticals are available to address each of these targets. Sirt1 activation can be promoted with ferulic acid, N1-methylnicotinamide, melatonin, nicotinamide riboside, glucosamine, and thymoquinone. Berberine, such as the drug metformin, is a clinically useful activator of AMPK. Many agents, including lipoic acid, melatonin, thymoquinone, astaxanthin, and crucifera-derived sulforaphane, can promote Nrf2 activity. Pharmacological doses of biotin can directly stimulate sGC. Additionally, certain flavonols, notably quercetin, can inhibit CK2 in high nanomolar concentrations that may be clinically relevant. Many, though not all, of these agents have shown favorable effects on bone density and structure in rodent models of bone loss. Complex nutraceutical regimens providing a selection of these nutraceuticals in clinically meaningful doses may have an important potential for preserving bone health. Concurrent supplementation with taurine, N-acetylcysteine, vitamins D and K2, and minerals, including magnesium, zinc, and manganese, plus a diet naturally high in potassium, may also be helpful in this regard.
High Expression of the Lysosomal Protease Cathepsin D Confers Better Prognosis in Neuroblastoma Patients by Contrasting EGF-Induced Neuroblastoma Cell Growth
Authors: Secomandi Eleonora , Salwa Amreen , Vidoni Chiara , Ferraresi Alessandra , Follo Carlo , Isidoro Ciro
Published: April 2022

Neuroblastoma is a malignant extracranial solid tumor arising from the sympathoadrenal lineage of the neural crest and is often associated with N-MYC amplification. Cathepsin D has been associated with chemoresistance in N-MYC-overexpressing neuroblastomas. Increased EGFR expression also has been associated with the aggressive behavior of neuroblastomas. This work aimed to understand the mechanisms linking EGFR stimulation and cathepsin D expression with neuroblastoma progression and prognosis. Gene correlation analysis in pediatric neuroblastoma patients revealed that individuals bearing a high EGFR transcript level have a good prognosis only when CTSD (the gene coding for the lysosomal protease Cathepsin D, CD) is highly expressed. Low CTSD expression was associated with poor clinical outcome. CTSD expression was negatively correlated with CCNB2, CCNA2, CDK1 and CDK6 genes involved in cell cycle division. We investigated the biochemical pathways downstream to EGFR stimulation in human SH-SY5Y neuroblastoma cells engineered for overexpressing or silencing of CD expression. Cathepsin D overexpression decreased the proliferative potential of neuroblastoma cells through downregulation of the pro-oncogenic MAPK signaling pathway. EGFR stimulation downregulated cathepsin D expression, thus favoring cell cycle division. Our data suggest that chemotherapeutics that inhibit the EGFR pathway, along with stimulators of cathepsin D synthesis and activity, could benefit neuroblastoma prognosis.
Sacrificial Zinc Oxide Strategy-Enhanced Mesoporosity in MIL-53-Derived Iron–Carbon Composite for Methylene Blue Adsorption
Authors: Dekyvere Sander , Hilal Mohamed Elhousseini , Chaemchuen Somboon , Zhuiykov Serge , Verpoort Francis
Published: April 2022

MOF-derived carbon-based materials have attracted widespread attention due to their relatively large surface area, morphology, and their stability in water. Considering these advantages, these materials present themselves as excellent adsorbents. In this work, a novel method was designed for the fabrication of a nano zero-valent-iron (nZVI) carbon composite. The utilization of zinc oxide nanorods (ZnONRs) in the role of sacrificial consumable nuclei for the synthesis of MIL-53 sacrificial zinc oxide nanorods (MIL-53-SNR) and the subsequent pyrolysis at 700 °C in the inert atmosphere led to a graphitic-supported nZVI material (Fe-C-SNR). Fe-C-SNR was compared with a commercial zinc oxide bulk (MIL-53-SB) and with a pristine MIL-53. By virtue of the ZnONRs, Fe-C-SNR exhibited a greatly improved mesoporous structure. Consequently, the pyrolyzed materials were applied as adsorbents for methylene blue. Fe-C-SNR’s performance increased to more than double of the pyrolyzed MIL-53 (Fe-C), with a remarkably fast adsorption time (10 min) for a concentration of 10 mg L−1 with only 200 mg L−1 adsorbent required. This functional composite also displayed exceptional recyclability; after ten complete cycles, Fe-C-SNR was still capable of completely adsorbing the methylene blue. The utilization of ZnONRs proves itself advantageous and could further be extended to other MOFs for a wide range of applications.
Interfaces between Ceramic and Polymer Electrolytes: A Comparison of Oxide and Sulfide Solid Electrolytes for Hybrid Solid-State Batteries
Authors: Spencer Jolly Dominic , Melvin Dominic L. R. , Stephens Isabella D. R. , Brugge Rowena H. , Pu Shengda D. , Bu Junfu , Ning Ziyang , Hartley Gareth O. , Adamson Paul , Grant Patrick S. , Aguadero Ainara , Bruce Peter G.
Published: April 2022

Hybrid solid-state batteries using a bilayer of ceramic and solid polymer electrolytes may offer advantages over using a single type of solid electrolyte alone. However, the impedance to Li+ transport across interfaces between different electrolytes can be high. It is important to determine the resistance to Li+ transport across these heteroionic interfaces, as well as to understand the underlying causes of these resistances; in particular, whether chemical interphase formation contributes to giving high resistances, as in the case of ceramic/liquid electrolyte interfaces. In this work, two ceramic electrolytes, Li3PS4 (LPS) and Li6.5La3Zr1.5Ta0.5O12 (LLZTO), were interfaced with the solid polymer electrolyte PEO10:LiTFSI and the interfacial resistances were determined by impedance spectroscopy. The LLZTO/polymer interfacial resistance was found to be prohibitively high but, in contrast, a low resistance was observed at the LPS/polymer interface that became negligible at a moderately elevated temperature of 50 °C. Chemical characterization of the two interfaces was carried out, using depth-profiled X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry, to determine whether the interfacial resistance was correlated with the formation of an interphase. Interestingly, no interphase was observed at the higher resistance LLZTO/polymer interface, whereas LPS was observed to react with the polymer electrolyte to form an interphase.
A High-Density Polarized 3He Gas–Jet Target for Laser–Plasma Applications
Authors: Fedorets Pavel , Zheng Chuan , Engels Ralf , Engin Ilhan , Feilbach Herbert , Giesen Ulrich , Glückler Harald , Kannis Chrysovalantis , Klehr Franz , Lennartz Manfred , Pfeifer Heinz , Pfennings Johannes , Schneider Claus Michael , Schnitzler Norbert , Soltner Helmut , Swaczyna Robert , Büscher Markus
Published: April 2022

A laser-driven spin-polarized 3He2+-beam source for nuclear–physics experiments and for the investigation of polarized nuclear fusion demands a high-density polarized 3He gas-jet target. Such a target requires a magnetic system providing a permanent homogeneous holding field for the nuclear spins plus a set of coils for adjusting the orientation of the polarization. Starting from a transport vessel at a maximum pressure of 3 bar, the helium gas is compressed for a short time and can be injected into a laser–interaction chamber through a non-magnetic opening valve and nozzle, thus forming jets with densities of about a few 1019 cm−3 and widths of about 1 mm. The target comprises a 3D adjustment system for precise positioning of the jet relative to the laser focus. An auxiliary gas system provides remote target operation and flushing of the gas lines with Ar gas, which helps to reduce polarization losses. The design of the target, its operation procedures and first experimental results are presented.
Soluble (Pro)renin Receptor Is Adversely Associated with Indices of Left Ventricular Structure and Function: The African-PREDICT Study
Authors: Gafane-Matemane Lebo F. , Kruger Ruan , Van Rooyen Johannes M. , Gona Philimon N. , Schutte Aletta E.
Published: April 2022

This study aims to compare soluble (pro)renin receptor [s(P)RR] levels between black and white adults and to explore the associations of left ventricular (LV) structure and function with s(P)RR in the total and ethnicity-stratified groups. The study sample included 1172 apparently healthy black (n = 587) and white (n = 585) participants of the African-PREDICT study aged 20–30 years. Echocardiography was performed to determine relative wall thickness (RWT), LV mass index, LV ejection fraction and stroke volume index (SVi). s(P)RR was analyzed from serum samples, while plasma renin activity-surrogate (PRA-S) and eq angiotensin II were determined using the RAS™ Fingerprint. s(P)RR was higher in the white participants compared to the black participants (p < 0.001). In multivariable-adjusted linear regression analyses, we observed a positive association between RWT and s(P)RR (β = 0.141; p = 0.005) and negative associations of LV ejection fraction (β = −0.123; p = 0.016) and SVi (β = −0.144; p = 0.004) with s(P)RR only in white adults. Higher s(P)RR observed in white vs. black participants was associated with higher RWT and poorer LV function only in young white adults but not in their black counterparts. These results suggest that s(P)RR may contribute to LV remodeling and dysfunction in white populations due to its role in volume–pressure regulation and its proinflammatory as well as profibrotic effects.
Exercise Training and Interventions for Coronary Artery Disease
Authors: Fernández-Rubio Hugo , Becerro-de-Bengoa-Vallejo Ricardo , Rodríguez-Sanz David , Calvo-Lobo César , Vicente-Campos Davinia , Chicharro José López
Published: April 2022

Coronary artery disease (CAD) may be considered a main cause of mortality and the prevalence of CAD is increasing nowadays, leading to high health costs in many countries. Despite the fact of the regression of the atherosclerotic plaque, the decrease in blood viscosity and the growth of collateral vessels have been proposed as improvements that CAD patients may obtain under exercise performance. Thus, the present narrative review aimed to carry out a brief specific analysis of the results achieved when performing endurance, strength or inspiratory muscle training. Exercise attenuates certain pathophysiological processes of this disease, such as endothelial dysfunction or the vulnerability of atherosclerotic plaques, and produces improvements in functional capacity and muscle strength, among others. Within the different exercise modalities, the most important parameter to be considered seems to be the total caloric expenditure, and not so much the modality itself. As such, in cardiac rehabilitation, when prescribing exercise, we should possibly focus on the modality that obtains more adherence in patients. To conclude, it must be highlighted that total caloric expenditure is not being taken into account when comparing interventions and this relevant information should be considered in future studies.
Signaling Pathways Involved in Myocardial Ischemia–Reperfusion Injury and Cardioprotection: A Systematic Review of Transcriptomic Studies in Sus scrofa
Authors: Salazar-Gonzalez Hector , Gutierrez-Mercado Yanet Karina , Munguia-Galaviz Francisco Javier , Echavarria Raquel
Published: April 2022

Myocardial damage in acute myocardial infarctions (AMI) is primarily the result of ischemia–reperfusion injury (IRI). Recognizing the timing of transcriptional events and their modulation by cardioprotective strategies is critical to address the pathophysiology of myocardial IRI. Despite the relevance of pigs for translational studies of AMI, only a few have identified how transcriptomic changes shape cellular signaling pathways in response to injury. We systematically reviewed transcriptomic studies of myocardial IRI and cardioprotection in Sus scrofa. Gene expression datasets were analyzed for significantly enriched terms using the Enrichr analysis tool, and statistically significant results (adjusted p-values of <0.05) for Signaling Pathways, Transcription Factors, Molecular Functions, and Biological Processes were compared between eligible studies to describe how these dynamic changes transform the myocardium from an injured and inflamed tissue into a scar. Then, we address how cardioprotective interventions distinctly modulate the myocardial transcriptome and discuss the implications of uncovering gene regulatory networks for cardiovascular pathologies and translational applications.
β-Caryophyllene Ameliorates Cyclophosphamide Induced Cardiac Injury: The Association of TLR4/NFκB and Nrf2/HO1/NQO1 Pathways
Authors: Younis Nancy S.
Published: April 2022

Background: β-caryophyllene (BCP), a natural sesquiterpene, is extensively present in the essential oils of several plants. Cyclophosphamide (CYC) is an anticancer drug. However, its clinical usage is inadequate due to its cardiotoxicity. The aim of this study was to study the effects of BCP on cardiac injury induced by CYC exposure, and to identify the underlying mechanism of action. Methods: Five groups of Wistar rats were allocated. Group I (Normal), II (BCP), and III (CYC) acted as controls. Group IV, V (CYC + BCP) received BCP in two doses (100 and 200 mg/kg, orally, respectively) for 14 days after CYC challenge. CYC groups received 200 mg/kg, i.p. of the drug once on the first day of experiments. Results: CYC group displayed numerous ECG and histological irregularities and cardiac markers elevation. CYC induced lipid peroxidation and oxidative stress intensification, as well as inflammatory and apoptotic markers escalation. Treatment with BCP resulted in modified ECG traces and histological sections. BCP mitigated cardiac markers and lipid peroxidation whereas intensified antioxidant capacity. BCP activated Nrf2, with subsequent HO1 and NQO1 amplification. BCP diminished TLR4/NFκB pathway, which consequently lessened the inflammatory and apoptosis responses. Conclusion: BCP administration was associated with activated Nrf2/HO1/NQO1 and inhibited TLR4/NFκB pathways with subsequent enhanced anti-oxidative capacity and diminished inflammatory and apoptosis responses.
Potential Values of Circulating microRNA-21 to Predict Early Recurrence in Patients with Colorectal Cancer after Treatments
Authors: Hao Yun-Jie , Yang Chih-Yung , Chen Ming-Hsien , Chang Lu-Wey , Lin Chien-Ping , Lo Liang-Chuan , Huang Sheng-Chieh , Lyu You-You , Jiang Jeng-Kai , Tseng Fan-Gang
Published: April 2022

Insufficient prognosis of local recurrence contributes to the poor progression-free survival rate and death in colorectal cancer (CRC) patients. Various biomarkers have been explored in predicting CRC recurrence. This study investigated the expressions of plasma/exosomal microRNA-21 (miR-21) in 113 CRC patients by qPCR, their values of predicting CRC recurrence, and the possibility to improve the prognostic efficacy in early CRC recurrence in stratified patients by combined biomarkers including circulating miR-21s, circulating tumour cells/microemboli (CTCs/CTM), and serum carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9). Expressions of plasma and exosomal miR-21s were significantly correlated (p < 0.0001) in all and late-stage patients, presenting similar correlations with other biomarkers. However, stage IV patients stratified by a high level of exosomal miR-21 and stage I to III patients stratified by a high level of plasma miR-21 displayed significantly worse survival outcomes in predicting CRC recurrence, suggesting their different values to predict CRC recurrence in stratified patients. Comparable and even better performances in predicting CRC recurrence in late-stage patients were found by CTCs/CTM from our blood samples as sensitive biomarkers. Improved prognosing efficacy in CRC recurrence and better outcomes to significantly differentiate recurrence in stratified patients could be obtained by analysing combined biomarkers.
Analysis of COVID-19 Spread in Tokyo through an Agent-Based Model with Data Assimilation
Authors: Sun Chang , Richard Serge , Miyoshi Takemasa , Tsuzu Naohiro
Published: April 2022

In this paper, we introduce an agent-based model together with a particle filter approach to study the spread of COVID-19. Investigations are mainly performed on the metropolis of Tokyo, but other prefectures of Japan are also briefly surveyed. A novel method for evaluating the effective reproduction number is one of the main outcomes of our approach. Other unknown parameters are also evaluated. Uncertain quantities, such as, for example, the probability that an infected agent develops symptoms, are tested and discussed, and the stability of our computations is examined. Detailed explanations are provided for the model and for the assimilation process.
The Agreement of a Two- and a Three-Dimensional Speckle-Tracking Global Longitudinal Strain
Authors: Plášek Jiří , Rychlý Tomáš , Drieniková Diana , Cisovský Ondřej , Grézl Tomáš , Homza Miroslav , Václavík Jan
Published: April 2022

Background: Two-dimensional (2D) and three-dimensional (3D) speckle-tracking echocardiography (STE) enables assessment of myocardial function. Here, we examined the agreement between 2D and 3D STE measurement of a global longitudinal strain (GLS) in patients with normal left ventricle, reduced ejection fraction, and cardiac pacing. Methods: Our analysis included 90 consecutive patients (59% males; average age: 73.2 ± 11.2 years) examined between May 2019–December 2020, with valid 2D and 3D loops for further speckle-tracking strain analysis. Linear regression, Pearson correlation, and a Bland–Altman plot were used to quantify the association between 2D and 3D GLS and related segments, using the 17-segment American Heart Association (AHA) model. Analyses were performed in the entire study group and subgroups. Intra- and inter-observer variability of 2D and 3D GLS measurement was also performed in all participants. Results: We observed a strong correlation between 2D and 3D GLS measurements (R = 0.76, p < 0.001), which was higher in males (R = 0.78, p < 0.001) than females (R = 0.69, p < 0.001). Associated segment correlation was poor (R = 0.2–0.5, p < 0.01). The correlation between 2D and 3D GLS was weaker in individuals with ventricular pacing of >50% (R = 0.62, p < 0.001) than <50% (R = 0.8, p < 0.001), and in patients with LVEF of <35% (R = 0.69, p = 0.002) than >35% (R = 0.72, p < 0.001). Intra-observer variability for 2D and 3D GLS was 2 and 2.3%, respectively. Inter-observer variability for 2D and 3D GLS was 3.8 and 3.6%, respectively Conclusion: Overall 2D and 3D GLS were closely associated but not when analyzed per segment. It seems that GLS comparison is more representative of global shortening than local displacement. Right ventricular pacing and reduced left ventricular ejection fraction were associated with a reduced correlation between 2D and 3D GLS.
Association between Frequency of Central Respiratory Events and Clinical Outcomes in Heart Failure Patients with Sleep Apnea
Authors: Naito Ryo , Kasai Takatoshi , Narui Koji , Momomura Shin-Ichi
Published: April 2022

Heart failure (HF) is a progressive cardiac disorder associated with high mortality and morbidity. Previous studies have shown that sleep apnea (SA) is associated with a poor prognosis in HF patients. When HF coexists with SA, both central and obstructive respiratory events often occur. However, few studies have investigated the association between the frequency of central respiratory events coexisting with obstructive events and clinical outcomes in patients with HF and SA. This was a retrospective observational study. Patients with stable HF, defined as a left ventricular ejection fraction of ≤50%, New York Heart Association class ≥ II, and SA (apnea–hypopnea index of ≥15/h on overnight polysomnography) were enrolled. The primary endpoint was a composite of all-cause death and hospitalization for HF. Overall, 144 patients were enrolled. During a period of 23.4 ± 16 months, 45.8% of patients experienced the outcome. The cumulative event-free survival rates were higher in the central SA-predominant group. Multivariate analyses showed that a greater percentage of central respiratory events was associated with an increased risk of clinical outcomes. In patients with HF and SA, the frequency of central respiratory events was an independent factor for all-cause death and hospitalization for HF.
Corneal Confocal Microscopy Features and Tear Molecular Profile in Study Participants with Discordance between Ocular Surface Disease Clinical Signs and Discomfort
Authors: D’Souza Sharon , Shetty Rohit , Nair Archana Padmanabhan , Agrawal Ruchika , Dickman Mor M. , Khamar Pooja , Nuijts Rudy M. M. A. , Ghosh Arkasubhra , Sethu Swaminathan
Published: April 2022

Various ocular surface conditions such as dry eye disease can present with severe discomfort and pain. However, it is clinically challenging to establish etiology and prescribe correct treatment in patients who have a lot of discordance between symptoms and signs. To understand the basis of such discordance, we stratified subjects with ocular surface pain based on concordance between the severity of signs and symptoms and evaluated corneal structural features and tear molecular factors. All subjects underwent slit lamp examination, dry eye evaluation, and ocular surface disease index (OSDI) scoring. Subjects were stratified into group 1—without symptoms or clinical signs; group 2—without symptoms but with signs; group 3—with similar severity of symptoms and signs; and group 4—with symptom severity greater than that of the signs. Laser scanning in vivo confocal microscopy (IVCM) and tear fluid analysis for soluble factors by multiplex ELISA was performed for all subjects. Patients with a higher grade of symptoms and signs showed increased corneal dendritic cell (cDC) density (p < 0.05) which was more pronounced in subjects with discordance between the symptoms and signs (group 4). A significantly higher proportion of microneuroma-like structures and cDC were observed in group 4. IL-17A levels were significantly elevated in the tears of subjects with more discomfort. Our results demonstrate that corneal IVCM and the measurement of tear film factors can help clinicians improve diagnosis and treatment choice. Stratifying patients with ocular surface discomfort on the basis of discordance between symptoms and clinical signs may help identify patients who need additional adjunctive targeted therapy to resolve their condition.
A Disseminated Mycobacterium Abscessus Infection in a Patient Affected by Pulmonary Graft versus Host Disease: Case Report with a Revision of Literature
Authors: Bernardelli Andrea , Schena Alberto , Savoldi Alessia , Colato Chiara , Baretta Valentina , D’Alessandro Emiliano , Zamboni Giulia , Shoushtari Zadeh Naseri Mehrdad , Favaro Flavio , Peracchi Marta , Schena Donatella , Andreini Angelo , Cesaro Simone , Tecchio Cristina
Published: April 2022

Mycobacterium abscessus complex, hereinafter Mab, is a taxonomic group of rapidly growing, nontuberculous mycobacteria (NTM). Despite major advances in understanding virulence, pathogenicity and mechanism of antibiotic resistance, Mab remains a significant cause of pulmonary and extra-pulmonary disease. Herein, we describe a disseminated, macrolide-resistant, Mab subspecies abscessus infection occurring in a severely immune-compromised 34-year-old allotransplanted female patient affected by pulmonary chronic graft versus host disease (cGVHD). The infection was characterized by hematogenous spread, and besides lungs, it involved skin, and soft tissues, resulting in a highly debilitating, painful, and finally fatal disease. Our case describes the severe impact of Mab infections in the setting of allogeneic hematopoietic stem cells transplant (alloHSCT) and related complications. It also highlights the unmet need of preventive and surveillance measures together with the urgency of developing effective vaccines and drugs against emerging NTM. The scarce literature regarding Mab infections in alloHSCT patients is also reviewed.
The Association between Vision Impairment and Depression: A Systematic Review of Population-Based Studies
Authors: Virgili Gianni , Parravano Mariacristina , Petri Davide , Maurutto Erica , Menchini Francesca , Lanzetta Paolo , Varano Monica , Mariotti Silvio Paolo , Cherubini Antonio , Lucenteforte Ersilia
Published: April 2022

We conducted a systematic review and meta-analysis to investigate whether depression is associated with vision impairment (VI) in population-based studies in adults. MEDLINE and EMBASE were searched, from inception to June 2020. Studies were included if they provided two-by-two data for calculating the OR of association between VI and depression, or crude and/or an adjusted odds ratio (OR) with a corresponding 95% confidence interval (CI) were reported. The proportion of VI and depression was also extracted. ORs were pooled using random-effect models, proportions were pooled using random intercepts logistic regression models. Overall, 29 articles (31 studies) were included: of those, 18 studies used survey data (622,312 participants), 10 used clinical examination data (69,178 participants), and 3 used administrative databases (48,162,290 participants). The proportion of depression (95%CI) was 0.17 (0.13–0.22) overall and 0.27 (0.21–0.33) in VI subjects. The proportion of VI was 0.10 (0.07–0.16) overall and 0.20 (0.13–0.29) in depressed subjects. The association between VI and depression was direct: crude ORs were 1.89 (1.51–2.37) for survey data, 2.17 (1.76–2.67) for clinical examination data, and 3.34 (1.01–11.11) for administrative databases; adjusted ORs were 1.75 (1.34–2.30), 1.59 (1.22–1.96), and 2.47 (0.97–6.33), respectively. In conclusion, VI and depression are prevalent morbidities and should be actively sought when either is identified, especially in older adults.
Nutritional and Functional Impact of Acute SARS-CoV-2 Infection in Hospitalized Patients
Authors: Gómez-Uranga Angie , Guzmán-Martínez Javier , Esteve-Atiénzar Pedro Jesús , Wikman-Jorgensen Philip , Núñez-Cruz Juan Manuel , Espinosa-del-Barrio Leticia , Hernández-Isasi Isidro , Pomares-Gómez Francisco J. , Perelló-Camacho Eva , Fernández-García Nuria , Sánchez-Miralles Ángel , Giner-Galvañ Vicente
Published: April 2022

Aim: To assess the prevalence of malnutrition, frailty, and sarcopenia and the relationships between them in patients hospitalized for COVID-19. Methods: This was a cross-sectional study of the prevalence, determinants, and associations between malnutrition (GLIM 2019 criteria), sarcopenia (SARC-F scale, dynamometry, and calf circumference), and frailty (FRAIL scale) upon discharge following hospitalization for COVID 19. Results: A total of 101 patients (67.3% men, mean age 66.3 years) were recruited. Malnutrition was diagnosed in 49.5%, sarcopenia in 32.7%, and frailty in 28.7% of patients. Of the patients with malnutrition, 48% were also sarcopenic, and 42% were frail. There was a significant association between malnutrition and the severity of pneumonia according to the CURB-65 scale (odds ratio [OR] 2.61, p = 0.036), between sarcopenia and a Barthel score lower than 60 points (OR 29.52, p < 0.001), and between frailty and both a Barthel score lower than 60 points (OR 32.27, p < 0.001) and a length of hospital stay of over 30 days (OR 9.11, p = 0.008). Conclusions: Malnutrition, sarcopenia, and frailty are prevalent and interrelated entities in patients hospitalized for acute SARS CoV-2 infection, especially in patients with greater baseline functional impairment prior to admission and a higher infection severity.
Comparing the Time-Dependent Evolution of Microcirculation in Gracilis vs. ALT Flaps Using Laser-Doppler Flowmetry and Tissue-Spectrometry
Authors: Moellhoff Nicholas , Heidekrueger Paul , Frank Konstantin , Pistek Svenja , Alt Verena , Giunta Riccardo , Ehrl Denis
Published: April 2022

Postoperative free flap monitoring is considered a key component of care after microsurgical reconstruction. To achieve successful flap salvage after surgical revision, early recognition of vascular compromise is required. The aim of this study was to assess and compare the time-dependent evolution of microcirculation in gracilis muscle (GM) and anterolateral thigh (ALT) flaps. This study included continuous measurements of blood flow (flow), hemoglobin oxygenation (SO2) and the relative amount of hemoglobin (rHb) using laser-doppler flowmetry and tissue-spectrometry (O2C, LEA Medizintechnik, Gießen, Germany) over a time-period of 72 h. Microcirculation was assessed in a total of 66 viable free flaps (GM n = 40; ALT n = 26). A statistically significant positive correlation between time post-anastomosis and microvascular flow was found for both GM and ALT flaps with rs = 0.384 (p < 0.001) and rs = 0.178 (p = 0.015), respectively. No significant positive or negative correlations between time post-anastomosis and SO2 were found for both GM and ALT flaps with rs = 0.052 (p = 0.387) and rs = −0.018 (p = 0.805), respectively. Overall, a significant negative correlation between time post-anastomosis and rHb was found for GM flaps with rs = −0.140 (p = 0.019). For ALT flaps, no significant positive or negative correlation was found with rs = −0.011 (p = 0.887). Microcirculation differs in different flap entities, and surgeons should be aware of these differences in order to correctly evaluate and classify the values of flow, SO2 and rHb obtained when using the O2C device for postoperative monitoring.
How Is Body Composition and Nutrition Status Associated with Erythropoietin Response in Hemodialyzed Patients? A Single-Center Prospective Cohort Study
Authors: Feret Wiktoria , Safranow Krzysztof , Ciechanowski Kazimierz , Kwiatkowska Ewa
Published: April 2022

Background: Anemia is the most common finding in patients with end-stage kidney disease undergoing renal replacement therapy. A certain percentage of patients does not respond adequately to erythropoietin (EPO) treatment, not being able to reach desirable hemoglobin levels even when treated with large-dose EPO and intravenous/oral iron. In our study, we wanted to further investigate how nutritional status is associated with erythropoietin responsiveness. To quantify EPO response, we used the Erythropoietin Resistance Index (ERI), which is defined as the weekly weight-adjusted dose of EPO divided by the hemoglobin level. Patients and methods: Seventy-eight patients undergoing hemodialysis were included. All of them were measured by a SECA mBCA body composition analyzer and evaluated by Kalantar-Zadeh’s MIS score. Routine biochemical tests were also taken into account. The Shapiro-Wilk test was used to study the distributions of quantitative variables, which were significantly different from normal (p < 0.05). We used nonparametric Mann-Whitney U-test to compare groups. Correlations were studied by means of Spearman’s rank correlation coefficient. Bonferroni correction for multiple testing was performed. To find independent determinants of ERI, we additionally performed multivariate analysis using the General Linear Model (GLM). Results: In terms of body composition, factors that are associated with high ERI are low BMI, low fat mass, low visceral fat volume, high total body water percentage, low phase angle and low fat-free mass. In addition to body composition parameters, total MIS score and IL-6 serum levels correlated positively with ERI value. IL-6 was an independent determinant of ERI value, based on multivariate analysis. After correction for multiple analysis, BMI and eGFR both remained significant factors associated with EPO response. Conclusions: It seems crucial to prevent inflammatory malnutrition as a part of a holistic approach to anemia treatment in dialysis patients.