bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracing Genealogies of Mixedness: Social Representations and Definitions of “Eurasian” in Singapore
Authors: Rocha Zarine L. , Yeoh Brenda S. A.
Published: May 2021

Social representations theory provides a key lens through which to approach mixed racial and ethnic identities. The concept and contextual histories of “mixedness” highlight how meanings are ascribed and constructed, and social representations of mixed identities shape and are shaped by what it means to be mixed. This paper explores mixedness in Singapore from a social representations perspective, drawing out and comparing the state representations of the Eurasian community, and social experiences of mixedness. Utilizing data from 30 interviews with participants who self-describe as Eurasian, the paper explores the interactions between historical and contemporary state representations of mixedness and popular representations of Eurasians as a mixed racial/ethnic group in the diverse and racialized context of Singapore. By tracing the genealogy of Eurasian identity (and mixedness) in this context, it contributes to the theoretical development around social representations of mixedness, and how the constructed realities of singular and/or mixed identities interact and develop.
Tobacco Use and Risk Factors for Hypertensive Individuals in Kenya
Authors: Walekhwa Silvia Nanjala , Kisa Adnan
Published: May 2021

This study aimed to examine the association between hypertension and tobacco use as well as other known hypertensive risk factors (BMI, waist–hip ratio, alcohol consumption, physical activity, and socio-economic factors among adults) in Kenya. The study utilized the 2015 Kenya STEPs survey (adults aged 18–69) and investigated the association between tobacco use and hypertension. Descriptive statistics, correlation, frequencies, and regression (linear and logistic) analyses were used to execute the statistical analysis. The study results indicate a high prevalence of hypertension in association with certain risk factors—body mass index (BMI), alcohol, waist–hip ratio (WHR), and tobacco use—that were higher in males than females among the hypertensive group. Moreover, the findings noted an exceptionally low awareness level of hypertension in the general population. BMI, age, WHR, and alcohol use were prevalent risks of all three outcomes: hypertension, systolic blood pressure, and diastolic blood pressure. Healthcare authorities and policymakers can employ these findings to lower the burden of hypertension by developing health promotion and intervention policies.
The Research on Patient Satisfaction with Remote Healthcare Prior to and during the COVID-19 Pandemic
Authors: Hawrysz Liliana , Gierszewska Grażyna , Bitkowska Agnieszka
Published: May 2021

The issue of research on patient satisfaction with healthcare services took on a completely new dimension due to the COVID-19 pandemic and the developing telehealth services. This results from the fact that during the pandemic, remote healthcare was often the only possible form of care provision to the patient. The COVID-19 pandemic has substantially accelerated the implementation of remote healthcare in healthcare institutions and made it an essential tool for providing healthcare services. The objective of the literature review was to study the research on patient satisfaction with remote healthcare services prior to and during the pandemic. The study featured a literature review of electronic databases, such as: Medline, ProQuest, PubMED, Ebsco, Google Scholar, WoS. The identified empirical papers were classified in two groups concerning the research on patient satisfaction prior to and during the COVID-19 pandemic, and were divided and descriptively synthesised. Certain limitations to the methodical quality of the research were demonstrated as result of the conducted analyses. It was also ascertained that researchers lack clarity on the method of defining and measuring satisfaction prior to and during the COVID-19 pandemic.
What Is the Shape of Geographical Time-Space? A Three-Dimensional Model Made of Curves and Cones
Authors: L’Hostis Alain , Abdou Farouk
Published: May 2021

Geographical time-spaces exhibit a series of properties, including space inversion, that turns any representation effort into a complex task. In order to improve the legibility of the representation and leveraging the advances of three-dimensional computer graphics, the aim of the study is to propose a new method extending time-space relief cartography introduced by Mathis and L’Hostis. The novelty of the model resides in the use of cones to describing the terrestrial surface instead of graph faces, and in the use of curves instead of broken segments for edges. We implement the model on the Chinese space. The Chinese geographical time-space of reference year 2006 is produced by the combination and the confrontation of the fast air transport system and of the 7.5-times slower road transport system. Slower, short range flights are represented as curved lines above the earth surface with longer length than the geodesic, in order to account for a slower speed. The very steep slope of cones expresses the relative difficulty of crossing terrestrial time-space, as well as the comparably extreme efficiency of long-range flights for moving between cities. Finally, the whole image proposes a coherent representation of the geographical time-space where fast city-to-city transport is combined with slow terrestrial systems that allow one to reach any location.
Combination Chemotherapy with Cisplatin and Chloroquine: Effect of Encapsulation in Micelles Formed by Self-Assembling Hybrid Dendritic–Linear–Dendritic Block Copolymers
Authors: González-Pastor Rebeca , Lancelot Alexandre , Morcuende-Ventura Violeta , San Anselmo María , Sierra Teresa , Serrano José L. , Martin-Duque Pilar
Published: May 2021

Clinical outcomes of conventional drug combinations are not ideal due to high toxicity to healthy tissues. Cisplatin (CDDP) is the standard component for many cancer treatments, yet its principal dose-limiting side effect is nephrotoxicity. Thus, CDDP is commonly used in combination with other drugs, such as the autophagy inhibitor chloroquine (CQ), to enhance tumor cell killing efficacy and prevent the development of chemoresistance. In addition, nanocarrier-based drug delivery systems can overcome chemotherapy limitations, decreasing side effects and increasing tumor accumulation. The aim of this study was to evaluate the toxicity of CQ and CDDP against tumor and non-tumor cells when used in a combined treatment. For this purpose, two types of micelles based on Pluronic® F127 hybrid dendritic–linear–dendritic block copolymers (HDLDBCs) modified with polyester or poly(esteramide) dendrons derived from 2,2′-bis(hydroxymethyl)propionic acid (HDLDBC-bMPA) or 2,2′-bis(glycyloxymethyl)propionic acid (HDLDBC-bGMPA) were explored as delivery nanocarriers. Our results indicated that the combined treatment with HDLDBC-bMPA(CQ) or HDLDBC-bGMPA(CQ) and CDDP increased cytotoxicity in tumor cells compared to the single treatment with CDDP. Encapsulations demonstrated less short-term cytotoxicity individually or when used in combination compared to the free drugs. However, and more importantly, a low degree of cytotoxicity against non-tumor cells was maintained, even when drugs were given simultaneously.
Distinct Concentration-Dependent Molecular Pathways Regulate Bone Cell Responses to Cobalt and Chromium Exposure from Joint Replacement Prostheses
Authors: Shah Karan M. , Dunning Mark J. , Gartland Alison , Wilkinson J. Mark
Published: May 2021

Systemic cobalt (Co) and chromium (Cr) concentrations may be elevated in patients with metal joint replacement prostheses. Several studies have highlighted the detrimental effects of this exposure on bone cells in vitro, but the underlying mechanisms remain unclear. In this study, we use whole-genome microarrays to comprehensively assess gene expression in primary human osteoblasts, osteoclast precursors and mature resorbing osteoclasts following exposure to clinically relevant circulating versus local periprosthetic tissue concentrations of Co2+ and Cr3+ ions and CoCr nanoparticles. We also describe the gene expression response in osteoblasts on routinely used prosthesis surfaces in the presence of metal exposure. Our results suggest that systemic levels of metal exposure have no effect on osteoblasts, and primarily inhibit osteoclast differentiation and function via altering the focal adhesion and extracellular matrix interaction pathways. In contrast, periprosthetic levels of metal exposure inhibit both osteoblast and osteoclast activity by altering HIF-1α signaling and endocytic/cytoskeletal genes respectively, as well as increasing inflammatory signaling with mechanistic implications for adverse reactions to metal debris. Furthermore, we identify gene clusters and KEGG pathways for which the expression correlates with increasing Co2+:Cr3+ concentrations, and has the potential to serve as early markers of metal toxicity. Finally, our study provides a molecular basis for the improved clinical outcomes for hydroxyapatite-coated prostheses that elicit a pro-survival osteogenic gene signature compared to grit-blasted and plasma-sprayed titanium-coated surfaces in the presence of metal exposure.
The Chemistry of the Ketogenic Diet: Updates and Opportunities in Organic Synthesis
Authors: Williams Michael Scott , Turos Edward
Published: May 2021

The high-fat, low-carbohydrate (ketogenic) diet has grown in popularity in the last decade as a weight loss tool. Research into the diet’s effects on the body have revealed a variety of other health benefits. The use of exogenous ketone supplements to confer the benefits of the diet without strict adherence to it represents an exciting new area of focus. Synthetic ketogenic compounds are of particular interest that has received very little emphasis and is an untapped area of focus for chemical synthesis. In this review, we summarize the chemical basis for ketogenicity and opportunities for further advancement of the field.
The Potential Protective Role of RUNX1 in Nonalcoholic Fatty Liver Disease
Authors: Bertran Laia , Pastor Angela , Portillo-Carrasquer Marta , Binetti Jessica , Aguilar Carmen , Martínez Salomé , Vives Margarita , Sabench Fàtima , Porras José Antonio , Riesco David , Del Castillo Daniel , Richart Cristóbal , Auguet Teresa
Published: May 2021

The pathogenic mechanisms underlying nonalcoholic fatty liver disease (NAFLD) are beginning to be understood. RUNX1 is involved in angiogenesis, which is crucial in inflammation, but its role in nonalcoholic steatohepatitis (NASH) remains unclear. The aim of this study was to analyze RUNX1 mRNA hepatic and jejunal abundance in women with morbid obesity (MO) and NAFLD. RUNX1, lipid metabolism-related genes, and TLRs in women with MO and normal liver (NL, n = 28), NAFLD (n = 41) (simple steatosis (SS, n = 24), or NASH (n = 17)) were analyzed by RT-qPCR. The RUNX1 hepatic expression was higher in SS than in NL or NASH, as likewise confirmed by immunohistochemistry. An increased expression of hepatic FAS was found in NAFLD. Hepatic RUNX1 correlated positively with FAS. There were no significant differences in the jejunum RUNX1 expressions in the different groups. Jejunal FXR expression was lower in NASH than in NL, while the TLR9 expression increased as NAFLD progressed. Jejunal RUNX1 correlated positively with jejunal PPARγ, TLR4, and TLR5. In summary, the hepatic expression of RUNX1 seems to be involved in the first steps of the NAFLD process; however, in NASH, it seems to be downregulated. Our findings provide important insights into the role of RUNX1 in the context of NAFLD/NASH, suggesting a protective role.
Development of Phosphodiesterase–Protein-Kinase Complexes as Novel Targets for Discovery of Inhibitors with Enhanced Specificity
Authors: Tulsian Nikhil K. , Sin Valerie Jia-En , Koh Hwee-Ling , Anand Ganesh S.
Published: May 2021

Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to modulate multiple signaling events in cells. PDEs are recognized to actively associate with cyclic nucleotide receptors (protein kinases, PKs) in larger macromolecular assemblies referred to as signalosomes. Complexation of PDEs with PKs generates an expanded active site that enhances PDE activity. This facilitates signalosome-associated PDEs to preferentially catalyze active hydrolysis of cyclic nucleotides bound to PKs and aid in signal termination. PDEs are important drug targets, and current strategies for inhibitor discovery are based entirely on targeting conserved PDE catalytic domains. This often results in inhibitors with cross-reactivity amongst closely related PDEs and attendant unwanted side effects. Here, our approach targeted PDE–PK complexes as they would occur in signalosomes, thereby offering greater specificity. Our developed fluorescence polarization assay was adapted to identify inhibitors that block cyclic nucleotide pockets in PDE–PK complexes in one mode and disrupt protein-protein interactions between PDEs and PKs in a second mode. We tested this approach with three different systems—cAMP-specific PDE8–PKAR, cGMP-specific PDE5–PKG, and dual-specificity RegA–RD complexes—and ranked inhibitors according to their inhibition potency. Targeting PDE–PK complexes offers biochemical tools for describing the exquisite specificity of cyclic nucleotide signaling networks in cells.
Protein Kinase C Activation Drives a Differentiation Program in an Oligodendroglial Precursor Model through the Modulation of Specific Biological Networks
Authors: Damato Marina , Cardon Tristan , Wisztorski Maxence , Fournier Isabelle , Pieragostino Damiana , Cicalini Ilaria , Salzet Michel , Vergara Daniele , Maffia Michele
Published: May 2021

Protein kinase C (PKC) activation induces cellular reprogramming and differentiation in various cell models. Although many effectors of PKC physiological actions have been elucidated, the molecular mechanisms regulating oligodendrocyte differentiation after PKC activation are still unclear. Here, we applied a liquid chromatography–mass spectrometry (LC–MS/MS) approach to provide a comprehensive analysis of the proteome expression changes in the MO3.13 oligodendroglial cell line after PKC activation. Our findings suggest that multiple networks that communicate and coordinate with each other may finally determine the fate of MO3.13 cells, thus identifying a modular and functional biological structure. In this work, we provide a detailed description of these networks and their participating components and interactions. Such assembly allows perturbing each module, thus describing its physiological significance in the differentiation program. We applied this approach by targeting the Rho-associated protein kinase (ROCK) in PKC-activated cells. Overall, our findings provide a resource for elucidating the PKC-mediated network modules that contribute to a more robust knowledge of the molecular dynamics leading to this cell fate transition.
Heterogeneity of Colorectal Cancer Progression: Molecular Gas and Brakes
Authors: Gaiani Federica , Marchesi Federica , Negri Francesca , Greco Luana , Malesci Alberto , de’Angelis Gian Luigi , Laghi Luigi
Published: May 2021

The review begins with molecular genetics, which hit the field unveiling the involvement of oncogenes and tumor suppressor genes in the pathogenesis of colorectal cancer (CRC) and uncovering genetic predispositions. Then the notion of molecular phenotypes with different clinical behaviors was introduced and translated in the clinical arena, paving the way to next-generation sequencing that captured previously unrecognized heterogeneity. Among other molecular regulators of CRC progression, the extent of host immune response within the tumor micro-environment has a critical position. Translational sciences deeply investigated the field, accelerating the pace toward clinical transition, due to its strong association with outcomes. While the perturbation of gut homeostasis occurring in inflammatory bowel diseases can fuel carcinogenesis, micronutrients like vitamin D and calcium can act as brakes, and we discuss underlying molecular mechanisms. Among the components of gut microbiota, Fusobacterium nucleatum is over-represented in CRC, and may worsen patient outcome. However, any translational knowledge tracing the multifaceted evolution of CRC should be interpreted according to the prognostic and predictive frame of the TNM-staging system in a perspective of clinical actionability. Eventually, we examine challenges and promises of pharmacological interventions aimed to restrain disease progression at different disease stages.
Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D
Authors: Peng Ming-Yieh , Liu Wen-Chih , Zheng Jing-Quan , Lu Chien-Lin , Hou Yi-Chou , Zheng Cai-Mei , Song Jenn-Yeu , Lu Kuo-Cheng , Chao You-Chen
Published: May 2021

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still an ongoing global health crisis. Immediately after the inhalation of SARS-CoV-2 viral particles, alveolar type II epithelial cells harbor and initiate local innate immunity. These particles can infect circulating macrophages, which then present the coronavirus antigens to T cells. Subsequently, the activation and differentiation of various types of T cells, as well as uncontrollable cytokine release (also known as cytokine storms), result in tissue destruction and amplification of the immune response. Vitamin D enhances the innate immunity required for combating COVID-19 by activating toll-like receptor 2. It also enhances antimicrobial peptide synthesis, such as through the promotion of the expression and secretion of cathelicidin and β-defensin; promotes autophagy through autophagosome formation; and increases the synthesis of lysosomal degradation enzymes within macrophages. Regarding adaptive immunity, vitamin D enhances CD4+ T cells, suppresses T helper 17 cells, and promotes the production of virus-specific antibodies by activating T cell-dependent B cells. Moreover, vitamin D attenuates the release of pro-inflammatory cytokines by CD4+ T cells through nuclear factor κB signaling, thereby inhibiting the development of a cytokine storm. SARS-CoV-2 enters cells after its spike proteins are bound to angiotensin-converting enzyme 2 (ACE2) receptors. Vitamin D increases the bioavailability and expression of ACE2, which may be responsible for trapping and inactivating the virus. Activation of the renin–angiotensin–aldosterone system (RAS) is responsible for tissue destruction, inflammation, and organ failure related to SARS-CoV-2. Vitamin D inhibits renin expression and serves as a negative RAS regulator. In conclusion, vitamin D defends the body against SARS-CoV-2 through a novel complex mechanism that operates through interactions between the activation of both innate and adaptive immunity, ACE2 expression, and inhibition of the RAS system. Multiple observation studies have shown that serum concentrations of 25 hydroxyvitamin D are inversely correlated with the incidence or severity of COVID-19. The evidence gathered thus far, generally meets Hill’s causality criteria in a biological system, although experimental verification is not sufficient. We speculated that adequate vitamin D supplementation may be essential for mitigating the progression and severity of COVID-19. Future studies are warranted to determine the dosage and effectiveness of vitamin D supplementation among different populations of individuals with COVID-19.
A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth
Authors: Chimento Adele , Santarsiero Anna , Iacopetta Domenico , Ceramella Jessica , De Luca Arianna , Infantino Vittoria , Parisi Ortensia Ilaria , Avena Paola , Bonomo Maria Grazia , Saturnino Carmela , Sinicropi Maria Stefania , Pezzi Vincenzo
Published: May 2021

Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer.
The Impact of the “Osteo” Component of Osteosarcopenia on Fragility Fractures in Post-Menopausal Women
Authors: Lin Yen-Huai , Shih Yu-Tai , Teng Michael Mu Huo
Published: May 2021

Osteosarcopenia, the coexistence of bone and muscle loss, is common in older adults, but its definition lacks international consensus. This cross-sectional study (n = 1199 post-menopausal women) aimed to determine the association between osteosarcopenia and fragility fractures and to investigate the impact of the definition of the “osteo” component. Bone mineral density and bone microarchitecture were measured by dual-energy X-ray absorptiometry and the trabecular bone score (TBS), respectively. The “osteo” component of osteosarcopenia was classified as osteoporosis (T-score ≤ −2.5 SD), osteopenia/osteoporosis (T-score < −1 SD), and high-fracture-risk osteopenia (−2.5 SD < T-score < −1 SD)/osteoporosis (T-score ≤ −2.5 SD). The Fracture Risk Assessment Tool was used to identify high-fracture-risk osteopenia. Altogether, 30.3%, 32.2%, 14.4%, and 23.1% of participants had osteosarcopenia, osteoporosis alone, sarcopenia alone, and neither condition, respectively. The odds ratios between osteosarcopenia and fragility fractures were 3.70 (95% CI: 1.94–7.04) for osteosarcopenia, 2.48 (95% CI: 1.30–4.71) for osteoporosis alone, and 1.87 (95% CI: 0.84–4.14) for sarcopenia alone. Women with osteosarcopenia also had lower TBS, indicating worse bone microarchitecture. In conclusion, women with osteosarcopenia were more likely to have previously sustained a fracture compared to those without osteosarcopenia, with sarcopenia alone, and with osteoporosis alone. The relationship between osteosarcopenia and fracture risk may be best identified when considering high-fracture-risk osteopenia and osteoporosis.
Tissue-Nonspecific Alkaline Phosphatase in Central Nervous System Health and Disease: A Focus on Brain Microvascular Endothelial Cells
Authors: Nwafor Divine C. , Brichacek Allison L. , Ali Ahsan , Brown Candice M.
Published: May 2021

Tissue-nonspecific alkaline phosphatase (TNAP) is an ectoenzyme bound to the plasma membranes of numerous cells via a glycosylphosphatidylinositol (GPI) moiety. TNAP’s function is well-recognized from earlier studies establishing its important role in bone mineralization. TNAP is also highly expressed in cerebral microvessels; however, its function in brain cerebral microvessels is poorly understood. In recent years, few studies have begun to delineate a role for TNAP in brain microvascular endothelial cells (BMECs)—a key component of cerebral microvessels. This review summarizes important information on the role of BMEC TNAP, and its implication in health and disease. Furthermore, we discuss current models and tools that may assist researchers in elucidating the function of TNAP in BMECs.
G-Protein Coupled Receptors (GPCRs): Signaling Pathways, Characterization, and Functions in Insect Physiology and Toxicology
Authors: Liu Nannan , Wang Yifan , Li Ting , Feng Xuechun
Published: May 2021

G-protein-coupled receptors (GPCRs) are known to play central roles in the physiology of many organisms. Members of this seven α-helical transmembrane protein family transduce the extracellular signals and regulate intracellular second messengers through coupling to heterotrimeric G-proteins, adenylate cyclase, cAMPs, and protein kinases. As a result of the critical function of GPCRs in cell physiology and biochemistry, they not only play important roles in cell biology and the medicines used to treat a wide range of human diseases but also in insects’ physiological functions. Recent studies have revealed the expression and function of GPCRs in insecticide resistance, improving our understanding of the molecular complexes governing the development of insecticide resistance. This article focuses on the review of G-protein coupled receptor (GPCR) signaling pathways in insect physiology, including insects’ reproduction, growth and development, stress responses, feeding, behaviors, and other physiological processes. Hormones and polypeptides that are involved in insect GPCR regulatory pathways are reviewed. The review also gives a brief introduction of GPCR pathways in organisms in general. At the end of the review, it provides the recent studies on the function of GPCRs in the development of insecticide resistance, focusing in particular on our current knowledge of the expression and function of GPCRs and their downstream regulation pathways and their roles in insecticide resistance and the regulation of resistance P450 gene expression. The latest insights into the exciting technological advances and new techniques for gene expression and functional characterization of the GPCRs in insects are provided.
Nucleic Acid Delivery with Red-Blood-Cell-Based Carriers
Authors: Della Pelle Giulia , Kostevšek Nina
Published: May 2021

Gene therapy has the potential to become a staple of 21st-century medicine. However, to overcome the limitations of existing gene-delivery therapies, that is, poor stability and inefficient and delivery and accumulation of nucleic acids (NAs), safe drug-delivery systems (DDSs) allowing the prolonged circulation and expression of the administered genes in vivo are needed. In this review article, the development of DDSs over the past 70 years is briefly described. Since synthetic DDSs can be recognized and eliminated as foreign substances by the immune system, new approaches must be found. Using the body’s own cells as DDSs is a unique and exciting strategy and can be used in a completely new way to overcome the critical limitations of existing drug-delivery approaches. Among the different circulatory cells, red blood cells (RBCs) are the most abundant and thus can be isolated in sufficiently large quantities to decrease the complexity and cost of the treatment compared to other cell-based carriers. Therefore, in the second part, this article describes 70 years of research on the development of RBCs as DDSs, covering the most important RBC properties and loading methods. In the third part, it focuses on RBCs as the NA delivery system with advantages and drawbacks discussed to decide whether they are suitable for NA delivery in vivo.
Fluorescence Study of Riboflavin Interactions with Graphene Dispersed in Bioactive Tannic Acid
Authors: San Andrés María Paz , Baños-Cabrera Marina , Gutiérrez-Fernández Lucía , Díez-Pascual Ana María , Vera-López Soledad
Published: May 2021

The potential of tannic acid (TA) as a dispersing agent for graphene (G) in aqueous solutions and its interaction with riboflavin have been studied under different experimental conditions. TA induces quenching of riboflavin fluorescence, and the effect is stronger with increasing TA concentration, due to π-π interactions through the aromatic rings, and hydrogen bonding interactions between the hydroxyl moieties of both compounds. The influence of TA concentration, the pH, and the G/TA weight ratio on the quenching magnitude, have been studied. At a pH of 4.1, G dispersed in TA hardly influences the riboflavin fluorescence, while at a pH of 7.1, the nanomaterial interacts with riboflavin, causing an additional quenching to that produced by TA. When TA concentration is kept constant, quenching of G on riboflavin fluorescence depends on both the G/TA weight ratio and the TA concentration. The fluorescence attenuation is stronger for dispersions with the lowest G/TA ratios, since TA is the main contributor to the quenching effect. Data obey the Stern–Volmer relationship up to TA 2.0 g L−1 and G 20 mg L−1. Results demonstrate that TA is an effective dispersant for graphene-based nanomaterials in liquid medium and a green alternative to conventional surfactants and synthetic polymers for the determination of biomolecules.
COVID-19 Mortality in English Neighborhoods: The Relative Role of Socioeconomic and Environmental Factors
Authors: Congdon Peter
Published: May 2021

Factors underlying neighborhood variation in COVID-19 mortality are important to assess in order to prioritize resourcing and policy intervention. As well as characteristics of area populations, such as health status and ethnic mix, it is important to assess the role of more specifically environmental variables (e.g., air quality, green space access). The analysis of this study focuses on neighborhood mortality variations during the first wave of the COVID-19 epidemic in England against a range of postulated area risk factors, both socio-demographic and environmental. We assess mortality gradients across levels of each risk factor and use regression methods to control for multicollinearity and spatially correlated unobserved risks. An analysis of spatial clustering is based on relative mortality risks estimated from the regression. We find mortality gradients in most risk factors showing appreciable differences in COVID mortality risk between English neighborhoods. A regression analysis shows that after allowing for health deprivation, ethnic mix, and ethnic segregation, environment (especially air quality) is an important influence on COVID mortality. Hence, environmental influences on COVID mortality risk in the UK first wave are substantial, after allowing for socio-demographic factors. Spatial clustering of high mortality shows a pronounced metropolitan-rural contrast, reflecting especially ethnic composition and air quality.
The Aging Vasculature: Glucose Tolerance, Hypoglycemia and the Role of the Serum Response Factor
Authors: Aberdeen Hazel , Battles Kaela , Taylor Ariana , Garner-Donald Jeranae , Davis-Wilson Ana , Rogers Bryan T. , Cavalier Candice , Williams Emmanuel D.
Published: May 2021

The fastest growing demographic in the U.S. at the present time is those aged 65 years and older. Accompanying advancing age are a myriad of physiological changes in which reserve capacity is diminished and homeostatic control attenuates. One facet of homeostatic control lost with advancing age is glucose tolerance. Nowhere is this more accentuated than in the high proportion of older Americans who are diabetic. Coupled with advancing age, diabetes predisposes affected subjects to the onset and progression of cardiovascular disease (CVD). In the treatment of type 2 diabetes, hypoglycemic episodes are a frequent clinical manifestation, which often result in more severe pathological outcomes compared to those observed in cases of insulin resistance, including premature appearance of biomarkers of senescence. Unfortunately, molecular mechanisms of hypoglycemia remain unclear and the subject of much debate. In this review, the molecular basis of the aging vasculature (endothelium) and how glycemic flux drives the appearance of cardiovascular lesions and injury are discussed. Further, we review the potential role of the serum response factor (SRF) in driving glycemic flux-related cellular signaling through its association with various proteins.
Frequency and Effectiveness of Empirical Anti-TNF Dose Intensification in Inflammatory Bowel Disease: Systematic Review with Meta-Analysis
Authors: Guberna Laura , Nyssen Olga P. , Chaparro María , Gisbert Javier P.
Published: May 2021

Loss of response to antitumor necrosis factor (anti-TNF) therapies in inflammatory bowel disease occurs in a high proportion of patients. Our aim was to evaluate the loss of response to anti-TNF therapy, considered as the need for dose intensification (DI), DI effectiveness and the possible variables influencing its requirements. Bibliographical searches were performed. Selection: prospective and retrospective studies assessing DI in Crohn’s disease and ulcerative colitis patients treated for at least 12 weeks with an anti-TNF drug. Exclusion criteria: studies using anti-TNF as a prophylaxis for the postoperative recurrence in Crohn’s disease or those where DI was based on therapeutic drug monitoring. Data synthesis: effectiveness by intention-to-treat (random effects model). Data were stratified by medical condition (ulcerative colitis vs. Crohn’s disease), anti-TNF drug and follow-up. Results: One hundred and seventy-three studies (33,241 patients) were included. Overall rate of the DI requirement after 12 months was 28% (95% CI 24–32, I2 = 96%, 41 studies) in naïve patients and 39% (95% CI 31–47, I2 = 86%, 18 studies) in non-naïve patients. The DI requirement rate was higher both in those with prior anti-TNF exposure (p = 0.01) and with ulcerative colitis (p = 0.02). The DI requirement rate in naïve patients after 36 months was 35% (95% CI 28–43%; I2 = 98%; 18 studies). The overall short-term response and remission rates of empirical DI in naïve patients were 63% (95% CI 48–78%; I2 = 99%; 32 studies) and 48% (95% CI: 39–58%; I2 = 92%; 25 studies), respectively. The loss of response to anti-TNF agents―and, consequently, DI―occurred frequently in inflammatory bowel disease (approximately in one-fourth at one year and in one-third at 3 years). Empirical DI was a relatively effective therapeutic option.
Impact of Operative Timing in Infective Endocarditis with Cerebral Embolism—The Risk of Intermediate Deterioration
Authors: Dashkevich Alexey , Bratkov Georg , Li Yupeng , Joskowiak Dominik , Peterss Sven , Juchem Gerd , Hagl Christian , Luehr Maximilian
Published: May 2021

Cerebral embolism due to infective endocarditis (IE) is associated with significant morbidity and mortality. The optimal time-interval between symptomatic stroke and cardiac surgery remains unclear. This study aimed to analyze the patients’ outcomes and define the potential risk factors with regard to surgical timing for IE patients with preoperative symptomatic cerebral embolism (CE). A total of 119 IE patients with CE were identified and analyzed with regard to operative timing: early (1–7 days), intermediate (8–21 days), and late (>22 days). The preoperative patient data, comorbidities and previous cardiac surgical procedures were analyzed to identify potential predictors and independent risk factors for in-hospital mortality using univariate and multivariate regression analysis. Actuarial survival was estimated by the Kaplan-Meier method. In-hospital mortality for the entire study cohort was 15.1% (n = 18), and in comparison, between groups was found to be highest in the intermediate surgical group (25.7%). Univariate analysis identified preoperative mechanical ventilation dependent respiratory insufficiency (p = 0.006), preoperative renal insufficiency (p = 0.019), age (p = 0.002), large vegetations (p = 0.018) as well as intermediate (p = 0.026), and late (p = 0.041) surgery as predictors of in-hospital mortality. The presence of large vegetations (>8 mm) (p = 0.019) and increased age (p = 0.037)—but not operative timing—were identified as independent risk factors for in-hospital mortality. In the presence of large vegetations (>8 mm), cardiac surgery should be performed early and independently from the entity of cerebral embolic stroke. Postponing surgery to achieve clinical stabilization and better postoperative outcomes of IE patients with CE is reasonable, however, worsening of the disease process with deterioration and resulting heart failure during the first 3 weeks after CE results in a significantly higher in-hospital mortality and inferior long-term survival.
An Experimental Pre-Post Study on the Efficacy of Respiratory Physiotherapy in Severe Critically III COVID-19 Patients
Authors: Battaglini Denise , Caiffa Salvatore , Gasti Giovanni , Ciaravolo Elena , Robba Chiara , Herrmann Jacob , Gerard Sarah , Bassetti Matteo , Pelosi Paolo , Ball Lorenzo ,   on behalf of the GECOVID Group
Published: May 2021

Background: Respiratory physiotherapy (RPT) is considered essential in patients’ management during intensive care unit (ICU) stay. The role of RPT in critically ill COVID-19 patients is poorly described. We aimed to investigate the effects of RPT on oxygenation and lung aeration in critically ill COVID-19 patients admitted to the ICU. Methods: Observational pre-post study. Patients with severe COVID-19 admitted to the ICU, who received a protocolized CPT session and for which a pre-and post-RPT lung ultrasound (LUS) was performed, were included. A subgroup of patients had an available quantitative computed tomography (CT) scan performed within 4 days from RPT. The primary aim was to evaluate whether RPT improved oxygenation; secondary aims included correlations between LUS, CT and response to RPT. Results: Twenty patients were included. The median (1st–3rd quartile) PaO2/FiO2 was 181 (105–456), 244 (137–497) and 246 (137–482) at baseline (T0), after RPT (T1), and after 6 h (T2), respectively. PaO2/FiO2 improved throughout the study (p = 0.042); particularly, PaO2/FiO2 improved at T1 in respect to T0 (p = 0.011), remaining higher at T2 (p = 0.007) compared to T0. Correlations between LUS, volume of gas (rho = 0.58, 95%CI 0.05–0.85, p = 0.033) and hyper-aerated mass at CT scan (rho = 0.54, 95% CI 0.00–0.84, p = 0.045) were detected. No significant changes in LUS score were observed before and after RPT. Conclusions: RPT improved oxygenation and the improvement persisted after 6 h. Oxygenation improvement was not reflected by aeration changes assessed with LUS. Further studies are warranted to assess the efficacy of RPT in COVID-19 ICU patients.
The Effectiveness of Different Concepts of Bracing in Adolescent Idiopathic Scoliosis (AIS): A Systematic Review and Meta-Analysis
Authors: Costa Lorenzo , Schlosser Tom P. C. , Jimale Hanad , Homans Jelle F. , Kruyt Moyo C. , Castelein René M.
Published: May 2021

Brace treatment is the most common noninvasive treatment in adolescent idiopathic scoliosis (AIS); however it is currently not fully known whether there is a difference in effectiveness between brace types/concepts. All studies on brace treatment for AIS were searched for in PubMed and EMBASE up to January 2021. Articles that did not report on maturity of the study population were excluded. Critical appraisal was performed using the Methodological Index for Non-Randomized Studies tool (MINORS). Brace concepts were distinguished in prescribed wearing time and rigidity of the brace: full-time, part-time, and night-time, rigid braces and soft braces. In the meta-analysis, success was defined as ≤5° curve progression during follow-up. Of the 33 selected studies, 11 papers showed high risk of bias. The rigid full-time brace had on average a success rate of 73.2% (95% CI 61–86%), night-time of 78.7% (72–85%), soft braces of 62.4% (55–70%), observation only of 50% (44–56%). There was insufficient evidence on part-time wear for the meta-analysis. The majority of brace studies have significant risk of bias. No significant difference in outcome between the night-time or full-time concepts could be identified. Soft braces have a lower success rate compared to rigid braces. Bracing for scoliosis in Risser 0–2 and 0–3 stage of maturation appeared most effective.
Contrast Associated Acute Kidney Injury and Mortality in Older Adults with Acute Coronary Syndrome: A Pooled Analysis of the FRASER and HULK Studies
Authors: Pavasini Rita , Tebaldi Matteo , Bugani Giulia , Tonet Elisabetta , Campana Roberta , Cimaglia Paolo , Maietti Elisa , Grazzi Giovanni , Pompei Graziella , Fabbri Gioele , Fiorio Alessio , Rubboli Andrea , Mazzoni Gianni , Vitali Francesco , Serenelli Matteo , Campo Gianluca , Biscaglia Simone
Published: May 2021

Whether contrast-associated acute kidney injury (CA-AKI) is only a bystander or a risk factor for mortality in older patients undergoing percutaneous coronary intervention (PCI) is not well understood. Data from FRASER (NCT02386124) and HULK (NCT03021044) studies have been analysed. All patients enrolled underwent coronary angiography. The occurrence of CA-AKI was defined based on KDIGO criteria. The primary outcome of the study was to test the relation between CA-AKI and 3-month mortality. Overall, 870 older ACS adults were included in the analysis (mean age 78 ± 5 years; 28% females). CA-AKI occurred in 136 (16%) patients. At 3 months, 13 (9.6%) patients with CA-AKI died as compared with 13 (1.8%) without it (p < 0.001). At multivariable analysis, CA-AKI emerged as independent predictor of 3-month mortality (HR 3.51, 95%CI 1.05–7.01). After 3 months, renal function returned to the baseline value in 78 (63%) with CA-AKI. Those without recovered renal function (n = 45, 37%) showed an increased risk of mortality as compared to recovered renal function and no CA-AKI subgroups (HR 2.01, 95%CI 1.55–2.59, p = 0.009 and HR 2.71, 95%CI 1.45–5.89, p < 0.001, respectively). In conclusion, CA-AKI occurs in a not negligible portion of older MI patients undergoing invasive strategy and it is associated with short-term mortality.
Presepsin in the Rapid Response System for Cancer Patients: A Retrospective Analysis
Authors: Lee Min-Jung , Han Won-Ho , Chun June-Young , Kim Sun-Young , Kim Jee-Hee
Published: May 2021

Introduction: Early diagnosis of sepsis is paramount to effective management. The present study aimed to compare the prognostic accuracy of presepsin levels and other biomarkers in the assessment of septic shock and mortality risk in cancer patients. Materials and methods: A total of 74 cancer patients were evaluated for presepsin, lactic acid, C-reactive protein (CRP) levels, and white blood cell count (WBC). Specificity and sensitivity values for septic shock and death were compared between four biomarkers in all patients and those with and without acute kidney injury (AKI). Results: A total of 27 and 29 patients experienced septic shock and died, respectively. The area under the curve (AUC) and sensitivity and specificity estimated for presepsin levels for septic shock were 60%, 74%, and 51%, respectively. The corresponding values for mortality were 62%, 72%, and 49%, respectively. In patients without AKI, AUC of presepsin levels for septic shock and death were 62% and 65%, respectively; in those with AKI, these values were 44% and 58%, respectively. Presepsin levels showed higher sensitivity and specificity values than WBC and higher specificity than CRP but were similar to those of lactic acid levels. Conclusions: Presepsin levels are similar to lactic acid levels in the assessment of septic shock and mortality risk in cancer patients. In patients with AKI, presepsin levels should be considered carefully.
A Practical Guide for the Management of Steroid Induced Hyperglycaemia in the Hospital
Authors: Aberer Felix , Hochfellner Daniel A. , Sourij Harald , Mader Julia K.
Published: May 2021

Glucocorticoids represent frequently recommended and often indispensable immunosuppressant and anti-inflammatory agents prescribed in various medical conditions. Despite their proven efficacy, glucocorticoids bear a wide variety of side effects among which steroid induced hyperglycaemia (SIHG) is among the most important ones. SIHG, potentially causes new-onset hyperglycaemia or exacerbation of glucose control in patients with previously known diabetes. Retrospective data showed that similar to general hyperglycaemia in diabetes, SIHG in the hospital and in outpatient settings detrimentally impacts patient outcomes, including mortality. However, recommendations for treatment targets and guidelines for in-hospital as well as outpatient therapeutic management are lacking, partially due to missing evidence from clinical studies. Still, SIHG caused by various types of glucocorticoids is a common challenge in daily routine and clinical guidance is needed. In this review, we aimed to summarize clinical evidence of SIHG in inpatient care impacting clinical outcome, establishment of diagnosis, diagnostic procedures and therapeutic recommendations.
Targeting Alcohol Septal Ablation in Patients with Obstructive Hypertrophic Cardiomyopathy Candidates for Surgical Myectomy: Added Value of Three-Dimensional Intracoronary Myocardial Contrast Echocardiography
Authors: La Canna Giovanni , Scarfò Iside , Arendar Irina , Colombo Antonio , Torracca Lucia , Margonato Davide , Montorfano Matteo , Alfieri Ottavio
Published: May 2021

Background: Myocardial contrast two-dimensional echocardiography (MC-2DE) is widely used to address alcohol septal ablation (ASA) in obstructive hypertrophic cardiomyopathy (HCM). Owing to its limited cut-planes, MC-2DE may inaccurately identify the contrast misplacement associated with an unsuccessful or complicated ASA outcome. Objective: The aim of this study was to assess the added value of myocardial contrast three-dimensional echocardiography (MC-3DE) compared with MC-2DE to identify the appropriate matching between the target septal zone (TSZ) and coronary artery branch for safe and long-term effective ASA in HCM patients. Methods: A consecutive series of 52 symptomatic obstructive HCM patients referred for isolated surgical myectomy (SM) was analyzed with MC-2DE and MC-3DE following injection of echocontrast into one or more septal branches. MC-2DE and MC-3DE patterns were categorized according to complete (Type 1) or incomplete (Type 2) TSZ covering, high-risk (Type 3) exceeding TSZ, or life-threatening outside TSZ distribution (Type 4). Results: MC-2DE per patient analysis showed a Type 1 pattern in 32 patients and Types 2–4 in the remaining 20 patients; subsequent MC-3DE analysis provided a re-phenotyping of MC-2DE findings in 22 of the 52 patients (42%), showing a high-risk Type 2 pattern in 17 of the 32 patients with Type 1, and a new life-threatening Type 4 in three patients with Type 2, respectively. All patients with MC-3DE Type 1 pattern underwent safe and effective ASA with a long-term uneventful follow-up, while the remaining patients underwent SM. Conclusions: Refining high risk or life-threatening contrast misplacement, MC-3DE is more accurate than conventional MC-2DE to target safe and long-term effective septal reduction with ASA in obstructive HCM patients referred for isolated SM.