bluuebunny/crossref_metadata_2025 huggingface dataset:
Aluminum, Arsenic, Beryllium, Cadmium, Chromium, Cobalt, Copper, Iron, Lead, Mercury, Molybdenum, Nickel, Platinum, Thallium, Titanium, Vanadium, and Zinc: Molecular Aspects in Experimental Liver Injury
Authors: Teschke Rolf
Published: October 2022

Experimental liver injury with hepatocelluar necrosis and abnormal liver tests is caused by exposure to heavy metals (HMs) like aluminum, arsenic, beryllium, cadmium, chromium, cobalt, copper, iron, lead, mercury, molybdenum, nickel, platinum, thallium, titanium, vanadium, and zinc. As pollutants, HMs disturb the ecosystem, and as these substances are toxic, they may affect the health of humans and animals. HMs are not biodegradable and may be deposited preferentially in the liver. The use of animal models can help identify molecular and mechanistic steps leading to the injury. HMs commonly initiate hepatocellular overproduction of ROS (reactive oxygen species) due to oxidative stress, resulting in covalent binding of radicals to macromolecular proteins or lipids existing in membranes of subcellular organelles. Liver injury is facilitated by iron via the Fenton reaction, providing ROS, and is triggered if protective antioxidant systems are exhausted. Ferroptosis syn pyroptosis was recently introduced as mechanistic concept in explanations of nickel (Ni) liver injury. NiCl2 causes increased iron deposition in the liver, upregulation of cyclooxygenase 2 (COX-2) protein and mRNA expression levels, downregulation of glutathione eroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), nuclear receptor coactivator 4 (NCOA4) protein, and mRNA expression levels. Nickel may cause hepatic injury through mitochondrial damage and ferroptosis, defined as mechanism of iron-dependent cell death, similar to glutamate-induced excitotoxicity but likely distinct from apoptosis, necrosis, and autophagy. Under discussion were additional mechanistic concepts of hepatocellular uptake and biliary excretion of mercury in exposed animals. For instance, the organic anion transporter 3 (Oat3) and the multidrug resistance-associated protein 2 (Mrp2) were involved in the hepatic handling of mercury. Mercury treatment modified the expression of Mrp2 and Oat3 as assessed by immunoblotting, partially explaining its impaired biliary excretion. Concomitantly, a decrease in Oat3 abundance in the hepatocyte plasma membranes was observed that limits the hepatic uptake of mercury ions. Most importantly and shown for the first time in liver injury caused by HMs, titanium changed the diversity of gut microbiota and modified their metabolic functions, leading to increased generation of lipopolysaccharides (LPS). As endotoxins, LPS may trigger and perpetuate the liver injury at the level of gut-liver. In sum, mechanistic and molecular steps of experimental liver injury due to HM administration are complex, with ROS as the key promotional compound. However, additional concepts such as iron used in the Fenton reaction, ferroptosis, modification of transporter systems, and endotoxins derived from diversity of intestinal bacteria at the gut-liver level merit further consideration.
Maternal Fructose Intake, Programmed Mitochondrial Function and Predisposition to Adult Disease
Authors: Smith Erin Vanessa LaRae , Dyson Rebecca Maree , Weth Freya Rebecca , Berry Mary Judith , Gray Clint
Published: October 2022

Fructose consumption is now recognised as a major risk factor in the development of metabolic diseases, such as hyperlipidaemia, diabetes, non-alcoholic fatty liver disease and obesity. In addition to environmental, social, and genetic factors, an unfavourable intrauterine environment is now also recognised as an important factor in the progression of, or susceptibility to, metabolic disease during adulthood. Developmental trajectory in the short term, in response to nutrient restriction or excessive nutrient availability, may promote adaptation that serves to maintain organ functionality necessary for immediate survival and foetal development. Consequently, this may lead to decreased function of organ systems when presented with an unfavourable neonatal, adolescent and/or adult nutritional environment. These early events may exacerbate susceptibility to later-life disease since sub-optimal maternal nutrition increases the risk of non-communicable diseases (NCDs) in future generations. Earlier dietary interventions, implemented in pregnant mothers or those considering pregnancy, may have added benefit. Although, the mechanisms by which maternal diets high in fructose and the vertical transmission of maternal metabolic phenotype may lead to the predisposition to adult disease are poorly understood. In this review, we will discuss the potential contribution of excessive fructose intake during pregnancy and how this may lead to developmental reprogramming of mitochondrial function and predisposition to metabolic disease in offspring.
Defense Mechanisms of Cotton Fusarium and Verticillium Wilt and Comparison of Pathogenic Response in Cotton and Humans
Authors: Man Mingwu , Zhu Yaqian , Liu Lulu , Luo Lei , Han Xinpei , Qiu Lu , Li Fuguang , Ren Maozhi , Xing Yadi
Published: October 2022

Cotton is an important economic crop. Fusarium and Verticillium are the primary pathogenic fungi that threaten both the quality and sustainable production of cotton. As an opportunistic pathogen, Fusarium causes various human diseases, including fungal keratitis, which is the most common. Therefore, there is an urgent need to study and clarify the resistance mechanisms of cotton and humans toward Fusarium in order to mitigate, or eliminate, its harm. Herein, we first discuss the resistance and susceptibility mechanisms of cotton to Fusarium and Verticillium wilt and classify associated genes based on their functions. We then outline the characteristics and pathogenicity of Fusarium and describe the multiple roles of human neutrophils in limiting hyphal growth. Finally, we comprehensively compare the similarities and differences between animal and plant resistance to Fusarium and put forward new insights into novel strategies for cotton disease resistance breeding and treatment of Fusarium infection in humans.
Regulation of CRE-Dependent Transcriptional Activity in a Mouse Suprachiasmatic Nucleus Cell Line
Authors: Langiu Monica , Bechstein Philipp , Neumann Sonja , Spohn Gabriele , Maronde Erik
Published: October 2022

We evaluated the signalling framework of immortalized cells from the hypothalamic suprachiasmatic nucleus (SCN) of the mouse. We selected a vasoactive intestinal peptide (VIP)-positive sub-clone of immortalized mouse SCN-cells stably expressing a cAMP-regulated-element (CRE)-luciferase construct named SCNCRE. We characterized these cells in terms of their status as neuronal cells, as well as for important components of the cAMP-dependent signal transduction pathway and compared them to SCN ex vivo. SCNCRE cells were treated with agents that modulate different intracellular signalling pathways to investigate their potency and timing for transcriptional CRE-dependent signalling. Several activating pathways modulate SCN neuronal signalling via the cAMP-regulated-element (CRE: TGACGCTA) and phosphorylation of transcription factors such as cAMP-regulated-element-binding protein (CREB). CRE-luciferase activity induced by different cAMP-signalling pathway-modulating agents displayed a variety of substance-specific dose and time-dependent profiles and interactions relevant to the regulation of SCN physiology. Moreover, the induction of the protein kinase C (PKC) pathway by phorbol ester application modulates the CRE-dependent signalling pathway as well. In conclusion, the cAMP/PKA- and the PKC-regulated pathways individually and in combination modulate the final CRE-dependent transcriptional output.
Transcriptome Analysis Reveals the Genes Related to Pollen Abortion in a Cytoplasmic Male-Sterile Soybean (Glycine max (L.) Merr.)
Authors: Bai Zhiyuan , Ding Xianlong , Zhang Ruijun , Yang Yuhua , Wei Baoguo , Yang Shouping , Gai Junyi
Published: October 2022

Cytoplasmic male sterility (CMS) lays a foundation for the utilization of heterosis in soybean. The soybean CMS line SXCMS5A is an excellent CMS line exhibiting 100% male sterility. Cytological analysis revealed that in SXCMS5A compared to its maintainer SXCMS5B, its tapetum was vacuolated and abnormally developed. To identify the genes and metabolic pathways involving in pollen abortion of SXCMS5A, a comparative transcriptome analysis was conducted between SXCMS5A and SXCMS5B using flower buds. A total of 372,973,796 high quality clean reads were obtained from 6 samples (3 replicates for each material), and 840 differentially expressed genes (DEGs) were identified, including 658 downregulated and 182 upregulated ones in SXCMS5A compared to SXCMS5B. Among them, 13 DEGs, i.e., 12 open reading frames (ORFs) and 1 COX2, were mitochondrial genome genes in which ORF178 and ORF103c were upregulated in CMS lines and had transmembrane domain(s), therefore, identified as CMS candidate mitochondrial genes of SXCMS5A. Furthermore, numerous DEGs were associated with pollen wall development, carbohydrate metabolism, sugar transport, reactive oxygen species (ROS) metabolism and transcription factor. Some of them were further confirmed by quantitative real time PCR analysis between CMS lines with the same cytoplasmic source as SXCMS5A and their respective maintainer lines. The amount of soluble sugar and adenosine triphosphate and the activity of catalase and ascorbic acid oxidase showed that energy supply and ROS scavenging decreased in SXCMS5A compared to SXCMS5B. These findings provide valuable information for further understanding the molecular mechanism regulating the pollen abortion of soybean CMS.
Transcriptome Analysis Reveals Genes and Pathways Associated with Salt Tolerance during Seed Germination in Suaeda liaotungensis
Authors: Song Jieqiong , Liu Xinjie , Li Xinxin , Wang Hongfei , Chu Ruowen , Qu Fangfang , Zhang Sixue , Li Qiuli
Published: October 2022

Seed germination is susceptible to external environmental factors, especially salt stress. Suaeda liaotungensis is a halophyte with strong salt tolerance, and the germination rate of brown seeds under 1000 mM NaCl treatment still reached 28.9%. To explore the mechanism of salt stress response during brown seed germination in Suaeda liaotungensis, we conducted transcriptomic analysis on the dry seeds (SlD), germinated seeds under the control condition (SlG_C), and salt treatment (SlG_N). Transcriptome analysis revealed that 13314 and 755 differentially expressed genes (DEGs) from SlD vs. SlG_C and SlG_C vs. SlG_N were detected, respectively. Most DEGs were enriched in pathways related to transcription regulation and hormone signal transduction, ROS metabolism, cell wall organization or biogenesis, and carbohydrate metabolic process in two contrasting groups. Compared with the control condition, POD and CAT activity, H2O2, soluble sugar, and proline contents were increased during germinated seeds under salt stress. Furthermore, functional analysis demonstrated that overexpression of SlNAC2 significantly enhanced salt tolerance during the germination stage in Arabidopsis. These results not only revealed the tolerant mechanism of brown seed germination in response to salinity stress but also promoted the exploration and application of salt-tolerant gene resources of Suaeda liaotungensis.
Hydrogen Bonding Drives Helical Chirality via 10-Membered Rings in Dipeptide Conjugates of Ferrocene-1,1′-Diamine
Authors: Kovačević Monika , Markulin Dora , Zelenika Matea , Marjanović Marko , Lovrić Marija , Polančec Denis , Ivančić Marina , Mrvčić Jasna , Molčanov Krešimir , Milašinović Valentina , Roca Sunčica , Kodrin Ivan , Barišić Lidija
Published: October 2022

Considering the enormous importance of protein turns as participants in various biological events, such as protein–protein interactions, great efforts have been made to develop their conformationally and proteolytically stable mimetics. Ferrocene-1,1′-diamine was previously shown to nucleate the stable turn structures in peptides prepared by conjugation with Ala (III) and Ala–Pro (VI). Here, we prepared the homochiral conjugates of ferrocene-1,1′-diamine with l-/d-Phe (32/35), l-/d-Val (33/36), and l-/d-Leu (34/37) to investigate (1) whether the organometallic template induces the turn structure upon conjugation with amino acids, and (2) whether the bulky or branched side chains of Phe, Val, and Leu affect hydrogen bonding. Detailed spectroscopic (IR, NMR, CD), X-ray, and DFT studies revealed the presence of two simultaneous 10-membered interstrand hydrogen bonds, i.e., two simultaneous β-turns in goal compounds. A preliminary biological evaluation of d-Leu conjugate 37 showed its modest potential to induce cell cycle arrest in the G0/G1 phase in the HeLa cell line but these results need further investigation.
Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies
Authors: Abo Elmaaty Ayman , Eldehna Wagdy , Khattab Muhammad , Kutkat Omnia , Alnajjar Radwan , El-Taweel Ahmed , Al-Rashood Sara , Abourehab Mohammed , Binjubair Faizah , Saleh Mohamed , Belal Amany , Al-Karmalawy Ahmed
Published: October 2022

In this article, 34 anticoagulant drugs were screened in silico against the main protease (Mpro) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 Mpro. A molecular dynamics study at 200 ns was also carried out for the most promising anticoagulants to provide insights into the dynamic and thermodynamic properties of promising compounds. Moreover, a quantum mechanical study was also conducted which helped us to attest to some of the molecular docking and dynamics findings. A biological evaluation (in vitro) of the most promising compounds was also performed by carrying out the MTT cytotoxicity assay and the crystal violet assay in order to assess inhibitory concentration 50 (IC50). It is worth noting that ticagrelor displayed the highest intrinsic potential for the inhibition of SARS-CoV-2 with an IC50 value of 5.60 µM and a safety index of 25.33. In addition, fondaparinux sodium and dabigatran showed promising inhibitory activities with IC50 values of 8.60 and 9.40 µM, respectively, and demonstrated safety indexes of 17.60 and 15.10, respectively. Moreover, the inhibitory potential of the SARS-CoV-2 Mpro enzyme was investigated by utilizing the SARS-CoV-2 Mpro assay and using tipranavir as a reference standard. Interestingly, promising SARS-CoV-2 Mpro inhibitory potential was attained for fondaparinux sodium with an IC50 value of 2.36 µM, surpassing the reference tipranavir (IC50 = 7.38 µM) by more than three-fold. Furthermore, highly eligible SARS-CoV-2 Mpro inhibitory potential was attained for dabigatran with an IC50 value of 10.59 µM. Finally, an SAR was discussed, counting on the findings of both in vitro and in silico approaches.
A Hydrogen-Sulfide-Repressed Methionine Synthase SlMS1 Acts as a Positive Regulator for Fruit Ripening in Tomato
Authors: Geng Zhi-Kun , Ma Lin , Rong Yu-Lei , Li Wan-Jie , Yao Gai-Fang , Zhang Hua , Hu Kang-Di
Published: October 2022

Ethylene is a key phytohormone that regulates the ripening of climacteric fruits, and methionine is an indirect precursor of ethylene. However, whether methionine synthase plays a role in fruit ripening in Solanum lycopersicum (tomato) is still unknown. In this study, we find that a tomato methionine synthase (named SlMS1), which could be repressed at the transcriptional level by hydrogen sulfide (H2S), acts as a positive regulator for tomato fruit ripening. By a bioinformatics analysis, it is found that SlMS1 and SlMS2 in tomato are highly homologous to methionine synthases in Arabidopsis thaliana. The expression pattern of SlMS1 and SlMS2 is analyzed in tomato, and SlMS1 expression is up-regulated during fruit ripening, suggesting its potential role in regulating fruit ripening. A potential bipartite nuclear localization signal is found in the amino acid sequence of SlMS1; thus, SlMS1 is tagged with GFP and observed in the leaves of Nicotiana benthamiana. Consistently, SlMS1-GFP shows strong nuclear localization and also cytoplasmic localization. The role of SlMS1 in regulating fruit ripening is investigated in tomato fruit by transient silencing (virus-induced gene silencing, VIGS) and transient overexpression. The results show that SlMS1 silencing causes delayed fruit ripening, evidenced by more chlorophyll and less carotenoid accumulation, while SlMS1 overexpression accelerates fruit ripening significantly compared with control. Further investigation shows that SlMS1 overexpression could up-regulate the expression of carotenoid-synthesis-related genes (PSY1, PDS, ZDS), chlorophyll-degradation-related genes (NYC1, PAO, PPH, SGR1), cell-wall-metabolism-related genes (CEL2, EXP, PG, TBG4, XTH5) and ethylene-synthesis-pathway-related genes (ACO1, ACO3, ACS2), while SlMS1 silencing causes the opposite results. The correlation analysis indicates that SlMS1 expression is negatively correlated with chlorophyll content and positively correlated with carotenoid and ripening-related gene expressions. Taken together, our data suggest that SlMS1 is a positive regulator of tomato fruit ripening and a possible target gene for the ripening-delaying effect of H2S.
Metabolic Regulation and Lipidomic Remodeling in Relation to Spermidine-induced Stress Tolerance to High Temperature in Plants
Authors: Li Zhou , Cheng Bizhen , Zhao Yue , Luo Lin , Zhang Yan , Feng Guangyan , Han Liebao , Peng Yan , Zhang Xinquan
Published: October 2022

Beneficial effects of spermidine (Spd) on alleviating abiotic stress damage have been explored in plants for hundreds of years, but limited information is available about its roles in regulating lipids signaling and metabolism during heat stress. White clover (Trifolium repens) plants were pretreated with 70 μM Spd and then subjected to high temperature (38/33 °C) stress for 20 days. To further investigate the effect of Spd on heat tolerance, transgenic Arabidopsisthaliana overexpressing a TrSAMS encoding a key enzyme involved in Spd biosynthesis was exposed to high temperature (38/33 °C) stress for 10 days. A significant increase in endogenous Spd content in white clover by exogenous application of Spd or the TrSAMS overexpression in Arabidopsisthaliana could effectively mitigate heat-induced growth retardation, oxidative damage to lipids, and declines in photochemical efficiency and cell membrane stability. Based on the analysis of metabolomics, the amino acids and vitamins metabolism, biosynthesis of secondary metabolites, and lipids metabolism were main metabolic pathways regulated by the Spd in cool-season white clover under heat stress. Further analysis of lipidomics found the TrSAMS-transgenic plants maintained relatively higher accumulations of total lipids, eight phospholipids (PC, phosphatidylcholine; PG, phosphatidylglycerol; PS, phosphatidylserine; CL, cardiolipin; LPA, lysophosphatidic acid; LPC, lyso phosphatidylcholine; LPG, lyso phosphatidylglycerol; and LPI, lyso phosphatidylinositol), one glycoglycerolipid (DGDG, digalactosyl diacylglycerol), and four sphingolipids (Cer, ceramide; CerG2GNAc1, dihexosyl N-acetylhexosyl ceramide; Hex1Cer, hexosyl ceramide; and ST, sulfatide), higher ratio of DGDG: monogalactosyl diacylglycerol (MGDG), and lower unsaturation level than wild-type Arabidopsisthaliana in response to heat stress. Spd-induced lipids accumulation and remodeling could contribute to better maintenance of membrane stability, integrity, and functionality when plants underwent a long period of heat stress. In addition, the Spd significantly up-regulated PIP2 and PA signaling pathways, which was beneficial to signal perception and transduction for stress defense. Current findings provide a novel insight into the function of Spd against heat stress through regulating lipids signaling and reprograming in plants.
Structural Disparity of Avocado Rootstocks In Vitro for Rooting and Acclimation Success
Authors: Hiti-Bandaralage Jayeni , Hayward Alice , Mitter Neena
Published: October 2022

Improving clonal rootstock propagation of avocado has been a major industry/research challenge globally for many decades. Tissue culture has been a focus for clonal propagation with substantial advancements in recent years. In the process of tissue culture, avocado rootstocks display differences in rooting and acclimation capacity. Such differences may relate to the specific structural characteristics of the rootstock. This study aimed to investigate the structural difference during tissue culture in two rootstocks ‘Reed’ and ‘Velvick’, with differing rooting and acclimation capacity. Histological investigations were carried out of stem vasculature, leaves and roots of tissue cultured plantlets. Quantitative parameters; stomatal index, stomatal density, trichome density, vein-islet density and vein termination density were also analysed. Prominent fascicular cambium and fewer phloem fibres in stems positively correlated with rooting capacity. Acclimation success positively correlated to the presence of fully differentiated secondary xylem in root. Presence of smaller epidermal cells, high stomatal density and reduced vein termination density was associated with reduced acclimation success. These findings will support optimisation strategies for micropropagation of not only difficult-to-root and difficult-to-acclimate avocado rootstocks, but also, other woody perennials experiencing similar problems.
Mosquito Surveillance and Insecticide Resistance Monitoring Conducted by the Florida Keys Mosquito Control District, Monroe County, Florida, USA
Authors: Hribar Lawrence J. , Boehmler Michael B. , Murray Heidi L. , Pruszynski Catherine A. , Leal Andrea L.
Published: October 2022

Mosquito control programs in the State of Florida are charged with protecting human and animal health, fostering economic development of the State, permitting enjoyment of the natural attractions in Florida, and improving the quality of life of citizens. Mosquito control programs must accomplish these tasks in such a manner as will protect the environment and terrestrial, marine, and freshwater ecosystems. The Florida Keys Mosquito Control District provides a science-based Integrated Pest Management mosquito control program to the residents of the Florida Keys, Monroe County, Florida. Operational decisions are based on surveillance of adult and immature mosquitoes. Mosquito populations are monitored by means of carbon dioxide-baited light traps BG Sentinel traps, truck traps, gravid traps, oviposition traps, and human landing rate counts. Larvae and pupae are monitored by inspections of natural and human-made immature habitats. Due to past and current reliance on chemical pesticides for control of mosquitoes, the District maintains a pesticide resistance detection program consisting of CDC bottle bioassays and larval bioassays, challenging local mosquito species with currently used adulticides and larvicides.
Effects of Nano-Graphene Oxide on the Growth and Reproductive Dynamics of Spodoptera frugiperda Based on an Age-Stage, Two-Sex Life Table
Authors: Li Cao , Hu Chaoxing , Zhi Junrui , Yue Wenbo , Li Hongbo
Published: October 2022

The development and reproduction of the fall armyworm (FAW), Spodoptera frugiperda, which were reared on artificial diets containing nano-graphene oxide (GO), were determined based on age-stage, two-sex life table analysis. The results showed that GO had adverse effects on FAWs. Compared with the control, the duration of the egg stage and first, second, and sixth instar larval stages increased with increasing GO concentrations; however, the lifespan of male and female adults decreased with increasing GO concentrations. Weights of FAW pupae that were supplied with GO-amended diets increased by 0.17–15.20% compared to the control. Intrinsic growth, limited growth, and net reproductive rates of FAWs feeding on GO supplemented diets were significantly lower than the control, while mean generational periods (0.5 mg/g: 38.47; 1 mg/g: 40.38; 2 mg/g: 38.42) were significantly longer than the control. The expression of genes encoding vitellogenin (Vg) and vitellogenin receptor (VgR) expression was abnormal in female FAW adults feeding on GO-amended diets; the number of eggs laid decreased relative to the control, but Vg expression increased. In conclusion, GO prolonged the developmental period of FAWs, decreased fecundity, and led to a decline in the population size. The study provides a basis for the rational use of GO as a pesticide synergist for FAW control.
Insecticidal Activities of Atriplex halimus L., Salvia rosmarinus Spenn. and Cuminum cyminum L. against Dactylopius opuntiae (Cockerell) under Laboratory and Greenhouse Conditions
Authors: Naboulsi Imane , El Fakhouri Karim , Lamzira Rachid , Ramdani Chaimae , Bitchagno Gabin Thierry M. , Boulamtat Rachid , Bakrim Widad Ben , Mahdi Ismail , Aboulmouhajir Aziz , Yasri Abdelaziz , El Bouhssini Mustapha , Ward Jane L. , Sobeh Mansour
Published: October 2022

The wild cochineal Dactylopius opuntiae (Hemiptera: Dactylopiidae) is one of the major insect pests of the prickly pear Opuntia ficus-indica (L.) in Morocco, a well-known fruit and vegetable crop of arid and semi-arid regions around the world. The present study investigated the insecticidal potential of six extracts (three aqueous and three hydroalcoholic (MeOH/H2O, 20/80 (v/v)) from Atriplex halimus (leaves), Salvia rosmarinus (leaves) and Cuminum cyminum (seeds) to control nymphs and adult females of D. opuntiae under laboratory and greenhouse conditions. Out of the tested samples, A. halimus aqueous extract showed the highest activity, inducing mortality rates of 67.04% (after 4 days) and 85% (after 8 days) on nymphs and adult females of D. opuntiae, respectively, at a concentration of 5% under laboratory conditions. It also showed the highest mortality rate of nymphs with 100% (4 days after application) and 83.75% of adult females (7 days after the second application) at a concentration of 5% when combined with black soap at 10 g/L under greenhouse conditions. The difference in the toxicity of plant species of the study was correlated with their saponin content. A total of 36 of these triterpene glucosides were suggested after a comprehensive LC-MSn profiling of the most active extract, A. halimus, in addition to phytoecdysones and glycosylated phenolic acids and flavonoids. These findings provided evidence that the aqueous leaf extract of A. halimus could be incorporated in the management of the wild cochineal as an alternative to chemical insecticides.
Diagnosis and Management of Autoimmune Hemolytic Anemias
Authors: Barcellini Wilma , Fattizzo Bruno
Published: October 2022

Autoimmune hemolytic anemia (AIHA) is usually categorized, as other immune-mediated cytopenias, in so-called benign hematology, and it is consequently managed in various settings, namely, internal medicine, transfusion centers, hematology and, more rarely, onco-hematology departments [...]
Bariatric Surgery Outcomes in Patients with Kidney Transplantation
Authors: Pané Adriana , Molina-Andujar Alicia , Olbeyra Romina , Romano-Andrioni Bárbara , Boswell Laura , Montagud-Marrahi Enrique , Jiménez Amanda , Ibarzabal Ainitze , Viaplana Judith , Ventura-Aguiar Pedro , Amor Antonio J. , Vidal Josep , Flores Lilliam , de Hollanda Ana
Published: October 2022

Obesity and kidney transplantation (KTx) are closely related. Obesity increases the risk of chronic kidney disease and can be a relative contraindication for KTx. Besides, KTx recipients are predisposed to obesity and its comorbidities. Consequently, bariatric surgery (BS) emerges as a powerful therapeutic tool either before or after KTx. Since evidence regarding the best approach is still scarce, we aimed to describe renal and metabolic outcomes in a single centre with more than 15-year experience in both surgeries. Methods: A retrospective study including patients who had received a KTx either before or after BS. Usual metabolic and renal outcomes, but also new variables (as renal graft dysfunction) were collected for a minimum follow-up of 1-year post-BS. Results: A total of 11 patients were included: n = 6 (BS-post-KTx) and n = 5 (BS-pre-KTx). One patient was assessed in both groups. No differences in the main outcomes were identified, but BS-post-KTx group tended to gain more weight during the follow-up. The incidence of renal graft dysfunction was comparable (4/6 for BS-post-KTx, 3/5 for BS-pre-KTx) between groups. Conclusions: BS in patients with KTx appears to be safe and effective attending to metabolic and renal outcomes. These results seem irrespective of the time course, except for weight regain, which appears to be a common pattern in the BS-post-KTx group.
Disease Reactivation in Secondary Progressive Multiple Sclerosis Patients Switching from Fingolimod to Siponimod: A Case Series
Authors: Abbadessa Gianmarco , Maida Elisabetta , Miele Giuseppina , Bile Floriana , Lavorgna Luigi , Bonavita Simona
Published: October 2022

Siponimod, a selective modulator of sphingosine 1-phosphate receptors 1 (S1P1) and 5 (S1P5), has recently been marketed for patients with Secondary Progressive Multiple Sclerosis (SPMS). Herein, we report three SPMS patients presenting disease reactivation in the first three months after switching from fingolimod to siponimod. Fingolimod binds to S1P1, S1P3, S1P4 and S1P5 receptors. S1P3 holds a central role in eliciting central proinflammatory responses, thus it has been hypothesized that upregulation of S1P3 may be the mechanism behind relapses after switching from fingolimod to siponimod. Further studies are needed to investigate the safety and efficacy of this treatment sequencing.
Determinants of the Impact of Fatigue on the Health of Polish Nursing Students during the COVID-19 Pandemic
Authors: Kupcewicz Ewa , Rachubińska Kamila , Gaworska-Krzemińska Aleksandra , Andruszkiewicz Anna , Kawalec-Kajstura Ewa , Kozieł Dorota , Młynarska Katarzyna , Grochans Elżbieta
Published: October 2022

(1) Lockdown-related fatigue occurring during the COVID-19 pandemic is a complex problem that can be experienced in different social groups. The objective of the current study is to attempt to identify socio-demographic and lifestyle-related factors that determine the impact of fatigue on health in general as well as in physical, cognitive, and psychosocial terms and to determine whether, and to what extent, these were predictors of fatigue in nursing students during the COVID-19 pandemic. (2) The study was conducted by the diagnostic poll method between 20 March and 15 December 2021 among 894 nursing students at six Polish universities. To collect the data, a validated Modified Fatigue Impact Scale (MFIS) was used. (3) Students from the age group of ≤20 experienced a significantly greater impact of fatigue on health in general as well as in physical and cognitive terms. The study demonstrated a significant negative relationship between the year of study and the impact of fatigue on health in general terms (r = −0.12; p < 0.0001) and the analyzed health terms, on physical (r = −0.12; p < 0.0001), cognitive (r = −0.10; p < 0.002), and psychosocial (r = −0.07; p < 0.041). In predicting the impact of fatigue on health in general and physical terms, it was the variable related to a reduction in physical activity during the COVID-19 pandemic that had the greatest contribution, while for the cognitive and psychosocial functions, it was the number of meals consumed per day. (4) It is recognized that action is needed to reduce the impact of fatigue on student health by modifying the predictors related to student lifestyles.
The Importance of PTH for Heart Failure. Comment on Thiele et al. The Role of Vitamin D3 as an Independent Predicting Marker for One-Year Mortality in Patients with Acute Heart Failure. J. Clin. Med. 2022, 11, 2733
Authors: Grant William B. , Jude Edward B.
Published: October 2022

The communication by Thiele et al. reported that there were no significant differences in serum 25-hydroxyvitamin D (25(OH)D) for the 22 of 118 acute heart failure (HF) patients, 71% with de novo HF and 29% with chronic HF, who died within 12 months after admission to the intermediate care unit of a maximum care hospital in Germany compared to those who survived [...]
Intramuscular Electrical Stimulation to Trigger Points: Insights into Mechanisms and Clinical Applications—A Scoping Review
Authors: Perreault Thomas , Ball Andrew , Dommerholt Jan , Theiss Robert , Fernández-de-las-Peñas César , Butts Raymond
Published: October 2022

Intramuscular electrical stimulation (IMES) is a modality used by clinicians to treat myofascial pain. Recent studies have shown positive results for the use of IMES on pain outcomes, yet studies investigating the potential mechanisms of IMES directly to trigger points (TrPs) are lacking. We performed a scoping review of the literature to summarize the current evidence from human and animal studies on the mechanisms of IMES to the TrP location, and to identify gaps in the existing literature. Electronic literature searches were conducted across five databases from inception to 15 August 2022, including PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), Scopus and Cochrane Register of Controlled Trials. Four studies met our full criteria for inclusion in this review. Three studies assessed the effects of IMES to TrPs on human subjects with MPS, and only one study used an animal model with experimentally generated TrPs. Based on the results of the included studies, IMES within a TrP region was reported to normalize muscle blood flow, decrease endplate noise of the TrP and elicit antinociceptive effects, at least partially, through engaging supraspinal descending pain inhibitory systems. At present, no clinical implications can be determined on the use of IMES to TrPs due to the limited amount and quality of the available evidence. Further studies investigating the clinical effectiveness and also underlying mechanisms of IMES to TrPs are clearly needed.
Lipoprotein(a): Evidence for Role as a Causal Risk Factor in Cardiovascular Disease and Emerging Therapies
Authors: Bhatia Harpreet S. , Wilkinson Michael J.
Published: October 2022

Lipoprotein(a) (Lp(a)) is an established risk factor for multiple cardiovascular diseases. Several lines of evidence including mechanistic, epidemiologic, and genetic studies support the role of Lp(a) as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis/calcific aortic valve disease (AS/CAVD). Limited therapies currently exist for the management of risk associated with elevated Lp(a), but several targeted therapies are currently in various stages of clinical development. In this review, we detail evidence supporting Lp(a) as a causal risk factor for ASCVD and AS/CAVD, and discuss approaches to managing Lp(a)-associated risk.
The Use of Matriderm® for Scalp Full-Thickness Defects Reconstruction: A Case Series
Authors: Dell’Aversana Orabona Giovanni , Maffia Francesco , Audino Giovanni , Abbate Vincenzo , Germano Cristiana , Bonavolontà Paola , Romano Antonio , Villari Riccardo , Mormile Mauro , Califano Luigi
Published: October 2022

Background: The scalp region represent a common area affected by benignant and malignant skin tumor, and it represents a surgical challenge when it is needed to be reconstructed. The aim of this study is to present our experience with full-thickness scalp skin defects, reconstructed using Matriderm® dermal substitute and split-thickness skin graft (STSG). Methods: A retrospective analysis of patients treated for scalp region reconstruction was conducted with 16 patients. All patients underwent the same procedure: scalp full-thickness tumor excision with simultaneous reconstruction with Matriderm® and the application of a split-thickness skin graft in the same surgical time. During follow-ups, the surgical outcome was evaluated by accurate clinical examination of the wound, adopting the Vancouver Scar Scale (VSS). Results: The outcomes obtained were satisfying: wound healing at the end of the procedures was optimal, grafted skin resulted similar to surrounding tissue, and pigmentation and vascularity showed a decrease in the period between 6 months and 1 follow-up. Conclusions: The use of Matriderm® and split-thickness skin grafting for scalp full-thickness defects reconstruction resulted in an optimal, stable, and safe procedure, suitable for elderly patients.
Prevalence and Quality of Endodontic Treatment in Patients with Cardiovascular Disease and Associated Risk Factors
Authors: Dash Gathani , Mishra Lora , Singh Naomi Ranjan , Behera Rini , Misra Satya Ranjan , Kumar Manoj , Sokolowski Krzysztof , Agarwal Kunal , Behera Suresh Kumar , Mishra Sunil , Lapinska Barbara
Published: October 2022

This study aimed to determine the prevalence and quality of endodontic treatment, by radiographically assessing the periapical periodontitis and endodontic treatment status in patients with cardiovascular disease (CVD) and cardiovascular risk (CVR) factors. Patients who visited the Out Patient Department of Institute of Dental Sciences and Department of Cardiology, Institute of Medical Sciences and SUM Hospital, Siksha ‘O’ Anusandhan University, Bhubaneswar, from August 2021 to February 2022, for a check-up or dental problem were considered as participants in this study. After obtaining informed consent, the participants were enrolled on the Oral Infections and Vascular Disease Epidemiology Study (INVEST) IDS, BHUBANESWAR. After testing negative for COVID-19, patients’ demographic details, such as age and gender were recorded, followed by a panoramic radiographic examination (OPG). A total sample of 408 patients were divided into three groups: Group 1/control (without any cardiovascular manifestation) consisting of 102 samples, group 2 of 222 CVR patients, and group 3 of 84 CVD cases. The CVR and CVD groups had a preponderance of elderly age groups between 60 to 70 years, with a significantly higher proportion of males. Co-morbidities such as diabetes mellitus, hypertension, and dyslipidemia were significantly associated with the CVR and CVD groups. From OPG interpretation, it was observed that the periapical radiolucency was greater in the CVR and CVD groups than in the control group (p = 0.009). The prevalence of endodontically treated teeth was higher in CVR and CVD than in the control group (p = 0.028). A high prevalence of dental caries, about 70%, was reported in all three groups (p = 0.356). The presence of dental restoration among all the groups was low (p = 0.079). The proportion of periodontal bone loss in the control group was significantly lower than CVR and CVD (p = 0.000). There was a strong association between periapical radiolucency, endodontically treated teeth, and periodontal bone loss in CVR and CVD patients. Notably, the associations reported herein do not reflect a cause-effect relationship; however, individuals with endodontic pathologies may accumulate additional risk factors predisposing them to hypertension or other CVDs. The results emphasize that eliminating local infections may decrease the systemic infection burden.
Preeclampsia and Fetal Growth Restriction as Risk Factors of Future Maternal Cardiovascular Disease—A Review
Authors: Sławek-Szmyt Sylwia , Kawka-Paciorkowska Katarzyna , Ciepłucha Aleksandra , Lesiak Maciej , Ropacka-Lesiak Mariola
Published: October 2022

Cardiovascular diseases (CVDs) remain the leading cause of death in women worldwide. Although traditional risk factors increase later-life CVD, pregnancy-associated complications additionally influence future CVD risk in women. Adverse pregnancy outcomes, including preeclampsia and fetal growth restriction (FGR), are interrelated disorders caused by placental dysfunction, maternal cardiovascular maladaptation to pregnancy, and maternal abnormalities such as endothelial dysfunction, inflammation, hypercoagulability, and vasospasm. The pathophysiologic pathways of some pregnancy complications and CVDs might be linked. This review aimed to highlight the associations between specific adverse pregnancy outcomes and future CVD and emphasize the importance of considering pregnancy history in assessing a woman’s CVD risk. Moreover, we wanted to underline the role of maternal cardiovascular maladaptation in the development of specific pregnancy complications such as FGR.
Viscoelastic Biomechanical Properties of the Conventional Aqueous Outflow Pathway Tissues in Healthy and Glaucoma Human Eyes
Authors: Karimi Alireza , Razaghi Reza , Padilla Steven , Rahmati Seyed Mohammadali , Downs J. Crawford , Acott Ted S. , Kelley Mary J. , Wang Ruikang K. , Johnstone Murray
Published: October 2022

Background: Although the tissues comprising the ocular conventional outflow pathway have shown strong viscoelastic mechanical response to aqueous humor pressure dynamics, the viscoelastic mechanical properties of the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm’s canal (SC) inner wall are largely unknown. Methods: A quadrant of the anterior segment from two human donor eyes at low- and high-flow (LF and HF) outflow regions was pressurized and imaged using optical coherence tomography (OCT). A finite element (FE) model of the TM, the adjacent JCT, and the SC inner wall was constructed and viscoelastic beam elements were distributed in the extracellular matrix (ECM) of the TM and JCT to represent anisotropic collagen. An inverse FE-optimization algorithm was used to calculate the viscoelastic properties of the ECM/beam elements such that the TM/JCT/SC model and OCT imaging data best matched over time. Results: The ECM of the glaucoma tissues showed significantly larger time-dependent shear moduli compared to the heathy tissues. Significantly larger shear moduli were also observed in the LF regions of both the healthy and glaucoma eyes compared to the HF regions. Conclusions: The outflow tissues in both glaucoma eyes and HF regions are stiffer and less able to respond to dynamic IOP.
Glenoid Inclination: Choosing the Transverse Axis Is Critical—A 3D Automated versus Manually Measured Study
Authors: Gauci Marc-Olivier , Jacquot Adrien , Boux de Casson François , Deransart Pierric , Letissier Hoël , Berhouet Julien
Published: October 2022

The aim of this study was to evaluate the variation in measured glenoid inclination measurements between each of the most used methods for measuring the scapular transverse axis with computed tomography (CT) scans, and to investigate the underlying causes that explain the differences. Methods: The glenoid center, trigonum and supraspinatus fossa were identified manually by four expert shoulder surgeons on 82 scapulae CT-scans. The transverse axis was generated either from the identified landmarks (Glenoid-Trigonum line (GT-line), Best-Fit Line Fossa (BFLF)) or by an automatic software (Y-axis). An assessment of the interobserver reliability was performed. We compared the measured glenoid inclination when modifying the transverse axis to assess its impact. Results: Glenoid inclination remained stable between 6.3 and 8.5°. The variations occurred significantly when changing the method that determined the transverse axis with a mean biase from −1.7 (BFLF vs. Y-axis) to 0.6 (BFLF vs. GT-line). The Y-axis method showed higher stability to the inclination variation (p = 0.030). 9% of cases presented more than 5° of discrepancies between the methods. The manual methods presented a lower ICC (BFLF = 0.96, GT-line = 0.87) with the widest dispersion. Conclusion: Methods that determine the scapular transverse axis could have a critical impact on the measurement of the glenoid inclination. Despite an overall good concordance, around 10% of cases may provide high discrepancies (≥5°) between the methods with a possible impact on surgeon clinical choice. Trigonum should be used with caution as its anatomy is highly variable and more than two single points provide a better interrater concordance. The Y-axis is the most stable referential for the glenoid inclination.
Physicians’ Considerations and Practice Recommendations Regarding the Use of Sodium-Glucose Cotransporter-2 Inhibitors
Authors: Jabbour Serge A. , Ibrahim Nasrien E. , Argyropoulos Christos P.
Published: October 2022

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), although initially developed as glucose-lowering drugs, provide significant beneficial effects on cardiorenal outcomes, including heart failure, regardless of type 2 diabetes status. Integration of SGLT-2is into clinical practice requires practical guidance for physicians about their use. To overcome physicians’ clinical inertia for SGLT-2i use, including addressing safety, potentially a barrier to their use, a roundtable discussion with physicians from three specialties (cardiology, endocrinology, and nephrology) was conducted. This review summarizes the physicians’ clinical experience and recommendations about SGLT-2i use across different patient populations, taking into consideration the beneficial effects of SGLT-2is and their safety. The key aspects discussed regarding SGLT-2i safety include acute effects on kidney function (estimated glomerular filtration rate acute dip upon SGLT-2i initiation and acute kidney injury), volume depletion, diabetic ketoacidosis, genitourinary infections, hyperkalemia, and hypoglycemia. To mitigate any potential risks related to SGLT-2i safety, physicians can make minor adjustments to an individual patient’s treatment plan, while retaining the SGLT-2i cardiorenal benefits for effective disease management. Recognition by physicians that the benefits of SGLT-2i use on clinical outcomes outweigh the risks will result in the integration of SGLT-2is into clinical practice and lead to improved patient care and outcomes.
Effect of Choline Alphoscerate on the Survival of Glioblastoma Patients: A Retrospective, Single-Center Study
Authors: Kim Yeong Jin , Lee Tae-Kyu , Noh Myung-Giun , Jung Tae-Young , Kim In-Young , Jung Shin , Lee Kyung-Hwa , Moon Kyung-Sub
Published: October 2022

Cognitive impairment often occurs in glioblastoma (GBM) patients due to the tumor itself and treatment side effects. Choline alphoscerate (L-alpha-glycerylphosphorylcholine, GPC) is frequently used to compensate for cognitive impairment in GBM patients. This study was conducted to determine whether GPC affects the overall survival (OS) and progression-free survival (PFS) of GBM patients. From 2011 to 2020, 187 isocitrate dehydrongenase (IDH)-wild-type GBM patients were analyzed. The patients were classified based on whether GPC was continuously used for at least 3 or 12 months (mos) after GBM diagnosis. Although GPC usage (≥3 mos) did not make significant differences in survival extension, median OS in the long-term GPC group (≥12 mos) was longer with statistical significance, compared to the control group (<12 mos) (38.3 vs. 24.0 mos, p = 0.004). In addition to younger age, supratentorial location, complete resection, and MGMT promoter methylation, long-term use of GPC (≥12 mos) was significantly associated with longer OS in multivariate analysis (p = 0.019, hazard ratio [HR] 0.532, 95% confidence interval [CI] 0.314–0.900). Despite the limitations of this study, long-term GPC use was possibly associated with prolonged survival in GBM patients. Multi-center prospective randomized studies with a large number of patients are needed to validate these findings.