bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal Patterns of Dominant Microbes Involved in Central Nutrient Cycles in the Subsurface
Authors: Lohmann Patrick , Benk Simon , Gleixner Gerd , Potthast Karin , Michalzik Beate , Jehmlich Nico , Bergen Martin von
Published: October 2020

Microbial communities play a key role for central biogeochemical cycles in the subsurface. Little is known about whether short-term seasonal drought and rewetting events influence the dominant microbes involved in C- and N-cycles. Here, we applied metaproteomics at different subsurface sites in winter, summer and autumn from surface litter layer, seepage water at increasing subsoil depths and remote located groundwater from two wells within the Hainich Critical Zone Exploratory, Germany. We observed changes in the dominance of microbial families at subsurface sampling sites with increasing distances, i.e., Microcoleaceae dominated in topsoil seepage, while Candidatus Brocadiaceae dominated at deeper and more distant groundwater wells. Nitrifying bacteria showed a shift in dominance from drought to rewetting events from summer by Nitrosomandaceae to autumn by Candidatus Brocadiaceae. We further observed that the reductive pentose phosphate pathway was a prominent CO2-fixation strategy, dominated by Woeseiaceae in wet early winter, which decreased under drought conditions and changed to a dominance of Sphingobacteriaceae under rewetting conditions. This study shows that increasing subsurface sites and rewetting event after drought alter the dominances of key subsurface microbes. This helps to predict the consequences of annual seasonal dynamics on the nutrient cycling microbes that contribute to ecosystem functioning.
Potential of Native Arbuscular Mycorrhizal Fungi, Rhizobia, and/or Green Compost as Alfalfa (Medicago sativa) Enhancers under Salinity
Authors: Ben-Laouane Raja , Baslam Marouane , Ait-El-Mokhtar Mohamed , Anli Mohamed , Boutasknit Abderrahim , Ait-Rahou Youssef , Toubali Salma , Mitsui Toshiaki , Oufdou Khalid , Wahbi Said , Meddich Abdelilah
Published: October 2020

Salinity is one of the devastating abiotic stresses that cause reductions in agricultural production. The increased salinization affects alfalfa growth, metabolism, and rhizobium capacity for symbiotic N2 fixation negatively. This study was undertaken to investigate the efficiency of green compost (C; made from green waste), arbuscular mycorrhizal fungi (M; field-sourced native consortium), and/or rhizobium (R; a salt-tolerant rhizobium strain) individually or in combination as an effective strategy to improve alfalfa productivity under non-saline and high-saline (120 mM NaCl) conditions. In addition, we aimed to understand the agro-physiological and metabolic basis as well as glomalin content in the soil of biofertilizers-induced salt tolerance in alfalfa. Here, we show that mycorrhizal infection was enhanced after MR inoculation, while C application decreased it significantly. Salinity reduced growth, physiological functioning, and protein concentration, but the antioxidant system has been activated. Application of the selected biofertilizers, especially C alone or combined with M and/or R improved alfalfa tolerance. The tri-combination CMR mitigated the negative effects of high salinity by stimulating plant growth, roots and nodules dry matters, mineral uptake (P, N, and K), antioxidant system, synthesis of compatible solutes, and soil glomalin content, sustaining photosynthesis-related performance and decreasing Na+ and Cl− accumulation, lipid peroxidation, H2O2 content, and electrolyte leakage.
Arsenic Fixation in Polluted Soils by Peat Applications
Authors: Aguilar-Garrido Antonio , Romero-Freire Ana , García-Carmona Minerva , Martín Peinado Francisco J. , Sierra Aragón Manuel , Martínez Garzón Francisco J.
Published: October 2020

Soil arsenic (As) pollution is still a major concern due to its high toxicity and carcinogenicity, thus, the study of decontamination techniques, as the organic amendment applications, keeps upgrading. This research evaluates the potential remediation of peat in different As-polluted soils, by assessing the decrease of As solubility and its toxicity through bioassays. Obtained reduction in As solubility by peat addition was strongly related to the increase of humic substances, providing colloids that allow the complexation of As compounds. Calcareous soils have been the least effective at buffering As pollution, with higher As concentrations and worse biological response (lower soil respiration and inhibition of lettuce germination). Non-calcareous soils showed lower As concentrations due to the higher iron content, which promotes As fixation. Although in both cases, peat addition improves the biological response, it also showed negative effects, hypothetically due to peat containing toxic polyphenolic compounds, which in the presence of carbonates appears to be concealed. Both peat dose tested (2% and 5%) decreased drastically As mobility; however, for calcareous soils, as there is no phytotoxic effect, the 5% dose is the most recommended; while for non-calcareous soils the efficient peat dose for As decontamination could be lower.
Submarine Hydrothermal Discharge and Fluxes of Dissolved Fe and Mn, and He Isotopes at Brothers Volcano Based on Radium Isotopes
Authors: Neuholz René , Kleint Charlotte , Schnetger Bernhard , Koschinsky Andrea , Laan Patrick , Middag Rob , Sander Sylvia , Thal Janis , Türke Andreas , Walter Maren , Zitoun Rebecca , Brumsack Hans-Jürgen
Published: October 2020

Hydrothermal venting is an important transfer process of energy and elements between the Earth’s solid material and the oceans. Compared to mid-ocean-ridge hydrothermal vent fields, those at intra-oceanic island arcs are typically in shallower water depth and have a more variable geochemical fluid composition. Biologically essential trace elements (such as Fe and Mn) are generally elevated in fluids of both deep and shallow hydrothermal vent fields, while vents at shallower water depth influence the photic zone more directly and thus are potentially more relevant for marine primary productivity. However, fluid flux estimations of island arc hydrothermal systems into the surrounding water column are scarce. This study (I) presents a method based on short-lived radium isotopes to estimate submarine hydrothermal discharge (SHD), (II) applies this method at Brothers volcano in the southern Kermadec arc, located northeast of New Zealand, and (III) gives dissolved Fe, Mn and He isotope flux estimates for the Earth´s longest intra-oceanic island arc, the Kermadec arc. The comparison between measured inert He isotope concentrations in the plume with calculated concentrations based on Ra isotopes matched reasonably well, which supports the use of a Ra-based discharge model. Overall, this study represents a novel approach to assess fluid and thus trace element fluxes from one hydrothermal vent field, which can be applied in future studies on various hydrothermal systems to improve geochemical models of element cycling in the ocean.
Design and Optimization of Piezoresistive PEO/PEDOT:PSS Electrospun Nanofibers for Wearable Flex Sensors
Authors: Verpoorten Eve , Massaglia Giulia , Ciardelli Gianluca , Pirri Candido Fabrizio , Quaglio Marzia
Published: October 2020

Flexible strain sensors are fundamental devices for application in human body monitoring in areas ranging from health care to soft robotics. Stretchable piezoelectric strain sensors received an ever-increasing interest to design novel, robust and low-cost sensing units for these sensors, with intrinsically conductive polymers (ICPs) as leading materials. We investigated a sensitive element based on crosslinked electrospun nanofibers (NFs) directly collected and thermal treated on a flexible and biocompatible substrate of polydimethylsiloxane (PDMS). The nanostructured active layer based on a blend of poly(ethylene oxide) (PEO) and poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) as the ICP was optimized, especially in terms of the thermal treatment that promotes electrical conductivity through crosslinking of PEO and PSS, preserving the nanostructuration and optimizing the coupling between the sensitive layer and the substrate. We demonstrate that excellent properties can be obtained thanks to the nanostructured active materials. We analyzed the piezoresistive response of the sensor in both compression and traction modes, obtaining an increase in the electrical resistance up to 90%. The Gauge Factors (GFs) reflected the extraordinary piezoresistive behavior observed: 45.84 in traction and 208.55 in compression mode, which is much higher than the results presented in the literature for non-nanostructurated PEDOT.
Bioinspired Extracellular Vesicles: Lessons Learned From Nature for Biomedicine and Bioengineering
Authors: Zinger Assaf , Brozovich Ava , Pasto Anna , Sushnitha Manuela , Martinez Jonathan O. , Evangelopoulos Michael , Boada Christian , Tasciotti Ennio , Taraballi Francesca
Published: October 2020

Efficient communication is essential in all layers of the biological chain. Cells exchange information using a variety of signaling moieties, such as small molecules, proteins, and nucleic acids. Cells carefully package these messages into lipid complexes, collectively named extracellular vesicles (EVs). In this work, we discuss the nature of these cell carriers, categorize them by their origin, explore their role in the homeostasis of healthy tissues, and examine how they regulate the pathophysiology of several diseases. This review will also address the limitations of using EVs for clinical applications and discuss novel methods to engineer nanoparticles to mimic the structure, function, and features of EVs. Using lessons learned from nature and understanding how cells use EVs to communicate across distant sites, we can develop a better understanding of how to tailor the fundamental features of drug delivery carriers to encapsulate various cargos and target specific sites for biomedicine and bioengineering.
Publisher’s Note: Continued Publication of Neurology International by MDPI
Authors: Lin Shu-Kun , Vazquez Franck , Vicario Unai
Published: October 2020

Neurology International was launched in 2009 and it has been published over the past eleven years by PAGEPress Publications [...]
Chronological Age Interacts with the Circadian Melatonin Receptor 1B Gene Variation, Determining Fasting Glucose Concentrations in Mediterranean Populations. Additional Analyses on Type-2 Diabetes Risk
Authors: Sorlí Jose V. , Barragán Rocío , Coltell Oscar , Portolés Olga , Pascual Eva C. , Ortega-Azorín Carolina , González José I. , Estruch Ramon , Saiz Carmen , Pérez-Fidalgo Alejandro , Ordovas Jose M. , Corella Dolores
Published: October 2020

Gene-age interactions have not been systematically investigated on metabolic phenotypes and this modulation will be key for a better understanding of the temporal regulation in nutrigenomics. Taking into account that aging is typically associated with both impairment of the circadian system and a decrease in melatonin secretion, we focused on the melatonin receptor 1B (MTNR1B)-rs10830963 C>G variant that has been associated with fasting glucose concentrations, gestational diabetes, and type-2 diabetes. Therefore, our main aim was to investigate whether the association between the MTNR1B-rs10830963 polymorphism and fasting glucose is age dependent. Our secondary aims were to analyze the polymorphism association with type-2 diabetes and explore the gene-pregnancies interactions on the later type-2 diabetes risk. Three Mediterranean cohorts (n = 2823) were analyzed. First, a cross-sectional study in the discovery cohort consisting of 1378 participants (aged 18 to 80 years; mean age 41 years) from the general population was carried out. To validate and extend the results, two replication cohorts consisting of elderly individuals were studied. In the discovery cohort, we observed a strong gene-age interaction (p = 0.001), determining fasting glucose in such a way that the increasing effect of the risk G-allele was much greater in young (p = 5.9 × 10−10) than in elderly participants (p = 0.805). Consistently, the association of the MTNR1B-rs10830963 polymorphism with fasting glucose concentrations in the two replication cohorts (mean age over 65 years) did not reach statistical significance (p > 0.05 for both). However, in the elderly cohorts, significant associations between the polymorphism and type-2 diabetes at baseline were found. Moreover, in one of the cohorts, we obtained a statistically significant interaction between the MTNR1B polymorphism and the number of pregnancies, retrospectively assessed, on the type-2 diabetes risk. In conclusion, the association of the MTNR1B-rs10830963 polymorphism with fasting glucose is age-dependent, having a greater effect in younger people. However, in elderly subjects, associations of the polymorphism with type-2 diabetes were observed and our exploratory analysis suggested a modulatory effect of the number of past pregnancies on the future type-2 diabetes genetic risk.
Understanding Vietnamese Urban Consumers’ Nutrition Label Use, Health Concerns, and Consumption of Food and Beverages with Added Sugars
Authors: Nguyen-Anh Duc , Umberger Wendy J. , Zeng Di
Published: October 2020

Vietnam is experiencing a diet and nutrition transition. Increasing consumption of food and beverages with added sugars is a significant public health concern. Policies and interventions, such as mandatory nutrition labelling, are being considered to improve consumers’ awareness and understanding of diet and health implications of added sugars in food and beverages. The effectiveness of various policy approaches relies on an improved understanding of the interrelationships between urban Vietnamese consumers’ health concerns, nutrition label use, and intake of sugars. We empirically disentangle these relationships for urban Vietnamese households using novel intra-household data covering 4047 adults and 737 adolescents from 1590 households in Hanoi and Ho Chi Minh City. The data are from comprehensive household surveys and 24-hour food diaries. Simultaneous equation regression models are estimated using three-stage least squares (3SLS) to account for possible endogeneity. Nutrition label use is significantly associated with a lower share of calories from foods and beverages with added sugars. These findings suggest that nutrition labelling programs may be an effective policy mechanism to reduce the negative health implications of increasing availability and consumption of food and beverages with added sugars in urban Vietnam.
Pulse Consumption among Portuguese Adults: Potential Drivers and Barriers towards a Sustainable Diet
Authors: Duarte Mariana , Vasconcelos Marta , Pinto Elisabete
Published: October 2020

The transition from diets rich in animal products to plant-based protein foods—like pulses—is crucial, for both environmental sustainability and human health. The aim of this study was to characterize the current consumption and to describe the drivers of and barriers to pulse intake in Portugal. Using a quantitative approach, a semi-structured questionnaire was distributed online, and 1174 valid responses were obtained. The most consumed pulses were beans and peas, consumed at least once a week by 48.3% and 44.4% of the sample, respectively. When participants were asked about the possibility of replacement, even partially, of animal products for pulses, 15.0% stated they would not substitute even in a food scarcity scenario. In the qualitative study, ten individuals involved at different steps of pulses’ supply and value chain were interviewed in order to study individual behaviors and experiences linked knowledge and consumption of pulses. It was noticed that the lack of recognition of their nutritional value, the high cooking time and the effect of the anti-nutritional factors were commonly pointed out as barriers. The identification and understanding of perceived barriers for that low consumption will leverage the development of new strategies to promote this promising alternative.
Lactoferrin Metal Saturation—Which Form Is the Best for Neonatal Nutrition?
Authors: Majka Grzegorz , Pilarczyk-Zurek Magdalena , Baranowska Agnieszka , Skowron Beata , Strus Magdalena
Published: October 2020

We evaluated the impact of metal saturation of lactoferrin (with iron and manganese) on population numbers of pathogenic species relevant for neonatal sepsis that commonly originates from the gut due to bacterial translocation. Little attention has been paid to how metal ions bound to the protein affect its activity. Several reference and clinical strains as well as probiotic strains were incubated with different forms of lactoferrin: metal-depleted (apolactoferrin), iron-saturated (hololactoferrin) and manganese-saturated lactoferrin. We also attempted to confirm the observed effects of lactoferrin forms in vivo using rat pups. The observed decrease in population numbers of Gram-negative rods could not be confirmed by quantitative plating—lactoferrin may regulate these populations diversely (e.g., by anti-biofilm activity) and contribute to the inhibition of inflammatory response. We did not see any effect of lactoferrin forms on staphylococci and bifidobacteria. However, we have noted a significant increase of population numbers of Lactobacillus strains upon incubation with manganese-saturated lactoferrin. These results were confirmed in vivo in a rat model. Metal saturation is an underestimated factor regulating lactoferrin activity. Some forms are more potent in the inhibition of pathogenic species while others, such as manganese-saturated lactoferrin, could contribute to the restoration of gut homeostasis.
The Effect of Soluble Fiber Dextrin on Subjective and Physiological Markers of Appetite: A Randomized Trial
Authors: Emilien Christine , Hsu Walter , Hollis James
Published: October 2020

Obesity is a leading public health problem throughout the world. The development of foods that increase satiety and reduce food may aid weight management. This study determined the effect of consuming soluble fiber dextrin (SFD) on appetite, appetitive hormones, breath hydrogen and food intake in adults. Forty-three participants completed this study. For each treatment, 50% of the SFD was provided in liquid form as part of breakfast and 50% in solid form as a morning snack. Appetite questionnaires, blood and breath samples were collected immediately before breakfast and at regular intervals during the test session. The participants consumed an ad libitum lunch meal, afternoon snack and dinner meal, and the amount eaten was recorded. Following dinner, participants left the laboratory but were required to keep a diet diary for the remainder of the day. Breath hydrogen concentration was significantly higher following the consumption of SFD compared to control (p < 0.05). There was no observed overall treatment effect of consuming SFD on GLP-1 (Glucagon-Like-Peptide-1), ghrelin, CCK-8 (Cholecystokinin) or PYY3-36 (Petptide YY) (p > 0.05). Moreover, consuming foods containing SFD had no effect on subjective appetite or food intake (p > 0.05). Consuming foods containing SFD increased breath hydrogen but did not influence food intake, appetite or appetitive hormones. However, the limitations of this study may have individually or collectively masked an effect of SFD on food intake and appetite.
Identification of Cyclopropane Fatty Acids in Human Plasma after Controlled Dietary Intake of Specific Foods
Authors: Lolli Veronica , Dall’Asta Margherita , Del Rio Daniele , Caligiani Augusta
Published: October 2020

Cyclopropane fatty acids (CPFAs) are an investigated class of secondary fatty acids of microbial origin recently identified in foods. Even though the dietary daily intake of this class of compounds it has been recently estimated as not negligible, to date, no studies specifically have investigated their presence in human plasma after consumption of CPFA-rich sources. Therefore, the aims of this study were (i) to test CPFAs concentration in human plasma, thus demonstrating their in vivo bioaccessibility and potential bioavailability, (ii) to investigate a dose-response relationship between medium term chronic intake of CPFAs-rich foods and both CPFAs and plasma total fatty acid profiles in healthy subjects. Ten healthy normal weight adults were enrolled for conducting an in vivo study. Participants were asked to follow a CPFA-controlled diet for 3 weeks, consuming 50 g of Grana Padano cheese (GP) and 250 mL of whole cow milk, which correspond to a total of 22.1 mg of CPFAs. Fasting CPFAs concentration were monitored for eight timepoints during the whole study and plasma total fatty acids composition was determined by GC-MS. CPFAs, mainly dihydrosterculic acid (DHSA), were identified in plasma total fatty acids profile at the beginning of the study and after dietary treatment. A significant (p < 0.05) increase of CPFAs mean plasma concentration (n = 10) were observed at the end of the dietary intervention. Contrarily, the total fatty acids composition of the general plasma fatty acids profile did not significantly change (p ≥ 0.05) during the dietary intervention period. This is the first investigation demonstrating that CPFAs are bioaccessible in vivo and, as expected, their plasmatic concentration may be affected by consumption of CPFAs-rich foods. This research will open the door to further detailed research, which may better elucidate the role of these compounds in human health.
Effects of Vitamin D Supplementation on Lipid Profile in Adults with the Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: AlAnouti Fatme , Abboud Myriam , Papandreou Dimitrios , Mahboub Nadine , Haidar Suzan , Rizk Rana
Published: October 2020

Background: Metabolic syndrome (MetS) increases the risk of cardiovascular disease, with atherogenic dyslipidemia being a major contributing factor. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to assess whether vitamin D supplementation (VDS) alleviates dyslipidemia in adults with MetS. Scientific databases (PUBMED, MEDLINE, CINAHL, EMBASE, Cochrane Library, ClinicalTrials.gov, International Clinical Trials Registry Platform) and the gray literature were searched for randomized controlled trials of VDS, reporting on blood lipids. A narrative review, meta-analyses, sensitivity analyses, and appraisal of the risk of bias and overall quality of evidence produced were conducted. Results: Seven studies were included, and four were meta-analyzed. The risk of bias was generally low, and the final quality of evidence was low or very low. VDS, whether in high or low dose, significantly increased endline vitamin D blood levels; did not affect total, low-density, high-density cholesterol levels, and novel lipid-related biomarkers; yet, significantly increased triglycerides (TG) levels compared with placebo (MD: 30.67 (95%CI: 4.89–56.45) mg/dL; p = 0.02 for low-dose VDS; and MD: 27.33 (95%CI: 2.06–52.59) mg/dL; p = 0.03 for high-dose VDS). Pertaining heterogeneity was high (I2 = 86%; and I2 = 51%, respectively), and some included studies had significantly higher baseline TG in the intervention arm. The sensitivity analyses revealed robust results. Conclusion: VDS seems not to affect blood lipids in adults with MetS.
Parental Child-Feeding in the Context of Child Temperament and Appetitive Traits: Evidence for a Biopsychosocial Process Model of Appetite Self-Regulation and Weight Status
Authors: Liew Jeffrey , Zhou Zhiqing , Perez Marisol , Yoon Myeongsun , Kim Mirim
Published: October 2020

Pediatric obesity is a serious public health challenge and there is a need for research that synthesizes the various linkages among the child and parental factors that contribute to pediatric overweight and obesity. The main objective of this study was to examine potential mechanisms and pathways that might explain how child temperament is indirectly related to child body composition through appetitive traits and parental child-feeding practices. Participants consisted of 221 children between 4–6 years of age (51% males, mean age = 4.80 years, standard deviation = 0.85) and their parents (90.5% biological mothers, (Mage) = 32.02 years, (SDage) = 6.43) with 71% of the parents being married. Study variables included child temperament (negative affectivity and effortful control), child appetitive traits (food avoidance and food approach), controlling parental child-feeding practices (restrictive feeding and pressure to eat), and child body composition. Body composition were indexed by parent perceptions, body mass index (BMI), and percent body fat. Results showed that children with low levels of effortful control are more prone to exhibit food avoidance, which in turn is likely to elicit parental pressure to eat that in turn is linked to high child weight status. In addition, children with high levels of negative affectivity are prone to exhibit a food approach, which in turn is likely to elicit restrictive feeding from parents that in turn is linked to high child objective weight status. Findings situate controlling parental child-feeding practices in the context of child temperament and appetitive traits using a biopsychosocial framework of appetite self-regulation and weight. Results highlight that child appetite self-regulation processes and parental child-feeding practices could be essential components to target in childhood obesity preventive interventions.
Cystic Echinococcosis: Clinical, Immunological, and Biomolecular Evaluation of Patients from Sardinia (Italy)
Authors: Santucciu Cinzia , Bonelli Piero , Peruzzu Angela , Fancellu Alessandro , Marras Vincenzo , Carta Antonello , Mastrandrea Scilla , Bagella Giorgio , Piseddu Toni , Profili Stefano , Porcu Alberto , Masala Giovanna
Published: October 2020

Cystic echinococcosis (CE), a zoonotic disease caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato (s.l.), is a worldwide public health problem. Echinococcus granulosus sensu stricto (s.s.), associated with G1 and G3 genotypes, is endemic with high prevalence in the Mediterranean basin. The parasite’s life cycle comprises definitive hosts (canids) and intermediate hosts (ruminants) and can occasionally involve humans. The main aim of this research was to confirm the diagnosis of 13 patients suspected of CE who presented different complications and needed the surgical removal of the cysts. We also wanted to understand and clarify more the diagnosis of echinococcosis in humans. For this purpose, the patients first underwent cyst evaluation by ultrasound (US), immunological analysis, and then total pericystectomy, followed by parasitological, histopathological, and molecular biology examinations of the cysts. US stadiated one CE1, one CE2, eight CE3b, one CE4, and two CE5; immunology evidenced nine positives; histopathology confirmed 11 CE cysts, of which 8 fertile presenting protoscoleces were identified as E. granulosus s.s. by molecular biology, genotyped as three G1 and four G3 by neighbor-joining (NJ) phylogenetic tree. In conclusion, the results showed that 11 patients were affected by E. granulosus s.s. G1 orG3, and 2 cystic neoformations were of non-parasitic origin.
Irritability, Poor Feeding and Respiratory Alkalosis in Newborns: Think about Metabolic Emergencies. A Brief Summary of Hyperammonemia Management
Authors: Del Re Stefano , Empain Aurélie , Vicinanza Alfredo , Balasel Ovidiu , Johansson Anne-Britt , Stalens Jean-Philippe , De Laet Corinne
Published: October 2020

The urea cycle is a series of metabolic reactions that convert ammonia into urea in order to eliminate it from the body. Urea cycle disorders are characterized by hyperammonemia, which can cause irreversible damages in central nervous system. We report a series of three newborns presenting irritability, poor feeding and tachypnea. Their first gas analysis revealed respiratory alkalosis. Hyperammonemia was confirmed, and three different enzymatic blocks in the urea cycle were diagnosed. Immediate treatment consisted in the removal of ammonia by reduction of the catabolic state, dietary adjustments, use of nitrogen scavenging agents and ultimately hemodiafiltration. Hyperammonemia is a medical emergency whose treatment should not be delayed. This report aims to highlight the importance of suspecting urea cycle disorders in newborns with aspecific signs of hyperammonemia and respiratory alkalosis, and to sum up the broad lines of hyperammonemia management.
Testis-Sparing Surgery for Non-Palpable Leydig Cell Tumors in Prepubertal Children
Authors: Lambropoulos Vassilis , Theodorakopoulos Antonios , Mouravas Vasileios , Pazarli Elissavet , Godosis Dimitrios , Kepertis Chrysostomos , Anastasiadis Kleanthis , Spyridakis Ioannis
Published: October 2020

Leydig cell tumor (LCT) is an infrequent stromal neoplasm of the testis with an incidence of less than 3% of all gonadal tumors in the general male population. Only 25% is found in prepubertal children, where Leydig cell tumors are always reported benign. The hospital records of two prepubertal male children, who underwent organ sparing surgery for testicular LCT the last five years, were retrospectively reviewed. In both of them, the lesion was incidentally found during a scrotal ultrasonography for testicular pain. The diagnosis of a benign LCT was based on the pre-operative physical examination and imaging (Ultrasound-US, Magnetic Resonance Imaging-MRI) as well as the negative tumor markers. A testicle-sparing procedure was decided and the pathologic examination of the surgical specimen confirmed the diagnosis. No tumor recurrence was noted on follow-up. Testis-sparing surgery provides the possibility of complete excision of such lesions and should be considered as the treatment of choice.
The Fakir Child: Clinical Observation or Invasive Treatment?
Authors: Gatto Antonio , Angelici Serenella , Di Pangrazio Claudia , Nanni Lorenzo , Buonsenso Danilo , Paradiso Filomena Valentina , Chiaretti Antonio
Published: October 2020

Accidental swallowing of foreign bodies is a common problem among the pediatric population (6 months to 3 years), especially if the foreign body (FB) presents a sharp end that could potentially lead to perforation of the gastrointestinal (GI) tract, resulting in infection and complications. We report the case of a 2-year-old, admitted to the Emergency Department of our hospital after ingesting two FBs classifiable as sharp objects, specifically two metal nails, both approximately 4-cm long, which had been swallowed in one go, as reported by the parents. The patient had been previously admitted to another hospital in the same region, where the Emergency Department (ED) doctors took an X-ray to confirm the ingestion. The foreign bodies ingestion was thus confirmed, and they were, according to their report, located in the GI tract over the stomach. The patient has been monitored through all of his stay in the hospital and the progression of the foreign bodies has been documented with serial X-rays. Since neither clinical nor radiological signs of perforation were present, putting the FBs in the small bowel, a non-operative expectant management was followed. After 4 days of admission, the patient had passed one of the two FBS and later on the second one, without any complication. Thereafter the patient was discharged. The management of sharp gastrointestinal foreign objects ingestion is still debated, and the data of the current literature are poor. A number of case reports and small case series describe successful conservative management for the majority of ingested sharp objects. According to the literature data, our report confirms that the ingestion of sharp objects and relatively big objects in a baby can be successfully non-operatively managed, even despite the age of the patient and though the FBs are multiple.
Phenolic Compounds Reduce the Fat Content in Caenorhabditis elegans by Affecting Lipogenesis, Lipolysis, and Different Stress Responses
Authors: Aranaz Paula , Navarro-Herrera David , Zabala María , Romo-Hualde Ana , López-Yoldi Miguel , Vizmanos José Luis , Milagro Fermín I. , González-Navarro Carlos J.
Published: October 2020

Supplementation with bioactive compounds capable of regulating energy homeostasis is a promising strategy to manage obesity. Here, we have screened the ability of different phenolic compounds (myricetin, kaempferol, naringin, hesperidin, apigenin, luteolin, resveratrol, curcumin, and epicatechin) and phenolic acids (p-coumaric, ellagic, ferulic, gallic, and vanillic acids) regulating C. elegans fat accumulation. Resveratrol exhibited the strongest lipid-reducing activity, which was accompanied by the improvement of lifespan, oxidative stress, and aging, without affecting worm development. Whole-genome expression microarrays demonstrated that resveratrol affected fat mobilization, fatty acid metabolism, and unfolded protein response of the endoplasmic reticulum (UPRER), mimicking the response to calorie restriction. Apigenin induced the oxidative stress response and lipid mobilization, while vanillic acid affected the unfolded-protein response in ER. In summary, our data demonstrates that phenolic compounds exert a lipid-reducing activity in C. elegans through different biological processes and signaling pathways, including those related with lipid mobilization and fatty acid metabolism, oxidative stress, aging, and UPR-ER response. These findings open the door to the possibility of combining them in order to achieve complementary activity against obesity-related disorders.
Development of a Curcumin-Loaded Polymeric Microparticulate Oral Drug Delivery System for Colon Targeting by Quality-by-Design Approach
Authors: Hales Dana , Tefas Lucia Ruxandra , Tomuță Ioan , Moldovan Cristian , Gulei Diana , Munteanu Raluca , Porfire Alina
Published: October 2020

The purpose of this study was to apply the quality-by-design (QbD) approach for the development of colon-targeted curcumin-loaded polymeric microparticles (Col-CUR-MPs). The proportion of the enterosoluble polymer (Eudragit® FS) in the polymeric matrix, curcumin concentration, and the concentration of the polymer mixture (Eudragit® FS-polycaprolactone) were identified as potential risk factors for the quality of the final product following risk assessment. The influence of these variables on the critical quality attributes (CQAs) of Col-CUR-MPs was investigated. Therefore, a central composite face experimental design was used in order to determine the functional relationships between variables and product CQAs. The obtained regression model and contour plots were used to establish the design space. Finally, the model was validated by preparing two microparticulate formulations, one corresponding to the robust setpoint from within the design space and one outside the established design space, and calculating the percentage bias between the experimental and predicted values. The in vivo study, which was conducted on a fluorescein-loaded formulation that corresponded to the robust setpoint determined by QbD and that contained a mixture of polycaprolactone and Eudragit® FS (60:40, w/w), confirmed the colon-targeting qualities of this formulation.
Timeline of Translational Formulation Technologies for Cancer Therapy: Successes, Failures, and Lessons Learned Therefrom
Authors: Pérez-López Alexandre , Martín-Sabroso Cristina , Torres-Suárez Ana Isabel , Aparicio-Blanco Juan
Published: October 2020

Over the past few decades, the field of cancer therapy has seen a significant change in the way in which formulations are designed and developed, resulting in more efficient products that allow us to ultimately achieve improved drug bioavailability, efficacy, and safety. However, although many formulations have entered the market, many others have fallen by the wayside leaving the scientific community with several lessons to learn. The successes (and failures) achieved with formulations that have been approved in Europe and/or by the FDA for the three major types of cancer therapy (peptide-based therapy, chemotherapy, and radiotherapy) are reviewed herein, covering the period from the approval of the first prolonged-release system for hormonal therapy to the appearance of the first biodegradable microspheres intended for chemoembolization in 2020. In addition, those products that have entered phase III clinical trials that have been active over the last five years are summarized in order to outline future research trends and possibilities that lie ahead to develop clinically translatable formulations for cancer treatment.
Prodrugs for Improved Drug Delivery: Lessons Learned from Recently Developed and Marketed Products
Authors: Markovic Milica , Ben-Shabat Shimon , Dahan Arik
Published: October 2020

Prodrugs are bioreversible, inactive drug derivatives, which have the ability to convert into a parent drug in the body. In the past, prodrugs were used as a last option; however, nowadays, prodrugs are considered already in the early stages of drug development. Optimal prodrug needs to have effective absorption, distribution, metabolism, and elimination (ADME) features to be chemically stable, to be selective towards the particular site in the body, and to have appropriate safety. Traditional prodrug approach aims to improve physicochemical/biopharmaceutical drug properties; modern prodrugs also include cellular and molecular parameters to accomplish desired drug effect and site-specificity. Here, we present recently investigated prodrugs, their pharmaceutical and clinical advantages, and challenges facing the overall prodrug development. Given examples illustrate that prodrugs can accomplish appropriate solubility, increase permeability, provide site-specific targeting (i.e., to organs, tissues, enzymes, or transporters), overcome rapid drug metabolism, decrease toxicity, or provide better patient compliance, all with the aim to provide optimal drug therapy and outcome. Overall, the prodrug approach is a powerful tool to decrease the time/costs of developing new drug entities and improve overall drug therapy.
Development of Self-Associating SN-38-Conjugated Poly(ethylene oxide)-Poly(ester) Micelles for Colorectal Cancer Therapy
Authors: Sadat Sams M. A. , Vakili Mohammad Reza , Paiva Igor M. , Weinfeld Michael , Lavasanifar Afsaneh
Published: October 2020

The clinical use of 7-ethyl-10-hydroxy-camptothecin (SN-38), which is the active metabolite of irinotecan, has been hampered because of its practical water-insolubility. In this study, we successfully synthesized two self-associating SN-38-polymer drug conjugates to improve the water-solubility of SN-38, while retaining its anticancer activity. The polymeric micellar SN-38 conjugates were composed of either methoxy-poly(ethylene oxide)-block-poly(α-benzyl carboxylate-ε-caprolactone) conjugated to SN-38 at the PBCL end (mPEO-b-PBCL/SN-38) or mPEO-block-poly(α-carboxyl-ε-caprolactone) attached to SN-38 from the pendent-free carboxyl site (mPEO-b-PCCL/SN-38). The chemical structure of block copolymers was confirmed by 1H NMR. The physicochemical characterizations of their self-assembled structures including size, surface charge, polydispersity, critical micellar concentration, conjugation content and efficiency, morphology, kinetic stability, and in vitro release of SN-38 were compared between the two formulations. In vitro anticancer activities were evaluated by measuring cellular cytotoxicity and caspase activation by MTS and Caspase-Glo 3/7 assays, respectively. The hemolytic activity of both micellar structures against rat red blood cells was also measured. The results showed the formation of SN-38-polymeric micellar conjugates at diameters < 50 nm with a narrow size distribution and sustained release of SN-38 for both structures. The loading content of SN-38 in mPEO-b-PBCL and mPEO-b-PCCL were 11.47 ± 0.10 and 12.03 ± 0.17 (% w/w), respectively. The mPEO-b-PBCL/SN-38, end-capped micelles were kinetically more stable than mPEO-b-PCCL/SN-38. The self-assembled mPEO-b-PBCL/SN-38 and mPEO-b-PCCL/SN-38 micelles resulted in significantly higher cytotoxic effects than irinotecan against human colorectal cancer cell lines HCT116, HT-29, and SW20. The CRC cells were found to be 70-fold to 330-fold more sensitive to micellar SN-38 than irinotecan, on average. Both SN-38-incorporated micelles showed two-fold higher caspase-3/7 activation levels than irinotecan. The mPEO-b-PBCL/SN-38 micelles were not hemolytic, but mPEO-b-PCCL/SN-38 showed some hemolysis. The overall results from this study uphold mPEO-b-PBCL/SN-38 over mPEO-b-PCCL/SN-38 micellar formulation as an effective delivery system of SN-38 that warrants further preclinical investigation.
Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban
Authors: Ngo Lien Thi , Yang Sung-yoon , Tran Quyen Thi , Kim Sang Kyum , Yun Hwi-yeol , Chae Jung-woo
Published: October 2020

Rivaroxaban (RIV) is commonly prescribed with carbamazepine or phenytoin (CBZ/PHT) in post-stroke seizure or post-stroke epilepsy patients. Although adverse events have been reported in several previous studies when they are coadministered, there are no studies of the interactions between these drugs. Therefore, our study was conducted to solve this lack of information. The potential effects of CBZ/PHT were investigated by comparing the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of RIV between the control group (RIV alone) and the test groups (RIV administered with CBZ/PHT) in rats using the noncompartmental analysis (NCA) and the compartmental model approach. The NCA results indicate that AUCt of RIV decreased by 57.9% or 89.7% and Cmax of RIV decreased by 43.3% or 70.0% after administration of CBZ/PHT, respectively. In addition, both CBZ and PHT generally reduced the effects of RIV on the prothrombin times of the blood samples. PK profiles of RIV were most properly described by a two-compartment disposition model with a mixed first- and zero-order absorption kinetics and a first-order elimination kinetics. The compartmental model approach showed that a 211% or 1030% increase in CL/F of RIV and a 33.9% or 43.4% increase in D2 of RIV were observed in the test groups by the effects of CBZ/PHT, respectively. In conclusion, CBZ and PHT significantly reduced RIV exposure and therefore reduced the therapeutic effects of RIV. Consequently, this might result in adverse events due to insufficient RIV concentration to attain its therapeutic effects. Further studies are needed to validate this finding.
Coplanar Electrode Polymer Modulators Incorporating Fluorinated Polyimide Backbone Electro-Optic Polymer
Authors: Lee Eun-Su , Kim Sung-Moon , Yi Mi-Hye , Ka Jae-Won , Oh Min-Cheol
Published: October 2020

High-speed coherent optical communication has been expanding to handle the ever-increasing data traffic, and the large modulation bandwidth of electro-optic (EO) polymer modulators has been especially appreciated. However, to be useful in optical communication, the EO polymer device should address several issues, such as thermal stability, photo-oxidation, and bias drift. In this work, as a part of the experiments to address these challenges, an EO polymer with a fluorinated polyimide backbone is utilized to create EO polymer modulators with improved thermal stability. A coplanar electrode structure is introduced to enhance the poling efficiency and reduce the bias drift.
Impact of Seed Dressing and Soil Application of Potassium Humate on Cotton Plants Productivity and Fiber Quality
Authors: Ullah Asmat , Ali Muqarrab , Shahzad Khurram , Ahmad Fiaz , Iqbal Shahid , Rahman Muhammad Habib Ur , Ahmad Shakeel , Iqbal Muhammad Mazhar , Danish Subhan , Fahad Shah , Alkahtani Jawaher , Soliman Elshikh Mohamed , Datta Rahul
Published: October 2020

Humus is the stable form of added crop and animal residues. The organic matter after a long-term decomposition process converts into humic substances. The naturally occurring humus is present in less amount in soils of the arid and semi-arid regions. The addition of commercially available humic acid can, therefore, contribute to improving soil health and crop yields. The present study was conducted to evaluate the effect of potassium humate, applied through soil seed dressing, on cotton productivity and fiber quality attributes. Seed dressing with potassium humate was done at the rate of 0, 100, 150 and 200 mL kg−1 seed while in soil potassium humate was applied at the rate of 0, 10, 20 and 30 L ha−1. Results showed that the combined application of potassium humate by seed dressing and through soil application improved the soil properties, productivity and fiber quality traits of cotton. All levels of soil applied potassium humate (10, 20 and 30 L ha−1) performed better over seed dressing in terms of cotton productivity and fiber quality attributes. Among the soil application rates, 20 L ha−1 potassium humate proved better as compared to other rates (0, 10 and 30 L ha−1). Higher soil application of potassium humate (30 L ha−1) showed depressing effects on all the traits studied like the reduction of 12.4% and 6.6% in Ginning out turn and fiber length, respectively, at a seeding dressing of 200 mL kg−1. In conclusion, potassium humate seed dressing and soil application at the rate of 200 mL kg−1 and 20 L ha−1, respectively, is a better approach to improve cotton productivity. Soil potassium humate should not exceed a rate of 20 L ha−1 when the seed dressing of potassium is also practiced.
Breaking the Dormancy of Snake’s Head Fritillary (Fritillaria meleagris L.) In Vitro Bulbs—Part 1: Effect of GA3, GA Inhibitors and Temperature on Fresh Weight, Sprouting and Sugar Content
Authors: Marković Marija , Trifunović Momčilov Milana , Uzelac Branka , Cingel Aleksandar , Milošević Snežana , Jevremović Slađana , Subotić Angelina
Published: October 2020

Bulbs are the main vegetative reproductive organs of Fritillaria meleagris L. In nature, as well as in vitro, they become dormant and require low temperatures for further growth during the next vegetative period. In the present study, using 10 μM of gibberellic acid (GA3), or gibberellin biosynthesis (GA) inhibitors—ancymidol (A) and paclobutrazol (P)—the dynamic changes in soluble sugars, fructose and glucose content, fresh weight and sprouting capacity were investigated. F. meleagris bulbs were cultured on medium with GA3 and GA inhibitors for 1, 2 and 5 weeks at two different temperatures (24 and 7 °C). GA3 improved bulb fresh weight, as well as sprouting percentage at both tested temperatures, compared to the control. The highest fresh weight increase (57.7%) and sprouting rate (29.02%) were achieved when bulbs were grown at 24 °C for 5 weeks. In addition, soluble sugar content was the highest in bulbs grown for 5 weeks on medium supplemented with GA3. The main sugar in fritillary bulbs was glucose, while fructose content was lower. The sensitivity of bulbs to GA inhibitors differed and significantly affected sugar content in bulbs. To our knowledge, this is the first study of the sugar composition in F. meleagris bulbs during breaking of the bulb’s dormancy and its sprouting.