bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrients in the Prevention of Osteoporosis in Patients with Inflammatory Bowel Diseases
Authors: Ratajczak Alicja Ewa , Rychter Anna Maria , Zawada Agnieszka , Dobrowolska Agnieszka , Krela-Kaźmierczak Iwona
Published: June 2020

The chronic character of inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, results in various complications. One of them is osteoporosis, manifested by low bone mineral density, which leads to an increased risk of fractures. The aetiology of low bone mineral density is multifactorial and includes both diet and nutritional status. Calcium and vitamin D are the most often discussed nutrients with regard to bone mineral density. Moreover, vitamins A, K, C, B12; folic acid; calcium; phosphorus; magnesium; sodium; zinc; copper; and selenium are also involved in the formation of bone mass. Patients suffering from inflammatory bowel diseases frequently consume inadequate amounts of the aforementioned minerals and vitamins or their absorption is disturbed, resulting innutritional deficiency and an increased risk of osteoporosis. Thus, nutritional guidelines for inflammatory bowel disease patients should comprise information concerning the prevention of osteoporosis.
“It’s Healthy Because It’s Natural.” Perceptions of “Clean” Eating among U.S. Adolescents and Emerging Adults
Authors: Ambwani Suman , Sellinger Gina , Rose Kelsey L. , Richmond Tracy K. , Sonneville Kendrin R.
Published: June 2020

Definitions for the culturally trendy “clean” eating phenomenon vary: whereas some characterize it as natural and healthy, others adopt more restrictive, moralizing, and affectively-laden definitions that may reflect disordered eating. We examined levels of familiarity with “clean” eating, sources of information, and perceptions of this dietary trend among a large, diverse sample of U.S. adolescents and emerging adults recruited from the National MyVoice Text Message Cohort (n = 1266; ages 14–24 years). Participants answered five questions assessing knowledge of “clean” eating, definitions, perceived healthiness vs. harm, and willingness to adopt “clean” eating, and responses were coded by three trained researchers. Results indicate that 55% of respondents had previously heard of “clean” eating, most commonly through social media, other online sources, and peers. Definitions were heterogeneous, with 40% offering “non-processed” or “whole foods” and 13% noting “non-GMO” or “organic” components. Few respondents (0.6%) expressed outright skepticism about “clean” eating, but many (30%) identified dietary avoidance and restriction as part of the definition. Overall, 71% characterized “clean” eating as a healthy approach, whereas 6% flagged it as “unhealthy”, and 18% noted elements of both healthfulness and harm. Notably, 41% reported they “probably would” try “clean” eating themselves, with greater willingness to try “clean” eating among cisgender women. Present findings highlight high levels of awareness and positive attitudes toward “clean” eating among young people in the U.S., with little recognition of the potential risks of dietary restriction. Further research should examine actual dietary behaviors to clarify potential risks of “clean” eating and related trends and thus inform strategies for eating disorder prevention.
Eveningness in Energy Intake among Adolescents with Implication on Anthropometric Indicators of Nutritional Status: The CRO-PALS Longitudinal Study
Authors: Rešetar Josip , Pfeifer Danijela , Mišigoj-Duraković Marjeta , Sorić Maroje , Gajdoš Kljusurić Jasenka , Šatalić Zvonimir
Published: June 2020

Shifting of energy intake towards a later time in the day is associated with an increased risk of obesity in adults. However, there is a lack of data for adolescents. The aim of this study was to investigate adolescents eveningness in energy intake (EV) and its association with anthropometric indicators of nutritional status. This investigation was based on results from the Croatian physical activity in adolescence longitudinal study (CRO-PALS). The cohort included 607 adolescents (50.25% females and 49.75% males) who were assessed at the age of 15/16 and 18/19. A single multi-pass 24-h recall was used as a dietary assessment method, while anthropometric indicators of nutritional status included body mass index (BMI), waist to hip ratio (WHR) and the sum of four skinfolds. The School Health Action, Planning and Evaluation System (SHAPES) questionnaire was used to assess active daily energy expenditure and sedentary behaviors. EV was significantly higher at 18/19 years compared to 15/16 years in whole population (p < 0.01), among male adolescents (p < 0.01), but not among female adolescents (p > 0.05). Although a significant correlation between EV and WHR was found in females at the age of 15/16 (p < 0.01), the results of this study suggest that EV has no or a minor effect on anthropometric indicators of nutritional status in adolescence.
Pitfalls in the Diagnosis of Coeliac Disease and Gluten-Related Disorders
Authors: Schiepatti Annalisa , Savioli Jessica , Vernero Marta , Borrelli de Andreis Federica , Perfetti Luca , Meriggi Antonio , Biagi Federico
Published: June 2020

The spectrum of gluten-related disorders (GRD) has emerged as a relevant phenomenon possibly impacting on health care procedures and costs worldwide. Current classification of GRD is mainly based on their pathophysiology, and the following categories can be distinguished: immune-mediated disorders that include coeliac disease (CD), dermatitis herpetiformis (DH), and gluten ataxia (GA); allergic reactions such as wheat allergy (WA); and non-coeliac gluten sensitivity (NCGS), a condition characterized by both gastrointestinal and extra-intestinal symptoms subjectively believed to be induced by the ingestion of gluten/wheat that has recently gained popularity. Although CD, DH, and WA are well-defined clinical entities, whose diagnosis is based on specific diagnostic criteria, a diagnosis of NCGS may on the contrary be considered only after the exclusion of other organic disorders. Neither allergic nor autoimmune mechanisms have been found to be involved in NCGS. Mistakes in the diagnosis of GRD are still a relevant clinical problem that may result in overtreatment of patients being unnecessary started on a gluten-free diet and waste of health-care resources. On the basis of our clinical experience and literature, we aim to identify the main pitfalls in the diagnosis of CD and its complications, DH, and WA. We provide a practical methodological approach to guide clinicians on how to recognize and avoid them.
Quantifying the Effect of Supplementation with Algae and Its Extracts on Glycolipid Metabolism: A Meta-Analysis of Randomized Controlled Trials
Authors: Ding Kun-xiang , Gao Tian-lin , Xu Rui , Cai Jing , Zhang Hua-qi , Sun Yong-ye , Zhong Feng , Ma Ai-guo
Published: June 2020

Aims: The effect of algae and its extract supplementation on glycolipid metabolism has not been finalized. Therefore, the purpose of the meta-analyses was to assess the effects of its supplementation on glycolipid metabolism concentration. Methods: We have systematically searched PubMed, Web of Science, the Cochrane Library and Embase to identify randomized controlled trials (RCTs) that investigated the impact of algae and its extracts supplementation on glycolipid metabolism. Effect size analysis was performed using weighted mean difference (WMD) and 95% CI between the methods of the experiment group and the control group. Subgroup analyses were performed to explore the possible influences of study characteristics. Publication bias and sensitivity analysis were also performed. Results: A total of 27 RCTs (31 trials) with 1221 participants were finally selected for the meta-analysis. The algae and its extract intervention significantly decreased glycosylated hemoglobin (HbA1c, WMD = −0.18%; 95% CI: −0.27 to −0.10; p < 0.001), high-density lipoprotein cholesterol (HDL-C, WMD = −0.22 mmol/L; 95% CI: −0.38 to −0.06; p = 0.008), and triglycerides (TC, WMD = −0.31 mmol/L; 95% CI: −0.37 to −0.25; p < 0.001) levels and increased insulin (WMD = 6.05 pmol/mL; 95% CI: 4.01 to 8.09; p < 0.001) levels. It did not significantly change the blood glucose, homeostasis model assessment-insulin resistance index (HOMA-IR), 2-h post-meal blood glucose (2hPBG) and other lipid profiles. Subgroup analyses based on the duration of intervention and subjects demonstrated that the intervention of algae and its extracts for 10 weeks or fewer and more than 40 subjects decreased TC levels (p < 0.05). Moreover, the intervention reduced TC and 2hPBG concentrations for East Asians (p < 0.05). Conclusions: Our findings provided evidence that algae and its extract interventions were beneficial for the regulation of human glycolipid metabolism. More precise RCTs on subjects are recommended to further clarify the effect of algae, seaweed polysaccharide, seaweed polypeptide, algae polyphenol and its products intervention on glycolipid metabolism.
Moderate Folic Acid Supplementation in Pregnant Mice Results in Behavioral Alterations in Offspring with Sex-Specific Changes in Methyl Metabolism
Authors: Cosín-Tomás Marta , Luan Yan , Leclerc Daniel , Malysheva Olga V. , Lauzon Nidia , Bahous Renata H. , Christensen Karen E. , Caudill Marie A. , Rozen Rima
Published: June 2020

Fifteen to 20% of pregnant women may exceed the recommended intake of folic acid (FA) by more than four-fold. This excess could compromise neurocognitive and motor development in offspring. Here, we explored the impact of an FA-supplemented diet (5× FASD, containing five-fold higher FA than recommended) during pregnancy on brain function in murine offspring, and elucidated mechanistic changes. We placed female C57BL/6 mice for one month on control diets or 5× FASD before mating. Diets were maintained throughout pregnancy and lactation. Behavioural tests were conducted on 3-week-old pups. Pups and mothers were sacrificed at weaning. Brains and livers were collected to examine choline/methyl metabolites and immunoreactive methylenetetrahydrofolate reductase (MTHFR). 5× FASD led to hyperactivity-like behavior and memory impairment in 3-week-old pups of both sexes. Reduced MTHFR protein in the livers of FASD mothers and male pups resulted in choline/methyl metabolite disruptions in offspring liver (decreased betaine) and brain (decreased glycerophosphocholine and sphingomyelin in male pups, and decreased phosphatidylcholine in both sexes). These results indicate that moderate folate supplementation downregulates MTHFR and alters choline/methyl metabolism, contributing to neurobehavioral alterations. Our findings support the negative impact of high FA on brain development, and may lead to improved guidelines on optimal folate levels during pregnancy.
Profiles of Human Milk Oligosaccharides and Their Relations to the Milk Microbiota of Breastfeeding Mothers in Dubai
Authors: Ayoub Moubareck Carole , Lootah Maryam , Tahlak Muna , Venema Koen
Published: June 2020

The composition of human breast milk is affected by several factors, including genetics, geographic location and maternal nutrition. This study investigated the human milk oligosaccharides (HMOs) of breastfeeding mothers living in Dubai and their relations with the milk microbiota. A total of 30 breast milk samples were collected from healthy Emirati and UAE-expatriates at Latifa Hospital. HMO profiling was performed using UHPLC-MS. Microbiota profiles were determined by sequencing amplicons of the V3-V4 region of the 16S rRNA gene. HMO concentrations were significantly higher in Emirati, and dropped with the lactation period in both groups of mothers. The Le (a−b+)-secretor (Le+Se+) type was the most abundant in Dubai mothers (60%), followed by the Le(a−b−)-secretor (Le−Se+) type (23%). Bifidobacterium and Lactobacillus were considerably lower in Dubai-based mothers, while Pseudomonas and Delftia (Hydrogenophaga) were detected at a higher abundance compared to mothers from other countries. Atopobium was correlated with sialyl-lacto-N-tetraose c, Leptotrichia and Veillonella were correlated with 6’-sialyl-lactose, and Porphyromonas was correlated with lacto-N-hexaose. The study highlights the HMO profiles of breastfeeding mothers in Dubai and reveals few correlations with milk microbial composition. Targeted genomic analyses may help in determining whether these differences are due to genetic variations or to sociocultural and environmental factors.
Total and Free Sugars Consumption in a Slovenian Population Representative Sample
Authors: Zupanič Nina , Hristov Hristo , Gregorič Matej , Blaznik Urška , Delfar Nataša , Koroušić Seljak Barbara , Ding Eric L. , Fidler Mis Nataša , Pravst Igor
Published: June 2020

Excessive free sugars consumption is associated with poor health outcomes. Thus, the World Health Organization (WHO) recommends limiting free sugars intake to no more than 10% of total energy intake. To evaluate current intakes of dietary sugars and monitor the adherence to the guidelines, the objective of this study was to comprehensively assess total and free sugars consumption of different age groups within the Slovenian population. The Slovenian national food consumption survey SI.Menu 2017/18 was conducted on representative samples of adolescents (10–17 years), adults (18–64 years), and the elderly (65–74 years) using two non-consecutive 24-h dietary recalls. The analyses were carried out on a sample of 1248 study participants. Free sugars content in food was estimated based on previously established databases. The population weighted median free sugars intake accounted for 10.1% of total energy intake (TEI) among adolescents, 6.4% among adults, and 6.5% in the elderly population. Both total and free sugars consumption in the percentage of TEI were higher among women than men, in participants with lower education, and those with higher family net income. The main sources of free sugars in adolescents were beverages, cakes, muffins, pastry, and dairy products; for adults and the elderly, the key sources of free sugars were beverages, cakes, muffins, pastry, and sugars, honey, and related products. A total of 56% of adolescents, 84% of adults, and 81% of the elderly population adhered to the WHO free sugars guidelines. Additional measures will be required to further decrease free sugars consumption among the teenage population, in which dietary patterns are still of greatest concern.
Microsatellite Investigations of Multiple Echinococcus granulosus Sensu Stricto Cysts in Single Hosts Reveal Different Patterns of Infection Events between Livestock and Humans
Authors: M’rad Selim , Oudni-M’rad Myriam , Bastid Vanessa , Bournez Laure , Mosbahi Sana , Nouri Abdelallatif , Babba Hamouda , Grenouillet Frédéric , Boué Franck , Umhang Gérald
Published: June 2020

Cystic echinococcosis (CE) caused by the cestode Echinococcus granulosus sensu lato (s.l.) is a worldwide zoonosis and E. granulosus sensu stricto (s.s.) is the most common species associated with animal and human diseases. The objective of this study was to obtain a better understanding of CE infection in livestock and humans from very low and high endemic areas—France and Tunisia—by studying the genetic diversity of E. granulosus s.s. at the intra-individual host level. This genetic diversity was studied using EgSca6 and EgSca11 microsatellite profiles in 93 sheep from France and Tunisia, and in 12 cattle and 31 children from Tunisia only, all presenting multiple CE cysts (2 to 10 cysts). Overall, 96% of sheep, 92% of cattle, and 48% of children had at least two cysts with different microsatellite profiles. Inversely, 35% of sheep, 17% of cattle, and 65% of children had at least two cysts with the same microsatellite profile. The genotyping results for the CE samples highlight high and similar genetic diversity in France and Tunisia, suggesting that the probability of being successively infected by CE of the same microsatellite profile was rare in both countries. Therefore, our results suggest that in rare cases, several eggs of the same microsatellite profile, from two to seven in our data, can be ingested simultaneously in a single infection event and develop into several cysts in livestock and children. They also indicate that multiple infection events are frequent in livestock, even in a low endemic country such as France, and are less frequent but not negligible in children in a high endemic country such as Tunisia. Moreover, this is the first time that genetic evidence of secondary CE has been found. Further studies are needed to better assess the pattern of infection events in livestock and humans, especially by studying the genetic diversity of adult worms in definitive hosts.
The Role of Sensor-Activated Faucets in Surgical Handwashing Environment as a Reservoir of Legionella
Authors: Mazzotta Marta , Girolamini Luna , Pascale Maria Rosaria , Lizzadro Jessica , Salaris Silvano , Dormi Ada , Cristino Sandra
Published: June 2020

Surgical handwashing is a mandatory practice to protect both surgeons and patients in order to control Healthcare-Associated Infections (HAIs). The study is focused on Legionella and Pseudomonas aeruginosa contamination in Surgical Handwashing Outlets (SHWOs) provided by sensor-activated faucets with Thermostatic Mixer Valves (TMVs), as correlated to temperature, technologies, and disinfection used. Samples were analyzed by standard culture techniques, comparing hot- and cold-water samples. Legionella isolates were typed by an agglutination test and by mip sequencing. Legionella contamination showed the same distribution between hot and cold samples concerning positive samples and mean concentration: 44.5% and 1.94 Log10 cfu/L vs. 42.6% and 1.81 Log10 cfu/L, respectively. Regarding the distribution of isolates (Legionella pneumophila vs. Legionella non-pneumophila species), significant differences were found between hot- and cold-positive samples. The contamination found in relation to ranges of temperature showed the main positive samples (47.1%) between 45.1–49.6 °C, corresponding to high Legionella concentrations (2.17 Log10 cfu/L). In contrast, an increase of temperature (>49.6 °C) led to a decrease in positive samples (23.2%) and mean concentration (1.64 Log10 cfu/L). A low level of Pseudomonas aeruginosa was found. For SHWOs located in critical areas, lack of consideration of technologies used and uncorrected disinfection protocols may lead to the development of a high-risk environment for both patients and surgeons.
Mitigation of Expression of Virulence Genes in Legionella pneumophila Internalized in the Free-Living Amoeba Willaertia magna C2c Maky
Authors: Mameri Rayane Mouh , Bodennec Jacques , Bezin Laurent , Demanèche Sandrine
Published: June 2020

Legionella pneumophila is a human pathogen responsible for a severe form of pneumonia named Legionnaire disease. Its natural habitat is aquatic environments, being in a free state or intracellular parasites of free-living amoebae, such as Acanthamoeba castellanii. This pathogen is able to replicate within some amoebae. Willaertia magna C2c Maky, a non-pathogenic amoeba, was previously demonstrated to resist to L. pneumophila and even to be able to eliminate the L. pneumophila strains Philadelphia, Lens, and Paris. Here, we studied the induction of seven virulence genes of three L. pneumophila strains (Paris, Philadelphia, and Lens) within W. magna C2c Maky in comparison within A. castellanii and with the gene expression level of L. pneumophila strains alone used as controls. We defined a gene expression-based virulence index to compare easily and without bias the transcript levels in different conditions and demonstrated that W. magna C2c Maky did not increase the virulence of L. pneumophila strains in contrast to A. castellanii. These results confirmed the non-permissiveness of W. magna C2c Maky toward L. pneumophila strains.
Early-Onset HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis
Authors: Schwalb Alvaro , Pérez-Muto Valeria , Cachay Rodrigo , Tipismana Martín , Álvarez Carolina , Mejía Fernando , González-Lagos Elsa , Gotuzzo Eduardo
Published: June 2020

Background: Vertical transmission of HTLV-1 could lead to the early development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This significantly affects quality of life and increases morbimortality. Objective: To describe the epidemiological and clinical characteristics of patients with early-onset HAM/TSP, defined as disease onset before 20 years of age. Methods: This is a retrospective study from an HTLV-1 clinical cohort between 1989 and 2019. We searched for medical records of patients with (1) diagnosis of HTLV-1 infection using two ELISA and/or one Western blot, (2) clinical diagnosis of HAM/TSP by neurological assessment, and (3) HAM/TSP symptom-onset before 20 years of age. Results: A total of 38 cases were identified in the cohort; 25 were female (66%). The median age of onset was 14 years old. 31 (82%) cases had HTLV-1 testing done among family members; 22 out of 25 tested mothers (88%) were HTLV-1 positive. Most patients (27/34) were breastfed for more than one year. Disease progression measured through EDSS and IPEC-1 showed an upward trend towards worsening spasticity with 18 patients (47%) eventually requiring mobility aids. Conclusions: Cases of early-onset HAM/TSP are not of rare occurrence, which translates into many more years of dependency, the use of mobility aids, and increased overall morbidity.
Interleukin-18, Functional IL-18 Receptor and IL-18 Binding Protein Expression in Active and Latent Tuberculosis
Authors: Wawrocki Sebastian , Kielnierowski Grzegorz , Rudnicka Wieslawa , Seweryn Michal , Druszczynska Magdalena
Published: June 2020

A thorough understanding of the processes modulating the innate and acquired immune response to Mycobacterium tuberculosis (M.tb) infection in the context of gene expression is still a scientific and diagnostic problem. The study was aimed to assess IL-18, IL-18 binding protein (IL-18BP), IL-18R, IFN-γ, and IL-37 mRNA expression in patients with active tuberculosis (ATB) and healthy volunteers with latent M.tb-infection (LTB) or M.tb-uninfected healthy controls (Control). The relative mRNA expression was assessed in the buffy coat blood fraction using the qPCR method. In total, 97 BCG-vaccinated Polish adults were enrolled in the study. The relative expression of IL-18 and IL-18BP mRNA was significantly elevated in the ATB and LTB groups. In ATB, but not LTB individuals, the overexpression of IL-18 and IL-18BP, as well as a significant increase in IFN-γ mRNA expression, might be considered as a manifestation of active tuberculosis disease. No statistically significant differences were observed in the IL-37 mRNA expression among the studied groups. Particularly noteworthy is the outstanding reduction in the relative expression of IL-18R mRNA in the LTB group as compared to the ATB and Control group. Reduced expression of IL-18R in LTB group may, at least partially, prevent the development of a pathological inflammatory reaction and promote the maintenance of homeostatic conditions between host immunity and M.tb.
Molecular Detection of Borrelia burgdorferi Sensu Lato and Anaplasma phagocytophilum in Ticks Collected from Dogs in Urban Areas of North-Eastern Poland
Authors: Michalski Mirosław M. , Kubiak Katarzyna , Szczotko Magdalena , Chajęcka Marta , Dmitryjuk Małgorzata
Published: June 2020

From 2016 to 2018, ticks were collected from 272 dogs admitted to veterinary clinics in the city of Olsztyn (north-eastern Poland). Among 522 collected ticks, 423 were identified as Ixodes ricinus (413 females and 10 males) and 99 as Dermacentor reticulatus (62 females and 37 males). Non-engorged (86 individuals) and engorged (436 individuals) ticks were screened for the presence of Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum DNA. Borrelia and A. phagocytophilum species detection was determined based on the sequence of the fla B and 16S RNA genes, respectively. DNA of B. burgdorferi s.l. was identified in 31.6% (165/522, 95% CI: 27.6–35.8%) of ticks (I. ricinus 151/423, 35.7%, 95% CI: 31.1–40.4%; D. reticulates 14/99, 14.1%, 95% CI: 7.9–22.6%). A. phagocytophilum was identified in 0.96% (5/522, 95% CI: 0.3–2.2%) of specimens. All positive samples were engorged I. ricinus females (5/402, 1.2%, 95% CI: 0.4–2.9%). In 85.4% (141/165, 95% CI: 79.1–90.4%) of Borrelia infected ticks, the DNA of one genospecies was revealed. The DNA of at least two different genospecies was detected in 14.5% of specimens (24/165, 95% CI: 9.5–20.8). The coexistence of B. burgdorferii s.l. and A. phagocytophilum was not detected.
Local Lung Immune Response to Mycobacterium bovis Challenge after BCG and M. bovis Heat-Inactivated Vaccination in European Badger (Meles meles)
Authors: Blanco Vázquez Cristina , Prieto Miguel , Barral Marta , Juste Ramón Antonio , Lesellier Sandrine , Salguero Francisco Javier , Davé Dipesh , Martínez Ileana Zorhaya , de Garnica García María Gracia , Casais Rosa , Balseiro Ana
Published: June 2020

Tuberculosis (TB) vaccination could be used as a key part of integrated strategies for the disease’s control if an effective and safe vaccine under field conditions is obtained. Recent studies in Spain have evaluated the protective efficacy of two oral vaccines against experimental challenge with live intra-bronchial Mycobacterium bovis in captive badgers: the live-attenuated M. bovis BCG vaccine (Danish strain) and a heat-inactivated M. bovis (HIMB) vaccine. With the objective of increasing the knowledge of the cellular development progress of infection and generating further tools to discriminate between mild and severe TB lesions between and within animals, the immunopathology of tuberculous lesions was studied to characterize the local immune response (cell type profile) within lung granulomas from control (non-vaccinated), BCG vaccinated and HIMB-vaccinated experimentally infected badgers with M. bovis. Four immunohistochemical protocols, for the specific detection of macrophages, T lymphocytes, B lymphocytes and plasma cells within TB granulomas in formalin fixed sections of the right middle lung lobe (lobe targeted for the M. bovis delivery), were performed. Immunolabelled sections were scanned and five randomly selected areas were analyzed with digital image analysis software. The results were expressed as the proportion of the positively immunolabelled area within the total area of the selected site. Data was analyzed using the statistical analysis software (SAS). In the three treatment groups, macrophages were the most abundant inflammatory cells within the granulomas, followed by B lymphocytes and plasma cells. T lymphocyes were absent in those granulomas. This would suggest a predominance of a non-specific innate response mediated by phagocytic cells over an adaptative humoral immune response. The proportion of macrophages and plasma cells was higher in BCG and HIMB-vaccinated badgers, respectively, suggesting the establishment of an adaptative humoral response in HIMB-vaccinated badgers. The lower bacterial load at the lung level, as well as the volume of lesions in lungs using magnetic resonance imaging in badgers with the HIMB vaccine in relation with local immune response presented, must be highlighted, since it would be an advantage in favor of its use under field conditions in terms of reducing TB transmission and environmental contamination.
Genetic Diversity of Porcine Circovirus Isolated from Korean Wild Boars
Authors: Song Sok , Park Gyu-Nam , Choe SeEun , Cha Ra Mi , Kim Song-Yi , Hyun Bang-Hun , Park Bong-Kyun , An Dong-Jun
Published: June 2020

In Korea, three genotypes of porcine circovirus type 2 (PCV2a, PCV2b, and PCV2d) have been identified on domestic pig farms, while two genotypes (PCV2a and PCV2b) have been identified in wild boar populations. Here, we investigated genotype diversity and genotypic shift in 91 PCV2 isolates from 1340 wild boars captured in South Korea between 2013 and 2017. Phylogenetic analyses based on the complete ORF2 showed that the 91 PCV2 strains were detected as four genotypes by qPCR screening assay: PCV2a (2.2%, 2/91), PCV2b (16.5%, 15/91), PCV2d (80.2%, 73/91), and PCV2h (1.1%, 1/91). Only one intergenotype recombinant event was detected between PCV2 ORF2 in wild boars (PCV2b) and domestic pigs (PCV2a). Amino acid positions 86–89 within ORF2, which distinguishes the different genotypes, were conserved in all PCV2 genotypes isolated from South Korean wild boars, including TNKI in PCV2a/PCV2h, SNPR in PCV2b, and SNPL in PCV2d. The estimated nucleotide substitution rates in the ORF2 region of viruses from South Korean wild boars and domestic pigs were 5.8145 × 10−4 and 4.5838 × 10−4 substitutions per site per year (s/s/y), respectively. The times to the most recent common ancestor (tMRCA) for South Korean domestic pig PCV2 were 1937 (PCV2a), 1972 (PCV2b), 1999 (PCV2d-1), and 2000 (PCV2d-2). By contrast, the tMRCA for South Korean wild boar PCV2b and PCV2d were 1989 and 2001, respectively. Thus, the PCV2d genotype is prevalent among South Korean wild boars and domestic pigs.
Effects of Carbamazepine, Lacosamide and Zonisamide on Gliotransmitter Release Associated with Activated Astroglial Hemichannels
Authors: Fukuyama Kouji , Ueda Yuto , Okada Motohiro
Published: June 2020

Recent studies using the genetic partial epilepsy model have demonstrated that hyperfunction of astroglial hemichannels contributes to pathomechanism of epileptic seizure. Therefore, to explore the novel anticonvulsive mechanisms, the present study determined the effects of voltage-dependent Na+ channel (VDSC)-inhibiting anticonvulsants, carbamazepine (CBZ), lacosamide (LCM), and zonisamide (ZNS) on the astroglial release of l-glutamate and adenosine triphosphate (ATP). The effects of subchronic administration of therapeutic-relevant dose of three anticonvulsants on the release of l-glutamate and ATP in the orbitofrontal cortex (OFC) were determined using microdialysis. The concentration-dependent effects of acute and subchronic administrations of anticonvulsants on astroglial gliotransmitter release were determined using primary cultured astrocytes. The concentration-dependent effects of subchronic administrations of anticonvulsants on connexin43 (Cx43) expression in the plasma membrane of primary cultured astrocytes were determined using the Simple Western system. An increase in the levels of extracellular K+ resulted in a concentration-dependent increase in the astroglial release of l-glutamate and ATP. The depleted levels of extracellular Ca2+ alone did not affect astroglial gliotransmitter release but did accelerate K+-evoked gliotransmitter release via activation of astroglial hemichannels. Both non-selective hemichannel inhibitor carbenoxolone (CBX) and selective Cx43 inhibitor GAP19 prevented both gliotransmitter release through activated astroglial hemichannels and the hemichannel-activating process induced by elevation of the levels of extracellular K+ with depletion of the levels of extracellular Ca2+. ZNS subchronically decreased Cx43 expression and acutely/subchronically inhibited Cx43 hemichannel activity. LCM acutely inhibited hemichannel activity but did not subchronically affect Cx43 expression. Therapeutic-relevant concentration of CBZ did not affect hemichannel activity or Cx43 expression, but supratherapeutic concentration of CBZ decreased Cx43 expression and hemichannel activity. Therefore, the present study demonstrated the distinct effects of CBZ, LCM, and ZNS on gliotransmitter release via modulation of astroglial hemichannel function. The different features of the effects of three VDSC-inhibiting anticonvulsants on astroglial transmission associated with hemichannels, at least partially, possibly contributing to the formation of the properties of these three anticonvulsants, including the antiepileptic spectrum and adverse effects regarding mood and cognitive disturbance.
Design and Development of Novel Urea, Sulfonyltriurea, and Sulfonamide Derivatives as Potential Inhibitors of Sphingosine Kinase 1
Authors: Roy Sonam , Mahapatra Amarjyoti Das , Mohammad Taj , Gupta Preeti , Alajmi Mohamed F. , Hussain Afzal , Rehman Md. Tabish , Datta Bhaskar , Hassan Md. Imtaiyaz
Published: June 2020

Sphingosine kinase 1 (SphK1) is one of the well-studied drug targets for cancer and inflammatory diseases. Recently discovered small-molecule inhibitors of SphK1 have been recommended in cancer therapeutics; however, selectivity and potency of first-generation inhibitors are great challenge. In search of effective SphK1 inhibitors, a set of small molecules have been designed and synthesized bearing urea, sulfonylurea, sulfonamide, and sulfonyltriurea groups. The binding affinity of these inhibitors was measured by fluorescence-binding assay and isothermal titration calorimetry. Compounds 1, 5, 6, and 7 showed an admirable binding affinity to the SphK1 in the sub-micromolar range and significantly inhibited SphK1 activity with admirable IC50 values. Molecular docking studies revealed that these compounds fit well into the sphingosine binding pocket of SphK1 and formed significant number of hydrogen bonds and van der Waals interactions. These molecules may be exploited as potent and selective inhibitors of SphK1 that could be implicated in cancer therapeutics after the required in vivo validation.
A Spray-Dried, Co-Processed Rice Starch as a Multifunctional Excipient for Direct Compression
Authors: Trisopon Karnkamol , Kittipongpatana Nisit , Kittipongpatana Ornanong Suwannapakul
Published: June 2020

A new co-processed, rice starch-based excipient (CS) was developed via a spray-drying technique. Native rice starch (RS) was suspended in aqueous solutions of 10%–15% cross-linked carboxymethyl rice starch (CCMS) and 0.5%–6.75% silicon dioxide (in the form of sodium silicate), before spray drying. The resulting CSs were obtained as spherical agglomerates, with improved flowability. The compressibility study revealed an improved plastic deformation profile of RS, leading to better compaction and tensile strength. The presence of CCMS also ensured a rapid disintegration of the compressed tablets. CS-CCMS:SiO2 (10:2.7), prepared with 10% CCMS, 2.7% silicon dioxide, and 40% solid content, was found to exhibit the best characteristics. Compared to the two commercial DC excipients, Prosolv® and Tablettose®, the flow property of CS-CCMS:SiO2 (10:2.7) was not significantly different, while the tensile strength was 23%: lower than that of Prosolv® but 4 times higher than that of Tablettose® at 196 MPa compression force. The disintegration time of CS-CCMS:SiO2 (10:2.7) tablet (28 s) was practically identical to that of Tablettose® tablet (26 s) and far superior to that of Prosolv® tablet (>30 min). These results show that CSs could potentially be employed as a multifunctional excipient for the manufacturing of commercial tablets by DC.
Hot Melt Coating of Amorphous Carvedilol
Authors: Bannow Jacob , Koren Lina , Salar-Behzadi Sharareh , Löbmann Korbinian , Zimmer Andreas , Rades Thomas
Published: June 2020

The use of amorphous drug delivery systems is an attractive approach to improve the bioavailability of low molecular weight drug candidates that suffer from poor aqueous solubility. However, the pharmaceutical performance of many neat amorphous drugs is compromised by their tendency for recrystallization during storage and lumping upon dissolution, which may be improved by the application of coatings on amorphous surfaces. In this study, hot melt coating (HMC) as a solvent-free coating method was utilized to coat amorphous carvedilol (CRV) particles with tripalmitin containing 10% (w/w) and 20% (w/w) of polysorbate 65 (PS65) in a fluid bed coater. Lipid coated amorphous particles were assessed in terms of their physical stability during storage and their drug release during dynamic in vitro lipolysis. The release of CRV during in vitro lipolysis was shown to be mainly dependent on the PS65 concentration in the coating layer, with a PS65 concentration of 20% (w/w) resulting in an immediate release profile. The physical stability of the amorphous CRV core, however, was negatively affected by the lipid coating, resulting in the recrystallization of CRV at the interface between the crystalline lipid layer and the amorphous drug core. Our study demonstrated the feasibility of lipid spray coating of amorphous CRV as a strategy to modify the drug release from amorphous systems but at the same time highlights the importance of surface-mediated processes for the physical stability of the amorphous form.
Vancomycin Loaded Glycerol Monooleate Liquid Crystalline Phases Modified with Surfactants
Authors: Milak Spomenka , Chemelli Angela , Glatter Otto , Zimmer Andreas
Published: June 2020

The influence of two tuning agents, polyglycerol ester (PE) and triblock copolymer (TC), on the properties of glycerol monooleate (MO) liquid crystalline phase (LCP) was investigated to achieve the therapeutic concentration of vancomycin hydrochloride (VHCl) into the eye, topically during 60 min (1 h) and intravitreally during 2880 min (48 h). Different techniques were used to elucidate the impact of surfactants on the structure of the LCP: polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), and in vitro release tests I and II (simulating local and intravitreal application in the eye). The structure analysis by SAXS depicts that the inclusion of PE into the MO LCP provided partial transition of a hexagonal phase into a lamellar phase, and TC induced a partial transition of a hexagonal phase into an LCP which identification was difficult. The LCP modulated with PE and TC demonstrated different VHCl’s release patterns and were evaluated by comparing our release data with the literature data. The comparison indicated that the LCP modulated with 30% w/w PE could be a promising VHCl delivery system intravitreally during 2880 min.
Development of a Self-Emulsifying Drug Delivery System for Optimized Topical Delivery of Clofazimine
Authors: van Staden Daniélle , du Plessis Jeanetta , Viljoen Joe
Published: June 2020

A quality-by-design and characterization approach was followed to ensure development of self-emulsifying drug delivery systems (SEDDSs) destined for topical delivery of the highly lipophilic clofazimine. Solubility and water-titration experiments identified spontaneous emulsification capacity of different excipient combinations and clofazimine. After identifying self-emulsification regions, check-point formulations were selected within the self-emulsification region by considering characteristics required to achieve optimized topical drug delivery. Check-point formulations, able to withstand phase separation after 24 h at an ambient temperature, were subjected to characterization studies. Experiments involved droplet size evaluation; size distribution; zeta-potential; self-emulsification time and efficacy; viscosity and pH measurement; cloud point assessment; and thermodynamic stability studies. SEDDSs with favorable properties, i.e., topical drug delivery, were subjected to dermal diffusion studies. Successful in vitro topical clofazimine delivery was observed. Olive oil facilitated the highest topical delivery of clofazimine probably due to increased oleic acid levels that enhanced stratum corneum lipid disruption, followed by improved dermal clofazimine delivery. Finally, isothermal microcalometric experiments studied the compatibility of excipients. Potential interactions were depicted between argan oil and clofazimine as well as between Span®60 and argan-, macadamia- and olive oil, respectively. However, despite some mundane incompatibilities, successful development of topical SEDDSs achieved enhanced topical clofazimine delivery.
Mesoporous Silica Nanoparticles for Co-Delivery of Drugs and Nucleic Acids in Oncology: A Review
Authors: Paris Juan L. , Vallet-Regí María
Published: June 2020

Mesoporous silica nanoparticles have attracted much attention in recent years as drug and gene delivery systems for biomedical applications. Among their most beneficial features for biomedicine, we can highlight their biocompatibility and their outstanding textural properties, which provide a great loading capacity for many types of cargos. In the context of cancer nanomedicine, combination therapy and gene transfection/silencing have recently been highlighted as two of its most promising fields. In this review, we aim to provide an overview of the different small molecule drug-nucleic acid co-delivery combinations that have been developed using mesoporous silica nanoparticles as carriers. By carefully selecting the chemotherapeutic drug and nucleic acid cargos to be co-delivered by mesoporous silica nanoparticles, different therapeutic goals can be achieved by overcoming resistance mechanisms, combining different cytotoxic mechanisms, or providing an additional antiangiogenic effect. The examples here presented highlight the great promise of this type of strategies for the development of future therapeutics.
Multimodal Decorations of Mesoporous Silica Nanoparticles for Improved Cancer Therapy
Authors: Barui Sugata , Cauda Valentina
Published: June 2020

The presence of leaky vasculature and the lack of lymphatic drainage of small structures by the solid tumors formulate nanoparticles as promising delivery vehicles in cancer therapy. In particular, among various nanoparticles, the mesoporous silica nanoparticles (MSN) exhibit numerous outstanding features, including mechanical thermal and chemical stability, huge surface area and ordered porous interior to store different anti-cancer therapeutics with high loading capacity and tunable release mechanisms. Furthermore, one can easily decorate the surface of MSN by attaching ligands for active targeting specifically to the cancer region exploiting overexpressed receptors. The controlled release of drugs to the disease site without any leakage to healthy tissues can be achieved by employing environment responsive gatekeepers for the end-capping of MSN. To achieve precise cancer chemotherapy, the most desired delivery system should possess high loading efficiency, site-specificity and capacity of controlled release. In this review we will focus on multimodal decorations of MSN, which is the most demanding ongoing approach related to MSN application in cancer therapy. Herein, we will report about the recently tried efforts for multimodal modifications of MSN, exploiting both the active targeting and stimuli responsive behavior simultaneously, along with individual targeted delivery and stimuli responsive cancer therapy using MSN.
Engineered Extracellular Vesicles/Exosomes as a New Tool against Neurodegenerative Diseases
Authors: Ferrantelli Flavia , Chiozzini Chiara , Leone Patrizia , Manfredi Francesco , Federico Maurizio
Published: June 2020

Neurodegenerative diseases are commonly generated by intracellular accumulation of misfolded/aggregated mutated proteins. These abnormal protein aggregates impair the functions of mitochondria and induce oxidative stress, thereby resulting in neuronal cell death. In turn, neuronal damage induces chronic inflammation and neurodegeneration. Thus, reducing/eliminating these abnormal protein aggregates is a priority for any anti-neurodegenerative therapeutic approach. Although several antibodies against mutated neuronal proteins have been already developed, how to efficiently deliver them inside the target cells remains an unmet issue. Extracellular vesicles/exosomes incorporating intrabodies against the pathogenic products would be a tool for innovative therapeutic approaches. In this review/perspective article, we identify and describe the major molecular targets associated with neurodegenerative diseases, as well as the antibodies already developed against them. Finally, we propose a novel targeting strategy based on the endogenous engineering of extracellular vesicles/exosomes constitutively released by cells of the central nervous system.
Preserving the Integrity of Liposomes Prepared by Ethanol Injection upon Freeze-Drying: Insights from Combined Molecular Dynamics Simulations and Experimental Data
Authors: Franzè Silvia , Selmin Francesca , Rocco Paolo , Colombo Giuseppe , Casiraghi Antonella , Cilurzo Francesco
Published: June 2020

The freeze-drying of complex formulations, such as liposomes, is challenging, particularly if dispersions contain residual organic solvents. This work aimed to investigate the effects of possible protectants, namely sucrose, trehalose and/or poly(vinyl pyrrolidone) (PVP), on the main features of the dried product using a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-based liposomal dispersion prepared by ethanol injection and containing ethanol up to 6%, as a model. The interactions among vesicles and protectants were preliminary screened by Molecular Dynamics (MD) simulations, which have been proved useful in rationalizing the selection of protectant(s). The freeze-drying protocol was based on calorimetric results. Overall data suggested a stronger cryo-protectant effect of trehalose, compared with sucrose, due to stronger interactions with the DPPC bilayer and the formation of highly ordered clusters around the lipids. The effect further improved in the presence of PVP. Differently from the other tested protectants, the selected trehalose/PVP combination allows to preserve liposome size, even in the presence of 6% ethanol, as demonstrated by Nanoparticle Tracking Analysis (NTA). Nevertheless, it should be also underlined that cakes blew out at an ethanol concentration higher than 1% v/v, probably due to the poor cohesion within the cake and solvent vapour pressure upon sublimation.
Pharmacy Technicians Help to Push Boundaries in Delivering Quality Care
Authors: Desselle Shane P. , Hohmeier Kenneth C.
Published: June 2020

We are so pleased that Pharmacy dedicated a themed Special Issue to pharmacy workforce supportpersonnel, namely technicians [...]
Covid-19 Predictions Using a Gauss Model, Based on Data from April 2
Authors: Schüttler Janik , Schlickeiser Reinhard , Schlickeiser Frank , Kröger Martin
Published: June 2020

We study a Gauss model (GM), a map from time to the bell-shaped Gaussian function to model the deaths per day and country, as a simple, analytically tractable model to make predictions on the coronavirus epidemic. Justified by the sigmoidal nature of a pandemic, i.e., initial exponential spread to eventual saturation, and an agent-based model, we apply the GM to existing data, as of 2 April 2020, from 25 countries during first corona pandemic wave and study the model’s predictions. We find that logarithmic daily fatalities caused by the coronavirus disease 2019 (Covid-19) are well described by a quadratic function in time. By fitting the data to second order polynomials from a statistical χ 2 -fit with 95% confidence, we are able to obtain the characteristic parameters of the GM, i.e., a width, peak height, and time of peak, for each country separately, with which we extrapolate to future times to make predictions. We provide evidence that this supposedly oversimplifying model might still have predictive power and use it to forecast the further course of the fatalities caused by Covid-19 per country, including peak number of deaths per day, date of peak, and duration within most deaths occur. While our main goal is to present the general idea of the simple modeling process using GMs, we also describe possible estimates for the number of required respiratory machines and the duration left until the number of infected will be significantly reduced.