bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of a Multidisciplinary Approach on Cardiometabolic Risk Reduction in a Multiracial Cohort of Adults: A 1-Year Pilot Study
Authors: Nieto-Martínez Ramfis , Velásquez-Rodríguez Andrés , Neira Claudia , Mou Xichen , Neira Andres , Garcia Gabriela , Velásquez-Rodríguez Pedro , Levy Marian , Mechanick Jeffrey I. , Velásquez-Mieyer Pedro A.
Published: August 2022

Evidence examining specific effects of a multidisciplinary team (MDT) on cardiometabolic risk factors (CMRFs) among multi-ethnic patients in real-world clinical settings is lacking. This one-year retrospective chart review (2018) analyzed 598 adults (African American 59%, Hispanic 35%, and Caucasian 6%) with mean age of 43.8 ± 14.0 years. Qualifying patients with primary inclusion criteria of having body mass indices and blood pressure (BP) measurements in the first and last quarter of the study period were treated under an MDT protocol and compared to those qualifying for MDT but treated solely by a primary care provider (PCP). MDT included endocrinologist-directed visits, lifestyle counseling, and shared medical appointments. MDT patients experienced a greater reduction (β; 95% CI) in weight (−4.29 kg; −7.62, −0.97), BMI (−1.43 kg/m2; −2.68, −0.18), systolic BP (−2.18 mmHg; −4.09, −0.26), and diastolic BP (−1.97 mmHg; −3.34, −0.60). Additionally, MDT patients had 77%, 83%, and 59% higher odds of reducing ≥5% of initial weight, 1 BMI point, and ≥2 mmHg DBP, respectively. Improvements in hemoglobin A1C measurements were observed in the MDT group (insufficient data to compare with the PCP group). Compared to PCP only, MDT co-management improves CMRF related to adiposity and hypertension in a multiethnic adult cohort in real-world clinical settings. Patient access to best practices in cardiometabolic care is a priority, including the incorporation of culturally adapted evidence-based recommendations translated within a multi-disciplinary infrastructure, where competing co-morbidities are better managed, and associated research and education programs can promote operational sustainability.
Post-Diagnosis Vitamin D Supplement Use and Survival among Cancer Patients: A Meta-Analysis
Authors: Chen Qiao-Yi , Kim Sohyun , Lee Bohyoon , Jeong Gyeongin , Lee Dong Hoon , Keum NaNa , Manson JoAnn E. , Giovannucci Edward L.
Published: August 2022

Vitamin D administered pre-diagnostically has been shown to reduce mortality. Emerging evidence suggests a role of post-diagnosis vitamin D supplement intake for survival among cancer patients. Thus, we conducted a meta-analysis to evaluate the relationship. PubMed and Embase were searched for relevant observational cohort studies and randomized trials published through April 2022. Summary relative risk (SRR) and 95% confidence interval (CI) were estimated using the DerSimonian–Laird random-effects model. The SRR for post-diagnosis vitamin D supplement use vs. non-use, pooling cohort studies and randomized trials, was 0.87 (95% CI, 0.78–0.98; p = 0.02; I2 = 0%) for overall survival, 0.81 (95% CI, 0.62–1.06; p = 0.12; I2 = 51%) for progression-free survival, 0.86 (95% CI, 0.72–1.03; p = 0.10; I2 = 0%) for cancer-specific survival, and 0.86 (95% CI, 0.64–1.14; p = 0.29; I2 = 0%) for relapse. Albeit not significantly heterogeneous by variables tested, a significant inverse association was limited to cohort studies and supplement use during cancer treatment for overall survival, and to studies with ≤3 years of follow-up for progression-free survival. Post-diagnosis vitamin D supplement use was associated with improved overall survival, but not progression-free or cancer-specific survival or relapse. Our findings require confirmation, as randomized trial evidence was insufficient to establish cause-and-effect relationships.
IL-1 Receptor Antagonist (IL-1Ra) Levels and Management of Metabolic Disorders
Authors: Luotola Kari
Published: August 2022

Low-grade inflammation is a major player in obesity and the metabolic syndrome predicting development of type 2 diabetes (T2DM). The interleukin-1 receptor antagonist (IL-1Ra) is a vital and natural anti-inflammatory factor and mediator in glucose homeostasis disturbances. The predictive role is independent of multiple confounders, and elevated levels appear few years before T2DM. The role of IL-1Ra is important for accumulated risk factors, dysregulated metabolism and glucose homeostasis, and dietary interventions. Longitudinal and cross-sectional population study cohorts have enabled the approximation of IL-1Ra limit values for metabolic dysregulation and guide further analysis as a potential biomarker. The limit value of IL-1Ra is reaching 400 pg/mL with prediabetes and before T2DM. However, subjects with metabolic syndrome are suggested to have lower limit values, especially among men. Future research may evaluate the role of IL-1Ra in actual glucose homeostasis together with routine fasted laboratory tests, such as glucose and C-reactive protein (CRP) instead of the oral glucose tolerance test. The significance of intermediate low IL-1Ra levels in metabolic abnormalities should be further analyzed. It is possible to specify the impact of multiple lifestyle and metabolic parameters together with age and sex. IL-1Ra could be studied in multiple approaches including interventional studies of metabolic diseases.
Uncovering the Effect of European Policy-Making Initiatives in Addressing Nutrition-Related Issues: A Systematic Literature Review and Bibliometric Analysis on Front-of-Pack Labels
Authors: Mazzù Marco Francesco , Baccelloni Angelo , Finistauri Piera
Published: August 2022

The last decades have been marked by the introduction of front-of-pack labels (FoPL) as an institutional corrective action against obesity and nutrition-related illnesses. However, FoPL-related policy-making initiatives issued by the European Union evolved over time and led to a diversity of labels with different effects on consumers’ decisions. As a result, the extant literature adapted to the regulative scenario over the years and investigated the effects of the labels, creating consensus on some topics while being fragmented on others. Similarly, policy-makers adapted some regulations to the evidence supported by the research. With the aim to systematize the overall structure and evolution of the literature on FoPL, investigate the presence of a consensus on specific topics through a co-citation analysis, and examine the evolution of the consensus and co-citation networks over the years and potential research gaps, we report the results of bibliometric and co-citation analyses and a systematic literature review involving 170 papers and a selection of 49 articles published in the last months, for a total of 219 articles, analysed according to three timespans (Period 1 (1989–2011); Period 2 (2012–2016) and Period 3 (2017–2022)). Our findings highlight the interplay of policy development and FoPL research, the presence of few self-reinforcing and well-established co-citation networks based on validated evidence in the literature and the presence of alternative emerging theories that offer different and valid perspectives overlooked by mainstream co-citation research networks.
Dietary Nutrient Intake and Blood Micronutrient Status of Children with Crohn’s Disease Compared with Their Shared-Home Environment, Healthy Siblings
Authors: Brown Stephanie , Wall Catherine L. , Frampton Chris , Gearry Richard B. , Day Andrew S.
Published: August 2022

(1) The nutritional status of children with Crohn’s disease (CD) is rarely described. This study aimed to assess the dietary intake and blood micronutrient status of children with CD compared with their healthy, shared-environment siblings. (2) Methods: This observational study included children with CD (cases) and their shared-environment siblings (controls). The dietary nutrient intake was assessed with a four-day food/beverage diary and was compared with the recommended daily intakes (RDI). Blood micronutrient concentrations were measured using laboratory methods. The nutritional analyses were completed through a multivariate analysis of variance between groups. Between-group comparisons of single-nutrients were assessed using a Mann–Whitney U-test. Chi-squared analyses compared the proportion of children who did not meet the RDI for each nutrient. The results were significant at 0.05. (3) Results: The dietary intake was similar for most nutrients, except the controls had a lower intake of vitamins A and E, copper, zinc, iron, and selenium (p < 0.05). Children using partial enteral nutrition had significantly higher intakes of many micronutrients. It was common for both groups to not meet the RDI’s—more than 50% of cases for 9 nutrients and more than 50% of controls for 13 nutrients. (4) Conclusion: New Zealand children with CD and their shared-environment siblings did not meet the RDI for several micronutrients. Dietary education and/or micronutrient supplementation may be required.
Processed Dietary Patterns during Pregnancy Are Associated with Low Birth Weight at Term among Women of Advanced and Non-Advanced Age
Authors: Chen Tzu-Ling , Cheng Su-Fen , Gau Meei-Ling , Lin Li-Li
Published: August 2022

Inappropriate dietary intake during pregnancy is a key factor in low birth weight (LBW). This study compares LBW between healthy and processed dietary patterns by focusing on women of advanced maternal age. A cross-sectional survey was conducted with 327 postpartum women in Taiwan. The participants were assigned to two groups according to their age (≥35 years, n = 151; and 20–34 years, n = 176). An online questionnaire asked women how often they consumed 27 food items during their pregnancy. The prevalence of LBW was higher in the processed dietary pattern (79.3%) than in the healthy pattern (13.78%, p < 0.001). LBW was positively correlated with advanced maternal age (≥35 ages), low pre-pregnancy weight (BMI less than 18.5 kg/m2), insufficient gestational weight gain (GWG), and processed dietary patterns. Older mothers were 5.8 times more likely to have infants with LBW (odds ratio = 5.8; 95% confidence interval 2.0–16.6). A processed dietary pattern was 9.4 times more likely to result in LBW. Insufficient GWG was significantly positively associated with LBW (OR = 4.0; 95%CI 1.4–11.6). Maternal diet during pregnancy is an important modifiable factor for LBW. Prenatal advice should emphasize optimal nutrition, especially in older and underweight women.
Bergamot Polyphenol Extract Reduces Hepatocyte Neutral Fat by Increasing Beta-Oxidation
Authors: Mirarchi Angela , Mare Rosario , Musolino Vincenzo , Nucera Saverio , Mollace Vincenzo , Pujia Arturo , Montalcini Tiziana , Romeo Stefano , Maurotti Samantha
Published: August 2022

Background: Bergamot polyphenolic fraction (PF) extract exerts a beneficial against liver steatosis. However, the fundamental processes underlying this beneficial effect of bergamot PF remain elusive. In this work, we examined the effect of bergamot PF extract on 2D and 3D hepatocyte cultures. Material and Methods: We evaluated the effect of bergamot PF in 2D and 3D cultures from rat, human hepatoma cells, and human primary hepatocytes. Results: In 2D cell culture, we demonstrated that incubation with bergamot PF decreases intracellular lipid content and is associated with an increase in expression levels of ß-oxidation genes (Acox1, Pparα, and Ucp2) and lipophagy (Atg7). Moreover, we confirm this effect on 3D spheroids and organoids. Conclusion: Incubation with bergamot PF reduces intracellular lipid neutral fat potentially by increasing intracellular pathways related to beta-oxidation.
Testosterone Replacement Therapy in Chronic Kidney Disease Patients
Authors: Skiba Ryszard , Rymarz Aleksandra , Matyjek Anna , Dymus Jolanta , Woźniak-Kosek Agnieszka , Syryło Tomasz , Zieliński Henryk , Niemczyk Stanisław
Published: August 2022

(Background) The aim of our study was to evaluate the efficacy and safety of testosterone replacement therapy (TRT) in men with chronic kidney disease and hypogonadism on conservative and hemodialysis treatment. (Methods) The studied population consisted of 38 men on hemodialysis (HD), 46 men with CKD stages II-IV (predialysis group, PreD) and 35 men without kidney disease who were similar in age to others (control group). Serum total testosterone level (TT) was measured, and free testosterone level (fT) was calculated. Hypogonadism criteria according to the EAU definition were fulfilled by 26 men on HD (68.4%) and by 24 men from the PreD group (52%). Testosterone replacement therapy (TRT) with testosterone enanthate in intramuscular injections every 3 weeks was applied in 15 men from HD and in 14 men from PreD. The safety of TRT was monitored by measuring PSA and overhydration. (Results) A significant rise of TT and fT was observed after 3 months of TRT, but no significant changes were observed after 6 and 12 months in the HD and PreD group. An intensity of clinical symptoms of hypogonadism measured by ADAM (androgen deficiency in the ageing male) questionnaire gradually decreased, and the intensity of erectile dysfunction measured by the IIEF-5 (international index of erectile functioning) questionnaire also decreased after 3, 6 and 12 months of TRT in the HD and PreD group. (Conclusions) The applied model of TRT is effective in the correction of clinical signs of hypogonadism without a significant risk of overhydration or PSA changes.
The Exploration of Complement-Resistance Mechanisms of Pathogenic Gram-Negative Bacteria to Support the Development of Novel Therapeutics
Authors: Ruest Marta K. , Dennis Jonathan J.
Published: August 2022

Resistance to antibiotics in Bacteria is one of the biggest threats to human health. After decades of attempting to isolate or design antibiotics with novel mechanisms of action against bacterial pathogens, few approaches have been successful. Antibacterial drug discovery is now moving towards targeting bacterial virulence factors, especially immune evasion factors. Gram-negative bacteria present some of the most significant challenges in terms of antibiotic resistance. However, they are also able to be eliminated by the component of the innate immune system known as the complement system. In response, Gram-negative bacteria have evolved a variety of mechanisms by which they are able to evade complement and cause infection. Complement resistance mechanisms present some of the best novel therapeutic targets for defending against highly antibiotic-resistant pathogenic bacterial infections.
Dirofilaria immitis: Genotyping Randomly Selected European Clinical Samples and USA Laboratory Isolates with Molecular Markers Associated with Macrocyclic Lactone Susceptibility and Resistance
Authors: Curry Emily , Traversa Donato , Carretón Elena , Kramer Laura , Sager Heinz , Young Lisa , Prichard Roger
Published: August 2022

Dirofilaria immitis is a parasitic nematode and causes dirofilariosis, a potentially fatal pulmonary infection which primarily infects canids. Dirofilariosis infections are controlled via prophylactic macrocyclic lactone (ML) regimens. Recent evidence has confirmed the development of ML-resistant isolates in the USA, which are genetically distinct from wildtype populations. Single nucleotide polymorphisms (SNP) associated with ML-resistant phenotypes were clinically validated in USA populations. In this study, 3 USA laboratory-maintained isolates (Berkeley, Georgia II, and WildCat) and 11 randomly selected European clinical samples from 7 hosts were analyzed. The samples tested were fresh microfilaria (mf) in blood or adult worms preserved in ethanol. The samples underwent MiSeq sequencing of the top 9 SNP associated with ML resistance. The results provide the first genotypic analysis of the three USA laboratory-maintained isolates and any European samples. The European clinical samples show no genomic evidence of ML resistance based on the 9 SNP. The early adoption of genotyping of clinical D. immitis samples could provide an early indication of the potential development of ML resistance and aid to distinguish clinical cases of heartworm infection due to ML resistance from those due to a lack compliance with the recommended treatments, as has been seen in North America.
An Experiment in Denmark to Infect Wounded Sitka Spruce with the Rotstop Isolate of Phlebiopsis gigantea, and Its Implications for the Control of Heterobasidion annosum in Britain
Authors: Pratt Jim , Thomsen Iben M.
Published: August 2022

The formulation of a Finnish isolate of the saprotrophic wood-rotting fungus Phlebiopsis gigantea into the biocontrol agent (BCA) Rotstop, which is used to prevent infection of Norway spruce stumps by aerial basidiospores of H. annosum, has led to its application to more than 200,000 ha of forest in Scandinavia and North Europe. The success of this treatment opens the possibility of introducing the Rotstop strain into Britain for use on Sitka spruce stumps, which at present (2022) are lacking adequate prophylactic treatment. However, Rotstop is probably non-native to Britain and to North America (the ancestral home of this spruce), and we do not know if this xylem-decaying BCA can invade standing trees. In this paper, we describe a trial into this issue conducted for the U.K. Forestry Commission in Denmark, in a country where both Rotstop and Sitka spruce have been naturalised. It was preliminary to further stump treatment trials, and is relevant to long-term issues surrounding stump treatment in Britain. Inoculations into 44-year-old standing Sitka spruce with 20 mm wooden Scots pine plugs pre-colonised with Rotstop resulted in decay of the S1, S2, S3 and middle lamellae of sapwood above and below the wounds after 11–18 months. In contrast, infection of sapwood occurred in only one of 39 wounds on the same trees challenged with oidial spore inoculants adpressed to undamaged xylem sapwood during the same period. While the results suggest that release of Rotstop into the productive stands of Sitka spruce in Britain would be unlikely to cause long-term commercial losses to wounded trees, the work highlights issues relating to the assessment of risk associated with the introduction of non-native BCAs within the forest environment.
TLC–Densitometry for Determination of Omeprazole in Simple and Combined Pharmaceutical Preparations
Authors: Parys Wioletta , Pyka-Pająk Alina
Published: August 2022

TLC combined with densitometry was used and chromatographic conditions developed to separate omeprazole and diclofenac sodium from their potential impurities. The development of the TLC–densitometry method is based on the elaboration of new chromatographic conditions allowing for the simultaneous determination of omeprazole and diclofenac sodium in a pharmaceutical preparation. Identification and quantification of omeprazole in simple and combined (with diclofenac) pharmaceutical preparations was performed on silica gel 60F254 using one mobile phase: chloroform–methanol–ammonia (36:4:0.60, v/v). Diclofenac sodium was determined in the presence of omeprazole after 2D separation on silica gel using two mobile phases of the first phase of chloroform–methanol–ammonia (36:4:0.60, v/v) and the second mobile phase cyclohexane–chloroform–methanol–glacial acetic acid (6:3:0.5:0.5 v/v). The developed method is simple, economical, specific, precise, accurate, sensitive, and robust, with a good range of linearity for the quantification of omeprazole and diclofenac sodium. TLC in combination with densitometry can be used as an effective analytical tool for quality control and quantitative determination of omeprazole in simple and combined pharmaceutical preparations containing diclofenac sodium. TLC in combination with densitometry can be recommended for the analysis of omeprazole and diclofenac sodium in the absence of HPLC or spectrophotometer in the laboratory or to confirm results obtained with other analytical techniques.
Asperuloside Prevents Peri-Implantitis via Suppression of NF-κB and ERK1/2 on Rats
Authors: Wang Xinge , Chen Xutao , Zhang Zhaoxin , Chen Ji , Ge Zeyang , Huang Shitou , Wei Hongbo , Li Dehua
Published: August 2022

Peri-implantitis is characterized by inflammatory cell infiltration and hyperactivation of the osteoclasts surrounding dental implants which can result in bone resorption and ultimately implant failure. Therefore, coordinating the activity of inflammatory response and bone-resorbing osteoclasts is crucial for the prevention of peri-implantitis. Asperuloside (ASP), an iridoid glycoside, has significant anti-inflammatory activities, suggesting the great potential in attenuating peri-implantitis bone resorption. A ligature-induced peri-implantitis model in the maxilla of rats was established, and the effects of ASP on preventing peri-implantitis were evaluated after four weeks of ligation using micro-CT and histological staining. RT-PCR, western blotting, tartrate-resistant acid phosphatase (TRAP), and immunofluorescent staining were conducted on osteoclasts to confirm the mechanisms of ASP on osteoclastogenesis. The results show that ASP could lead to attenuation of alveolar bone resorption in peri-implantitis by inhibiting osteoclast formation and decreasing pro-inflammatory cytokine levels in vivo. Furthermore, ASP could inhibit osteoclastogenesis by downregulating expression levels of transcription factors nuclear factor of activated T-cell (NFATc1) via restraining the activations of nuclear factor kappa beta (NF-κB) and the phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2). In conclusion, ASP could significantly attenuate bone resorption in peri-implantitis via inhibition of osteoclastogenesis by suppressing NF-κB and ERK1/2 signaling pathways activations.
Roles of Bromodomain Extra Terminal Proteins in Metabolic Signaling and Diseases
Authors: Wu Dayu , Duan Qiong
Published: August 2022

BET proteins, which recognize and bind to acetylated histones, play a key role in transcriptional regulation. The development of chemical BET inhibitors in 2010 greatly facilitated the study of these proteins. BETs play crucial roles in cancer, inflammation, heart failure, and fibrosis. In particular, BETs may be involved in regulating metabolic processes, such as adipogenesis and metaflammation, which are under tight transcriptional regulation. In addition, acetyl-CoA links energy metabolism with epigenetic modification through lysine acetylation, which creates docking sites for BET. Given this, it is possible that the ambient energy status may dictate metabolic gene transcription via a BET-dependent mechanism. Indeed, recent studies have reported that various BET proteins are involved in both metabolic signaling regulation and disease. Here, we discuss some of the most recent information on BET proteins and their regulation of the metabolism in both cellular and animal models. Further, we summarize data from some randomized clinical trials evaluating BET inhibitors for the treatment of metabolic diseases.
Formulation Development of Fluconazole-Loaded Lactose Agglomerate Tablets as a Disinfectant for Candida-Associated Dentures
Authors: Jarungsirawat Rapee , Kajthunyakarn Wanassnant , Siriwachirachai Chaipat , Pongjanyakul Thaned
Published: August 2022

Denture stomatitis is induced by irritation or an inflammatory response when wearing a denture for a long time. Candida species are the leading cause of biofilm formation on the surfaces and fissures of dentures. Thus, this study aimed to formulate and evaluate fluconazole tablets for use in preparing a disinfectant mixture with anticandidal activity. For size enlargement of lactose, a tablet diluent, using polyvinylpyrrolidone (PVP) as an agglomerating agent, was developed to enhance the flowability and compactability of the tablet preparation using direct compression. Lactose agglomerates with 6% PVP were used as a diluent for the fluconazole tablets. Furthermore, other excipients were used, such as a buffering agent, disintegrant, surfactant, and lubricant. The fluconazole tablets obtained could be dispersed and dissolved within 10 min in distilled water to achieve a clear mixture, providing a neutral pH and 96% transmittance. Furthermore, the fluconazole mixtures displayed anticandidal efficiency against C. albicans with a similar effect to the standard fluconazole solution. These findings suggest that the fluconazole-loaded lactose agglomerate tablets show strong potential when prepared using direct compression. The fluconazole mixtures made by dispersing the tablets can be used as a disinfectant for Candida-associated dentures, particularly in patients with oral candidiasis.
Efficient Sustained-Release Nanoparticle Delivery System Protects Nigral Neurons in a Toxin Model of Parkinson’s Disease
Authors: Wang Qun , Ma Rui , Liu Piaoxue , Cheng Guowang , Yang Qi , Chen Xiaojia , Wu Zhenfeng , Yuan Dongsheng , Chen Tongkai
Published: August 2022

Parkinson’s disease (PD) is a serious neurodegenerative disease wherein the progressive destruction of dopaminergic neurons results in a series of related movement disorders. Effective oral delivery of anti-Parkinson’s drugs is challenging owing to the blood-brain barrier (BBB) and the limited plasma exposure. However, polymeric nanoparticles possess great potential to enhance oral bioavailability, thus improving drug accumulation within the brain. In this work, biodegradable poly(ethylene glycol)-b-poly(trimethylene carbonate) (PEG-PTMC) nanoparticles (PPNPs) were developed to deliver Ginkgolide B (GB) as a potent treatment for PD, aiming to enhance its accumulation within both the blood and the brain. The resultant GB-PPNPs were able to facilitate sustained GB release for 48 h and to protect against 1-methyl-4-phenylpyridine (MPP+)-induced neuronal cytotoxicity without causing any toxic damage. Subsequent pharmacokinetic studies revealed that GB-PPNPs accumulated at significantly higher concentrations in the plasma and brain relative to free GB. Oral GB-PPNP treatment was also linked to desirable outcomes in an animal model of PD, as evidenced by improvements in locomotor activity, levels of dopamine and its metabolites, and tyrosine hydroxylase activity. Together, these data suggest that PPNPs may represent promising tools for the effective remediation of PD and other central nervous system disorders.
Innovations in Chewable Formulations: The Novelty and Applications of 3D Printing in Drug Product Design
Authors: Rodríguez-Pombo Lucía , Awad Atheer , Basit Abdul W. , Alvarez-Lorenzo Carmen , Goyanes Alvaro
Published: August 2022

Since their introduction, chewable dosage forms have gained traction due to their ability to facilitate swallowing, especially in paediatric, geriatric and dysphagia patients. Their benefits stretch beyond human use to also include veterinary applications, improving administration and palatability in different animal species. Despite their advantages, current chewable formulations do not account for individualised dosing and palatability preferences. In light of this, three-dimensional (3D) printing, and in particular the semi-solid extrusion technology, has been suggested as a novel manufacturing method for producing customised chewable dosage forms. This advanced approach offers flexibility for selecting patient-specific doses, excipients, and organoleptic properties, which are critical for ensuring efficacy, safety and adherence to the treatment. This review provides an overview of the latest advancements in chewable dosage forms for human and veterinary use, highlighting the motivations behind their use and covering formulation considerations, as well as regulatory aspects.
Degradable and Non-Degradable Chondroitin Sulfate Particles with the Controlled Antibiotic Release for Bacterial Infections
Authors: Suner Selin S. , Sahiner Mehtap , Ayyala Ramesh S. , Sahiner Nurettin
Published: August 2022

Non-degradable, slightly degradable, and completely degradable micro/nanoparticles derived from chondroitin sulfate (CS) were synthesized through crosslinking reactions at 50%, 40%, and 20% mole ratios, respectively. The CS particles with a 20% crosslinking ratio show total degradation within 48 h, whereas 50% CS particles were highly stable for up to 240 h with only 7.0 ± 2.8% weight loss in physiological conditions (pH 7.4, 37 °C). Tobramycin and amikacin antibiotics were encapsulated into non-degradable CS particles with high loading at 250 g/mg for the treatment of corneal bacterial ulcers. The highest release capacity of 92 ± 2% was obtained for CS-Amikacin particles with sustainable and long-term release profiles. The antibacterial effects of CS particles loaded with 2.5 mg of antibiotic continued to render a prolonged release time of 240 h with 24 ± 2 mm inhibition zones against Pseudomonas aeruginosa. Furthermore, as a carrier, CS particles significantly improved the compatibility of the antibiotics even at high particle concentrations of 1000 g/mL with a minimum of 71 ± 7% fibroblast cell viability. In summary, the sustainable delivery of antibiotics and long-term treatment of bacterial keratitis were shown to be afforded by the design of tunable degradation ability of CS particles with improved biocompatibility for the encapsulated drugs.
Development and In Vitro-Ex Vivo Evaluation of Novel Polymeric Nasal Donepezil Films for Potential Use in Alzheimer’s Disease Using Experimental Design
Authors: Papakyriakopoulou Paraskevi , Rekkas Dimitrios M. , Colombo Gaia , Valsami Georgia
Published: August 2022

The objective and novelty of the present study is the development and optimization of innovative nasal film of Donepezil hydrochloride (DH) for potential use in Alzheimer’s disease. Hydroxypropyl-methyl-cellulose E50 (factor A) nasal films, with Polyethylene glycol 400 as plasticizer (factor B), and Methyl-β-Cyclodextrin, as permeation enhancer (factor C), were prepared and characterized in vitro and ex vivo. An experimental design was used to determine the effects of the selected factors on permeation profile of DH through rabbit nasal mucosa (response 1), and on film flexibility/foldability (response 2). A face centered central composite design with three levels was applied and 17 experiments were performed in triplicate. The prepared films exhibited good uniformity of DH content (90.0 ± 1.6%–99.8 ± 4.9%) and thickness (19.6 ± 1.9–170.8 ± 11.5 μm), storage stability characteristics, and % residual humidity (<3%), as well as favourable swelling and mucoadhesive properties. Response surface methodology determined the optimum composition for flexible nasal film with maximized DH permeation. All selected factors interacted with each other and the effect of these interactions on responses is strongly related to the factor’s concentration ratios. Based on these encouraging results, in vivo serum and brain pharmacokinetic study of the optimized nasal film, in comparison to DH oral administration, is ongoing in an animal model.
Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation
Authors: Singkham Noppaket , Phrommintikul Arintaya , Pacharasupa Phongsathon , Norasetthada Lalita , Gunaparn Siriluck , Prasertwitayakij Narawudt , Wongcharoen Wanwarang , Punyawudho Baralee
Published: August 2022

Low-dose rivaroxaban has been used in Asian patients with direct oral anticoagulants (DOACs) eligible for atrial fibrillation (AF). However, there are few pharmacokinetic (PK) data in Thai patients to support precise dosing. This study aimed to develop a population PK model and determine the optimal rivaroxaban doses in Thai patients. A total of 240 Anti-Xa levels of rivaroxaban from 60 Thai patients were analyzed. A population PK model was established using the nonlinear mixed-effect modeling approach. Monte Carlo simulations were used to predict drug exposures at a steady state for various dosages. Proportions of patients having rivaroxaban exposure within typical exposure ranges were determined. A one-compartment model with first-order absorption best described the data. Creatinine clearance (CrCl) and body weight significantly affected CL/F and V/F, respectively. Regardless of body weight, a higher proportion of patients with CrCl < 50 mL/min receiving the 10-mg once-daily dose had rivaroxaban exposures within the typical exposure ranges. In contrast, a higher proportion of patients with CrCl ≥ 50 mL/min receiving the 15-mg once-daily dose had rivaroxaban exposures within the typical exposure ranges. The study’s findings suggested that low-dose rivaroxaban would be better suited for Thai patients and suggested adjusting the medication’s dose in accordance with renal function.
Enhanced Ocular Anti-Aspergillus Activity of Tolnaftate Employing Novel Cosolvent-Modified Spanlastics: Formulation, Statistical Optimization, Kill Kinetics, Ex Vivo Trans-Corneal Permeation, In Vivo Histopathological and Susceptibility Study
Authors: Aziz Diana , Mohamed Sally A. , Tayel Saadia , Makhlouf Amal
Published: August 2022

Tolnaftate (TOL) is a thiocarbamate fungicidal drug used topically in the form of creams and ointments. No ocular formulations of TOL are available for fungal keratitis (FK) treatment due to its poor water solubility and unique ocular barriers. Therefore, this study aimed at developing novel modified spanlastics by modulating spanlastics composition using different glycols for enhancing TOL ocular delivery. To achieve this goal, TOL basic spanlastics were prepared by ethanol injection method using a full 32 factorial design. By applying the desirability function, the optimal formula (BS6) was selected and used as a nucleus for preparing and optimizing TOL-cosolvent spanlastics according to the full 31.21 factorial design. The optimal formula (MS6) was prepared using 30% propylene glycol and showed entrapment efficiency percent (EE%) of 66.10 ± 0.57%, particle size (PS) of 231.20 ± 0.141 nm, and zeta potential (ZP) of −32.15 ± 0.07 mV. MS6 was compared to BS6 and both nanovesicles significantly increased the corneal permeation potential of TOL than drug suspension. Additionally, in vivo histopathological experiment was accomplished and confirmed the tolerability of MS6 for ocular use. The fungal susceptibility testing using Aspergillus niger confirmed that MS6 displayed more durable growth inhibition than drug suspension. Therefore, MS6 can be a promising option for enhanced TOL ocular delivery.
Implementation of Photonic Phase Gate and Squeezed States via a Two-Level Atom and Bimodal Cavity
Authors: Tang Shiqing , Jiang Xi , Wang Xinwen , Zhao Xingdong
Published: August 2022

We propose a theoretical model for realizing a photonic two-qubit phase gate in cavity QED using a one-step process. The fidelity and probability of success of the conditional quantum phase gate is very high in the presence of cavity decay. Our scheme only employs one two-level atom, and thus is much simpler than other schemes involving multi-level atoms. This proposal can also be applied to generate two-mode squeezed states; therefore, we give three examples, i.e., the two-mode squeezed vacuum state, two-mode squeezed odd coherent state, and two-mode squeezed even coherent state, to estimate the variance of Duan’s criterion when taking into account cavity decay. It is shown that the variance is smaller than 2 for the three squeezed states in most cases. Furthermore, we utilize logarithmic negativity to measure the entanglement, and find that these squeezed states have very high degrees of entanglement.
Nonreciprocity Steered with a Spinning Resonator
Authors: Shang Xiao , Xie Hong , Lin Gongwei , Lin Xiumin
Published: August 2022

An approach is presented to study the controllable nonreciprocal transmission in a spinning resonator. It has been demonstrated in optomechanics that an optical signal field can only be affected when it propagates in the same direction as the driving field. We show that such an optomechanically induced nonreciprocity can be controlled by rotating the resonator, which introduces a frequency shift with different signs for clockwise and counterclockwise optical fields in the resonator. In our scheme, the transmission probabilities of the clockwise and counterclockwise input signal fields can be reversed by tuning the rotation velocity of the resonator. By studying the transmission spectra of the signal field, we also reveal that the nonreciprocity response can be realized in the spinning resonators in the absence of optomechanical coupling, which extends its utility.
Specific Phase Modulation with Dynamic Variable Spectral Width of Nanosecond Optical Pulse in High-Power Lasers
Authors: Qian Xinlei , Wang Xiaochao , Xu Shouying , Xiao Zhuli , Wang Yue , Zhou Shenlei , Fan Wei
Published: August 2022

High-power laser pulse transmitted by phase modulation with certain spectrum distribution can suppress the buildup of transverse stimulated Brillouin scattering (TSBS) in large aperture laser optics and smooth the speckle pattern illuminating the target by spectral smoothing dispersion (SSD). In this paper, based on the requirements of the double-cone ignition scheme including simultaneously realizing that the focal spot is variable at different times in size and the spatial intensity distribution is uniform, we propose a novel phase modulation technology with a rapid variable modulation index in the nanosecond scale instead of utilizing conventional constant amplitude sinusoidal curve. The relevant simulation results indicate that the proposed technology can realize the dynamic nanosecond spectral distribution and the trend correlates with the variety of modulation index. Particularly, we indirectly measure this rapid changeable spectral distribution based on the mapping relationship between frequency and time domain. We believe that the new technology is expected to meet the requirements of SSD and the dynamic focus simultaneously.
Monoterpenoids Evolution and MEP Pathway Gene Expression Profiles in Seven Table Grape Varieties
Authors: Zhou Xiaomiao , Liu Songyu , Gao Wengping , Hu Binfang , Zhu Baoqing , Sun Lei
Published: August 2022

This research investigated the evolution of both monoterpenoids and expression profiles of related biosynthesis genes in the MEP pathway in seven different table grape varieties from veraison to maturity stage in two seasons, and the correlation was further evaluated between monoterpenoid accumulation and expression of these genes studied in these varieties. Results showed that linalool, trans-furan linalool oxide, geraniol, and cis-furan linalool oxide were the main compounds in the five Muscat varieties two seasons. ‘Zaomeiguixiang’ had the highest contents of geraniol and β-Citronellol. ‘Xiangfei’ had the most abundant of linalool and cis-furan linalool oxide, whereas the neutral varieties of ‘Moldova’ and ‘Christmas Rose’ had the least amount. Monoterpenoid volatiles have been grouped in three evolutionary patterns in the berry development of these varieties. ‘Zaomeiguixiang’ and ‘Xiangfei’ had distinct different pattern of terpenoids evolution profiles. Pearson’s correlation analysis showed that in the MEP pathway, the first biosynthesis gene VvDXS3 was significantly correlated to the accumulation of monoterpenoids, and appeared to be an important candidate gene for synthesis of the monoterpenoids.
Descriptive Genomic Analysis and Sequence Genotyping of the Two Papaya Species (Vasconcellea pubescens and Vasconcellea chilensis) Using GBS Tools
Authors: Carrasco Basilio , Arévalo Bárbara , Perez-Diaz Ricardo , Rodríguez-Alvarez Yohaily , Gebauer Marlene , Maldonado Jonathan E. , García-Gonzáles Rolando , Chong-Pérez Borys , Pico-Mendoza José , Meisel Lee A. , Ming Ray , Silva Herman
Published: August 2022

A genotyping by sequencing (GBS) approach was used to analyze the organization of genetic diversity in V. pubescens and V. chilensis. GBS identified 4675 and 4451 SNPs/INDELs in two papaya species. The cultivated orchards of V. pubescens exhibited scarce genetic diversity and low but significant genetic differentiation. The neutrality test yielded a negative and significant result, suggesting that V. pubescens suffered a selective sweep or a rapid expansion after a bottleneck during domestication. In contrast, V. chilensis exhibited a high level of genetic diversity. The genetic differentiation among the populations was slight, but it was possible to distinguish the two genetic groups. The neutrality test indicated no evidence that natural selection and genetic drift affect the natural population of V. chilensis. Using the Carica papaya genome as a reference, we identified critical SNPs/INDELs associated with putative genes. Most of the identified genes are related to stress responses (salt and nematode) and vegetative and reproductive development. These results will be helpful for future breeding and conservation programs of the Caricaceae family.
Performance Evaluation of CNT Reinforcement on Electroless Plating on Solid Free-Form-Fabricated PETG Specimens for Prosthetic Limb Application
Authors: Siddikali Palaiam , Sreekanth P. S. Rama
Published: August 2022

The utility of polymers in the present decade is consistently increasing, giving scope to many applications from automobiles to prosthetics. Polymers used for solid free-form fabrication (SFFF), also known as 3D printing, comprise a quick fabrication process adopted by many industries to increase productivity and decrease the run time to cope with the market demands. In this research work, pure polyethylene terephthalate glycol (PETG) and multi-walled carbon nanotube (MWCNT)-PETG with an electroless metal layer coating and without a coating are discussed. The effect of the electroless metal layer coating on the reinforced PETG-MWCNT results in improved mechanical, tribological, and other surface properties. Pure PETG was incorporated with MWCNT nanofillers at 0.3 wt.% and extruded as a filament through a twin screw extruder with a 1.75 mm diameter and printed on ASTM standards. Tensile testing was performed on all four types of un-coated pure PETG, PETG-MWCNT, and metal-layer-coated PETG and PETG-MWCNT with a coating thickness of 26, 32, 54, and 88 μm. Dynamic mechanical analysis (DMA) showed that the coated PETG-MWCNT had the highest storage and loss modulus. The heat deflection temperature was improved to 88 °C for the coated PETG-MWCNT. The wear volume against the sliding distance at a load of 40, 50, and 60 N showed that the coefficient of friction decreased with an increase in the load. The scratch test results revealed the lowest penetration depth and lowest friction coefficient for the coated PETG-MWCNT sample. The water contact angle test showed that a greater coating thickness makes the sample surface more hydrophobic, and the microhardness test indicated that the indentation hardness value for the PETG-MWCNT was 92 HV. The study revealed that the metal-layer-coated PETG-MWCNT had better performance compared to the other specimens due to a good metal layer bonding on the PETG substrate. It was concluded that adding MWCNTs to a metal layer electroless coating improved the surface and mechanical properties of the PETG, and this may be suitable for many applications.
In-Built Fabrication of MOF Assimilated Porous Hollow Carbon from Pre-Hydrolysate for Supercapacitor
Authors: Zhao Xin , Li Changwei , Sha Lei , Yang Kang , Gao Min , Chen Honglei , Jiang Jianchun
Published: August 2022

With the fast consumption of traditional fossil fuels and the urgent requirement for a low-carbon economy and sustainable development, supercapacitors are gaining more and more attention as a clean energy storage and conversion device. The research on electrode materials for supercapacitors has become a hot topic nowadays. An electrode material for a supercapacitor, comprising the ZIF-67 in-built carbon-based material, was prepared from a biomass pre-hydrolysate via a hydrothermal process. As a by-product of dissolving slurry, the pre-hydrolysate is rich in carbon, which is an excellent biomass resource. The utilization of pre-hydrolysate to prepare carbon energy materials could realize the high value utilization of pre-hydrolysate and the efficient energy conversion of biomass. Meanwhile, the cobalt-based MOF (such as ZIF-67), as a porous crystalline material, has the advantages of having a regular order, high specific surface area and controllable pore size, as well as good thermal and chemical stability. The addition of ZIF-67 modified the morphology and pore structure of the carbon, and the obtained samples showed outstanding electrochemical performance. One- and two-step synthetic processes generated specimens with a coral-like cross-linked structure and a new type of rough, hollow, dandelion-like structure, respectively, and the pore size was in the range of 2.0–5.0 nm, which is conducive to ion transport and charge transfer. In C2-ZIF-67, the hollow structures could effectively prevent the accumulation of the electrochemical active center, which could provide enough space for the shrinkage and expansion of particles to protect them from the interference of electrolytes and the formation of solid electrolyte interphase film layers. Additionally, the plush tentacle structure with low density and a large specific surface area could expose more active sites and a large electrolyte electrode contact area, and short electron and charge transport paths. Importantly, active, free electrons of small amounts of Co-MOF (1 wt%) could be stored and released through the redox reaction, further improving the electrical conductivity of Carbon-ZIF-67 materials in this work. Consequently, C2-ZIF-67 exhibited superior specific capacitance (400 F g−1, at 0.5 A g−1) and stability (90%, after 10,000 cycles).
Mechanical and Fire Performance of Innovative Hollow Glue-Laminated Timber Beams
Authors: Perković Nikola , Rajčić Vlatka
Published: August 2022

Fire safety greatly contributes to feeling safe, and it is a key parameter for the selection of building materials. The combustibility of timber is one of the main reasons to have the strict restriction on timber for use as a building material, especially for multistory buildings. Therefore, the main prerequisite for the use of timber in buildings is to ensure adequate fire resistance, using passive and active fire protection measures. This article contains the results of mechanical and fire experimental tests of both normal and innovative hollow glued laminated timber beams. A total of 10 timber beams were tested at ambient temperature, and 3 timber beams in fire conditions, which differed in cross-section type but also in the applied fire protection. The first beam was a normal GL beam without fire protection, the second a hollow beam covered by intumescent paint, while the third was also hollow, additionally protected by mineral wool infill inside the holes. The load-carrying capacity of the hollow beam in ambient conditions was estimated at 65% of the load-carrying capacity of a normal GL beam. Fire tests indicated that hollow timber beams with both intumescent paint and mineral wool infill failed at a similar time as a normal GL beam without fire protection. One-dimensional β0 and notional charring rates βn were obtained. Time to the protective material failure was 17 min. The main cause of failure of hollow beams was the appearance of delamination due to the reduction of the lamella bonding surface.