bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple Sclerosis Treatment in the COVID-19 Era: A Risk-Benefit Approach
Authors: Immovilli Paolo , Morelli Nicola , Terracciano Chiara , Rota Eugenia , Marchesi Elena , Vollaro Stefano , De Mitri Paola , Zaino Domenica , Bazzurri Veronica , Guidetti Donata
Published: April 2022

The COVID-19 pandemic poses an ongoing global challenge, and several risk factors make people with multiple sclerosis (pwMS) particularly susceptible to running a severe disease course. Although the literature does report numerous articles on the risk factors for severe COVID-19 and vaccination response in pwMS, there is a scarcity of reviews integrating both these aspects into strategies aimed at minimizing risks. The aim of this review is to describe the risk of vulnerable pwMS exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues related to the SARS-CoV-2 vaccine and to evidence possible future strategies in the clinical management of pwMS. The authors searched for papers on severe COVID-19 risk factors, SARS-CoV-2 vaccination and people with multiple sclerosis in support of this narrative literature review. We propose a multilevel strategy aimed at: the evaluation of risk factors for severe COVID-19 in people with multiple sclerosis, identifying the most appropriate vaccination schedule that is safe for people on disease-modifying drugs (DMDs) and a strict follow-up of high-risk people with multiple sclerosis to allow for the prompt administration of monoclonal antibodies to manage COVID-19 risks in this patient population.
Impact of Cafeteria Service Discontinuation at a Dialysis Facility on Medium-Term Nutritional Status of Elderly Patients Undergoing Hemodialysis
Authors: Notomi Satoko , Kitamura Mineaki , Yamaguchi Kosei , Harada Takashi , Nishino Tomoya , Funakoshi Satoshi , Kuno Kazue
Published: April 2022

Despite evident lifestyle changes due to measures against the coronavirus disease 2019 (COVID-19) outbreak, few reports focus on the effects of eating-behavior changes on the nutritional status of elderly patients undergoing hemodialysis (HD). Thus, we examined dry-weight reduction, the simplest indicator of malnutrition among patients undergoing dialysis, and its association with the discontinuation of cafeteria services at a dialysis facility as per COVID-19 measures. This retrospective study included elderly patients (aged ≥ 65 years) undergoing HD at the Nagasaki Renal Center between December 2020 and October 2021. We collected nutrition-related data and patient characteristics and evaluated the association between the service discontinuation and dry-weight reduction 10 months after the discontinuation using multivariable logistic regression. This study included 204 patients, 79 of which were cafeteria users. During the observation period, cafeteria users showed significant dry-weight reduction; however, this was not observed among non-users. Multivariable logistic regression analysis indicated a close association between dry-weight reduction and the service discontinuation. That is, the dietary services cancelation caused dry-weight reduction in patients who relied on the cafeteria. As elderly patients undergoing HD are vulnerable to changes in their eating environment, alternative nutritional management methods need to be considered.
New Insights in Cow’s Milk and Allergy: Is the Gut Microbiota the Missing Link?
Authors: Verduci Elvira , Zuccotti Gian Vincenzo , Peroni Diego G.
Published: April 2022

The present Editorial derives from the Special Issue “New Insights into Cow’s Milk and Allergy” recently published in Nutrients [...]
Changes in Parenteral Nutrition Requirements and BMI in Patients with Parenteral Nutrition-Dependent Short Bowel Syndrome after Stopping Teduglutide—9 Years of Follow-Up
Authors: Zaczek Zuzanna , Jurczak-Kobus Paulina , Panczyk Mariusz , Braszczyńska-Sochacka Joanna , Majewska Krystyna , Kunecki Marek , Dąbrowska Karolina , Sobocki Jacek
Published: April 2022

Teduglutide (TED) is widely used in patients with short-bowel-syndrome-associated intestinal failure (SBS-IF) to enhance intestinal adaptation and reduce the need for parenteral support (PS). There are limited data on the effects of discontinuing TED. In this study, we describe the changes in parenteral nutrition (PN) requirements and body mass index (BMI) in a 9-year follow-up of patients receiving home parenteral nutrition after discontinuation of the TED treatment. We performed a retrospective analysis of changes in weekly PN orders and BMI in all patients with PN-dependent SBS from two Polish home parenteral nutrition (HPN) centers who received teduglutide between 2009 and 2013 and still required HPN 9 years after discontinuation of the TED treatment. Data included in the analysis were collected prospectively at mandatory visits to the HPN centers at 12, 24, 60, 84, and 108 months after drug discontinuation and compared with values before and after TED treatment. Weekly PN volume values varied significantly between all of the above time points from baseline to 9 years after TED discontinuation (χ2 = 34.860, p < 0.001). After an initial increase within the first year after treatment discontinuation (not statistically significant), the PN volume requirements remained stable for 4 years and increased 5–9 years after treatment discontinuation. The rate of patients requiring an increase in PN volume was 84.62% at 60 and 84 months and 92.30% at 108 months. At 9 years after cessation of the TED treatment, 53.85% of the study group required a 21.21% increase in PN volume compared with values before treatment. The need for PN volume in patients with PN-dependent SBS who discontinued the TED treatment increased within the first year and 4–5 years after treatment cessation, and in some cases might even exceed pretreatment values after 9 years.
Iron Bioavailability from Ferrous Ammonium Phosphate, Ferrous Sulfate, and Ferric Pyrophosphate in an Instant Milk Drink—A Stable Isotope Study in Children
Authors: Hurrell Richard , Trinidad Trinidad , Mallillin Aida , Sagum Rosario , Foman Jasmin , Li Qiaoji , Zeder Christophe , Kastenmayer Peter , Rytz Andreas , Sabatier Magalie , Egli Ines
Published: April 2022

Ferrous ammonium phosphate (FAP) is an iron salt that has been developed for the fortification of food matrices sensitive to color and flavor changes. The objective of the study was to measure iron absorption from FAP in young children and compare it to a previous evaluation of FAP in young women. A double-blind randomized crossover study with two parallel arms was used to evaluate the iron absorption from FAP added to reconstituted milk powder in comparison to that from ferrous sulfate (FeSO4) and ferric pyrophosphate (FePP). Iron absorption was measured in 39 children aged 3- to 6-years-old using erythrocyte incorporation of stable Fe isotopes (57Fe, 58Fe). The geometric mean iron absorption in iron replete children from FAP, FeSO4 and FePP from milk was 8.3%, 7.6% and 2.1%, respectively. Iron absorption from FAP and FeSO4 fortified milk was not significantly different (p = 0.199); however, it was significantly higher than from FePP fortified milk (p < 0.001). Iron bioavailability from FAP and FePP relative to FeSO4 (relative bioavailability (RBV)) was 110% and 33%, respectively. The RBV of FAP (110%) in iron replete children was higher than previously reported RBV (71%) in mainly iron deficient women. The difference in iron status between the children and women in the respective studies may explain the different RBV values and is discussed.
Prolonged or Transition to Metabolically Unhealthy Status, Regardless of Obesity Status, Is Associated with Higher Risk of Cardiovascular Disease Incidence and Mortality in Koreans
Authors: Lee Juhee , Kwak So-Young , Park Dahyun , Kim Ga-Eun , Park Clara Yongjoo , Shin Min-Jeong
Published: April 2022

The risk of chronic disease and mortality may differ by metabolic health and obesity status and its transition. We investigated the risk of cardiovascular disease (CVD) and cancer incidence and mortality according to metabolic health and obesity status and their transition using the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) and the Ansan-Ansung (ASAS) cohort of the Korean Genome and Epidemiology Study. Participants that agreed to mortality linkage (n = 28,468 in KNHANES and n = 7530 adults in ASAS) were analyzed (mean follow-up: 8.2 and 17.4 years, respectively). Adults with no metabolic risk factors and BMI <25 or ≥25 kg/m2 were categorized as metabolically healthy non-obese (MHN) or metabolically healthy obese (MHO), respectively. Metabolically unhealthy non-obese (MUN) and metabolically unhealthy obese (MUO) adults had ≥1 metabolic risk factor and a BMI < or ≥25 kg/m2, respectively. In KNHANES participants, MUN, and MUO had higher risks for cardiovascular mortality, but not cancer mortality, compared with MHN adults. MHO had 47% and 35% lower risks of cancer mortality and all-cause mortality, respectively, compared to MHN. Similar results were observed in the ASAS participants. Compared to those persistently MHN, the risk of CVD was greater when continuously MUN or MUO. Transitioning from a metabolically healthy state to MUO also increased the risk of CVD. Few associations were found for cancer incidence. Using a nationally representative cohort and an 18-year follow-up cohort, we observed that the risk of CVD incidence and mortality and all-cause mortality, but not cancer incidence or mortality, increases with a continuous or a transition to an unhealthy metabolic status in Koreans.
Exploring the Gut Microbiome in Myasthenia Gravis
Authors: Thye Angel Yun-Kuan , Law Jodi Woan-Fei , Tan Loh Teng-Hern , Thurairajasingam Sivakumar , Chan Kok-Gan , Letchumanan Vengadesh , Lee Learn-Han
Published: April 2022

The human gut microbiota is vital for maintaining human health in terms of immune system homeostasis. Perturbations in the composition and function of microbiota have been associated with several autoimmune disorders, including myasthenia gravis (MG), a neuromuscular condition associated with varying weakness and rapid fatigue of the skeletal muscles triggered by the host’s antibodies against the acetylcholine receptor (AChR) in the postsynaptic muscle membrane at the neuromuscular junction (NMJ). It is hypothesized that perturbation of the gut microbiota is associated with the pathogenesis of MG. The gut microbiota community profiles are usually generated using 16S rRNA gene sequencing. Compared to healthy individuals, MG participants had an altered gut microbiota’s relative abundance of bacterial taxa, particularly with a drop in Clostridium. The microbial diversity related to MG severity and the overall fecal short-chain fatty acids (SCFAs) were lower in MG subjects. Changes were also found in terms of serum biomarkers and fecal metabolites. A link was found between the bacterial Operational Taxonomic Unit (OTU), some metabolite biomarkers, and MG’s clinical symptoms. There were also variations in microbial and metabolic markers, which, in combination, could be used as an MG diagnostic tool, and interventions via fecal microbiota transplant (FMT) could affect MG development. Probiotics may influence MG by restoring the gut microbiome imbalance, aiding the prevention of MG, and lowering the risk of gut inflammation by normalizing serum biomarkers. Hence, this review will discuss how alterations of gut microbiome composition and function relate to MG and the benefits of gut modulation.
The Dose-Response Effects of Consuming High Fructose Corn Syrup-Sweetened Beverages on Hepatic Lipid Content and Insulin Sensitivity in Young Adults
Authors: Sigala Desiree M. , Hieronimus Bettina , Medici Valentina , Lee Vivien , Nunez Marinelle V. , Bremer Andrew A. , Cox Chad L. , Price Candice A. , Benyam Yanet , Abdelhafez Yasser , McGahan John P. , Keim Nancy L. , Goran Michael I. , Pacini Giovanni , Tura Andrea , Sirlin Claude B. , Chaudhari Abhijit J. , Havel Peter J. , Stanhope Kimber L.
Published: April 2022

Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the development of cardiometabolic diseases. Therefore, our objective was to investigate the dose-response effects of consuming high fructose corn syrup (HFCS)-sweetened beverages for two weeks on hepatic lipid content and insulin sensitivity in young (18–40 years) adults (BMI 18–35 kg/m2). In a parallel, double-blinded study, participants consumed three beverages/day providing 0% (aspartame: n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) daily energy requirements from HFCS. Magnetic resonance imaging for hepatic lipid content and oral glucose tolerance tests (OGTT) were conducted during 3.5-day inpatient visits at baseline and again at the end of a 15-day intervention. During the 12 intervening outpatient days participants consumed their usual diets with their assigned beverages. Significant linear dose-response effects were observed for increases of hepatic lipid content (p = 0.015) and glucose and insulin AUCs during OGTT (both p = 0.0004), and for decreases in the Matsuda (p = 0.0087) and Predicted M (p = 0.0027) indices of insulin sensitivity. These dose-response effects strengthen the mechanistic evidence implicating consumption of HFCS-sweetened beverages as a contributor to the metabolic dysregulation that increases risk for nonalcoholic fatty liver disease and type 2 diabetes.
Relationship between Nutrient Intake and Hearing Loss According to the Income Level of Working-Aged Adults: A Korean National Health and Nutrition Survey
Authors: Lee Juhyung , Lee Ji-Hyeon , Yoon Chulyoung , Kwak Chanbeom , Ahn Jae-Joon , Kong Tae-Hoon , Seo Young-Joon
Published: April 2022

The relationship between hearing impairment and nutrition has been extensively investigated; however, few studies have focused on this topic in working-age adults by income level. Herein, we aimed to determine the differences in hearing impairment among working-age adults by income level and identify the nutritional factors that affect hearing loss in various socioeconomic groups. Seven-hundred-and-twenty participants had hearing impairment, while 10,130 had normal hearing. After adjustment for propensity score matching, income and smoking status were identified as significant variables. By assessing the relationship between hearing impairment and nutrient intake by income level using multiple regression analyses, significant nutrients differed for each income category. Carbohydrate and vitamin C levels were significant in the low-income group; protein, fat, and vitamin B1 levels were significant in the middle-income group; and carbohydrates were significant in the high-income group. Income was significantly associated with hearing impairment in working-age adults. The proportion of individuals with hearing impairment increased as income decreased. The association between hearing impairment and nutritional intake also differed by income level. Our findings may enable the establishment of health policies for preventing hearing impairment in working-age adults by income level.
Pernicious Anemia: The Hematological Presentation of a Multifaceted Disorder Caused by Cobalamin Deficiency
Authors: Esposito Gianluca , Dottori Ludovica , Pivetta Giulia , Ligato Irene , Dilaghi Emanuele , Lahner Edith
Published: April 2022

Pernicious anemia is still a neglected disorder in many medical contexts and is underdiagnosed in many patients. Pernicious anemia is linked to but different from autoimmune gastritis. Pernicious anemia occurs in a later stage of autoimmune atrophic gastritis when gastric intrinsic factor deficiency and consequent vitamin B12 deficiency may occur. The multifaceted nature of pernicious anemia is related to the important role of cobalamin, which, when deficient, may lead to several dysfunctions, and thus, the proteiform clinical presentations of pernicious anemia. Indeed, pernicious anemia may lead to potentially serious long-term complications related to micronutrient deficiencies and their consequences and the development of gastric cancer and type 1 gastric neuroendocrine tumors. When not recognized in a timely manner or when pernicious anemia is diagnosed with delay, these complications may be potentially life-threatening and sometimes irreversible. The current review aimed to focus on epidemiology, pathogenesis, and clinical presentations of pernicious anemia in an attempt to look beyond borders of medical specialties. It aimed to focus on micronutrient deficiencies besides the well-known vitamin B12 deficiency, the diagnostic approach for pernicious anemia, its long-term complications and optimal clinical management, and endoscopic surveillance of patients with pernicious anemia.
Association between Iron Intake and Progression of Knee Osteoarthritis
Authors: Wu Limin , Si Haibo , Zeng Yi , Wu Yuangang , Li Mingyang , Liu Yuan , Shen Bin
Published: April 2022

Background: Iron overload is drawing attention in the development of knee osteoarthritis (OA). To identify the modifiable risk factors for iron-related pathological conditions, we examined the association between iron intake and the risk of knee OA progression. Methods: A total of 1912 participants in the Osteoarthritis Initiative (OAI), aged 45–79 years and with at least one knee radiographic OA at baseline, were identified and were followed up to 6 years. The iron and other nutrient intake was measured by the validated Block Brief 2000 Food Frequency Questionnaire. The outcome measures were by radiographic progression on the basis of the Kellgren–Lawrence (KL) grade and the joint-space-narrowing (JSN) score. The association between the iron intake and the knee OA progression was examined by Cox proportional hazards models and restricted cubic spline (RCS) regression. Results: Among the study participants, 409 participants experienced KL-grade progression, and 684 participants experienced JSN-score progression within 6 years. Overall, the association between iron intake and the risk of KL-grade progression followed a U shape (p for nonlinearity < 0.001). The risk of KL-grade progression was significantly lower in participants with iron intakes of <16.5 mg/day (per mg/day: adjusted hazard ratio (HR), 0.75; 95% CI (confidence interval), 0.64–0.89), and it was higher in those with iron intakes ≥16.5 mg/day (per mg/day: HR, 1.20; 95% CI, 1.04–1.38). Consistently, when the iron intake was assessed as deciles, compared to those in Deciles 3–5 (10.9–23.3 mg/day), the risk of KL-grade progression was higher for Deciles 1–2 (≤10.9 mg/day: HR, 1.57; 95% CI, 1.17–2.10) and for Deciles 6–10 (>23.3 mg/day: adjusted HR, 1.60; 95% CI, 1.19–2.16). Similar U-shaped relations were found for iron intake with the risk of JSN-score progression (p for nonlinearity = 0.035). Conclusions: There was a U-shaped association between the iron intake and the progression of knee OA, with an inflection point at about 16.5 mg/day, and minimal risk from 10.9 to 23.3 mg/day of iron intake. An appropriate iron intake was advisable for knee OA, whereas excessive or deficient iron intake increased the risk of knee OA progression.
Protective Effect of a Water-Soluble Carotenoid-Rich Extract of Cordyceps militaris against Light-Evoked Functional Vision Deterioration in Mice
Authors: Chen Bo-Yie , Huang Ho-Shin , Tsai Kan-Jen , Wu Jia-Lain , Chang Ya-Ting , Chang Ming-Chih , Lu Chun-Mei , Yang Shih-Liang , Huang Hsiang-Shang
Published: April 2022

Light-evoked retinal photodamage is considered an important factor contributing to functional vision deterioration and can even lead to light maculopathy or dry age-related macular degeneration. Loss of visual acuity (VA) and visual contrast sensitivity function (VCSF) are the major symptoms of retinal degenerative diseases. Cordyceps militaris is a carotenoid-rich Chinese medicinal fungus with antioxidant, anti-inflammatory, and immunomodulatory functions. C. militaris extract is a natural substance, and its bioactive constituents have been shown to confer health benefits, but their application in retinal tissue and functional vision protection in vivo remain incompletely understood. In the present study, we evaluated the influence of water-soluble, carotenoid-rich C. militaris extracts on the visual performance of light-damaged mouse retinas in vivo, using adult female CD-1® (ICR) albino mice. We showed that oral administration of this C. militaris extract (10 mg/kg, twice daily) protected the neural retina tissue against light-evoked photoreceptor cell death, reduced Müller cell hypertrophic gliosis, and elevated GSH levels and promoted the recovery of VA- and VCSF-thresholds, especially for high spatial frequency-characterized vision. These results suggest that, probably because of its water-soluble carotenoids, C. militaris extract has the potential to prevent or treat light-induced visual dysfunction.
Analysis of Self-Regulation of Eating Behaviors within Polish Adolescents’ COVID-19 Experience (PLACE-19) Study
Authors: Guzek Dominika , Skolmowska Dominika , Głąbska Dominika
Published: April 2022

The self-regulation of eating behaviors (suppression of behavioral short-term impulse to consume food products in the interest of pursuing long-term weight goals), has been an important determinant for adopting a healthy lifestyle in the period of the COVID-19 pandemic in adults, but there have been no such studies conducted in the population of adolescents in this period. The aim of the presented study is to analyze self-regulation of eating behaviors in the population-based sample of Polish adolescents within the Polish Adolescents’ COVID-19 Experience (PLACE-19) Study. The Self-Regulation of Eating Behavior Questionnaire (SREBQ) was used to assess self-regulation of eating behaviors in the studied population of 1126 Polish adolescents (818 females and 308 males), aged 15–20, recruited based on a random quota sampling within a national sample. Based on the screening questions of the SREBQ, 145 individuals were excluded from the analysis. The participants of the study were categorized based on their gender, body mass index, body mass index change during the COVID-19 pandemic, and food products declared as tempting. The major factors associated with SREBQ score were body mass index change and tempting food products. The respondents losing weight during the COVID-19 pandemic were characterized by a higher SREBQ score than those maintaining stable body mass or gaining weight (3.4 vs. 3.2 vs. 3.2; p = 0.0001). The respondents declaring both sweet and salty food products as tempting were characterized by a lower SREBQ score than those declaring only sweet, only salty, or declaring no tempting products (3.2 vs. 3.4 vs. 3.4 vs. 3.4; p < 0.0001). The major factors associated with SREBQ categories were gender, body mass index change, and tempting food products. A higher share of respondents characterized by a high self-regulation of eating behaviors was observed for males than for females (27.4% vs. 18.8%; p = 0.0142); for respondents losing weight during the COVID-19 pandemic than for respondents gaining weight (25.9% vs. 15.5%; p = 0.0423); as well as for respondents declaring no tempting products than those declaring both sweet and salty food products (38.3% vs. 18.2%; p < 0.0001). It was concluded that the self-regulation of eating behaviors in adolescents is closely associated with food products perceived as tempting by them, as well as with gender. During the COVID-19 pandemic, the low self-regulation of eating behaviors was a significant determinant of the body mass gain. Taking this into account, female adolescents characterized by a low self-regulation of eating behaviors especially should be subjected to a dedicated intervention program to prevent overweight and obesity.
GABA and Fermented Curcuma longa L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice
Authors: Lee Hwa-Young , Lee Geum-Hwa , Hoang The-Hiep , Kim Yu-Mi , Jang Gi-Hyun , Seok Chang-Hwan , Gwak Yun-Geum-Sang , Lim Junghyun , Kim Junghyun , Chae Han-Jung
Published: April 2022

Gamma-aminobutyric acid (GABA) is a natural amino acid with antioxidant activity and is often considered to have therapeutic potential against obesity. Obesity has long been linked to ROS and ER stress, but the effect of GABA on the ROS-associated ER stress axis has not been thoroughly explored. Thus, in this study, the effect of GABA and fermented Curcuma longa L. extract enriched with GABA (FCLL-GABA) on the ROS-related ER stress axis and inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) sulfonation were examined with the HFD model to determine the underlying anti-obesity mechanism. Here, GABA and FCLL-GABA supplementations significantly inhibited the weight gain in HFD fed mice. The GABA and FCLL-GABA supplementation lowered the expressions of adipogenic transcription factors such as PPAR-γ, C/EBPα, FAS, and SREBP-1c in white adipose tissue (WAT) and liver from HFD-fed mice. The enhanced hyper-nutrient dysmetabolism-based NADPH oxidase (Nox) 4 and the resultant IRE1α sulfonation-RIDD-SIRT1 decay under HFD conditions were controlled with GABA and FCLL-GABA. Notably, GABA and FCLL-GABA administration significantly increased AMPK and sirtuin 1 (SIRT1) levels in WAT of HFD-fed mice. These significant observations indicate that ER-localized Nox4-induced IRE1α sulfonation results in the decay of SIRT1 as a novel mechanism behind the positive implications of GABA on obesity. Moreover, the investigation lays a firm foundation for the development of FCLL-GABA as a functional ingredient.
Cell Localization of DPI-Dependent Production of Superoxide in Reproductive Tissues of the Olive Tree (Olea europaea L.)
Authors: Jiménez-Quesada María José , Castro Antonio Jesús , Lima-Cabello Elena , Alché Juan de Dios
Published: April 2022

Reactive Oxygen Species (ROS) are compounds derived from oxygen with important implications in biological processes in plants, some of them related to reproduction. Among ROS, superoxide is the primary oxidant, since an array of other ROS are eventually derived from this anion. Therefore, analysis of the molecular systems able to generate this molecule and the cellular compartmentalization of these events is of paramount importance. We have used the fluorochrome DCFH2-DA and the chromogenic substrate NBT in association with DPI (a specific inhibitor of Rboh enzymes generating superoxide in plants) in combination with confocal microscopy and stereomicroscopy, respectively to identify cell localization of ROS in general, and superoxide accumulation in olive reproductive tissues. A significant production of both ROS and superoxide has been described, showing a fairly precise spatial and temporal location throughout olive flower development. The reduction of the NBT signal after the addition of DPI suggests that the generation of superoxide is largely due to Rboh or other flavin oxidase activity. At the subcellular level, accumulation of O2●− has been located in the plasma membrane of mature pollen and germinated pollen, as well as in the rough endoplasmic reticulum and in mitochondria.
Neuropsychological Outcomes in Adult Patients and Survivors of COVID-19
Authors: May Pamela E.
Published: April 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to affect central nervous system functions through various indirect, and possibly direct, mechanisms. We are only now beginning to understand the possible effects of the virus on human cognition. This review summarizes extant yet limited literature on clinical neuropsychological findings in adult coronavirus disease 2019 (COVID-19) patients and survivors. Neuropsychological outcomes were often in the form of cognitive screen results, although various studies administered comprehensive batteries. With respect to screens, the Montreal Cognitive Assessment appeared relatively sensitive to cognitive dysfunction associated with COVID-19. Patients and survivors presented with weaknesses on screens and comprehensive batteries, although the pattern of these weaknesses was not specific to etiology. Broadly, weaknesses were suggestive of executive dysfunction, although more than one study did not detect significant impairment. Weaknesses should be interpreted cautiously due to potential confounds/contributing factors (weaknesses may partly reflect psychiatric sequelae; weaknesses may be over-interpreted due to inadequate assessment of premorbid functioning). Studies reported different approaches in defining impairment, likely contributing to variable findings. The current review discusses ongoing efforts to harmonize approaches to evaluating neuropsychological functioning globally, as well as emphasizes taking a comprehensive approach towards understanding how the disease affects cognition.
Drug-Induced Lupus Secondary to Ethosuximide in Association with Acute Tubulointerstitial Nephritis and Nephrotic Syndrome
Authors: Aly Rasha , Zeng Xu , Upadhyay Kiran
Published: April 2022

Background. Drug-induced lupus (DIL) is an autoimmune phenomenon where the patient develops lupus-like symptoms after exposure to a long-term medication. Case Summary. Here we describe a 10-year-old female with absence seizures who developed a lupus-like syndrome after being on ethosuximide for three months. She presented with nephrotic syndrome (NS) and acute kidney injury. Four weeks prior to presentation, she had been prescribed a seven-day course of oral amoxicillin for submental swelling after dental extraction. Investigations showed high titer of antinuclear antibody (ANA) and anti-double stranded DNA, elevated serum IgE level, and positive Coombs’ test, along with positive anti-histone antibodies. Renal biopsy showed features of acute tubulointerstitial nephritis (TIN) and partial podocyte foot process effacement without evidence of lupus nephritis. The patient had an excellent response to the steroid therapy with remission within two weeks. The patient remained in remission for two months as evaluated during the most recent follow-up; the autoimmune antibodies and immunoglobulin E trended down. Ethosuximide has been reported to cause DIL, however its possible association with TIN has not been reported. Although amoxicillin could have caused the TIN and NS in this patient, a possible novel association of ethosuximide with this nephrotic-nephritic presentation (NNP) cannot be ruled out. Conclusions. A renal histology is important to determine the accurate etiology of NNP in patients with DIL. Further studies are necessary to determine any possible causal effect of ethosuximide with NNP.
4-Heteroaryl Substituted Amino-3,5-Dicyanopyridines as New Adenosine Receptor Ligands: Novel Insights on Structure-Activity Relationships and Perspectives
Authors: Catarzi Daniela , Varano Flavia , Vigiani Erica , Calenda Sara , Melani Fabrizio , Varani Katia , Vincenzi Fabrizio , Pasquini Silvia , Mennini Natascia , Nerli Giulia , Dal Ben Diego , Volpini Rosaria , Colotta Vittoria
Published: April 2022

A new set of amino-3,5-dicyanopyridines was synthesized and biologically evaluated at the adenosine receptors (ARs). This chemical class is particularly versatile, as small structural modifications can influence not only affinity and selectivity, but also the pharmacological profile. Thus, in order to deepen the structure–activity relationships (SARs) of this series, different substituents were evaluated at the diverse positions on the dicyanopyridine scaffold. In general, the herein reported compounds show nanomolar binding affinity and interact better with both the human (h) A1 and A2A ARs than with the other subtypes. Docking studies at hAR structure were performed to rationalize the observed affinity data. Of interest are compounds 1 and 5, which can be considered as pan ligands as binding all the ARs with comparable nanomolar binding affinity (A1AR: 1, Ki = 9.63 nM; 5, Ki = 2.50 nM; A2AAR: 1, Ki = 21 nM; 5, Ki = 24 nM; A3AR: 1, Ki = 52 nM; 5, Ki = 25 nM; A2BAR: 1, EC50 = 1.4 nM; 5, EC50 = 1.12 nM). Moreover, these compounds showed a partial agonist profile at all the ARs. This combined AR partial agonist activity could lead us to hypothesize a potential effect in the repair process of damaged tissue that would be beneficial in both wound healing and remodeling.
Special Issue “Anticancer Drugs 2021”
Authors: Meegan Mary J. , O’Boyle Niamh M.
Published: April 2022

This Special Issue of Pharmaceuticals is devoted to significant advances achieved in the field of Anticancer Drugs in 2021 [...]
A Theranostic Nanocomplex Combining with Magnetic Hyperthermia for Enhanced Accumulation and Efficacy of pH-Triggering Polymeric Cisplatin(IV) Prodrugs
Authors: Qu Yang , Wang Zhiqi , Sun Miao , Zhao Tian , Zhu Xuanlei , Deng Xiaoli , Zhang Man , Xu Ying , Liu Hongfei
Published: April 2022

Although polymeric platinum(IV) (Pt(IV)) prodrugs can reduce the side effects of cisplatin, the efficacy of the prodrug is still limited by its non-targeted distribution, poor penetration in deep tumor tissue, and low cytotoxicity in tumor cells. To improve the clinical potential of polymeric prodrug micelle, we synthesized amphiphilic polymeric Pt(IV) with high Pt content (22.5%), then developed a theranostic nanocomplex by integrating polymeric Pt(IV) with superparamagnetic Mn0.6Zn0.4Fe2O4 via simple self-assembly. Due to the high content of Mn0.6Zn0.4Fe2O4 (41.7% w/w), the theranostic nanocomplex showed high saturation magnetization (103.1 emu g−1) and excellent magnetocaloric effect (404 W g−1), both of them indicating its advantages in efficient magnetic targeting (MT), magnetic hyperthermia (MH), and magnetic resonance imaging (MRI). In vitro, in combination with MH, the theranostic nanocomplex showed as high cytotoxicity as cisplatin because of a significant increase in platinum of cellular uptake. In vivo, the accumulation of theranostic nanocomplex in tumors was increased by MT and confirmed by MRI. Furthermore, MH improved penetration of theranostic nanocomplex in tumors as expanding blackened area in tumors was observed by MRI. Based on these properties, the theranostic nanocomplex, under the assistance of MT and MH, showed the highest tumor growth inhibition rate (88.38%) after different treatments, while the body weight of mice increased slightly, indicating low side effects compared to those of cisplatin. The study provided an advanced theranostic nanocomplex with low toxicity and high efficacy, indicating a great clinical potential of polymeric Pt(IV).
Effectiveness and Cost-Effectiveness Profile of Second-Line Treatments with Nivolumab, Pembrolizumab and Atezolizumab in Patients with Advanced Non-Small Cell Lung Cancer
Authors: Franchi Matteo , Pellegrini Giacomo , Corrao Giovanni
Published: April 2022

No evidence is available on the head-to-head comparison of clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) in a real-world setting. We aimed to compare the effectiveness and cost-effectiveness profile of nivolumab, pembrolizumab and atezolizumab. We used a population-based retrospective cohort study based on the healthcare utilization databases of the Lombardy Region, Italy. The study cohort included all patients with a diagnosis of lung cancer, who started a second-line treatment for advanced NSCLC with nivolumab, pembrolizumab or atezolizumab from 2015 to 30 June 2020. Overall survival and average cumulative healthcare costs were measured from the start of second-line treatment until 31 December 2020. The study cohort included 1607 patients who started a second-line treatment with ICIs, of which there were 1193 with nivolumab, 138 with pembrolizumab and 276 with atezolizumab. No differences were observed between treatment arms in terms of sex, age or comorbidities. Median OS was very similar between groups, being 8.9, 9.4 and 8.7 months, respectively, in patients treated with nivolumab, pembrolizumab and atezolizumab (p = 0.898). The adjusted hazard ratio of death of patients treated with pembrolizumab and atezolizumab, as compared to nivolumab, were 1.01 (95% CI: 0.81 to 1.25) and 1.03 (0.88 to 1.21), respectively. Healthcare cumulative costs measured in the first two years of follow-up were EUR 43,764, 46,233 and 34,116, on average, associated with nivolumab, pembrolizumab and atezolizumab, respectively. In our real-world study, atezolizumab was the ICI associated with the most favorable cost-effectiveness profile.
Therapeutic Vaccines Targeting Neoantigens to Induce T-Cell Immunity against Cancers
Authors: Pao Shih-Cheng , Chu Mu-Tzu , Hung Shuen-Iu
Published: April 2022

Cancer immunotherapy has achieved multiple clinical benefits and has become an indispensable component of cancer treatment. Targeting tumor-specific antigens, also known as neoantigens, plays a crucial role in cancer immunotherapy. T cells of adaptive immunity that recognize neoantigens, but do not induce unwanted off-target effects, have demonstrated high efficacy and low side effects in cancer immunotherapy. Tumor neoantigens derived from accumulated genetic instability can be characterized using emerging technologies, such as high-throughput sequencing, bioinformatics, predictive algorithms, mass-spectrometry analyses, and immunogenicity validation. Neoepitopes with a higher affinity for major histocompatibility complexes can be identified and further applied to the field of cancer vaccines. Therapeutic vaccines composed of tumor lysates or cells and DNA, mRNA, or peptides of neoantigens have revoked adaptive immunity to kill cancer cells in clinical trials. Broad clinical applicability of these therapeutic cancer vaccines has emerged. In this review, we discuss recent progress in neoantigen identification and applications for cancer vaccines and the results of ongoing trials.
Evaluation of CTB-sLip for Targeting Lung Metastasis of Colorectal Cancer
Authors: Zhang Xiaoying , Tang Wenjing , Wen Haoyu , Wu Ercan , Ding Tianhao , Gu Jie , Lv Zhongwei , Zhan Changyou
Published: April 2022

Lung metastasis of colorectal cancer is common in the clinic; however, precise targeting for the diagnosis and therapy purposes of those lung metastases remains challenging. Herein, cholera toxin subunit b (CTB) protein was chemically conjugated on the surface of PEGylated liposomes (CTB-sLip). Both human-derived colorectal cancer cell lines, HCT116 and HT-29, demonstrated high binding affinity and cellular uptake with CTB-sLip. In vivo, CTB-sLip exhibited elevated targeting capability to the lung metastasis of colorectal cancer in the model nude mice in comparison to PEGylated liposomes (sLip) without CTB modification. CTB conjugation induced ignorable effects on the interaction between liposomes and plasma proteins but significantly enhanced the uptake of liposomes by numerous blood cells and splenic cells, leading to relatively rapid blood clearance in BALB/c mice. Even though repeated injections of CTB-sLip induced the production of anti-CTB antibodies, our results suggested CTB-sLip as promising nanocarriers for the diagnosis of lung metastasis of colorectal cancer.
Polymeric Nanocapsules Containing Fennel Essential Oil: Their Preparation, Physicochemical Characterization, Stability over Time and in Simulated Gastrointestinal Conditions
Authors: Granata Giuseppe , Riccobene Carla , Napoli Edoardo , Geraci Corrada
Published: April 2022

Plant essential oils, a source of biologically active compounds, represent a promising segment in the pharmaceutical market. However, their volatility, hydrophobicity, poor stability, and low toxicity limit direct use in pharmaceutical-related applications. Nanoencapsulation is a technique that allows overcoming these obstacles by improving bioaccessibility and bioavailability. Nanocapsules (NCs) based on biodegradable and biocompatible poly(ɛ-caprolactone) containing Foeniculum vulgare Mill. essential oil (FEO), known for its biological activities, were successfully prepared by interfacial deposition of the preformed polymer method. The composition of FEO (trans-anethole chemotype) was determined by gas chromatography analyses. The FEO presence inside the NCs was confirmed by nuclear magnetic resonance experiments. The FEO-NCs showed nanometer size (210 nm), low polydispersity index (0.10), negative zeta potential (−15 mV), non-Newtonian rheological behavior, and high efficiency of encapsulation (93%). Moreover, parameters such as FEO-NC particle size, bioactive compound retention, and FEO composition were monitored for 30 days at storage temperatures of 4 and 40 °C, confirming the robustness of the nanosystem. Finally, FEO-NCs were resistant to the simulated gastric digestion and showed an effective bioaccessibility of 29% in simulated intestinal digestion. Based on the results obtained, this FEO-NC nanosystem could find interesting applications in the nutraceutical and pharmaceutical sectors.
Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2
Authors: Faísca Francisco , Correia Vanessa , Petrovski Željko , Branco Luís C. , Rebelo-de-Andrade Helena , Santos Miguel M.
Published: April 2022

The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH2][C1SO3]2 and [HCQH2][GlcCOO]2, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH2][SO4]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH2][GlcCOO]2. Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra- and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.
Oleyl Conjugated Histidine-Arginine Cell-Penetrating Peptides as Promising Agents for siRNA Delivery
Authors: Sajid Muhammad Imran , Mandal Dindyal , El-Sayed Naglaa Salem , Lohan Sandeep , Moreno Jonathan , Tiwari Rakesh Kumar
Published: April 2022

Recent approvals of siRNA-based products motivated the scientific community to explore siRNA as a treatment option for several intractable ailments, especially cancer. The success of approved siRNA therapy requires a suitable and safer drug delivery agent. Herein, we report a series of oleyl conjugated histidine–arginine peptides as a promising nonviral siRNA delivery tool. The conjugated peptides were found to bind with the siRNA at N/P ratio ≥ 2 and demonstrated complete protection for the siRNA from early enzymatic degradation at N/P ratio ≥ 20. Oleyl-conjugated peptide -siRNA complexes were found to be noncytotoxic in breast cancer cells (MCF-7 and MDA-MB-231) and normal breast epithelial cells (MCF 10A) at N/P ratio of ~40. The oleyl-R3-(HR)4 and oleyl-R4-(HR)4 showed ~80-fold increased cellular uptake in MDA-MB-231 cells at N/P 40. Moreover, the conjugated peptides-siRNA complexes form nanocomplexes (~115 nm in size) and have an appropriate surface charge to interact with the cell membrane and cause cellular internalization. Furthermore, this study provides a proof-of-concept that oleyl-R5-(HR)4 can efficiently silence STAT-3 gene (~80% inhibition) in MDA-MB-231 cells with similar effectiveness to Lipofectamine. Further exploration of this approach holds a great promise in discovering a successful in vivo siRNA delivery agent with a favorable pharmacokinetic profile.
Optimizing and Quantifying Gold Nanospheres Based on LSPR Label-Free Biosensor for Dengue Diagnosis
Authors: Farooq Sajid , Wali Faiz , Zezell Denise Maria , de Araujo Renato E. , Rativa Diego
Published: April 2022

The localized surface plasmon resonance (LSPR) due to light–particle interaction and its dependence on the surrounding medium have been widely manipulated for sensing applications. The sensing efficiency is governed by the refractive index-based sensitivity (ηRIS) and the full width half maximum (FWHM) of the LSPR spectra. Thereby, a sensor with high precision must possess both requisites: an effective ηRIS and a narrow FWHM of plasmon spectrum. Moreover, complex nanostructures are used for molecular sensing applications due to their good ηRIS values but without considering the wide-band nature of the LSPR spectrum, which decreases the detection limit of the plasmonic sensor. In this article, a novel, facile and label-free solution-based LSPR immunosensor was elaborated based upon LSPR features such as extinction spectrum and localized field enhancement. We used a 3D full-wave field analysis to evaluate the optical properties and to optimize the appropriate size of spherical-shaped gold nanoparticles (Au NPs). We found a change in Au NPs’ radius from 5 nm to 50 nm, and an increase in spectral resonance peak depicted as a red-shift from 520 nm to 552 nm. Using this fact, important parameters that can be attributed to the LSPR sensor performance, namely the molecular sensitivity, FWHM, ηRIS, and figure of merit (FoM), were evaluated. Moreover, computational simulations were used to assess the optimized size (radius = 30 nm) of Au NPs with high FoM (2.3) and sharp FWHM (44 nm). On the evaluation of the platform as a label-free molecular sensor, Campbell’s model was performed, indicating an effective peak shift in the adsorption of the dielectric layer around the Au NP surface. For practical realization, we present an LSPR sensor platform for the identification of dengue NS1 antigens. The results present the system’s ability to identify dengue NS1 antigen concentrations with the limit of quantification measured to be 0.07 μg/mL (1.50 nM), evidence that the optimization approach used for the solution-based LSPR sensor provides a new paradigm for engineering immunosensor platforms.
Unsaturated Polyester Resin Nanocomposites Based on Post-Consumer Polyethylene Terephthalate
Authors: Kirshanov Kirill , Toms Roman , Melnikov Pavel , Gervald Alexander
Published: April 2022

A method for producing nanocomposites of unsaturated polyester resins (UPR) based on recycled polyethylene terephthalate (PET) as a matrix has been proposed. The upcycling method involves three successive stages: (1) oligoesters synthesis, (2) simultaneous glycolysis and interchain exchange of oligoesters with PET, (3) interaction of the obtained resins with glycol and maleic anhydride. UPRs were characterized by FTIR spectroscopy and gel permeation chromatography. The mechanical properties of nanocomposites obtained on the basis of these resins and titanium dioxide have been investigated. It has been shown that 1,2-propylene glycol units, despite their lower reactivity, significantly improve the properties of UPR. The most promising nanocomposite sample exhibited tensile strength 112.62 MPa, elongation at break 157.94%, and Young’s modulus 29.95 MPa. These results indicate that the proposed method made it possible to obtain nanocomposites with high mechanical properties based on recycled PET thus allowing one to create a valuable product from waste.