bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Disparities in Adults’ Macronutrient Intake Status: Results from the China Health and Nutrition 2011 Survey
Authors: Zhao Yajie , Araki Tetsuya
Published: August 2021

Little is known about the macronutrient intake status of adult Chinese people. This cross-sectional study assessed the macronutrient intake status of adults (aged ≥20 years) by comparing their intake level of macronutrients against the Dietary Reference Intakes (DRI). It further explored the associations between macronutrient intake status and age groups, genders, education levels, smoking status, drinking frequency, social classes, knowledge of Chinese Dietary Guidelines 2016 (CDGs), healthy diet priorities, and areas (urban and rural) within two regions (northern and southern). The analysis includes the dietary intake data of 7860 Chinese adults, with complete data entries in the China Health and Nutrition 2011 survey. Dietary data were obtained through the 24 h recall method. More than half had carbohydrate intake below the recommended level of intake, and more than half had fat intake above the recommended level of intake. There were significant associations between three macronutrient intakes and education levels, social classes, healthy diet priorities, areas, and regions. Disparities in macronutrient consumptions revealed geographical and socioeconomic variations in dietary patterns, as well as risks for many different noncommunicable diseases. Public health and nutrition interventions should take notice of regional differences in dietary intake and place more emphasis on vulnerable populations including women, rural residents, and people with lower education level.
Diet and Pre-Intervention Washout Modifies the Effects of Probiotics on Gestational Diabetes Mellitus: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Hasain Zubaidah , Che Roos Nur , Rahmat Frhana , Mustapa Marami , Raja Ali Raja , Mokhtar Norfilza
Published: August 2021

Dynamic interactions among gestational diabetes mellitus (GDM), gut microbiota, inflammation, oxidative stress, and probiotics are increasingly acknowledged. This meta-analysis aimed to summarize the effects of probiotics in GDM, focusing on lifestyle intervention and pre-intervention washout, in addition to metabolic, inflammation, oxidative stress, and pregnancy outcomes. Three electronic databases (i.e., PubMed, Scopus, and CENTRAL) were searched from inception until October 2020. A meta-analysis was performed, and the effect sizes were reported as either mean differences or odds ratios with 95% confidence intervals. Altogether, 10 randomized controlled trials enrolling 594 participants were included. The meta-analysis indicated that probiotics supplementation effectively reduced fasting plasma glucose by 3.10 mg/dL, and subgroup analyses suggested that the duration of intervention, number of species, pre-intervention washout period, and dietary intervention may determine the effects of probiotics. Probiotics also reduced the level of inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and malondialdehyde), incidence of macrosomia, and newborn hospitalization. In conclusion, this meta-analysis suggests that probiotics may have positive effects on metabolic, inflammation, oxidative stress, and neonatal outcomes in women with GDM. Additionally, diet and pre-intervention washout may modify the effects of probiotics. Future studies are warranted on a larger scale to ascertain the clinical significance.
Prevalence and Clinical Features of Celiac Disease in a Cohort of Italian Children with Autism Spectrum Disorders
Authors: Prosperi Margherita , Santocchi Elisa , Brunori Elena , Cosenza Angela , Tancredi Raffaella , Muratori Filippo , Calderoni Sara
Published: August 2021

Background: Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions whose etiopathogenesis derives from a complex interaction between genetic liability and environmental factors. In this framework, mounting evidence suggests that immune system dysfunction could be a risk factor contributing to the development of ASD in at least a subpopulation of individuals. In particular, some studies suggest an association between celiac disease (CD)—a long-term autoimmune disorder that primarily affects the small intestine triggered by the ingestion of gluten—and ASD, while others hypothesized a random link. This investigation aimed to evaluate the prevalence of CD in a large sample of school-aged children with ASD and to characterize their clinical profile. Methods: Medical records of 405 children with ASD aged 5–11 years (mean age: 7.2 years; SD: 1.8 years) consecutively referred to a tertiary-care university hospital between January 2014 and December 2018 were reviewed; among them, 362 had carried out serological testing for CD. Results: Nine patients with positive CD serology were identified, eight of which satisfied the criteria for CD diagnosis. The estimated CD prevalence in ASD children was 2.18% (95% CI, 0.8–3.7), which was not statistically different (1.58%; p = 0.36) from that of an Italian population, matched for age range, considered as a control group (95% CI, 1.26–1.90). Three out of the eight ASD patients with CD did not have any symptoms suggestive of CD. Conclusions: Our findings did not show a higher prevalence of CD in ASD children than in the control population, but could suggest the utility of routine CD screening, given its frequent atypical clinical presentation in this population.
Phenol Biological Metabolites as Food Intake Biomarkers, a Pending Signature for a Complete Understanding of the Beneficial Effects of the Mediterranean Diet
Authors: Mosele Juana I. , Motilva Maria-Jose
Published: August 2021

The Mediterranean diet (MD) has become a dietary pattern of reference due to its preventive effects against chronic diseases, especially relevant in cardiovascular diseases (CVD). Establishing an objective tool to determine the degree of adherence to the MD is a pending task and deserves consideration. The central axis that distinguishes the MD from other dietary patterns is the choice and modality of food consumption. Identification of intake biomarkers of commonly consumed foods is a key strategy for estimating the degree of adherence to the MD and understanding the protective mechanisms that lead to a positive impact on health. Throughout this review we propose potential candidates to be validated as MD adherence biomarkers, with particular focus on the metabolites derived from the phenolic compounds that are associated with the consumption of typical Mediterranean plant foods. Certain phenolic metabolites are good indicators of the intake of specific foods, but others denote the intake of a wide-range of foods. For this, it is important to emphasise the need to increase the number of dietary interventions with specific foods in order to validate the biomarkers of MD adherence. Moreover, the identification and quantification of food phenolic intake biomarkers encouraging scientific research focuses on the study of the biological mechanisms in which polyphenols are involved.
Energy-Adjusted Dietary Intakes Are Associated with Perceived Barriers to Healthy Eating but Not Food Insecurity or Sports Nutrition Knowledge in a Pilot Study of ROTC Cadets
Authors: Daniels Elizabeth , Hanson Jennifer
Published: August 2021

Military service is inherently demanding and, due to the nature of these demands, the term “tactical athlete” has been coined to capture the physical requirements of the profession. Reserve Officers’ Training Corps (ROTC) cadets are a unique subset of the military service community, and the complexity of their training and educational pursuits increases their susceptibility to unhealthy eating patterns. The purpose of this pilot study was to explore the relationship between the perceived barriers to healthy eating, food insecurity, sports nutrition knowledge, and dietary patterns among Army ROTC cadets. The usual dietary intake was gathered from (N = 37) cadets using the General Nutrition Assessment Food Frequency Questionnaire. The perceived barriers to healthy eating were measured using a set of scales consisting of social barriers (6 items, α = 0.86), access barriers (2 items, α = 0.95), and personal barriers (2 items, α = 0.67), with higher-scale scores indicating greater perceived barriers. Spearman correlation coefficients were used to measure the association between the energy-adjusted dietary intakes and the scores on the barriers scales. Energy-adjusted intakes of calcium (ρ = −0.47, p ≤ 0.01), fiber (ρ = −0.35, p = 0.03), vitamin A (ρ = −0.46, p ≤ 0.01), vitamin C (ρ = −0.43, p ≤ 0.01), fruit (ρ = −0.34, p = 0.04), and vegetables (ρ = −0.50, p ≤ 0.01) were negatively correlated with the perceived personal barrier scores. The energy-adjusted intakes of fiber (ρ = −0.36, p = 0.03), vitamin C (ρ = −0.37, p = 0.03), and vitamin E (ρ = −0.45, p ≤.01) were negatively correlated with perceived social barriers, while energy-adjusted vitamin C intake was negatively correlated with perceived access barriers (ρ = −0.40, p = 0.01). Although additional research is needed to better understand the dietary patterns of ROTC cadets, among the participants in this study, greater perceived personal, social, and access barriers were associated with less nutrient-dense eating patterns. Interventions aimed at addressing such barriers may prove beneficial for the improvement of diet quality among ROTC cadets.
Effect of Spirulina Supplementation on Systolic and Diastolic Blood Pressure: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Machowiec Piotr , Ręka Gabriela , Maksymowicz Marcela , Piecewicz-Szczęsna Halina , Smoleń Agata
Published: August 2021

Spirulina is a microalga that presents various important pro-health properties, for instance lowering blood pressure in the research. The study aims to appraise the efficacy of Spirulina administration on systolic (SBP) and diastolic blood pressure (DBP). Randomized controlled trials (RCTs) were retrieved by a systematic search of PubMed, Web of Science, and the Cochrane Library databases from inception to June 2021 according to a standardized protocol. The effect size of each study was counted from mean and standard deviation before and after the intervention and shown as Un-standardized mean difference and 95% confidence interval. Sensitivity analyses were performed. Meta-analysis on 5 RCTs with 230 subjects was eligible. The amount of Spirulina ranged from 1 to 8 g per day, and intervention durations ranged from 2 to 12 weeks. Data analysis indicated that Spirulina supplementation led to a significant lowering of SBP (Mean Difference (MD): −4.59 mmHg, 95% Confidence Interval (CI): −8.20 to −0.99, I square statistic (I2) = 65%) and significant lowering of DBP (MD: −7.02 mmHg, CI: −8.86 to −5.18, I2 = 11%), particularly in a subgroup of hypertensive patients. Spirulina administration might have a supportive effect on the prevention and treatment of hypertension. More exact randomized controlled trials are needed to clarify the effect of Spirulina supplementation on blood pressure.
Pulses Twice a Week in Replacement of Meat Modestly Increases Diet Sustainability
Authors: Gazan Rozenn , Maillot Matthieu , Reboul Emmanuelle , Darmon Nicole
Published: August 2021

The French food-based dietary guidelines recommend eating pulses at least twice a week and to reduce meat consumption. This study assessed the impact on the sustainability characteristics (nutrition, cost, environment) of individual diets of meeting the pulse guideline. Dietary data of 2028 adults from the Esteban survey were completed with the nutritional content (considering bioavailability on iron, zinc and protein), price and environmental impacts of foods. When the pulse guideline (i.e., 57 g/day) was not met, two substitution scenarios raised the quantity of pulses to the recommended level, in replacement of an equivalent portion of (i) starches or (ii) meat. Only 9.6% of the participants reached the pulse guideline. Diet sustainability characteristics improved with the meat scenario (nutritional indicators improved; diet cost, greenhouse gas emissions and acidification decreased), while several indicators deteriorated with the starches scenario. Zinc available for absorption slightly decreased in both scenarios while iron available for absorption decreased in the meat scenario only. Increasing pulse consumption to two portions/week could modestly improve the sustainability of diets when pulses replace meat but not starches. Cultural acceptability of that substitution still needs to be proven, and iron and zinc status of individuals at risk of deficiency should be monitored.
Factors Influencing the Compliance of Pregnant Women with Iron and Folic Acid Supplementation in the Philippines: 2017 Philippine Demographic and Health Survey Analysis
Authors: Felipe-Dimog Eva Belingon , Yu Chia-Hung , Ho Chung-Han , Liang Fu-Wen
Published: August 2021

Anemia in pregnancy, which is a public health concern for most developing countries, is predominantly caused by iron deficiency. At least, 180 days of iron and folic acid (IFA) supplementation is recommended for pregnant women to mitigate anemia and its adverse effects. This study aimed to examine compliance with the recommendation of IFA supplementation and its underlying factors using the 2017 Philippine National Demographic and Health Survey data. The variables assessed included age, highest level of education, occupation, wealth index, ethnicity, religion, residence, number of pregnancies, time of first antenatal care (ANC) visit and number of ANC visits. Compliance with the recommendation of at least 180 days of IFA supplementation was the outcome variable. The study assessed 7983 women aged 15–49 years with a history of pregnancy. Of these participants, 25.8% complied with the IFA supplementation recommendation. Multiple logistic regression analysis showed that pregnant women of Islamic faith and non-Indigenous Muslim ethnicity were less likely to comply with the IFA supplementation recommendation. Being aged between 25 and 34 years, having better education and higher wealth status, rural residency, initiating ANC visits during the first trimester of pregnancy and having at least four ANC visits positively influenced compliance with IFA supplementation. The effect of residence on IFA adherence differed across the wealth classes. Strategies targeted at specific groups, such as religious minorities, poor urban residents, the less educated and young women, should be strengthened to encourage early and regular antenatal care visits for improving compliance.
Irritable Bowel Syndrome, Depression, and Neurodegeneration: A Bidirectional Communication from Gut to Brain
Authors: Aziz Muhammad , Kumar Jaya , Muhammad Nawawi Khairul , Raja Ali Raja , Mokhtar Norfilza
Published: August 2021

Patients with irritable bowel syndrome (IBS) are increasingly presenting with a wide range of neuropsychiatric symptoms, such as deterioration in gastroenteric physiology, including visceral hypersensitivity, altered intestinal membrane permeability, and gastrointestinal motor dysfunction. Functional imaging of IBS patients has revealed several abnormalities in various brain regions, such as significant activation of amygdala, thinning of insular and anterior cingulate cortex, and increase in hypothalamic gray matter, which results in poor psychiatric and cognitive outcomes. Interrelations between the enteric and central events in IBS-related gastrointestinal, neurological, and psychiatric pathologies have compelled researchers to study the gut-brain axis—a bidirectional communication that maintains the homeostasis of the gastrointestinal and central nervous system with gut microbiota as the protagonist. Thus, it can be disrupted by any alteration owing to the gut dysbiosis or loss of diversity in microbial composition. Available evidence indicates that the use of probiotics as a part of a balanced diet is effective in the management of IBS and IBS-associated neurodegenerative and psychiatric comorbidities. In this review, we delineate the pathogenesis and complications of IBS from gastrointestinal and neuropsychiatric standpoints while also discussing the neurodegenerative events in enteric and central nervous systems of IBS patients and the therapeutic potential of gut microbiota-based therapy established on clinical and preclinical data.
Lower Dietary Intake of Plant Protein Is Associated with Genetic Risk of Diabetes-Related Traits in Urban Asian Indian Adults
Authors: Alsulami Sooad , Bodhini Dhanasekaran , Sudha Vasudevan , Shanthi Rani Coimbatore Subramanian , Pradeepa Rajendra , Anjana Ranjit Mohan , Radha Venkatesan , Lovegrove Julie A. , Gayathri Rajagopal , Mohan Viswanathan , Vimaleswaran Karani Santhanakrishnan
Published: August 2021

The increasing prevalence of type 2 diabetes among South Asians is caused by a complex interplay between environmental and genetic factors. We aimed to examine the impact of dietary and genetic factors on metabolic traits in 1062 Asian Indians. Dietary assessment was performed using a validated semi-quantitative food frequency questionnaire. Seven single nucleotide polymorphisms (SNPs) from the Transcription factor 7-like 2 and fat mass and obesity-associated genes were used to construct two metabolic genetic risk scores (GRS): 7-SNP and 3-SNP GRSs. Both 7-SNP GRS and 3-SNP GRS were associated with a higher risk of T2D (p = 0.0000134 and 0.008, respectively). The 3-SNP GRS was associated with higher waist circumference (p = 0.010), fasting plasma glucose (FPG) (p = 0.002) and glycated haemoglobin (HbA1c) (p = 0.000066). There were significant interactions between 3-SNP GRS and protein intake (% of total energy intake) on FPG (Pinteraction = 0.011) and HbA1c (Pinteraction = 0.007), where among individuals with lower plant protein intake (<39 g/day) and those with >1 risk allele had higher FPG (p = 0.001) and HbA1c (p = 0.00006) than individuals with ≤1 risk allele. Our findings suggest that lower plant protein intake may be a contributor to the increased ethnic susceptibility to diabetes described in Asian Indians. Randomised clinical trials with increased plant protein in the diets of this population are needed to see whether the reduction of diabetes risk occurs in individuals with prediabetes.
Associations between Early-Life Food Deprivation and Risk of Frailty of Middle-Age and Elderly People: Evidence from the China Health and Retirement Longitudinal Study
Authors: Ye Chen , Aihemaitijiang Sumiya , Wang Ruoyu , Halimulati Mairepaiti , Zhang Zhaofeng
Published: August 2021

Background: The association between childhood food deprivation (FD) and health in later life has been extensively studied; however, studies on the association between childhood food deprivation and frailty are scarce. This study assessed the associations between childhood FD and the risk of frailty at middle-age and old age. Methods: Three waves of the China Health and Retirement Longitudinal Study (CHARLS), including 11,615 individuals aged over 45 years, were used for this research. Frailty was operationalized according to the FRAIL scale as a sum of fatigue, resistance, ambulation, illness, and the loss of weight. Childhood FD experiences and levels were measured by self-reported FD and historical content. Logistic mixed-effects models and proportional odds ordered logistic regression models were used to analyse the association between childhood FD and frailty. Findings: Childhood FD increased the odds of frailty at old age (1.30, 95% CI: 1.26–1.36). Compared with subjects with mild FD, those with extreme FD experiences had increased risks of frailty (1.34, 95% CI: 1.26–1.43). Subjects exposed to hunger at different ages all had an increased risk of frailty, and subjects who had FD during ages 6–12 (1.15, 95% CI: 1.09–1.22) were more likely to have an increased risk of frailty than those who had experienced FD in younger ages. The interaction of experience of FD at ages 0–6 and the experience of FD at ages 6–12 is not statistically significant after adjusting all covariates. Conclusions: Our findings suggest that childhood FD exerts long-lasting effects on frailty among older adults in China. The prevention of childhood FD may delay or even avert the emergence of frailty in people of middle-age and old age.
The Enigma of Low-Density Granulocytes in Humans: Complexities in the Characterization and Function of LDGs during Disease
Authors: Seman Brittany G. , Robinson Cory M.
Published: August 2021

Low-density granulocytes (LDGs) have been characterized as important immune cells during healthy and disease states in humans, including microbial infections, cancer, and autoimmune dysfunction. However, the classification of this cell type is similar to other immune cells (e.g., neutrophils, myeloid-derived suppressor cells) and ambiguous functional standards have rendered LDG identification and isolation daunting. Furthermore, most research involving LDGs has mainly focused on adult cells and subjects, leaving increased uncertainty surrounding younger populations, especially in vulnerable neonatal groups where LDG numbers are elevated. This review aims to bring together the current research in the field of LDG biology in the context of immunity to disease, with a focus on infection. In addition, we propose to highlight the gaps in the field that, if filled, could improve upon isolation techniques and functional characterizations for LDGs separate from neutrophils and myeloid-derived suppressor cells (MDSCs). This will not only enhance understanding of LDGs during disease processes and how they differ from other cell types but will also aid in the interpretation of comparative studies and results with the potential to inform development of novel therapeutics to improve disease states in patients.
Association between Suicide and Toxoplasma gondii Seropositivity
Authors: Mendoza-Larios Laura Alejandra , García-Dolores Fernando , Sánchez-Anguiano Luis Francisco , Hernández-Tinoco Jesús , Alvarado-Esquivel Cosme
Published: August 2021

This study aimed to determine the association between suicide and Toxoplasma gondii (T. gondii) seropositivity. Serum samples of 89 decedents who committed suicide (cases) and 58 decedents who did not commit suicide (controls) were tested for anti-T. gondii IgG and IgM antibodies using enzyme-linked immunosorbent assays. Anti-T. gondii IgM antibodies were further detected by enzyme-linked fluorescence assay (ELFA). A total of 8 (9.0%) of the 89 cases and 6 (10.3%) of the 58 controls were positive for anti-T. gondii IgG antibodies (OR: 0.85; 95% CI: 0.28–2.60; p = 0.78). Anti-T. gondii IgG levels were higher than 150 IU/mL in two (2.2%) cases and in five (8.6%) controls (OR: 0.24; 95% CI: 0.04–1.30; p = 0.11). Anti-T. gondii IgM antibodies were not found in any case or control using the enzyme immunoassay and were found in only one (1.7%) control using ELFA (p = 0.39). Rates of IgG seropositivity and high levels of anti-T. gondii antibodies were similar in cases and in controls regardless of their sex or age groups. The results do not support an association between T. gondii seropositivity and suicide. However, the statistical power of the test was low. Further research is necessary to confirm this lack of association.
Genomic Variability of Canine Parvoviruses from a Selected Population of Dogs and Cats in Sri Lanka
Authors: Jinadasa Rasika , Ghosh Sayani , Hills Simon , Premalal Thushini , Atapattu Ushani , Fuward Manohari , Kalupahana Wasantha , Dunowska Magdalena
Published: August 2021

The aim of the study was to identify canine parvovirus type 2 (CPV-2) subtypes circulating among a selected population of domestic dogs and cats in Sri Lanka and to investigate the evolutionary patterns among Sri Lankan viruses in the context of contemporary global CPV-2 sequences. Altogether, 40/61 (65.6%) samples tested were positive for CPV-2 DNA, including 31/48 (64.6%) dogs and 9/13 (69%) cats. All three subtypes (CPV-2a, CPV-2b and CPV-2c) were detected, with CPV-2a being most common. International median joining haplotype network of 291 CPV-2 sequences suggested that there was little barrier for CPV-2 moving between different geographical regions worldwide, including Sri Lanka, and that there was no correlation between the genetic structure within the molecular network and the decade of sample collection. By contrast, there was correlation between CPV-2 subtype and genetic structure, both within the international network and within the network built from 31 Sri Lankan CPV-2 sequences only. The structure within the latter was not correlated with the location of the veterinary clinic where the samples were submitted, the age or species of the host. Altogether, we have shown that there is considerable variability of CPV-2 genotypes circulating in Sri Lanka, which is likely driven by both local evolution and introduction from other countries. The similarity of CPV-2 obtained from cats and dogs suggests that cats may play a role in the epidemiology of CPV-2 in Sri Lanka.
Asymptomatic COVID-19 Individuals Tend to Establish Relatively Balanced Innate and Adaptive Immune Responses
Authors: Li Miao , Zhang Yue , Lu Jianhua , Li Li , Gao Huixia , Ma Cuiqing , Dai Erhei , Wei Lin
Published: August 2021

The sharp increase in the proportion of asymptomatic cases and the potential risk of virus transmission have greatly increased the difficulty of controlling the COVID-19 pandemic. The individual immune response is closely associated with clinical outcomes and pathogenic mechanisms of COVID-19. However, the clinical characteristics and immunophenotyping features of immune cells of asymptomatic individuals remain somewhat mysterious. To better understand and predict the disease state and progress, we performed a comprehensive analysis of clinical data, laboratory indexes and immunophenotyping features in 41 patients with SARS-CoV-2 (including 24 asymptomatic cases and 17 symptomatic individuals). Firstly, from the perspective of demographic characteristics, the rate of asymptomatic infection was significantly higher in those with younger age. Secondly, the laboratory test results showed that some indexes, such as CRP (acute phase reaction protein), D-Dimer and fibrinogen (the marker for coagulation) were lower in the asymptomatic group. Finally, symptomatic individuals were prone to establishing a non-protective immune phenotype by abnormally decreasing the lymphocyte count and percentage, abnormally increasing the Th17 percentage and decreasing Treg percentage, which therefore cause an increase in the neutrophil/lymphocyte ratio (NLR), monocytes/lymphocytes ratio (MLR) and Th17/Treg ratio. On the other hand, asymptomatic individuals tended to establish a more effective and protective immune phenotype by maintaining a normal level of lymphocyte count and percentage and a high level of NK cells. At the same time, asymptomatic individuals can establish a relatively balanced immune response through maintaining a low level of monocytes, a relatively low level of Th17 and high level of Treg, which therefore lead to a decrease in MNKR and Th17/Treg ratio and finally the avoidance of excessive inflammatory responses. This may be one of the reasons for their asymptomatic states. This study is helpful to reveal the immunological characteristics of asymptomatic individuals, understand immune pathogenesis of COVID-19 and predict clinical outcomes more precisely. However, owing to small sample sizes, a future study with larger sample size is still warranted.
Discrete Survival Model Analysis of Plasmodium falciparum Response to Artemisinin-Based Combination Therapies among Children in Regions of Varying Malaria Transmission in Cameroon
Authors: Nji Akindeh M. , Ali Innocent M. , Niba Peter Thelma Ngwa , Marie-Solange Evehe , Heumann Christian , Froeschl Guenter , Mbacham Wilfred F.
Published: August 2021

The need to monitor changes in parasite clearance following treatment with artemisinin-based combination therapies (ACTs) is important in the containment of drug resistance. This study aimed to model Plasmodium falciparum response to ACTs among children in two different transmission settings (Mutengene and Garoua) in Cameroon. Using the step function, a discrete-time survival model was fitted with all the covariates included that might play a role in parasite clearance. The probability of clearing parasites within 24 h following treatment was 21.6% and 70.3% for younger children aged 6 to 59 months and 29.3% and 59.8% for older children aged 60 to 120 months in Mutengene and Garoua, respectively. After two days of treatment, the conditional probability of clearing parasites given that they were not cleared on day 1 was 76.7% and 96.6% for children aged 6–59 months and 83.1% and 93.5% for children aged 60–120 months in Mutengene and Garoua, respectively. The model demonstrated that the ecological setting, age group and pretreatment serum levels of creatinine and alanine aminotransferase were the main factors that significantly influenced parasite clearance in vivo after administration of ACTs (p < 0.05). The findings highlight the need for further investigations on host differential response to ACTs in current practice.
Molecular Investigation of Zoonotic Intestinal Protozoa in Pet Dogs and Cats in Yunnan Province, Southwestern China
Authors: Wang Yu-Gui , Zou Yang , Yu Ze-Zhong , Chen Dan , Gui Bin-Ze , Yang Jian-Fa , Zhu Xing-Quan , Liu Guo-Hua , Zou Feng-Cai
Published: August 2021

Giardia duodenalis, Enterocytozoon bieneusi and Cryptosporidium spp. are common enteric pathogens that reside in the intestines of humans and animals. These pathogens have a broad host range and worldwide distribution, but are mostly known for their ability to cause diarrhea. However, very limited information on prevalence and genotypes of G. duodenalis, E. bieneusi and Cryptosporidium spp. in pet dogs and cats are available in China. In the present study, a total of 433 fecal samples were collected from 262 pet dogs and 171 pet cats in Yunnan province, southwestern China, and the prevalence and the genotypes of G. duodenalis, E. bieneusi and Cryptosporidium spp. were investigated by nested PCR amplification and DNA sequencing. The prevalence of G. duodenalis, E. bieneusi and Cryptosporidium spp. was 13.7% (36/262), 8.0% (21/262), and 4.6% (12/262) in dogs, and 1.2% (2/171), 2.3% (4/171) and 0.6% (1/171) in cats, respectively. The different living conditions of dogs is a risk factor that is related with the prevalence of G. duodenalis and E. bieneusi (p < 0.05). However, there were no statistically significant difference in prevalence of three pathogens in cats. DNA sequencing and analyses showed that four E. bieneusi genotypes (PtEb IX, CD9, DgEb I and DgEb II), one Cryptosporidium spp. (C. canis) and two G. duodenalis assemblages (C and D) were identified in dogs; two E. bieneusi genotypes (Type IV and CtEb I), one Cryptosporidium spp. (C. felis) and one G. duodenalis assemblage (F) were identified in cats. Three novel E. bieneusi genotypes (DgEb I, DgEb II and CtEb I) were identified, and the human-pathogenic genotypes/species Type IV C. canis and C. felis were also observed in this study, indicating a potential zoonotic threat of pet dogs and cats. Our results revealed the prevalence and genetic diversity of G. duodenalis, E. bieneusi and Cryptosporidium spp. infection in pet dogs and cats in Yunnan province, southwestern China, and suggested the potential threat of pet dogs and cats to public health.
Clinico-Genomic Analysis Reveals Mutations Associated with COVID-19 Disease Severity: Possible Modulation by RNA Structure
Authors: Mehta Priyanka , Alle Shanmukh , Chaturvedi Anusha , Swaminathan Aparna , Saifi Sheeba , Maurya Ranjeet , Chattopadhyay Partha , Devi Priti , Chauhan Ruchi , Kanakan Akshay , Vasudevan Janani Srinivasa , Sethuraman Ramanathan , Chidambaram Subramanian , Srivastava Mashrin , Chakravarthi Avinash , Jacob Johnny , Namagiri Madhuri , Konala Varma , Jha Sujeet , Priyakumar U. Deva , Vinod P. K. , Pandey Rajesh
Published: August 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests a broad spectrum of clinical presentations, varying in severity from asymptomatic to mortality. As the viral infection spread, it evolved and developed into many variants of concern. Understanding the impact of mutations in the SARS-CoV-2 genome on the clinical phenotype and associated co-morbidities is important for treatment and preventionas the pandemic progresses. Based on the mild, moderate, and severe clinical phenotypes, we analyzed the possible association between both, the clinical sub-phenotypes and genomic mutations with respect to the severity and outcome of the patients. We found a significant association between the requirement of respiratory support and co-morbidities. We also identified six SARS-CoV-2 genome mutations that were significantly correlated with severity and mortality in our cohort. We examined structural alterations at the RNA and protein levels as a result of three of these mutations: A26194T, T28854T, and C25611A, present in the Orf3a and N protein. The RNA secondary structure change due to the above mutations can be one of the modulators of the disease outcome. Our findings highlight the importance of integrative analysis in which clinical and genetic components of the disease are co-analyzed. In combination with genomic surveillance, the clinical outcome-associated mutations could help identify individuals for priority medical support.
Antibiogram Profile of Acinetobacterbaumannii Recovered from Selected Freshwater Resources in the Eastern Cape Province, South Africa
Authors: Adewoyin Mary Ayobami , Ebomah Kingsley Ehi , Okoh Anthony Ifeanyi
Published: August 2021

Acinetobacter species have been found in a variety of environments, including soil, food, plants, hospital environments and water. Acinetobacter baumannii is an opportunistic and emerging waterborne pathogen. It has been implicated in several nosocomial infections that demonstrate resistance to commonly administered antibiotics. We investigated phenotypic antibiotic resistance (PAR) and relevant antibiotic resistance genes (ARGs) in A. baumannii isolated from three freshwater resources in the Eastern Cape Province, South Africa; A. baumannii (410) was confirmed by the recA and gyrB genes of 844 suspected Acinetobacter species in the water samples. The PAR of the confirmed isolates was assessed using a panel of 11 antibiotics by the disc diffusion method, while ARGs were investigated in isolates exhibiting PAR. The A. baumannii isolates were resistant to piperacillin-tazobactam (11.2%), ceftazidime (12%), cefotaxime (18.8%), cefepime (8.8%), imipenem (2.7%), meropenem (4.15%), amikacin (2.4%), gentamicin (8.8%), tetracycline (16.8%), ciprofloxacin (11%) and trimethoprim/sulfamethoxazole (20.5%). For multidrug resistance (MDR), two isolates were resistant to all antibiotics and 28 isolates were resistant to imipenem and meropenem. Moreover, β-lactamases blaTEM (64.4%) and blaOXA-51 (28.70%) as well as sulphonamides sul1 (37.1%) and sul2 (49.4%) were common ARGs. Overall, PAR and ARGs had positive correlations (r) in all rivers. Detection of MDR-A. baumannii in freshwater resources could be linked to possible wastewater discharge from the nearby animal farms, indicating potential implications for public health.
Biodegradable Zinc Oxide Nanoparticles Doped with Iron as Carriers of Exogenous Iron in the Living Organism
Authors: Kiełbik Paula , Jończy Aneta , Kaszewski Jarosław , Gralak Mikołaj , Rosowska Julita , Sapierzyński Rafał , Witkowski Bartłomiej , Wachnicki Łukasz , Lawniczak-Jablonska Krystyna , Kuzmiuk Piotr , Lipiński Paweł , Godlewski Marek , Godlewski Michał Marek
Published: August 2021

Iron plays an important role in various crucial processes in the body and its deficiency is considered currently as a serious health problem. Thus, iron supplementation strategies for both humans and animals need to be effective and safe. According to our previous studies, zinc-based nanoparticles provide safe, biodegradable, fast and efficient transport system of orally given substances to the tissues. In the current manuscript we present results of a study aimed at investigation of the ZnO nanoparticle-based Fe supplementation system (average size 100 × 250 nm). Nanostructures were orally (gavage) administered to adult mice. Animals were sacrificed at different time points with collection of blood and internal organs for analyses (tissue iron concentration, hepatic level of hepcidin, blood parameters, liver and spleen levels of ferritin, histopathology). Initial experiment was performed to compare the biological effect of doping type (Fe3+ doping vs. a mixture of Fe3+ and Fe2+). Then, the effect of acute/chronic exposure models was determined. The increase in ferritin, along with improved, crucial hematological parameters and lack of the influence on hepcidin expression indicated the chronic application of Fe3+,2+ doped ZnO nanostructures to be the most effective among tested.
Privileged Quinolylnitrones for the Combined Therapy of Ischemic Stroke and Alzheimer’s Disease
Authors: Alonso José M. , Escobar-Peso Alejandro , Palomino-Antolín Alejandra , Diez-Iriepa Daniel , Chioua Mourad , Martínez-Alonso Emma , Iriepa Isabel , Egea Javier , Alcázar Alberto , Marco-Contelles José
Published: August 2021

Cerebrovascular diseases such as ischemic stroke are known to exacerbate dementia caused by neurodegenerative pathologies such as Alzheimer’s disease (AD). Besides, the increasing number of patients surviving stroke makes it necessary to treat the co-occurrence of these two diseases with a single and combined therapy. For the development of new dual therapeutic agents, eight hybrid quinolylnitrones have been designed and synthesized by the juxtaposition of selected pharmacophores from our most advanced lead-compounds for ischemic stroke and AD treatment. Biological analyses looking for efficient neuroprotective effects in suitable phenotypic assays led us to identify MC903 as a new small quinolylnitrone for the potential dual therapy of stroke and AD, showing strong neuroprotection on (i) primary cortical neurons under oxygen–glucose deprivation/normoglycemic reoxygenation as an experimental ischemia model; (ii), neuronal line cells treated with rotenone/oligomycin A, okadaic acid or β-amyloid peptide Aβ25–35, modeling toxic insults found among the effects of AD.
Synthesis and Biological Evaluation of 1,2,3-Triazole Tethered Thymol-1,3,4-Oxadiazole Derivatives as Anticancer and Antimicrobial Agents
Authors: Almalki Abdulraheem S. A. , Nazreen Syed , Malebari Azizah M. , Ali Nada M. , Elhenawy Ahmed A. , Alghamdi Abdullah A. A. , Ahmad Abrar , Alfaifi Sulaiman Y. M. , Alsharif Meshari A. , Alam Mohammad Mahboob
Published: August 2021

A library of 1,2,3-triazole-incorporated thymol-1,3,4-oxadiazole derivatives (6–18) hasbeen synthesized and tested for anticancer and antimicrobial activities. Compounds 7, 8, 9, 10, and 11 exhibited significant antiproliferative activity. Among these active derivatives, compound 2-(4-((5-((2-isopropyl-5-methylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol (9) was the best compound against all three tested cell lines, MCF-7 (IC50 1.1 μM), HCT-116 (IC50 2.6 μM), and HepG2 (IC50 1.4 μM). Compound 9 was found to be better than the standard drugs, doxorubicin and 5-fluorouracil. These compounds showed anticancer activity through thymidylate synthase inhibition as they displayed significant TS inhibitory activity with IC50 in the range 1.95–4.24 μM, whereas the standard drug, Pemetrexed, showed IC50 7.26 μM. The antimicrobial results showed that some of the compounds (6, 7, 9, 16, and 17) exhibited good inhibition on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The molecular docking and simulation studies supported the anticancer and antimicrobial data. It can be concluded that the synthesized 1,2,3-triazole tethered thymol-1,3,4-oxadiazole conjugates have both antiproliferative and antimicrobial potential.
Exacerbation of Liver Tumor Metastasis in twist1a+/xmrk+ Double Transgenic Zebrafish following Lipopolysaccharide or Dextran Sulphate Sodium Exposure
Authors: Lu Jeng-Wei , Sun Yuxi , Lin Liang-In , Liu Dong , Gong Zhiyuan
Published: August 2021

The poor prognosis for patients with hepatocellular carcinoma (HCC) is related directly to metastasis. The Twist1 gene encodes for a transcription factor essential to embryogenesis. It has also been shown to promote epithelial-to-mesenchymal transition (EMT), invasion, and metastasis; however, there is currently no in vivo evidence that Twist1 plays a role in the metastasis of liver tumors. Zebrafish are increasingly being used as an alternative cancer model. In the current study, an adult-stage zebrafish HCC model was used to examine the synergistic effects of twist1a and xmrk, a well characterized oncogene, during HCC metastasis. We also examined the effects of two inflammatory agents, lipopolysaccharides (LPS) and dextran sulfate sodium (DSS), on the hepatocyte-specific expression of transgenic twist1a and xmrk. The conditional overexpression of twist1a and xmrk was shown to promote liver tumor metastasis in zebrafish, resulting in increased apoptosis and cell proliferation as well as tumor maintenance and propagation independent of the inherent EMT-inducing activity of xmrk. Exposing twist1a+/xmrk+ transgenic zebrafish to LPS or DSS was shown to promote metastasis, indicating that the overexpression of twist1a and xmrk led to crosstalk between the signaling pathways involved in EMT. This study provides important evidence pertaining to the largely overlooked effects of signaling crosstalk between twist1a and xmrk in regulating HCC metastasis. Our results also suggest that the co-expression of twist1a/xmrk in conjunction with exposure to LPS or DSS enhances HCC metastasis, and provides a valuable in vivo platform by which to investigate tumor initiation and metastasis in the study of liver cancer.
New Incretin Combination Treatments under Investigation in Obesity and Metabolism: A Systematic Review
Authors: Kakouri Agni , Kanti Georgia , Kapantais Efthymios , Kokkinos Alexandros , Lanaras Leonidas , Farajian Paul , Galanakis Christos , Georgantopoulos Georgios , Vlahos Nikos F. , Mastorakos George , Bargiota Alexandra , Valsamakis Georgios
Published: August 2021

The worldwide upward trend in obesity in adults and the increased incidence of overweight children suggests that the future risk of obesity-related illnesses will be increased. The existing anti-obesity drugs act either in the central nervous system (CNS) or in the peripheral tissues, controlling the appetite and metabolism. However, weight regain is a common homeostatic response; current anti-obesity medications show limited effectiveness in achieving long-term weight loss maintenance; in addition to being linked to various side effects. Combined anti-obesity medications (per os or injectable) target more than one of the molecular pathways involved in weight regulation, as well as structures in the CNS. In this systematic review, we conducted a search of PubMed and The ClinicalTrials.gov up to February 2021. We summarized the Food and Drug Administration (FDA)-approved medications, and we focused on the combined pharmacological treatments, related to the incretin hormones, currently in a clinical trial phase. We also assessed the mechanism of action and therapeutic utility of these novel hybrid peptides and potential interactions with other regulatory hormones that may have beneficial effects on obesity. As we improve our understanding of the pathophysiology of obesity, we hope to identify more novel treatment strategies.
Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies
Authors: Alam Mohammad Mahboob , Nazreen Syed , Almalki Abdulraheem S. A. , Elhenawy Ahmed A. , Alsenani Nawaf I. , Elbehairi Serag Eldin I. , Malebari Azizah M. , Alfaifi Mohammad Y. , Alsharif Meshari A. , Alfaifi Sulaiman Y. M.
Published: August 2021

A library of novel naproxen based 1,3,4-oxadiazole derivatives (8–16 and 19–26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15) was the most potent compound against MCF-7 and HepG2cancer cells with IC50 of 2.13 and 1.63 µg/mL, respectively, and was equipotent to doxorubicin (IC50 1.62 µg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC50 0.41 μM compared to standard drug Erlotinib (IC50 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.
PRODH/POX-Dependent Celecoxib-Induced Apoptosis in MCF-7 Breast Cancer
Authors: Misiura Magdalena , Ościłowska Ilona , Bielawska Katarzyna , Pałka Jerzy , Miltyk Wojciech
Published: August 2021

Celecoxib (Cx), an inhibitor of cyclooxygenase 2, induces apoptosis of cancer cells. However, the mechanism of the chemopreventive effect remains not fully understood. We aimed to investigate the role of PRODH/POX that is involved in the regulation of apoptosis induced by celecoxib. MCF-7 breast cancer cell line and the corresponding MCF-7 cell line with silenced PRODH/POX (MCF-7shPRODH/POX) were used. The effects of Cx on cell viability, proliferation, and cell cycle were evaluated. The expressions of protein markers for apoptosis (Bax, caspase 9, and PARP) and autophagy (Atg5, Beclin 1, and LC3A/B) were investigated by Western immunoblotting. To analyze the proline metabolism, collagen biosynthesis, prolidase activity, proline concentration, and the expression of proline-related proteins were evaluated. The generation of ATP, ROS, and the ratio of NAD+/NADH and NADP+/NADPH were determined to test the effect of Cx on energetic metabolism in breast cancer cells. It has been found that Cx attenuated MCF-7 cell proliferation via arresting the cell cycle. Cx induced apoptosis in MCF-7 breast cancer cells, while in MCF-7shPRODH/POX, autophagy occurred more predominantly. In MCF-7 breast cancer cells, Cx affected proline metabolism through upregulation of proline biosynthesis, PRODH/POX and PYCRs expressions, PEPD activity, and downregulation of collagen biosynthesis. In MCF-7shPRODH/POX clones, these processes, as well as energetic metabolism, were remarkably suppressed. The data for the first time suggest that celecoxib induces apoptosis through upregulation of PRODH/POX in MCF-7 breast cancer cells.
Fusion-Based Neutron Generator Production of Tc-99m and Tc-101: A Prospective Avenue to Technetium Theranostics
Authors: Mausolf Edward J. , Johnstone Erik V. , Mayordomo Natalia , Williams David L. , Guan Eugene Yao Z. , Gary Charles K.
Published: August 2021

Presented are the results of 99mTc and 101Tc production via neutron irradiation of natural isotopic molybdenum (Mo) with epithermal/resonance neutrons. Neutrons were produced using a deuterium-deuterium (D-D) neutron generator with an output of 2 × 1010 n/s. The separation of Tc from an irradiated source of bulk, low-specific activity (LSA) Mo on activated carbon (AC) was demonstrated. The yields of 99mTc and 101Tc, together with their potential use in medical single-photon emission computed tomography (SPECT) procedures, have been evaluated from the perspective of commercial production, with a patient dose consisting of 740 MBq (20 mCi) of 99mTc. The number of neutron generators to meet the annual 40,000,000 world-wide procedures is estimated for each imaging modality: 99mTc versus 101Tc, D-D versus deuterium-tritium (D-T) neutron generator system outputs, and whether or not natural molybdenum or enriched targets are used for production. The financial implications for neutron generator production of these isotopes is also presented. The use of 101Tc as a diagnostic, therapeutic, and/or theranostic isotope for use in medical applications is proposed and compared to known commercial nuclear diagnostic and therapeutic isotopes.