Search results for: immune modulation

Authors: Shilpa Mukundaraj, Nagaraju Shivaiah

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Amyloidogenic conditions, driven by protein aggregation into insoluble fibrils, which pose significant challenges in the clinical condition of diabetes management, particularly through the amyloidogenic LVEALYL sequence in insulin B-chain. This study explores a dual therapeutic strategy involving cysteine protease enzymes such as papain and ficin and inhibitory peptides to target insulin amyloidosis. Combining in silico, in vitro, and in vivo methodologies, the research aims to inhibit amyloid formation and degrade preformed fibrils. Inhibitory peptides were designed using structure-guided approaches in Rosetta to specifically target the LVEALYL sequence. Concurrently, cysteine protease enzymes, including papain and ficin, were evaluated for their fibril disassembly potential. In vitro experiments, utilizing SDS- PAGE and spectroscopic techniques, confirmed dose-dependent degradation 50 to 300ug in vitro and 60mg/kg in vivo of amyloid aggregates by these enzymes, with significant disaggregation observed at higher concentrations 20mg. Peptide inhibitors effectively reduced fibril formation, as evidenced by reduced Thioflavin T fluorescence and circular dichroism spectroscopy. Complementary in silico analyses, including molecular docking and dynamic simulations, provided structural insights into enzyme binding interactions with amyloidogenic regions. Key residues involved in substrate recognition and cleavage were identified, with computational findings aligning strongly with experimental data. These insights confirmed the specificity of papain and ficin in targeting insulin fibrils. For translational potential, an in vivo rat model was developed, involving subcutaneous insulin amyloid injections to induce localized amyloid deposits. Over six days of enzyme treatment, a marked reduction in amyloid burden was observed through histological findings and biochemical assay superoxide dismutase can provide insights into oxidative damage due to amyloid deposition. Furthermore, inflammatory markers IL-6, TNFα were significantly attenuated in treated groups, emphasizing the dual role of enzymes in amyloid clearance and inflammation modulation. This integrative study highlights the promise of cysteine protease enzymes and inhibitory peptides as complementary therapeutic strategies for managing insulin amyloidosis. By targeting both the formation and persistence of amyloid fibrils, this dual approach offers a novel and effective avenue for amyloidosis treatment.

Keywords: insulin amyloidosis, peptide inhibitors, cysteine protease enzymes, amyloid degradation

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Authors: Carolina N. França, Jônatas B. do Amaral, Maria C.O. Izar, Ighor L. Teixeira, Francisco A. Fonseca

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Introduction: Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large-caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes, and smoking are associated with endothelial dysfunction. There is a frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5, and CX3CR1, to promote the migration of monocytes to the inflammatory site. The aim of this study was to evaluate the effect of lipid-lowering treatment by six months in the monocyte phenotype and chemokine receptor levels of patients after Acute Myocardial Infarction (AMI). Methods: This is a PROBE (prospective, randomized, open-label trial with blinded endpoints) study (ClinicalTrials.gov Identifier: NCT02428374). Adult patients (n=147) of both genders, ageing 18-75 years, were randomized in a 2x2 factorial design for treatment with rosuvastatin 20 mg/day or simvastatin 40 mg/day plus ezetimibe 10 mg/day as well as ticagrelor 90 mg 2x/day and clopidogrel 75 mg, in addition to conventional AMI therapy. Blood samples were collected at baseline, after one month and six months of treatment. Monocyte subtypes (classical - inflammatory, intermediate - phagocytic and nonclassical – anti-inflammatory) were identified, quantified and characterized by flow cytometry, as well as the expressions of the chemokine receptors (CCR2, CCR5 and CX3CR1) were also evaluated in the mononuclear cells. Results: After six months of treatment, there was an increase in the percentage of classical monocytes and reduction in the nonclassical monocytes (p=0.038 and p < 0.0001 Friedman Test), without differences for intermediate monocytes. Besides, classical monocytes had higher expressions of CCR5 and CX3CR1 after treatment, without differences related to CCR2 (p < 0.0001 for CCR5 and CX3CR1; p=0.175 for CCR2). Intermediate monocytes had higher expressions of CCR5 and CX3CR1 and lower expression of CCR2 (p = 0.003; p < 0.0001 and p = 0.011, respectively). Nonclassical monocytes had lower expressions of CCR2 and CCR5, without differences for CX3CR1 (p < 0.0001; p = 0.009 and p = 0.138, respectively). There were no differences after the comparison between the four treatment arms. Conclusion: The data suggest a time-dependent modulation of classical and nonclassical monocytes and chemokine receptor levels. The higher percentage of classical monocytes (inflammatory cells) suggest a residual inflammatory risk, even under preconized treatments to AMI. Indeed, these changes do not seem to be affected by choice of the lipid-lowering strategy.

Keywords: acute myocardial infarction, chemokine receptors, lipid-lowering treatment, monocyte subtypes

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Authors: Danna Jia, Bin Li

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Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

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Authors: Oluwafunmibi Omotayo Fasanya, Augustine Kena Adjei

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Background and Aims: This meta-analysis aimed to evaluate the effect of vitamin D supplementation on key metabolic and cardiovascular parameters, such as glycated hemoglobin (HbA1C), fasting blood sugar (FBS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), systolic blood pressure (SBP), and total vitamin D levels in patients with Type 2 diabetes mellitus (T2DM). Methods: A systematic search was performed across databases, including PubMed, Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, from January 1990 to January 2024. A total of 4,177 relevant studies were initially identified. Using an unsupervised K-means clustering algorithm, publications were grouped based on common text features. Maximum entropy classification was then applied to filter studies that matched a pre-identified training set of 139 potentially relevant articles. These selected studies were manually screened for relevance. A parallel manual selection of all initially searched studies was conducted for validation. The final inclusion of studies was based on full-text evaluation, quality assessment, and meta-regression models using random effects. Sensitivity analysis and publication bias assessments were also performed to ensure robustness. Results: The unsupervised K-means clustering algorithm grouped the patients based on their responses to vitamin D supplementation, using key biomarkers such as HbA1C, FBS, LDL, HDL, SBP, and total vitamin D levels. Two primary clusters emerged: one representing patients who experienced significant improvements in these markers and another showing minimal or no change. Patients in the cluster associated with significant improvement exhibited lower HbA1C, FBS, and LDL levels after vitamin D supplementation, while HDL and total vitamin D levels increased. The analysis showed that vitamin D supplementation was particularly effective in reducing HbA1C, FBS, and LDL within this cluster. Furthermore, BMI, weight gain, and disease duration were identified as factors that influenced cluster assignment, with patients having lower BMI and shorter disease duration being more likely to belong to the improvement cluster. Conclusion: The findings of this machine learning-assisted meta-analysis confirm that vitamin D supplementation can significantly improve glycemic control and reduce the risk of cardiovascular complications in T2DM patients. The use of automated screening techniques streamlined the process, ensuring the comprehensive evaluation of a large body of evidence while maintaining the validity of traditional manual review processes.

Keywords: HbA1C, T2DM, SBP, FBS

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Authors: Ewuola E. O., Sokunbi O. A., Oyedemi O. M., Sanni K. M

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Moringa oleifera leaf has been traditionally used in the local medicine as an ingredient in some herbal formulations for blood purifier, cholesterol reducing agent, immune and reproductive enhancers. Twenty-four pubertal rabbit are divided equally into four groups were administered with varied concentrations of crude extract of the leaves of Moringa oleifera gavage at doses of 2.5ml/kg body weight (BW) in every 48 hours for 63 days. These rabbits were allotted into four treatments and each treatment was replicated six times to investigate the effect of administered crude Moringa oleifera leaf extract (CMOLE) on haematology and reproductive performance of pubertal rabbit does. Four experimental treatments were used. The animals on the control (T1) were administered water only. Rabbits on treatments 2, 3, and 4 were administered 100ml CMOLE/L, 200ml CMOLE/L, and 300ml CMOLE/L, respectively. The does were placed on extract two weeks before mating, five weeks after mating and continued for another two weeks after kindling. Six proven untreated bucks were used for the mating of the twenty-four treated does and these bucks were randomly allotted to the does such that each buck mated at least one treated does in each treatment. The same management practices and experimental diets were given ad libitum to all animals. Blood was sampled from the gestating does at the third trimester for haematological analysis. The haematology results showed that treated rabbits with 100ml CMOLE/L with mean corpuscular volume value of 93.38fl significantly (p < 0.05) higher than those on the control which is water only (82.24fl) but not significantly different from T3 (200ml CMOLE/L) and T4 (300ml CMOLE/L) which had mean values of 91.69fl and 91.49fl, respectively. While the erythrocyte counts, leukocyte counts, haematocrit, haemoglobin concentration, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, lymphocyte, neutrophil, monocyte, and eosinophil count were not significantly different across the treatments. For platelets, treated animals on T2 (100ml CMOLE/L) had the highest numerical value of 148.80 x 109/L which was identical with those on T3 (200ml CMOLE/L) with mean value of 141.50x109/L but significantly (p < 0.05) higher than those on T4 (300ml CMOLE/L) with mean value of 135.00 x 109/L and those on the control which had the least mean value of 126.60 x 109/L. The percentage conception rate of the treated animals was higher than those in the control group. The animals administered 300ml CMOLE/L had the apparently highest litter size of 5.75, while gestation length and litter weight tended to decline with increase in CMOLE concentrations The investigation demonstrated the potential effect of crude Moringa oleifera leaf extract on pubertal rabbit does. The administration of up to 300ml crude Moringa oleifera leaf extract per liter did not adversely affect but improved the haematological response and reproductive potential in gestating rabbit does.

Keywords: conception, haematology, moringa leaf extract, rabbit does

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Authors: G. C. Santini, C. Potrich, L. Lunelli, L. Vanzetti, S. Marasso, M. Cocuzza, C. Pederzolli

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The relevance of circulating miRNAs as non-invasive biomarkers for several pathologies is nowadays undoubtedly clear, as they have been found to have both diagnostic and prognostic value able to add fundamental information to patients’ clinical picture. The availability of these data, however, relies on a time-consuming process spanning from the sample collection and processing to the data analysis. In light of this, strategies which are able to ease this procedure are in high demand and considerable effort have been made in developing Lab-on-a-chip (LOC) devices able to speed up and standardise the bench work. In this context, a very promising polydimethylsiloxane (PDMS)-based microdevice which integrates the processing of the biological sample, i.e. purification of extracellular miRNAs, and reverse transcription was previously developed in our lab. In this study, we aimed at the improvement of the miRNA extraction performances of this micro device by increasing the ability of its surface to absorb extracellular miRNAs from biological samples. For this purpose, we focused on the modulation of two properties of the material: roughness and charge. PDMS surface roughness was modulated by casting with several templates (terminated with silicon oxide coated by a thin anti-adhesion aluminum layer), followed by a panel of curing conditions. Atomic force microscopy (AFM) was employed to estimate changes at the nanometric scale. To introduce modifications in surface charge we functionalized PDMS with different mixes of positively charged 3-aminopropyltrimethoxysilanes (APTMS) and neutral poly(ethylene glycol) silane (PEG). The surface chemical composition was characterized by X-ray photoelectron spectroscopy (XPS) and the number of exposed primary amines was quantified with the reagent sulfosuccinimidyl-4-o-(4,4-dimethoxytrityl) butyrate (s-SDTB). As our final end point, the adsorption rate of all these different conditions was assessed by fluorescence microscopy by incubating a synthetic fluorescently-labeled miRNA. Our preliminary analysis identified casting on thermally grown silicon oxide, followed by a curing step at 85°C for 1 hour, as the most efficient technique to obtain a PDMS surface roughness in the nanometric scaleable to trap miRNA. In addition, functionalisation with 0.1% APTMS and 0.9% PEG was found to be a necessary step to significantly increase the amount of microRNA adsorbed on the surface, therefore, available for further steps as on-chip reverse transcription. These findings show a substantial improvement in the extraction efficiency of our PDMS microdevice, ultimately leading to an important step forward in the development of an innovative, easy-to-use and integrated system for the direct purification of less abundant circulating microRNAs.

Keywords: circulating miRNAs, diagnostics, Lab-on-a-chip, polydimethylsiloxane (PDMS)

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Authors: Xiao-Mei Zhang, Sian-Hong Tseng, Ming-Yen Lu

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Two-dimensional (2D) transition metal dichalcogenides (TMDCs), such as MoS₂, have attracted considerable attention owing to the unique optical and electronic properties related to its 2D ultrathin atomic layer structure. MoS₂ is becoming prevalent in post-silicon digital electronics and in highly efficient optoelectronics due to its extremely low thickness and its tunable band gap (Eg = 1-2 eV). For low-power, high-performance complementary logic applications, both p- and n-type MoS₂ FETs (NFETs and PFETs) must be developed. NFETs with an electron accumulation channel can be obtained using unintentionally doped n-type MoS₂. However, the fabrication of MoS₂ FETs with complementary p-type characteristics is challenging due to the significant difficulty of injecting holes into its inversion channel. Plasma treatments with different species (including CF₄, SF₆, O₂, and CHF₃) have also been found to achieve the desired property modifications of MoS₂. In this work, we demonstrated a p-type multilayer MoS₂ enabled by selective-area doping using CHF₃ plasma treatment. Compared with single layer MoS₂, multilayer MoS₂ can carry a higher drive current due to its lower bandgap and multiple conduction channels. Moreover, it has three times the density of states at its minimum conduction band. Large-area growth of MoS₂ films on 300 nm thick SiO₂/Si substrate is carried out by thermal decomposition of ammonium tetrathiomolybdate, (NH₄)₂MoS₄, in a tube furnace. A two-step annealing process is conducted to synthesize MoS₂ films. For the first step, the temperature is set to 280 °C for 30 min in an N₂ rich environment at 1.8 Torr. This is done to transform (NH₄)₂MoS₄ into MoS₃. To further reduce MoS₃ into MoS₂, the second step of annealing is performed. For the second step, the temperature is set to 750 °C for 30 min in a reducing atmosphere consisting of 90% Ar and 10% H₂ at 1.8 Torr. The grown MoS₂ films are subjected to out-of-plane doping by CHF₃ plasma treatment using a Dry-etching system (ULVAC original NLD-570). The radiofrequency power of this dry-etching system is set to 100 W and the pressure is set to 7.5 mTorr. The final thickness of the treated samples is obtained by etching for 30 s. Back-gated MoS₂ PFETs were presented with an on/off current ratio in the order of 10³ and a field-effect mobility of 65.2 cm²V⁻¹s⁻¹. The MoS₂ PFETs photodetector exhibited ultraviolet (UV) photodetection capability with a rapid response time of 37 ms and exhibited modulation of the generated photocurrent by back-gate voltage. This work suggests the potential application of the mild plasma-doped p-type multilayer MoS₂ in UV photodetectors for environmental monitoring, human health monitoring, and biological analysis.

Keywords: photodetection, p-type doping, multilayers, MoS₂

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Authors: Henry O. Chibudike, Olubamike A. Adeyoju, Bolanle O. Oluwole, Kayode O. Adebowale, Bamidele I. Olu-Owolabi, Chinedum E. Chibudike

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Studies on the Mineral Content of Solojo Flour and Protein Isolates from the two varieties (DAS and BS) of Nigeria cultivated solojo cowpeas were conducted to determine their nutritional value. These inorganic elements or minerals were classified into 3 categories: the ultra-trace minerals, which are the third category; the microelements, also known as the trace minerals, in the second category; while the first category is the macro elements, also known as major minerals. Some of the macro-elements are Ca, P, Na and Cl; the second category, micro-elements include iron, copper, cobalt, potassium, magnesium, iodine, zinc, manganese, molybdenum, F, Cr, Se and S. Results show that the proportion of Sodium (Na) which is ingested into the body in the form of NaCl through food intake maintenance of body pH and to retain water ranged from 728.97 to 253.37 ppm (72.90 to 25.34 mg/100 g); 715.24 to 235.45 ppm; 735.28 to 270.37 ppm; 726.59 to 264.35ppm, for FFDAS, FFBS, DAS and BS respectively with all values of the germinated samples all bellow the control. While FFDAS iron content ranged from 4.25 to 13.50 mg/100 g; FFBS ranged from 3.15 to 12.56 mg/100 g; DAS ranged from 3.81 to 12.90 mg/100g; BS ranged from 3.42 to 9.40 mg/100 g. The values of the germinated flours were all greater than the ungerminated flour. Iron helps to transport oxygen round the body and also helps in red blood cells building and to convert food into needed energy by the body. While Manganese an element that is needed in micro quantity but necessary to convert food into energy, is also crucial for healthy bone and cartilage creation. Results also show that zinc quantity increased as germination proceeded, and the values ranged from 38.80 ppm to 230.00 ppm (3.880 mg/100 g to 23.00 mg/100 g; 0.003880% to 0.0230%); 40.84 to 250.01 ppm; 32.85 to 93.41 ppm; 37.07 to 115.00 ppm, for FFDAS, FFBS, DAS and BS respectively. The Ca content improved significantly (p<0.05) with sprouting; the value extended from 250.56 ppm to 760.03 ppm (25.056 to 76.00 mg/100g or 0.0251 to 0.0760 %); 400.40 to 998.22 ppm; 116.87 to 195.69 ppm; 113.48 to 220.75 ppm, for FFDAS, FFBS, DAS and BS respectively. Zinc element although needed at the micro level in the body, is essential for a strong immune system to keep the body in good health. It is also crucial for the maintenance of a healthy sense of taste and odor, while Calcium is critical for strong bones and teeth, blood coagulation, and muscle tightening and relaxation. Magnesium is needed to build enzymes and antioxidants and also for healthy bones, while Potassium is needed to maintain water balance, muscle movement, and nerve impulses. It functions in conjunction with Na to regulate blood pressure.

Keywords: Solojo cowpea, underutilized legumes, protein isolates, BS, DAS, ungerminated

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is a clinical state associated with low-grade inflammation. It is also a major risk factor for insulin resistance (IR). In its advanced stages, metabolic syndrome (MetS), a much more complicated disease which may lead to life-threatening problems, may develop. Obesity-mediated IR seems to correlate with the inflammation. Human studies performed particularly on pediatric population are scarce. The aim of this study is to detect possible associations between inflammation and IR in terms of some related ratios. 549 children were grouped according to their age- and sex-based body mass index (BMI) percentile tables of WHO. MetS components were determined. Informed consent and approval from the Ethics Committee for Clinical Investigations were obtained. The principles of the Declaration of Helsinki were followed. The exclusion criteria were infection, inflammation, chronic diseases and those under drug treatment. Anthropometric measurements were obtained. Complete blood cell, fasting blood glucose, insulin, and C-reactive protein (CRP) analyses were performed. Homeostasis model assessment of insulin resistance (HOMA-IR), systemic immune inflammation (SII) index, tense index, alanine aminotransferase to aspartate aminotransferase ratio (ALT/AST), neutrophils to lymphocyte (NLR), platelet to lymphocyte, and lymphocyte to monocyte ratios were calculated. Data were evaluated by statistical analyses. The degree for statistical significance was 0.05. Statistically significant differences were found among the BMI values of the groups (p < 0.001). Strong correlations were detected between the BMI and waist circumference (WC) values in all groups. Tense index values were also correlated with both BMI and WC values in all groups except overweight (OW) children. SII index values of children with normal BMI were significantly different from the values obtained in OW, obese, morbid obese and MetS groups. Among all the other lymphocyte ratios, NLR exhibited a similar profile. Both HOMA-IR and ALT/AST values displayed an increasing profile from N towards MetS3 group. BMI and WC values were correlated with HOMA-IR and ALT/AST. Both in morbid obese and MetS groups, significant correlations between CRP versus SII index as well as HOMA-IR versus ALT/AST were found. ALT/AST and HOMA-IR values were correlated with NLR in morbid obese group and with SII index in MetS group, (p < 0.05), respectively. In conclusion, these findings showed that some parameters may exhibit informative differences between the early and late stages of obesity. Important associations among HOMA-IR, ALT/AST, NLR and SII index have come to light in the morbid obese and MetS groups. This study introduced the SII index and NLR as important inflammatory markers for the discrimination of normal and obese children. Interesting links were observed between inflammation and IR in morbid obese children and those with MetS, both being late stages of obesity.

Keywords: children, inflammation, insulin resistance, metabolic syndrome, obesity

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Authors: Vibha Devi, Shabina Khanam

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Hemp (Cannabis sativa) possesses a rich content of ω-6 linoleic and ω-3 linolenic essential fatty acid in the ratio of 3:1, which is a rare and most desired ratio that enhances the quality of hemp oil. These components are beneficial for the development of cell and body growth, strengthen the immune system, possess anti-inflammatory action, lowering the risk of heart problem owing to its anti-clotting property and a remedy for arthritis and various disorders. The present study employs supercritical fluid extraction (SFE) approach on hemp seed at various conditions of parameters; temperature (40 - 80) °C, pressure (200 - 350) bar, flow rate (5 - 15) g/min, particle size (0.430 - 1.015) mm and amount of co-solvent (0 - 10) % of solvent flow rate through central composite design (CCD). CCD suggested 32 sets of experiments, which was carried out. As SFE process includes large number of variables, the present study recommends the application of resampling techniques for cross-validation of the obtained data. Cross-validation refits the model on each data to achieve the information regarding the error, variability, deviation etc. Bootstrap and jackknife are the most popular resampling techniques, which create a large number of data through resampling from the original dataset and analyze these data to check the validity of the obtained data. Jackknife resampling is based on the eliminating one observation from the original sample of size N without replacement. For jackknife resampling, the sample size is 31 (eliminating one observation), which is repeated by 32 times. Bootstrap is the frequently used statistical approach for estimating the sampling distribution of an estimator by resampling with replacement from the original sample. For bootstrap resampling, the sample size is 32, which was repeated by 100 times. Estimands for these resampling techniques are considered as mean, standard deviation, variation coefficient and standard error of the mean. For ω-6 linoleic acid concentration, mean value was approx. 58.5 for both resampling methods, which is the average (central value) of the sample mean of all data points. Similarly, for ω-3 linoleic acid concentration, mean was observed as 22.5 through both resampling. Variance exhibits the spread out of the data from its mean. Greater value of variance exhibits the large range of output data, which is 18 for ω-6 linoleic acid (ranging from 48.85 to 63.66 %) and 6 for ω-3 linoleic acid (ranging from 16.71 to 26.2 %). Further, low value of standard deviation (approx. 1 %), low standard error of the mean (< 0.8) and low variance coefficient (< 0.2) reflect the accuracy of the sample for prediction. All the estimator value of variance coefficients, standard deviation and standard error of the mean are found within the 95 % of confidence interval.

Keywords: resampling, supercritical fluid extraction, hemp oil, cross-validation

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Authors: K. Azadeh, M. Ghasemi, S. Fazelifar

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Aim: Changes in stress hormones can be modify response of immune system. Cortisol as the most important body corticosteroid is anti-inflammatory and immunosuppressive hormone. Normal levels of cortisol in humans has fluctuated during the day, In other words, cortisol is released periodically, and regulate through the release of ACTH circadian rhythm in every day. Therefore, the aim of this study was to determine the effects of Chamomile on serum levels of inflammatory indexes to a bout of eccentric exercise in young women. Methodology: 32 women were randomly divided into 4 groups: high dose of Chamomile, low dose of Chamomile, ibuprofen and placebo group. Eccentric exercise included 5 set and rest period between sets was 1 minute. For this purpose, subjects warm up 10 min and then done eccentric exercise. Each participant completed 15 repetitions with optional 20 kg weight or until can’t continue moving. When the subject was no longer able to continue to move, immediately decreased 5 kg from the weight and the protocol continued until cause exhaustion or complete 15 repetitions. Also, subjects received specified amount of ibuprofen and Chamomile capsules in target groups. Blood samples in 6 stages (pre of starting pill, pre of exercise protocol, 4, 24, 48 and 72 hours after eccentric exercise) was obtained. The levels of cortisol and adrenocorticotropic hormone levels were measured by ELISA way. K-S test to determine the normality of the data and analysis of variance for repeated measures was used to analyze the data. A significant difference in the p < 0/05 accepted. Results: The results showed that Individual characteristics including height, weight, age and body mass index were not significantly different among the four groups. Analyze of data showed that cortisol and ACTH basic levels significantly decreased after supplementation consumption, but then gradually significantly increased in all stages of post exercise. In High dose of Chamomile group, increasing tendency of post exercise somewhat less than other groups, but not to a significant level. The inter-group analysis results indicate that time effect had a significant impact in different stages of the groups. Conclusion: The results of this study, one session of eccentric exercise increased cortisol and ACTH hormone. The results represent the effect of high dose of Chamomile in the prevention and reduction of increased stress hormone levels. As regards use of medicinal plants and ibuprofen as a pain medication and inflammation has spread among athletes and non-athletes, the results of this research can provide information about the advantages and disadvantages of using medicinal plants and ibuprofen.

Keywords: chamomile, inflammatory indexes, eccentric exercise, young girls

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Authors: Roger WUMBA

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The objective of this study was to determine the prevalence of intestinal parasites, with special emphasis on microsporidia and Cryptosporidium, as well as their association with human immunodeficiency virus (HIV) symptoms, risk factors, and other digestive parasites. We also wish to determine the molecular biology definitions of the species and genotypes of microsporidia and Cryptosporidium in HIV patients. In this cross-sectional study, carried out in Kinshasa, Democratic Republic of the Congo, stool samples were collected from 242 HIV patients (87 men and 155 women) with referred symptoms and risk factors for opportunistic intestinal parasites. The analysis of feces specimen were performed using Ziehl–Neelsen stainings, real-time polymerase chain reaction (PCR), immunofluorescence indirect monoclonal antibody, nested PCR-restriction fragment length polymorphism, and PCR amplification and sequencing. Odds ratio (OR) and 95% confidence intervals were used to quantify the risk. Of the 242 HIV patients, 7.8%, 0.4%, 5.4%, 0.4%, 2%, 10.6%, and 2.8% had Enterocytozoon bieneusi, Encephalitozoon intestinalis, Cryptosporidium spp., Isospora belli, pathogenic intestinal protozoa, nonpathogenic intestinal protozoa, and helminths, respectively. We found five genotypes of E. bieneusi: two older, NIA1 and D, and three new, KIN1, KIN2, and KIN3. Only 0.4% and 1.6% had Cryptosporidium parvum and Cryptosporidium hominis, respectively. Of the patients, 36.4%, 34.3%, 31%, and 39% had asthenia, diarrhea, a CD4 count of ,100 cells/mm³, and no antiretroviral therapy (ART), respectively. The majority of those with opportunistic intestinal parasites and C. hominis, and all with C. parvum and new E. bieneusi genotypes, had diarrhea, low CD4+ counts of ,100 cells/mm³, and no ART. There was a significant association between Entamoeba coli, Kaposi sarcoma, herpes zoster, chronic diarrhea, and asthenia, and the presence of 28 cases with opportunistic intestinal parasites. Rural areas, public toilets, and exposure to farm pigs were the univariate risk factors present in the 28 cases with opportunistic intestinal parasites. In logistic regression analysis, a CD4 count of ,100 cells/mm³ (OR = 4.60; 95% CI 1.70–12.20; P = 0.002), no ART (OR = 5.00; 95% CI 1.90–13.20; P , 0.001), and exposure to surface water (OR = 2.90; 95% CI 1.01–8.40; P = 0.048) were identified as the significant and independent determinants for the presence of opportunistic intestinal parasites. E. bieneusi and Cryptosporidium are becoming more prevalent in Kinshasa, Congo. Based on the findings, we recommend epidemiology surveillance and prevention by means of hygiene, the emphasis of sensitive PCR methods, and treating opportunistic intestinal parasites that may be acquired through fecal–oral transmission, surface water, normal immunity, rural area-based person–person and animal–human nfection, and transmission of HIV. Therapy, including ART and treatment with fumagillin, is needed.

Keywords: diarrhea, enterocytozoon bieneusi, cryptosporidium hominis, cryptosporidium parvum, risk factors, africans

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Authors: Hossein Rezaie

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Academic institutions, esp. universities, have been known as cradles of learning and teaching great thinkers while creating the type of knowledge that is supposed to be bereft of utilitarian motives. Nonetheless, it seems that such intellectual centers have entered into a competition with each other for attracting the attention of potential clients. The traditional values of (higher) education such as nurturing criticality and fostering intellectuality in students have been replaced with strategic planning, quality assurance, performance assessment, and academic audits. Not being immune from the whims and wishes of marketization, the system of higher education in the UK has been recalibrated by policy makers to address the demand and supply of student education, academic research and other university activities on the basis of monetary factors. As an immediate example in this vein, the Russell Group in the UK, which is comprised of 24 leading UK research universities, has explicitly expressed it policy on its official website as follows: ‘Russell Group universities are global businesses competing for staff, students and funding with the best in the world’. Furthermore, certain attempts have been made to corporatize the system of HE which have been manifested in remodeling of university governing bodies on corporate lines and developing measurement scales for indicating the performance of teaching practitioners. Nevertheless, it seems that such structural changes in policies toward the system of HE have bearing on the practices of practitioners and educators as well as the identity of students who are the customers of educational services. The effects of marketization have been examined mainly in terms of students’ perceptions and motivation, institutional policies and university management. However, the teaching practitioner side seems to be an under-studied area with regard to any changes in its expectations, satisfaction and perception of professional identity in the aftermath of introducing market-wise values into HE of the UK. As a result, this research aims to investigate the possible outcomes of market-driven values on the practitioner side of HE in the UK and finally seeks to address the following research questions: 1-How is the change in the mission of HE in the UK reflected in institutional documents? 1-A- How is the change of mission represented in job adverts? 1-B- How is the change of mission represented in university prospectuses? 2-How are teaching practitioners represented regarding their roles and obligations in the prospectuses and job ads published by UK HE institutions? In order to address these questions, the researcher will analyze 30 prospectuses and job ads published by Russel Group universities by taking Critical Discourse Analysis as his point of departure and the analytical methods of genre analysis and Systemic Functional Linguistics to probe into the generic features and representation of participants, in this case teaching practitioners, in the selected corpus.

Keywords: higher education, job advertisements, marketization of higher education, prospectuses

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Authors: Sara T. K. Li, Belinda H. J. Chung, Jeffery C. N. Yip, Janet H. Hsiao

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Music notation and text reading both involve statistical learning of music or linguistic structures. However, it remains unclear how music reading expertise influences text reading behavior. The present study examined this issue through an eye-tracking study. Chinese-English bilingual musicians and non-musicians read English sentences, Chinese sentences, musical phrases, and sentences in Tibetan, a language novel to the participants, with their eye movement recorded. Each set of stimuli consisted of two conditions in terms of structural regularity: syntactically correct and syntactically incorrect musical phrases/sentences. They then completed a sentence comprehension (for syntactically correct sentences) or a musical segment/word recognition task afterwards to test their comprehension/recognition abilities. The results showed that in reading musical phrases, as compared with non-musicians, musicians had a higher accuracy in the recognition task, and had shorter reading time, fewer fixations, and shorter fixation duration when reading syntactically correct (i.e., in diatonic key) than incorrect (i.e., in non-diatonic key/atonal) musical phrases. This result reflects their expertise in music reading. Interestingly, in reading Tibetan sentences, which was novel to both participant groups, while non-musicians did not show any behavior differences between reading syntactically correct or incorrect Tibetan sentences, musicians showed a shorter reading time and had marginally fewer fixations when reading syntactically correct sentences than syntactically incorrect ones. However, none of the musicians reported discovering any structural regularities in the Tibetan stimuli after the experiment when being asked explicitly, suggesting that they may have implicitly acquired the structural regularities in Tibetan sentences. This group difference was not observed when they read English or Chinese sentences. This result suggests that music reading expertise facilities reading texts in a novel language (i.e., Tibetan), but not in languages that the readers are already familiar with (i.e., English and Chinese). This phenomenon may be due to the similarities between reading music notations and reading texts in a novel language, as in both cases the stimuli follow particular statistical structures but do not involve semantic or lexical processing. Thus, musicians may transfer their statistical learning skills stemmed from music notation reading experience to implicitly discover structures of sentences in a novel language. This speculation is consistent with a recent finding showing that music reading expertise modulates the processing of English nonwords (i.e., words that do not follow morphological or orthographic rules) but not pseudo- or real words. These results suggest that the modulation of music reading expertise on language processing depends on the similarities in the cognitive processes involved. It also has important implications for the benefits of music education on language and cognitive development.

Keywords: eye movement behavior, eye-tracking, music reading expertise, sentence reading, structural regularity, visual processing

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Authors: Manel Hammami, Gabriele Grandi

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In recent years, multilevel inverters have become more attractive for single-phase photovoltaic (PV) systems, due to their known advantages over conventional H-bridge pulse width-modulated (PWM) inverters. They offer improved output waveforms, smaller filter size, lower total harmonic distortion (THD), higher output voltages and others. The most common multilevel converter topologies, presented in literature, are the neutral-point-clamped (NPC), flying capacitor (FC) and Cascaded H-Bridge (CHB) converters. In both NPC and FC configurations, the number of components drastically increases with the number of levels what leads to complexity of the control strategy, high volume, and cost. Whereas, increasing the number of levels in case of the cascaded H-bridge configuration is a flexible solution. However, it needs isolated power sources for each stage, and it can be applied to PV systems only in case of PV sub-fields. In order to improve the ratio between the number of output voltage levels and the number of components, several hybrids and asymmetric topologies of multilevel inverters have been proposed in the literature such as the FC asymmetric H-bridge (FCAH) and the NPC asymmetric H-bridge (NPCAH) topologies. Another asymmetric multilevel inverter configuration that could have interesting applications is the cascaded asymmetric H-bridge (CAH), which is based on a modular half-bridge (two switches and one capacitor, also called level doubling network, LDN) cascaded to a full H-bridge in order to double the output voltage level. This solution has the same number of switches as the above mentioned AH configurations (i.e., six), and just one capacitor (as the FCAH). CAH is becoming popular, due to its simple, modular and reliable structure, and it can be considered as a retrofit which can be added in series to an existing H-Bridge configuration in order to double the output voltage levels. In this paper, an original and effective method for the analysis of the DC-link voltage ripple is given for single-phase asymmetric H-bridge multilevel inverters based on level doubling network (LDN). Different possible configurations of the asymmetric H-Bridge multilevel inverters have been considered and the analysis of input voltage and current are analytically determined and numerically verified by Matlab/Simulink for the case of cascaded asymmetric H-bridge multilevel inverters. A comparison between FCAH and the CAH configurations is done on the basis of the analysis of the DC and voltage ripple for the DC source (i.e., the PV system). The peak-to-peak DC and voltage ripple amplitudes are analytically calculated over the fundamental period as a function of the modulation index. On the basis of the maximum peak-to-peak values of low frequency and switching ripple voltage components, the DC capacitors can be designed. Reference is made to unity output power factor, as in case of most of the grid-connected PV generation systems. Simulation results will be presented in the full paper in order to prove the effectiveness of the proposed developments in all the operating conditions.

Keywords: asymmetric inverters, dc-link voltage, level doubling network, single-phase multilevel inverter

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Authors: Thais O. de Paula, Marjorie R. A. Sarmiento, Francis M. Borges, Alessandra B. Ferreira-Machado, Juliana A. Resende, Dioneia E. Cesar, Vania L. Silva, Claudio G. Diniz

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Obesity is currently a worldwide public health threat, being considered a pandemic multifactorial disease related to the human gut microbiota (GM). Add to that GM is considered an important reservoir of antimicrobial resistance genes (ARG) and little is known on GM and ARG in obesity, considering the altered physiology and xenobiotics intake. As regional and social behavior may play important roles in GM modulation, and most of the studies are based on small sample size and various methodological approaches resulting in difficulties for data comparisons, this study was focused on the investigation of GM bacterial diversity in obese (OB), overweight (OW) and eutrophic individuals (ET) considering their nutritional, clinical and social characteristics; and comparative screening of AGR related to their physiology and xenobiotics intake. Microbial community was accessed by FISH considering phyla as a taxonomic level, and PCR-DGGE followed by dendrograms evaluation (UPGMA method) from fecal metagenome of 72 volunteers classified according to their body mass index (BMI). Nutritional, clinical, social parameters and xenobiotics intake were recorded for correlation analysis. The fecal metagenome was also used as template for PCR targeting 59 different ARG. Overall, 62% of OB were hypertensive, and 12% or 4% were, regarding the OW and ET individuals. Most of the OB were rated as low income (80%). Lower relative bacterial densities were observed in the OB compared to ET for almost all studied taxa (p < 0.05) with Firmicutes/Bacteroidetes ratio increased in the OB group. OW individuals showed a bacterial density representative of GM more likely to the OB. All the participants were clustered in 3 different groups based on the PCR-DGGE fingerprint patterns (C1, C2, C3), being OB mostly grouped in C1 (83.3%) and ET mostly grouped in C3 (50%). The cluster C2 showed to be transitional. Among 27 ARG detected, a cluster of 17 was observed in all groups suggesting a common core. In general, ARG were observed mostly within OB individuals followed by OW and ET. The ratio between ARG and bacterial groups may suggest that AGR were more related to enterobacteria. Positive correlations were observed between ARG and BMI, calories and xenobiotics intake (especially use of sweeteners). As with nutritional and clinical characteristics, our data may suggest that GM of OW individuals behave in a heterogeneous pattern, occasionally more likely to the OB or to the ET. Regardless the regional and social behaviors of our population, the methodological approaches in this study were complementary and confirmatory. The imbalance of GM over the health-disease interface in obesity is a matter of fact, but its influence in host's physiology is still to be clearly elucidated to help understanding the multifactorial etiology of obesity. Although the results are in agreement with observations that GM is altered in obesity, the altered physiology in OB individuals seems to be also associated to the increased xenobiotics intake and may interfere with GM towards antimicrobial resistance, as observed by the fecal metagenome and ARG screening. Support: FAPEMIG, CNPQ, CAPES, PPGCBIO/UFJF.

Keywords: antimicrobial resistance, bacterial diversity, gut microbiota, obesity

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Authors: Aleksander Ejsmont, Stefan Wuttke, Joanna Goscianska

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Gaining control over particle shape, size and crystallinity is an ongoing challenge for many materials. Especially metalorganic frameworks (MOFs) are recently widely studied. Besides their remarkable porosity and interesting topologies, morphology has proven to be a significant feature. It can affect the further material application. Thus seeking new approaches that enable MOF morphology modulation is important. MOFs are reticular structures, where building blocks are made up of organic linkers and metallic nodes. The most common strategy of ensuring metal source is using salts, which usually exhibit high solubility and hinder morphology control. However, there has been a growing interest in using metal oxides as structure-directing agents towards MOFs due to their very low solubility and shape preservation. Metal oxides can be treated as a metal reservoir during MOF synthesis. Up to now, reports in which receiving MOFs from metal oxides mostly present ZnO conversion to ZIF-8. However, there are other oxides, for instance, Co₃O₄, which often is overlooked due to their structural stability and insolubility in aqueous solutions. Cobalt-based materials are famed for catalytic activity. Therefore the development of their efficient synthesis is worth attention. In the presented work, an optimized Co₃O₄transition to Co-MOFviaa solvothermal approach was proposed. The starting point of the research was the synthesis of Co₃O₄ flower petals and needles under hydrothermal conditions using different cobalt salts (e.g., cobalt(II) chloride and cobalt(II) nitrate), in the presence of urea, and hexadecyltrimethylammonium bromide (CTAB) surfactant as a capping agent. After receiving cobalt hydroxide, the calcination process was performed at various temperatures (300–500 °C). Then cobalt oxides as a source of cobalt cations were subjected to reaction with trimesic acid in solvothermal environment and temperature of 120 °C leading to Co-MOF fabrication. The solution maintained in the system was a mixture of water, dimethylformamide, and ethanol, with the addition of strong acids (HF and HNO₃). To establish how solvents affect metal oxide conversion, several different solvent ratios were also applied. The materials received were characterized with analytical techniques, including X-ray powder diffraction, energy dispersive spectroscopy,low-temperature nitrogen adsorption/desorption, scanning, and transmission electron microscopy. It was confirmed that the synthetic routes have led to the formation of Co₃O₄ and Co-based MOF varied in shape and size of particles. The diffractograms showed receiving crystalline phase for Co₃O₄, and also for Co-MOF. The Co₃O₄ obtained from nitrates and with using low-temperature calcination resulted in smaller particles. The study indicated that cobalt oxide particles of different size influence the efficiency of conversion and morphology of Co-MOF. The highest conversion was achieved using metal oxides with small crystallites.

Keywords: Co-MOF, solvothermal synthesis, morphology control, core-shell

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Authors: Ching-Yi Yiu, Hui-Chen Hsu

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Objectives: Head and neck cancer (HNC) is a big global health problem in the world. Despite the development of diagnosis and treatment, the overall survival of HNC is still low. The well recognition of the interaction of the host immune system and cancer cells has led to realizing the processes of tumor initiation, progression and metastasis. Many systemic inflammatory responses have been shown to play a crucial role in cancer progression. The pre and post-treatment nutritional and immunological status of HNC patients is a reliable prognostic indicator of tumor outcomes and survivors. Methods: Between July 2020 to June 2022, We have enrolled 60 HNC patients, including 59 males and 1 female, in Chi Mei Medical Center, Liouying, Taiwan. The age distribution was from 37 to 81 years old (y/o), with a mean age of 57.6 y/o. We evaluated the pre-and post-treatment nutritional and immunological status of these HNC patients with body weight, body weight loss, body mass index (BMI), whole blood count including hemoglobin (Hb), lymphocyte, neutrophil and platelet counts, biochemistry including prealbumin, albumin, c-reactive protein (CRP), with the time period of before treatment, post-treatment 3 and 6 months. We calculated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to assess how these biomarkers influence the outcomes of HNC patients. Results: We have carcinoma of the hypopharynx in 21 cases with 35％, carcinoma of the larynx in 9 cases, carcinoma of the tonsil and tongue every 6 cases, carcinoma soft palate and tongue base every 5 cases, carcinoma of buccal mucosa, retromolar trigone and mouth floor every 2 cases, carcinoma of the hard palate and low lip each 1 case. There were stage I 15 cases, stage II 13 cases, stage III 6 cases, stage IVA 10 cases, and stage IVB 16 cases. All patients have received surgery, chemoradiation therapy or combined therapy. We have wound infection in 6 cases, 2 cases of pharyngocutaneous fistula, flap necrosis in 2 cases, and mortality in 6 cases. In the wound infection group, the average BMI is 20.4 kg/m2; the average Hb is 12.9 g/dL, the average albumin is 3.5 g/dL, the average NLR is 6.78, and the average PLR is 243.5. In the PC fistula and flap necrosis group, the average BMI is 21.65 kg/m2; the average Hb is 11.7 g/dL, the average albumin is 3.15 g/dL, average NLR is 13.28, average PLR is 418.84. In the mortality group, the average BMI is 22.3 kg/m2; the average Hb is 13.58 g/dL, the average albumin is 3.77 g/dL, the average NLR is 6.06, and the average PLR is 275.5. Conclusion: HNC is a big challenging public health problem worldwide, especially in the high prevalence of betel nut consumption area Taiwan. Besides the definite risk factors of smoking, drinking and betel nut related, the other biomarkers may play significant prognosticators in the HNC outcomes. We concluded that the average BMI is less than 22 kg/m2, the average Hb is low than 12.0 g/dL, the average albumin is low than 3.3 g/dL, the average NLR is low than 3, and the average PLR is more than 170, the surgical complications and mortality will be increased, and the prognosis is poor in HNC patients.

Keywords: nutritional, immunological, neutrophil-to-lymphocyte ratio, paltelet-to-lymphocyte ratio.

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Authors: Adeleke G. E., Bello M. A., Abdulateef R. B., Olasinde T. T., Oriaje K. O., AransiI A., Elaigwu K. O., Omidoyin O. S., Shoyinka E. D., Awoyomi M. B., Akano M., Adaramoye O. A.

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Hymenocardia acidatul belongs to the genus, Hymenocardiaceae, which is widely distributed in Africa. Both the leaf and stem bark of the plant have been used in the treatment of several diseases. The present study examined the chemical constituents of the H. acida stem bark extract (HASBE) and its effects on some antioxidant indices and esterase enzymes in female Wistar rats. The HASBE was obtained by Soxhlet extraction using methanol and then subjected to Atomic Absorption Spectroscopy (AAS) for elemental analysis, and Fourier-Transform Infrared (FT-IR) spectroscopy, ultraviolet (UV) spectroscopy, for functional group analysis, while High-performance liquid chromatography (HPLC), and Gas Chromatography-Flame ionization detection (GC-FID) were carried out for compound identification. Forty-eight female Wistar rats were assigned into eight groups of six rats each and separately administered orally with normal saline (Control), 50, 100, 150, 200, 250, 300, 350 mg/kg of HASBE twice per week for eight weeks. The rats were sacrificed under chloroform anesthesia, and kidneys and heart were excised and processed to obtain homogenates. The levels of superoxide dismutase (SOD), catalase, Malondialdehyde (MDA), glutathione peroxidase (GPx), acetylcholinesterase (AChE), and carboxylesterase (CE) were determined spectrophotometrically. The AAS of HASBE shows the presence of eight elements, including Cobalt (0.303), Copper (0.222), Zinc (0.137), Iron (2.027), Nickel (1.304), Chromium (0.313), Manganese (0.213), and Magnesium (0.337 ppm). The FT-IR result of HASBE shows four peaks at 2961.4, 2926.0, 1056.7, and 1034.3 cm-1, while UV analysis shows a maximum absorbance (0.522) at 205 nm. The HPLC spectrum of HASBE indicates the presence of four major compounds, including orientin (77%), β-sitosterol (6.58%), rutin (5.02%), and betulinic acid (3.33%), while GC-FID result shows five major compounds, including rutin (53.27%), orientin (13.06%) and stigmasterol (11.73%), hymenocardine (6.43%) and homopterocarpin (5.29%). The SOD activity was significantly (p < 0.05) lowered in the kidney but elevated in the heart, while catalase was elevated in both organs relative to control rats. The GPx activity was significantly elevated only in the kidney, while MDA was not significantly (p > 0.05) affected in the two organs compared with controls. The activity of AChE was significantly elevated in both organs, while CE activity was elevated only in the kidney relative to control rats. The present study reveals that Hymenocardia acida stem bark extract majorly contains orientin, rutin, stigmasterol, hymenocardine, β-sitosterol, homopterocarpin, and betulinic acid. In addition, these compounds could possibly enhance redox status and esterase activities in the kidney and heart of Wistar rats.

Keywords: hymenocardia acida, elemental analysis, compounds identification, redox status, organs

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Authors: I. Cerrillo, A. Carrillo-Vico, M. A. Ortega, B. Escudero-López, N. Álvarez-Sánchez, F. Martín, M. S. Fernández-Pachón

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Melatonin is a bioactive compound involved in multiple biological activities such as glucose tolerance, circadian rhythm regulation, antioxidant defense or immune system action. In elderly subjects the intake of foods and drinks rich in melatonin is very important due to its endogenous level decreases with age. Alcoholic fermentation is a process carried out in fruits, vegetables and legumes to obtain new products with improved bioactive compounds profile in relation to original substrates. Alcoholic fermentation process carried out by Saccharomycetaceae var. Pichia kluyveri induces an important synthesis of melatonin in orange juice. A novel beverage derived of fermented orange juice could be a promising source of this bioactive compound. The aim of the present study was to determine whether the acute intake of fermented orange juice increase the levels of urinary 6-sulfatoxymelatonin in healthy humans. Nine healthy volunteers (7 women and 2 men), aged between 20 and 25 years old and BMI of 21.1  2.4 kg/m2, were recruited. On the study day, participants ingested 500 mL of fermented orange juice. The first urine collection was made before fermented orange juice consumption (basal). The rest of urine collections were made in the following time intervals after fermented orange juice consumption: 0-2, 2-5, 5-10, 10- 15 and 15-24 hours. During the experimental period only the consumption of water was allowed. At lunch time a meal was provided (60 g of white bread, two slices of ham, a slice of cheese, 125 g of sweetened natural yoghurt and water). The subjects repeated the protocol with orange juice following a 2-wk washout period between both types of beverages. The levels of 6-sulfatoxymelatonin (6-SMT) were measured in urine recollected at different time points using the Melatonin-Sulfate Urine ELISA (IBL International GMBH, Hamburg, Germany). Levels of 6-SMT were corrected to those of creatinine for each sample. A significant (p < 0.05) increase in urinary 6-SMT levels was observed between 2-5 hours after fermented orange juice ingestion with respect to basal values (increase of 67,8 %). The consumption of orange juice did not induce any significant change in urinary 6-SMT levels. In addition, urinary 6-SMT levels obtained between 2-5 hours after fermented orange juice ingestion (115,6 ng/mg) were significantly different (p < 0.05) from those of orange juice (42,4 ng/mg). The enhancement of urinary 6-SMT after the ingestion of 500 mL of fermented orange juice in healthy humans compared to orange juice could be an important advantage of this novel product as an excellent source of melatonin. Fermented orange juice could be a new functional food, and its consumption could exert a potentially positive effect on health in both the maintenance of health status and the prevention of chronic diseases.

Keywords: fermented orange juice, functional beverage, healthy human, melatonin

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Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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Authors: Wisdom Robert Duruji

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The outbreak of SARS-CoV-2 serotype infection was recorded in January 2020 in Wuhan City, Hubei Province, China. This study examines the concepts of the COVID-19 pandemic and the implications of vaccines for health security in Nigeria and Diasporas. It challenges the widely accepted assumption that the first case of coronavirus infection in Nigeria was recorded on February 27th, 2020, in Lagos. The study utilizes a range of research methods to achieve its objectives. These include the double-layered culture technique, literature review, website knowledge, Google search, news media information, academic journals, fieldwork, and on-site observations. These diverse methods allow for a comprehensive analysis of the concepts and the implications being studied. The study finds that coronavirus infection can be asymptomatic; it may be the antigenicity of the leukocytes (white blood cells), which produce immunogenic hapten or interferons (α, β and γ) that fight infectious parasites, was an immune response that prevented severe virulence in healthy individuals; the reason healthy patients of coronavirus infection in Nigeria naturally recovered after two to three weeks of on-set of infection and test negative. However, the fatality data from the Nigerian Centre for Disease Control (NCDC) is incorrect in this study’s finding; it perused that the fatalities were primarily due to underlying ailments, hunger, and malnutrition in debilitated, comorbid, or compromised patients. This study concluded that the kits and Polymerase Chain Reaction (PCR) machine currently used by the Nigerian Centre for Disease Control (NCDC) in testing and confirming COVID-19 in Nigeria is not ideal; it is programmed and negates separating the strain to its specific serotypes amongst its genera coronavirus, and family Coronaviridae; and might have confirmed patients with the symptoms of febrile caused by cough, catarrh, typhoid and malaria parasites as Covid-19 positive. Therefore, it is recommended that the coronavirus species infected in Nigeria are opportunistic parasites that thrive in human immuno-suppressed conditions like the herpesvirus; it cannot be eradicated by vaccines; the only virucides are interferons, immunoglobulins, and probably synthetic antiviral guanosine drugs like copegus or ribavirin. The findings emphasized that COVID-19 is not the primary pandemic disease in Nigeria; the lockdown was a mirage and not necessary; but rather, pandemic diseases in Nigeria are corruption, nepotism, hunger, and malnutrition caused by ineptitude in governance, religious dichotomy, and ethnic conflicts.

Keywords: coronavirus, corruption, Covid-19 pandemic, lock-down, Nigeria, vaccine

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Authors: N. Selvi Gunel, L. M. Oktay, H. Memmedov, B. Durmaz, H. Kalkan Yildirim, E. Yildirim Sozmen

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Object: Propolis which consists of compounds that are accepted as antioxidant, antimicrobial, antiseptic, antibacterial, anti-inflammatory, anti-mutagenic, immune-modulator and cytotoxic, is frequently used in current therapeutic applications. However, some of them result in allergic side effects, causing consumption to be restricted. Previously our group has succeeded in producing a new biotechnological product which was less allergenic. In this study, we purpose to optimize production conditions of this biologically-transformed propolis and determine the cytotoxic effects of obtained new products on colon cancer cell line (HCT-116). Method: Firstly, solid propolis samples were dissolved in water after weighing, grinding and sizing (sieve-35mesh) and applied 40 kHz/10 min ultrasonication. Samples were prepared according to inoculation with Lactobacillus plantarum in two different proportions (2.5% and 3.5%). Chromatographic analyzes of propolis were performed by UPLC-MS/MS (Waters, Milford, MA) system. Results were analysed by UPLC-MS/MS system MassLynx™ 4.1 software. HCT-116 cells were treated with propolis examples at 25-1000 µg/ml concentrations and cytotoxicity were measured by using WST-8 assay at 24, 48, and 72 hours. Samples with biological transformation were compared with the non-transformed control group samples. Our experiment groups were formed as follows: untreated (group 1), propolis dissolved in water ultrasonicated at 40 kHz/10 min (group 2), propolis dissolved in water ultrasonicated at 40 kHz/10 min and inoculated 2.5% L. plantarum L1 strain (group 3), propolis dissolved in water ultrasonicated at 40 kHz/10 min and inoculated 3.5% L. plantarum L3 strain (group 4). Obtained data were calculated with Graphpad Software V5 and analyzed by two-way ANOVA test followed by Bonferroni test. Result: As a result of our study, the cytotoxic effect of propolis samples on HCT-116 cells was evaluated. There was a 7.21 fold increase in group 3 compared to group 2 in the concentration of 1000 µg/ml, and it was a 6.66 fold increase in group 3 compared to group 1 at the end of 24 hours. At the end of 48 hours, in the concentration of 500 µg/ml, it was determined 4.7 fold increase in group 4 compared to group 3. At the same time, in the concentration of 750 µg/ml it was determined 2.01 fold increase in group 4 compared to group 3 and in the same concentration, it was determined 3.1 fold increase in group 4 compared to group 2. Also, at the 72 hours, in the concentration of 750 µg/ml, it was determined 2.42 fold increase in group 3 according to group 2 and in the same time, in the concentration of 1000 µg/ml, it was determined 2.13 fold increase in group 4 according to group 2. According to cytotoxicity results, the group which were ultrasonicated at 40 kHz/10min and inoculated 3.5% L. plantarum L3-strain had a higher cytotoxic effect. Conclusion: It is known that bioavailability of propolis is halved in six months. The data obtained from our results indicated that biologically-transformed propolis had more cytotoxic effect than non-transformed group on colon cancer cells. Consequently, we suggested that L. plantarum-transformation provides both reduction of allergenicity and extension of bioavailability period by enhancing healthful polyphenols.

Keywords: bio-transformation, propolis, colon cancer, cytotoxicity

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Authors: Hanan Bin Nakhi, Asaad M. Albadrawi, Maged Al Shahat, ‎Entesar Mandani

Abstract:

Background:‎ Kawasaki disease (KD) is one of the most common vasculitis of childhood. ‎It is considered the leading cause of acquired heart disease in children. The ‎peak age of occurrence is 6 to 24 months, with 80% of affected children being ‎less than 5 years old. There are only a few reports of KD in infants younger ‎than 6 months. Infants had a higher incidence of atypical KD and of coronary ‎artery complications. This case report from Kuwait will reinforce considering ‎atypical KD in case of sepsis like condition with negative cultures and ‎unresponding to systemic antibiotics. Early diagnosis allows early treatment ‎with intravenous immune globulin (IVIG) and so decreases the incidence of ‎cardiac aneurysm.‎ Case Report:‎ A 2 month old female infant, product of full term normal delivery to ‎consanguineous parents, presented with fever and poor feeding. She was ‎admitted and treated as urinary tract infection as her urine routine revealed ‎pyurea. The baby continued to have persistent fever and hypoactivity inspite ‎of using intravenous antibiotics. Latter, she developed non purulent ‎conjunctivitis, skin mottling, oedema of the face / lower limb and was treated ‎in intensive care unit as a case of septic shock. In spite of her partial general ‎improvement, she continued to look unwell, hypoactive and had persistent ‎fever. Septic work up, metabolic, and immunologic screen were negative. KD ‎was suspected when the baby developed polymorphic erythematous rash and ‎noticed to have peeling of skin at perianal area and periangular area of the ‎fingers of the hand and feet. IVIG was given in dose of 2 gm/kg/day in single ‎dose and aspirin 100 mg/kg/day in four divided doses. The girl showed marked ‎clinical improvement. The fever subsided dramatically and the level acute ‎phase reactant markedly decreased but the platelets count increased to ‎‎1600000/mm3. Echo cardiography showed mild dilatation of mid right ‎coronary artery. Aspirin was continued in a dose of 5 mg/kg/d till repeating ‎cardiac echo. ‎Conclusion:‎ A high index of suspicion of KD must be maintained in young infants with ‎prolonged unexplained fever. Accepted criteria should be less restrictive to ‎allow early diagnosis of a typical KD in infants less than 6 months of age. ‎Timely appropriate treatment with IVIG is essential to avoid severe coronary ‎sequels.‎

Keywords: Kawasaki disease, atypical Kawasaki disease, infantile Kawasaki disease, hypo activity‎ ‎

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Authors: Marcel Schulze, Behrem Aslan, Silke Lux, Alexandra Philipsen

Abstract:

Objective: Patients with Attention Deficit/Hyperactivity Disorder (ADHD) often report that they are being flooded by sensory impressions. Studies investigating sensory processing show hypersensitivity for sensory inputs across the senses in children and adults with ADHD. Especially the auditory modality is affected by deficient acoustical inhibition and modulation of signals. While studying unimodal signal-processing is relevant and well-suited in a controlled laboratory environment, everyday life situations occur multimodal. A complex interplay of the senses is necessary to form a unified percept. In order to achieve this, the unimodal sensory modalities are bound together in a process called multisensory integration (MI). In the current study we investigate MI in an adult ADHD sample using the McGurk-effect – a well-known illusion where incongruent speech like phonemes lead in case of successful integration to a new perceived phoneme via late top-down attentional allocation . In ADHD neuronal dysregulation at rest e.g., aberrant within or between network functional connectivity may also account for difficulties in integrating across the senses. Therefore, the current study includes resting-state functional connectivity to investigate a possible relation of deficient network connectivity and the ability of stimulus integration. Method: Twenty-five ADHD patients (6 females, age: 30.08 (SD:9,3) years) and twenty-four healthy controls (9 females; age: 26.88 (SD: 6.3) years) were recruited. MI was examined using the McGurk effect, where - in case of successful MI - incongruent speech-like phonemes between visual and auditory modality are leading to a perception of a new phoneme. Mann-Whitney-U test was applied to assess statistical differences between groups. Echo-planar imaging-resting-state functional MRI was acquired on a 3.0 Tesla Siemens Magnetom MR scanner. A seed-to-voxel analysis was realized using the CONN toolbox. Results: Susceptibility to McGurk was significantly lowered for ADHD patients (ADHDMdn:5.83%, ControlsMdn:44.2%, U= 160.5, p=0.022, r=-0.34). When ADHD patients integrated phonemes, reaction times were significantly longer (ADHDMdn:1260ms, ControlsMdn:582ms, U=41.0, p<.000, r= -0.56). In functional connectivity medio temporal gyrus (seed) was negatively associated with primary auditory cortex, inferior frontal gyrus, precentral gyrus, and fusiform gyrus. Conclusion: MI seems to be deficient for ADHD patients for stimuli that need top-down attentional allocation. This finding is supported by stronger functional connectivity from unimodal sensory areas to polymodal, MI convergence zones for complex stimuli in ADHD patients.

Keywords: attention-deficit hyperactivity disorder, audiovisual integration, McGurk-effect, resting-state functional connectivity

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Authors: Martyna Chotomska, Aleksandra Studzinska, Marta Lisowska, Justyna Szubert, Aleksandra Tabis, Jacek Bania, Arkadiusz Miazek

Abstract:

Objectives: Assessing antigen-specific T cell responses is of utmost importance for the pre-clinical testing of prototype vaccines against intracellular pathogens and tumor antigens. Mainly two types of in vitro assays are used for this purpose 1) enzyme-linked immunospot (ELISpot) and 2) intracellular cytokine staining (ICS). Both are time-consuming, relatively expensive, and require manual dexterity. Here, we assess if a straightforward detection of luciferase activity in blood samples of transgenic reporter mice expressing a secreted Lucia luciferase under the transcriptional control of IFN-γ promoter parallels the sensitivity of IFNγ ELISpot assay. Methods: IFN-γ-LUCIA mouse strain carrying multiple copies of Lucia luciferase transgene under the transcriptional control of IFNγ minimal promoter were generated by pronuclear injection of linear DNA. The specificity of transgene expression and mobilization was assessed in vitro using transgenic splenocytes exposed to various mitogens. The IFN-γ-LUCIA mice were immunized with 50mg of ovalbumin (OVA) emulsified in incomplete Freund’s adjuvant three times every two weeks by subcutaneous injections. Blood samples were collected before and five days after each immunization. Luciferase activity was assessed in blood serum. Peripheral blood mononuclear cells were separated and assessed for frequencies of OVA-specific IFNγ-secreting T cells. Results: We show that in vitro cultured splenocytes of IFN-γ-LUCIA mice respond by 2 and 3 fold increase in secreted luciferase activity to T cell mitogens concanavalin A and phorbol myristate acetate, respectively but fail to respond to B cell-stimulating E.coli lipopolysaccharide. Immunization of IFN-γ-LUCIA mice with OVA leads to over 4 fold increase in luciferase activity in blood serum five days post-immunization with a barely detectable increase in OVA-specific, IFNγ-secreting T cells by ELISpot. Second and third immunizations, further increase the luciferase activity and coincidently also increase the frequencies of OVA-specific T cells by ELISpot. Conclusions: We conclude that minimally invasive monitoring of luciferase secretions in blood serum of IFN-γ-LUCIA mice constitutes a sensitive method for evaluating primary and memory Th1 responses to protein antigens. As such, this method may complement existing methods for rapid immunogenicity assessment of prototype vaccines.

Keywords: ELISpot, immunogenicity, interferon-gamma, reporter mice, vaccines

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Authors: Maria E. V. Amarante, Carolina L. Cerdeira, Julia V. Cortes, Fiorita G. L. Mundim

Abstract:

Basal cell carcinoma (BCC) is the most prevalent type of skin cancer in humans. It arises from the basal cells of the epidermis and cutaneous appendages. The role of sunlight exposure as a risk factor for BCC is very well defined due to its power to influence genetic mutations, in addition to having a suppressor effect on the skin immune system. Despite showing low metastasis and mortality rates, the tumor is locally infiltrative, aggressive, and destructive. Considering the high prevalence rate of this carcinoma and the importance of early detection, a retrospective study was carried out in order to correlate the clinical data available on BBC, characterize it epidemiologically, and thus enable effective prevention measures for the population. Data on the period from January 2015 to December 2019 were collected from the medical records of patients registered at one pathology service located in the southeast region of Brazil, known as SVO, which delivers skin biopsy results. The study was aimed at correlating the variables, sex, age, and subtypes found. Data analysis was performed using the chi-square test at a nominal significance level of 5% in order to verify the independence between the variables of interest. Fisher's exact test was applied in cases where the absolute frequency in the cells of the contingency table was less than or equal to five. The statistical analysis was performed using the R® software. Ninety-three basal cell carcinoma were analyzed, and its frequency in the 31-to 45-year-old age group was 5.8 times higher in men than in women, whereas, from 46 to 59 years, the frequency was found 2.4 times higher in women than in men. Between the ages of 46 to 59 years, it should be noted that the sclerodermiform subtype appears more than the solid one, with a difference of 7.26 percentage points. Reversely, the solid form appears more frequently in individuals aged 60 years or more, with a difference of 8.57 percentage points. Among women, the frequency of the solid subtype was 9.93 percentage points higher than the sclerodermiform frequency. In males, the same percentage difference is observed, but sclerodermiform is the most prevalent subtype. It is concluded in this study that, in general, there is a predominance of basal cell carcinoma in females and in individuals aged 60 years and over, which demonstrates the tendency of this tumor. However, when rarely found in younger individuals, the male gender prevailed. The most prevalent subtype was the solid one. It is worth mentioning that the sclerodermiform subtype, which is more aggressive, was seen more frequently in males and in the 46-to 59-year-old range.

Keywords: basal cell carcinoma, epidemiology, sclerodermiform basal cell carcinoma, skin cancer, solar radiation, solid basal cell carcinoma

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Authors: Görkem Cemali̇, Avram Aruh, Gamze Torun Köse, Erde Can ŞAfak

Abstract:

In order to heal bone disorders, the conventional methods which involve the use of autologous and allogenous bone grafts or permanent implants have certain disadvantages such as limited supply, disease transmission, or adverse immune response. A biodegradable material that acts as structural support to the damaged bone area and serves as a scaffold that enhances bone regeneration and guides bone formation is one desirable solution. Poly(propylene fumarate) (PPF) which is an unsaturated polyester that can be copolymerized with appropriate vinyl monomers to give biodegradable network structures, is a promising candidate polymer to prepare bone tissue engineering scaffolds. In this study, hydroxyl-terminated PPF was synthesized and thermally cured with vinyl phosphonic acid (VPA) and diethyl vinyl phosphonate (VPES) in the presence of radical initiator benzoyl peroxide (BP), with changing co-monomer weight ratios (10-40wt%). In addition, the synthesized PPF was cured with VPES comonomer at body temperature (37oC) in the presence of BP initiator, N, N-Dimethyl para-toluidine catalyst and varying amounts of Beta-tricalcium phosphate (0-20 wt% ß-TCP) as filler via radical polymerization to prepare composite materials that can be used in injectable forms. Thermomechanical properties, compressive properties, hydrophilicity and biodegradability of the PPF/VPA and PPF/VPES copolymers were determined and analyzed with respect to the copolymer composition. Biocompatibility of the resulting polymers and their composites was determined by the MTS assay and osteoblast activity was explored with von kossa, alkaline phosphatase and osteocalcin activity analysis and the effects of VPA and VPES comonomer composition on these properties were investigated. Thermally cured PPF/VPA and PPF/VPES copolymers with different compositions exhibited compressive modulus and strength values in the wide range of 10–836 MPa and 14–119 MPa, respectively. MTS assay studies showed that the majority of the tested compositions were biocompatible and the overall results indicated that PPF/VPA and PPF/VPES network polymers show significant potential for applications as bone tissue engineering scaffolds where varying PPF and co-monomer ratio provides adjustable and controllable properties of the end product. The body temperature cured PPF/VPES/ß-TCP composites exhibited significantly lower compressive modulus and strength values than the thermal cured PPF/VPES copolymers and were therefore found to be useful as scaffolds for cartilage tissue engineering applications.

Keywords: biodegradable, bone tissue, copolymer, poly(propylene fumarate), scaffold

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Authors: Manali Chakraborty

Abstract:

In the developing countries the most prevalent pathological state is malnutrition and under nutrition due to deficiency of essential nutrients. This condition is more seen between the woman population, especially in the adolescent girls. It is causing childhood deaths along with others cognitive, degenerative diseases. Born of low weight babies and stillbirth are also major problems associated with the malnutrition. Along with the increased level of population, people not only should concern about their quantity of food but also for the quality of the food to be healthy. Lethargy, depression caused due to iron deficiency often quoted as normal or unimportant issues. Children of malnourished women are more likely associated with cognitive impairment, immune dysfunction leading to a higher risk of being attacked by diseases. Malnourishment also affects the productivity of women. Low social status, lack of proper nutritional education is an important cause of this nutrient deficiency among women. Iron deficiency and anemia are mostly famous nutritional deficiencies among women worldwide. Mostly women from below poverty lined area are anemic due to less consumption of iron-rich foods or having foods that might inhibit the iron absorption. Growing females like adolescents or lactating females need more iron supply. Less supplement causes iron deficiency. Though malaria also might cause anemia, it is more likely endemic one in some specific areas. Folate deficiency in females also may cause neurological defects in the infants. Other Vitamin B, A deficiencies along with low iodine level is also noted in malnourished women. According to tradition, still in some areas in developing countries females have their food at the end. According to some survey and collected data, these females are often into the risk zone of being malnourished. Regularly they have the very lesser amount, or food sometimes may start to lose its nutrients. Women are the one who maintains the responsibility to cook foods in the home. Lack of proper nutritional education and proper food preparation not only make those foods lose the nutrients leading to impairment in proper nutrient intake of the family members but also impairing own nutritional status. Formulation and development of food products from iron or other nutrient affluent sources viz., traditional herbs can be helpful in the prevention of such malnutrition condition in females. Keeping low cost and smooth maintenance of the food product development from the natural sources like pulses, cereals or other vegetation also can be beneficial to sustain socio-economic condition. Consumption of such kind of foodstuff is much healthier rather than taking continuous supplements like capsules. Utilization of proper scientific and cost-effective techniques for this food product development and their distribution among rural women population might be an enormous initiative.

Keywords: anemia, food supplements, malnutrition, rural places, women population

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Authors: Vanessa H. S. Zago, Ana Maria H. de Avila, Paula P. Costa, Welington Corozolla, Liriam S. Teixeira, Eliana C. de Faria

Abstract:

Objectives: The outcome of cardiovascular disease is affected by environment and climate. This study evaluated the possible relationships between climatic and environmental changes and the occurrence of biological rhythms in serum lipids and lipoproteins in a large population sample in the city of Campinas, State of Sao Paulo, Brazil. In addition, it determined the temporal variations of death due to atherosclerotic events in Campinas during the time window examined. Methods: A large 8-year retrospective study was carried out to evaluate the lipid profiles of individuals attended at the University of Campinas (Unicamp). The study population comprised 27.543 individuals of both sexes and of all ages. Normolipidemic and dyslipidemic individuals classified according to Brazilian guidelines on dyslipidemias, participated in the study. For the same period, the temperature, relative humidity and daily brightness records were obtained from the Centro de Pesquisas Meteorologicas e Climaticas Aplicadas a Agricultura/Unicamp and frequencies of death due to atherosclerotic events in Campinas were acquired from the Brazilian official database DATASUS, according to the International Classification of Diseases. Statistical analyses were performed using both Cosinor and ARIMA temporal analysis methods. For cross-correlation analysis between climatic and lipid parameters, cross-correlation functions were used. Results: Preliminary results indicated that rhythmicity was significant for LDL-C and HDL-C in the cases of both normolipidemic and dyslipidemic subjects (n =respectively 11.892 and 15.651 both measures increasing in the winter and decreasing in the summer). On the other hand, for dyslipidemic subjects triglycerides increased in summer and decreased in winter, in contrast to normolipidemic ones, in which triglycerides did not show rhythmicity. The number of deaths due to atherosclerotic events showed significant rhythmicity, with maximum and minimum frequencies in winter and summer, respectively. Cross-correlation analyzes showed that low humidity and temperature, higher thermal amplitude and dark cycles are associated with increased levels of LDL-C and HDL-C during winter. In contrast, TG showed moderate cross-correlations with temperature and minimum humidity in an inverse way: maximum temperature and humidity increased TG during the summer. Conclusions: This study showed a coincident rhythmicity between low temperatures and high concentrations of LDL-C and HDL-C and the number of deaths due to atherosclerotic cardiovascular events in individuals from the city of Campinas. The opposite behavior of cholesterol and TG suggest different physiological mechanisms in their metabolic modulation by climate parameters change. Thus, new analyses are underway to better elucidate these mechanisms, as well as variations in lipid concentrations in relation to climatic variations and their associations with atherosclerotic disease and death outcomes in Campinas.

Keywords: atherosclerosis, climatic variations, lipids and lipoproteins, associations

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