Evaluation of health-related quality of life and muscular strength in children with beta thalassemia major

Background: Thalassemia is an inherited blood disorder that requires repeated blood transfusions and chelation regimes. This may lead to restrictions in physical activities, social participation as well as decreased muscle strength.Aim: The aim of this study was to evaluate the health-related quality of life (HRQoL), muscular strength and pain in children with β-thalassemia major.Patients and method: One hundred and twenty children (60 with β-thalassemia major and 60 age-matched healthy) were participated in a cross-sectional study from both sexes (57 girls and 63 boys) with ages ranging from two to twelve years. HRQoL (physical, emotional, social and school functioning), muscular strength and pain were evaluated for all children by using the pediatric quality of life inventoryTM (PedsQLTM) 4.0 generic core scale, hand-held dynamometer and visual analogue scale (VAS) respectively.Results: Children with β-thalassemia major showed a significant decrease in all domains of health-related quality of life and handgrip strength with a significant increase in VAS score (p ≤ 0.0001).Conclusions: The study concluded that thalassemia as a chronic disease has a negative impact on HRQoL and muscle strength of children in different age group.Keywords: Beta thalassemia, Quality of life, Handgrip strength, childre

Parents’ Acceptance to Alveolar and Nasoalveolar Molding Appliances during Early Cleft Lip and Palate Care: A Call for High-Quality Research

AIM: Acceptance and compliance of the parents are an essential pillar in the success of pre-surgical infant orthopedic (PSIO) treatment. The aim of this systematic review is to evaluate the burden of care associated with the alveolar molding (AM) and nasoalveolar molding (NAM) appliances as experienced by the parents with unilateral complete cleft lip and palate (UCLP) infants. METHODS: An electronic search was carried on by two reviewers in eight search engines, as well as a manual search till July 2019. Randomized controlled trials (RCTs) comparing AM/NAM appliances to controls in infants with UCLP were selected. Risk of bias was evaluated using Cochrane risk of bias assessment tool for RCTs. RESULTS: One RCT was included in the qualitative analysis. Non-significant differences were found in the amount of mothers’ satisfaction between the intervention and control groups. CONCLUSIONS: Insufficient low-quality evidence is available regarding the effects of AM and NAM on parents’ satisfaction and burden of care. No conclusions can be withdrawn from the existing studies. High-quality research is needed to elucidate the degree of parents’ acceptance to the molding appliances. PROSPERO registration number: CRD42016043174

Candidate malaria susceptibility/protective SNPs in hospital and population-based studies: the effect of sub-structuring

Background: Populations of East Africa including Sudan, exhibit some of the highest indices of genetic diversity in the continent and worldwide. The current study aims to address the possible impact of population structure and population stratification on the outcome of case-control association-analysis of malaria candidate-genes in different Sudanese populations, where the pronounced genetic heterogeneity becomes a source of concern for the potential effect on the studies outcome. Methods: A total of 72 SNPs were genotyped using the Sequenom iPLEX Gold assay in 449 DNA samples that included; cases and controls from two village populations, malaria patients and out-patients from the area of Sinnar and additional controls consisting of healthy Nilo-Saharan speaking individuals. The population substructure was estimated using the Structure 2.2 programme. Results & Discussion: The Hardy-Weinberg Equilibrium values were generally within expectation in Hausa and Massalit. However, in the Sinnar area there was a notable excess of homozygosity, which was attributed to the Whalund effect arising from population amalgamation within the sample. The programme STRUCTURE revealed a division of both Hausa and Massalit into two substructures with the partition in Hausa more pronounced than in Massalit; in Sinnar there was no defined substructure. More than 25 of the 72 SNPs assayed were informative in all areas. Some important SNPs were not differentially distributed between malaria cases and controls, including SNPs in CD36 and NOS2. A number of SNPs showed significant p-values for differences in distribution of genotypes between cases and controls including: rs1805015 (in IL4R1) (P=0001), rs17047661 (in CR1) (P=0.02) and rs1800750 (TNF-376) (P=0.01) in the hospital samples; rs1050828 (G6PD+202) (P=0.02) and rs1800896 (IL10-1082) (P=0.04) in Massalit and rs2243250 (IL4-589) (P=0.04) in Hausa. Conclusions: The difference in population structure partly accounts for some of these significant associations, and the strength of association proved to be sensitive to all levels of sub-structuring whether in the hospital or population-based study

Cytotoxicity of nickel zinc ferrite nanoparticles on cancer cells of epithelial origin

In this study, in vitro cytotoxicity of nickel zinc (NiZn) ferrite nanoparticles against human colon cancer HT29, breast cancer MCF7, and liver cancer HepG2 cells was examined. The morphology, homogeneity, and elemental composition of NiZn ferrite nanoparticles were investigated by scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy, respectively. The exposure of cancer cells to NiZn ferrite nano-particles (15.6-1,000 μg/mL; 72 hours) has resulted in a dose-dependent inhibition of cell growth determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The quantification of caspase-3 and -9 activities and DNA fragmentation to assess the cell death pathway of the treated cells showed that both were stimulated when exposed to NiZn ferrite nanoparticles. Light microscopy examination of the cells exposed to NiZn ferrite nanoparticles demonstrated significant changes in cellular morphology. The HepG2 cells were most prone to apoptosis among the three cells lines examined, as the result of treatment with NiZn nanoparticles. In conclusion, NiZn ferrite nanoparticles are suggested to have potential cytotoxicity against cancer cells

Bilosomes as a promising nanoplatform for oral delivery of an alkaloid nutraceutical:improved pharmacokinetic profile and snowballed hypoglycemic effect in diabetic rats

Diabetes mellitus is a life-threatening metabolic disease. At the moment, there is no effective treatment available to combat it. In this study, we aimed to develop berberine-loaded bilosomes (BER-BLS) to boost the oral bioavailability and therapeutic efficacy of berberine, a natural antidiabetic medication. The BER-BLS was fabricated using a thin-film hydration strategy and optimized using a central composite design (face-centered). The average vesicle size, entrapment efficiency, and surface charge of the optimized BER-BLS preparation were 196.5 nm, 89.7%, (−) 36.4 mV, respectively. In addition, it exhibited higher stability and better-sustained release of berberine than the berberine solution (BER-SOL). BER-BLS and BER-SOL were administered to streptozocin-induced diabetic rats. The optimized BER-BLS formulation had a significant hypoglycemic impact, with a maximum blood glucose decrease of 41%, whereas BER-SOL only reduced blood glucose by 19%. Furthermore, the pharmacological effect of oral BER-BLS and BER-SOL corresponded to 99.3% and 31.7%, respectively, when compared to subcutaneous insulin (1 IU). A pharmacokinetic analysis found a 6.4-fold rise in the relative bioavailability of berberine in BER-BLS when compared to BER-SOL at a dosage of 100 mg/kg body weight. Histopathological investigation revealed that BER-BLS is suitable for oral administration. Our data demonstrate that BLS is a potential nanocarrier for berberine administration, enhancing its oral bioavailability and antidiabetic activity

Evaluation and prediction of groundwater quality for irrigation using an integrated water quality indices, machine learning models and GIS approaches: a representative case study

Agriculture has significantly aided in meeting the food needs of growing population. In addition, it has boosted economic development in irrigated regions. In this study, an assessment of the groundwater (GW) quality for agricultural land was carried out in El Kharga Oasis, Western Desert of Egypt. Several irrigation water quality indices (IWQIs) and geographic information systems (GIS) were used for the modeling development. Two machine learning (ML) models (i.e., adaptive neuro-fuzzy inference system (ANFIS) and support vector machine (SVM)) were developed for the prediction of eight IWQIs, including the irrigation water quality index (IWQI), sodium adsorption ratio (SAR), soluble sodium percentage (SSP), potential salinity (PS), residual sodium carbonate index (RSC), and Kelley index (KI). The physicochemical parameters included T°, pH, EC, TDS, K+, Na+, Mg2+, Ca2+, Cl−, SO42−, HCO3−, CO32−, and NO3−, and they were measured in 140 GW wells. The hydrochemical facies of the GW resources were of Ca-Mg-SO4, mixed Ca-Mg-Cl-SO4, Na-Cl, Ca-Mg-HCO3, and mixed Na-Ca-HCO3 types, which revealed silicate weathering, dissolution of gypsum/calcite/dolomite/ halite, rock–water interactions, and reverse ion exchange processes. The IWQI, SAR, KI, and PS showed that the majority of the GW samples were categorized for irrigation purposes into no restriction (67.85%), excellent (100%), good (57.85%), and excellent to good (65.71%), respectively. Moreover, the majority of the selected samples were categorized as excellent to good and safe for irrigation according to the SSP and RSC. The performance of the simulation models was evaluated based on several prediction skills criteria, which revealed that the ANFIS model and SVM model were capable of simulating the IWQIs with reasonable accuracy for both training “determination coefficient (R2)” (R2 = 0.99 and 0.97) and testing (R2 = 0.97 and 0.76). The presented models’ promising accuracy illustrates their potential for use in IWQI prediction. The findings indicate the potential for ML methods of geographically dispersed hydrogeochemical data, such as ANFIS and SVM, to be used for assessing the GW quality for irrigation. The proposed methodological approach offers a useful tool for identifying the crucial hydrogeochemical components for GW evolution assessment and mitigation measures related to GW management in arid and semi-arid environments

Lipid nanocarriers overlaid with chitosan for brain delivery of berberine via the nasal route

This research aimed to design, optimize, and evaluate berberine-laden nanostructured lipid carriers overlaid with chitosan (BER-CTS-NLCs) for efficient brain delivery via the intranasal route. The nanostructured lipid carriers containing berberine (BER-NLCs) were formulated via hot homogenization and ultrasonication strategy and optimized for the influence of a variety of causal variables, including the amount of glycerol monostearate (solid lipid), poloxamer 407 (surfactant) concentration, and oleic acid (liquid lipid) amount, on size of the particles, entrapment, and the total drug release after 24 h. The optimal BER-NLCs formulation was then coated with chitosan. Their diameter, in vitro release, surface charge, morphology, ex vivo permeability, pH, histological, and in vivo (pharmacokinetics and brain uptake) parameters were estimated. BER-CTS-NLCs had a size of 180.9 ± 4.3 nm, sustained-release properties, positive surface charge of 36.8 mV, and augmented ex-vivo permeation via nasal mucosa. The histopathological assessment revealed that the BER-CTS-NLCs system is safe for nasal delivery. Pharmacokinetic and brain accumulation experiments showed that animals treated intranasally with BER-CTS-NLCs had substantially greater drug levels in the brain. The ratios of BER brain/blood levels at 30 min, AUCbrain/AUCblood, drug transport percentage, and drug targeting efficiency for BER-CTS-NLCs (IN) were higher compared to BER solution (IN), suggesting enhanced brain targeting. The optimized nanoparticulate system is speculated to be a successful approach for boosting the effect of BER in treating CNS diseases, such as Alzheimer’s disease, through intranasal therapy

Follow up and comparative assessment of IgG, IgA, and neutralizing antibody responses to SARS-CoV-2 between mRNA-vaccinated naïve and unvaccinated naturally infected individuals over 10 months

BackgroundEvidence on the effectiveness of vaccination-induced immunity compared to SARS-CoV-2 natural immunity is warranted to inform vaccination recommendations. AimIn this study, we aimed to conduct a comparative assessment of antibody responses between vaccinated naïve (VN) and unvaccinated naturally infected individuals (NI) over 10 Months. MethodThe study comprised fully-vaccinated naïve individuals (VN; n = 596) who had no history of SARS-CoV-2 infection, and received two doses of either BNT162b2 or mRNA-1273, and naturally infected individuals who had a documented history of SARS-CoV-2 infection and no vaccination record (NI cohort; n = 218). We measured the levels of neutralizing total antibodies (NtAbs), anti-S-RBD IgG, and anti-S1 IgA titers among VN and NI up to ∼10 months from administration of the first dose, and up to ∼7 months from SARS-CoV-2 infection, respectively. To explore the relationship between the antibody responses and time, Spearman's correlation coefficient was computed. Furthermore, correlations between the levels of NtAbs/anti-S-RBD IgG and NtAbs/anti-S1 IgA were examined through pairwise correlation analysis. ResultsUp to six months, VN individuals had a significantly higher NtAb and anti-S-RBD IgG antibody responses compared to NI individuals. At the 7th month, there was a significant decline in antibody responses among VN individuals, but not NI individuals, with a minimum decrease of 3.7-fold (p < 0.001). Among VN individuals, anti-S1 IgA levels began to decrease significantly (1.4-fold; p = 0.007) after two months, and both NtAb and S-RBD IgG levels began to decline significantly (NtAb: 2.0-fold; p = 0.042, S-RBD IgG: 2.4-fold; p = 0.035) after three months. After 10 months, the most significant decline among VN individuals was observed for S-RBD-IgG (30.0-fold; P < 0.001), followed by NtAb (15.7-fold; P < 0.001) and S-IgA (3.7-fold; P < 0.001) (most stable). Moreover, after 5 months, there was no significant difference in the IgA response between the two groups. ConclusionThese findings have important implications for policymakers in the development of vaccination strategies, particularly in the consideration of booster doses to sustain long-lasting protection against COVID-19.This work was made possible by WHO grant number COVID-19-22-43 and grant number UREP28-173-3-057 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors

Induction of apoptosis in cancer cells by NiZn ferrite nanoparticles through mitochondrial cytochrome C release

The long-term objective of the present study was to determine the ability of NiZn ferrite nanoparticles to kill cancer cells. NiZn ferrite nanoparticle suspensions were found to have an average hydrodynamic diameter, polydispersity index, and zeta potential of 254.2±29.8nm, 0.524 ±0.013, and -60±14mV, respectively. We showed that NiZn ferrite nanoparticles had selective toxicity towards MCF-7, HepG2, and HT29cells, with a lesser effect on normal MCF 10A cells. The quantity of Bcl-2, Bax, p53, and cytochrome C in the cell lines mentioned above was determined by colorimetric methods in order to clarify the mechanism of action of NiZn ferrite nanoparticles in the killing of cancer cells. Our results indicate that NiZn ferrite nanoparticles promote apoptosis in cancer cells via caspase-3 and caspase-9, downregulation of Bcl-2, and upregulation of Bax and p53, with cytochrome C translocation. There was a concomitant collapse of the mitochondrial membrane potential in these cancer cells when treated with NiZn ferrite nanoparticles. This study shows that NiZn ferrite nanoparticles induce glutathione depletion in cancer cells, which results in increased production of reactive oxygen species and eventually, death of cancer cells

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London