20 research outputs found
ZOLMITRIPTAN BRAIN TARGETING VIA INTRANASAL ROUTE USING SOLID LIPID NANOPARTICLES FOR MIGRAINE THERAPY: FORMULATION, CHARACTERIZATION, IN-VITRO AND IN-VIVO ASSESSMENT
Objective: Zolmitriptan, a class of antidepressant drugs with poor bioavailability due to its first-pass metabolism. The aim of this study was to improve systemic bioavailability and explore the brain targeting impact of nasal Zolmitriptan (Zol) solid lipid nanoparticles (SLNs) gel for migraine treatment.
Methods: Stearic acid and cholesterol used as solid lipid and lecithin as a surfactant, emulsion solvent evaporation technique was used to produce Zolmitriptan SLNs. (Zol) SLNs were characterized for particle size, percent entrapment efficiency and in vitro drug release. Formula S6 showed greater percent entrapment efficiency (PEE), adequate particle size and sustained drug release behavior. Formula S6 was integrated into HPMC gel (3%) to prepare nasal gel. Zol SLN nasal gel was subjected to histopathological study to ensure brain targeting.
Results: It was observed that all prepared Zol SLNs were in the nano-sized range with a polydispersity index of<0.5. In the cholesterol/lecithin combination, higher PEE%, better stability, and less agglomeration inclination were discovered. Results of the release profiles showed that developed Zol-SLNs were able to release Zolmitriptan in a sustained manner. Histopathological study of the brain tissues showed that Zolmitriptan SLN nasal gel can reach brain cells and localized for 24 h although the hydrophobicity of the target drug.
Conclusion: Intranasal administration of Solid lipid nanostructure of Zolmitriptan through the olfactory pathway in which it travels from the nasal cavity to brain tissue achieved drug targeting potential of about 90% compared with conventional Zolmitriptan tablets. The small particle size helped them to squeeze themselves through the small opening in the olfactory neurons to the brain via different endo-cystic pathways of neuronal cells in nasal tissue membranes
Prevalence and characterization of plasmid-mediated quinolone resistance genes in Proteus species isolated from different patients
Proteus spp. are widely distributed opportunistic pathogens that can cause various human infections. A total of 361 clinical specimens were obtained from patients who were attending to different hospitals in El-Minia governorate, Egypt. Approximately 23 % of the samples belong to Proteus spp. isolates which were obtained from various clinical sources. After biochemical identification, 42.1 % of isolates were found to belong to Proteus vulgaris and 57.8 % to P. mirabilis. The urine samples collected from catheterized patients represented 32.6 % of all the clinical specimens, and the majority of the recorded isolates were Proteus spp. The antibacterial sensitivity of the Proteus spp. was examined using 16 different antibiotics from various families. The most effective antibiotics were Amikacin; Levofloxacin, and Meropenem, recording 68.6 %, 66.2 %, and 62.2 % of the isolates sensitivity to each of these antibiotics, respectively. Using the ureR-based PCR, 48 % of the isolates were identified as P. mirabilis. Moreover, the Qnr genes (i.e., qnrA, qnrB, qnrS, qnrD, and qnrC) and the aac (6')-Ib-cr gene had been identified in 40 % of P. mirabilis isolates. The aims of the study were to investigate the prevalence of Proteus spp. in El-Minia, Egypt; determine the antibacterial susceptibility pattern of these isolates, and characterize the PMQR genes in Proteus spp. Quinolone resistance in P. mirabilis isolates might have been brought on by mechanisms other than qnr and aac (6')-Ib genes. Finally, since Proteus spp. are widespread in the environment; healthcare facilities must uphold stringent sanitation standards to reduce the incidence of the nosocomial infections
The genetic architecture of the human cerebral cortex
The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20
[1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030
The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance
INTRODUCTION
Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic.
RATIONALE
We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs).
RESULTS
Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants.
CONCLUSION
Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century
A hybrid model to predict best answers in question answering communities
Question answering communities (QAC) are nowadays becoming widely used due to the huge facilities and flow of information that it provides. These communities target is to share and exchange knowledge between users. Through asking and answering questions under large number of categories.
Unfortunately there are a lot of issues existing that made knowledge process difficult. One of those issues is that not every asker has the knowledge and ability to select the best answer for his question, or even selecting the best answer based on subjective matters. Our analysis in this paper is conducted on stack overflow community. We proposed a hybrid model for predicting the best answer. The proposed model is consisting of two modules. The first module is the content feature which consists of three types of features; question-answer features, answer content features, and answer-answer features. In the second module we examine the use of non-content feature in predicting best answers by using novel reputation score function. Then we merge both of content and non-content features and use them in prediction. We conducted experiments to train three different classifiers using our new added features. The prediction accuracy is very promising
Effect of Monkeypox Nano-Teaching Sessions versus Self-Learning on Nurses’ Knowledge, Attitude, and Confidence in Disease Diagnosis and Management
Background: Infectious diseases pose a constant threat to public health, necessitating a robust and continually evolving response from healthcare professionals. Despite advancements in medical education, there remains a persistent deficiency in disease-related knowledge among nurses. This study addresses this gap by investigating the impact of nano-teaching sessions compared to self-directed learning on enhancing nurses' knowledge, attitude, and confidence in the diagnosis and management of Monkeypox. Aim: This study aims to assess and compare the effectiveness of nano-teaching sessions and self-learning in improving nurses' knowledge, attitude, and confidence levels regarding mpox diagnosis and management. Methods: In the Quasi experimental study, 50 nurses from clinics at both the Students' University Hospital and Mansoura University colleges, Egypt, were randomly assigned to nano-teaching or self-learning groups. Nano-teaching involved interactive sessions over three months, while the self-learning group received study materials. Pre- and post-intervention assessments measured changes using various tools. Statistical analyses were performed using SPSS for Windows version 20.0 (SPSS, Chicago, IL). Approval was obtained from the Research Ethics Committee at the Faculty of Nursing, Mansoura University, under reference number P.0287. Results: The study involved participants with diverse backgrounds. They primarily relied on the internet for mpox information. Pre-intervention, both study and control groups had low knowledge and confidence levels. Post-intervention, the study group showed significant improvements in knowledge, confidence, attitude, and practice compared to the control. For instance, 88 % of the study group demonstrated high knowledge post-intervention, contrasting with only 22 % in the control (p < 0.001). Correlation analysis revealed strong connections among knowledge, confidence, attitude, and practice, especially post-intervention within the intervention group. Regression analysis highlighted the significant impact of educational level and years of experience on knowledge, confidence, attitude, and practice, underscoring their pivotal role in shaping understanding and behavior concerning mpox. Conclusion: Nano-teaching sessions emerged as a more effective intervention for enhancing nurses' knowledge, attitude, and confidence in Monkeypox diagnosis and management compared to self-learning. The results underscore the importance of innovative educational strategies tailored to the specific needs of healthcare professionals.Recommendations:Based on the study findings, it is recommended that healthcare institutions integrate nano-teaching methodologies into their ongoing education programs. Additionally, further research is warranted to explore the long-term impact of nano-teaching on nurses' clinical practices and patient outcomes
Prevalence of Pseudomonas spp. in Marine Water Fish Intended for Human Consumption
This study aimed at investigation of the prevalence and antimicrobial susceptibility of Pseudomonas spp., in two marine water fish, namely Pagrus, and saurus intended for human consumption. In the current study, Pseudomonas spp., was isolated and identified from two marine water fishes. Fifty Pagrus fish and 50 Saurus (Saurida undosquamis) fish were sampled from fish markets at Sharkia governorate, Egypt. The prevalence rates of Pseudomonas spp. were 84%, and 40% in Pagrus fish, and Saurus respectively. The identified Pseudomonas spp., from Saurus was Pseudomonas aeruginosa (P. aeruginosa), P. fluorescens, P. fragi, P. cepacia, at 20% for each. P. alcaligenes and P. lundensis were recovered at 10%. In Pagrus, the prevalence rates were 31.3%, 56.3%, and 6.2% for P. aeruginosa, P. fluorescens, P. fragi and P. stutzeri. Seven serotypes of P. aeruginosa were identified with the serotypes O11 at the top prevalence (42.8%), and O6, O5, O1, O8 at 19.3% for each. The virulence-associated genes were lasB (Elastase B gene), exoS (Exoenzyme S) and pilB (pili gene) were detected in the recovered P. aeruginosa at 100%, 71.4%, and 28.6%, respectively. The recovered Pseudomonas species had high antimicrobial resistance to erythromycin, amoxicillin, ampicillin and gentamycin at 100%, 88.5%, 65.4%, and 50%, respectively. In conclusion, Pagrus and Saurus fish species are considered as potential sources of multidrug resistant Pseudomonas spp
Impact of Omega-3 Fatty Acids Nano-Formulation on Growth, Antioxidant Potential, Fillet Quality, Immunity, Autophagy-Related Genes and <i>Aeromonas hydrophila</i> Resistance in Nile Tilapia (<i>Oreochromis niloticus</i>)
In modern aquaculture, enriching Nile tilapia’s diet with omega-3 poly-unsaturated fatty acids (PUFAs) not only plays an important role in its general health but also fortifies its fillet with omega-3-PUFAs. However, the major challenge affecting their delivery is their high instability due to oxidative deterioration. Thus, the prospective incorporation of omega-3-PUFAs into nanocarriers can enhance their stability and bioactivity. In this regard, the effect of reformulated omega-3-NPs was investigated on Nile tilapia’s performance, flesh antioxidant stability, immunity, and disease resistance. Four fish groups supplemented with omega-3-PUFAs-loaded nanoparticles (omega-3 NPs) at levels of 0, 1, 2, and 3 g/kg diet and at the end of feeding trial fish challenged with Aeromonas hydrophila. Fish performance (weight gain and feed conversion) was improved in groups supplemented with omega-3-NPs (2 and 3 g/kg diet). The deposition of omega-3-PUFAs in fish flesh elevated with increasing dietary omega-3-NPs. Simultaneously the oxidative markers (H2O2, MDA, and reactive oxygen species) in fish flesh were reduced, especially with higher omega-3-NPs. Post-challenge, downregulation of IL-1β, IL-6, IL-8, TNF-α, and caspase-1 were noticed after dietary supplementation of omega-3-NPs. Moreover, mRNA expression of autophagy-related genes was upregulated while the mTOR gene was downregulated with higher omega-3 NPs levels. Lower expression of A. hydrophila ahyI and ahyR genes were detected with omega-3 NPs supplementation. In conclusion, omega-3-NPs application can fortify tilapia flesh with omega-3-PUFAs and augment its performance, immunity, and disease resistance against Aeromonas hydrophila