Susceptible exposed infectious recovered-machine learning for COVID-19 prediction in Saudi Arabia

Susceptible exposed infectious recovered (SEIR) is among the epidemiological models used in forecasting the spread of disease in large populations. SEIR is a fitting model for coronavirus disease (COVID-19) spread prediction. Somehow, in its original form, SEIR could not measure the impact of lockdowns. So, in the SEIR equations system utilized in this study, a variable was included to evaluate the impact of varying levels of social distance on the transmission of COVID-19. Additionally, we applied artificial intelligence utilizing the deep neural network machine learning (ML) technique. On the initial spread data for Saudi Arabia that were available up to June 25th, 2021, this improved SEIR model was used. The study shows possible infection to around 3.1 million persons without lockdown in Saudi Arabia at the peak of spread, which lasts for about 3 months beginning from the lockdown date (March 21st). On the other hand, the Kingdom's current partial lockdown policy was estimated to cut the estimated number of infections to 0.5 million over nine months. The data shows that stricter lockdowns may successfully flatten the COVID-19 graph curve in Saudi Arabia. We successfully predicted the COVID-19 epidemic's peaks and sizes using our modified deep neural network (DNN) and SEIR model

Ozonated saline intradermal injection: promising therapy for accelerated cutaneous wound healing in diabetic rats

IntroductionThe use of ozonized water is gaining importance in medicine due to its effects on hyperglycemia and wound healing mechanisms.MethodsThis experiment was conducted to assess the impacts of intradermal administration of ozonated water on acute skin wound healing in a diabetic rat model. Sixty-four adult male Wistar rats were randomly divided into two groups: an ozonated water group (O3W) and a control group (CG). Experimental diabetes was chemically induced in the rats by the intraperitoneal administration of 60 mg/kg streptozotocin. One week later, full-thickness skin surgical wounds (1 cm2) were created between the two shoulders of the rats under general anesthesia. The wounds were then daily irrigated with normal saline (CG) or intradermally injected with 1 mL of ozonated water at 10 mg/L O3W. Wound healing was evaluated through macroscopic analysis, measuring wound size, diameter, and percentage of contraction rate before wounding and at 3, 7, 9, 12, 14, 18, 21, 24, and 28 days post-wounding. On days 7, 14, 21, and 28 after induction of the wounds, the body weights and blood glucose levels of rats (8 per group) were measured before the rats were euthanized. Moreover, the morphological structure of the tissue, vascular endothelial and transforming growth factor (VEGF and TGF) affinity and gene expression were examined.ResultsThe O3W group had significantly lower blood glucose levels and wound size and gained body weight. Additionally, epithelial vascularization, stromal edema, TGF, and VEGF gene expression significantly improved in the O3W group.DiscussionTherefore, ozonated water has the potential to enhance and promote cutaneous wound healing in diabetic rats

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

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

Vascular hypertrophy-associated hypertension of profilin1 transgenic mouse model leads to functional remodeling of peripheral arteries

Increased mechanical stress/hypertension in the vessel wall triggers the hypertrophic signaling pathway, resulting in structural remodeling of vasculature. Vascular hypertrophy of resistance vessels leads to reduced compliance and elevation of blood pressure. We showed before that increased expression of profilin1 protein in the medial layer of the aorta induces stress fiber formation, triggering the hypertrophic signaling resulting in vascular hypertrophy and, ultimately, hypertension in older mice. Our hypothesis is that profilin1 induced vascular hypertrophy in resistance vessels, which led to elevation of blood pressure, both of which contributed to the modulation of vascular function. Our results showed significant increases in the expression of α1- and β1-integrins (280 ± 6.3 and 325 ± 7.4%, respectively) and the activation of the Rho/Rho-associated kinase (ROCK) II pathway (260 and 350%, respectively, P < 0.05) in profilin1 mesenteric arteries. The activation of Rho/ROCK led to the inhibition of endothelial nitric oxide synthase expression (39 ± 5.4%; P < 0.05) and phosphorylation (35 ± 4.5%; P < 0.05) but also an increase in myosin light chain 20 phosphorylation (372%, P < 0.05). There were also increases in hypertrophic signaling pathways in the mesenteric arteries of profilin1 mice such as phospho-extracellular signal-regulated kinase 1/2 and phospho-c-Jun NH2-terminal kinase (312.15 and 232.5%, respectively, P < 0.05). Functional analyses of mesenteric arteries toward the vasoactive drugs were assessed using wire-myograph and showed significant increases in the vascular responses of profilin1 mesenteric arteries toward phenylephrine, but significant decreases in response toward ROCK inhibitor Y-27632, ACh, sodium nitrite, and cytochalasin D. The changes in vascular responses in the mesenteric arteries of profilin1 mice are due to vascular hypertrophy and the elevation of blood pressure in the profilin1 transgenic mice

Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats

The current study aimed to determine how palm date aqueous fruit extracts (AFE) affected the autistic-like behaviors brought on by valproic acid (VPA) injection, as well as any potential contributions from Sirt-1, oxidative stress, apoptosis, and autophagy. The pregnant Sprague Dawley females were treated with VPA at 12.5th gestation day and pregnant females and their offspring were treated with AFE orally at doses of 4 mg/Kg by gastric gavage for 45 days after birth. The elevated plus-T maze, water maze, and rotarod tests were used to examine autism-like behaviors. At the end of the study, the expression of Nrf2, heme oxygenase (HO-1), Sirt-1, caspase-3 (a marker of apoptosis), LC3 (a marker of autophagy), and NFκB (inflammatory cytokines) were evaluated along with the oxidative stress in brain tissues and the histological changes in the cerebellum and hippocampus. The neurobehavioral assessments significantly declined due to VPA, which also significantly increased oxidative stress in the brain tissues and significantly decreased Nrf2 and HO-1 expression. Additionally, VPA administration caused significant increase in the expression of caspase-3 in the cerebellar cortex, not in the hippocampus; LC3 and NFκB in the hippocampus, not in the cerebellar cortex; and significant reduction in the expression of Sirt-1 in the hippocampus, not in the cerebellum. On the other hand, AFE treatment significantly improved the neurobehavioral changes as well as it improved significantly the oxidative stress and the expression of LC3, NFκB, NrF2, HO-1, and Sirt-1 in the cerebellum and hippocampus. Conclusions: AFE administration might improve the autistic-like symptoms induced by VPA in rats via attenuation of the oxidative stress, upregulation of Nrf2 and HO-1, Sirt-1 and LC3 expression with downregulation of caspase-3, and NFκB expression in the cerebellum and hippocampus