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Several reasons may underlie the dramatic increase in type2 diabetes mellitus. One of these reasons is the genetic basis and variations. Vitamin D receptor polymorphisms are associated with different diseases such as rheumatoid arthritis and diabetes. The aim of this study is to investigate the possible association of two identified mutations ApaI (rs7975232) and TaqI (rs731236). Eighty-nine healthy individuals and Fifty-six Type 2 Diabetic (T2D) patients were investigated using RFLP technique for genotyping and haplotyping as well. The distribution of Apal genotypes was not statistically significant among the control (P=0.65) as well as for diabetic patients (P=0.58). For Taql allele frequencies of T allele was 0.61 where of G allele was 0.39. The frequency distribution of Taql genotypes was not statistically significant among the control (P=0.26) as well as diabetic patients (P=0.17). Relative risk of the allele T of Apa1 gene is 1.28 and the odds ratio of the same allele is 1.53, while both estimates were < 1.0 of the allele G. Similarly, with the Taq1 gene the relative risk and the odds ratio values for the allele T are 1.09 and 1.27 respectively and both estimates of the allele C were 0.86 for the relative risk and 0.79 for the odds ratio. The pairwise linkage disequilibrium between the two SNPs Taq1/apa1 was statistically significant in control group (D = 0.218, D' = 0.925 and P value < 0.001) and similar data in diabetic groups (D = 0.2, D' = 0.875 and P value < 0.001). These data suggest that the T allele of both genes Apa1 and Taq1 is associated with the increased risk of type 2 diabetes. We think that we need a larger number of volunteers to reach a more accurate conclusion. Resumo Várias razões podem estar subjacentes ao aumento dramático da diabetes mellitus tipo 2. Um desses motivos é a base genética e variações. Os polimorfismos do receptor da vitamina D estão associados a diferentes doenças, como artrite reumatoide e diabetes. O objetivo deste estudo é investigar a possível associação de duas mutações identificadas ApaI (rs7975232) e TaqI (rs731236). Oitenta e nove indivíduos saudáveis e 56 pacientes com diabetes tipo 2 (T2D) foram investigados usando a técnica RFLP para genotipagem e haplotipagem também. A distribuição dos genótipos Apal não foi estatisticamente significativa entre o controle (P = 0,65), bem como para os pacientes diabéticos (P = 0,58). Para as frequências do alelo Taql, o alelo T foi de 0,61, onde o alelo G foi de 0,39. A distribuição de frequência dos genótipos Taql não foi estatisticamente significativa entre o controle (P = 0,26), bem como os pacientes diabéticos (P = 0,17). O risco relativo do alelo T do gene Apa1 é 1,28 e a razão de chances do mesmo alelo é 1,53, enquanto ambas as estimativas foram < 1,0 do alelo G. Da mesma forma, com o gene Taq1, os valores de risco relativo e razão de chances para o alelo T são 1,09 e 1,27, respectivamente, e ambas as estimativas do alelo C foram de 0,86 para o risco relativo e 0,79 para o odds ratio. O desequilíbrio de ligação par a par entre os dois SNPs Taq1 / apa1 foi estatisticamente significativo no grupo de controle (D = 0,218, D' = 0,925 e valor P < 0,001) e dados semelhantes em grupos diabéticos (D = 0,2, D' = 0,875 e valor P < 0,001). Esses dados sugerem que o alelo T de ambos os genes Apa1 e Taq1 está associado ao aumento do risco de diabetes tipo 2. Achamos que precisamos de um número maior de voluntários para chegar a uma conclusão mais precisa.

Fast-track construction projects that begin with inadequate design information have become more common in response to a rising construction industry demand. Fast-tracking shortens project duration while increasing rework. To meet project deadlines while minimising rework, specialists must select the best fast-tracking strategy. As a result, a questionnaire was developed to assess the success characteristics of fast-track construction and to provide constraints for these features and variables in national construction projects. National construction projects address specific government needs or investments to maximise the national return. The survey limited these factors by specifying maximum and minimum percentages. These percentages were chosen to expedite project building. The period in national projects varies from that of the typical construction approach to the shortest time that can be achieved with a plan. Cost and quality are within 20 and 10% of those of national project traditional construction methods, respectively. The best setting for various construction projects is determined by these proportions. It is preferable to use these percentages as a reference to complete construction projects within the shortest time, with the highest quality and at the lowest cost. This questionnaire was completed by 211 building experts.

Background: Hypertension acquired in paediatric critical patients is a recognised challenge, with variable reported frequency. Pain, agitation, and/or medications such as beta stimulants and corticosteroids are well-known risk factors. Sympathomimetics in septic patients can cause high blood pressure, especially with unobserved haemodynamic monitors. Beyond haemodynamic factors, several endocrinal-metabolic factors – including catecholamines, insulin, renin, angiotensin, the aldosterone system, and sodium consumption – may contribute to the left ventricular growth. It is well known that the sympathetic tone has a trophic effect on the heart muscle. Method: A prospective cohort study was conducted during the year 2021. The children were divided into two groups: those who were critically ill with paediatric intensive care unit-acquired hypertension (n = 59) and those without paediatric intensive care unit-acquired hypertension (n = 62). We used the American Academy of Pediatrics’ 2017 definition of hypertension to diagnose paediatric intensive care unit-acquired hypertension. Measurement of cardiac output and systemic vascular resistance was performed by cardiometry. Left ventricular myocardial performance and left ventricular mass index were measured by bedside echocardiography at the onset of hypertension diagnosis. Results: Critically ill children with acquired hypertension had a higher cardiac index (p = 0.0001), systemic vascular resistance index ( Conclusion: Both myocardial performance and left ventricle mass index increased in critically ill children with paediatric intensive care unit-acquired hypertension.

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can involve any organ system. SLE often involves the musculoskeletal system to varying degrees and it is frequently joints of the hands that are most likely to give discomfort to patients. Objectives: To assess by ultrasound the presence of joint inflammation in patients with juvenile Systemic Lupus Erythematosus (JSLE) not complaining of painful joints of the hand and wrist (asymptomatic), and to compare the findings with those in JSLE patients complaining of painful hand and wrist joints (symptomatic) and in healthy controls. Methods: This was a cross-sectional case control study on 37 JSLE patients. Thirty were asymptomatic for joint complaint. Ultrasound examination of wrists and joints of both hands, 11 joints in each hand, to assess synovial hypertrophy, effusion and pathological vascularization [using power Doppler] (PD), and were given a score of 0-3. Patients were compared with 8 healthy controls. Results: Ultrasound abnormalities (synovial hypertrophy and increased vascularity) were detected in 22/30 of the asymptomatic patients (73.3%) and in all 7 symptomatic patients (100%). In asymptomatic children, 29 joints were affected (4.4% of all joints), compared to 13 joints in the symptomatic patients (8.4% of all joints). Synovitis score was mild or moderate (1 or 2) in both symptomatic and asymptomatic patients, with all showing increased vascularity. In the control group, 5 joints (2.8% of all joints) showed synovial hypertrophy but no increased vascularity. Conclusion: Increased vascularity (PD more than 0) is a more reliable indicator of inflammation than synovial hypertrophy which may be detected in healthy individuals.

Background: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. Design: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (e.g., severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The two independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the two co-primary outcomes. Summary: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery. Population Health Research Institute

Deep learning algorithms are able to automatically handle point clouds over a broad range of 3D imaging implementations. They have applications in advanced driver assistance systems, perception and robot navigation, scene classification, surveillance, stereo vision, and depth estimation. According to prior studies, the detection of objects from point clouds of a 3D dataset with acceptable accuracy is still a challenging task. The Point-Pillars technique is used in this work to detect a 3D object employing 2D convolutional neural network (CNN) layers. Point-Pillars architecture includes a learnable encoder to use Point-Nets for learning a demonstration of point clouds structured with vertical columns (pillars). The Point-Pillars architecture operates a 2D CNN to decode the predictions, create network estimations, and create 3D envelop boxes for various object labels like pedestrians, trucks, and cars. This study aims to detect objects from point clouds of a 3D dataset by Point-Pillars neural network architecture that makes it possible to detect a 3D object by means of 2D convolutional neural network (CNN) layers. The method includes producing a sparse pseudo-image from a point cloud using a feature encoder, using a 2D convolution backbone to process the pseudo-image into high-level, and using detection heads to regress and detect 3D bounding boxes. This work utilizes an augmentation for ground truth data as well as additional augmentations of global data methods to include further diversity in the data training and associating packs. The obtained results demonstrated that the average orientation similarity (AOS) and average precision (AP) were 0.60989, 0.61157 for trucks, and 0.74377, 0.75569 for cars., Алгоритми глибокого навчання дозволяють автоматично обробляти хмари точок у широкому діапазоні реалізацій тривимірної візуалізації. Вони застосовуються в сучасних системах допомоги водієві, в області сприйняття та навігації роботів, класифікації сцен, спостереження, стереобачення та оцінки глибини. Згідно з попередніми дослідженнями, виявлення об'єктів з хмар точок тривимірного набору даних з прийнятною точністю все ще є складним завданням. У роботі використовується метод Point-Pillars для виявлення тривимірного об'єкта з використанням шарів двовимірної згорткової нейронної мережі (CNN). Архітектура Point-Pillars включає навчальний кодувальник для використання Point-Nets для навчання демонстрації хмар точок, структурованих вертикальними стовпцями (pillars). Архітектура Point-Pillars використовує двовимірну CNN для декодування прогнозів, створення оцінок мережі та тривимірних оболонок для позначення різних об'єктів, таких як пішоходи, вантажівки та легкові автомобілі. Метою даного дослідження є виявлення об'єктів із хмар точок тривимірного набору даних за допомогою архітектури нейронної мережі Point-Pillars, що дозволяє виявляти тривимірний об'єкт за допомогою шарів двовимірної згорткової нейронної мережі (CNN). Даний метод включає в себе отримання розрідженого псевдозображення з хмари точок за допомогою кодувальника ознак, використання магістралі двовимірної згортки для обробки псевдозображення у високорівневе та використання детекторних головок для регресії і виявлення тривимірних обмежуючих рамок. У роботі використовується доповнення до даних підсупутникових спостережень, а також додаткові доповнення до глобальних методів збору даних для включення подальшої різноманітності в пакети даних навчання та ідентифікації. Отримані результати показали, що середня подібність орієнтації (AOS) та середня точність (AP) склали 0,60989, 0,61157 для вантажних автомобілів та 0,74377, 0,75569 для легкових автомобілів.

Background: Microbial keratitis (MK) is caused by bacteria, fungi, and protozoa. It is very important to differentiate between these three causative microorganisms very early as they differ in their treatment, and some of these microorganisms, like Pseudomonas aeurogenosa, may result in eye perforation within 72 hours .The purpose of this study was to evaluate impression cytology smear to be used as a guide for early accurate treatment of cases. This study was conducted on 80 patients suspected of having MK. A corneal smear was taken with impression cytology paper (a non-invasive technique) and transported to the microbiology laboratory for examination. Results: The IC smear examination results were as follows: 30 (37.5%) were Aspergillus fungus, 14 (17.5%) were Acanthamoeba, 15 (18.75%) were Gram-negative bacilli, 4 (5%) were Staphylococci, 1 (1.25%) was Streptococci, 14 (17.5%) were both Gram-negative bacilli and Aspergillus fungus, and 2 (2.5%) were both Staphylococci and Aspergillus fungus. There was no significant difference between the diagnosis of MK by the culture method and the IC smear method. Conclusion: The impression cytology smear can be used as guide for early treatment of MK.

BACKGROUND: The 69th World Health Assembly endorsed the global health sector strategy on viral hepatitis to eliminate viral hepatitis as a public health threat by 2030. Achieving and measuring the 2030 targets requires a substantial increase in the capacity to test and treat viral hepatitis infections and a mechanism to monitor the progress of hepatitis elimination. This study aimed to identify the gaps in data availability or quality and create a new mechanism to monitor the progress of hepatitis elimination. METHODS: In 2020, using a questionnaire, we collected empirical, systematic, modelled, or surveyed data-reported by WHO country and WHO regional offices-on indicators of progress towards elimination of viral hepatitis, including burden of infection, incidence, mortality, and the cascade of care, and validated these data. FINDINGS: WHO received officially validated country-provided data from 130 countries or territories, and used partner-provided data for 70 countries or territories. We estimated that in 2019, globally, 295·9 million (3·8%) people were living with chronic hepatitis B virus (HBV) infection and 57·8 million (0·8%) people were living with chronic hepatitis C virus (HCV) infection. Globally, there were more than 3·0 million new infections with HBV and HCV and more than 1·1 million deaths due to the viruses in 2019. In 2019, 30·4 million (95% CI 24·3-38·0) individuals living with hepatitis B knew their infection status and 6·6 million (5·3-8·3) people diagnosed with hepatitis B received treatment. Among people with HCV infection, 15·2 million (95% CI 12·1-19·0) had been diagnosed between 2015 and 2019, and 9·4 million (7·5-11·7) people diagnosed with hepatitis C infection were treated with direct-acting antiviral drugs between 2015 and 2019. INTERPRETATION: There has been notable global progress towards hepatitis elimination. In 2019, 30·4 million (10·3%) people living with hepatitis B knew their infection status, which was slightly higher than in 2015 (22·0 million; 9·0%), and 6·6 million (22·7%) of those diagnosed with hepatitis B received treatment, compared with 1·7 million (8·0%) in 2015. Mortality from hepatitis C has declined since 2019, driven by an increase in HCV treatment ten times that of the strategy baseline. However, an estimated 89·7% of HBV infections and 78·6% of HCV infections remain undiagnosed. A new global strategy for 2022-30, based on these new estimates, should be implemented urgently to scale up the screening and treatment of viral hepatitis. FUNDING: World Health Organization.

Background and Aim: Esophageal obstruction is a common occurrence and a serious condition in camels. This study aimed to assess the effects of mineral deficiency on esophageal obstruction rates in dromedary camels and describe their clinical presentation and treatment outcomes. Materials and Methods: Twenty-eight camels were allocated to two groups. Group 1 (control) was composed of 10 sound camels. Group 2 included 18 camels with esophageal obstruction which were based on clinical and imaging evaluations. Hematobiochemical examinations in control and affected camels were compared and statistically analyzed. Results: In camels with esophageal obstruction when compared with controls, hematological analyses showed significant increases (p < 0.05) in neutrophils, lymphocytes, and monocytes, along with significantly decreased total white blood counts. Aspartate transaminase, alanine transaminase, alkaline phosphatase, creatine phosphokinase, glucose, albumin, creatinine, and blood urea nitrogen concentrations were significantly higher in affected camels when compared with controls. Furthermore, gamma-glutamyl transferase, globulin, sodium, chloride, cobalt, iron, manganese, and selenium concentrations were significantly reduced. Affected camels were treated by stomach tube or surgery and were completely recovered, except for one camel with an esophageal fistula. Conclusion: A lack of trace elements could have a significant role in esophageal obstruction in dromedaries. Clinical, ultrasonographic, and hematobiochemical evaluations are useful for the accurate diagnosis, prognosis, and treatment of esophageal obstruction in camels. Keywords: animals, diagnostic imaging, esophagus, fistula, pathology.

While the potential of biochar (BC) to immobilize potentially toxic elements (PTEs) in contaminated soils has been studied and reviewed, no review has focused on the potential use of BC for enhancing the phytoremediation efficacy of PTE-contaminated soils. Consequently, the overarching purpose in this study is to critically review the effects of BC on the mobilization, phytoextraction, phytostabilization, and bioremediation of PTEs in contaminated soils. Potential mechanisms of the interactions between BC and PTEs in soils are also reviewed in detail. We discuss the promises and challenges of various approaches, including potential environmental implications, of BC application to PTE-contaminated soils. The properties of BC (e.g., surface functional groups, mineral content, ionic content, and π-electrons) govern its impact on the (im)mobilization of PTEs, which is complex and highly element-specific. This review demonstrates the contrary effects of BC on PTE mobilization and highlights possible opportunities for using BC as a mobilizing agent for enhancing phytoremediation of PTEs-contaminated soils.

In this study, the soil has been numerically modeled as the Mohr-Columb model because it is simple to capture essential features of soil behavior. Plaxis 2D software program has been used for modeling. The dynamic analyses depend on some data, such as grain size gradation for materials, stiffness and water level. This data has been used in the calculation process. Simple applications have been chosen to calculate the relations. The program computes entered data automatically. Earthquakes result in dynamic loading on soil which has a significant effect on the soil properties. The model is formed of five soil layers. Sands and mud deposits covered the area and Delta also. Some of the study results can be estimated by using the modeling method. The applied load value is 100 kN/m2. The amplification factor (S %) to the soil in the study area is 108 % when soil is without the foundation load and 150 % when soil with foundation load. Thus, the soil is classified as type – D (Moderate) and no liquefaction is expected in the results, but subduction or landslide, so piling foundations are recommended within the area of study. As well, numerical modeling is recommended in several locations in Egypt to obtain suitable areas for the foundation constructions.

Autophagy is a cellular response to diverse stresses within tumor microenvironment (TME) such as hypoxia. It enhances cell survival and triggers resistance to therapy. This study investigated the prognostic importance of HIF-1α and miR-210 in triple negative breast cancer (TNBC). Also, we studied the relation between beclin-1 and Bcl-2 and their prognostic relevance in triple negative breast cancer. Furthermore, the involvement of hypoxia-related markers, beclin-1 and Bcl-2 in mediating resistance to neoadjuvant chemotherapy (NACT) in TNBC was evaluated. Immunohistochemistry was performed to evaluate HIF-1α, beclin-1 and Bcl-2 expression whereas, miR-210 mRNA was detected by quantitative reverse transcription PCR (q-PCR) in 60 TNBC patients. High HIF-1α expression was related to larger tumors, grade III cases, positive lymphovascular invasion, advanced stage, high Ki-67 and poor overall survival (OS). High miR-210 and negative Bcl-2 expression were related to nodal metastasis, advanced stage and poor OS. High beclin-1 was associated with grade III, nodal metastasis, advanced stage and poor OS. Also, high beclin-1 and negative Bcl-2 were significantly associated with high HIF-1α and high miR-210. High HIF- 1α, miR-210 and beclin-1 as well as negative Bcl-2 were inversely related to pathologic complete response following NACT. High beclin-1 and lack of Bcl-2 are significantly related to hypoxic TME in TNBC. High HIF-1α, miR-210, and beclin-1 expression together with lack of Bcl-2 are significantly associated with poor prognosis as well as poor response to NACT. HIF-1α and miR-210 could accurately predict response to NACT in TNBC.

Introductions Revision surgery because of weight recurrence is performed in 2.5–33% of primary vertical banded gastroplasty (VBG), laparoscopic sleeve gastrectomy (LSG), and gastric band (GB) cases. These cases qualify for revisional Roux-en-Y gastric bypass (RRYGB). Methods This retrospective cohort study analyzed data from 2008 to 2019. A stratification analysis and multivariate logistic regression for prediction modeling compared the possibility of sufficient % excess weight loss (%EWL) ≥ 50 or insufficient %EWL Results A total of 558 patients underwent PRYGB, and 338 underwent RRYGB after VBG, LSG, and GB, and completed 2 years of follow-up. Overall, 32.2% of patients after RRYGB had a sufficient %EWL ≥ 50 after 2 years, compared to 71.3% after PRYGB (p ≤ 0.001). The total %EWL after the revision surgeries for VBG, LSG, and GB was 68.5%, 74.2%, and 64.1%, respectively (p ≤ 0.001). After correcting for confounding factors, the baseline odds ratio (OR) or sufficient %EWL ≥ 50 after PRYGB, LSG, VBG, and GB was 2.4, 1.45, 0.29, and 0.32, respectively (p ≤ 0.001). Age was the only significant variable in the prediction model (p = 0.0016). It was impossible to develop a validated model after revision surgery because of the differences between stratification and the prediction model. The narrative review showed only 10.2% presence of validation in the prediction models, and 52.5% had external validation. Conclusion Overall, 32.2% of all patients after revisional surgery had a sufficient %EWL ≥ 50 after 2 years, compared to PRYGB. LSG had the best outcome in the revisional surgery group in the sufficient %EWL group and the best outcome in the insufficient %EWL group. The skewness between the prediction model and stratification resulted in a partially non-functional prediction model. Graphical Abstract

Lemon balm (Melissa officinals) is one of the most valuable medicinal plants in herbal medicine. Bio-stimulants are likely to gain popularity as an alternative strategy for providing plants with nutrients, vitamins, and hormones that increase yield and quality. Field trials were conducted during two successive seasons, 2017/2018 and 2018/2019, to assess lemon balm's growth and essential oil response to natural plant extracts with various concentrations. Lemon balm plants were exposed to moringa leaf extract (1, 2, 3 %), pomegranate peel extract (0.5, 1, 1.5 %) and banana peel extract (1, 2, 3 %) as a foliar spray. Growth characters (plant height, fresh and dry weights /plant) and chemical contents (NPK and total carbohydrates) were recorded. Moringa extract at 3% surpassed, in most cases, other plant extracts in improving the vegetative growth traits of lemon balm. Banana peel extract was more effective in increasing oil percent than moringa or pomegranate extracts. Besides, all extracts caused increase in N,P,K and carbohydrates over control while they yielded volatile oil without significantly altering the quality.

Purpose The purpose of this study is to investigate the extent of digital surveillance by Arab authorities, which face risks and threats of surveillance, and how journalists seek to press freedom by using tools and techniques to communicate securely. Design/methodology/approach The study used focus group discussions with 14 journalists from Syria, Saudi Arabia, Libya, Yemen, Oman, Jordan and Egypt. While in Egypt, questionnaires were distributed to 199 journalists from both independent and semi-governmental outlets to investigate how Egyptian journalists interpret the new data protection law and its implications for press freedom. Findings The study indicated that journalists from these countries revealed severe censorship by their respective governments, an element inconsistent with the Arab Constitution. The recommendation of the study encourages media organisations to play a more active role in setting policies that make it easier for journalists to adopt and use digital security tools, while Egyptian journalists see the law as a barrier to media independence because it allows the government to exercise greater information control through digital policy and imposes regulatory rules on journalists. Practical implications The study identifies practical and theoretical issues in Arab legislation and may reveal practices of interest to scientists researching the balance between data protection, the right of access to information and media research as an example of contemporary government indirect or “soft” censorship methods. Originality/value To the best of the authors’ knowledge, this paper is one of the first research contributions to analyse the relationships between Arab authoritarians who used surveillance to restrict freedom of the press after the Arab Spring revolutions of 2011 to keep themselves in power as long as they could. In addition, Egypt's use of surveillance under new laws allowed the regimes to install software on the journalists’ phones that enabled them to read the files and emails and track their locations; accordingly, journalists can be targeted by the cyberattack and can be arrested.

Worldwide, populations face significant burdens from neurodegenerative disorders (NDDs), especially Alzheimer's and Parkinson's diseases. Although there are many proposed etiologies for neurodegenerative disorders, including genetic and environmental factors, the exact pathogenesis for these disorders is not fully understood. Most patients with NDDs are given lifelong treatment to improve their quality of life. There are myriad treatments for NDDs; however, these agents are limited by their side effects and difficulty in passing the blood–brain barrier (BBB). Furthermore, the central nervous system (CNS) active pharmaceuticals could offer symptomatic relief for the patient's condition without providing a complete cure or prevention by targeting the disease's cause. Recently, Mesoporous silica nanoparticles (MSNs) have gained interest in treating NDDs since their physicochemical properties and inherent ability to pass BBB make them possible drug carriers for several drugs for NDDs treatment. This paper provides insight into the pathogenesis and treatment of NDDs, along with the recent advances in applying MSNs as fibril scavengers. Moreover, the application of MSNs-based formulations in enhancing or sustaining drug release rate, and brain targeting via their responsive release properties, besides the neurotoxicity of MSNs, have been reviewed.

PURPOSE: The clinical study of fulminant hepatic failure is challenging due to its high mortality and relative rarity, necessitating reliance on pre-clinical models to gain insight into its pathophysiology and develop potential therapies. METHODS AND RESULTS: In our study, the combination of the commonly used solvent dimethyl sulfoxide to the current-day model of lipopolysaccharide/d-galactosamine-caused fulminant hepatic failure was found to cause significantly greater hepatic damage, as indicated by alanine aminotransferase level. The effect was dose-dependent, with the maximum increase in alanine aminotransferase observed following 200 μl/kg dimethyl sulfoxide co-administration. Co-administration of 200 μl/kg dimethyl sulfoxide also remarkably increased histopathological changes induced by lipopolysaccharide/d-galactosamine. Importantly, alanine aminotransferase levels and survival rate in the 200 μl/kg dimethyl sulfoxide co-administration groups were both greater than those in the classical lipopolysaccharide/d-galactosamine model. We found that dimethyl sulfoxide co-administration aggravated lipopolysaccharide/d-galactosamine-caused liver damage by stimulating inflammatory signaling, as indicated by tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) levels. Further, nuclear factor kappa B (NF-kB) and transcription factor activator 1 (STAT1) were upregulated, as was neutrophil recruitment, indicated by myeloperoxidase activity. Hepatocyte apoptosis was also increased, and greater nitro‐oxidative stress was noted, as determined based on nitric oxide, malondialdehyde, and glutathione levels. CONCLUSION: Co-treatment with low doses of dimethyl sulfoxide enhanced the lipopolysaccharide/d-galactosamine-caused hepatic failure in animals, with higher toxicity and greater survival rates. The current findings also highlight the potential danger of using dimethyl sulfoxide as a solvent in experiments involving the hepatic immune system, suggesting that the new lipopolysaccharide/d-galactosamine/dimethyl sulfoxide model described herein could be used for pharmacological screening with the goal to better understand hepatic failure and evaluate treatment approaches.