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Abstract Background Higher doses of vancomycin are currently prescribed due to the emergence of bacterial tolerance and resistance. This study aimed to evaluate the efficacy and safety of the currently adopted vancomycin dosing guide in pediatric cardiology. Methods This was a single-center prospective cohort study with pediatric cardiac patients, younger than 14 years, from June 2020 to March 2021. The patients received intravenous vancomycin (40 mg/kg/day divided every 6–8 h) according to the department’s vancomycin medication administration guide (MAG) for at least three days. Results In total, 88 cardiac patients were included, with a median age of 0.82 years (IQR: 0.25–2.9), and 51 (58%) received cardiopulmonary bypass surgery (CPB). The majority (71.6%, n = 61) achieved a serum vancomycin level within the therapeutic range (7–20 mg/L). Infants, young children, and children exposed to CPB surgery had an increased incidence of subtherapeutic vancomycin levels, [7 (29.2%); P = 0.033], [13 (54.2%); P = 0.01], and [21 (87.5%); P = 0.009] respectively. After the treatment, 8 (10%) patients had an elevated Serum creatinine (SCr) and 2 (2.5%) developed acute kidney injury (AKI). However, no significant difference was found between the patients developing AKI or an elevated SCr and the group who did not, in terms of clinical, therapeutic, and demographic characteristics, except for the decreased incidence of SCr elevation in patients receiving an ACE inhibitor, [4 (36.4%); P = 0.036]. Conclusion Our institution followed MAG recommendations; however, subtherapeutic serum concentrations were evident in infants, young children, and CPB patients. Strategies to prevent AKI should be investigated, as the possible causes have not been identified in this study.

Traumatic brain injury (TBI), a progressive neurological disease caused by physical injury to the brain tissue, impacting its functions. This study employed metabolomics based on untargeted mass spectrometry method to examine plasma specimens from well-established mouse models with induced TBI (n = 6) and control mice (n = 6). The objective was to assess the metabolomics profile and the associated biochemical pathways in TBI. There was a noticeable segregation between TBI and reference groups (Q2 = 0.342, R2 = 0.993), according to orthogonal partial least square-discriminant analysis, indicating significant difference in metabolic expression. Moreover, 102 metabolites were significantly altered in TBI mice; 59 were upregulated, while 43 were downregulated in TBI mice. Correspondingly, the TBI model showed a significant dysregulation in number of key metabolic pathways, including metabolism of glycerophospholipids, linoleic acid, glycine, serine, threonine, pyrimidine, tryptophan, nicotinate and nicotinamide. Additionally, isoleucyl-asparagine, 2′-deoxyinosine triphosphate, diglycosyl diacylglycerols (25:0/26/2), and phosphatidylethanolamine (24:0/22:4) demonstrated excellent performance for TBI detection with an area under the curve ≥ 0.8. This study identified putative plasma biomarkers of TBI and highlighted the dysregulated biochemical pathways, providing valuable clinical insights into TBI research.

Objectives: The aim of the research was to study the impact of the Deir Ezzor revolution and its introductions in Iraq on the twentieth revolution in Iraq, which was the idea of a long time ago, especially for British mismanagement and the severity of taxes and poor economic and social conditions as well as the promises made by Britain to the independence of Iraq, all factors encouraged Iraqis to carry out the revolution, as the Iraqi leaders in Syria had a major role in the trend towards the revolution, the Iraqis noted that the occupation was serious in looting the country's bounties and that Freedom and independence were just slogans launched by Britain to calm the already volatile situation, and therefore the Iraqis embarked on a comprehensive revolution to change the turbulent situation and the policy of occupation. Methodology: The study relied on the historical research method to analyze the events and factors they derived from the Deir Ezzor revolution to work on mobilizing Iraqis to carry out the revolution, which was the nucleus of the city of Tal Afar and the western regions of Iraq, as well as the use of the historical descriptive approach to describe the battles that took place between the Iraqis and the British occupation forces. Results: The study concluded that the launch of the spark of the revolution from Deir Ezzor towards all Iraqi territory had a major role in the multiple uprisings, whether in Tal Afar or in the western regions of Iraq, which received wide support from all leaders and clans to resist the British occupation, which reneged on all the covenants and promises he made during his occupation of Iraq, and thus led to the twentieth revolution, which gave lessons to generations represented by sacrifice and redemption for the sake of love of the homeland and not to succumb to the whims of colonialism in all The Tal Afar uprising achieved successive successes within days and worried the British side despite its failure, and the western regions of Iraq achieved clear progress against the British occupation, which was represented by the killing of Colonel Lajman, one of the most prominent British leaders, which greatly affected Britain's military reputation, as well as the continuous withdrawals of the British military sectors from western Iraq to the fierce resistance shown by the Iraqis against the British occupation. Recommendations: The study recommends the need to intensify research and studies that shed light on the uprisings that took place before the twentieth revolution in Iraq, as well as studying the external factors that had a direct impact on the launch of the twentieth revolution in Iraq, especially the impact of the Deir Ezzor revolution in Syria

In an era of cost pressure, substituting generic drugs represents one of the main cost-containment strategies of healthcare systems. Despite the obvious financial benefits, in a minority of cases, substitution may require caution or even be contraindicated. In most jurisdictions, to obtain approval, the bioequivalence of generic products with the brand-name equivalent needs to be shown via bioavailability studies in healthy subjects. Rare diseases, defined as medical conditions with a low prevalence, are a group of heterogenous diseases that are typically severe, disabling, progressive, degenerative, and life-threatening or chronically debilitating, and disproportionally affect the very young and elderly. Despite these unique features of rare diseases, generic bioequivalence studies are typically carried out with single doses and exclude children or the elderly. Furthermore, the excipients and manufacturing processes for generic/biosimilar products can differ from the brand products which may affect the shelf-life of the product, its appearance, smell, taste, bioavailability, safety and potency. This may result in approval of generics/biosimilars which are not bioequivalent/comparable in their target population or that meet bioequivalence but not therapeutic equivalence criteria. Another concern relates to the interchangeability of generics and biosimilars which cannot be guaranteed due to the phenomenon of biocreep. This review summarizes potential concerns with generic substitution of orphan drugs and discusses potentially problematic cases including narrow therapeutic index drugs or critical conditions where therapeutic failure could lead to serious complications or even death. Finally, we put forward the need for refining regulatory frameworks, with emphasis on Saudi Arabia, for generic substitution and recent efforts toward this direction.

William Chelepy, Saif Yousif, Paul Robert Nichols Department of Neurosurgery, Princess Alexandra Hospital, Brisbane, Queensland, AustraliaCorrespondence: William Chelepy, Tel +614 33308553, Email william.chelepy@health.qld.gov.auAbstract: Intraosseous schwannoma is a rare diagnosis, particularly so in the skull. Accordingly, little data exists to unify common features of this disease. Here, we present the fourth known case of a primary intraosseous schwannoma of the frontal bone: a 46-year-old male with severe, progressive headache and an osteolytic frontal bone lesion. Gross total resection of the lesion was performed with excellent clinical outcome. Histological analysis confirmed the diagnosis. The limited existing literature on this topic was reviewed to identify emerging trends surrounding presenting symptoms and treatment. Early literature suggests symptoms are often nonspecific, except for lesions of the petrous apex. No cases of recurrence have been demonstrated after gross total resection, though incomplete resection has been associated with recurrence. This diagnosis appears to be becoming a more often-considered differential for osteolytic, expansile skull lesions.Keywords: schwannoma, intraosseous, frontal bone, skull

Opioid-related deaths are attributed to overdoses, and fentanyl overdose has been on the rise in many parts of the world, including the USA. Glutamate transporter 1 (GLT-1) has been identified as a therapeutic target in several preclinical models of substance use disorders, and β-lactams effectively enhance its expression and function. In the current study, we characterized the metabolomic profile of the nucleus accumbens (NAc) in fentanyl-overdose mouse models, and we evaluated the protective effects of the functional enhancement of GLT-1 using β-lactams, ceftriaxone, and MC-100093. BALB/c mice were divided into four groups: control, fentanyl, fentanyl/ceftriaxone, and fentanyl/MC-100093. While the control group was intraperitoneally (i.p.) injected with normal saline simultaneously with other groups, all fentanyl groups were i.p. injected with 1 mg/kg of fentanyl as an overdose after habituation with four repetitive non-consecutive moderate doses (0.05 mg/kg) of fentanyl for a period of seven days. MC-100093 (50 mg/kg) and ceftriaxone (200 mg/kg) were i.p. injected from days 5 to 9. Gas chromatography–mass spectrometry (GC-MS) was used for metabolomics, and Western blotting was performed to determine the expression of target proteins. Y-maze spontaneous alternation performance and the open field activity monitoring system were used to measure behavioral manifestations. Fentanyl overdose altered the abundance of about 30 metabolites, reduced the expression of GLT-1, and induced the expression of inflammatory mediators IL-6 and TLR-4 in the NAc. MC-100093 and ceftriaxone attenuated the effects of fentanyl-induced downregulation of GLT-1 and upregulation of IL-6; however, only ceftriaxone attenuated fentanyl-induced upregulation of TRL4 expression. Both of the β-lactams attenuated the effects of fentanyl overdose on locomotor activities but did not induce significant changes in the overall metabolomic profile. Our findings revealed that the exposure to a high dose of fentanyl causes alterations in key metabolic pathways in the NAc. Pretreatment with ceftriaxone and MC-100093 normalized fentanyl-induced downregulation of GLT-1 expression with subsequent attenuation of neuroinflammation as well as the hyperactivity, indicating that β-lactams may be promising drugs for treating fentanyl use disorder.

Scientific evidences reported the deleterious effect of cigarette smoking or passive smoking on brain health particularly cognitive functions, blood–brain barrier (BBB) permeability, up-regulation of inflammatory cascades, and depletion of the antioxidant system. These combined effects become more progressive in the events of stroke, traumatic brain injury (TBI), and many other neurodegenerative diseases. In the current study, we investigated the long-term administered therapeutic potential of quercetin in ameliorating the deleterious neurobiological consequences of chronic tobacco smoke exposure in TBI mice. After exposure to 21 days of cigarette smoke and treatment with 50 mg/kg of quercetin, C57BL/6 mice were challenged for the induction of TBI by the weight drop method. Subsequently, a battery of behavioral tests and immunohistochemical analyses revealed the beneficial effect of quercetin on the locomotive and cognitive function of TBI + smoked group mice (p

A novel nano-catalyst based on iron oxide (MnO2/Fe2O3) was developed to promote wet oxidation of phenol. MnO2 was doped in Fe2O3 matrix to prepare composite nano-catalyst with different doping percentage (0, 2 and 5%). The catalytic phenol oxidation was conducted under different reaction temperatures and residence times. To evaluate the optimal kinetic parameters aiming to maximize phenol removal under the optimal conditions for the catalytic wet phenol oxidation process, modeling was applied on the batch reactor using the novel synthesis nano-catalyst (MnO2/Fe2O3) and the model developed was fed with the experimental data. gPROMS package was used to model the process of phenol oxidation and to optimize the experimental data. The error predicted between the simulated and experimental data was less than 5%. The optimal operating conditions were 294 min residence time, 70oC reaction temperature, and 764 ppm initial concentration of phenol over the prepared 5% MnO2/Fe2O3. Running of wet oxidation of phenol under the optimal operating conditions resulted in 98% removal of phenol from refinery wastewater.

ObjectiveThis study sought to understand the mental health issues, mental health support and efficacy of that support among university students.ParticipantsAll students enrolled in a College of Arts and Sciences at one mid-size university received an email that contained a link to an anonymous, online questionnaire developed and disseminated through PsychData. 162 students completed the questionnaire.MethodsMixed methods: Data was summarized using descriptive analysis, testing for significance, testing for differences, and content analysis.ResultsParticipants reported high levels of anxiety (76%) and depression (65%). Results indicated that participant demographics were associated with types of mental access, and support. Unexpected results included lack of knowledge or information on cost, and how to access mental health services hindered access for participants, and although telehealth was the most widely used support, in contrast to other studies, participants indicated a preference for face-to-face mental health services.ConclusionResults highlight the need for improving communication about and access to mental health services in higher education Recommendations and implications for policy and support services are provided.

Background: The association of hyponatremia with vasopressin therapy in children is controversial. We aimed to evaluate the incidence and severity of hyponatremia associated with the administration of vasopressin in critically ill pediatric patients. Methods: This retrospective cross-sectional study included children younger than 14 years who were admitted to the pediatric or pediatric cardiac intensive care units and received vasopressin for at least 24 h. Results: In total, 176 critically ill pediatric patients were enrolled, with a median age of 22 days (7.3–146). The mean sodium level was notably decreased from 143.5 mEq/L ± 7.15 at the baseline to 134.3 mEq/L ± 7.7 at the 72-hour measurement after the initiation of vasopressin and varied significantly at all intervals from the baseline measurement (P

The research deals with the role of Syrian women during the French Mandate. Syrian women did not neglect the revolutions and associations, but tried and made all efforts to get rid of the French Mandate. The Syrian woman stood with the man and supported him in his wars against the French colonialist. In addition to the associations that it founded until independence was achieved in 1946, many politicians supported the participation of women in political and social life, as Syrian women had a great role, whether during the Ottoman era, the Faisal era, or during the mandate, as they actively participated with Her brother, the man, was in the fight against French colonialism and demanded freedom and independence like men. She also participated socially through forums and associations in the fight against colonialism or through education, which she considered a weapon in the face of the French enemy until Syria gained its independence in 1946, in which Syrian women had a role in that.

Background: An asthma exacerbation is an anticipated sudden worsening of the disease severity, which usually does not respond to conservative therapy. The management of asthma depends on the severity of the disease symptoms, which includes an inhaled corticosteroid (ICS) and a bronchodilator. This study aimed to assess the efficacy of combining a long-acting B2-agonist (LABA) with ICS, compared to ICS alone, to reduce the incidence of asthma exacerbations in pediatric patients, diagnosed with severe persistent asthma. Methods: A retrospective analysis of the medical records was conducted for 586 children, admitted to the Emergency Department (ED) at King Abdullah Specialized Children Hospital in Riyadh, Saudi Arabia, for the management of severe persistent asthma symptoms, from January 2016 to September 2019. Results: The majority (n = 480, 81.9%) of the patients received fluticasone (Flovent)® as the standard of care ICS treatment for controlling asthma, and a small proportion (n = 106, 18.1%) were treated with a combination of LABA and ICS. A significant increase in the frequency of recurrent asthma exacerbation episodes occurred in the group receiving ICS alone (98.5%), compared to 67.0% in the combination group (p

Background: There is conflicting evidence regarding the effect of asthma and its different therapeutic options on COVID-19 severity and the clinical outcomes. Aim: This study aimed to investigate the relationship between using inhaled corticosteroids (ICS) by asthmatic patients and the severity of COVID-19. Materials and methods: This retrospective observational study was conducted from March 15 to October 23, 2020 and included data of all COVID-19 asthmatic patients (n = 287) at King Abdulaziz Medical City. Twelve patients were excluded due to poor medication history documentation or using ICS for non-asthma indication. Ordinal logistic regression was used to determine the clinical variables that affect COVID-19 severity. The clinical outcomes of ICS and non-ICS users were compared. Results: Of the sample (n = 275), 198 (72%) were using ICS therapy. No significant difference was found between ICS and non-ICS users in disease severity (P = 0.12), mortality (P = 0.45), ICU admission (P = 0.78), and the occurrence of complications. However, the number of days on ventilation were significantly increased in ICS users (P = 0.006). Being prescribed the ICS/LABA combination (adj OR: 0.72 [0.15,1.2]; P = 0.021), being hypertensive (adj OR: 0.98 [0.28,1.6]; P = 0.006), having cancer (adj OR: 1.49 [0.12, 2.8]; P = 0.033), or having diabetes (adj OR: 0.75 [0.09, 1.4]; P = 0.024) could not increase the risk for more severe disease. Conclusion: Overall, ICS therapy did not alter the COVID-19 severity or mortality in asthmatic patients. The continued use of ICS during the pandemic should be encouraged to prevent asthma exacerbations.

The amount and characteristics of wastewater produced are determined by the process configuration. Refineries produce contaminated effluent of phenol levels up to 300–600 mg/L. For wet oxidation of phenol, multiloading and multifunctional MnO2/Fe2O3 were utilized in the present study to develop a cost-effective nanocatalyst to clean refinery wastewater at a high rate of phenol removal and a long lifetime of catalyst activity. The catalysts were doped with two different loading of 2% and 5% of MnO2. For full oxidation of carcinogenic phenolic compounds into the unharmful CO2 and H2O, the catalytic breakdown of H2O2 as an oxidation agent produces oxygen bubbles and hydroxyl radicals. The prepared catalysts were evaluated in a batch reactor and the results showed that the loading of MnO2 over the Fe2O3 has a positive impact on the oxidation of phenol as increasing the MnO2 loading increased the rate of phenol oxidation and did not result in the deactivation of the available catalyst pores. The highest conversion of phenol achieved was 94 wt% at 80 min and 75 °C over the 5% MnO2/Fe2O3 catalyst. Also, it was observed that the prepared catalyst sustained the deactivation for several cycles of catalytic oxidation of phenol as the catalyst activity remained almost constant as time proceeds to 120 min.

A reliable and successful micropropagation protocol was developed for pepino plant (Solanum muricatum Aiton) from nodal segment explants grown on MS medium. The best values of shoot multiplication traits were recorded from the addition of 3 mg.l-1 kinetin by producing 2.3 shoots/explant, 3.6 cm and 9.6 leaves/ explant which was significantly superior upon the addition of BA at the same levels. In case of adding 3 mg.l-1 kinetin, the best root formation attributes were achieved from the use of 0.2 mg.l-l IAA that resulted a maximum number of roots (14.33 roots/ explant). The longest root length (15.33 cm) was achieved when 0.3 mg.l-l IAA was used. A 100% rooting percentage was recorded from the all tested auxins including IAA, IBA and NAA. The gradually moved plantlets from the heterotrophic phase in the lab to the autotrophic phase in the greenhouse showed 100% success. The plantlets did not show any abnormal growth or morphological changes. It is concluded that this important plant can be easily propagated by tissue culture technique through a reliable micropropagation protocol.

Opioid-related deaths are attributed to overdoses, and fentanyl overdose has been on the rise in many parts of the world, including the USA. Glutamate transporter 1 (GLT-1) has been identified as a therapeutic target in several preclinical models of substance use disorders, and β-lactams effectively enhance its expression and function. In the current study, we characterized the metabolomic profile of the nucleus accumbens (NAc) in fentanyl-overdose mouse models, and we evaluated the protective effects of the functional enhancement of GLT-1 using β-lactams, ceftriaxone, and MC-100093. BALB/c mice were divided into four groups: control, fentanyl, fentanyl/ceftriaxone, and fentanyl/MC-100093. While the control group was intraperitoneally (i.p.) injected with normal saline simultaneously with other groups, all fentanyl groups were i.p. injected with 1 mg/kg of fentanyl as an overdose after habituation with four repetitive non-consecutive moderate doses (0.05 mg/kg) of fentanyl for a period of seven days. MC-100093 (50 mg/kg) and ceftriaxone (200 mg/kg) were i.p. injected from days 5 to 9. Gas chromatography–mass spectrometry (GC-MS) was used for metabolomics, and Western blotting was performed to determine the expression of target proteins. Y-maze spontaneous alternation performance and the open field activity monitoring system were used to measure behavioral manifestations. Fentanyl overdose altered the abundance of about 30 metabolites, reduced the expression of GLT-1, and induced the expression of inflammatory mediators IL-6 and TLR-4 in the NAc. MC-100093 and ceftriaxone attenuated the effects of fentanyl-induced downregulation of GLT-1 and upregulation of IL-6; however, only ceftriaxone attenuated fentanyl-induced upregulation of TRL4 expression. Both of the β-lactams attenuated the effects of fentanyl overdose on locomotor activities but did not induce significant changes in the overall metabolomic profile. Our findings revealed that the exposure to a high dose of fentanyl causes alterations in key metabolic pathways in the NAc. Pretreatment with ceftriaxone and MC-100093 normalized fentanyl-induced downregulation of GLT-1 expression with subsequent attenuation of neuroinflammation as well as the hyperactivity, indicating that β-lactams may be promising drugs for treating fentanyl use disorder. [ABSTRACT FROM AUTHOR]

In an era of cost pressure, substituting generic drugs represents one of the main cost-containment strategies of healthcare systems. Despite the obvious financial benefits, in a minority of cases, substitution may require caution or even be contraindicated. In most jurisdictions, to obtain approval, the bioequivalence of generic products with the brand-name equivalent needs to be shown via bioavailability studies in healthy subjects. Rare diseases, defined as medical conditions with a low prevalence, are a group of heterogenous diseases that are typically severe, disabling, progressive, degenerative, and life-threatening or chronically debilitating, and disproportionally affect the very young and elderly. Despite these unique features of rare diseases, generic bioequivalence studies are typically carried out with single doses and exclude children or the elderly. Furthermore, the excipients and manufacturing processes for generic/biosimilar products can differ from the brand products which may affect the shelf-life of the product, its appearance, smell, taste, bioavailability, safety and potency. This may result in approval of generics/biosimilars which are not bioequivalent/comparable in their target population or that meet bioequivalence but not therapeutic equivalence criteria. Another concern relates to the interchangeability of generics and biosimilars which cannot be guaranteed due to the phenomenon of biocreep. This review summarizes potential concerns with generic substitution of orphan drugs and discusses potentially problematic cases including narrow therapeutic index drugs or critical conditions where therapeutic failure could lead to serious complications or even death. Finally, we put forward the need for refining regulatory frameworks, with emphasis on Saudi Arabia, for generic substitution and recent efforts toward this direction. [ABSTRACT FROM AUTHOR]

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