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The bromate is used in bread making as agent of maturation, however it has a high potential toxic. A rapid and reliable spectrophotometric method was validated to determine the level of bromate in bread; this method is based on the red-ox reaction between bromate and promethazin in acidic medium. This produced a red-pink product with maximum absorption at 515nm. The calibration curve was linear (r = 0.9989) over the range 0.5 μg/ml - 4.5 μg/ml of bromate, the proposed method has been successfully applied to determination of bromate in commercial bread. [ABSTRACT FROM AUTHOR]

In the title mol-ecule, C 17 H 20 N 2 O 4 , the inner part of the ester substituent is nearly perpendicular to the di-hydro-pyridazine ring, forming a dihedral angle of 83.21 (7)°. In the crystal, inversion dimers are formed by pairwise C-H⋯O inter-actions with the dimers connected into chains extending along the b -axis direction by C-H⋯π(ring) inter-actions. The chains are connected by π-stacking inter-actions to give corrugated layers parallel to the ab plane. The terminal ethyl group is disordered over two two sets of sites with the major component having a site occupancy factor of 0.715 (10)., (© Zaoui et al. 2022.)

The asymmetric unit of the title mol-ecule, C 12 H 12 O 3 , contains two independent mol-ecules having opposite conformations and each forming self-dimers through complementary O-H⋯O hydrogen bonds. These dimers are linked by weak C-H⋯π inter-actions and C-H⋯O hydrogen bonds into a three-dimensional structure in which one can discern layers parallel to the bc plane. A Hirshfeld surface analysis of the inter-molecular inter-actions is included., (© Assila et al. 2022.)

The hydantoin scaffold is of substantial importance and it is commonly used in drug discovery. Herein, we report the synthesis of a novel phenytoine (a hydantoin derivative) with high yield by the reaction of phenytoin with 1-bromodecyl agent. Namely, 3-decyl-5,5- diphenylimidazolidine-2,4-dione (3DDID). The optimized geometry of the compound was calculated using density functional theory (DFT) method by B3LYP with 6-311++G(d,p) basis set. For this calculation, the X-ray data were used as initial values. Molecular electrostatic potential (MEP) surface and Frontier molecular orbitals (FOMs) were prepared for the compound. The crystal structure of the title compound contains intermolecular N-H···O, C-H···O hydrogen bonds and weak C-H···π interactions. Hirshfeld surface analysis and 2D fingerprint plots of the molecule aid comparison of intermolecular interactions and these analysis reveals that two close contacts are associated with intermolecular hydrogen bonds. The psychotropic activity evaluation of the synthesized compound was further explored using hole bored test for exploratory behaviors, dark//light box test for anxiolytic activity and Rota-road, traction, chimney testes were used to assess the myrelaxant effect. In addition, molecular modeling study was also conducted to rationalize the potential as neurotherapeutic drugs of our synthesized compound by predicting their binding modes, binding affinities and optimal orientation at the active site of the GABA-A receptor and Na + channel. Finally, in silico ADMET predictions was also examined. HighlightsSynthesis, structural, and molecular characterization of a novel phenytoin derivative.DFT, XRD, and the Hirshfeld surface analysis of crystal structure was studied.Acute toxicity and psychotropic activity evaluation of 3-decyl-5,5 diphenylimidazolidine-2,4-dione (3DDID).Molecular modeling studies have been conducted to rationalize the obtained data and to determine the probable binding mode.Communicated by Ramaswamy H. Sarma.

Background: Clinical pharmacists are contributing to safe medication use by providing comprehensive management to patients and medical staff. The aim of this study is to document and evaluate the role of clinical pharmacy services in oncology department., Patients and Methods: A prospective, descriptive, observational study was carried out from July 2018 through June 2019 at the Department of Medical Oncology at the National Institute of Oncology, Morocco. Medication reviews concerning hospitalized adult cancer patients were performed every day by the clinical pharmacist assigned to the department., Results: A total of 3542 prescriptions of 526 adult cancer patients were analyzed. The pharmacist identified 450 drug-related problems (12.7% of the prescriptions) primarily related to the analgesics (31.5%). Medication problems included mostly untreated indications (31.3%), overdosing (17.1%), drug-drug interactions (12.4%), underdosing (11.1%), administration omissions (6.7%), drug not indicated (6.0%), and contraindication (5.3%). Interventions ( n  = 450) led to drug additions (30.7%), drug dosing adjustments (27.1%), treatment discontinuations (20.0%), recall of the treatment (6.2%), replacement of a drug with another one (5.1%), administration optimization (4.0%), therapeutic drug monitoring (3.1%), alternate routes of administration (2.5%), and extension of treatment duration (1.3%). Most (98%) of the interventions were accepted and implemented by the medical staff-172 (38.2%) having a significant clinical impact on the patient, 88 (19.6%) as having a very significant clinical impact, and 71(15.8%) as having a potential vital impact., Conclusion: This work highlights the positive clinical relevance of pharmacists' interventions in oncology and the importance of medicopharmaceutical collaboration to prevent medication error.

Introduction: The health care consumption for the population insured by the Basic Health Insurance in Morocco are paid directly to the care providers for the health care or health products from the health insurance funds. The level of expenditure recorded is changing at an accelerated rate than the financial resources. The objective of this study is to evaluate the health care consumption care by the insured population under the Basic Health Insurance., Methods: This is a cross-sectional study analysis of the economic data collected by the National Moroccan Health Insurance Agency Related to the expenditures from the health insurance fund for both public and private sectors to identify the behavior of the consumption of health care by the insured population under the Basic Health Insurance., Results: The medical expenditure of the covered population by the basic Health Insurance in Morocco has almost doubled from 354800 to 652500 US Dollars between 2009 and 2014 with significant increase in the public sector than the private sector. The share of expenditures in the public ambulatory care sector under Basic Health Insurance is higher relative to the hospital care. Although in the private sector the share of expenditures for both types of care varies. In 2014, the drug item expenditure accounted for 33% of Health Insurance expenses for both sectors. The level of health care consumption among the population in Long-Term Illness (LTI) represents 49,29% of the total expenditure by the Health Insurance whereas its insured covered population does not exceed 2,78%., Conclusion: Controlling the medical expenditure of the health insurance requires strengthening and the development of regulatory measures that contribute to the health reforms. For chronic diseases, it is necessary to put in place prevention actions., Competing Interests: The authors declare no competing of interest., (© Amal Yassine et al.)

Introduction: Hemodialysis is a technique of extra-renal purification associated with high level of risk. The objective is to assess infectious risk during a hemodialysis session on hygiene around the patient in hospital., Methods: An a priori risk assessment by Failure Modes, Effects and Criticality Analysis method (FMECA) was carried out from May to August 2018, in order to overview infectious risk during the process of hemodialysis in the Ibn Sina Hospital (Rabat, Morocco)., Results: Twenty eight failure modes were identified during the hemodialysis process around the patient: fourteen criticality level 1, ten level 2, and four level 3. A prevention plan has been drafted. Three of the four level 3 failure modes were reduced to level 1 and one to level 2., Discussion: FMECA have enabled us to identify the potential risks, to reconsider certain procedures and to suggest measure matrix for the coverage of the most critical risks., Conclusion: This analysis makes it possible, through periodic evaluations, to enter a real quality approach, which reinforces the satisfaction of the patients as well as all the actors of the hemodialysis center., (Copyright © 2020 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

The phosphoinositide 3-kinase (PI3K) pathway is an important regulator of cell proliferation and metabolism. PI3K activation initiates a signal transduction cascade, of which the major effectors are the kinases AKT and mTOR. Aberrant activation of the PI3K/AKT/mTOR pathway is frequently observed in many human malignancies and the combination of compounds simultaneously targeting different related molecules in the PI3K/AKT/mTOR pathway leads to synergistic activity. To explore the competing common ATP inhibitors PI3K/AKT and PI3K/mTOR we developed a model PI3K-SAR 2D which made it possible to predict the bioactivity of inhibitors of AKT and mTOR towards PI3K; the interaction of the best inhibitors was evaluated by docking analysis and compared to that of dactolisib and pictilisib. A PI3K-SAR model with a correlation coefficient (R2) of 0.81706 and an RMSE of 0.16029 was obtained, which was validated and evaluated by a cross-validation method, LOO. The most predicted AKT and mTOR inhibitors present respectively pIC50 activities between 9.26-9.93 and 9.59-9.87. After docking and several comparisons, inhibitors with better predictions showed better affinity and interaction with PI3K compared to pictilisib and dactolisib, so we found that 4 inhibitors of AKT and 14 mTOR inhibitors met the criteria of Lipinski and Veber and could be future drugs., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia Sp. z o. o.)

Background: In cancer cells, the intracellular antioxidant capacity and the redox homeostasis are mainly maintained by the glutathione- and thioredoxin-dependent systems which are considered as promising targets for anticancer drugs. Pyridazinones constitute an interesting source of heterocyclic compounds for drug discovery. The present investigation focused on studying the in-vitro antitumor activity of newly synthesized Pyridazin-3(2h)-ones derivatives against P815 (Murin mastocytoma) cell line., Methods: The in-vitro cytotoxic activities were investigated toward the P815 cell line using tetrazolium-based MTT assay. Lipid peroxidation and the specific activities of antioxidant enzymes were also determined., Results: The newly compounds had a selective dose-dependent cytotoxic effect without affecting normal cells (PBMCs). Apoptosis was further confirmed through the characteristic apoptotic morphological changes and DNA fragmentation. Two compounds (6F: and 7H: ) were highly cytotoxic and were submitted to extend biological testing to determine the likely mechanisms of their cytotoxicity. Results showed that these molecules may induce cytotoxicity via disturbing the redox homeostasis. Importantly, the anticancer activity of 6F: and 7H: could be due to the intracellular reactive oxygen species hypergeneration through significant loss of glutathione reductase and thioredoxin reductase activities. This eventually leads to oxidative stress-mediated P815 cell apoptosis. Furthermore, the co-administration of 6F: or 7H: with Methotrexate exhibited a synergistic cytotoxic effect., Conclusions: considering their significant anticancer activity and chemosensitivity, 6F: and 7H: may improve the therapeutic efficacy of the current treatment for cancer., Competing Interests: No conflict of interest has been declared by the authors., (© Georg Thieme Verlag KG Stuttgart · New York.)

The title compound, C 16 H 18 N 2 O 3 , is constructed about a central oxopyridazinyl ring (r.m.s. deviation = 0.0047 Å), which is connected to an ethyl-acetate group at the N atom closest to the carbonyl group, and benzyl and methyl groups second furthest and furthest from the carbonyl group, respectively. An approximately orthogonal relationship exists between the oxopyridazinyl ring and the best plane through the ethyl-acetate group [dihedral angle = 77.48 (3)°]; the latter lies to one side of the central plane [the N r -N r -C m -C c (r = ring, m = methyl-ene, c = carbon-yl) torsion angle being 104.34 (9)°]. In the crystal, both H atoms of the N-bound methyl-ene group form methyl-ene-C-H⋯O(ring carbon-yl) or N(pyridazin-yl) inter-actions, resulting in the formation of a supra-molecular tape along the a -axis direction. The tapes are assembled into a three-dimensional architecture by methyl- and phenyl-C-H⋯O(ring carbon-yl) and phenyl-C-H⋯O(ester carbon-yl) inter-actions. The analysis of the calculated Hirshfeld surface indicates the dominance of H⋯H contacts to the overall surface ( i.e. 52.2%). Reflecting other identified points of contact between mol-ecules noted above, O⋯H/H⋯O (23.3%), C⋯H/H⋯C (14.7%) and N⋯H/H⋯N (6.6%) contacts also make significant contributions to the surface.

Introduction: The sustainability of medical assistance, considered necessary in middle-income countries, requires permanent regulation. In Morocco, the medical assistance scheme (MAS) is confronted with the lack of regulation tools and the difficulty of affixing these tools effectively in the absence of a regulator. In this sense, the shortcomings of the current practice of its regulation should be identified in order to recommend actions and tools to improve its implementation and guarantee its continuity., Methods: The analysis and the proposed recommendations are based on the review of the available literature, the review of the legal texts framing the basic medical coverage and the analysis of the current practice of regulation of the MAS., Results: The regulation of the MAS was not treated in the same way as the compulsory health insurance. There is no proper regulator as the case of the compulsory health insurance. In substance, the planned measures remain very insufficient and scattered between several actors and sometimes difficult to apply. Based on a reference framework designed along four axes (resources, expenditures, health care offer and population), the analysis identified fifteen actions and tools to correct deficiencies and support its sustainability., Conclusion: The proposed recommendations need a durable commitment from all the actors who must trigger as quickly as possible urgent actions to optimize the implementation of the medical assistance scheme and improve its perception in the citizen.

Triple-negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer characterized by high morbidity and mortality. In the absence of targeted therapy, only chemotherapy is available in this case of cancer. The current study investigated the antitumor effect of new pyridazin-3(2H)-one derivatives on the human TNBC cell line, MD-MB-468. The in vitro cytotoxic activities were investigated using the tetrazolium-based MTT assay. Lipid peroxidation, H 2 O 2 content, and the specific activities of antioxidant enzymes were also determined. Two molecules, 6f and 7h, were found to be selectively highly active against tumor cells with IC 50 values of 3.12 and 4.9 µM, respectively. Furthermore, cells exposed to 6f showed a significant increase in H 2 O 2 and lipid peroxidation levels, accompanied by a decrease in the enzyme activities of glutathione reductase (GR) and thioredoxin reductase (TrxR). The cytotoxicity of the compound 6f may improve the therapeutic efficacy of the current treatment for TNBC via the inhibition of GR and TrxR activities., (© 2018 Deutsche Pharmazeutische Gesellschaft.)

Introduction: Five years after its implementation, the Medical Assistance scheme (Ramed) has been able to cover more than eleven million people. Nevertheless, its financing remains the main challenge. Its initial financial structure was exceeded after its implementation. A reconfiguration of the financial package has become a necessity in order to guarantee sustainable financing., Methods: A review of the literature and a situational analysis through disseminated reports and documents made it possible to identify the initial financial package and its limits in order to design a new financial package., Results: The current financing is out of step with the regulations, which has a negative impact on it. Funds are insufficient to cover needs and do not even exceed half of the planned funding, set at three billion dirhams, due to a partial collection of resources. In order to meet the needs of the beneficiaries and follow their growing rhythm, at least 4 billion dirhams annually must be collected. This amount can only be ensured with a revision of the contributions of the State and local authorities., Conclusion: The current funds do not meet the needs, which undermines the social acceptability of the regime and threatens its sustainability. It is essential to improve its funding through a diversity of resources and more commitment from stakeholders to ensure sustainable funding managed according to the principles of good governance.