New pyranopyrazole based derivatives: Design, synthesis, and biological evaluation as potential topoisomerase II inhibitors, apoptotic inducers, and antiproliferative agents.

A new series of pyranopyrazole-based derivatives were designed and synthesized. The synthesized compounds were assessed for their cytotoxic efficacy against A549 human lung carcinoma and MCF-7 human breast carcinoma cell lines. Three compounds (1b, 4b, and 7b) exhibited 1.3- to 2.3-fold more antiproliferative activity than that of doxorubicin against the A549 cell line. In comparison to doxorubicin, compounds 1d and 3b were 4.1- and 1.04-fold, respectively more powerful against MCF-7 cancer cells. All the synthesized compounds were found to be more selective toward A549 cancer cells than the normal human fibroblast BJ cells. Of interest, compounds 1b and 7b exhibited promising cytotoxicity and SIs of 27.72 and 25.30, respectively, towards A549 cancer cells, higher than that of doxorubicin (SI 4.81). The most potent compounds 1b, 1d, 3b, 4b, and 7b were then subjected to in vitro Topo II inhibition assay. They showed IC50 values in the range of 2.07 to 8.86 µM. Of particular interest, compound 7b (IC50 = 2.07 µM), exhibited higher Topo II inhibitory activity than that of doxorubicin (IC50 = 2.56 µM). The significant Topo II inhibition of compound 7b was explained by molecular docking simulations into the Topo II active site. Compound 7b halted the cell cycle in the S phase in A549 cancer cells. It induced total apoptosis and necrosis of 20.73- and 4-fold, respectively, greater than the control. This evidence was supported by a 3.59-fold increase in the level of apoptotic caspase-9 and a remarkable elevation of the Bax/BCL-2 ratio. The physiochemical parameters of compound 7b were aligned with Lipinski's rule of five.

Exploring research gaps and trends in the management of acute phosphide poisoning: a systematic review.

Metal phosphides are highly toxic pesticides that result in high morbidities and mortalities worldwide. This systematic review included 350 studies that fulfilled the eligibility criteria. There were significant rising trends of studies on acute aluminum phosphide (AlP) and zinc phosphide (Zn3P2) poisoning (p-values = <.001), pointing to an increased number of phosphide-intoxicated patients. Acute AlP poisoning studies represented 81%, 89.3%, and 97.7% of all descriptive, analytical, and experimental interventional studies included in this review, respectively. High AlP poisoning mortality explains great research interest in AlP poisoning. Thus, after 2016, nearly half (49.7%) of studies on acute AlP poisoning were issued. Also, 78.82% of experimental interventional studies on AlP poisoning were published after 2016. The trends of in-vitro, animal, and clinical studies on AlP poisoning significantly increased with p-values equal to .021, <.001, and <.001, respectively. Seventy-nine treatment modalities for acute AlP poisoning were pooled from 124 studies; 39 management-related case reports, 12 in-vitro studies, 39 animal studies, and 34 clinical studies. All therapeutic modalities were summarized to formulate an integrated and comprehensive overview. For clinicians, therapeutic modalities significantly decreased mortality of acute AlP poisoning in clinical trials included extracorporeal membrane oxygenation (ECMO), N-acetyl cysteine (NAC), vitamin E, glucose-insulin-potassium (GIK) infusion, fresh packed RBCs infusion, and GIT decontamination using oils. However, meta-analyses are needed to provide solid evidence regarding their efficacies. To date, there is no effective antidote nor evidence-based standardized protocol for managing acute AlP poisoning. This article outlined the potential research gaps in phosphide poisoning that might promote and direct future medical research in this context.

Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors.

New thiazolopyrimidine derivatives 2, 3a-d, 4a-c, 5, 6a-c, and 7a,b were synthesised. All prepared compounds were evaluated by MTT cytotoxicity assay against three human tumour cell lines. Compounds 3c, 3d, 4c, 6a, 6b, and 7b exhibited potent to strong anticancer activity that was nearly comparable or superior to Doxorubicin. Compounds exhibiting significant cytotoxicity were further selected to study their inhibitory activity on the Topo II enzyme. Compound 4c was the most potent Topo II inhibitor with an IC50 value of 0.23 ± 0.01 µM, which was 1.4-fold and 3.6-fold higher than the IC50 values of Etoposide and Doxorubicin. Furthermore, compound 4c showed significant cell cycle disruption and apoptosis on A549 cells compared to control cells. Molecular docking of the most active compounds illustrated proper fitting to the Topo II active site, suggesting that our designed compounds are promising candidates for the development of effective anticancer agents acting through Topo II inhibition.

Design, synthesis, docking, MD simulations, and anti-proliferative evaluation of thieno[2,3-d]pyrimidine derivatives as new EGFR inhibitors.

A group of EGFR inhibitors derived from thieno[2,3-d]pyrimidine nucleus was designed, synthesised, and examined as anti-proliferative lead compounds. MCF-7 and A549 cell lines were inhibited by 5b, the most active member. It had inhibitory partialities of 37.19 and 204.10 nM against EGFRWT and EGFRT790M, respectively. Compound 5b was 2.5 times safer against the WI-38 normal cell lines than erlotinib. Also, it demonstrated considerable potentialities for both early and late apoptosis induction in A549. Simultaneously, 5b arrested A549's growth at G1 and G2/M phases. Harmoniously, 5b upregulated the BAX and downregulated the Bcl-2 genes by 3-fold and increased the BAX/Bcl-2 ratio by 8.3-fold comparing the untreated A549 cells. Molecular docking against EGFRWT and EGFRT790M indicated the correct binding modes. Furthermore, MD simulations confirmed the precise binding of 5b against the EGFR protein over 100 ns. Finally, various computational ADMET studies were carried out and indicated high degrees of drug-likeness and safety.

A novel thieno[2,3-d]pyrimidine derivative inhibiting vascular endothelial growth factor receptor-2: A story of computer-aided drug discovery.

Following the pharmacophoric features of vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors, a novel thieno[2,3-d]pyrimidine derivative has been designed and its activity against VEGFR-2 has been demonstrated by molecular docking studies that showed an accurate binding mode and an excellent binding energy. Furthermore, the recorded binding was confirmed by a series of molecular dynamics simulation studies, which also revealed precise energetic, conformational, and dynamic changes. Additionally, molecular mechanics with generalized Born and surface area solvation and polymer-induced liquid precursors studies were conducted and verified the results of the MD simulations. Next, in silico absorption, distribution, metabolism, excretion, and toxicity studies have also been conducted to examine the general drug-like nature of the designed candidate. According to the previous results, the thieno[2,3-d]pyrimidine derivative was synthesized. Fascinatingly, it inhibited VEGFR-2 (IC50 = 68.13 nM) and demonstrated strong inhibitory activity toward human liver (HepG2), and prostate (PC3) cell lines with IC50 values of 6.60 and 11.25 µM, respectively. As well, it was safe and showed a high selectivity index against normal cell lines (WI-38). Finally, the thieno[2,3-d]pyrimidine derivative arrested the growth of the HepG2 cells at the G2/M phase inducing both early and late apoptosis. These results were further confirmed through the ability of the thieno[2,3-d]pyrimidine derivative to induce significant changes in the apoptotic genes levels of caspase-3, caspase-9, Bcl-2 associated X-protein, and B-cell lymphoma 2.

New pyrrole derivatives as DNA gyrase and 14α-demethylase inhibitors: Design, synthesis, antimicrobial evaluation, and molecular docking.

An efficient one-pot reaction utilizing readily available chemical reagents was used to prepare novel 2-amino-1,5-diaryl-1H-pyrrole-3-carbonitrile derivatives and the structures of these compounds were validated by spectroscopic data and elemental analyses. All the synthetic compounds were evaluated for their antimicrobial activities (MZI assay). The tested compounds proved high activities on Staphylococcus aureus (Gram-positive bacteria) and Candida albicans (Pathogenic fungi). However, they did not show any activity on Escherichia coli (Gram-negative bacteria). The most effective compounds in MZI assay 7c, 9a, 9b, 11a, and 11b were selected to determine their MIC on S. aureus and C. albicans. Furthermore, DNA gyrase and 14-α demethylase inhibitory assays were performed to study the inhibitory activities of 7c, 9a, 9b, 11a, and 11b. The results illustrated that compound 9b was the most DNA gyrase inhibitor (IC50 of 0.0236 ± 0.45 µM, which was 1.3- fold higher than gentamicin reference IC50 values of 0.0323 ± 0.81 µM). In addition, compound 9b demonstrated the highest 14-α demethylase inhibitory effect with IC50 of 0.0013 ± 0.02 µM, compared to ketoconazole (IC50 of 0.0008 ± 0.03 µM) and fluconazole (IC50 of 0.00073 ± 0.01 µM), as antifungal reference drugs. Lastly, docking studies were performed to rationalize the dual inhibitory activities of the highly active compounds on both DNA gyrase and 14-α demethylase enzymes.

Sociodemographic and clinical characteristics of early COVID-19 deaths in Almadinah Almonawarah, Saudi Arabia: An analytical cross-sectional study.

Background and Objective: Identification of clinical characteristics and risk factors for mortality in COVID-19 is important for early detection and precise case management. The study aimed to describe the sociodemographic, clinical, and laboratory characteristics of in-hospital COVID-19 deaths in Almadinah Almonawarah city, Saudi Arabia, and to identify risk factors for early mortality among them. Methods: This is an analytical cross-sectional study. The main outcomes were demographic and clinical characteristics of COVID 19 patients who died from March till December 2020, during the hospital stay. We collected 193 records of COVID-19 patients, from two major hospitals in Al Madinah region, Saudi Arabia. Descriptive and inferential analysis were performed to identify and relate the factors of early death. Results: Out of the total deaths, 110 died during the first 14 days of admission (Early death group) and 83 died after 14 days of admission (Late death group). Early death group had a significantly higher percentages of old age patients (p=0.027) and males (72.7%). Comorbidities were found in 166 (86%) of cases. Multimorbidity were significantly higher in early deaths than in late deaths 74.5% (p=<0.001). Women had significantly higher mean values of CHA2SD2 comorbidity scores (3.28 versus 1.89 for men; p <0.001). Moreover, predictors of high comorbidity scores were older age (p=0.005), higher respiratory rate (p=0.035), and raised alanine transaminase (p=0.047). Conclusion: Old age, comorbid illness, and severe respiratory involvement were prevalent among COVID-19 deaths. Comorbidity scores were significantly higher in women. Comorbidity was found to be significantly more associated with early deaths.

New benzothienopyrimidine derivatives as dual EGFR/ARO inhibitors: Design, synthesis, and their cytotoxic effect on MCF-7 breast cancer cell line.

New cytotoxic agents based on benzothienopyrimidine scaffold were designed, synthesized, and evaluated against the MCF-7 breast cancer line in comparison to erlotinib and letrozole as reference drugs. Eight compounds demonstrated up to 20-fold higher anticancer activity than erlotinib, and five of these compounds were up to 11-fold more potent than letrozole in MTT assay. The most promising compounds were evaluated for their inhibitory activity against EGFR and ARO enzymes. Compound 12, which demonstrated potent dual EGFR and ARO inhibitory activity with IC50 of 0.045 and 0.146 µM, respectively, was further evaluated for caspase-9 activation, cell cycle analysis, and apoptosis. The results revealed that the tested compound 12 remarkably induced caspase-9 activation (IC50 = 16.29 ng/ml) caused cell cycle arrest at the pre-G1 /G1 phase and significantly increased the concentration of cells at both early and late stage of apoptosis. In addition, it showed a higher safety profile on normal MCF-10A cells, and higher antiproliferative activity on cancer cells (IC50 = 8.15 µM) in comparison to normal cells (IC50 = 41.20 µM). It also revealed a fivefold higher selectivity index than erlotinib towards MCF-7 cancer cells. Docking studies were performed to rationalize the dual inhibitory activity of compound 12.

New benzothieno[2,3-c]pyridines as non-steroidal CYP17 inhibitors: design, synthesis, anticancer screening, apoptosis induction, and in silico ADME profile studies.

A series of [1]benzothieno[2,3-c]pyridines was synthesised. Most compounds were chosen by NCI-USA to evaluate their anticancer activity. Compounds 5a-c showed prominent growth inhibition against most cell lines. 5c was selected at five dose concentration levels. It exhibited potent broad-spectrum anticancer activity with a GI50 of 4 nM-37 µM. Cytotoxicity of 5a-c was further evaluated against prostate, renal, and breast cancer cell lines. 5c showed double and quadruple the activity of staurosporine and abiraterone, respectively, against the PC-3 cell line with IC50 2.08 µM. The possible mechanism of anti-prostate cancer was explored via measuring the CYP17 enzyme activity in mice prostate cancer models compared to abiraterone. The results revealed that 5c suppressed the CYP17 enzyme to 15.80 nM. Moreover, it was found to be equipotent to abiraterone in testosterone production. Cell cycle analysis and apoptosis were performed. Additionally, the ADME profile of compound 5c demonstrated both good oral bioavailability and metabolic stability.

Knowledge about electronic cigarettes and its perception: a community survey, Egypt.

BACKGROUND: Electronic cigarettes are promoted as safer products than traditional cigarettes and as smoking cessation devices. Awareness and perception are key elements for the adoption of new habits. Little is known about electronic cigarettes and public opinions towards it. This study aims to identify the prevalence of knowledge about electronic cigarettes, its perception, and use among Egyptian population. METHODS: An observational cross-sectional study using self-administered questionnaire in Arabic language was conducted between March and April 2015 among a sample of Egyptian population aged 15-75 years (N = 1239). We compared between respondent's who know e-cigarettes and those who do not know it. RESULTS: More than half (57.5 %) of the respondents had heard about e-cigarettes, 51.8 % were non-smokers and nobody of them reported use of e-cigarettes. There were statistically significant differences between those who know and those who do not know e-cigarettes regarding age, educational levels and history of smoking. Among those who know e-cigarettes, 41.6 % believed that e-cigarettes help smoking cessation and 31.9 % believed it is less harmful than traditional cigarettes. CONCLUSIONS: A considerable level of knowledge about e-cigarettes is found among young people aged 15-39 years. E-cigarettes were perceived as less harmful than traditional cigarettes or a smoking cessation aid. None of the respondents reported use of e-cigarettes.

Retrospective analysis of an outbreak of scarlet fever in United Arab Emirates.

Background: Scarlet fever is an infectious disease caused by Streptococcus pyogenes. However, there is limited data regarding the disease in the Arab World, including the United Arab Emirates. Objective: To analyse a scarlet fever outbreak in United Arab Emirates. Methods: This retrospective cross-sectional study included scarlet fever cases diagnosed at the Kanad Hospital, Al Ain, United Arab Emirates in 2022 and 2023. Data were retrieved from the hospital records and analysed using SPSS version 23.0. Chi-Square, Mann-Whitney, and Monte Carlo tests were applied. Results: Two hundred and twenty-two cases (13.5% in 2022 and 86.5% in 2023) were confirmed (P<0.001). Majority (67.1%) of the patients were aged 3-6 years, with a mean age of 4.56 ± 1.99 years. Rash, fever and sore throat were observed in 100%, 99.1%, and 82.0% of cases, respectively. The majority (85.1%) were managed as outpatients and 77.0% responded to oral penicillin. Patients' age was not significantly associated with nonresponse to penicillin and in-hospital admission. The outbreak had winter and summer peaks, with the highest incidence occurring during January and February 2023. Conclusion: This study serves as a valuable reference for other studies, which should include antimicrobial susceptibility testing and the prevailing genetic variance of Streptococcus pyogenes.

New Thieno[2,3-d]pyrimidines as Anticancer VEGFR-2 Inhibitors with Apoptosis Induction: Design, Synthesis, and Biological and In Silico Studies.

BACKGROUND: Vascular endothelial growth factor receptor-2 (VEGFR-2) is a critical protein involved in tumor progression, making it an attractive target for cancer therapy. OBJECTIVE: This study aimed to synthesize and evaluate novel thieno[2,3-d]pyrimidine analogues as potential anticancer VEGFR-2 inhibitors. METHODS: The thieno[2,3-d]pyrimidine analogues were synthesized following the pharmacophoric features of VEGFR-2 inhibitors. The anticancer potential was assessed against PC3 and HepG2 cell lines. The VEGFR-2 inhibition was evaluated through IC50 determination. Cell cycle analysis and apoptosis assays were performed to elucidate the mechanisms of action. Molecular docking, molecular dynamics simulations, MM-GBSA, and PLIP studies were conducted to investigate the binding affinities and interactions with VEGFR-2. Additionally, in silico ADMET studies were performed. RESULTS: Compound 8b demonstrated significant anti-proliferative activities with IC50 values of 16.35 µM and 8.24 µM against PC3 and HepG2 cell lines, respectively, surpassing sorafenib and exhibiting enhanced selectivity indices. Furthermore, compound 8b showed an IC50 value of 73 nM for VEGFR-2 inhibition. Cell cycle analysis revealed G2-M phase arrest, while apoptosis assays demonstrated increased apoptosis in HepG2 cells. Molecular docking and dynamic simulations confirmed the binding affinity and interaction of compound 8b with VEGFR-2, supported by MMGBSA and PLIP studies. In silico ADMET studies indicated the drug development potential of the synthesized thieno[2,3-d]pyrimidines. CONCLUSION: The study highlights compound 8b as a promising VEGFR-2 inhibitor with potent anti-proliferative activities. Its mechanism of action involves cell cycle arrest and induction of apoptosis. Further, molecular docking and dynamic simulations support the strong binding affinity of compound 8b to VEGFR-2.

Computer aided drug discovery (CADD) of a thieno[2,3-d]pyrimidine derivative as a new EGFR inhibitor targeting the ribose pocket.

Depending on the pharmacophoric characteristics of EGFR inhibitors, a new thieno[2,3-d]pyrimidine derivative has been developed. Firstly, the potential inhibitory effect of the designed compound against EGFR has been proven by docking experiments that showed correct binding modes and excellent binding energies of -98.44 and -88.00 kcal/mol, against EGFR wild-type and mutant type, respectively. Furthermore, MD simulations studies confirmed the precise energetic, conformational, and dynamic alterations that occurred after binding to EGFR. The correct binding was also confirmed by essential dynamics studies. To further investigate the general drug-like properties of the developed candidate, in silico ADME and toxicity studies have also been carried out. The thieno[2,3-d]pyrimidine derivative was synthesized following the earlier promising findings. Fascinatingly, the synthesized compound (4) showed promising inhibitory effects against EGFRWT and EGFRT790M with IC50 values of 25.8 and 182.3 nM, respectively. Also, it exhibited anticancer potentialities against A549 and MCF-7cell lines with IC50 values of 13.06 and 20.13 µM, respectively. Interestingly, these strong activities were combined with selectivity indices of 2.8 and 1.8 against the two cancer cell lines, respectively. Further investigations indicated the ability of compound 4 to arrest the cancer cells' growth at the G2/M phase and to increase early and late apoptosis percentages from 2.52% and 2.80 to 17.99% and 16.72%, respectively. Additionally, it was observed that compound 4 markedly increased the levels of caspase-3 and caspase-9 by 4 and 3-fold compared to the control cells. Moreover, it up-regulated the level of BAX by 3-fold and down-regulated the level of Bcl-2 by 3-fold affording a BAX/Bcl-2 ratio of 9.Communicated by Ramaswamy H. Sarma.

Effect of the Dynamic Orthotic Garment on Postural Control, and Endurance in Children with Spastic Diplegic Cerebral Palsy: A Randomized Controlled Trial.

Purpose: To investigate the effect of dynamic orthotic garments (Thera togs) on foot pressure distribution, postural control, and endurance in children with spastic diplegic CP. Patients and Methods: This is a single-blind randomized controlled clinical trial involving 34 (8-10 years) with spastic diplegic CP. The control group received conventional physical therapy (CPT), whereas the study group received CPT in addition to wearing TheraTogs. We recorded foot pressure distribution, trunk control measurement scale, trunk position sense, Pediatric Berg Balance Scale (PBS), and six-minute walking distance (6MWD). Results: Both groups showed improvement. The study group had significant improvement in foot pressure distribution (p-value 0.003, 0.001, <0.001 for forefoot, midfoot, and rearfoot mean pressures respectively, and 0.005, <0.001, and 0.005 for forefoot, midfoot, and rearfoot peak pressures respectively), Pediatric balance scale, The trunk control measurement scale, and Trunk position sense (p-value < 0.001) and six-minute walking distance (p-value 0.029). Our data suggest that adding TheraTogs to conventional physiotherapy improves foot pressure, postural control, and endurance in children with spastic diplegic cerebral palsy. Conclusion: Both TheraTogs and conventional physical therapy corrected foot pressure distribution, trunk control, improved balance, and increased 6MWD in children with spastic diplegic CP but the improvement was more significant in TheraTogs group. Clinical Trial Registration: NCT05271149.

Discovery of new thieno[2,3-d]pyrimidines as EGFR tyrosine kinase inhibitors for cancer treatment.

Background: EGFR has been considered a vital molecular target in cancer management. Aim: The discovery of new thieno[2,3-d]pyrimidine derivatives as EGFR tyrosine kinase inhibitors. Methods: Nine derivatives were designed, synthesized and subjected to in vitro and in silico studies. Results: Compound 7a significantly inhibited the growth of HepG2 and PC3 cells for both EGFR wild-type and EGFRT790M. Compound 7a caused a significant apoptotic effect, arresting HepG2 cells' growth in the S and G2/M phases. Docking and molecular dynamics simulation studies confirmed the correct and stable binding modes of the synthesized compounds against the active sites. Conclusion: Compound 7a is a promising dual EGFR inhibitor for cancer treatment.

Antimicrobial stewardship in the era of the COVID-19 pandemic: A systematic review protocol on the opportunities and challenges for Sub-Saharan Africa.

BACKGROUND: Antimicrobial resistance (AMR) remains one of the leading threats to global public health and this may increase following COVID-19 pandemic. This is particularly the case in Africa where regulations on antimicrobial usage are weak. This protocol outlines the steps to undertake a systematic review to synthesize evidence on drivers of AMR and evaluate existing approaches to strengthening antimicrobial stewardship (AMS) programs in Sub-Saharan Africa (SSA). On the basis of the evidence generated from the evidence synthesis, the overarching goal of this work is to provide recommendations to support best practices in AMS implementation in SSA. METHODS: A systematic search will be conducted using the following databases: Global Health Library, PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, Google Scholar, Global Health, Embase, African Journals Online Library, Web of Science, antimicrobial databases (WHO COVID-19, TrACSS, NDARO, and JPIAMR), and the Cochrane databases for systematic reviews. Studies will be included if they assess AMR and AMS in SSA from January 2000 to January 31, 2023. RESULTS: The primary outcomes will include the drivers of AMR and approaches to AMS implementation in SSA. The Preferred Reporting Items for Systematic Reviews and Meta-analyses will guide the reporting of this systematic review. CONCLUSIONS: The findings are expected to provide evidence on best practices and resource sharing for policy consideration to healthcare providers and other stakeholders both at the local and international levels. Additionally, the study seeks to establish drivers specific to AMR during the COVID-19 era in the SSA, for example, with the observed increasing trend of antimicrobial misuse during the first or second year of the pandemic may provide valuable insights for policy recommendation in preparedness and response measures to future pandemics. PROSPERO REGISTRATION NUMBER: CRD42022368853.

Diaphragmatic excursion by ultrasound: reference values for the normal population; a cross-sectional study in Egypt.

Background: Measurement of diaphragmatic motion by ultrasound is being utilized in different aspects of clinical practice. Defining reference values of the diaphragmatic excursion is important to identify those with diaphragmatic motion abnormalities. This study aimed to define the normal range of diaphragmatic motion (reference values) by Mmode ultrasound for the normal population. Methods: Healthy volunteers were included in this study. Those with comorbidities, skeletal deformity, acute or chronic respiratory illness were excluded. Diaphragmatic ultrasound in the supine position was performed using a lowfrequency probe. The B-mode was applied for diaphragmatic identification, and the M-mode was employed for the recording of the amplitude of diaphragm contraction during quiet breathing, deep breathing and sniffing. Results: The study included 757 healthy subjects [478 men (63.14%) and 279 women (36.86%)] with normal spirometry and negative history of previous or current respiratory illness. Their mean age and BMI were 45.17 ±14.84 years and 29.36±19.68 (kg/m2). The mean right hemidiaphragmatic excursion was 2.32±0.54, 5.54±1.26 and 2.90±0.63 for quiet breathing, deep breathing and sniffing, respectively, while the left hemidiaphragmatic excursion was 2.35±0.54, 5.30±1.21 and 2.97±0.56 cm for quiet breathing, deep breathing and sniffing, respectively. There was a statistically significant difference between right and left diaphragmatic excursion among all studied subjects. The ratio of right to left diaphragmatic excursion during quiet breathing was (1.009±0.19); maximum 181% and minimum 28%. Only 19 cases showed a right to left ratio of less than 50% (5 men and 14 women). The diaphragmatic excursion was higher in males than females. There was a significant difference in diaphragmatic excursion among age groups. Age, sex and BMI significantly affected the diaphragmatic motion. Conclusions: Diaphragmatic excursion values presented in this study can be used as reference values to detect diaphragmatic dysfunction in clinical practice. Diaphragmatic motion is affected by several factors including age, sex and body mass index.

Cardiovascular system and coronavirus disease-2019 (COVID-19): mutual injuries and unexpected outcomes.

BACKGROUND: Cardiovascular system involvement in coronavirus disease-2019 (COVID-19) has gained great interest in the scientific community. MAIN BODY: Several studies reported increased morbidity and mortality among COVID-19 patients who had comorbidities, especially cardiovascular diseases like hypertension and acute coronary syndrome (ACS). COVID-19 may be associated with cardiovascular complications as arrhythmia, myocarditis, and thromboembolic events. We aimed to illustrate the interactions of COVID-19 disease and the cardiovascular system and the consequences on clinical decision as well as public health. CONCLUSIONS: COVID-19 has negative consequences on the cardiovascular system. A high index of suspicion should be present to avoid poor prognosis of those presenting with unusual presentation.

Synthesis of certain benzothieno[3,2-d]pyrimidine derivatives as a selective SIRT2 inhibitors.

A series of new benzothieno[3,2-d]pyrimidine derivatives were designed and synthesized. The National Cancer Institute (NCI, USA) evaluated all synthesized compounds against 60 human tumor cell lines. Most of the compounds showed good cytotoxicity against MCF-7 breast cancer cell line and UO-31 renal cancer cell line (growth inhibitory range: 17.88%-68.65%). IC50 of twelve most active compounds was determined against MCF-7 and UO-31 cell lines. Compounds 7, 10, 13, 16 and 17 proved a prominent anticancer activity against tested cell lines (IC50 range 0.23-26.25 µg/mL). IC50 against SIRT2 enzyme was evaluated for the most active compounds to explore the mechanism of antiproliferative activity. The best activity was displayed by compound 7 (IC50 = 2.10 µg/mL), which is 6.6 more potent than cambinol as a reference. Moreover, compound 7 displayed high selectivity against SIRT1 and SIRT2 over SIRT3 in the selectivity studies and displayed twice activity of cambinol in hyperacetylation of α-tubulin protein with IC50 = 32.05 µg/mL. Molecular docking study of the synthesized compounds into SIRT2 active site was performed to rationalize the remarkable SIRT2 inhibitory activity.

Effects of silver diamine fluoride/potassium iodide on artificial root caries lesions with adjunctive application of proanthocyanidin.

Treatment of carious root surfaces remains challenging due to the complex pathological processes and difficulty in restoring the original structure of root dentine. Current treatments targeting the de-/re-mineralisation processes are not entirely satisfactory in terms of the protection of the dentinal organic matrix and the highly organised structure of dentine. In this in vitro study, a cross-linking agent - proanthocyanidin (PA) was used in conjunction with a fluoride-based treatment - silver diamine fluoride/potassium iodide (SDF/KI) to putatively stabilise the organic dentinal framework as well as strengthen the collagen-mineral phase interaction. The effectiveness of this strategy was evaluated 24 h after application in terms of the distribution of ion uptake and microstructure of dentine after treatment as well as analysis of the nano-mechanical properties using a dynamic behaviour model. Results showed that individual use of SDF/KI significantly improved the surface microhardness and integrated mineral density (Z) up to 60 µm depth and the recovery of creep behaviour of demineralised dentine in the surface area compared to that treated with deionised distilled water (DDW). The combined treatment of PA and SDF/KI achieved a more homogenous mineral distribution throughout the lesions than SDF/KI alone; a more significant incremental increase in surface microhardness and Z was observed. Specifically, a superior effect on the subsurface area occurred with PA + SDF/KI, with significant improvements in microhardness, elastic modulus and recovery of creep behaviour of the demineralised dentine. Application of SDF/KI induced small discrete crystal formation distributed over the dentine surface and PA contributed to the formation of slit-shaped orifices of the dentinal tubules that were partially occluded. STATEMENT OF SIGNIFICANCE: Demographic transitions and improved oral health behaviour have resulted in increased tooth retention in elderly people. As a consequence, the risk of root dentine caries is increasing due to the age-associated gingival recession and the related frequent exposure of cervical root dentine. Root caries is difficult to repair because of the complex aetiology and dentine structure. The recovery of dentine quality depends not only on reincorporation of minerals but also an intact dentinal organic matrix and the organic-inorganic interfacial structure, which contribute to the biomechanics of dentine. With the capability of dentine modification, cross-linking agents were applied with a fluoride regimen, which improved its treatment efficacy of root caries regarding the distribution of ion uptake and recovery of dentine biomechanics.