A comparative analysis of the passivity of fit of complete arch implant-supported frameworks fabricated using different acquisition techniques.

STATEMENT OF PROBLEM: The accuracy of intraoral scanners (IOSs) in recording edentulous jaws has improved recently. However, improvement in accuracy does not necessarily imply the clinical validity of the scans, and limited information is available regarding the manufacture of passively fitting prostheses. PURPOSE: The purpose of this in vitro study was to analyze the passivity of complete arch screw-retained frameworks fabricated using different acquisition techniques. MATERIAL AND METHODS: A 3-dimensional maxillary edentulous model to receive all-on-4 screw-retained frameworks was prototyped. Eighteen polymethylmethacrylate (PMMA) frameworks were fabricated with a 5-axis milling machine and divided into 3 groups according to the acquisition technique (n=6): scanned by using an IOS (CEREC Primescan; Dentsply Sirona), scanned with the aid of an auxiliary device by using the same IOS, and by using a conventional impression and then scanning the stone cast with an extraoral scanner (EOS). The passivity of fit of the frameworks was tested with the 1-screw test, the terminal screw of the framework assembly was tightened on the multiunit abutment (MUA), and the vertical marginal gap (µm) was measured at the other 3 framework-to-abutment interfaces by using a digital microscope at ×40 magnification. A modification to the 1-screw test was analyzed by tightening all screws and then unscrewing all except 1 of the anterior abutments. Data were explored for normality by using the theoretical quantile-quantile (Q-Q) plots and the Shapiro-Wilk test of normality. The Friedman test compared data between the different acquisition techniques; the tightening methods and locations (buccal and palatal) were used as the block variable. The post hoc Dunn test was used when the Friedman test was significant. The Kruksal-Wallis test compared the data from the 2 groups of the tightening methods and the 2 location groups. The aligned rank transformation (ART) ANOVA test was used for the interaction effects among the 3 variables. A multiway ANOVA was applied to the ranked data. (α=.05 for all tests). RESULTS: Significant differences were found among all groups (P<.001). Regarding the passivity of fit, the mean vertical marginal gap was 50 µm for frameworks fabricated from an intraoral scan with the aid of an auxiliary device, 62 µm for frameworks fabricated by using an IOS, and 140 µm for frameworks fabricated by using an EOS. No significant difference was found among all groups regarding the tightening method (P=.355) or location measured (P=.175). CONCLUSIONS: Digital scanning with the aid of an auxiliary device resulted in the best fit; however, digital approaches with or without the auxiliary device resulted in a more accurate fit with a smaller marginal gap than with the conventional impression.

Psychological effect of COVID-19 pandemic on healthcare professionals of Yemen and coping strategies.

COVID-19 pandemic has triggered psychological stress such as anxiety and depression among people around the globe. Due to the nature of the job, healthcare professionals (HCPs) are at high risk of infection and are facing social stigma as well. This research was conducted with the objective to evaluate the psychological influence of the COVID-19 pandemic among HCPs in Yemen and the coping strategies adopted thereof. A web-based, as well as face-to-face cross-sectional study was carried out from July to December 2021 among HCPs of Yemen. The generalized anxiety disorder (GAD-7), patient health questionnaire (PHQ-9), and Brief-COPE scales were applied for the evaluation of anxiety, depression, and coping strategies. A total of 197 HCPs participated in the study where 28.4% and 43.1% had anxiety and depression respectively. The prevalence of both anxiety and depression in the majority were found of the minimal to none and mild categories (71.6% vs. 56.9% respectively). The respondents who had received training on COVID-19 had statistically significant lower GAD-7 scores than those who did not (6.32 vs. 8.02 respectively). A significant statistical difference was observed between physicians versus nurses regarding depression based on the working area (p < 0.05). The physician and pharmacist had a significant positive association with brief COPE scores at the 50th centile compared to other HCPs. The female respondents had statistically significant higher mean Brief COPE scores than male respondents (78.11 vs. 69.50 respectively). Our findings illustrate the requirement for efficient policies through administrative, clinical, and welfare perspectives from the regulatory body in preparedness and preventive measures towards such a pandemic that aids HCPs to provide service in a stress-free condition and assurance of a better healthcare system..

Effectiveness of Antimicrobial Stewardship Program in Long-Term Care: A Five-Year Prospective Single-Center Study.

Objective: To report the effectiveness of the antimicrobial stewardship program (ASP) in a long-term care (LTC) facility, by analyzing the change in antimicrobial consumption and cost and multidrug resistance (MDR) rates over a 5-year period. Method: A prospective interventional study was conducted at a 106-bed facility (nursing home: 100 beds and an intensive care unit (ICU): 6 beds). The ASP was designed and led by a multidisciplinary team including an infectious disease consultant, two clinical pharmacists, a clinical microbiologist, and an infection control preventionist. Five key performance indicators were monitored: (1) intravenous (IV)-to-oral switch rate, (2) consumption of restricted IV antimicrobials (raw consumption and defined daily doses (DDD) index), (3) cost of restricted IV antimicrobials, (4) antimicrobial sensitivity profiles, and (5) MDR rate among hospital-acquired infections (MDR-HAI). Result: A ∼5.5-fold enhancement of the IV-to-oral switch and a 40% reduction in the overall consumption of restricted IV antimicrobials were observed. Regarding the cost, the cumulative cost saving was estimated as 5.64 million SAR (US$1.50 million). Microbiologically, no significant change in antimicrobial sensitivity profiles was observed; however, a large-size reduction in the MDR-HAI rate was observed, notably in ICU where it declined from 3.22 per 1,000 patient days, in 2015, to 1.14 per 1,000 patient days in 2020. Interestingly, the yearly overall MDR rate was strongly correlated with the level of antimicrobial consumption. Conclusion: The implementation of a multidisciplinary ASP in LTC facilities should be further encouraged, with emphasis on physicians' education and active involvement to enhance the success of the strategy.

New Series of VEGFR-2 Inhibitors and Apoptosis Enhancers: Design, Synthesis and Biological Evaluation.

Background: Cancer is still a major world health threat, causing a high rate of mortality. VEGFR-2 inhibitor anticancer agents are of great significance. However, they showed some serious side effects. Purpose: To discover new effective and safer anticancer agents, a new series of piperazinylquinoxaline-based derivatives was designed and synthesized on the basis of the pharmacophoric features of VEGFR-2 inhibitor drugs. Methods: The new candidates were evaluated against A549 lung cancer cells, HepG-2 hepatoma cells, Caco-2 colon cancer cells, MDA breast cancer cells, and VEGFR-2 kinase. Moreover, cell cycle kinetics and apoptosis rates were studied in HepG-2 cells treated with compound 11, which was the most promising candidate. Results: The new derivatives revealed better antitumor results (IC50 from 6.48 to 38.58 µM) against the aforementioned cancer cell lines than sorafenib. Also, the new candidates showed VEGFR-2 inhibition with IC50 values ranging from 0.19 to 0.60 µM compared to 0.08 µM for sorafenib. Compound 11, meanwhile, showed IC50 values equal to 10.61, 9.52, 12.45, 11.52, and 0.19 µM against the cancer cell lines and VEGFR-2, respectively. Moreover, compound 11 raised the apoptosis rate in HepG-2 cells from 5% to 44% and caused 4, 2.3, and 3-fold increases in BAX/Bcl-2 ratio, caspase-3 level, and P53 expression, respectively, compared to control untreated cells. Finally, the new derivatives displayed the correct binding mode into VEGFR-2 kinase pocket, giving interactions with the essential residues. Conclusion: This work suggests that compound 11 is a very significant anticancer candidate, and piperazinylquinoxaline is an important scaffold in the development of new potential effective and safer VEGFR-2 inhibitor agents.

Synthesis, biological evaluation, and molecular docking of new series of antitumor and apoptosis inducers designed as VEGFR-2 inhibitors.

Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15a, 15b, and 15d showed IC50 from 17.39 to 47.10 µM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15d which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 µM against aforementioned cell lines, respectively. Furthermore, Compound 15d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15d showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively.

Design, synthesis and molecular modeling of new quinazolin-4(3H)-one based VEGFR-2 kinase inhibitors for potential anticancer evaluation.

Globally cancer is the second leading cause of death. So that this work is an attempt to develop new effective anti-cancer agents. In line with pharmacophoric features of VEGFR-2 kinase inhibitors, new nineteen quinazolin-4-one derivatives were designed, synthesized and biologically evaluated for their potential anticancer activity. All target compounds were evaluated in vitro for VEGFR-2 tyrosine kinase inhibition. Then, nine compounds of best results were further investigated by in vitro assay against three human cancer cell lines, namely HepG2, PC3 and MCF. N'-{2-](3-Ethyl-6-nitro-4-oxo-3,4-dihydroquinazoline-2-yl)thio[acetyl}benzohydrazide (36) was found to be the most potent candidate as it showed IC50 = 4.6 ± 0.06 µM against VEGFR-2 kinase. It also exhibited IC50 = 17.23 ± 1.5, 26.10 ± 2.2 and 30.85 ± 2.3 µg/mL against HepG2, PC3 and MCF, respectively. At the same time it showed IC50 = 145.93 ± 1.1 µg/mL against the normal human lung fibroblasts cell line (WI-38), indicating good selectivity index. Further investigation into HepG2 cell cycle showed the ability of compound 36 to induce apoptosis and arrest cell growth at G2/M phase. Moreover, docking studies demonstrated the ability of compound 36 to bind VEGFR-2 in a correct manner making three essential hydrogen bonds with the key residues Glu885, Asp1046 and Cys919. In sum, this work suggests that compound 36 can serve as a lead for development of effective anticancer agents targeting VEGFR-2.

Activation of aryl hydrocarbon receptor signaling by a novel agonist ameliorates autoimmune encephalomyelitis.

BACKGROUND: Multiple sclerosis (MS) is a widespread neurological autoimmune disease that includes episodes of demyelination in the central nervous system (CNS). The accumulated evidence has suggested that aryl hydrocarbon receptor (Ahr), a ligand-activated transcription factor, is a promising treatment target for MS. Thus, the current study aimed to identify a novel Ahr ligand with anti-inflammatory potential in experimental autoimmune encephalomyelitis (EAE). METHODS: An in silico analysis was carried out to predict interactions between Ahr and potential natural ligands. The effects of a predicted interaction were examined in vitro using CD4+ T cells under T helper17 (Th17) cell-polarizing conditions and lipopolysaccharide (LPS)-stimulated macrophages. Silencing Ahr and microRNA (miR)-132 was achieved by electroporation. Myelin oligodendrocyte glycoprotein (MOG)35-55 and the adoptive transfer of encephalitogenic CD4+ T cells were used to induce EAE. RESULTS: Molecular docking analysis and in vitro data identified gallic acid (GA) as a novel Ahr ligand with potent activation potential. GA induced the expression of Ahr downstream genes, including cytochrome P450 family 1 subfamily A member 1 (Cyp1a1) and the miR-212/132 cluster, and promoted the formation of the Ahr/Ahr nuclear translocator (Arnt) complex. In vivo, GA-treated mice were resistant to EAE and exhibited reduced levels of proinflammatory cytokines and increased levels of transforming growth factor-ß (TGF-ß). Furthermore, GA reduced infiltration of CD4+CD45+ T cells and monocytes into the CNS. The anti-inflammatory effects of GA were concomitant with miR-132-potentiated cholinergic anti-inflammation and the regulation of the pathogenic potential of astrocytes and microglia. Inducing EAE by adoptive transfer revealed that CD4+ T cells were not entirely responsible for the ameliorative effects of GA. CONCLUSION: Our findings identify GA as a novel Ahr ligand and provide molecular mechanisms elucidating the ameliorative effects of GA on EAE, suggesting that GA is a potential therapeutic agent to control inflammation in autoimmune diseases such as MS.

Use of sildenafil citrate in cases of intrauterine growth restriction (IUGR); a prospective trial.

OBJECTIVE: Intrauterine growth restriction (IUGR) is one of the most serious complications of pregnancy. Up to date, there is no evidence of achieving antenatal treatment of IUGR with abnormal placentation. Although, Sildenafil citrate has shown promising results, there are no firm conclusion till now. The aim of our study is to evaluate the use of Sildenafil citrate in the treatment of IUGR cases associated with impaired placental circulation. MATERIALS AND METHODS: This was a prospective non-randomized study conducted at Mansoura university hospitals starting from March 2016 till October 2017. The studied population included singleton pregnancy and suffering from IUGR associated with impaired placental circulation. RESULTS: This study included 50 pregnant women. Cases were divided into two groups. The first group received sildenafil citrate and the second control group did not receive sildenafil citrate. After 4 weeks after the 1st dose of Sildenafil significant decrease in umbilical artery Doppler indices. There was a statistically significant difference in the mean birth weight at delivery and neonatal admission to the newborn nursery in sildenafil group. CONCLUSION: sildenafil citrate treatment may present a new hope towards better perinatal outcomes for pregnancies complicated by IUGR and impaired placental circulation that may help to decrease neonatal admission to the newborn nursery.

Radiologic Relation of the Colon to the Trajectory of Percutaneous Nephrolithotomy Access in Prone Versus Flank-free Modified Supine Position: A Prospective Study of Intra and Interindividual Influencing Factors.

OBJECTIVE: To compare the distance between the colon and the trajectory of percutaneous nephrolithotomy (PCNL) access both in prone and flank-free modified supine (FFMS) positions as measured on computed tomography and to study the effect of age, gender, BMI, side, and previous renal surgery as influencing factors. PATIENTS AND METHODS: In this prospective study, we included 367 patients scheduled for PCNL. All patients underwent low dose abdominal computed tomography both in prone and FFMS positions. Patients <18 years and those with previous colonic surgery or renal congenital anomalies were excluded. The perpendicular distance between the imaginary line of the renal access and the colon was measured. Findings were correlated to different influencing factors. RESULTS: Two hundred nineteen patients were males, and 148 were females. BMI of <30 were reported in 158 patients whereas BMI >30 in 209 patients. Data analysis showed that the mean perpendicular distance between colon and the renal access in FFMS and prone positions were 35.92 ± 0.22 mm and 17.78 ± 0.09 mm, respectively. In prone position only obesity, age, and overall interaction effect were the significant factors on the studied distance. In FFMS position, in addition to the effect of the prior factors, previous renal surgery also significantly reduces this distance. CONCLUSION: The distance between the colon and assumed PCNL trajectory at a puncture on the posterior axillary line was influenced mainly by patient position. In FFMS position the colon appears to be farther than in prone position. BMI and age significantly influence this distance to a lesser extent.

Is scoring system of computed tomography based metric parameters can accurately predicts shock wave lithotripsy stone-free rates and aid in the development of treatment strategies?

OBJECTIVE: The objective was to determine the predicting success of shock wave lithotripsy (SWL) using a combination of computed tomography based metric parameters to improve the treatment plan. PATIENTS AND METHODS: Consecutive 180 patients with symptomatic upper urinary tract calculi 20 mm or less were enrolled in our study underwent extracorporeal SWL were divided into two main groups, according to the stone size, Group A (92 patients with stone ≤10 mm) and Group B (88 patients with stone >10 mm). Both groups were evaluated, according to the skin to stone distance (SSD) and Hounsfield units (≤500, 500-1000 and >1000 HU). RESULTS: Both groups were comparable in baseline data and stone characteristics. About 92.3% of Group A rendered stone-free, whereas 77.2% were stone-free in Group B (P = 0.001). Furthermore, in both group SWL success rates was a significantly higher for stones with lower attenuation <830 HU than with stones >830 HU (P < 0.034). SSD were statistically differences in SWL outcome (P < 0.02). Simultaneous consideration of three parameters stone size, stone attenuation value, and SSD; we found that stone-free rate (SFR) was 100% for stone attenuation value <830 HU for stone <10 mm or >10 mm but total number SWL sessions and shock waves required for the larger stone group were higher than in the smaller group (P < 0.01). Furthermore, SFR was 83.3% and 37.5% for stone <10 mm, mean HU >830, SSD 90 mm and SSD >120 mm, respectively. On the other hand, SFR was 52.6% and 28.57% for stone >10 mm, mean HU >830, SSD <90 mm and SSD >120 mm, respectively. CONCLUSION: Stone size, stone density (HU), and SSD is simple to calculate and can be reported by radiologists to applying combined score help to augment predictive power of SWL, reduce cost, and improving of treatment strategies.

Assessment of microbiological water quality and its relation to human health in Gaza Governorate, Gaza Strip.

OBJECTIVE: To assess the contamination level of total and faecal coliforms in water wells and distribution networks, and their association with human health in Gaza Governorate, Gaza Strip. METHODS: Data were obtained from the Palestinian Ministry of Health on contamination of total and faecal coliforms in water wells and distribution networks, and on the incidence of water-related diseases in Gaza Governorate. An interview questionnaire was conducted with 150 residents of Gaza. RESULTS: The contamination level of total and faecal coliforms exceeded that of the World Health Organization (WHO) limit for water wells and networks. However, the contamination percentages in networks were higher than that in wells. Giardiasis was strongly correlated with faecal coliform contamination in water networks (r=0.7) compared with diarrhoeal diseases and hepatitis A (r=0.3 and 0.1, respectively). Diarrhoeal diseases were the highest self-reported diseases among interviewees in Gaza city. Such diseases were more prevalent among people using municipal water than people using desalinated water and water filtered at home for drinking (OR=1.6). Intermittent water supply and sewage flooding seemed to contribute largely to self-reported diseases. People in Gaza Strip have good knowledge on drinking water contamination, and this is reflected in good practice. CONCLUSIONS: Water quality has deteriorated in Gaza Strip. This may contribute to the prevalence of water-related diseases. Self-reported diseases among interviewees in Gaza City were associated with source of drinking water, intermittent water supply, sewage flooding and age of water, and wastewater networks.