Design and discovery of new antiproliferative 1,2,4-triazin-3(2H)-ones as tubulin polymerization inhibitors targeting colchicine binding site.

Thirty-five new colchicine binding site inhibitors have been designed and synthesized based on the 1,2,4-triazin-3(2H)-one nucleus. Such molecules were synthesized through a cascade reaction between readily accessible α-amino ketones and phenyl carbazate as a masked N-isocyanate precursor. The synthesized derivatives are cisoid restricted combretastatin A4 analogues containing 1,2,4-triazin-3(2H)-one in place of the olefinic bond, and they have the same essential pharmacophoric features of colchicine binding site inhibitors. The synthesized compounds were evaluated in vitro for their antiproliferative activities against a panel of three human cancer cell lines (MCF-7, HepG-2, and HCT-116), using colchicine as a positive control. Among them, two compounds 5i and 6i demonstrated a significant antiproliferative effect against all cell lines with IC50 ranging from 8.2 - 18.2 µM. Further investigation was carried out for the most active cytotoxic agents as tubulin polymerization inhibitors. Compounds 5i and 6i effectively inhibited microtubule assembly with IC50 values ranging from 3.9 to 7.8 µM. Tubulin polymerization assay results were found to be comparable with the cytotoxicity results. The cell cycle analysis revealed significant G2/M cell cycle arrest of the analogue 5i in HepG-2 cells. The most active compounds 4i, 4j, 5 g, 5i and 6i did not induce significant cell death in normal human lung cells Wl-38, suggesting their selectivity against cancer cells. Also, These compounds upregulated the level of active caspase-3 and boosted the levels of the pro-apoptotic protein Bax by five to seven folds in comparison to the control. Moreover, apoptosis analyses were conducted for compound 5i to evaluate its apoptotic potential. Finally, in silico studies were conducted to reveal the probable interaction with the colchicine binding site. ADME prediction study of the designed compounds showed that they are not only with promising tubulin polymerization inhibitory activity but also with favorable pharmacokinetic and drug-likeness properties.

Ultrasensitive and selective molecularly imprinted electrochemical oxaliplatin sensor based on a novel nitrogen-doped carbon nanotubes/Ag@cu MOF as a signal enhancer and reporter nanohybrid.

A sensitive and selective molecular imprinted polymeric network (MIP) electrochemical sensor is proposed for the determination of anti-cancer drug oxaliplatin (OXAL). The polymeric network [poly(pyrrole)] was electrodeposited on a glassy carbon electrode (GCE) modified with silver nanoparticles (Ag) functionalized Cu-metal organic framework (Cu-BDC) and nitrogen-doped carbon nanotubes (N-CNTs). The MIP-Ag@Cu-BDC /N-CNTs/GCE showed an observable reduction peak at -0.14 V, which corresponds to the Cu-BDC reduction. This peak increased and decreased by eluting and rebinding of OXAL, respectively. The binding constant between OXAL and Cu-BDC was calculated to be 3.5 ± 0.1 × 107 mol-1 L. The electrochemical signal (∆i) increased with increasing OXAL concentration in the range 0.056-200 ng mL-1 with a limit of detection (LOD, S/N = 3) of 0.016 ng mL-1. The combination of N-CNTs and Ag@Cu-BDC improves both the conductivity and the anchoring sites for binding the polymer film on the surface of the electrode. The MIP-based electrochemical sensor offered outstanding sensitivity, selectivity, reproducibility, and stability. The MIP-Ag@Cu-BDC /N-CNTs/GCE was applied to determine OXAL in pharmaceutical injections, human plasma, and urine samples with good recoveries (97.5-105%) and acceptable relative standard deviations (RSDs = 1.8-3.2%). Factors affecting fabrication of MIP and OXAL determination were optimized using standard orthogonal design using L25 (56) matrix. This MIP based electrochemical sensor opens a new venue for the fabrication of other similar  sensors and biosensors.

Disinfection by methylthionine chloride and chitosan in combination with Photo radiation therapy on caries affected dentin nano hardness, adhesive integrity, and bond failure.

OBJECTIVE: The aim of the study was to assess the disinfection efficacy, bond integrity, and nano hardness of caries-affected dentin (CAD) surface bonded to resin cement when disinfected with chlorhexidine (CHX), Methylene blue activated by Photodynamic therapy (MB-PDT), chitosan, silver diamine fluoride (SDF), chitosan activated by PDT, and SDF-diode laser against S. mutans. MATERIALS AND METHODS: A total of 60 human mandibular molars were extracted non-traumatically and gathered using ICDAS criteria. The dentin surface was prepared, leaving CAD to receive a disinfection procedure. After inoculation with S. mutans, the CAD samples were divided into six groups and disinfected with various disinfectants (n = 10) CHX, MB-PDT, chitosan, chitosan-PDT, SDF, and SDF+ diode laser. Survival rates of S. mutans were analyzed following the restoration of samples with resin cement via the etch and rinse method to assess SBS. Also, nano hardness was analyzed. Statistical analysis was performed by using the ANOVA and the Tukey multiple test (p<0.05). The Kruskal-Wallis test was used to evaluate the change in survival rate. RESULTS: Related to the survival rates, the SDF+ diode laser displayed the highest reduction in S. mutans levels and chitosan presented the lowest level of disinfection. The intergroup comparison revealed that CHX and chitosan-PDT displayed comparable outcomes of S. mutans survival rate to that of SDF+ diode laser (p>0.05). Likewise, MB-PDT and SDF displayed a comparable survival rate of S. mutans to Chitosan disinfection (p>0.05). Considering SBS and nano hardness, the highest SBS and NH were exhibited by the SDF+ diode laser, and the lowest SBS and NH values were exhibited by MB-PDT. The intragroup comparison revealed that CAD specimens disinfected with Chitosan-PDT showed comparable SBS and NH values to the SDF+ diode laser (p>0.05). CHX, chitosan, and SDF exhibited bond values and NH comparable to MB-PDT (p<0.05). CONCLUSIONS: Synergistic use of Silver diamine fluoride with diode laser and chitosan activated by PDT can be used as an alternative to CHX for controlling S. mutans growth, promoting enhanced bond efficacy and nano hardness for bonding resin cement to the caries-affected dentin.

Antileishmanial effects, cellular mechanisms, and cytotoxicity of Elettaria cardamomum essential oil against Leishmania major infection.

Leishmaniasis is an infectious disease with various clinical manifestations. We studied the therapeutic effects of Elettaria cardamomum essential oil (ECEO) against Leishmania major infection. In vitro effects of ECEO against L. major were examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and macrophage assays. Nitric oxide (NO) production, infection inhibition in macrophages, and the apoptotic activity of ECEO in treated parasites were also measured. By calculating the 50% cytotoxic concentrations (CC50), we studied the cytotoxicity effects of ECEO on human macrophage cells (THP-1). The efficacy of ECEO for improving cutaneous leishmaniasis (CL) lesions in mice (BALB/c) was determined by evaluating the size of lesions and the number of amastigotes before and after four weeks of treatment. The effects of ECEO on liver and kidney function in the tested mice were also evaluated. ECEO dose-dependently (p<0.001) inhibited the viability and the mean number of promastigotes and amastigote forms of L. tropica. Four weeks of treatment with ECEO at the doses of 2.5 and 5 mg/kg/ day significantly (p<0.001) improved the CL lesions and reduced the number of parasites in the infected mice. ECEO significantly increased NO production, apoptosis induction, and infection rate in parasites. The CC50 value for ECEO and MA was 303.4 µg/mL and 835.2 µg/mL, respectively. In the mice receiving ECEO at the doses of 2.5 and 5 mg/kg/day for 28 days, no significant change was reported between the serum level of liver enzymes and kidney factors when compared with the control group. ECEO displayed promising efficacy in parasite reduction in vitro and in the animal model. ECEO can thus be used as an alternative medicine to treat CL.

Development of Perovskite (MACl)0.33FA0.99MA0.01Pb(I0.99Br0.01)3 Solar Cells via n-Octylammonium Iodide Surface Passivation.

The influence of n-octylammonium iodide (OAI, passive layer) on the types of phases formed in a (MACl)0.33FA0.99MA0.01Pb(I0.99Br0.01)3 perovskite film was studied using X-ray diffraction. Using UV spectrophotometric techniques, it was determined how varied OAI additive layer ratios affected the linear and nonlinear optical characteristics of glass substrates/FTO/compact TiO2/mesoporous TiO2/(MACl)0.33FA0.99MA0.01Pb(I0.99Br0.01)3 films. All films' direct optical bandgap energies were determined to be 1.54 eV. The effects of OAI addition on the films' photoluminescence intensity and emitted colors were also investigated. For the fabricated perovskite solar cells (PSCs) without an OAI passivation layer, the corresponding power conversion efficiency (PCE), open-circuit voltage (VOC), short-circuit current density (JSC), and fill factor (FF) values were 18.8%, 1.02 V, 24.6 mAcm-2, and 75%, respectively. When the concentration of OAI reached 2 mg, the maximum obtained values of PCE, VOC, JSC, and FF were 20.2%, 1.06 V, 24.2 mAcm-2, and 79%, respectively. The decreased trap density and increased recombination resistance were responsible for the improvement in solar cell performance.

Acaricidal, larvacidal, and repellent activity of green synthesized silver nanoparticles against Hyalomma dromedarii.

We aimed at determination of acaricidal, larvacidal, and repellent activities of green synthesized silver nanoparticles (SNP) against Hyalomma dromedarii as one of the most common ticks in camels. SNP were green synthesized by reducing Lupinus albus extract through the precipitation technique. The acaricidal, larvicidal, and repellent activity of SNP against H. dromedarii was studied through the adult immersion test (AIT), the larval packet test (LPT), the vertical movement behavior of tick's larvae method, anti-acetylcholinesterase (AChE) activity, and oxidative enzyme activity. The green synthesized SNP displayed a spherical form with a size ranging from 25-90 nm; whereas the most distribution of particles size was reported at 50-65 nm. SNP dose-dependently (p<0.001) increased the mortality rate of H. dromedarii adult; whereas at 16 and 32 µg/mL completely killed the adult females. Treatment of exposure of H. dromedarii adult to SNP markedly (p<0.001) declined the mean number, weight, and hatchability of eggs. Treatment of H. dromedarii larvae with SNP reduced the viability rate of larvae with the LC50 and LC90 values of 3.1 and 6.9 µg/mL, respectively. Exposure of H. dromedarii larvae to SNP, especially at ½ LC50 and LC50, markedly (p<0.001) increased the oxidative stress and declined the level of antioxidant enzymes in H. dromedarii larvae; whereas, markedly suppressed the AChE activity of the larvae stage of H. dromedarii in comparison to the control group. These results showed that SNP green synthesized by L. albus extract had promising acaricidal, larvicidal and repellent activity against H. dromedarii adults and larvae as a dose-dependent response. SNP also considrably decreased the level of acetylcholinesterase and antioxidant activity and also provokes oxidative stress in H. dromedarii larvae. However, more investigation must be designed to clear the accurate mechanisms and the efficacy of SNP in practical use.

The small molecule Erk1/2 signaling pathway inhibitor PD98059 improves DNA repair in an experimental autoimmune encephalomyelitis SJL/J mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disorder in which the myelin sheath covering the central nervous system axons is damaged or lost, disrupting action potential conduction and leading to various neurological complications. The pathogenesis of MS remains unclear, and no effective therapies are currently available. MS is triggered by environmental factors in genetically susceptible individuals. DNA damage and DNA repair failure have been proposed as MS genetic risk factors; however, inconsistent evidence has been found in multiple studies. Therefore, more investigations are needed to ascertain whether DNA damage/repair is altered in this disorder. In this context, therapies that prevent DNA damage or enhance DNA repair could be effective strategies for MS treatment. The overactivation of the extracellular-signal-related kinase 1 and 2 (Erk1/2) pathway can lead to DNA damage and has been linked to MS pathogenesis. In our study, we observed substantially elevated oxidative DNA damage and slower DNA repair rates in an experimentally autoimmune encephalomyelitis animal model of MS (EAE). Moreover, statistical decreases in oxidative DNA strand breaks and faster repair rates were observed in EAE animals injected with the Erk1/2 inhibitor PD98059 (PD). Moreover, the expression of several genes associated with DNA strand breaks and repair changed in EAE mice at both the mRNA and protein levels, as revealed by the RT2 Profiler PCR array and verified by RT-PCR and protein analyses. The treatment with PD mitigated these changes and improved DNA repair gene expression. Our results demonstrate clear associations between Erk1/2 activation, DNA damage/repair, and MS pathology, and further suggest that PD therapy may be a promising adjuvant therapeutic strategy.

Effectiveness of neck stabilization and Contrology training in comparison to conventional therapy amongst individuals with text neck syndrome.

OBJECTIVE: Cell phones are carried by 79% of people between 18 and 44 years of age for nearly the entire day. Smartphone users spend an average of three hours/per day on their devices, whereas heavy smartphone users spend 8-10 hours/per day on their devices. Text neck is a dangerous disorder that can accelerate the degeneration of the spine. This study aimed to investigate the efficacy of neck stabilization training vs. Contrology or Pilates training in individuals with Text Neck Syndrome. PATIENTS AND METHODS: Participants (n=75) with a history of recurrent neck pain in the previous four months, having moderate pain (at least 4/10 on the numeric pain rating scale, NPRS), and constantly using mobile phones (>4 hours/day) were randomly allocated to one of three groups: a control group (neck isometric training) and two intervention groups (neck stabilization training and Contrology). They were assessed for craniovertebral angle (CVA), NPRS, and neck disability index (NDI) at baseline and at 4 weeks post-intervention. RESULTS: There was a significant difference in the CVA, NPRS, and NDI among individuals with Text Neck Syndrome following intervention as compared to the control. Both the neck stabilization and Contrology training increased CVA and reduced neck pain and neck disability in individuals with Text Neck Syndrome. The two intervention groups showed similar effects in all the clinical outcome measures, suggesting almost equivalent effectiveness in the individuals with Text Neck Syndrome. CONCLUSIONS: Neck stabilization seems to work better than Contrology training when it comes to increasing the craniovertebral angle, reducing pain intensity, and making it easier for individuals with Text Neck Syndrome to move their necks.

Development of lumbar spine MRI referrals vetting models using machine learning and deep learning algorithms: Comparison models vs healthcare professionals.

INTRODUCTION: Referrals vetting is a necessary daily task to ensure the appropriateness of radiology referrals. Vetting requires extensive clinical knowledge and may challenge those responsible. This study aims to develop AI models to automate the vetting process and to compare their performance with healthcare professionals. METHODS: 1020 lumbar spine MRI referrals were collected retrospectively from two Irish hospitals. Three expert MRI radiographers classified the referrals into indicated or not indicated for scanning based on iRefer guidelines. The reference label for each referral was assigned based on the majority voting. The corpus was divided into two datasets, one for the models' development with 920 referrals, and one included 100 referrals used as a held-out for the final comparison of the AI models versus national and international MRI radiographers. Three traditional models were developed: SVM, LR, RF, and two deep neural models, including CNN and Bi-LSTM. For the traditional models, four vectorisation techniques applied: BoW, bigrams, trigrams, and TF-IDF. A textual data augmentation technique was applied to investigate the influence of data augmentation on the models' performances. RESULTS: RF with BoW achieved the highest AUC reaching 0.99. CNN model outperformed Bi-LSTM with AUC = 0.98. With the augmented dataset, the performance significantly improved with an increase in F1 scores ranging from 1% to 7%. All models outperformed the national and international radiographers when compared on the hold-out dataset. CONCLUSION: The models assigned the referrals' appropriateness with higher accuracies than the national and international radiographers. Applying data augmentation significantly improved the models' performances. IMPLICATIONS FOR PRACTICE: The outcomes suggest that the use of AI for checking referrals' eligibility could serve as a supporting tool to improve the referrals' management in radiology departments.

Knowledge, attitude, and practice toward COVID-19 among the public in three Gulf countries - a cross-sectional survey.

OBJECTIVE: This study investigated the knowledge, attitude, and practice toward COVID-19 among residents/citizens of Saudi Arabia (KSA), the United Arab Emirates (UAE), and Kuwait. PATIENTS AND METHODS: A cross-sectional online survey on 3,920 citizens/residents from three Gulf-countries (KSA, UAE, and Kuwait) was conducted between June 15 and August 25, 2020. The survey instrument consisted of demographic characteristics, 13 items on knowledge, 4 items on attitudes, and 7 items on practice towards prevention and control of COVID-19. The Survey link was constructed to be available in Arabic and English. Descriptive statistics of frequency distribution and percentages were calculated, and non-parametric tests were applied to compare the mean knowledge, attitude, and practice scores among different countries. RESULTS: This study included participants from KSA (2,938, 74.9%), UAE (403, 10.3%), and Kuwait (579, 14.8%). The study subjects from KSA, UAE, and Kuwait showed significant differences in the mean knowledge (10.13, 10.52, and 9.19, p<0.001), attitude (2.84, 3.12, and 5.98, p<0.001), and practice (6.11, 5.98 and 5.38, p<0.001) scores towards COVID-19. In addition, Kuwaiti citizens and residents showed significantly lower knowledge, attitude, and practice scores toward COVID-19 than UAE and KSA participants. Participants from Kuwait showed significantly lower knowledge, attitude, and practice scores than the UAE and KSA. However, in general (38.2%), the study participants were optimistic about controlling Coronavirus. Nearly 48.6% started to take an immune-boosting diet to protect themselves from the Coronavirus. CONCLUSIONS: Study participants from KSA, UAE, and Kuwait demonstrated adequate knowledge, positive attitude, and acceptable practices towards COVID-19 control. Electronic and social media should be effectively utilized to spread awareness of COVID-19 among the public.

Stachys lavandulifolia Vahl. exhibits promising in vitro and in vivo antileishmanial activity against Leishmania major infection.

This study aimed to consider the in vitro and in vivo effects of the Stachys lavandulifolia methanolic extract (SLME) (2.5, 5, 10, 25, 50, 100 µg/mL) against Leishmania major infection. The in vitro antileishmanial effects of SLME was studies on promastigote and amastigote forms of L. major. The effect of SLME on the nitric oxide (NO) and apoptosis, secretion of Th1/2 cytokines, and infectivity rate in macrophages cells were also studies. The cytotoxicity of SLME on human (THP-1) and murine (J774-A1 cell) macrophage cells was investigated through the measuring the 50% cytotoxic concentrations (CC50). Moreover, the in vivo effects of SLME for healing the cutaneous leishmaniasis (CL) lesions in infected BALB/c mice studied by assessing the lesions size and the parasite load during four weeks of treatment. The calculated 50% inhibitory concentration (IC50) valuesfor SLME and meglumine antimoniate (MA) against the promastigote stage were 23.4 and 71.1 µg/mL, respectively. For amastigote stage, the IC50 values for SLME and MA were 39.3 µg/mL and 44.3 µg/mL, respectively. Followed by 28 days' topically therapy with SLME at doses of 50 and 100 mg/kg/day, the CL lesions size as well as parasite load were significantly (p<0.001) reduced; such that the recovery percentage of the infected mice was 80% and 97% after treatment with SLME at the dose of 50 and 100 mg/kg, respectively. SLME also markedly induced the NO production and apoptosis; whereas decreased infection rate in macrophage cells. After incubation of infected macrophages with SLME, the level interferon gamma was meaningfully (p<0.001) elevated as a dose-dependent response; in contrast, release of interleukin 10 (IL-10) and IL-4 markedly (p<0.001) decreased. The CC50 value for SLME against THP-1 and J774-A1 cell was 996.4 µg/mL and 741.3 µg/mL, respectively. The calculated selectivity index of >10 for SLME and MA confirmed their specificity to amastigotes and the low toxicity for macrophages. Our results showed the potent effects of SLME in eliminating and controlling Leishmania parasites in both in vitro and in vivo assays. Based on the current experimental study, SLME can be suggested as an alternative medicine for the isolation and production of a new agent for treating CL caused by L. major. Although, we found some cellular mechanisms of SLME against Leishmania parasites, but, additional surveys are necessary to specify the accurate mechanisms of action, toxicity, and its efficacy mainly in human subjects.

Gastrointestinal manifestations of COVID-19: An updated systematic review.

Lack of knowledge about the type and prevalence of gastrointestinal symptoms as a clinical manifestation is one of the reasons for delayed diagnosis and treatment of COVID-19 patients. This review study aimed to systematically review the type and prevalence of gastrointestinal symptoms in COVID-19 patients. To study the gastrointestinal manifestations of COVID-19, we used the 06- PRISMA registered in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-Analysis Facility (SyRF) database. PubMed, Embase, Web of Science, Google Scholar, and Scopus databases were searched for publications on the gastrointestinal manifestations of COVID-19 with no publication time frame. Articles were found using the following terms and search strategy: ["COVID-19, Coronavirus, 2019-nCoV, Clinical SymptomsGastrointestinal or gastric or intestinal manifestations"]. Out of 27652 papers, 35 papers on a total of 6730 COVID-19 patients up to 2022 met the inclusion criteria. Remarkably, most articles (28 papers, 77.8%) were from China (77.8%). The most common gastrointestinal manifestations were nausea or vomiting (13.1%), diarrhea (11.05%), anorexia (8.7%), and abdominal pain (2.4%), respectively. The findings of the present review revealed that contrary to what was initially assumed in the COVID-19 outbreak, this infection does not manifest only as respiratory symptoms but also as gastrointestinal symptoms. Therefore, clinicians and gastroenterologists must be alert to these unusual cases and fecal-oral transmission during the COVID-19 pandemic and implement preventive strategies.

An investigation of lumbar spine magnetic resonance referrals in two Irish university teaching centres: Radiology clinical judgement versus iRefer guideline compliance.

INTRODUCTION: With the annual increase in medical imaging demand, the appropriateness of the lumbar spine magnetic resonance imaging LSMRI referrals is worldwide gaining attention. This study aims to determine the appropriateness of LSMRI referrals and compare radiology clinical decisions to iRefer compliance based solely on referral text content. METHODS: Referral text was extracted from 1021 LSMRI referrals. Two review panels were recruited: three expert radiologists and three MRI radiographers. Radiologists classified cases as indicated or not indicated for scanning based on their clinical judgement. The radiographers classified based solely on iRefer guidelines. Majority voting for each case was applied to both review panels and reviewer agreement was tested using Kappa analysis. Logistic regression models were developed to identify medical disciplines associated with high rates of indicated referrals. RESULTS: 21.7% and 11.9% of the cases were found not indicated for MRI for radiologists and radiographers, respectively. Radiology review identified 18% of the GPs referrals as not indicated and 17% in the radiographers' review. Panel agreement was fair: Kappa values of 0.23 and0.26 for the radiologists and radiographers respectively. Neurosurgery was associated with the highest rate of indicated referrals across both review panels: oncology referrals raised the highest number of open comments. CONCLUSION: The study identified a lower number of not indicated referrals compared to previous research. Findings indicate the importance of both guidelines compliance and clinical judgement to optimise practice. IMPLICATIONS FOR PRACTICE: Findings in this study found that even when strict instructions were given to the MR radiographers to vet referrals using the iRefer guidelines, ambiguity within the guidelines resulted in variations in decision-making. This suggests that detailed protocols are required to support radiographers in the vetting process to ensure a standardised approach.

Correlation between hamstring muscle tightness and incidence of low back pain in female students at Jouf University, Saudi Arabia.

OBJECTIVE: The current study aimed at determining the difference in hamstring tightness between dominant and non-dominant legs and to detect the correlation between LBP and hamstring tightness. PATIENTS AND METHODS: One hundred females with hamstring tightness of at least 15 degrees have been included in the study. Hamstring shortening was examined by the Active Knee Extension test (AKE) and Straight Leg Raising test (SLR), whilst the functional disability' degree was measured by Oswestry Disability Index (ODI). RESULTS: The straight leg raising and the AKE of the dominant leg were significantly more flexible than the non-dominant ones. There was a weak positive non-significant correlation between ODI and AKE of the dominant side (r = 0.162, p = 0.1) and the non-dominant side (r = 0.071, p = 0.48). There was a weak negative non-significant correlation between ODI and SLR of the dominant side (r = - 0.29, p = 0.77) and the non-dominant side (r = - 0.53, p = 0.6). CONCLUSIONS: There was no relation between the degree of hamstring tightness and LBP in female students at Jouf University.

Implications of impacted mandibular cuspids on mental foramen position.

OBJECTIVE: To determine the horizontal and vertical locations and dimensions of the mental foramen (MF) in digital panoramic images (DPI), and to evaluate the effect of impacted mandibular cuspids (IMC) on the position of the MF. MATERIALS AND METHODS: 715 Digital panoramic images were obtained from the archives of oral radiology clinics of the College of Dentistry, Jouf University. Altogether 236 DPI that met inclusion and exclusion criteria were investigated. One specialist principal investigator examined and analyzed the DPI on a computer screen for horizontal location, average position, and vertical location of the MF. RESULTS: The most common horizontal location of MF with the apices of the teeth in the non-impacted group (NIG) was found to be c = 64.70%, and in the impacted group (IG) d = 47.10%. The average magnitude of MF relative to the apex of second bicuspid in the NIG was found to be 47.10% on the mesial side, and in IG 44.10% on the distal side. The average vertical distance of MF from the lower border of the mandible to the lower border of MF (DLM) in NIG was 14.13 mm (SD ± 1.75 mm), and in IG was 16.85 mm (SD ± 3.06 mm). The average vertical distance of MF from the alveolar crest to the superior border of MF (DAC) in NIG was 6.56 mm (SD ± 2.02 mm), and in IG was 6.67 mm (SD ± 2.28 mm). CONCLUSION: The impacted mandibular cuspid has a definite influence on the location and position of the MF.

Evaluation of indigenous plants' extracts for mosquitocidal activity against different stages of Culex quinquefasciatus say (Diptera: Culicidae).

Being vector of West Nile Virus and falariasis the control of Culex quinquefasciatus is likely to be essential. Synthetic insecticide treatment is looking most effective for vectors mosquito control. However, these products are toxic to the environment and non-target organisms. Consequently, ecofriendly control of vectors mosquito is needed. In this regard botanical insecticide is looking more fruitful. Therefore, the present research aimed to investigate the effectiveness of methanolic extract and various fractions, including, n-hexane, ethyl-acetate, chloroform, and aqueous fraction, obtained from methanolic extract of Ailanthus altissima, Artemisia scoparia, and Justicia adhatoda using separating funnel against larval, pupal, and adult stages of Culex quinquefasciatus. The larvae and pupae of Culex quinquefasciatus were exposed to various concentrations (31.25-1000 ppm) of methanolic extract and its fractions for 24 hours of exposure period. For knock-down bioassay (filter paper impregnation bioassay) different concentration of the methanolic extract and its various fractions (i.e. 0.0625, 0.125, 0.25, 0.5 and 1mg/mL) were applied for 1 hour exposure period. The results were statistically analysed using standard deviation, probit analysis, and linear regression. The R2 values of larvae, pupae, and adult range from 0.4 to 0.99. The values of LC50 (concentration causing 50% mortality) for late 3rd instar larvae after 24 hours exposure period range from 93-1856.7 ppm, while LC90 values range from 424 -7635.5ppm. The values of LC50for pupae range form 1326.7-6818.4ppm and and values of LC90 range from 3667.3-17427.9ppm, respectively. The KDT50 range from 0.30 to 2.8% and KDT90 values range from1.2 to 110.8%, respectively. In conclusion, Justicia adhatoda may be effective for controlling populations of vector mosquito.

Molecular detection of Candidatus Anaplasma camelii in camels (Camelus dromedarius) from Asir Province, Saudi Arabia.

Knowledge of molecular identification of tick-borne pathogens in camels in Saudi Arabia is very limited; few molecular epidemiological studies have been under taken. This study was to detect Anaplasma spp. and Piroplasma spp. in camels from Asir Province, Saudi Arabia. A total of 150 blood samples were collected from camels in Asir Province and investigated by polymerase chain reaction (PCR) that targeted 18S rRNA and 23S rRNA to detect the DNA of Piroplasma spp. and Anaplasma spp., respectively. The positive samples for 23S rRNA were assayed again by PCR targeting the 16S rRNA. All the blood samples were free from Piroplasma spp. infection. Three camels (2%) were found to be positive for Anaplasma infection through use of PCR that targeted the 23S rRNA gene. There were no significant differences between ages or sexes in the camels that tested positive for Anaplasma. All positive Anaplasma infections were recorded in camels that were infested by ticks. Two Anaplasma sequences for the16S rRNA gene were deposited in GenBank with accession numbers MN882724 and MN882725. They recorded 99.16% and 99.34% similarities (respectively) with KF843825.1 (Candidatus Anaplasma camelii reported in Unizah, Saudi Arabia). Phylogenetic analyses revealed that the two sequences recorded in this study were close to each other; both were located in one cluster with Candidatus Anaplasma camelii isolates that were recorded before in the adjacent areas of Unizah in Saudi Arabia and Iran. In conclusion: two new Anaplasma genotypes close to Candidatus Anaplasma camelii were found in camels in Asir Province, Saudi Arabia for the first time. The camels in this province were found to be free of Piroplasma infection.

Bioactive Principles and Potentiality of Hot Methanolic Extract of the Leaves from Artemisia absinthium L "in vitro Cytotoxicity Against Human MCF-7 Breast Cancer Cells, Antibacterial Study and Wound Healing Activity".

BACKGROUND: Artemisia absinthium L is an ornamental plant widespread in Saudi Arabia. Traditionally, the plant has been used in the Arabic medicine. But the scientific evidence of the bioactive compounds and their medicinal value was not yet explored widely. OBJECTIVE: The study was designed to analyse the bioactive principles and medicinal properties of Artemisia absinthium L, a traditional herb grown in southern part of Saudi Arabia. METHODS: The bioactive compounds present in Hot Methanolic Extract of the Leaves (HMEL) of Artemisia absinthium L. was explored by GC-MS analysis. The cytotoxicity effect of HMEL was determined against MCF-7 breast cancer cells ATCC and human colon cancer cells HCT 116 ATCC by performing MTT assay. Morphological changes of HMEL treated MCF-7 were observed under a phasecontrast microscope by staining the cells with neutral red. A Reaction Mixture (RM) of HMEL was prepared in Milli-Q water and antibacterial susceptibility was performed against both Gram-positive and Gram-negative bacteria. Furthermore, in vivo wound healing properties of the RM was screened in male rats and their efficacy was compared with standard povidone iodine cream. Biomarkers such as IL-1ß, IL- 6, TNF- α, caspase-9 and caspase-3 levels were determined to qualify the wound healing property. RESULTS: Epiyangambin, flavone, octadecanoic acid, 2,3-dihydroxypropyl ester, palmitic acid ß - monoglyceride, á-D-mannofuranoside, camphor, and terpineol were identified as possible compounds through GC-MS analysis. The HMEL of Artemisia absinthium L was actively inhibiting the proliferation of breast cancer cells MCF-7 ATCC at the concentration of 80.96 ± 3.94 µg/ml as IC50 value but failed to inhibit the proliferation against the treated human colon cancer cells HCT 116 cells ATCC. HMEL of Artemisia absinthium L was showing a moderate spectrum of antibacterial effect against the screened bacteria. RM showed better wound healing property than standard povidone iodine cream that modulates cytokine networks and apoptosis markers levels indicated the healing of wound. CONCLUSION: The study suggested that novel anticancer, antibacterial and immune modulatory molecules can be developed from the leaves of Artemisia absinthium L.