Search results for: Mona Lamine

Authors: Nayera E. Hassan, Sahar A. El-Masry, Rokia A. El Banna, Mones M. Abu Shady, Muhammad Al-Tohamy, Manal Mouhamed Ali, Mehrevan M. Abd El-Moniem, Mona Anwar

Abstract:

Association between vitamin D, adiponectin and obesity is a matter of debate, as they play important role in linking obesity with different cardiometabolic risk factors. Objectives: Evaluation of the association between metabolic risk factors with both adiponectin and vitamin D levels and that between adiponectin and vitamin D among obese Egyptian children. Subjects and Methods: This case-control cross-sectional study consisted of 65 obese and 30 healthy children, aged 8-11 years. 25-hydroxy vitamin D (25(OH) D) level, serum adiponectin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) were measured. Results: The mean 25(OH) D levels in the obese and control groups were 29.9± 10.3 and 39.7 ± 12.7 ng/mL respectively (P < 0.001). The mean 25(OH) D and adiponectin levels in the obese were lower than that in the control group (P < 0.0001). 25(OH) D were inversely correlated with body mass index (BMI), triglyceride, total cholesterol and LDL-cholesterol (LDL-C), while adiponectin level were inversely correlated with systolic blood pressure (SBP), and diastolic blood pressure (DBP), and positively correlated with HDL-C. However, there is no relation between 25(OH) D and adiponectin levels among obese children and total sample. Conclusion: In spite of strong association between vitamin D and adiponectin levels with metabolic risk factors and obesity, there is no relation between 25(OH) D and adiponectin levels. In obese children, there are significant negative correlations between 25(OH) D with lipid profile, and between adiponectin levels with blood pressure. At certain adiponectin level, the relation between it and BMI disappears.

Keywords: 25-hydroxy vitamin D, adiponectin, lipid profile, blood pressure, children

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Authors: Mona Afifi, Yara Al Qahtani, Afnan Al Dosari, Amnah Hamdi

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Background: First aid is the care provided outside the hospital. It is important in saving lives. Delay in helping the victims may result in serious complication or even death. Many people die in Saudi Arabia because they don’t get proper first aid interventions. According to Traffic Safety council in KSA (2012), in the year of 2011 there was 7153 deaths from car accident in KAS. Subjects and method: Quasi-experimental research design was utilized to assess the effect of a structured 45-minute educational session on 82 undergraduate nursing students’ knowledge about first aid. Two tools were developed for the purpose of the current study. First tool containing the sociodemographic data including age, gender, level, and previous participation in a first aid course, and 55 statements specific to different situations that requires first aid. Concept and Knowledge of First Aid has 9 questions, cardiopulmonary resuscitation has 12 questions, Bleeding and Shock have 7 questions, Road Traffic Accidents has 5 questions, Fracture and Trauma have 4 questions, wound has 5 questions, sunstroke has 4 questions, bits and stings has 4 questions and burn has 5 questions. The second tool was to evaluate the campaign session. Result: The overall knowledge score showed significant difference between the pre and post awareness session (59.58 and 93.00 respectively, p=.000). Mean score shows significant difference in pre-tests between third and fourth year nursing students indicating that knowledge of fourth year students is higher compared to third year students with the mean knowledge scores of 69.56 and 60.88 respectively (p=0.006). Conclusion: Results of the current study indicate that the level of the knowledge in the post test session was higher than in the pre session. Also results showed that the fourth year student`s knowledge in pre-test was better compared to previous year.

Keywords: first aid, awareness campaign, undergraduate nursing students, knowledge

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Authors: Mostafa Mabrouk, Basma E. Abdel-Ghany, Mona Moaness, Bothaina M. Abdel-Hady, Hanan H. Beherei

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Tissue engineering became a promising field for bone repair and regenerative medicine in which cultured cells, scaffolds and osteogenic inductive signals are used to regenerate tissues. The annual cost of treating bone defects in Egypt has been estimated to be many billions, while enormous costs are spent on imported bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. The current study is aimed at developing a more strategic approach in order to speed-up recovery after bone damage. This will reduce the risk of fatal surgical complications and improve the quality of life of people affected with such fractures. 3D scaffolds loaded with cheap nano-particles that possess an osteogenic effect were prepared by nano-electrospinning. The Microstructure and morphology characterizations of the 3D scaffolds were monitored using scanning electron microscopy (SEM). The physicochemical characterization was investigated using X-ray diffractometry (XRD) and infrared spectroscopy (IR). The Physicomechanical properties of the 3D scaffold were determined by a universal testing machine. The in vitro bioactivity of the 3D scaffold was assessed in simulated body fluid (SBF). The bone-bonding ability of novel 3D scaffolds was also evaluated. The obtained nanofibrous scaffolds demonstrated promising microstructure, physicochemical and physicomechanical features appropriate for enhanced bone regeneration. Therefore, the utilized nanomaterials loaded with the drug are greatly recommended as cheap alternatives to growth factors.

Keywords: bone regeneration, cheap scaffolds, nanomaterials, active molecules

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Authors: Omneya M. Helmy, Mona T. Kashef

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Aminoglycosides are used in treating a wide range of infections caused by both Gram-negative and Gram positive bacteria. The presence of 16S rRNA methyl transferases (16S-RMTase) is among the newly discovered resistance mechanisms that confer high resistance to clinically useful aminoglycosides. Cephalosporins are the most commonly used antimicrobials in Egypt; therefore, this study was conducted to determine the isolation frequency of 16S rRNA methyl transferases among third generation cephalosporin-resistant clinical isolates in Egypt. One hundred and twenty three cephalosporin resistant Gram-negative clinical isolates were screened for aminoglycoside resistance by the Kirby Bauer disk diffusion method and tested for possible production of 16S-RMTase. PCR testing and sequencing were used to confirm the presence of 16S-RMTase and the associated antimicrobial resistance determinants, as well as the genetic region surrounding the armA gene. Out of 123 isolates, 66 (53.66%) were resistant to at least one aminoglycoside antibiotic. Only one Escherichia coli isolate (E9ECMO) which was totally resistant to all tested aminoglycosides, was confirmed to have the armA gene in association with blaTEM-1, blaCTX-M-15, blaCTX-M-14 and aac(6)-Ib genes. The armA gene was found to be carried on a large A/C plasmid. Genetic mapping of the armA surrounding region revealed, for the first time, the association of armA with aac(6)-Ib on the same transposon. In Conclusion, the isolation frequency of 16S-RMTase was low among the tested cephalosporin-resistant clinical samples. However, a novel composite transposon has been detected conferring high-level aminoglycosides resistance.

Keywords: aminoglcosides, armA gene, β lactmases, 16S rRNA methyl transferases

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Authors: Mona T. Kashef, Omneya M. Helmy

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Multidrug resistant (MDR) bacteria have become a significant public health threat. The prevalence rates, of Gram negative MDR bacteria, are in continuous increase. However, few data are available about these resistant strains. Since, third generation cephalosporins are one of the most commonly used antimicrobials, we set out to investigate the prevalence, different mechanisms and clonal relatedness of multidrug resistance among third generation resistant Gram negative clinical isolates. A total of 114 Gram negative clinical isolates, previously characterized as being resistant to at least one of 3rd generation cephalosporins, were included in this study. Each isolate was tested, using Kirby Bauer disk diffusion method, against its assigned categories of antimicrobials. The role of efflux pump in resistance development was tested by the efflux pump inhibitor-based microplate assay using chloropromazine as an inhibitor. Detecting different aminoglycosides, β-lactams and quinolones resistance genes was done using polymerase chain reaction. The genetic diversity of MDR isolates was investigated using Random Amplification of Polymorphic DNA technique. MDR phenotype was detected in 101 isolates (89%). Efflux pump mediated resistance was detected in 49/101 isolates. Aminoglycosides resistance genes; armA and aac(6)-Ib were detected in one and 53 isolates, respectively. The aac(6)-Ib-cr allele, that also confers resistance to floroquinolones, was detected in 28/53 isolates. β-lactam resistance genes; blaTEM, blaSHV, blaCTX-M group 1 and group 9 were detected in 52, 29, 61 and 35 isolates, respectively. Quinolone resistance genes; qnrA, qnrB and qnrS were detectable in 2, 14, 8 isolates respectively, while qepA was not detectable at all. High diversity was observed among tested MDR isolates. MDR is common among 3rd generation cephalosporins resistant Gram negative bacteria, in Egypt. In most cases, resistance was caused by different mechanisms. Therefore, new treatment strategies should be implemented.

Keywords: gram negative, multidrug resistance, RAPD typing, resistance genes

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Authors: Suzan Ghaddar, Aline Pinon, Manuel Gallardo-villagran, Mona Diab-assaf, Bruno Therrien, Bertrand Liagre

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Colorectal cancer (CRC) is the third most common cancer and exhibits a consistently rising incidence worldwide. Despite notable advancements in CRC treatment, frequent occurrences of side effects and the development of therapy resistance persistently challenge current approaches. Eventually, innovations in focal therapies remain imperative to enhance the patient’s overall quality of life. Photodynamic therapy (PDT) emerges as a promising treatment modality, clinically used for the treatment of various cancer types. It relies on the use of photosensitive molecules called photosensitizers (PS), which are photoactivated after accumulation in cancer cells, to induce the production of reactive oxygen species (ROS) that cause cancer cell death. Among commonly used metal-based drugs in cancer therapy, ruthenium (Ru) possesses favorable attributes that demonstrate its selectivity towards cancer cells and render it suitable for anti-cancer drug design. In vitro studies using distinct arene-Ru complexes, encapsulating porphin PS, are conducted on human HCT116 and HT-29 colorectal cancer cell lines. These studies encompass the evaluation of the antiproliferative effect, ROS production, apoptosis, cell cycle progression, molecular localization, and protein expression. Preliminary results indicated that these complexes exert significant photocytotoxicity on the studied colorectal cancer cell lines, representing them as promising and potential candidates for anti- cancer agents.

Keywords: colorectal cancer, photodynamic therapy, photosensitizers, arene-ruthenium complexes, apoptosis

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Authors: Diana A. Dobreva, Veselina Panayotova, Albena Merdzhanova, Lubomir Makedonski, Mona Stancheva

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Many studies suggest that marine mollusks are healthy food, characterized by low fat and high digestible proteins content. They are one of the most important dietary sources of fat soluble vitamins. The most common species of mollusks in the Bulgarian Black Sea waters are the black mussel (Mytilus galloprovincialis) and the sea snail Rapana (Rapana venosa). One of the main problems of the region is the lack of information about chemical composition of these important marine species. Due to these facts, the aim of the present work was to determine the fat soluble vitamins A, D2, D3, and E, carotenoids–β-carotene and astaxanthin, and total cholesterol contents of mollusk samples and compare them to sample of green algae (Ulva rigida). Samples were collected during autumn from north region of the Black Sea coast, and their wet tissues were used for evaluation of vitamins A, D2, D3, and E, astaxanthin, β-carotene and cholesterol compositions. All fat soluble analytes were simultaneously analyzed by RP- HPLC/UV/FL system. The results were calculated as milligrams per gram total lipid (mg.g-1TL). Alpha-tocopherol and b-carotene were most abundant in algae samples, while mussel samples presented the highest amounts of vitamin D3 (several times higher than the recommended daily intake in Bulgaria (Ordinance № 23 / 19.07.2005)). In all samples, cholesterol content was significantly low, which falls within recommendation of the same ordinance (upper daily consumption should not exceed 300 mg per day). From data, it can be concluded that all samples were characterized as beneficial sources of biologically active compounds.

Keywords: fat soluble vitamins, carotenoids, mussel, rapana, algae

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Authors: Mona Hejazi, Ali Motie Nasrabadi

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Epilepsy is a persistent neurological disorder that affects more than 50 million people worldwide. Hence, there is a necessity to introduce an efficient prediction model for making a correct diagnosis of the epileptic seizure and accurate prediction of its type. In this study we consider how the Effective Connectivity (EC) patterns obtained from intracranial Electroencephalographic (EEG) recordings reveal information about the dynamics of the epileptic brain and can be used to predict imminent seizures, as this will enable the patients (and caregivers) to take appropriate precautions. We use this definition because we believe that effective connectivity near seizures begin to change, so we can predict seizures according to this feature. Results are reported on the standard Freiburg EEG dataset which contains data from 21 patients suffering from medically intractable focal epilepsy. Six channels of EEG from each patients are considered and effective connectivity using Directed Transfer Function (DTF) and Granger Causality (GC) methods is estimated. We concentrate on effective connectivity standard deviation over time and feature changes in five brain frequency sub-bands (Alpha, Beta, Theta, Delta, and Gamma) are compared. The performance obtained for the proposed scheme in predicting seizures is: average prediction time is 50 minutes before seizure onset, the maximum sensitivity is approximate ~80% and the false positive rate is 0.33 FP/h. DTF method is more acceptable to predict epileptic seizures and generally we can observe that the greater results are in gamma and beta sub-bands. The research of this paper is significantly helpful for clinical applications, especially for the exploitation of online portable devices.

Keywords: effective connectivity, Granger causality, directed transfer function, epilepsy seizure prediction, EEG

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Authors: Abeer Mohammed, Nevein Mustafa Elashery, Mona Hassan Abdel Aal, Ereny Wilson Nagib

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The Aim of the current study is to investigate nutrition role in the management of psychiatric disorders. Research Design: A quasi- experimental research design was utilized for this study. Setting The study was conducted at outpatient clinic at Institute of Psychiatry affiliated to Ain Shams University hospitals, using a convenient sample of 50 psychiatric patients with depression, schizophrenia, bipolar disorders, and obsessive compulsive disorders. Tools: data were collected through; first, an interview questionnaire covering socio-demographic characteristics, second, nutrition assessment tools Third, nutrition risk assessment. Fourth, nutrition management program Results showed that there were highly statistically significant improvements in modified nutritional supplements for patients with depression, schizophrenia, bipolar disorders, and obsessive compulsive disorders' patients after conducting the nutrition management program. Regarding psychiatric patients’ knowledge about healthy food, healthy nutritional habits, and patients’ awareness & readiness for change, there were highly statistically significant improvements. Concerning signs and symptoms of psychiatric disorders, there were highly statistically significant improvements for depression, schizophrenia, bipolar disorders, and obsessive-compulsive patients after conducting the management program. In conclusion, the nutrition management program was effective in improving symptoms associated with, depression, schizophrenia, bipolar disorders, and obsessive compulsive disorders. The study recommended that nurses should have more contribution in counseling psychiatric patients, and their families about healthy diet and healthy habits. Further research should recommend studying the effectiveness of herbs on enhancing mental health for psychiatric patients.

Keywords: nutrition, role, management, psychiatric disorders

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Authors: Mani Mofidi, Neda Valizadeh, Ali Hashemaghaee, Mona Hashemaghaee, Soudabeh Shafiee Ardestani

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Background: Acute pain and its management remained the most complaint of emergency service admission. Diagnostic and therapeutic procedures add to patients’ pain. Diminishing the pain increases the quality of patient’s feeling and improves the patient-physician relationship. Aim: The aim of this study was to evaluate the outcomes and side effects of opioid administration in emergency patients. Material and Methods: patients admitted to ward II emergency service of Imam Khomeini hospital, who received one of the opioids: morphine, pethidine, methadone or fentanyl as an analgesic were evaluated. Their vital signs and general condition were examined before and after drug injection. Also, patient’s pain experience were recorded as numerical rating score (NRS) before and after analgesic administration. Results: 268 patients were studied. 34 patients were addicted to opioid drugs. Morphine had the highest rate of prescription (86.2%), followed by pethidine (8.5%), methadone (3.3%) and fentanyl (1.68). While initial NRS did not show significant difference between addicted patients and non-addicted ones, NRS decline and its score after drug injection were significantly lower in addicted patients. All patients had slight but statistically significant lower respiratory rate, heart rate, blood pressure and O2 saturation. There was no significant difference between different kind of opioid prescription and its outcomes or side effects. Conclusion: Pain management should be always in physicians’ mind during emergency admissions. It should not be assumed that an addicted patient complaining of pain is malingering to receive drug. Titration of drug and close monitoring must be in the curriculum to prevent any hazardous side effects.

Keywords: numerical rating score, opioid, pain, emergency department

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Authors: Aly Kassem, Eman A. Sabet, Hanaa A. El-Hady, Doha S. Mohamed, Abeer Sheneef, Mona Fattouh, Mamdouh M. Esmat

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Objective: Giardia lamblia parasite is the most common protozoal infection in human. Concomitant Helecobacter Pylori (H. pylori) and Giardia lamblia infection is common for their similar mode of transmission and strong correlation to socioeconomic levels. Only few reports had described gastric giardiasis. Our aim was to detect H. pylori and Giardia in gastric antral mucosal biopsies from patients with dyspepsia. The impact of both pathogens on clinical, endoscopic and histopathogical changes was studied. Methods: 48 patients with dyspepsia (group1) and 28 control patients (patients undergoing esophagogastroduodenoscopy EGD for reasons other than dyspepsia), (group 2) were studied. Endoscopic data were reported and gastric biopsy specimens were obtained for subsequent PCR assay for both organisms and for histopathological and electron microscopic examination. Results: Endoscopic antral gastritis and duodenal lesions were found in both groups, however, they were significantly more frequently in group 1 (p= 0.002 and P= 0.0005 respectively). Esophageal lesions, nodular antral gastritis, gastric ulcers and superficial corpal gastritis were found only in group 1. PCR detected H. pylori infection in 58% Vs 64 % for group 1 and group 2 respectively (P: NS). Giardia infection was present in 67 % Vs 42 % for group 1 and group 2 respectively (P=0.0003, Odd ratio=2.6). Co-infection with H. pylori and Giardia was present in 33% of group 1 Vs 36% for group 2 (P:NS). Abnormal histologic findings were found in both groups, however, intestinal metaplasia was found in group 1 only. Cellular abnormalities in the form of cytoplasmic vacuoles, mitochondrial destruction or nuclear abnormalities were found by Electron microscopic study in infected subjects of both groups. Conclusion: H. pylori is not the only gastric pathogen in our community, gastric giardiasis is another pathogen. Its contribution might be a factor in persistent dyspepsia after H. pylori eradication.

Keywords: dyspepsia, gastritis, Giardia lamblia, H. pylori

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Authors: Farhad Abbas Gandomkar, Mona Danesh

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This paper aims to determine Fundamental Natural Frequency (FNF) of a structural composite floor system known as Chromite. To achieve this purpose, FNFs of studied panels are determined by development of Finite Element Models (FEMs) in ABAQUS program. American Institute of Steel Construction (AISC) code in Steel Design Guide Series 11, presents a fundamental formula to calculate FNF of a steel framed floor system. This formula has been used to verify results of the FEMs. The variability in the FNF of the studied system under various parameters such as dimensions of floor, boundary conditions, rigidity of main and secondary beams around the floor, thickness of concrete slab, height of composite joists, distance between composite joists, thickness of top and bottom flanges of the open web steel joists, and adding tie beam perpendicular on the composite joists, is determined. The results show that changing in dimensions of the system, its boundary conditions, rigidity of main beam, and also adding tie beam, significant changes the FNF of the system up to 452.9%, 50.8%, -52.2%, %52.6%, respectively. In addition, increasing thickness of concrete slab increases the FNF of the system up to 10.8%. Furthermore, the results demonstrate that variation in rigidity of secondary beam, height of composite joist, and distance between composite joists, and thickness of top and bottom flanges of open web steel joists insignificant changes the FNF of the studied system up to -0.02%, -3%, -6.1%, and 0.96%, respectively. Finally, the results of this study help designer predict occurrence of resonance, comfortableness, and design criteria of the studied system.

Keywords: Fundamental Natural Frequency, Chromite Composite Floor System, Finite Element Method, low and high frequency floors, Comfortableness, resonance.

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Authors: Mona Hassan Aburahma, Alaa Hamed Salama

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Ufasomes “unsaturated fatty acids liposomes” are unique nano-sized self-assembled bilayered vesicles that can be easily created from the readily available unsaturated fatty acid. Ufasomes are formed due to weak associative interaction of the fully ionized and unionized fatty acids into bilayers structures. In the ufasomes constructs, the fatty acid molecules are oriented with their hydrocarbon tails directed toward the membrane interior and the carboxyl groups are in contact with water. Although ufasomes can be employed as a safe vesicular carrier for drugs, the extreme instability of their aqueous dispersions hinders their effective use in drug delivery field. Accordingly, in our study, lyophilized gels containing ufasomes were prepared using a simple assembling technique form the readily available oleic acid to overcome the colloidal instability of the ufasomes dispersions and convert them into accurate unit dosage forms. The influence of changing cholesterol percentage relative to oleic acid on the ufasomes vesicles were investigated using factorial design. The optimized oleic acid ufasomes comprised nanoscaled spherical vesicles. Scanning electron micrographs of the lyophilized gels revealed that the included ufasomes were intact, non-aggregating, and preserved their spherical morphology. Rheological characterization (viscosity and shear stress versus shear rate) of reconstituted ufasomal lyophilized gel ensured the ease of application. The capability of the ufasomes, included in the gel, to penetrate deep through the mucosa layers was illustrated using ex-vivo confocal laser imaging, thereby, highlighting the feasibility of stabilizing ufasomes using lyophilized gel platforms.

Keywords: ufasomes, lyophilized gel, confocal scanning microscopy, rheological characterization, oleic acid

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Authors: Ahmed R. Z. Baghdadi, Ibrahim M. I. Hamoda,  Mona H. Gamal Eldein, Ibrahim Magdy Elnaggar

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Background: High-velocity low amplitude thrust (HVLAT) manipulation and low-velocity low amplitude (LVLA) mobilization are an effective treatment for low back pain (LBP). Purpose: This study compared the effects of HVLAT versus LVLA on pain, functional deficits and segmental mobility in treatment of chronic mechanical LBP. Methods: Ninety patients suffering from chronic mechanical LBP are classified to three groups; Thirty patients treated by HVLAT (group I), thirty patients treated by LVLA (group II) and thirty patients as control group (group III) participated in the study. The mean age was 28.00±2.92, 27.83±2.28 and 28.07±3.05 years and BMI 27.98±2.60, 28.80±2.40 and 28.70±2.53 kg/m2 for group I, II and III respectively. The Visual Analogue Scale (VAS), the Oswestry low back pain disability questionnaire and modified schoper test were used for assessment. Assessments were conducted two weeks before and after treatment with the control group being assessed at the same time intervals. The treatment program group one was two weeks single session per week, and for group II two sessions per week for two weeks. Results: The One-way ANOVA revealed that group I had significantly lower pain scores and Oswestry score compared with group II two weeks after treatment. Moreover, the mobility in modified schoper increased significantly and the pain scores and Oswestry scores decreased significantly after treatment in group I and II compared with control group. Interpretation/Conclusion: HVLAT is preferable to LVLA mobilization, possibly due to a beneficial neurophysiological effect by Stimulating mechanically sensitive neurons in the lumbar facet joint capsule.

Keywords: low back pain, manipulation, mobilization, low velocity

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Authors: Salwa M. Almomen, Mona A. Almaghrabi, Saja M. Alhabardi, Adel A. Alrwisan

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Background: Hepatotoxicity is a major reason for medication withdrawal from the markets. Unfortunately, serious adverse hepatic effects can occur after marketing with limited indicators during clinical development. Therefore, finding possible predictors for hepatotoxicity might guide the monitoring program of various stakeholders. Methods: We examined the clinical review documents for drugs approved in the US from 2011 to 2016 to evaluate their hepatic safety profile. Predictors: we assessed whether these medications meet Hy’s Law with hepatotoxicity grade ≥ 3, labeled hepatic adverse effects at approval, or accelerated approval status. Outcome: post-marketing regulatory action related to hepatotoxicity, including product withdrawal or updates to warning, precaution, or adverse effects sections. Statistical analysis: drugs were included in the analysis from the time of approval until the end of 2019 or the first post-marketing regulatory action related to hepatotoxicity, whichever occurred first. The hazard ratio (HR) was estimated using Cox-regression analysis. Results: We included 192 medications in the study. We classified 48 drugs as having grade ≥ 3 hepatotoxicities, 43 had accelerated approval status, and 74 had labeled information about hepatotoxicity prior to marketing. The adjusted HRs for post-marketing regulatory action for products with grade ≥ 3 hepatotoxicity was 0.61 (95% confidence interval [CI], 0.17-2.23), 0.92 (95%CI, 0.29-2.93) for a drug approved via accelerated approval program, and was 0.91 (95%CI, 0.33-2.56) for drugs with labeled hepatotoxicity information at approval time. Conclusion: This study does not provide conclusive evidence on the association between post-marketing regulatory action and grade ≥ 3 hepatotoxicity, accelerated approval status, or availability of labeled information at approval due to sampling size and channeling bias.

Keywords: accelerated approvals, hepatic adverse effects, drug-induced liver injury, hepatotoxicity predictors, post-marketing withdrawal

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Authors: Golnar Hasheminasab, Mehrdad Faizi, Mona Khoramjouy

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Introduction: Benzodiazepines (BZDs) have pharmacological effects, including anxiolytic, sedative-hypnotic, anticonvulsant, and muscle relaxant properties. However, they have adverse effects such as interaction with alcohol, ataxia, impaired learning, and psychological and physical dependence. According to the structure of zolpidem and on the basis of the structure-activity relationship of BZD receptor ligands, six novel derivatives of 2-fluorobenzyloxy 4,6- diphenylpyramidin-2-ol have been synthesized. We studied the hypnotic, sedative, and anticonvulsant effects of the novel compounds. Method: In this study, we used male mice (18 to 25 g). All the substances were injected intraperitoneally. The hypnotic effect of the compounds was examined by pentobarbital induced sleeping test. The locomotor activities and sedative effects of the novel compounds were evaluated by open field and loss of righting reflex test, respectively. The anticonvulsant effects of the novel compounds were assessed by PTZ and MES tests. Results: In the pentobarbital induced sleeping and open field tests, compound 4-(2-((2-fluorobenzyl)oxy)phenyl)-6-(p-tolyl) pyrimidine-2-ol with ED50=14.20 mg/kg and ED50=47.88 mg/kg, respectively, was the most effective compound. None of the novel compounds showed a significant anticonvulsant effect in the PTZ test. In MES test, compound 4-(2-((2-fluorobenzyl)oxy)phenyl)-6-(p-tolyl)pyrimidine-2-ol with ED50=12.92 mg/kg was the most effective compound. Flumazenil blocked the sedation and hypnosis of all the compounds. Conclusion: All of the novel derivatives showed significant sedative-hypnotic activities and caused the reduction of locomotor activities. The results show that the methyl lipophilic substitutes on the phenyl ring of 4,6-diphenylpyramidin-2-ol derivatives can increase the sedative and hypnotic effects of the derivatives. Flumazenil antagonized the sedative, and the hypnotic effects of the compounds indicate that BZD receptors are involved in the effects.

Keywords: BZD, sedative, hyptonic, anticonvulsant, zolpidem, MES, PTZ, benzodiazepine, locomotor activities, pentobarbital induced sleeping tests

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Authors: Mona Vijayaran, Gurleen Oberoi, Sanjay Mishra

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Introduction: p190 BCR‐ABL1 in CML is often associated with monocytosis. In the case described here, monocytosis is associated with coexisting p210 BCR‐ABL and CMML clones. Mutation analysis using next‐generation sequence (NGS) in our case showed TET2 and SRSF2 mutations. Aims & Objectives: A 75-year male was evaluated for monocytosis and thrombocytopenia. CBC showed Hb-11.8g/dl, TLC-12,060/cmm, Monocytes-35%, Platelets-39,000/cmm. Materials & Methods: Bone marrow examination showed a hypercellular marrow with myeloid series showing sequential maturation up to neutrophils with 30% monocytes. Immunophenotyping by flow cytometry from bone marrow had 3% blasts. Making chronic myelomonocytic leukemia as the likely diagnosis. NGS for myeloid mutation panel had TET2 (48.9%) and SRSF2 (32.5%) mutations. This report further supported the diagnosis of CMML. To fulfil the WHO diagnostic criteria for CMML, a BCR ABL1 by RQ-PCR was sent. The report came positive for p210 (B3A2, B2A2) Major Transcript (M-BCR) % IS of 38.418. Result: The patient was counselled regarding the unique presentation of the presence of 2 clones- P210 CML and CMML. After discussion with an international faculty with vast experience in CMML. It was decided to start this elderly gentleman on Imatinib 200mg and not on azacytidine, as ASXL1 was not present; hence, his chances of progressing to AML would be less and on the other end, if CML is left untreated then chances of progression to blast phase would always be a possibility. After 3 months on Imatinib his platelet count improved to 80,000 to 90,000/cmm, but his monocytosis persists. His 3rd month BCR-ABL1 IS% is 0.004%. Conclusion: After searching the literature, there were no case reports of a coexisting CML p210 with CMML. This case might be the first case report. p190 BCR ABL1 is often associated with monocytosis. There are few case reports of p210 BCR ABL1 positivity in patients with monocytosis but none with coexisting CMML. This case highlights the need for extensively evaluating patients with monocytosis with next-generation sequencing for myeloid mutation panel and BCR-ABL1 by RT-PCR to correctly diagnose and treat them.

Keywords: CMML, NGS, p190 CML, Imatinib

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Authors: Dalila Chaid, Yacine Houmel, Mohamed Lamine Belloulou

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Peripheral neuropathy is a rare but worrying complication of peripheral local anaesthesia. It is caused either by needle contact with the nerve root or by the direct toxicity of local anaesthetics, leading to nerve damage, injury or irritation. Although uncommon, it remains a major concern for anaesthetists. The aim of the study was to assess the prevalence of nerve block-associated neuropathy in knee surgery and to identify the contributing factors in order to minimise the occurrence of this complication. The study also assessed the severity and evolution of lesions, as well as the factors leading to neuropathic pain. Methodology: It is a retrospective observational study on cases of neuropathy related to nerve blocks of the lower limb for knee surgery over a period of seven years (2016-2022). The study included a total of 6,000 patients Analyse the anaesthetic and neuropathic pain-related parameters received from these patients to determine the prevalence and severity of neuropathy. Findings: the prevalence of nerve block-related neuropathy in our study is 5.8‰ for the sciatic nerve and 0.9‰ for the femoral nerve. This was higher compared to the reported rates in the literature, which were between 0.0 to 5‰ for the Sciatic nerve and 0.0 to 3.4‰ for the femoral nerve. These findings highlight the importance of identifying and implementing an ideal anesthesia procedure to reduce the risk of neuropathy associated with nerve blocks. Theoretical Importance: The findings of this study contribute to the existing literature on peripheral neuropathy following locoregional anesthesia. By identifying the prevalence and severity of neuropathy related to nerve blocks, as well as the underlying factors, we provide valuable insights for anesthetists to improve patient safety. This study also emphasizes the need for compliance with technical safety rules to minimize the occurrence of neuropathy. Data Collection and Analysis Procedures: For this study, 25 clinics with retrospective data were collected of neuropathy associated with nerve blocks for knee surgery over a span of seven years. Parameters related to anaesthesia and neuropathic pain were analysed to determine prevalence,severity, and progression of neuropathy. Comparison of our results with the existing literature in order to assess their significance. Questions Addressed: This study aims to define the following points: 1. The prevalence of neuropathy associated with nerve blocks for knee surgery. 2. The factors underlying the development of neuropathy after nerve blocks. 3. Reducing the risk of neuropathy by complying with technical safety rules. 4. Assessing the severity and evolution of neuropathic pain in these cases. Conclusion: this study highlights the need for careful consideration and implementation of anesthesia procedures during nerve blocks for knee surgery. The prevalence of neuropathy linked to these blocks was higher compared to the literature, emphasizing the importance of identifying and minimizing contributing factors. Compliance with technical safety rules is crucial to reduce the risk of peripheral neuropathy. This study provides valuable insights to anesthetists and contributes to improving patient safety in the field of locoregional anesthesia.

Keywords: phantom limb, neuropathic pain, lower limb amputee, ultrasound-guided locoreginal anesthesia

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Authors: Norhan H. Mahdally, Bathini Thissera Riham A. ElShiekh, Noha M. Elhosseiny, Mona T. Kashef, Ali M. El Halawany, Mostafa E. Rateb, Ahmed S. Attia

Abstract:

Multidrug-resistant (MDR) pathogens pose a global threat to healthcare settings. The exhaustion of the current antibiotic arsenal and the scarcity of new antimicrobials in the pipeline aggravate this threat and necessitate a prompt and effective response. This study focused on two major pathogens that can cause serious infections: carbapenem-resistant Acinetobacter baumannii (CRAB) and methicillin-resistant Staphylococcus aureus (MRSA). Multiple soil isolates were collected from several locations throughout Egypt and screened for their conventional and non-conventional antimicrobial activities against MDR pathogens. One isolate exhibited potent antimicrobial activity and was subjected to multiple rounds of fractionation. After fermentation and bio-guided fractionation, we identified pure microbial secondary metabolites with two scaffolds that exhibited promising effects against CRAB and MRSA. Scaling up and chemical synthesis of derivatives of the identified metabolite resulted in obtaining a more potent derivative, which we designated as 2HP. Cytotoxicity studies indicated that 2HP is well-tolerated by human cells. Ongoing work is focusing on formulating the new compound into a nano-formulation to enhance its delivery. Also, to have a better idea about how this compound works, a proteomic approach is currently underway. Our findings suggest that 2HP is a potential new broad-spectrum antimicrobial agent. Further studies are needed to confirm these findings and to develop 2HP into a safe and effective treatment for MDR infections.

Keywords: broad-spectrum antimicrobials, carbapenem-resistant acinetobacter baumannii, drug discovery, methicillin-resistant staphylococcus aureus, multidrug-resistant, natural products

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Authors: Hidayati, Eni Rahmi, Deli Mona, Cytha Nilam Chairani, Aulina Refri Rahmi

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Background: Restoration materials could undergo changes in their clinical properties such as changes in roughness of the restoration's surface. An increase of surface roughness accelerates bacterial colonization and plaque maturation. It can be prevented by mechanically clean the tooth surface by brushing the teeth using toothpaste. Toothpaste may contain abrasives materials that usually found in whitening toothpaste. Those abrasive materials could increase the roughness of the restoration`s surface. Glass ionomer cement (GIC) is one of the restorative material widely used to this day. GC America has made an innovation called EQUIA to improve their wear resistance by coating the surface of GIC using G-Coat Plus. Objective: To determine the effect of teeth was brushing with whitening and non-whitening toothpaste to the surface roughness of coated and uncoated restoration (GIC). Methods: This research was a laboratory experimental with pretest-posttest group design. There were 28 samples which were divided into 2 groups. The first group was brushed with whitening toothpaste and the second group was brushed with non-whitening toothpaste. Each group was divided into group which coated by G-Coat Plus and group which left uncoated. The value of surface roughness was measured by using Roughness Tester. The data was analyzed by using independent t-test to determine differences between the surface roughness of coated samples and uncoated samples brushed with whitening and non-whitening toothpaste. Result: It was found that average roughness differences before and after being brushed by whitening toothpaste were smaller in coated samples than in uncoated samples (0.07 ± 0.09 < 0.12 ± 0.02). Similar results were also found in samples brushed by non-whitening toothpaste (0.02 ± 0.01 0.03 ± 0.01). The differences of average roughness in samples brushed with non-whitening toothpaste were smaller than samples brushed with whitening toothpaste. Conclusion: The data showed there were statistically significant differences between the surface roughness of coated samples and uncoated samples brushed with non-whitening toothpaste (p < 0.05) but the was no statistically significant to samples brushed with whitening toothpaste (p > 0.05).

Keywords: surface roughness, toothpaste, EQUIA, coating

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Authors: Mona Almanasef, Dalia Almaghaslah, Geetha Kandasamy, Rajalakshimi Vasudevan, Sadia Batool

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Background: Community pharmacists are one of the most accessible healthcare practitioners worldwide and their services are used by a large proportion of the population. Expanding the roles of community pharmacists could contribute to reducing pressure on general health practice and other areas of health services. This research aimed to evaluate the contribution of community pharmacists in the provision of public health services and to investigate the perceived barriers to the provision of these services in Saudi Arabia. Materials and Methods: This study followed a cross-sectional design using an online anonymous self-administered questionnaire. The study took place in the Asir region, Saudi Arabia, between September 2019 and February 2020. A convenience sampling strategy was used to select and recruit the study participants. The questionnaire was adapted from previous research and involved three sections: demographics, involvement in public health services and barriers to practicing public health roles. Results: The total number of respondents was 193. The proportion of respondents who reported that they were “very involved” or “involved” in each service was 61.7% for weight management, 60.6% for sexual health, 57.5% for healthy eating, 53.4% for physical activity promotion, 51.3% for dental health, 46.1% for smoking cessation, 39.4% for screening for diabetes, 35.7% for screening for hypertension, 31.1% for alcohol dependence and drug misuse counseling, 30.6% for screening for dyslipidaemia, and 21.8% for vaccination and immunization. Most of the barriers in the current research were rated as having low relevance to the provision of public health services. Conclusion: Findings in the current research suggest that community pharmacists in the Asir region have varying levels of involvement in public health roles. Further research needs to be undertaken to understand the barriers to the provision of public health services and what strategies would be beneficial for enhancing the public health role of community pharmacists in Saudi Arabia.

Keywords: community pharmacist, public health, Asir region, Saudi Arabia

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Authors: Ahmed R. Z. Baghdadi,  Mona H. Gamal Eldein

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Background: With the perceived pain and poor function experienced following knee arthroplasty, patients usually feel unsatisfied. Yet, a controversy still persists on the appropriate operative technique that doesn’t affect proprioception much. Purpose: This study compared the effects of Cruciate Retaining (CR) and Posterior Stabilized (PS) total knee arthroplasty (TKA on dynamic balance, pain and functional performance following rehabilitation. Methods: Thirty patients with CRTKA (group I), thirty with PSTKA (group II) and fifteen indicated for arthroplasty but weren’t operated on yet (group III) participated in the study. The mean age was 54.53±3.44, 55.13±3.48 and 55.33±2.32 years and BMI 35.7±3.03, 35.7±1.99 and 35.73±1.03 kg/m2 for group I, II, and III respectively. The Berg Balance Scale (BBS), WOMAC pain subscale and Timed-Up-and-Go (TUG) and Stair-Climbing (SC) tests were used for assessment. Assessments were conducted four weeks pre- and post-operatively, three, six and twelve months post-operatively with the control group being assessed at the same time intervals. The post-operative rehabilitation involved hospitalization (1st week), home-based (2nd-4th weeks), and outpatient clinic (5th-12th weeks) programs, follow-up to all groups for twelve months. Results: The Mixed design MANOVA revealed that group I had significantly lower pain scores and SC time compared with group II three, six and twelve months post-operatively. Moreover, the BBS scores increased significantly and the pain scores and TUG and SC time decreased significantly six months post-operatively compared with four weeks pre- and post-operatively and three months post-operatively in group I and II with the opposite being true four weeks post-operatively. But no significant differences in BBS scores, pain scores and TUG and SC time between six and twelve months post-operatively in group I and II. Interpretation/Conclusion: CRTKA is preferable to PSTKA, possibly due to the preserved human proprioceptors in the un-excised PCL.

Keywords: dynamic balance, functional performance, knee arthroplasty, long-term

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Authors: Soumia Hammadi, Imane Nouacer, Lamine Hamida, Younes A. Hammadi, Rachid Chaibi

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Aims and objective: In the present work, we investigate the impact of both acute and chronic diabetes mellitus induced by streptozotocin (STZ) on the hypothalamus of the small gerbil (Gerbillus gerbillus). In this purpose, we aimed to study the histologic structure of the gerbil’s hypothalamic supraoptic (NSO) and paraventricular nucleus (NPV) at two distinct time points: two days and 30 days after diabetes onset. Methods: We conducted our investigation using 19 adult male gerbils weighing 25 to 28 g, divided into three groups as follow: Group I: Control gerbils (n=6) received an intraperitoneal injection of citrate buffer. Group II: STZ-diabetic gerbils (n=8) received a single intraperitoneal injection of STZ at a dose of 165 mg/kg of body weight. Diabetes onset (D0) is considered with the first hyperglycemia level exceeding 2,5 g/L. This group was further divided into two subgroups: Group II-1: Experimental Gerbils, at acute state of diabetes (n=8) sacrificed after 02 days of diabetes onset, Group II-2: Experimental Gerbils at chronic state of diabetes (n=7) sacrificed after 30 days of diabetes onset. Two and 30 days after diabetes onset, gerbils had blood drawn from the retro-orbital sinus into EDTA tubes. After centrifugation at -4°C, plasma was frozen at -80°C for later measurement of Cortisol, ACTH, and insulin. Afterward, animals were decapitated; their brain was removed, weighed, fixed in aqueous bouin, and processed and stained with Toluidine Bleu stain for histo-stereological analysis. A comparison was done with control gerbils treated with citrate buffer. Results: Compared to control gerbils, at 02 Days post diabetes onset, the neuronal somata of the paraventricular (NPV) and supraoptic nuclei (NSO) expressed numerous vacuoles of various sizes, we distinct also a neuronal juxtaposition and several unidentifiable vacuolated profiles were also seen in the neuropile. At the same time, we revealed the presence of à shrunken and condensed nuclei, which seem to touch the parvocellular neurons ( NPV); this leads us to suggest the presence of an apoptotic process in the early stage of diabetes. At 30 days of diabetes mellitus, the NPV manifests a few neurons with a distant appearance, in addition the magnocellular neurons in both NPV and NSO were hypertrophied with a rich euchromatin nucleus, a well-defined nucleolus, and a granular cytoplasm. Despite the neuronal degeneration at this stage, unexpectedly, ACTH registers a continuous significant high level compared to the early stage of diabetes mellitus and to control gerbils. Conclusion: The results suggest that the induction of diabetes mellitus using STZ in the small gerbils lead to alterations in the structure and morphology of the hypothalamus and hyper-secretion of ACTH and cortisol, possibly indicating hyperactivity of the hypothalamo-pituitary adrenal axis (HPA) during both the early and later stages of the disease. The subsequent quantitative evaluation of CRH, immunehistochemical evaluation of apoptosis, and oxidative stress assessment could corroborate our results.

Keywords: diabetes type 1., streptozotocin., small gerbil., hypothalamus., paraventricular nucleus., supraoptic nucleus.

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Authors: Mona Almanasef, Angel Chater, Jane Portlock

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Introduction: A 'flipped classroom' uses technology to shift the traditional lecture outside the scheduled class time and uses the face-to-face time to engage students in interactive activities. Aim of the Study: Assess the feasibility, acceptability, and effectiveness of using the 'flipped classroom' teaching format with MPharm students in two pharmacy schools in the UK: UCL School of Pharmacy and the School of Pharmacy and Biomedical Sciences at University of Portsmouth. Methods: An experimental mixed methods design was employed, with final year MPharm students in two phases; 1) a qualitative study using focus groups, 2) a quasi-experiment measuring knowledge acquisition and satisfaction by delivering a session on rheumatoid arthritis, in two teaching formats: the flipped classroom and the traditional lecture. Results: The flipped classroom approach was preferred over the traditional lecture for delivering a pharmacy practice topic, and it was comparable or better than the traditional lecture with respect to knowledge acquisition. In addition, this teaching approach was found to overcome the perceived challenges of the traditional lecture method such as fast pace instructions, student disengagement and boredom due to lack of activities and/or social anxiety. However, high workload and difficult or new concepts could be barriers to pre-class preparation, and therefore successful flipped classroom. The flipped classroom encouraged learning scaffolding where students could benefit from application of knowledge, and interaction with peers and the lecturer, which might, in turn, facilitate learning consolidation and deep understanding. This research indicated that the flipped classroom was beneficial for all learning styles. Conclusion: Implementing the flipped classroom at both pharmacy institutions was successful and well received by final year MPharm students. Given the attention now being put on the Teaching Excellence Framework (TEF), understanding effective methods of teaching to enhance student achievement and satisfaction is now more valuable than ever.

Keywords: blended learning, flipped classroom, inverted classroom, pharmacy education

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Authors: Sataroopa Mishra, Mona Basker, Sneha Varkki, Ram Kumar Pandian, Grace Rebekah

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Background: Sleep deprivation is a matter of public health importance among adolescents. We used adolescent sleep wake scale and adolescent sleep hygiene scale to determine the sleep quality and sleep hygiene respectively of school going adolescents in Vellore city of India. The objective of the study was to do factorial analysis of the scales and validate it for use in local population. Methods: Observational questionnaire based cross sectional study. Setting: Community based school survey in a semi-urban setting in three schools in Vellore city. Data collection: Non probability sample was collected form students studying in standard 9 and 11. Students filled Adolescent Sleep Wake scale (ASWS) and Adolescent Sleep Hygiene Scale (ASHS) translated into vernacular language. Data Analysis: Exploratory Factorial Analysis was used to see the factor loading of various components of the two scales. Confirmatory factorial analysis is subsequently planned for assessing the internal validity of the scales.Results: 557 adolescents were included in the study of 12 – 17 years old. Exploratory factorial analysis of adolescent sleep hygiene scale indicated significant factor loading for 18 items from 28 items originally devised by the authors and has been reconstructed to four domains instead of 9 domains in the original scale namely sleep stability, cognitive – emotional, Physiological - bed time routine - behavioural arousal factor (activites before bedtime and during bed time), Sleep environment (lighting and bed sharing). Factorial analysis of Adolescent sleep wake scale showed factor loading of 18 items out of 28 items in original scale reconstructed into 5 aspects of sleep quality. Conclusions: The factorial analysis gives a reconstructed scale useful for the local population. Further a confirmatory factorial analysis has been subsequently planned to determine the internal consistency of the scale for local population.

Keywords: factorial analysis, sleep hygiene, sleep quality, adolescent sleep scale

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Authors: Metrek Almetrek, Naser Alqahtani, Eisa Ghazwani, Mona Asiri, Mohammed Alqahtani, Magboolah Balobaid

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Background: Advocacy of potential for community coalitions to positively address social determinants of health and quality of life, little is known about the views of stakeholders involved in such efforts. This study sought to assess the provinces leaders’ perspectives about social determinants related to the Health Neighborhood Initiative (HNI), a new county effort to support community coalitions. Method and Subjects: We used a descriptive, qualitative study using personal interviews in 2022. We conducted it in the community coalition's “main cities committees” set across service planning areas that serve vulnerable groups located in the seven registered healthy cities to WHO (Abha, Tareeb, Muhayel, Balqarn, Alharajah, Alamwah, and Bisha). We conducted key informant interviews with 76 governmental, profit, non-profit, and community leaders to understand their perspectives about the HNI. As part of a larger project, this study focused on leaders’ views about social determinants of health related to the HNI. All interviews were audio-recorded and transcribed. An inductive approach to coding was used, with text segments grouped by social determinant categories. Results: Provinces leaders described multiple social determinants of health and quality of life that were relevant to the HNI community coalitions: housing and safety, community violence, economic stability, city services coordination and employment and education. Leaders discussed how social determinants were interconnected with each other and the need for efforts to address multiple social determinants simultaneously to effectively improve health and quality of life. Conclusions: Community coalitions have an opportunity to address multiple social determinants of health and quality of life to meet the social needs of vulnerable groups. Future research should examine how community coalitions, like those in the HNI, can actively engage with community members to identify needs and then deliver evidence-based care.

Keywords: social determinants, health and quality of life, vulnerable groups, qualitative research

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Authors: Rawia M. Khalil, Ahmed A. Abd El Rahman, Mahfouz A. Kassem, Mohamed S. El Ridi, Mona M. Abou Samra, Ghada E. A. Awad, Soheir S. Mansy

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Solid lipid nanoparticles (SLNs) have gained great attention for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Our work deals with the preparation of nystatin loaded solid lipid nanoparticles (NystSLNs) using the hot homogenization and ultrasonication method. The prepared NystSLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, transmission electron microscopy, differential scanning calorimetry, rheological behavior and in vitro drug release. A stability study for 6 months was performed. A microbiological study was conducted in male rats infected with Candida albicans, by counting the colonies and examining the histopathological changes induced on the skin of infected rats. The results showed that SLNs dispersions are spherical in shape with particle size ranging from 83.26±11.33 to 955.04±1.09 nm. The entrapment efficiencies are ranging from 19.73±1.21 to 72.46±0.66% with zeta potential ranging from -18.9 to -38.8 mV and shear-thinning rheological Behavior. The stability studies done for 6 months showed that nystatin (Nyst) is a good candidate for topical SLN formulations. A least number of colony forming unit/ ml (cfu/ml) was recorded for the selected NystSLN compared to the drug solution and the commercial Nystatin® cream present in the market. It can be fulfilled from this work that SLNs provide a good skin targeting effect and may represent promising carrier for topical delivery of Nyst offering the sustained release and maintaining the localized effect, resulting in an effective treatment of cutaneous fungal infection.

Keywords: candida infections, hot homogenization, nystatin, solid lipid nanoparticles, stability, topical delivery

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Authors: Mona Alharbi

Abstract:

Melioidosis has emerged as a lethal disease. Unfortunately, the molecular mechanisms of virulence and pathogenicity of Burkholderia pseudomallei remain unknown. However, proteomics research has selected putative targets in B. pseudomallei that might play roles in the B. pseudomallei virulence. BPSL 2418 putative protein has been predicted as a free methionine sulfoxide reductase and interestingly there is a link between the level of the methionine sulfoxide in pathogen tissues and its virulence. Therefore in this work, we describe the cloning expression, purification, and crystallization of BPSL 2418 and the solution of its 3D structure using X-ray crystallography. Also, we aimed to identify the substrate binding and reduced forms of the enzyme to understand the role of BPSL 2418. The gene encoding BPSL2418 from B. pseudomallei was amplified by PCR and reclone in pETBlue-1 vector and transformed into E. coli Tuner DE3 pLacI. BPSL2418 was overexpressed using E. coli Tuner DE3 pLacI and induced by 300μM IPTG for 4h at 37°C. Then BPS2418 purified to better than 95% purity. The pure BPSL2418 was crystallized with PEG 4000 and PEG 6000 as precipitants in several conditions. Diffraction data were collected to 1.2Å resolution. The crystals belonged to space group P2 21 21 with unit-cell parameters a = 42.24Å, b = 53.48Å, c = 60.54Å, α=γ=β= 90Å. The BPSL2418 binding MES was solved by molecular replacement with the known structure 3ksf using PHASER program. The structure is composed of six antiparallel β-strands and four α-helices and two loops. BPSL2418 shows high homology with the GAF domain fRMsrs enzymes which suggest that BPSL2418 might act as methionine sulfoxide reductase. The amino acids alignment between the fRmsrs including BPSL 2418 shows that the three cysteines that thought to catalyze the reduction are fully conserved. BPSL 2418 contains the three conserved cysteines (Cys⁷⁵, Cys⁸⁵ and Cys¹⁰⁹). The active site contains the six antiparallel β-strands and two loops where the disulfide bond formed between Cys⁷⁵ and Cys¹⁰⁹. X-ray structure of free methionine sulfoxide binding and native forms of BPSL2418 were solved to increase the understanding of the BPSL2418 catalytic mechanism.

Keywords: X-Ray Crystallography, BPSL2418, Burkholderia pseudomallei, Melioidosis

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Authors: Mona Nada, Fahmy Fahmy

Abstract:

Background: Pleomorphic dermal sarcoma is a rare form of skin cancer affecting cutaneous layer and, in some cases associated with recurrence and metastasis, very commonly to seen in elderly patient affecting the area of head and neck. Pleomorphic dermal sarcoma rises in ultraviolet light exposed areas. The symptoms and severity of this kind of skin cancer varies according to histological factors. The differentiation of Pleomorphic dermal sarcoma needs extensive immunohistochemistry, as the diagnosis depends mainly on exclusion to rule out other malignancy like poorly differentiated squamous cell carcinoma, melanoma, angiosarcoma and leiomyosarcoma. Objective: assessing the management of Pleomorphic dermal sarcoma in our unit and compared to the updated guidelines. Design: Retrospective study Collection of patient data from medical records at countess of Chester plastic surgery unit of the last 5 years, all histologically confirmed Pleomorphic dermal sarcoma (2017-2023). Data were collected confirmed to be Pleomorphic dermal sarcoma were included in the study. The data collected: clinical description of the lesions at first presentation, operation time, multidisciplinary team discussion, plan, referral as well as second operation and investigation done. With comparison of histological examination, immunohistochemistry staining, the excision and rate of recurrence. Results: data collected N19 from (2017-2023) showed the disease predominantly affecting males and the lesion mainly in head and neck, the diagnosis needed extensive immunohistochemistry to differentiate between other malignancy. recurrence present in numbers of the cases which managed after multidisciplinary team discussion either by excision or radiotherapy. Conclusion: Pleomorphic dermal sarcoma is a rare malignancy which needs more understanding and avoid missing as it is aggressive form of skin cancer, there is a chance of metastasis and recurrence which makes it very important to understand the process of development of the cancer and frequent review of the management guidelines.

Keywords: pleomorphic dermal sarcoma, recurrence, radiotherapy, surgical

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Authors: Sundus Mona, Atif Adnan, Babar Ali, Fareeha Arshad, Allah Rakha

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Molecular diversity is the variation in the abundance of species. Forensic entomology is a neglected field in Pakistan. Insects collected from the crime scene should be handled by forensic entomologists who are currently virtually non-existent in Pakistan. Correct identification of insect specimen along with knowledge of their biodiversity can aid in solving many problems related to complicated forensic cases. Inadequate morphological identification and insufficient thermal biological studies limit the entomological utility in Forensic Medicine. Recently molecular identification of entomological evidence has gained attention globally. DNA barcoding is the latest and established method for species identification. Only proper identification can provide a precise estimation of postmortem intervals. Arthropods are known to be the first tourists scavenging on decomposing dead matter. The objective of the proposed study was to identify species by molecular techniques and analyze their phylogenetic importance with barcoded necrophagous insect species of early succession on human cadavers. Based upon this identification, the study outcomes will be the utilization of established DNA bar codes to identify carrion feeding insect species for concordant estimation of post mortem interval. A molecular identification method involving sequencing of a 658bp ‘barcode’ fragment of the mitochondrial cytochrome oxidase subunit 1 (CO1) gene from collected specimens of unknown dipteral species from cadavers of Lahore was evaluated. Nucleotide sequence divergences were calculated using MEGA 7 and Arlequin, and a neighbor-joining phylogenetic tree was generated. Three species were identified, Chrysomya megacephala, Chrysomya saffranea, and Chrysomya rufifacies with low genetic diversity. The fixation index was 0.83992 that suggests a need for further studies to identify and classify forensically relevant insects in Pakistan. There is an exigency demand for further research especially when immature forms of arthropods are recovered from the crime scene.

Keywords: molecular diversity, DNA barcoding, species identification, forensically relevant

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