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1.
Saudi Pharm J ; 32(4): 101996, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38414782

ABSTRACT

Objective: This study aimed to determine the intention of female Saudi pharmacy students to work in community pharmacies and the factors associated with this intention. Methods: This cross-sectional study was conducted between April 2022 and June 2022 and included female students from pharmacy colleges in Saudi Arabia. The survey was created based on the Theory of Planned Behavior. It included items that measure student intentions, attitudes, subjective norms, and perceived behavioral control regarding working in community pharmacies in Saudi Arabia. The study also included items that assessed sociodemographic characteristics, pharmacy program degrees, training, and job preferences of students. Results: A total of 407 participants completed the survey. The average age was 21.8 (±1.6) years, and most participants were Saudi nationals (97.79 %). The intention of participants to work in community pharmacies after graduation was low (mean = 3.2 ± 1.8; range: 1-7). Slightly positive attitudes toward working in a community pharmacy after graduation were revealed as participants showed an overall attitude mean of 4.5 ± 1.6 (range: 1-7). Furthermore, the participants perceived a low social pressure toward working in a community pharmacy after graduation (mean of 3.3 ± 1.9; range: 1-7). The intention of female pharmacy students to work in community pharmacies was significantly predicted by attitudes (p-value < 0.0001), perceived behavioral control (p-value = 0.0017), nationality (p-value = 0.0151), residence in the Saudi Arabian region (p-value = 0.0013), monthly income (p-value = 0.0231), pharmacy degree program (p-value = 0.0035), training received in community pharmacies (p-value = 0.0145), had a relative working in a community pharmacy (p-value = 0.0257), and preference to work in community pharmacies after graduation (p-value = 0.0001). Conclusion: Female pharmacy students in Saudi Arabia had a low intention to work in community pharmacies, a positive attitude toward working in community pharmacies, and perceived no social pressure to work in them. A positive attitude and behavioral perception of control toward working in community pharmacies were demonstrated among pharmacy students who study at a university outside Riyadh, undertaking a bachelor's degree in pharmacy, have a monthly income higher than 5000 Saudi riyals (USD 1,333.3), previously received training in community pharmacies, having a relative working in a community pharmacy, prefer to work in community pharmacies after graduation.

2.
J Infect Public Health ; 16(11): 1769-1772, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37741012

ABSTRACT

BACKGROUND: Surveillance data are very essential for the effective use of available resources, the prioritization of infection control practices, and setting goals for intervention. The aim was to present the current rates of healthcare-associated infections (HAIs) and device utilization ratios (DUR) among the Saudi Ministry of health (MOH) hospitals. METHODS: MOH analyzed the surveillance data collected from 106 MOH hospitals enrolled in the health electronic surveillance network (HESN) between January 2022 and December 2022. The surveillance methodology was similar to the methods of the US National Healthcare Safety Network (NHSN) and the Gulf Cooperation Council (GCC) center for infection control. RESULTS: More than one million device-days of surveillance were analyzed. The rate of central line associated bloodstream infection (CLABSI) was 2.57 per 1000 central lines days. The rate of catheter-associated urinary tract infection (CAUTI) was 1.08 per 1000 urinary catheter days. The rate of ventilator-associated events (VAE) was 4.21 per 1000 ventilator days. The average rate of pediatric/neonatal ventilator-associated pneumonia (VAP) was 1.53 per 1000 ventilator days. The average DURs were 0.33 for central line, 0.61 for urinary catheter, 0.44 for ventilator in adult patients, and 0.26 in ventilator in pediatric/neonatal patients. In 238632 months of surveillance, the rate of dialysis events (DE) was 0.97 per 100 patient-months. In 86324 surgeries monitored, the rate of surgical site infection (SSI) was 0.87 per 100 surgeries surveyed. CONCLUSIONS: The current report can serve as a national benchmark for MOH hospitals and a regional benchmark for similar hospitals in the region.

3.
Med Sci Monit ; 29: e940573, 2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37381591

ABSTRACT

BACKGROUND This study, employing an online questionnaire, aimed to assess and contrast the awareness, knowledge, and perceptions of dentists in Saudi Arabia (SA) regarding endocrowns (EC) as post-endodontic restorations with those of dentists educated in various other countries. MATERIAL AND METHODS We conducted a cross-sectional survey among dental interns and practicing dentists in government facilities, private dental centers, and dental colleges in SA, including participants of diverse nationalities. We disseminated validated, closed-ended questionnaires through WhatsApp via Google Forms. The Chi-square test was applied to assess associations between categorical variables, with a P-value of ≤0.05 indicating statistical significance. RESULTS The majority of participants (61.2%) indicated that EC restorations are best suited for molar teeth. Furthermore, 69.6% asserted that the primary objective of employing EC is to accomplish minimally invasive preparations while preserving the existing tooth structure. Among the responses, 68.3% pinpointed debonding of ECs as a significant cause of failure. Notably, substantial differences were observed in responses concerning the knowledge or practice of EC across various factors such as gender, educational attainment, country of graduation, and workplace. CONCLUSIONS The findings reveal a comparatively low adoption of ECs among the participants, irrespective of experience or country of education. This underscores the need for incorporating ECs into dental curricula through theoretical and clinical discussions or considering them as a subject for post-graduate continuing education programs.


Subject(s)
Curriculum , Molar , Humans , Cross-Sectional Studies , Educational Status , Dentists
4.
MethodsX ; 10: 102168, 2023.
Article in English | MEDLINE | ID: mdl-37095868

ABSTRACT

The Ball Clamping module of the Laparoscopic Surgery Training Box involves the transfer of beads across the training board using laparoscopic tools. Fundamentals of Laparoscopic Surgery (FLS) requires practitioners to move their hands at as short a distance as possible to perform the functions in the shortest amount of time. This study introduces a feedback tool that presents to the student, after attempting their exam, the right direction (step by step) of obtaining the optimal pathway for minimizing distance traveled in the Ball Clamping Module of the Laparoscopic Surgery Training Box. The shortest distance tour for the ball clamping task is determined using the Traveling Salesman Model (TSM). A sensitivity analysis is conducted to assess the model's applicability to different types and settings of trainer boxes.•Find the best sequence of points resulting in the shortest distance tour for the ball clamping task.•The effects of adding or removing columns from the box cannot be intuitively predicted.

5.
Med Sci Monit ; 28: e938084, 2022 Oct 04.
Article in English | MEDLINE | ID: mdl-36193012

ABSTRACT

BACKGROUND In this questionnaire-based study, we evaluated the prevalence and awareness level of occupational hazards among dental professionals (students, interns, dentists, and specialists) at different dentistry colleges. MATERIAL AND METHODS A self-administered questionnaire was designed from previously conducted studies and distributed to 310 participants from different dental colleges of dentistry in Sana'a City, Yemen. The questionnaire was divided into 4 parts. The first part comprised questions involving sex, age, and clinical professions; the second part, questions on awareness about different occupational hazards; the third part, questions about prevalence of occupational hazards; and the fourth part, questions related to bringing down the prevalence of occupational hazards associated with a dental practice. Data were analyzed using one­way analysis of variance and chi-square tests. RESULTS Significant differences were detected between sex, age groups, and clinical professions. Musculoskeletal disorders were the most common physical hazard, whereas infections were the greatest biological hazard, accounting for 68% and 74%, respectively. Of the participants, 63.5% answered that "patient, practice, and finance'' together were the most common causes of stress among practicing dentists and dental students. The use of gloves and/or masks was the most efficient preventive measure among participants. A significant difference was found among most of the parameters, with P≤0.001. Almost 50% of respondents answered "yes'' in relation to vaccination for hepatitis-B, with P=0.062. CONCLUSIONS The prevalence of occupational hazards was low among dentists and dental students among the tested participants, with significant differences for most of the parameters.


Subject(s)
Occupational Diseases , Dentists , Humans , Occupational Diseases/epidemiology , Occupational Diseases/prevention & control , Prevalence , Surveys and Questionnaires , Vaccination
6.
Int J Gen Med ; 15: 6849-6860, 2022.
Article in English | MEDLINE | ID: mdl-36061964

ABSTRACT

Aim: The root morphology and canal configuration (RMCC) of mandibular and maxillary canines among Saudi population is systematically reviewed and compared with international studies in this research. Methods: This study was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The electronic databases of PubMed, Science Direct, Scopus, Wiley Library, Google website search, and Web of Science were searched. Only local and international cross-sectional, comparative, evaluation, and validation studies or case reports published between 2016 and 2022 that directly evaluated canine RMCC and assessed participants using cone beam computed tomography were included. Results: Forty-three studies that investigated RMCCs (17 local and 26 international) were involved in this review. The original Saudi research recorded that almost 100% of maxillary canines had one root and one canal, whereas 98.4% and 94.1% had one root and one canal in the mandibular arch. Vertucci's class I had the highest percentages in the maxillary and mandibular arches at 98.3% and 95.8%, respectively, followed by class III with 0.7% and 1.9% for the same arches, respectively. International studies recorded that 100% of maxillary canines had one canal and root; the percentages of the mandibular arch were 92.3 and 98% for single canal and root, respectively; and the highest percentage was obtained by Vertucci's class I (91.1%), followed by class III (4.7%). Conclusion: This review reports and confirmed the symmetry of the RMCCs of maxillary and mandibular canines between Saudi studies and other populations. Moreover, Vertucci's classes I and III were the most frequent RMCCs, and two-rooted canines in both arches were considerably less frequently than single-rooted ones.

7.
Cureus ; 14(12): e32203, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36620815

ABSTRACT

Platypnea-orthodeoxia syndrome (POS) is a rare condition characterized by dyspnea and hypoxia worsening in the upright position and relieved in the recumbent position. POS can result from anatomical or functional conditions that cause interatrial communication or deformity of the atrial septum. Investigations with imaging and cardiac catheterization can aid in the evaluation. In cases where POS is caused by intracardiac shunting without pulmonary hypertension, closure of the intracardiac shunt can be curative. We report a case of POS in a 54-year-old male who was treated successfully with percutaneous closure of a patent foramen ovale (PFO).

8.
PLoS One ; 16(9): e0256999, 2021.
Article in English | MEDLINE | ID: mdl-34492066

ABSTRACT

A novel way of integrating the genetic algorithm (GA) and the analytic network process (ANP) is presented in this paper in order to develop a new warehouse assessment scheme, which is developed through various stages. First, we define the main criteria that influence a warehouse performance. The proposed algorithm that integrates the GA with the ANP is then utilized to determine the relative importance values of the defined criteria and sub-criteria by considering the interrelationships among them, and assign strength values for such interrelationships. Such an algorithm is also employed to linguistically present the relative importance and the strength of the interrelationships in a way that can circumvent the use of pairwise comparisons. Finally, the audit checklist that consists of questions related to the criteria is integrated with the proposed algorithm for the development of the warehouse assessment scheme. Validated on 45 warehouses, the proposed scheme has been shown to be able to identify the warehouse competitive advantages and the areas where more improvements can be achieved.


Subject(s)
Internationality , Marketing/economics , Safety/economics , Algorithms , Decision Making , Fuzzy Logic , Humans
9.
Am J Hypertens ; 34(12): 1328-1335, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34436555

ABSTRACT

BACKGROUND: Low-cost, automated interventions that increase knowledge and skills around diet and lifestyle modifications are recommended for cardiovascular disease risk reduction. METHODS: We initiated a quality improvement program to assess the impact of a web-based diet and lifestyle intervention utilizing short animated videos in adults with high blood pressure (BP) at a primary care clinic in Saudi Arabia. We enrolled adults with elevated BP, not on BP medications, who were identified using the electronic medical record. We delivered a web-linked diet and lifestyle intervention using animated videos covering diet and lifestyle topics. Videos and reminders were sent weekly for 5 weeks. Outcomes were proportion who engaged in the program, returned for a repeat BP within 3 months, and change in BP. RESULTS: We enrolled 269 adult participants, with a mean (SD) age of 41.6 (12.4) years; 77% were male. At the conclusion of the pilot, we demonstrated a high level of engagement: overall, 69% of materials were viewed and 67% of patients returned for BP. Patients who returned had a mean (SD) baseline systolic BP of 138.0 (7.2) mm Hg and a large mean reduction in systolic BP from baseline, -10.5 mm Hg (12.4; P < 0.001). CONCLUSIONS: Overall, the feasibility of a video-assisted, web-based, diet and lifestyle intervention as a support tool for hypertension management demonstrated a high participation rate and a high return rate for reassessment of BP. These findings suggest that this low-cost, automated intervention may have a great potential as a scalable tool for blood pressure management. However, randomized trials to understanding the effectiveness of the support tools are needed.


Subject(s)
Electronic Health Records , Hypertension , Adult , Blood Pressure , Humans , Hypertension/drug therapy , Hypertension/therapy , Male , Patient Education as Topic , Quality Improvement
10.
SAGE Open Med ; 9: 20503121211062796, 2021.
Article in English | MEDLINE | ID: mdl-34987815

ABSTRACT

PURPOSE: To assess the incidence of pulp stones in molar and premolar teeth of Southern Saudi Arabian adult sub-population. MATERIALS AND METHODS: Six hundred patient files were randomly selected from the database (records) of the College of Dentistry outpatient department screened by Oral Medicine and Radiology division. Orthopantomogram and bitewing radiographs using radiovisiographs of first and second maxillary and mandibular molars and premolars were interpreted by three examiners. Pulp stones were identified as definite radiopaque masses and scored as present or absent. Data were subjected to statistical analysis using SPSS version 19. RESULTS: Out of total 600 patients, pulp stones were found in 88 (14.7%) patients. Females showed statistically significant higher presence of pulp stones in mandibular molars than males. The patients belonging to middle age group (31-40 years) showed statistically significant higher presence of pulp stones than the other two groups in all first and second molar teeth in both arches. The presence of pulp stones was observed to be higher in maxillary arch than mandibular arch with left side having more frequency than the right side of the arch. CONCLUSION: The prevalence of pulp stones in the study population was found to be 14.7%, and it was higher in molars than premolars. It is quite significant to know the frequency distribution of pulp stones especially for an endodontist or a dentist to plan the root canal treatment of such teeth accordingly.

11.
Front Immunol ; 12: 779473, 2021.
Article in English | MEDLINE | ID: mdl-35185861

ABSTRACT

Bothrops jararaca venom (BjV) can induce mast cell degranulation. In order to investigate the role of mast cells and the interference of the host genetic background in the inflammation induced by BjV, we have used mouse strains selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory response (AIR). Mice were pretreated with an inhibitor of mast cell degranulation, cromolyn (CROM), and injected in footpads or intraperitoneally (i.p.) with BjV. Pain was measured with von Frey hairs, cell migration in the peritoneum by flow cytometry, and reactive oxygen species (ROS) production by chemiluminescence assays. The nociceptive response to BjV was higher in AIRmax than AIRmin mice; however, this difference was abolished by pretreatment with CROM. BjV induced peritoneal neutrophil (CD11b+ GR-1+) infiltration and ROS secretion in AIRmax mice only, which were partially inhibited by CROM. Our findings evidence a role for mast cells in pain, neutrophil migration, and ROS production triggered by BjV in AIRmax mice that are more susceptible to the action of BjV.


Subject(s)
Bothrops , Crotalid Venoms , Animals , Cell Movement , Crotalid Venoms/adverse effects , Inflammation/chemically induced , Mast Cells , Mice , Pain , Reactive Oxygen Species
12.
Front Immunol ; 11: 591563, 2020.
Article in English | MEDLINE | ID: mdl-33193433

ABSTRACT

Crotoxin (CTX), the main neurotoxin from Crotalus durissus terrificus snake venom, has anti-inflammatory, immunomodulatory and antinociceptive activities. However, the CTX-induced toxicity may compromise its use. Under this scenario, the use of nanoparticle such as nanostructured mesoporous silica (SBA-15) as a carrier might become a feasible approach to improve CTX safety. Here, we determined the benefits of SBA-15 on CTX-related neuroinflammatory and immunomodulatory properties during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis that replicates several histopathological and immunological features observed in humans. We showed that a single administration of CTX:SBA-15 (54 µg/kg) was more effective in reducing pain and ameliorated the clinical score (motor impairment) in EAE animals compared to the CTX-treated EAE group; therefore, improving the disease outcome. Of interest, CTX:SBA-15, but not unconjugated CTX, prevented EAE-induced atrophy and loss of muscle function. Further supporting an immune mechanism, CTX:SBA-15 treatment reduced both recruitment and proliferation of peripheral Th17 cells as well as diminished IL-17 expression and glial cells activation in the spinal cord in EAE animals when compared with CTX-treated EAE group. Finally, CTX:SBA-15, but not unconjugated CTX, prevented the EAE-induced cell infiltration in the CNS. These results provide evidence that SBA-15 maximizes the immunomodulatory and anti-inflammatory effects of CTX in an EAE model; therefore, suggesting that SBA-15 has the potential to improve CTX effectiveness in the treatment of MS.


Subject(s)
Crotoxin/administration & dosage , Encephalomyelitis, Autoimmune, Experimental/etiology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Immunomodulation/drug effects , Silicon Dioxide , Theranostic Nanomedicine , Animals , Biomarkers , Biopsy , Crotoxin/adverse effects , Crotoxin/chemistry , Cytokines/metabolism , Disease Management , Disease Models, Animal , Disease Susceptibility , Encephalomyelitis, Autoimmune, Experimental/diagnosis , Female , Mice , Muscle, Skeletal/immunology , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Severity of Illness Index , Spinal Cord/immunology , Spinal Cord/metabolism , Spinal Cord/pathology , Symptom Assessment
13.
J Contemp Dent Pract ; 21(3): 253-260, 2020 Mar 01.
Article in English | MEDLINE | ID: mdl-32434970

ABSTRACT

AIM: To investigate and compare the levels of dental anxiety (DA) in relation to khat and non-khat chewer subjects of both genders from Jazan subpopulation, Kingdom of Saudi Arabia (KSA). MATERIALS AND METHODS: A cross-sectional study was conducted to assess DA using the modified dental anxiety scale (MDAS). A total of 352 subjects from the city of Jazan who attended dental clinics for regular treatment were recruited for this study. A questionnaire was used to collect the required information, which consisted of three parts. Descriptive statistics including means, standard deviations, and percentages were calculated. Multiple group comparisons were analyzed using Chi-square tests using the Statistical Package for Social Science (SPSS) program. p < 0.05 was considered as the significance level. RESULTS: Among the participants, 75.6% was male, while 71.3% khat chewers, and most of them were male (91.2%). The percentage of the overall mean of MDAS was low; 40% to moderate; 38%, while sever anxiety were present in 4% only. Anxiety related to endodontic treatments represents 33.8% in both genders and 34.3% among the khat chewers, while fear was 42.1% among males and 45.4% among khat chewers. The local anesthesia injection in the gum and tooth drilling items of MDAS were represented by 36.6% for both khat and gender groups and resulted in a fairly and extremely anxious situation during dental treatments. All variables were significantly different. CONCLUSION: The overall DA level was low to moderate among the majority of the assessed subjects. Endodontic treatments were the first type of dental treatments for the subjects, while fear of pain was the most common cause of irregular dental visits. Significant differences were detected between khat and non-khat chewers and between genders in relation to anesthesia injection, and drilling of teeth in the MDAS items. CLINICAL SIGNIFICANCE: Community programs focusing on the high DA levels caused by khat chewing might be important in order to minimize the fear of dental treatments and improve and regularize the overall dental treatments.


Subject(s)
Catha , Mastication , Cross-Sectional Studies , Dental Anxiety , Female , Humans , Male , Saudi Arabia
14.
Neurosciences (Riyadh) ; 25(1): 18-24, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31982891

ABSTRACT

OBJECTIVE: To assess the effect of an educational program on the knowledge and perception of stroke in individuals at risk. METHODS: This quasi experiment study, conducted in Health Education Clinics at King Salman Armed Forces Hospital, was designed to assess the knowledge of people who were at risk for stroke, before and after delivering educational content. This content comprised 4-minute face-to-face explanation by a trained educator, 99-second video clip and a short hand-out. The assessment was performed by administering a structured questionnaire. RESULTS: A total of 313 people participated in this study. Before the intervention, 63.6% understood stroke to be due to a disturbance in blood flow resulting in loss of brain function. After delivery of the educational content, the percentage raised to 97.1%. Thirty-Four and Eight percent (109) of participants stated they knew stroke symptoms, and 55.96% knew 2 to 4 symptoms prior to intervention. Our educational content raised these percentages to 98.4% and 79.8% respectively. Good knowledge of stroke symptoms and risk factors was associated with younger age and higher level of education. CONCLUSION: Educational content by means of one-to-one interaction with trained educators, video clips and handouts results in significant improvement in understanding of stroke symptoms and risk factors among at-risk participants.


Subject(s)
Health Knowledge, Attitudes, Practice , Patient Education as Topic/methods , Stroke/epidemiology , Stroke/prevention & control , Surveys and Questionnaires , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pilot Projects , Risk Factors , Saudi Arabia/epidemiology , Stroke/diagnosis , Young Adult
15.
Int J Pharm ; 568: 118542, 2019 Sep 10.
Article in English | MEDLINE | ID: mdl-31330171

ABSTRACT

This study presents a modelling framework to predict the flowability of various commonly used pharmaceutical powders and their blends. The flowability models were trained and validated on 86 samples including single components and binary mixtures. Two modelling paradigms based on artificial intelligence (AI) namely, a radial basis function (RBF) and an integrated network were employed to model the flowability represented by the flow function coefficient (FFC) and the bulk density (RHOB). Both approaches were utilized to map the input parameters (i.e. particle size, shape descriptors and material type) to the flow properties. The input parameters of the blends were determined from the particle size, shape and material type properties of the single components. The results clearly indicated that the integrated network outperformed the single RBF network in terms of the predictive performance and the generalization capabilities. For the integrated network, the coefficient of determination of the testing data set (not used for training the model) for FFC was R2=0.93, reflecting an acceptable predictive power of this model. Since the flowability of the blends can be predicted from single component size and shape descriptors, the integrated network can assist formulators in selecting excipients and their blend concentrations to improve flowability with minimal experimental effort and material resulting in the (i) minimization of the time required, (ii) exploration and examination of the design space, and (iii) minimization of material waste.


Subject(s)
Models, Theoretical , Powders/chemistry , Rheology , Artificial Intelligence , Calcium Phosphates/chemistry , Cellulose/chemistry , Excipients/chemistry , Lactose/chemistry , Particle Size
16.
Biomed Res Int ; 2018: 1267038, 2018.
Article in English | MEDLINE | ID: mdl-30402460

ABSTRACT

Mouse lines selected for maximal (AIRmax) or minimal acute inflammatory reaction (AIRmin) were used to characterize the immune response and the influence of genetic background during pristane-induced arthritis (PIA). Susceptible AIRmax mice demonstrated exacerbated cellular profiles during PIA, with intense infiltration of lymphocytes, as well as monocytes/macrophages and neutrophils, producing higher levels of IL-1ß, IFN-γ, TNF-α, IL-10, total IgG3, and chemokines. Resistant AIRmin mice controlled cell activation more efficiently than the AIRmax during arthritis progression. The weight alterations of the spleen and thymus in the course of PIA were observed. Our data suggest that selected AIRmax cellular and genetic immune mechanisms contribute to cartilage damage and arthritis severity, evidencing many targets for therapeutic actions.


Subject(s)
Arthritis, Experimental/immunology , Cytokines/immunology , Immunoglobulin G/immunology , Terpenes/adverse effects , Acute Disease , Animals , Arthritis, Experimental/chemically induced , Arthritis, Experimental/genetics , Arthritis, Experimental/pathology , Cytokines/genetics , Immunoglobulin G/genetics , Inflammation , Mice , Spleen/immunology , Spleen/pathology , Terpenes/pharmacology , Thymus Gland/immunology , Thymus Gland/pathology
17.
Mol Carcinog ; 57(6): 745-751, 2018 06.
Article in English | MEDLINE | ID: mdl-29500885

ABSTRACT

Somatic KRAS mutations are common in human lung adenocarcinomas and are associated with worse prognosis. In mice, Kras is frequently mutated in both spontaneous and experimentally induced lung tumors, although the pattern of mutation varies among strains, suggesting that such mutations are not random events. We tested if the occurrence of Kras mutations is under genetic control in two mouse intercrosses. Codon 61 mutations were prevalent, but the patterns of nucleotide changes differed between the intercrosses. Whole genome analysis with SNPs in (A/J x C57BL/6)F4 mice revealed a significant linkage between a locus on chromosome 19 and 2 particular codon 61 variants (CTA and CGA). In (AIRmax × AIRmin) F2 mice, there was a significant linkage between SNPs located on distal chromosome 6 (around 135 Mbp) and the frequency of codon 61 mutation. These results reveal the presence of two loci, on chromosomes 6 and 19, that modulate Kras mutation frequency in different mouse intercrosses. These findings indicate that somatic mutation frequency and type are not simple random events, but are under genetic control.


Subject(s)
Adenocarcinoma/genetics , Genetic Predisposition to Disease/genetics , Lung Neoplasms/genetics , Mutation , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins p21(ras)/genetics , Animals , Codon/genetics , Crosses, Genetic , Female , Gene Frequency , Male , Mice, Inbred C57BL , Mice, Inbred Strains
18.
J Egypt Natl Canc Inst ; 30(1): 13-20, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29428373

ABSTRACT

INTRODUCTION: Breast cancer (BC) is the commonest cancer among females worldwide. Some patients present initially at advanced stages and more than 50% of them will develop metastasis (MBC) at some point. Compared to single agents, combination chemotherapy produces higher response rates (RR), longer progression-free survival (PFS) than single agents. This is associated with remarkably higher toxicities. At the same time, overall survival (OS) is comparable. This study aimed to compare safety and efficacy of combination and sequential chemotherapy. PATIENTS AND METHODS: Forty-six MBC patients were randomized to receive 6 cycles of the combination of paclitaxel (175 mg/m2) and cisplatin (70 mg/m2) (combination PC) or paclitaxel for 3 cycles followed by cisplatin for 3 cycles (sequential PC). Endpoints were RR, PFS, OS and safety. RESULTS: Both combination and sequential PC produced similar RR (52% in both arms) and disease control rates (78.3% vs. 73.9%, p = .652). Responses were faster in the combination arm. Median PFS was 8.2 months in the combination compared to 5.0 months in the sequential arm (p = .064). The median OS was 16.5 and 18.8 months in the combination and sequential arms, respectively (p = .866). The combination was more toxic than sequential PC. Grade 3 toxicities were higher with combination PC than to sequential PC (48% vs. 4.3%; p < .001). CONCLUSION: Sequential agent chemotherapy may provide similar response rate and overall survival to combination chemotherapy with much lower toxicities. The former can be considered the standard practice in most instances.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cisplatin/therapeutic use , Paclitaxel/therapeutic use , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/mortality , Cisplatin/administration & dosage , Combined Modality Therapy , Drug Administration Schedule , Female , Humans , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Paclitaxel/administration & dosage , Survival Analysis , Treatment Outcome
19.
Eur J Pharm Biopharm ; 124: 138-146, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29288806

ABSTRACT

In this research, a new systematic modelling framework which uses machine learning for describing the granulation process is presented. First, an interval type-2 fuzzy model is elicited in order to predict the properties of the granules produced by twin screw granulation (TSG) in the pharmaceutical industry. Second, a Gaussian mixture model (GMM) is integrated in the framework in order to characterize the error residuals emanating from the fuzzy model. This is done to refine the model by taking into account uncertainties and/or any other unmodelled behaviour, stochastic or otherwise. All proposed modelling algorithms were validated via a series of Laboratory-scale experiments. The size of the granules produced by TSG was successfully predicted, where most of the predictions fit within a 95% confidence interval.


Subject(s)
Cellulose/chemistry , Fuzzy Logic , Machine Learning , Models, Chemical , Models, Statistical , Technology, Pharmaceutical/methods , Algorithms , Dosage Forms , Drug Compounding , Particle Size , Stochastic Processes
20.
Inflamm Res ; 66(11): 969-980, nov. 2017.
Article in English | Sec. Est. Saúde SP, SESSP-IPPROD, Sec. Est. Saúde SP | ID: biblio-1016861

ABSTRACT

OBJECTIVE AND DESIGN: Pristane-induced arthritis (PIA) in AIRmax mice homozygous for Slc11a1 R and S alleles was used to characterize the influence of Slc11a1 gene polymorphism on immune responses during disease manifestation. Previous reports demonstrated that the presence of the Slc11a1 S allele increased the incidence and severity of PIA in AIRmax SS , suggesting that this gene could interact with inflammatory loci to modulate PIA. We investigated the effects of Slc11a1 alleles on the activation of phagocytes during PIA. TREATMENT: Mice were injected intraperitoneally with two doses of 0.5 mL of mineral oil pristane at 60-day intervals. Arthritis development was accompanied for 180 days. RESULTS: AIRmax SS mice showed differential peritoneal macrophage gene expression profiles during PIA, with higher expression and production of H2O2, NO, IL-1ß, IL-6, TNF-α, and several chemokines. The presence of the Slc11a1 R allele, on the other hand, diminished the intensity of macrophage activation, restricting arthritis development. CONCLUSION: Our data demonstrated the fine-tuning roles of Slc11a1 alleles modulating macrophage activation, and consequent PIA susceptibility, in those mouse lines. (AU)


Subject(s)
Animals , Arthritis, Rheumatoid/genetics , Inflammation/genetics , Polymorphism, Genetic , Arthritis, Experimental , Gene Expression , Cytokines , Macrophages , Mice
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