Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Effect of valproic acid on the pharmacokinetic profile of oxcarbazepine in the rat

The pharmacokinetics of oxcarbazepine (30 mg kg-1, po), administered for 1 week, was studied in rats pre-treated for 2 weeks with valproic acid (100 mg kg-1, po). Oxcarbazepine (OXC) plasma levels were measured over a period of 24 h from dosing, using a sensitive HPLC method. No significant changes were observed in the mean values of OXC pharmacokinetic parameters (Cmax, Tmax, t1/2 and AUC0-infinity) between the control and the pre-treated groups. The findings of this study suggest that OXC metabolism in the rat is apparently not affected by valproic acid, and the lack of effect may be attributed to the different pathways of biotransformation of the two drugs.     

Consumer attitudes towards community pharmacy services in Saudi Arabia

Objective The purpose of this study was to determine consumer attitudes towards community pharmacy and their preferences for the introduction of new services. Methods A self‐completion questionnaire was developed and 1,144 consumers in 55 community pharmacies were invited to complete it. The questionnaire covered consumers' choice of pharmacy; their perceptions of, and actual interactions with, community pharmacists; advice from pharmacists about general health and prescribed medicines; and privacy in the pharmacy. Respondents were asked for their views about five possible new services. Setting The study was based in community pharmacies in Riyadh City, Saudi Arabia. Key findings The response rate was 79.6%. Fifty‐nine per cent of respondents often or sometimes visited a particular pharmacy. One‐quarter of respondents perceived community pharmacists as having a good balance between health and business matters, while 56.1% thought pharmacists were more concerned with the business. The majority of respondents (69.7%) said they felt comfortable asking the pharmacist for advice. Just under half (44.8%) felt that pharmacists allowed them enough time to discuss their problem fully and listened well. In addition, 58.5% of respondents indicated that their pharmacists showed sensitivity to privacy by speaking more quietly across the counter. In 14.4% of situations pharmacists were reported to use a private area within the pharmacy when discussing personal or private matters. Most respondents (65.2%) indicated that their pharmacist was willing to discuss their health problems and tried to understand their feelings. Consumers' priorities for new services were: monitoring blood pressure; measuring weight, height and temperature; monitoring blood sugar; and monitoring cholesterol. Conclusion This study showed that most pharmacy customers feel comfortable seeking advice from their pharmacist. Although many pharmacists were reported to show sensitivity to a possible lack of privacy in the pharmacy, few respondents reported that their pharmacy had a private area for discussion. Customers' views on possible new services were generally positive, with the exception of patient medication records.     

Road towards promoting patient safety practices among hospital pharmacists: Hospital-based baseline patient safety culture assessment cross-sectional survey

Patient safety is a fundamental aspect of a healthcare system. The aim of this study was to assess the perception and determinants of the patient safety culture of pharmacists in hospitals, in Riyadh, Saudi Arabia.A survey was conducted with pharmacists in the pharmacies of governmental, /military and private hospitals in Riyadh, Saudi Arabia. The pharmacy survey on patient safety culture questionnaire developed by Agency for Healthcare Research and Qualtity, a hard copy was distriuted to the pharmacists. The positive response rate (RR) was calculated and compared across hospitals using a chi-square test. The predictors of patient safety grades were identified using the generalized estimating equation. The data was analyzed using SAS.A total of 538 questionnaires were distributed, of which 411 responded (RR 76.4%). Of the participants, 229 (56%) were females. The majority 255 (62%) were in the 18 to 34 years age range, and 361 (88%) had a bachelor''s degree. The majority of the sample 376 (92%) was a pharmacist. The Positive RR (PRR) ranged between (25.6%–74%). The highest PRR was observed in teamwork (74.4%), followed by ‘staff, training and skills’ (68%), and ‘organizational learning continuous improvement’ (66%). The lowest PRR was observed in ‘staffing, work pressure, and pace’ (25.5%). Comparing the PPR of the various healthcare sectors, the governmental hospitals scored the highest in all patient safety domains. Generalized Estimating Equation analysis showed that with increase in scores of all patient safety culture domains increased the likelihood of reporting a better patient safety grade, whereas respondents’ demographic characteristics had no effect except the working experience years 6 years and above had odds of poor reporting of the patient safety grade (odds ratio = 2.54, 95% confience interval (1.543, 4.194), (P = .0003).The grades achieved in the various domains of patient safety culture by pharmacists in Riyadh are below the expected standard. The highest scores were achieved in teamwork, with the lowest scores in staffing, work pressure and pace. Overall, pharmacists in government hospital settings have a better perception of patient safety than their peers in other settings. These results provide the baseline evidence for developing future interventional studies aiming at improving patient safety culture in hospital pharmacy settings.     

Role of fine-needle aspiration cytology in evaluating thyroid nodules: A retrospective study from a tertiary care center of Western region,Saudi Arabia

Objectives:To evaluate the accuracy and efficacy of fine-needle aspiration cytology (FNAC) in diagnosing thyroid nodules, correlating it with the histopathological findings.Methods:A retrospective evaluation of 314 patients was undertaken at a tertiary referral center of King Abdullah Medical City (KAMC), Makkah, Kingdom of Saudi Arabia, between 2010-2019. Patients who presented with thyroid swellings underwent ultrasonography and FNAC. If indicated, surgery was performed. The FNAC findings were compared to the final histopathological reports.Results:The findings for FNAC from our data set of 314 patients showed a sensitivity value of 79.8%, specificity of 82.1%, accuracy of 74.8%, positive predictive value of 74.8%, and negative predictive value of 85.9%.Conclusion:Our study showed that FNAC has high sensitivity and specificity in the initial evaluation of patients with thyroid nodules. When guided by ultrasonography, the accuracy can be markedly improved. Molecular markers once widely available can improve the diagnostic power of FNAC to be no less than the histopathologic evaluation of thyroid tissue.     

Befunde in den Hauptentwicklungsstufen des Gebisses bei Dysgnathieträgern

Zusammenfassung In dieser Arbeit wurden die Gebisse von 31 männlichen und 45 weiblichen Dysgnathieträgern mit Hilfe des Berliner Meßsystems vermessen und die Ergebnisse mit Hilfe eines Computers ausgewertet. Es erfolgt der Vergleich der Parameter zwischen Probanden mit Progenie, Kreuzbiß, offenem Biß und Schmalkiefer. Die Veränderung der Werte wurden longitudinal in den Hauptentwicklungsstufen Milchgebiß, Wechselgebiß und im bleibenden Gebiß untersucht. Dabei werden auch nach der Behandlung noch zwischen den Anomaliegruppen bei einzelnen Werten signifikante Unterschiede gefunden.

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Summary In this study dental plaster casts of 31 male and 45 female subjects were measured using the Berlin measurement system and evaluated with the aid of a computer. The parameters of subjects with class III malocclusion, crossbite, open bite and class II/1 malocclusion were compared. The changes were studied longitudinally in the main developmental stages, namely the deciduous, mixed and permanent dentitions. Significant differences were found also following treatment between the malocclusion groups.

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Résumé On a mesuré les dentures de 31 hommes et 45 femmes présentant des dysgnathies à l'aide du système de mesure mis au point à Berlin; les valeurs ainsi établies on fait l'objet d'un traitement sur ordinateur. On a procédé à la comparaison des paramètres des sujets atteints de prognathie inférieure, occlusion croisée, béance et endognathie. On a étudié la modification des valeurs de manière longitudinale, en suivant les principales étapes d'évolution: denture lactéale, denture mixte et denture permanente. L'examen a permis, même après le traitement, d'établir, pour chacune des valeurs, des différences importantes d'un groupe d'anomalie à l'autre.

     

Ameloblastoma: current etiopathological concepts and management

Ameloblastoma is a benign odontogenic tumor of epithelial origin. It is locally aggressive with unlimited growth capacity and has a high potential for malignant transformation as well as metastasis. Ameloblastoma has no established preventive measures although majority of patients are between ages 30 and 60 years. Molecular and genetic factors that promote oncogenic transformation of odontogenic epithelium to ameloblastoma are strongly linked to dysregulation of multiple genes associated with mitogen‐activated protein kinase, sonic hedgehog, and WNT/β‐catenin signaling pathways. Treatment of ameloblastoma is focused on surgical resection with a wide margin of normal tissue because of its high propensity for locoregional invasion; but this is often associated with significant patient morbidity. The relatively high recurrence rate of ameloblastoma is influenced by the type of molecular etiological factors, the management approach, and how early the patient presents for treatment. It is expected that further elucidation of molecular factors that orchestrate pathogenesis and recurrence of ameloblastoma will lead to new diagnostic markers and targeted drug therapies for ameloblastoma.