Key points The sinoatrial node (SAN) is the primary pacemaker of the heart. SAN dysfunction, or ‘sick sinus syndrome’, can cause excessively slow heart rates and pauses, leading to exercise limitation and syncope, currently treated by implantation of an electronic pacemaker.‘Biopacemaking’ utilises gene therapy to restore pacemaker activity by manipulating gene expression. Overexpressing the HCN pacemaker ion channel has been widely used with limited success.We utilised bradycardic rat subsidiary atrial pacemaker tissue to evaluate alternative gene targets: the Na+/Ca2+ exchanger NCX1, and the transcription factors TBX3 and TBX18 known to be involved in SAN embryonic development.TBX18 overexpression restored normal SAN function, as assessed by increased rate, improved heart rate stability and restoration of isoprenaline response. TBX3 and NCX1 were not effective in accelerating the rate of subsidiary atrial pacemaker tissue.Gene therapy targeting TBX18 could therefore have the potential to restore pacemaker function in human sick sinus syndrome obviating electronic pacemakers. AbstractThe sinoatrial node (SAN) is the primary pacemaker of the heart. Disease of the SAN, sick sinus syndrome, causes heart rate instability in the form of bradycardia and pauses, leading to exercise limitation and syncope. Biopacemaking aims to restore pacemaker activity by manipulating gene expression, and approaches utilising HCN channel overexpression have been widely used. We evaluated alternative gene targets for biopacemaking to restore normal SAN pacemaker physiology within bradycardic subsidiary atrial pacemaker (SAP) tissue, using the Na+/Ca2+ exchanger NCX1, and the transcription factors TBX3 and TBX18. TBX18 expression in SAP tissue restored normal SAN function, as assessed by increased rate (SAN 267.5 ± 13.6 bpm, SAP 144.1 ± 8.6 bpm, SAP‐TBX18 214.4 ± 14.4 bpm; P < 0.001), improved heart rate stability (standard deviation of RR intervals fell from 39.3 ± 7.2 ms to 6.9 ± 0.8 ms, P < 0.01; root mean square of successive differences of RR intervals fell from 41.7 ± 8.2 ms to 6.1 ± 1.2 ms, P < 0.01; standard deviation of points perpendicular to the line of identity of Poincaré plots (SD1) fell from 29.5 ± 5.8 ms to 7.9 ± 2.0 ms, P < 0.05) and restoration of isoprenaline response (increases in rates of SAN 65.5 ± 1.3%, SAP 28.4 ± 3.4% and SAP‐TBX18 103.3 ± 10.2%; P < 0.001). These changes were driven by a TBX18‐induced switch in the dominant HCN isoform in SAP tissue, with a significant upregulation of HCN2 (from 1.01 × 10−5 ± 2.2 × 10−6 to 2.8 × 10−5 ± 4.3 × 10−6 arbitrary units, P < 0.001). Biophysically detailed computer modelling incorporating isoform‐specific HCN channel electrophysiology confirmed that the measured changes in HCN abundance could account for the observed changes in beating rates. TBX3 and NCX1 were not effective in accelerating the rate of SAP tissue.
Background: Sickle-cell disease (SCD) is a group of genetic disorders characterized by abnormally shaped red blood cells (RBCs), which are destroyed at increased rates, leading to anemia. Recently, Saudi Arabia has been reported to have an increased prevalence of SCD. Objective: The aim of the present study was to assess perceptions about SCD among the general population in Albaha region, Saudi Arabia, and the possible relationship between their levels of knowledge and sociodemographic characteristics. Methods: The study was carried out on 218 Saudi subjects who completed the selfadministered questionnaires during the study period. Results: This study demonstrated that more than two-thirds of the respondents (68.80%) had good knowledge about basics of sickle cell disease. Those with poor knowledge (31.20%) were mainly younger males and works as businessmen and housewives, and all of them had no previous experience with SCD child. Despite the recorded favorable level of knowledge, certain gaps in knowledge were identified; most of them falsely believed that some foods like fava beans, lentils, falafel made with fava beans, vigna and /or nuts could precipitate sickle-cell crisis.Moreover, in depth information of our study population about pattern of inheritance of SCD and its complications were not sufficient. Conclusion: In our study, a good level of awareness regarding SCD was found. Some of the respondents were confused about the nature of inheritance, complications and dietary factors related to the disease. So, community health education meetings and/or media programs to increase the public awareness are recommended.
Background: Worldwide, more than one billion people are affected by hearing loss. Noise-induced hearing loss (NIHL) is reported among the most prevalent occupational diseases. However, little is known about the current level of knowledge and attitude towards NIHL among general population. Objective: The purpose of this study was to investigate the knowledge, behaviors, and attitudes of adult population in Albaha Region of the Kingdom of Saudi Arabia concerning the factors that contribute to Noise-induced hearing loss (NIHL) and the use of hearing protection. Methods: A 16-item self-administrated questionnaire was used to measure the knowledge, habits, attitudes, and perception of NIHL and each participant's use of hearing protection. The questionnaire included multiple choice and fill-in-the-blank format questions. The questionnaire was divided into two sections: 1) demographic information, including age, sex, college major, and prior coursework regarding hearing in noise; 2) knowledge of hearing, the auditory mechanism, and noise-induced hearing impairment. Results: we received 296 valid responses. Fifty-nine percentage were male, 37 % percentage were students, 21 % were soldiers and 17 % were teachers. Only 19 % said that hearing loss cannot be cured and 53 % knew that it can happen at any age. Interestingly, 94 % never wore an ear plug before. Conclusion: Our study showed low percentage of correct answers about causes and protective measures against hearing loss. Future health care program should consider initiatives and public health campaigns to improve the public's knowledge and attitude.
Background: The hospital emergency department (ED) is one of the most important components of the healthcare delivery system. This study aims to investigate the public awareness of the Emergency Rooms (ERs) in Saudi Arabia, what the public knows about the provided services, and if they know the difference between the outpatient clinics and the ERs. Methodology: It is a cross-sectional descriptive community-based study, carried out on 977 participants from all age groups, in different areas of Saudi Arabia, from 1 January to 31 July 2019. Data were collected by filling the pre-designed online questionnaire. We utilized the SPSS program version 16. The X2 test was used as a test of significance, and differences considered significant at P value less than 0.05. Results: Most of the participants (87.5%) reported that they knew the difference between the outpatient clinic and ER. The majority (68.1%) of subjects said that ERs mean rapid and unplanned medical care. Regarding evaluation of the provided services in ERs; 32.5% of the cases said it was satisfactory followed by 28.5% good, 19.8% excellent, 10.2% accepted and 10% reported it was unsatisfactory. There were significant relationships between the awareness and age (P=0.03) and education level (P=0.003), but no relationship was found with the gender of the participant (P>0.5). Conclusion: In the current study, most of the participants reported that they knew the difference between the outpatient clinics and ERs. There were significant relationships between the awareness and age and education level, but an insignificant relation was found with the gender of the participant.
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