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Background: Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. Methods: The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Results: Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. Conclusion: The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.
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Objective: Chronic lung-related diseases, with asthma being the most prominent example, characterized by diverse symptoms and triggers, present significant challenges in disease management and prediction of exacerbations across patients. This research aimed to devise a practical solution by introducing a personalized alert system tailored to individual lung function and environmental conditions, offering a holistic approach for the management of a range of chronic respiratory conditions. Methods: In response to these challenges, we developed a personalized alert system based on individual lung function tests conducted in diverse environmental conditions, as determined by air-quality sensors. Our research was substantiated through an observational pilot study involving twelve healthy participants. These participants were exposed to varying air quality, temperature, and humidity conditions, and their lung function, as indicated by peak expiratory flow (PEF) values, was monitored. Results: The study revealed pronounced variability in pulmonary responses across different environments. Leveraging these findings, we proposed a design of a personalized alarm system that monitors air quality in real-time and issues alerts under potentially unfavorable environmental conditions. Additionally, we investigated the use of basic machine learning techniques to predict PEF values in these varied environmental settings. Discussion: The proposed system offers a proactive approach for individuals, particularly those with asthma, to actively manage their respiratory health. By providing real-time monitoring and personalized alerts, it aims to minimize exposure to potential asthma triggers. Ultimately, our system seeks to empower individuals with the tools for timely intervention, potentially reducing discomfort and enhancing management of asthma symptoms.
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Introduction Asthma is a chronic heterogeneous inflammatory disease that affects millions of individuals around the globe. Standardized asthma management is crucial to maintain and control the disease. Caregivers are the leading players in managing asthma during childhood. Studies are lacking in the Tabuk region. The aim of this study was to elucidate knowledge levels and common practices of caregivers of pediatric patients with asthma in the Tabuk region of Saudi Arabia and its impact on asthma control. Methodology A validated cross-sectional survey of the population of the Tabuk region was conducted from July 1, 2022, to September 30, 2022. Convenience sampling via an internet-based questionnaire within the study area was deployed, followed by phone interviews. Results A total of 393 caregivers completed the questionnaire, and the data were analyzed. The median age of asthmatic children was nine years, and most of them were males (60.8%). Most caregivers had a higher education (62.1%). The symptoms of allergic rhinitis were found in almost 80% of children. Pulmonary function tests were performed in 42.5% of children, and only one-third underwent radioallergosorbent (RAST) skin testing. About half the children had an asthmatic attack and an emergency department visit once during the previous 12 months, and most were hospitalized during that period. Most caregivers showed good knowledge (score=7) about symptoms of asthma and factors that could worsen the child's asthma, as well as good asthma control practices (score ≥7). Children with poorly controlled asthma were younger, had significant allergic rhinitis symptoms (30%), and underwent pulmonary function tests (60%). Conclusion In the Tabuk region, the extent of asthma control was significantly associated with caregivers' knowledge and practices for children with asthma. Future public education campaigns should focus on closing the observed knowledge and practice gaps to reduce the impact of childhood asthma.
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Objectives This study aims to map the curriculum of the Faculty of Medicine at Tabuk University to assess its comparability with the SaudiMEDs competency framework. Methodology We developed a checklist based on the essential clinical presentations and skills listed in the SaudiMEDs to map our curriculum and determine the comparability. This cross-sectional descriptive study started on 1 September 2015 until 29 February 2016. The coordinators of the 34 modules completed the checklist and identified whether each clinical presentation or skill is taught in their relevant modules. Results Results showed that our curriculum is lacking in 3.9% of the clinical presentations and 23.9% of the skills deemed necessary by the SaudiMEDs, and require attention. Deficient skills were mainly hospital-based ones. The project yielded a content "expertise" map regarding where the main domains of knowledge and skills in the SaudiMEDs framework are addressed in our curriculum. The "SaudiMEDs barcode" is generated that we hypothesize as a novel method for the description of our program in relation to the national competency framework. Conclusion Curriculum mapping is a powerful tool for curriculum improvement. Our study elucidated a minor gap in the knowledge domains but a significant one in the essential skills in relation to the SaudiMEDs. We recommend structured training during the internship period as an essential supplement to undergraduate medical qualifications. During our experimentation with curriculum mapping, we articulated the "SaudiMEDs barcode" that we suggest as a novel method for curriculum alignment to the matrix of national competency and, hopefully, to aid in the accreditation projects.
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BACKGROUND: Immune dysregulation has been linked to morbidity and mortality in COVID-19 patients. Understanding the immunology of COVID-19 is critical for developing effective therapies, diagnostics, and prophylactic strategies to control the disease. AIM: The aim of this study was to correlate cytokine and chemokine serum levels with COVID-19 disease severity and mortality. SUBJECTS AND METHODS: A total of 60 hospitalized patients from the Tabuk region of Saudi Arabia with confirmed COVID-19 were included in the study. At hospital admission, the IL-1 ß, IL-2, IL-8, IL-10, LT-B4, and CCL-2 serum levels were measured. The cytokine levels in COVID-19 patients were compared to the levels in 30 healthy matched control subjects. RESULTS: The IL-1 ß, IL-2, LTB-4, CCL-2, and IL-8 levels (but not IL-10) were significantly higher in all COVID-19 patients (47 survivors and 13 non-survivors) compared with the levels in the healthy control group. In the non-survivor COVID-19 patients, patients' age, D-dimer, and creatinine kinase were significantly higher, and IL-1 ß, IL-2, and IL-8 were significantly lower compared with the levels in the survivors. CONCLUSION: Mortality rates in COVID-19 patients are associated with increased age and a failure to mount an effective immune response rather than developing a cytokine storm. These results warrant the personalized treatment of COVID-19 patients based on cytokine profiling.
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The recent coronavirus outbreak from Wuhan China in late 2019 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in a global pandemic of coronavirus-19 disease (COVID-19). Understating the underlying mechanism of the pathogenesis of coronavirus infection is important not only because it will help in accurate diagnosis and treatment of the infection but also in the production of effective vaccines. The infection begins when SARS-CoV-2 enters the cells through binding of its envelope glycoprotein to angiotensin-converting enzyme2 (ACE2). Gene variations of ACE2 and microRNA (miR)-196 are associated with viral infection and other diseases. The present study investigated the association of the ACE2 rs4343 G>A and miR-196a2 rs11614913 C>T gene polymorphisms with severity and mortality of COVID-19 using amplification refractory mutation system PCR in 117 COVID-19 patients and 103 healthy controls from three regions of Saudi Arabia. The results showed that ACE2 rs4343 GA genotype was associated with severity of COVID-19 (OR=2.10, P-value 0.0028) and ACE2 rs4343 GA was associated with increased mortality with OR=3.44, P-value 0.0028. A strong correlation between the ACE2 rs4343 G>A genotype distribution among COVID-19 patients was reported with respect to their comorbid conditions including sex (P<0.023), coronary artery disease (P<0.0001), oxygen saturation <60 mm Hg (P<0.0009) and antiviral therapy (0.003). The results also showed that the CT genotype and T allele of the miR-196a2 rs11614913 C>T were associated with decreased risk to COVID-19 with OR=0.76, P=0.006 and OR=0.54, P=0.005, respectively. These results need to be validated with future molecular genetic studies in a larger sample size and different populations.
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Genetic susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality continues to evolve. This report presents a case of an apparently healthy male adult who developed severe coronavirus disease 2019 (COVID-19) and a study on relevant genetic mutations, namely, angiotensin-converting enzyme 2 (ACE2-rs4646994 I/D) gene, glutathione S-transferase (GST) M1 and T1 gene, and miR-423 rs6505162 C>A gene polymorphism. Results showed that the ACE-DD genotype of ACE2, (GSTM1+/+) (GSTT1-/-) genotype of GST gene, and CA genotype (heterozygosity) of miR-423 rs6505162 genes, which were found in the patient, could be independent risk factors of severe COVID-19, even without comorbidities.
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BACKGROUND: The ongoing outbreak of SARS-CoV-2 represents a significant challenge to international health. Several reports have highlighted the importance of ACE2 on the pathogenesis of COVID-19. The spike protein of SARS-CoV-2 efficiently binds to the angiotensin-converting enzyme 2 (ACE2) receptors and facilitates virus entry into the host cell. In the present study, we hypothesize that a functional insertion/deletion polymorphism-rs4646994 I/D and rs4240157 T > C in the ACE gene could be associated with SARS-CoV-2 infection and mortality. METHODOLOGY: This study included 117 consecutive COVID-19 patients and 150 age matched healthy controls (ACE2-rs4646994 I/D) and 100 age matched healthy controls with ACE2 rs4240157 T > C. We used Mutation specific PCR (MSP) for ACE2-rs4646994 I/D genotyping and amplification refractory mutation system (ARMS-PCR) for ACE2 rs4240157 T > C genotyping. RESULTS: Results indicated that there were significant differences in the genotype distributions of ACE2-rs4646994 I/D polymorphisms (p < 0.030) and ACE2 rs4240157 T > C between COVID-19 patients and controls (p-values < 0.05). Higher frequency of DD genotype (48.71%) and D allele (0.67) was reported in COVID-19 patients than controls. Our results showed that the ACE2-DD genotype was strongly associated with increased COVID-19 severity (OR 2.37 (95%) CI = (1.19-4.70), RR = 1.39 (1.09-1.77), p < 0.013) and also a strong association was seen with ACE2-ID genotype with COVID-19 severity (OR 2.20 (95%) CI = (1.08-4.46), p < 0.020) in the codominant model. In allelic comparison, the D allele was strongly associated with COVID-19 severity (OR 1.58 (95% CI) (1.11-2.27), RR 1.21 (1.05-1.41) p < 0.010). A significant correlation of ACE2-I/D genotypes was reported with Age (p < 0.035), T2D (p < 0.0013), hypertension (p < 0.0031) and coronary artery disease (p < 0.0001). Our results indicated ACE2-DD genotype was strongly associated with increased COVID-19 mortality (OR 8.25 (95%) CI = (2.40 to 28.34), p < 0.008) and also ACE2-DD + DI genotype was strongly associated with increased COVID-19 mortality with OR 4.74 (95%) CI = (1.5214 to 14.7915), p < 0.007. A significant correlation was reported between COVID-19 patients and age matched controls (p < 0.0007). Higher frequency of heterozygosity TC (40%) followed by ACE2-CC genotype (24.78%) was reported among COVID-19 patients. Using multivariate analysis, ACE2-CT genotype was strong associated with SARS-CoV-2 severity with an OR 2.18 (95% CI) (1.92-3.99), p < 0.010 and also ACE2-CC genotype was linked with COVID-19 severity with an OR 2.66 (95% CI) (1.53-4.62), p < 0.005. A significant correlation of ACE2-T > C genotypes was reported with gender (p < 0.04), T2D (p < 0.035). ACE2-CC genotype was strongly associated with increased COVID-19 mortality OR 3.66 (95%) CI = (1.34 to 9.97), p < 0.011 and also ACE2-C allele was associated with COVID-19 mortality OR 2, 01 (1.1761-3.45), p < 0.010. CONCLUSIONS: It is concluded that ACE-DD genotype and D allele was strongly associated with increased COVID-19 patient severity. In addition, ACE I/D polymorphism were strongly associated with advanced age, diabetes and ischemic heart disease in COVID-19 patients whereas ACE-II genotype was a protective factor against the development of severe COVID-19. ACE2-DD genotype was strongly associated with increased COVID-19 mortality. Additionally, ACE2-CC and CT genotypes were strongly associated with COVID-19 severity. Therefore, our study might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.
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BACKGROUND: Ziziphus jujuba belongs to family Rhamnaceae widely distributed in subtropical and tropical countries. It is used traditionally for several pharmacological purposes including anti-inflammation, antidiarrhoeal and antibacterial, as well as tonic and sometimes as hypnotic (sedative). AIM: To determine the in vivo antidiarrhoeal, antibacterial and anti-inflammatory activities of Z. jujuba fruit ethanolic extract. METHOD: The fruit was macerated and extracted by 95% (v/v) ethanol. The antidiarrhoeal activity was evaluated using castor oil and Escherichia coli induced diarrhoea mouse model. The antidiarrhoeal and antibacterial activity was investigated at graded doses (400-1200 mg/kg). The anti-inflammatory effects were tested using the carrageenan-induced paw oedema in female Wistar rats. Rat's treatment groups received tragacanth, 100 mg/kg diclofenac sodium, 800 mg/kg, 1200 mg/kg or 1600 mg/kg of an ethanolic extract of Z. jujuba (EEZJ). All treatment groups were fed with the compounds one hour before carrageenan injection at of rat's paw. Also, the EEZJ was further analysed by HPLC-PDA system for identification of the presence of betulinic acid and quercetin. RESULTS: EEZJ different doses did not show inhibitory activity against castor oil induced diarrhoea except for the higher (1200 mg/kg) dose. However, the frequency of defecation of stools and watery stool were reduced significantly when compared to control group (P ≤ 0.05 and P ≤ 0.01 respectively), resulted in overall 67% inhibition of diarrhoea. Our anti-inflammatory results demonstrated that EEZJ was able to inhibit the carrageenan-induced paw oedema in rats to a significant degree (p ≤ 0.05) and the paw volume and thickness of both left and right paw were affected compared to the negative control group. CONCLUSION: EEZJ possesses antidiarrhoeal and antibacterial activity in a dose depending manner and may provide a pharmacological basis for its clinical use in diarrheal diseases. The activity may partially be due to the presence of betulinic acid and quercetin.
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Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness. AIM OF THE WORK: This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection. PATIENTS AND METHODS: This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects. RESULTS: The main symptoms among the included patients were: fever (96.87%), cough (93.75%), dyspnea (90.62%), sore throat (75%), runny nose (75%), sputum (50%), headache (43.75%), myalgia (40.62%), chest pain (37.50%), hemoptysis (37.50%), nausea and vomiting (34.37%), abdominal pain (21.87%) and diarrhea (15.62%). The presence of abdominal symptoms is significantly (P < 0.05) associated with bad prognosis. Out of the included 32 patients, 18 patients (56.25%) survived and 14 patients (43.75%) expired. There was a statistically significant difference in the duration of symptoms before hospitalization, mechanical ventilation and ICU and total hospital stay between the expired group and survivors (P < 0.01). Current smoking and smoking severity were statistically significantly (P < 0.01) higher in the expired group compared to survivors. Also, there was a statistically (P < 0.05) significant positive correlation between mortality and smoking severity (r = 0.640). Most of the expired patients presented with bilateral pulmonary infiltrates or unilateral infiltrates, but most of the survivors presented with normal radiology or increased bronchovascular markings, and this difference in the results was statistically highly significant (P < 0.01). There were statistically highly significant (P < 0.01) differences in the mean values of APACHE II score (21.11 ± 3.70 vs 24.21 ± 3.82), SOFA score (5.83 ± 2.64 vs 8.85 ± 2.17) and CPIS (7.55 ± 1.14 vs 8.64 ± 1.39) between the expired group and survivors respectively. Also, there was a statistically significant decrease in PH, PaO2, O2 saturation and HCO3 (P < 0.05) among the expired group in comparison with the survivors, but no statistical difference regarding PaCO2 (P > 0.05). There was a statistically significant positive correlation between mortality and old age (r = 0.633), obesity (r = 0.712), diabetes mellitus (r = 0.685), renal failure (r = 0.705), chronic heart diseases (0.591), COPD (r = 0.523), malignancy (r = 0.692), kidney transplantation (r = 0.644) and liver cirrhosis (r = 0.525) (P < 0.05). There was a statistically (P < 0.05) positive correlation between the number of associated co-morbidities and mortality (r = 0.735). CONCLUSIONS: Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.
