Knowledge, attitude, future expectations and perceived barriers of medical students and physicians regarding pharmacogenomics in Jordan.

BACKGROUND: Pharmacogenomics (PG) is a modern tool of personalising treatment protocols to improve the efficacy and safety of drug prescriptions. These benefits are offset by a slow uptake in clinical application due to a host of physician factors, patient factors and/or health system factors. Our study, thus, aimed to determine the knowledge, attitude, future expectations and perceived barriers of medical students and physicians in Jordan regarding PG testing. METHODS: A descriptive, cross-sectional study was conducted between February and August 2019. Physicians and senior medical students from academic and non-academic institutions in North Jordan (n = 424) were surveyed. A structured, self-administered questionnaire was designed and piloted for the purpose of the study. A scoring system for each dimension assessed was calculated and presented using means. Mean scores were compared by sociodemographic and professional variables. RESULTS: The response rate was 70.7%. The mean total PG knowledge score (±SD) was 5.42 (±1.51) out of 10, with a significantly higher mean among respondents aged <30 years (5.54 ± 1.43) compared with those ≥30 years old (5.21 ± 1.62; P = .03). The mean total PG attitude score was 21.18 (±2.58) out of 24, with significant differences by seniority levels evident (P = .03). The future expectations of PG among our sample were high, with a mean score of 10.44 (±1.64) out of 12. The top three perceived barriers in applying PG were the high cost, lack of clinical guidelines, and limited knowledge and awareness. CONCLUSION: Physicians and medical students in Jordan have low overall knowledge, albeit strongly positive attitude and future expectations towards PG, despite the perceived high cost and lack of clinical guidelines. Thus, we strongly recommend adopting a comprehensive educational strategy that aims to integrate PG concepts into medical curricula, and promote the culture of continuous medical education about PG among practitioners.

Stem cell-related knowledge and attitudes among physicians in Jordan.

BACKGROUND: Rapid advancement of stem cell (SC) therapies provides both opportunities and risks for patients and physicians alike. Physicians have a role in counselling patients about unproven SC therapies, requiring a basic level of knowledge and access to information about SCs. OBJECTIVE: This study sought to assess SC-related knowledge of and attitudes among physicians in Jordan to elucidate areas of deficiency that can be addressed. METHODS: A cross-sectional survey, comprising questions on demographics and SC knowledge and attitudes, was designed as a scoring system to evaluate physicians' knowledge and attitudes. Participants were recruited from 10 major hospitals in Jordan over 3 months between February and April 2019. The internal consistency of the scoring scales was calculated using Cronbach's alpha reliability coefficient. Gender differences were evaluated with an independent t-test. RESULTS: In total, 382 physicians in Jordan completed the survey (59.9% response rate). They demonstrated a low/moderate level of overall SC knowledge (51.3%), but most lacked confidence in their ability to answer patients' questions about SC therapies (64.7%). However, the total attitude score was moderate/high positive (66.8%) and most were interested in learning more about SCs (80.8%). Male physicians reported significantly more knowledge than females (P < .0001). CONCLUSIONS: This study reveals Jordanian physicians' hesitancy to counsel patients about SC therapies, largely because of gaps in knowledge. However, overall attitudes toward SC research and therapies are positive. The results of this study demonstrate a need to cover SC-related information in medical curricula in Jordan, as well as to support initiatives to regulate SC tourism in Jordan.

The relationship between depression and metabolic control parameters in type 2 diabetic patients: A cross-sectional and feasibility interventional study.

BACKGROUND: Substantial evidence supports a bidirectional relationship between diabetes and clinical depression. However, little is known about the effect of treating one condition on the control of the other. Thus, this study aimed to determine the prevalence of depression among Type II diabetes mellitus (T2DM) patients and to assess the efficacy and feasibility of escitalopram treatment of depression on their metabolic control parameters. METHODS: T2DM patients attending primary care clinics in the North of Jordan were enrolled in a cross-sectional study during the period from February to December 2019 (n = 157). Depressive symptoms were screened utilising the patient health questionnaire-9 (PHQ-9) tool. Metabolic control was assessed by measurement of glycated haemoglobin (HbA1c), triglycerides, cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Patients with moderate to severe depressive symptoms by PHQ-9 (n = 58) were interviewed by a psychiatrist to confirm a clinical diagnosis of depression. Eligible depressed patients were administered escitalopram 10 mg orally once daily for 3 months (n = 12). Thereafter, depressive symptoms and metabolic control measures were reassessed. RESULTS: The prevalence of moderate to severe depressive symptoms among T2DM patients, according to PHQ-9, was 36.94%, while the prevalence of clinical depression based on interview was 7.64%. Baseline PHQ-9 scores correlated significantly with baseline levels of HbA1c, HDL, cholesterol and triglycerides. Escitalopram treatment intervention resulted in significant improvement of PHQ-9 scores without significantly improving any of the metabolic control measures. CONCLUSION: The relationship between depression and T2DM in the context of metabolic syndrome is plausible. However, our results show that escitalopram treatment may not be associated with significant improvement in metabolic control parameters among these patients. Our study has laid the groundwork for future randomised clinical trials with larger sample size and longer follow-up.

Effects of Elemental Mercury Vapor Inhalation on Arterial Blood Gases, Lung Histology, and Interleukin-1 Expression in Pulmonary Tissues of Rats.

We investigated the effects of elemental mercury vapor inhalation on arterial blood gases (ABGs), lung histology, and interleukin-1 (IL-1) expression in pulmonary tissues in rats. A total of 42 Sprague Dawley rats were divided randomly into three groups. Rats in the first group were used as the control (CG). A short-term group (STG) and a long-term group (LTG) were exposed to 500 µg/m3 of mercury vapor 2 hrs/day for 21 days and 65 days, respectively. After exposure periods were completed, arterial blood samples were obtained, and ABGs were measured. Lung tissue sections were prepared for histology evaluation and immune-stained to detect IL-1 expression. There was a significant decrease in body weight in both STG (15%) and LTG (22%) compared with the CG. In the LTG, six out of 14 (43%) rats died, including two males and four females, while none of the rats in the STG died during the experiment. In both STG and LTG, a significant acid-base imbalance was characterized by a significant decrease in blood pH values and a significant increase in PCO2 values. Both PO2 and SpO2 blood values were significantly decreased in the STG and LTG, while no changes were observed in HCO3 values in all groups. Histological evaluation of lung tissues revealed severe lesions characterized by pulmonary emphysema and inflammatory cellular infiltrate. IL-1 expression in lung tissues was not significantly different between exposed rats and control subjects. These results indicate significant alterations in blood acid-base status characterized by severe respiratory acidosis with hypoxemia and no evidence of compensatory alkalosis in rats after exposure to short- and long-term elementary mercury vapor.

Trauma exposure, mental health and tobacco use among vulnerable Syrian refugee youth in Jordan.

BACKGROUND: Little is known about tobacco use among youth exposed to armed conflicts, or the influence of trauma on tobacco use in this context. This study examined patterns of smoking by tobacco product and gender among Syrian refugee youth living in host communities in Jordan and assessed the associations of post-traumatic stress disorder (PTSD) and depression symptoms, trauma exposure and social support with current smoking status in boys and girls. METHODS: Syrian refugee students (mean [standard deviation] age = 14.9 [1.33] years) were identified through the public school system. Data were collected using an online Arabic questionnaire that included questions about demographics, trauma exposure, current smoking (cigarette and waterpipe), PTSD, depression and perceived social support. Logistic regression was used to assess the adjusted effects of independent variables on current smoking status. RESULTS: One in 7 boys and one in 14 girls were current smokers, with boys reporting greater tobacco use than girls. Among boys, current smokers reported significantly higher family member loss and lower perceived family social support than nonsmokers; among girls, current smokers also reported significantly higher family member loss as well as greater PTSD symptoms and lower perceived significant other/special person social support. CONCLUSIONS: Tobacco use is established among this vulnerable group. The findings highlight the potential role of psychosocial support for tobacco prevention and cessation strategies.

Changes of serum growth factors profiles in patients with venous thromboembolism.

BACKGROUND AND RATIONALE: Venous thromboembolism (VTE) is a multifactorial disorder. Multiple hits to the tightly regulated blood hemostasis systems are required to trigger VTE. Growth factors, such as angiopoietins 1 and 2 (Ang-1 and Ang-2), and the epidermal growth factor (EGF) are critically involved in the maintenance of endothelial activity and vascular stability. The aim of this study was to evaluate the changes of these serum growth factors in patients with VTE. METHODS: This is a multi-institutional retrospective case-control study. The first arm included 50 patients diagnosed with deep vein thrombosis (DVT), pulmonary embolism (PE) or both. The control arm included 25 healthy subjects with no current or previous VTE. Both arms were investigated for changes in their serum levels of Ang-1, Ang-2 and EGF. RESULTS: Compared to healthy controls, Ang-2 was significantly higher (p = .001) while Ang-1 and EGF were significantly lower (p = .001 and p = .004; respectively) in VTE patients compared to healthy subjects. The type of VTE (DVT vs. PE) did not affect the observed changes in serum growth factors profiles. These changes were not time- or frequency-dependent, as there were no significant differences between acute versus chronic, or between the first-time versus recurrent cases of VTE. CONCLUSIONS: Serum profiles of Ang-1, Ang-2 and EGF change dramatically during VTE. This hints the significant role that these growth factors played in the pathogenesis of VTE. Thus, serum levels of growth factors may help in the first-time diagnosis of VTE, but not in diagnosing a recurrent episode of VTE. Larger studies are required to determine 'threshold levels' or 'likelihood ranges' of each biomarker for accurate diagnosis.

A novel vascular homing peptide strategy to selectively enhance pulmonary drug efficacy in pulmonary arterial hypertension.

A major limitation in the pharmacological treatment of pulmonary arterial hypertension (PAH) is the lack of pulmonary vascular selectivity. Recent studies have identified a tissue-penetrating homing peptide, CARSKNKDC (CAR), which specifically homes to hypertensive pulmonary arteries but not to normal pulmonary vessels or other tissues. Some tissue-penetrating vascular homing peptides have a unique ability to facilitate transport of co-administered drugs into the targeted cells/tissues without requiring physical conjugation of the drug to the peptide (bystander effect). We tested the hypothesis that co-administered CAR would selectively enhance the pulmonary vascular effects of i.v. vasodilators in Sugen5416/hypoxia/normoxia-exposed PAH rats. Systemically administered CAR was predominantly detected in cells of remodeled pulmonary arteries. Intravenously co-administered CAR enhanced pulmonary, but not systemic, effects of the vasodilators, fasudil and imatinib, in PAH rats. CAR increased lung tissue imatinib concentration in isolated PAH lungs without increasing pulmonary vascular permeability. Sublingual CAR was also effective in selectively enhancing the pulmonary vasodilation by imatinib and sildenafil. Our results suggest a new paradigm in the treatment of PAH, using an i.v./sublingual tissue-penetrating homing peptide to selectively augment pulmonary vascular effects of nonselective drugs without the potentially problematic conjugation process. CAR may be particularly useful as an add-on therapy to selectively enhance the pulmonary vascular efficacy of any ongoing drug treatment in patients with PAH.

Glucose-6-phosphate dehydrogenase plays a critical role in hypoxia-induced CD133+ progenitor cells self-renewal and stimulates their accumulation in the lungs of pulmonary hypertensive rats.

Although hypoxia is detrimental to most cell types, it aids survival of progenitor cells and is associated with diseases like cancer and pulmonary hypertension in humans. Therefore, understanding the underlying mechanisms that promote survival of progenitor cells in hypoxia and then developing novel therapies to stop their growth in hypoxia-associated human diseases is important. Here we demonstrate that the proliferation and growth of human CD133(+) progenitor cells, which contribute to tumorigenesis and the development of pulmonary hypertension, are increased when cultured under hypoxic conditions. Furthermore, glucose-6-phosphate dehydrogenase (G6PD) activity was increased threefold in hypoxic CD133(+) cells. The increased G6PD activity was required for CD133(+) cell proliferation, and their growth was arrested by G6PD inhibition or knockdown. G6PD activity upregulated expression of HIF1α, cyclin A, and phospho-histone H3, thereby promoting CD133(+) cell dedifferentiation and self-renewal and altering cell cycle regulation. When CD133(+) cells were cocultured across a porous membrane from pulmonary artery smooth muscle cells (PASMCs), G6PD-dependent H2O2 production and release by PASMCs recruited CD133(+) cells to the membrane, where they attached and expressed smooth muscle markers (α-actin and SM22α). Inhibition of G6PD reduced smooth muscle marker expression in CD133(+) cells under normoxia but not hypoxia. In vivo, CD133(+) cells colocalized with G6PD(+) cells in the perivascular region of lungs from rats with hypoxia-induced pulmonary hypertension. Finally, inhibition of G6PD by dehydroepiandrosterone in pulmonary arterial hypertensive rats nearly abolished CD133(+) cell accumulation around pulmonary arteries and the formation of occlusive lesions. These observations suggest G6PD plays a key role in increasing hypoxia-induced CD133(+) cell survival in hypertensive lungs that differentiate to smooth muscle cells and contribute to pulmonary arterial remodeling during development of pulmonary hypertension.

Temporal hemodynamic and histological progression in Sugen5416/hypoxia/normoxia-exposed pulmonary arterial hypertensive rats.

We have investigated the temporal relationship between the hemodynamic and histological/morphological progression in a rat model of pulmonary arterial hypertension that develops pulmonary arterial lesions morphologically indistinguishable from those in human pulmonary arterial hypertension. Adult male rats were injected with Sugen5416 and exposed to hypoxia for 3 wk followed by a return to normoxia for various additional weeks. At 1, 3, 5, 8, and 13 wk after the Sugen5416 injection, hemodynamic and histological examinations were performed. Right ventricular systolic pressure reached its maximum 5 wk after Sugen5416 injection and plateaued thereafter. Cardiac index decreased at the 3∼5-wk time point, and tended to further decline at later time points. Reflecting these changes, calculated total pulmonary resistance showed a pattern of progressive worsening. Acute intravenous fasudil markedly reduced the elevated pressure and resistance at all time points tested. The percentage of severely occluded small pulmonary arteries showed a similar pattern of progression to that of right ventricular systolic pressure. These small vessels were occluded predominantly with nonplexiform-type neointimal formation except for the 13-wk time point. There was no severe occlusion in larger arteries until the 13-wk time point, when significant numbers of vessels were occluded with plexiform-type neointima. The Sugen5416/hypoxia/normoxia-exposed rat shows a pattern of chronic hemodynamic progression similar to that observed in pulmonary arterial hypertension patients. In addition to vasoconstriction, nonplexiform-type neointimal occlusion of small arteries appears to contribute significantly to the early phase of pulmonary arterial hypertension development, and plexiform-type larger vessel occlusion may play a role in the late deterioration.

TRPC4 inactivation confers a survival benefit in severe pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure with lumen-occluding neointimal and plexiform lesions. Activation of store-operated calcium entry channels promotes contraction and proliferation of lung vascular cells. TRPC4 is a ubiquitously expressed store-operated calcium entry channel, but its role in PAH is unknown. We tested the hypothesis that TRPC4 promotes pulmonary arterial constriction and occlusive remodeling, leading to right ventricular failure in severe PAH. Severe PAH was induced in Sprague-Dawley rats and in wild-type and TRPC4-knockout Fischer 344 rats by a single subcutaneous injection of SU5416 [SU (semaxanib)], followed by hypoxia exposure (Hx; 10% O2) for 3 weeks and then a return to normoxia (Nx; 21% O2) for 3 to 10 additional weeks (SU/Hx/Nx). Although rats of both backgrounds exhibited indistinguishable pulmonary hypertensive responses to SU/Hx/Nx, Fischer 344 rats died within 6 to 8 weeks. Normoxic and hypertensive TRPC4-knockout rats recorded hemodynamic parameters similar to those of their wild-type littermates. However, TRPC4 inactivation conferred a striking survival benefit, due in part to preservation of cardiac output. Histological grading of vascular lesions revealed a reduction in the density of severely occluded small pulmonary arteries and in the number of plexiform lesions in TRPC4-knockout rats. TRPC4 inactivation therefore provides a survival benefit in severe PAH, associated with a decrease in the magnitude of occlusive remodeling.

The Status Quo of Pharmacogenomics of Tyrosine Kinase Inhibitors in Precision Oncology: A Bibliometric Analysis of the Literature.

Precision oncology and pharmacogenomics (PGx) intersect in their overarching goal to institute the right treatment for the right patient. However, the translation of these innovations into clinical practice is still lagging behind. Therefore, this study aimed to analyze the current state of research and to predict the future directions of applied PGx in the field of precision oncology as represented by the targeted therapy class of tyrosine kinase inhibitors (TKIs). Advanced bibliometric and scientometric analyses of the literature were performed. The Scopus database was used for the search, and articles published between 2001 and 2023 were extracted. Information about productivity, citations, cluster analysis, keyword co-occurrence, trend topics, and thematic evolution were generated. A total of 448 research articles were included in this analysis. A burst of scholarly activity in the field was noted by the year 2005, peaking in 2017, followed by a remarkable decline to date. Research in the field was hallmarked by consistent and impactful international collaboration, with the US leading in terms of most prolific country, institutions, and total link strength. Thematic evolution in the field points in the direction of more specialized studies on applied pharmacokinetics of available and novel TKIs, particularly for the treatment of lung and breast cancers. Our results delineate a significant advancement in the field of PGx in precision oncology. Notwithstanding the practical challenges to these applications at the point of care, further research, standardization, infrastructure development, and informed policymaking are urgently needed to ensure widespread adoption of PGx.

Hospital Mortality and Morbidity in Diabetic Patients with COVID-19: A Retrospective Analysis from the UAE.

BACKGROUND: Although we are four years into the pandemic, there is still conflicting evidence regarding the clinical outcomes of diabetic patients hospitalized with COVID-19. The primary objective of this study was to evaluate the in-hospital mortality and morbidity of diabetic versus nondiabetic patients hospitalized with COVID-19 in the Northern UAE Emirates. METHODS: A retrospective analysis was performed on clinical data from patients with or without diabetes mellitus (DM) who were admitted to the isolation hospital with COVID-19 during the first and second waves of the disease (March 2020 to April 2021). The assessed endpoints were all-cause in-hospital mortality, length of hospitalization, intensive care unit (ICU) admission, and mechanical ventilation. RESULTS: A total of 427 patients were included in the analysis, of whom 335 (78.5%) had DM. Compared to nondiabetics, diabetic COVID-19 patients had a significantly longer in-hospital stay (odds ratio (OR) = 2.35; 95% confidence interval (CI) = 1.19-4.62; p = 0.014), and a significantly higher frequency of ICU admission (OR = 4.50; 95% CI = 1.66-7.34; p = 0.002). The need for mechanical ventilation was not significantly different between the two groups (OR: distorted estimates; p = 0.996). Importantly, the overall in-hospital mortality was significantly higher among diabetic patients compared to their nondiabetic counterparts (OR = 2.26; 95% CI = 1.08-4.73; p = 0.03). CONCLUSION: DM was associated with a more arduous course of COVID-19, including a higher mortality rate, a longer overall hospital stay, and a higher frequency of ICU admission. Our results highlight the importance of DM control in COVID-19 patients to minimize the risk of detrimental clinical outcomes.

Dehydroepiandrosterone restores right ventricular structure and function in rats with severe pulmonary arterial hypertension.

Current therapy of pulmonary arterial hypertension (PAH) is inadequate. Dehydroepiandrosterone (DHEA) effectively treats experimental pulmonary hypertension in chronically hypoxic and monocrotaline-injected rats. Contrary to these animal models, SU5416/hypoxia/normoxia-exposed rats develop a more severe form of occlusive pulmonary arteriopathy and right ventricular (RV) dysfunction that is indistinguishable from the human disorder. Thus, we tested the effects of DHEA treatment on PAH and RV structure and function in this model. Chronic (5 wk) DHEA treatment significantly, but moderately, reduced the severely elevated RV systolic pressure. In contrast, it restored the impaired cardiac index to normal levels, resulting in an improved cardiac function, as assessed by echocardiography. Moreover, DHEA treatment inhibited RV capillary rarefaction, apoptosis, fibrosis, and oxidative stress. The steroid decreased NADPH levels in the RV. As a result, the reduced reactive oxygen species production in the RV of these rats was reversed by NADPH supplementation. Mechanistically, DHEA reduced the expression and activity of Rho kinases in the RV, which was associated with the inhibition of cardiac remodeling-related transcription factors STAT3 and NFATc3. These results show that DHEA treatment slowed the progression of severe PAH in SU5416/hypoxia/normoxia-exposed rats and protected the RV against apoptosis and fibrosis, thus preserving its contractile function. The antioxidant activity of DHEA, by depleting NADPH, plays a central role in these cardioprotective effects.

PTEN loss is not a determinant of time to castration-resistance following androgen-deprivation therapy in prostate cancer: a study from Jordan.

Androgen deprivation therapy (ADT) remains the principal treatment of advanced prostate cancer. However, most patients eventually experience treatment failure, resulting in castrate-resistant prostate cancer (CRPC). Loss of the tumor suppressor gene phosphatase and tensin homolog (PTEN) has been linked to poor survival in prostate cancer. We have recently shown that PTEN loss is evident in approximately 60% of prostate cancer cases in Jordan. However, the correlation between PTEN loss and response to ADT remains unclear. This study aimed to determine the relationship between PTEN loss and time to CRPC in Jordan. We conducted a retrospective analysis of confirmed CRPC cases at our institution from 2005 to 2019 (N=104). PTEN expression was assessed using immunohistochemistry. Time to CRPC was calculated from the initiation of ADT to the confirmed diagnosis of CRPC. Combination/sequential ADT was defined as the use of two or more classes of ADT concomitantly or switching from one class to another. We found that PTEN loss was evident in 60.6% of CRPC. Mean time to CRPC was not different between patients with PTEN loss (24.8 months) and those with intact PTEN (24.2 months; p=0.9). However, patients receiving combination/sequential ADT had a significantly delayed onset of CRPC compared to patients on monotherapy ADT (log-rank Mantel-Cox p=0.000). In conclusion, PTEN loss is not a major determinant of time to CRPC in Jordan. The use of combination/sequential ADT procures a significant therapeutic advantage over monotherapy regimens, delaying the onset of CRPC.

A Comparative Piloting of Determinants of Self-Medication Among University Students in the MENA Region; UAE and Jordan as an Example.

Purpose: Unsupervised self-medication (SM) is a global public health concern. University students are particularly vulnerable due to misperceptions of improved academic performance and thus are at risk of dependence, addiction, and drug overdose. Past studies have shown an alarming prevalence of SM among university students in the Middle East and North Africa (MENA) region. However, there is a scarcity of reports from the region dissecting determinants of SM. Therefore, this study aimed to determine the prevalence and epidemiological correlates of SM among university students and its perceived impact on their academic performance. Methods: Two countries in the MENA region were surveyed in a cross-sectional design; UAE and Jordan. Through a stratified sampling technique, undergraduate students in both healthcare and non-healthcare majors of study were recruited to participate. A structured, self-administered questionnaire developed for the purpose of this study was distributed to consented participants via the university's official email. Statistical analyses were performed using SPSS. Descriptive and inferential statistics were used to analyze data. A p-value <0.05 was considered statistically significant. Results: A total of 362 students participated in the study (74% were females, 60% were from the UAE, and 59% were in healthcare majors). Significantly higher prevalence rates and adjusted odds of SM were found among females, students from Jordan, and those in healthcare majors, particularly for paracetamol (90.2% of females [p=0.001], 88.3% from Jordan [p=0.03], 92.5% in healthcare majors [p=0.001]) and antibacterial drugs (48.9% of females [p=0.01], 60.7% from Jordan [p=0.001], 53.3% in healthcare majors [p=0.001]). Majoring in healthcare fields was the most consistent determinant of such practice, while social influences of family and friends represented the chief source of recommendation. Only 21% of respondents assumed SM boosts their academic performance. Conclusion: Our pilot study underlines the predominant determinants of SM among university students in the MENA region, namely female gender, students from Jordan, and those in healthcare majors. Informed data-driven awareness campaigns to mitigate such practice should be designed to focus on these susceptible populations.

Jordan's Pandemic Influenza Preparedness (PIP): A Reflection on COVID-19 Response.

The COVID-19 pandemic made it clear to the world that better preparedness for future pandemics is paramount. This study aims to explore how the 2018 Jordan's Pandemic Influenza Preparedness (PIP) assessment plan (conducted utilizing a standardized tool of the CDC National Inventory of Core Capabilities for Pandemic Influenza Preparedness and Response) reflected on the initial COVID-19 response. A qualitative, single intrinsic case study design, utilizing interpretivist approach, was utilized to interview subject-matter experts and explore the potential reflection of PIP assessment on COVID-19 response. Utilizing a mini-Delphi approach, the interviews aimed at generating an in-depth understanding of how the Jordan's PIP risk assessment reflects on the country's response to COVID-19. The following 12 core capabilities, along with their reflections on COVID-19, were assessed: country planning, research and use of findings, communications, epidemiologic capability, laboratory capability, routine influenza surveillance, national respiratory disease surveillance, outbreak response, resources for containment, community-based interventions to prevent the spread of influenza, infection control (IC), and health sector pandemic response. Jordan's experience and preparedness for influenza may have served as a crucial guide to establishing success in COVID-19 control and mitigation. Surveillance, outbreak, and research activities were very well established in Jordan's PIP, whereas surge capacity in human capital and health facility were identified as two high-risk areas. However, the limitation in these two areas was met during the COVID-19 response. Still, human capital suffered fatigue, and there was an evident lack of laboratory testing plans when COVID-19 cases increased. Jordan's experience with PIP may have served as a guide for establishing successful COVID-19 control and mitigation. The established PIP principles, systems, and capacities seem to have reflected well on fighting against COVID-19 in terms of more efficient utilization of available surveillance, laboratory, outbreak management, and risk communications. This reflection facilitated a better mitigation and control of COVID-19.

Effectiveness of interactive teaching intervention on medical students' knowledge and attitudes toward stem cells, their therapeutic uses, and potential research applications.

BACKGROUND: Stem cell science is rapidly developing with the potential to alleviate many non-treatable diseases. Medical students, as future physicians, should be equipped with the proper knowledge and attitude regarding this hopeful field. Interactive teaching, whereby the teachers actively involve the students in the learning process, is a promising approach to improve their interest, knowledge, and team spirit. This study aims to evaluate the effectiveness of an interactive teaching intervention on medical students' knowledge and attitudes about stem cell research and therapy. METHODS: A pre-post test study design was employed. A six-session interactive teaching course was conducted for a duration of six weeks as an intervention. Pre- and post-intervention surveys were used. The differences in the mean scores of students' knowledge and attitudes were examined using paired t-test, while gender differences were examined using an independent t-test. RESULTS: Out of 71 sixth-year medical students from different nationalities invited to participate in this study, the interactive teaching course was initiated by 58 students resulting in a participation rate of 81.7%. Out of 58 students, 48 (82.8%) completed the entire course. The mean age (standard deviation) of students was 24 (1.2) years, and 32 (66.7%) were males. The results showed poor knowledge about stem cells among the medical students in the pre-intervention phase. Total scores of stem cell-related knowledge and attitudes significantly improved post-intervention. Gender differences in knowledge and attitudes scores were not statistically significant post-intervention. CONCLUSIONS: Integrating stem cell science into medical curricula coupled with interactive learning approaches effectively increased students' knowledge about recent advances in stem cell research and therapy and improved attitudes toward stem cell research and applications.

Tyrosine kinase inhibitors are potent acute pulmonary vasodilators in rats.

Tyrosine kinase inhibitors are promising for the treatment of severe pulmonary hypertension. Their therapeutic effects are postulated to be due to inhibition of cell growth-related kinases and attenuation of vascular remodeling. Their potential vasodilatory activities have not been explored. Vasorelaxant effects of the tyrosine kinase inhibitors imatinib, sorafenib, and nilotinib were examined in isolated pulmonary arterial rings from normal and pulmonary hypertensive rats. Phosphorylation of myosin light chain phosphatase and myosin light chain was assessed by Western blots. Acute hemodynamic effects of imatinib were tested in the pulmonary hypertensive rats. In normal pulmonary arteries, imatinib reversed serotonin- and U46619-induced contractions in a concentration-dependent and endothelium-independent manner. Sorafenib and nilotinib relaxed U46619-induced contraction. Imatinib inhibited activation of myosin phosphatase induced by U46619 in normal pulmonary arteries. All three tyrosine kinase inhibitors concentration-dependently and completely reversed the spontaneous contraction of hypertensive pulmonary arterial rings unmasked by inhibition of nitric oxide synthase. Acute intravenous administration of imatinib reduced high right ventricular systolic pressure in pulmonary hypertensive rats, with little effect on left ventricular systolic pressure and cardiac output. We conclude that tyrosine kinase inhibitors have potent pulmonary vasodilatory activity, which could contribute to their long-term beneficial effect against pulmonary hypertension. Vascular smooth muscle relaxation mediated via activation of myosin light chain phosphatase (Ca(2+) desensitization) appears to play a role in the imatinib-induced pulmonary vasodilation.

Formation of plexiform lesions in experimental severe pulmonary arterial hypertension.

BACKGROUND: The plexiform lesion is the hallmark of severe pulmonary arterial hypertension. However, its genesis and hemodynamic effects are largely unknown because of the limited availability of lung tissue samples from patients with pulmonary arterial hypertension and the lack of appropriate animal models. This study investigated whether rats with severe progressive pulmonary hypertension developed plexiform lesions. METHODS AND RESULTS: After a single subcutaneous injection of the vascular endothelial growth factor receptor blocker Sugen 5416, rats were exposed to hypoxia for 3 weeks. They were then returned to normoxia for an additional 10 to 11 weeks. Hemodynamic and histological examinations were performed at 13 to 14 weeks after the Sugen 5416 injection. All rats developed pulmonary hypertension (right ventricular systolic pressure approximately 100 mm Hg) and severe pulmonary arteriopathy, including concentric neointimal and complex plexiform-like lesions. There were 2 patterns of complex lesion formation: a lesion forming within the vessel lumen (stalk-like) and another that projected outside the vessel (aneurysm-like). Immunohistochemical analyses showed that these structures had cellular and molecular features closely resembling human plexiform lesions. CONCLUSIONS: Severe, sustained pulmonary hypertension in a very late stage of the Sugen 5416/hypoxia/normoxia-exposed rat is accompanied by the formation of lesions that are indistinguishable from the pulmonary arteriopathy of human pulmonary arterial hypertension. This unique model provides a new and rigorous approach for investigating the genesis, hemodynamic effects, and reversibility of plexiform and other occlusive lesions in pulmonary arterial hypertension.

The Effect of Strict State Measures on the Epidemiologic Curve of COVID-19 Infection in the Context of a Developing Country: A Simulation from Jordan.

COVID-19 has posed an unprecedented global public health threat and caused a significant number of severe cases that necessitated long hospitalization and overwhelmed health services in the most affected countries. In response, governments initiated a series of non-pharmaceutical interventions (NPIs) that led to severe economic and social impacts. The effect of these intervention measures on the spread of the COVID-19 pandemic are not well investigated within developing country settings. This study simulated the trajectories of the COVID-19 pandemic curve in Jordan between February and May and assessed the effect of Jordan's strict NPI measures on the spread of COVID-19. A modified susceptible, exposed, infected, and recovered (SEIR) epidemic model was utilized. The compartments in the proposed model categorized the Jordanian population into six deterministic compartments: suspected, exposed, infectious pre-symptomatic, infectious with mild symptoms, infectious with moderate to severe symptoms, and recovered. The GLEAMviz client simulator was used to run the simulation model. Epidemic curves were plotted for estimated COVID-19 cases in the simulation model, and compared against the reported cases. The simulation model estimated the highest number of total daily new COVID-19 cases, in the pre-symptomatic compartmental state, to be 65 cases, with an epidemic curve growing to its peak in 49 days and terminating in a duration of 83 days, and a total simulated cumulative case count of 1048 cases. The curve representing the number of actual reported cases in Jordan showed a good pattern compatibility to that in the mild and moderate to severe compartmental states. The reproduction number under the NPIs was reduced from 5.6 to less than one. NPIs in Jordan seem to be effective in controlling the COVID-19 epidemic and reducing the reproduction rate. Early strict intervention measures showed evidence of containing and suppressing the disease.