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.

Diagnosing Parkinson's disease and monitoring its progression: Biomarkers from combined GC-TOF MS and LC-MS/MS untargeted metabolomics.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with a poorly understood etiology. An accurate diagnosis of idiopathic PD remains challenging as misdiagnosis is common in routine clinical practice. Moreover, current therapeutics focus on symptomatic management rather than curing or slowing down disease progression. Therefore, identification of potential PD biomarkers and providing a better understanding of the underlying disease pathophysiology are urgent. Herein, hydrophilic interaction liquid chromatography-mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-TOF MS) based metabolomics approaches were used to profile the serum metabolome of 50 patients with different stages of idiopathic PD (early, mid and advanced) and 45 age-matched controls. Levels of 57 metabolites including cysteine-S-sulfate and N-acetyl tryptophan were significantly higher in patients with PD compared to controls, with lower amounts of additional 51 metabolites including vanillic acid, and N-acetylaspartic acid. Xanthines, including caffeine and its downstream metabolites, were lowered in patients with PD relative to controls indicating a potential role caffeine and its metabolites against neuronal damage. Seven metabolites, namely cysteine-S-sulfate, 1-methylxanthine, vanillic acid, N-acetylaspartic acid, 3-N-acetyl tryptophan, 5-methoxytryptophol, and 13-HODE yielded a ROC curve with a high classification accuracy (AUC 0.977). Comparison between different PD stages showed that cysteine-S-sulfate levels were significantly increasing with the advancement of PD stages while LPI 20:4 was significantly decreasing with disease progression. Our findings provide new biomarker candidates to assist in the diagnosis of PD and monitor its progression. Unusual metabolites like cysteine-S-sulfate might point to therapeutic targets that could enhance the development of novel PD treatments, such as NMDA antagonists.

Hand hygiene knowledge, attitude, and practice before, during and post COVID-19: a cross-sectional study among university students in the United Arab Emirates.

Aims: Hand hygiene (HH) is an essential practice to evade the transmission of germs and minimize community-acquired infections. This study assesses the knowledge, attitude and practice (KAP) of HH and other health and safety measures before, during, and after the COVID-19 pandemic. in university students in the United Arab Emirates (UAE). Methods: A cross-sectional questionnaire study was conducted between December 2022 and March 2023, targeting university students from all disciplines and study levels. A 44-item questionnaire was used which included student demographics, knowledge, attitude, and practice of HH, as well as the anticipated risk of COVID-19 morbidity and mortality. Participants consented before commencing the questionnaire, and the collected data were analysed using the student's t-test and ANOVA test, as required. Results: A total of 378 responses were received nationwide, with a valid response rate of 98%. The HH knowledge revealed an average score of 62%, which was significantly higher in students with moderate family income. Additionally, the average attitude score was 74.7%, as measured on the Likert scale, and the score lacked any correlation with the other variables. HH practice showed an average score of 86.8%, which was correlated with the students' gender and field of study. Conclusions: This study showed a moderate level of knowledge, a good attitude, and good practice around HH and other safety measures among the UAE's university students. Socioeconomic status, gender, and field of study influenced the study outcomes. This study highlights the need for effective awareness campaigns to reinforce students' health and safety, especially for male and non-health science students, in order to protect against communicable diseases.

Unlocking the Therapeutic Potential of BCL-2 Associated Protein Family: Exploring BCL-2 Inhibitors in Cancer Therapy.

Apoptosis, programmed cell death pathway, is a vital physiological mechanism that ensures cellular homeostasis and overall cellular well-being. In the context of cancer, where evasion of apoptosis is a hallmark, the overexpression of anti-apoptotic proteins like Bcl2, Bcl-xL and Mcl-1 has been documented. Consequently, these proteins have emerged as promising targets for therapeutic interventions. The BCL-2 protein family is central to apoptosis and plays a significant importance in determining cellular fate serving as a critical determinant in this biological process. This review offers a comprehensive exploration of the BCL-2 protein family, emphasizing its dual nature. Specifically, certain members of this family promote cell survival (known as anti-apoptotic proteins), while others are involved in facilitating cell death (referred to as pro-apoptotic and BH3-only proteins). The potential of directly targeting these proteins is examined, particularly due to their involvement in conferring resistance to traditional cancer therapies. The effectiveness of such targeting strategies is also discussed, considering the tumor's propensity for anti-apoptotic pathways. Furthermore, the review highlights emerging research on combination therapies, where BCL-2 inhibitors are used synergistically with other treatments to enhance therapeutic outcomes. By understanding and manipulating the BCL-2 family and its associated pathways, we open doors to innovative and more effective cancer treatments, offering hope for resistant and aggressive cases.

Analysis and mapping of global scientific research on human monkeypox over the past 20 years.

Background and Aim: Human monkeypox is an emerging global threat. Hundreds of publications were disseminated in the last few months. This study aimed to map, analyze, and evaluate the bibliometric indicators of the global monkeypox research output. Materials and Methods: All documents published in the past 20 years were retrieved using the Scopus database. Papers published in English and peer-reviewed journals were included. VOSviewer was used to create density and network visualization maps. Results: A total of 1725 published documents were retrieved. Of these, 53% were published in 2022. The average number of authors per document was 4.2. Authors from the USA were the most active and published about 42.1% of the total documents. International collaboration was evident between the USA and both UK and Congo. Keywords mapping identified the main research lines in this field that correlate monkeypox with public health, smallpox, vaccination, and antiviral treatment. Conclusion: This study analyzed and mapped the expanding field of monkeypox research across the world. The bibliometric analysis revealed that the United States has contributed greatly in terms of both individual researchers and academic institutions. There was less cooperation on a global scale than was anticipated. Fostering international cooperation is essential for countering this worldwide danger. Additional scientific research should be conducted to investigate the link between smallpox immunization and monkeypox epidemics.

Knowledge, attitudes, perceptions, and practice toward seasonal influenza and its vaccine: A cross-sectional study from a country of conflict.

Background: The seasonal influenza vaccine is an important preventive measure against influenza and its associated complications. In Yemen, there is no seasonal influenza vaccination policy, and the influenza vaccine is excluded from the national immunization program. Data on vaccination coverage remain scarce with no previous surveillance programs or awareness campaigns implemented in the country. The current study aims to assess the awareness, knowledge, and attitudes of the public in Yemen toward seasonal influenza and their motivators and perceived barriers to receiving its vaccine. Methods: A cross-sectional survey was carried out using a self-administered questionnaire that was distributed to eligible participants using convenience sampling. Results: A total of 1,396 participants completed the questionnaire. The respondents showed a median knowledge score of influenza of 11.0/15.0, and most of them (70%) were able to recognize its modes of transmission. However, only 11.3% of the participants reported receiving the seasonal influenza vaccine. Physicians were the respondents' most preferred information source for influenza (35.2%), and their recommendation (44.3%) was the most cited reason for taking its vaccine. On the contrary, not knowing about the vaccine's availability (50.1%), concerns regarding the safety of the vaccine (17%), and not considering influenza as a threat (15.9%) were the main reported barriers to getting vaccinated. Conclusion: The current study showed a low uptake of influenza vaccines in Yemen. The physician's role in promoting influenza vaccination seems to be essential. Extensive and sustained awareness campaigns would likely increase the awareness of influenza and remove misconceptions and negative attitudes toward its vaccine. Equitable access to the vaccine can be promoted by providing it free of charge to the public.

Nationwide Routine Childhood Vaccination Coverage During the COVID-19 Pandemic in Jordan: Current Situation, Reasons, and Predictors of Vaccination.

Background: The healthcare system in Jordan faced substantial burden during the 2020 COVID-19 pandemic including disruption of routine childhood vaccination services. Aims: We sought, for the first time, to describe the impact of the 2020 pandemic on vaccination coverage of Jordanian children in Jordan and to identify the key contributing factors. Methods: Nationwide vaccination rates were retrieved from the electronic records at the Ministry of Health (2018-2020) enrolling crude births of 220,057 Jordanian children during 2020. Records of doses administered were compared for each month of 2020 with the baseline of 2018-2019. A cross-sectional survey (March-August 2021) was also conducted enrolling a convenient sample of adults aged ≥18 who were Jordanian caregivers for vaccine-eligible children (0-23 months) between 1 January 2020 and the date of the interview. The survey aimed to address caregivers' adherence to routine vaccination during 2020-2021 and to describe the determinants of the current and future adherence to vaccination where multiple logistic regression model was utilized. Results: The electronic records revealed a significant decline in vaccination coverage during 2020. The greatest decline was observed during the lockdown period from 21 March 2020 to 21 April 2020 (32.4%-46.8%) followed by the decline observed by the entry of the first wave during September-October 2020 (18.4%-22.8%). A drop of 14-16% was observed for the vaccines recommended under the age of 12 months and of 6-7% for those recommended in 1-2-year-old children. The yearly coverage rates for measles-1 (at 9 months), 2 (at 12 months as part of measles-mumps-rubella (MMR) vaccine), and 3 (at 18 months as part of MMR) were 76%, 90%, and 87%, respectively, and for hexavalent-1, 2, and 3 were 78%, 78%, and 77%, respectively. The results of the survey revealed that the main reason for vaccination delay for at least 1 month from the recommended administration time was the lockdown, followed by child illness and smart lockdowns (regional lockdown/health center closure). Vaccination delay was less likely to be observed in children aged ≥12 months (P value < 0.001; OR: 0.18; CI: 0.11-0.29) or children with chronic diseases (P value < 0.05; OR: 0.5; CI: 0.33-0.88). Conclusion: The current study demonstrates a decline in vaccination coverage of Jordanian children during the 2020 COVID-19 pandemic. It is important to formulate future strategies to promote catch-up vaccination and to avoid future backsliding of vaccination rates during further waves of the COVID-19 pandemic or other pandemics. These include improving health services, allaying caregivers' concerns about contracting COVID-19, and arranging vaccination campaigns outside health centers.

Clinical investigation of lipoprotein (a) levels in type 2 diabetics for cardiovascular diseases prediction and prognosis.

OBJECTIVES: We aimed to evaluate the levels of serum lipoprotein a, LP (a), in Jordanian patients with type 2 diabetes mellitus (DM); and to examine its relation to glycemic control, metabolic syndrome (MS) and duration of DM. The LP (a) is considered one of the independent risk factors for coronary artery disease (CAD) in the general population. METHODS: Fasting blood samples were drawn from 51 diabetic patients with type 2 DM and 31 non-diabetic age and sex control subjects. Serum LP (a) was measured along with other parameters, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and glycosylated haemoglobin (HbA1c). Correlation analyses were performed between LP (a) and the various variables measured. RESULTS: LP (a) measurement showed a skewed distribution towards the lower levels in both groups. Mean LP (a) levels showed a statistically insignificant difference between the two groups. No correlations of LP (a) were observed with age, sex or body mass index (BMI). No correlations of LP (a) with LDL-c, HDL-c, TG, TC, MS, DM duration or HbA1c were observed. The LP (a) serum levels were significantly higher in type 2 diabetic patients with retinopathy. CONCLUSIONS: LP (a) serum levels are not increased in type 2 diabetic patients; so, LP (a) may not be a reliable marker for early therapeutic interventions in DM patients, even in high-risk for thrombosis groups.

The impact of pharmacist-led educational intervention on pneumococcal vaccine awareness and acceptance among elderly in Jordan.

Limited data exist regarding pneumococcal vaccination coverage among the elderly in Middle Eastern countries including Jordan. The pharmacists' role in improving vaccine acceptance has become increasingly evident. Yet, large-scale studies of the assessment of the pharmacists' role on pneumococcal vaccines acceptance among the elderly are scarce. Hence, we assessed for the first time the current state of knowledge and pneumococcal vaccination coverage among the elderly and the role of pharmacist-led educational intervention on the attitude, awareness, vaccine acceptance, and prompts for physician consultation regarding pneumococcal vaccines in Jordan. This interventional study enrolled 916 randomly selected adults aged ≥ 65 years in Amman, Jordan. We showed that only 3.9% of the participants have ever heard about pneumococcal disease with 0.5% vaccination coverage. Immediately after educational intervention, 21.7% of the participants perceived pneumococcal disease as a threat, 52.1% of them believed in the importance of the vaccine, and 93.9% of them were willing to consult a physician in this regard. At a two-month follow-up, 30.5% had a positive attitude toward the vaccine and 36% consulted their physician regarding the vaccine. Vaccination coverage was significantly increased to 1.9% (P value = 0.008). The main obstacles against vaccination were a negative attitude and that physicians had not recommended the vaccine. Vaccine uptake was significantly associated with physician consultation (P value = 0.011). Insurance, employment, attitude, and reading the booklet significantly predicted physician consultation. In conclusion, very low pneumococcal vaccination coverage was observed among the elderly in Jordan. Enrollment of pharmacists in immunization education and recommendation is suggested to improve pneumococcal vaccine coverage among the elderly in Jordan.

Pregabalin inhibits in vivo and in vitro cytokine secretion and attenuates spleen inflammation in Lipopolysaccharide/Concanavalin A -induced murine models of inflammation.

Immune system alteration has been implicated in the pathogenesis of chronic pain conditions, epilepsy and generalized anxiety disorder. Targeting cytokines has recently been proposed for the management of such conditions. Pregabalin (PGB) is an antiepileptic agent used for the management of these conditions. However, little is known about its immunomodulatory effects on cytokine secretion in vivo and in vitro. Hence, a mitogen (Lipopolysaccharide [LPS] or Concanavalin A [ConA])-induced murine model of inflammation was used to investigate the effect of PGB on in vivo and in vitro IL-1ß, IL-6, TNF-α and IL-2 cytokine secretion using ELISA. In addition, PGB effect on spleen histology, as a lymphoid organ, was examined. Our results revealed that PGB significantly inhibited the secretion of ConA-induced IL-6 secretion, basal and ConA-induced TNF-α and IL-2 secretion in splenocytes in vitro. In vivo, PGB inhibited basal and LPS/ConA-induced IL-6 and TNF-α secretion in addition to LPS-induced IL-1ß and ConA-induced IL-2 secretion. Moreover, PGB attenuated mitogen-induced inflammatory changes in the spleen. These findings provide an evidence of the anti-inflammatory properties of PGB on cytokine secretion and lymphoid organ inflammation. This might give insights into the role of PGB in the management of the inflammatory state in PGB-indicated conditions.

Inhibition of monoglyceride lipase by proton pump inhibitors: investigation using docking and in vitro experiments.

BACKGROUND: Currently, there is overwhelming evidence linking elevated plasma free fatty acids with insulin resistance and inflammation. Monoglyceride lipase (MGL) plays a crucial metabolic role in lipolysis by mediating the release of fatty acids. Therefore, inhibiting MGL should be a promising pharmacological approach for treating type 2 diabetes and inflammatory disorders. Proton pump inhibitors (PPIs) have been reported to improve glycemic control in type 2 diabetes albeit via largely unknown mechanism. METHODS: The anti-MGL bioactivities of three PPIs, namely, lansoprazole, rabeprazole, and pantoprazole, were investigated using docking experiments and in vitro bioassay. RESULTS: The three PPIs inhibited MGL in low micromolar range with rabeprazole exhibiting the best IC50 at 4.2 µM. Docking experiments showed several binding interactions anchoring PPIs within MGL catalytic site. CONCLUSION: Our study provides evidence for a new mechanism by which PPIs improve insulin sensitivity independent of serum gastrin. The three PPIs effectively inhibit MGL and, therefore, serve as promising leads for the development of new clinical MGL inhibitors.

Serum level of insulin-like growth factor-I in type 2 diabetic patients: impact of obesity.

Background Insulin-like growth factor-I (IGF-I) is homologous to proinsulin and possesses glucose reducing activity. The association between the level of IGF-I and diabetes has been highlighted. However, this association is controversial due to the influence of different factors including obesity. The aim of the study was to evaluate serum level of IGF-I in type 2 diabetic patients compared to control subjects. Materials and methods A cross-sectional study involving 100 participants was conducted. Serum levels of IGF-I were measured using enzyme-linked immunosorbent assay (ELISA) and the fasting plasma glucose (FPG) levels were measured using the glucose oxidase method. Results IGF-I levels in the diabetic patients were significantly lower than in non-diabetic control subjects (105.13 ± 6.34 vs. 159.96 ± 9.62 ng/mL, p < 0.0001). Among the diabetic group, there was no significant difference in IGF-I levels between obese diabetic patients and non-obese diabetic patients, p = 0.18. Similarly, among the non-diabetic group, a non-significant difference was found in IGF-I levels between obese non-diabetic and non-obese non-diabetic subjects, p = 0.156. However, among the obese group, obese diabetic patients had significantly lower IGF-I serum levels compared to obese non-diabetic subjects (112.07 ± 7.97 vs. 147.07 ± 13.05 ng/mL, p = 0.02). Furthermore, among the non-obese group, the non-obese diabetic patients had significantly lower IGF-I serum levels compared to the non-obese non-diabetic subjects (91.66 ± 9.93 vs. 171.86 ± 13.86 ng/mL, p < 0.0001). No significant associations were observed between IGF-I level and any of the age, gender, body mass index (BMI), FPG levels, or the duration of diabetes. Conclusions Type 2 diabetes mellitus is associated with lower levels of IGF-I regardless to the presence or absence of obesity.

Travelers to U.S.: Zika Virus Knowledge, Attitudes, and Determinants of Practices in the Middle East-Insights for Future Awareness Campaigns.

Travelers act as sentinels for the spread of Zika virus. Imported Zika cases and the presence of Zika virus-transmitting mosquitoes have been documented in the Middle East. However, data on travelers' knowledge, attitude and practices regarding Zika and its prevention measures within the Middle East are scarce. This study aimed to address this issue in a sample of Jordanian and non-Jordanian travelers to U.S. in Jordan. A paper-based questionnaire was distributed to 301 travelers to U.S. in Queen Alia International airport, Amman, Jordan. Only 2.7% of the travelers knew that Zika is associated with birth defects. A total of 10.4% of the participants knew that the bite of infected mosquitoes is a route of Zika transmission. Only 12.6% of respondents correctly identified Zika prevention measures. The level of education and future plans for pregnancy were significantly associated with a high knowledge score (R2 = 0.140, p-value < 0.005). Although 76.2% of the travelers perceived Zika as a health threat, only 11.2% believed in the efficacy of the prevention measures. Formulation of educational campaigns within Middle Eastern countries and development of awareness strategies regarding Zika and its prevention within the airports are required. This is particularly essential with the upcoming 2022 FIFA World Cup in Qatar.

The Role of the Middle East in ZIKA Virus Circulation: Implications of a Cross-Sectional Study in Jordan.

ZIKA virus (ZIKAV) outbreak in Latin America was associated with international concerns of ZIKAV circulation. The lack of vaccine and Food and Drug Administration (FDA)-approved drugs against this virus rendered prevention as the single most effective method to control its spread. Hence, this study aimed to assess Jordanian population knowledge, attitude, and practices toward ZIKAV and its prevention. An anonymous questionnaire was administered to adults in Amman, Jordan. The overall knowledge of participants was poor (mean knowledge score of 13.7/32). Between 75% and 86% of the respondents did not know the highest risk group of ZIKAV infection, its complications, and the major routes of transmission. About 40% of the population did not know that ZIKAV is sexually transmitted. Only 40% of the population believed that prevention measures are effective. Female gender, working in the medical field, having children, and the source of medical information were associated with significantly higher level of knowledge (R 2 = 0.143, P-value < 0.0001). Being pregnant, however, was not associated with a significantly high knowledge score. Physician recommendations and government's role were the most important predictors of practices toward ZIKAV prevention. Of the 14 returnees from outbreak areas, only six were tested for ZIKAV on coming back and only three continued the use of prevention measures for a sufficient time. Therefore, formulation of a national health policy, preparedness plans against any potential transmission, and organization of educational campaigns to meet the population's health educational needs are required. Special emphasis should be placed on pregnant women and travelers to/returnees from ZIKAV-affected areas.

Physicians' knowledge, attitudes and practices towards Zika virus infection in Jordan.

INTRODUCTION: Zika virus (ZIKAV) disease is a public health problem of international concern. Recent evidence has documented imported ZIKAV cases into the Middle East and the existence of ZIKAV-transmitting mosquitoes in Jordan. However, limited data exist on the role of physicians in public awareness in this regard. This study aimed to assess ZIKAV knowledge, attitudes and counseling practices (KAP) of general physicians and gynecologists in Amman, Jordan. METHODOLOGY: In this cross-sectional study, a structured paper-based questionnaire was completed by 119 participants during 2016-2017. RESULTS: Only 4.2% of the physicians correctly addressed ZIKAV-complication questions. A misconception of considering direct contact between individuals and breastfeeding as modes of ZIKAV transmission was observed. Only one participant correctly recognized that isolation of infected or exposed persons is not recommended. Having at least five years of experience in medical practice was the only factor that was significantly associated with a high knowledge score (P-value=0.011). Although prevention measures are the sole method to control ZIKAV spread, only 50% of participants believed in the efficacy of such measures. Despite a quarter of participants perceiving ZIKAV as a threat to their patients, none of them have counseled a patient in this regard before. The presence of an evidence of ZIKAV in Jordan and health authorities' recommendations were the most important predictors for adoption of counseling practice. CONCLUSIONS: General physicians and gynecologists in Jordan had several gaps in knowledge of key aspects of ZIKAV disease, and there is a need for specific training programs of physicians and gynecologists.

Effect of lamotrigine on in vivo and in vitro cytokine secretion in murine model of inflammation.

Alteration in cytokine levels, particularly, IL-6, TNF-α, IL-1ß and IL-2, has been implicated in the pathogenesis of epilepsy and bipolar disorder. Lamotrigine (LTG), an antiepileptic drug with mood stabilizing properties, has documented immunomodulatory effects. However, its effect on cytokine secretion in vivo has not been examined. Besides, studies have reported inconsistent results of the in vitro effects of LTG on cytokine secretion. Hence, we used murine models of inflammation to characterize the in vivo and the in vitro effects of LTG on the secretion of the aforementioned cytokines, using ELISA. LTG significantly inhibited basal and mitogen-induced IL-6, TNF-α and IL-1ß secretion in vivo and in LPS-treated RAW264.7 cells in vitro. In PMs, LTG inhibited basal and LPS-induced IL-6 and TNF-α secretion. Our findings extend the current understanding of the anti-inflammatory properties of LTG and may be relevant to its role in modulating the immune system in epilepsy and bipolar disorder.

Immunomodulatory Effects of Tigecycline in Balb/C Mice.

Tigecycline is a glycylcycline antibiotic approved by the FDA for the treatment of complicated infections. Despite its effectiveness, the FDA announced a warning of increasing mortality associated with its use. There is, however, no clear explanation for this side effect. Previous reports found a possible effect of tigecycline on leukocyte proliferation and proinflammatory cytokine release. We t herefore i nvestigated the effect of tigecycline on the immune components and response in Balb/c mice in vivo and in vitro. It was found that tigecycline enhanced lymphocyte proliferation and significantly increased cellular infiltration within the footpad, as based on DTH testing, but reduced the hemagglutination titer. In splenocyte cultures, tigecycline suppressed splenocyte proliferation with IC50 3-5 mmol L-1, significantly increased IL-2 secretion and reduced IL-17 secretion in a dose dependent mode. In conclusion, tigecycline is safe at therapeutic and sub-therapeutic doses, but it could still have an immunomodulatory effect at higher doses. Use of higher doses of tigecycline requires further investigation.

Evaluation of immunomodulatory effects of lamotrigine in BALB/c mice.

Modulation of the immune system has recently been shown to be involved in the pharmacological effects of old antiepileptic drugs and in the pathogenesis of epilepsy. Therefore, the most recent guidelines for immunotoxicological evaluation of drugs were consulted to investigate the immunomodulatory effects of lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in vivo effects of lamotrigine on delayed-type hypersensitivity (DTH) response to sheep red blood cell (SRBC) antigens, hemagglutination titer assays and hematological changes. In vitro effects of lamotrigine on ConA-induced splenocyte proliferation and cytokine secretion were assessed. The results showed that lamotrigine treatment significantly increased the DTH response to SRBC in the mouse model of this study. This was accompanied by a significant increase in relative monocyte and neutrophil counts and in spleen cellularity. Lamotrigine significantly inhibited ConA-induced splenocyte proliferation in vitro and it significantly inhibited IL-2 and TNF-α secretion in ConA-stimulated splenocytes. In conclusion, the results demonstrated significant immunomodulatory effects of lamotrigine in BALB/c mice. These data could expand the understanding of lamotrigine-induced adverse reactions and its role in modulating the immune system in epilepsy.

The in vitro generation of multi-tumor antigen-specific cytotoxic T cell clones: Candidates for leukemia adoptive immunotherapy following allogeneic stem cell transplantation.

Adoptive T-cell immunotherapy is a promising approach to manage and maintain relapse-free survival of leukemia patients, especially following allogeneic stem cell transplantation. Post-transplant adoptive immunotherapy using cytotoxic T lymphocytes (CTLs) of the donor origin provide graft-versus-tumor effects, with or without graft-versus-host disease. Myeloid leukemias express immunogenic leukemia associated antigens (LAAs); such as WT-1, PRAME, MAGE, h-TERT and others, most of them are able to induce specific T cell responses whenever associated with the proper co-stimulation. We investigated the ability of a LAA-expressing hybridoma cell line to induce CTL clones in PBMCs of HLA-matched healthy donors in vitro. The CTL clones were induced by repetitive co-culture with LAAs-expressing, HLA-A*0201(+) hybrid cell line, generated by fusion of leukemia blasts to human immortalized APC (EBV-sensitized B-lymphoblastoid cell line; HMy2). The induced cytotoxic T cell clones were phenotypically and functionally characterized by pentamer analysis, IFN-γ release ELISPOT and cellular cytotoxicity assays. All T cell lines showed robust peptide recognition and functional activity when sensitized with HLA-A*0201-restricted WT-1235-243, hTERT615-624 or PRAME100-108 peptides-pulsed T2 cells, in addition to partially HLA-matched leukemia blasts. This study demonstrates the feasibility of developing multi-tumor antigen-specific T cell lines in allogeneic PBMCs in vitro, using LAA-expressing tumor/HMy2 hybrid cell line model, for potential use in leukemia adoptive immunotherapy in partially matched donor-recipient setting.

Knowledge, awareness and practices towards seasonal influenza and its vaccine: implications for future vaccination campaigns in Jordan.

BACKGROUND: Influenza is an underestimated contributor to morbidity and mortality. Population knowledge regarding influenza and its vaccination has a key role in enhancing vaccination coverage. OBJECTIVES: This study aimed to identify the gaps of knowledge among Jordanian population towards influenza and its vaccine, and to identify the major determinants of accepting seasonal influenza vaccine in adults and children in Jordan. METHODS: This was a cross-sectional study that enrolled 941 randomly selected adults in Amman, Jordan. A four-section questionnaire was used which included questions about the sociodemographic characteristics, knowledge about influenza and the factors that affect seasonal influenza vaccine acceptance and refusal. RESULTS: Only 47.3% of the participants were considered knowledgeable. About half of the participants (51.9%) correctly identified the main influenza preventative measures. Lack of knowledge about the important role of seasonal influenza vaccine in disease prevention was observed. Low vaccination rate (20% of adults) was reported. The most critical barrier against vaccination in adults and children was the concern about the safety and the efficacy of the vaccine, while the most important predictors for future vaccination in adults and children were physician recommendation and government role. In children, the inclusion of the vaccine within the national immunization program was an important determinant of vaccine acceptance. CONCLUSION: Formulating new strategies to improve the population's level of knowledge, assuring the population about the safety and the efficacy of the vaccine and the inclusion of the vaccine within the national immunization program are the essential factors to enhance vaccination coverage in Jordan.