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Dengue virus (DENV) remains one of the most common arboviral infections threatening humans. This study was conducted to systematically review the available literature and provide an updated overview of the overall prevalence of DENV infection in Saudi Arabia. The prevalence data was pooled from 21,891 participants recruited in 17 studies. Using random-effects model, the overall prevalence of DENV infection in Saudi Arabia was calculated as 30.8% (95% CI: 20.8-49.8%). The pooled IgM and IgG seroprevalence rates were 17.7% and 26.6%, respectively. Furthermore, the detection of DENV-NS1 antigen and viral RNA revealed pooled estimates of 16.4% and 37.0%, respectively. This study reports a relatively high burden of DENV infection in Saudi Arabia. The findings of this SRMA provide valuable information on the epidemiology of DENV infections in the country, highlighting the need for additional epidemiological investigations to assess the current situation of DENV infection in the country.

Introduction: This study aimed to evaluate the prevalence of Klebsiella pneumoniae contamination in raw lettuce from Risalpur, Pakistan, and to analyze the antibiotic susceptibility profiles of the isolated strains. The presence of foodborne pathogens such as K. pneumoniae poses significant public health risks, particularly in regions with suboptimal hygiene practices and improper food handling., Methods: Lettuce samples were collected from various sources in Risalpur and screened for K. pneumoniae . Antimicrobial susceptibility testing was performed to evaluate the effectiveness of various antibiotics against the isolated strains. Statistical analyses, including ANOVA and linear regression, were conducted to assess differences in inhibition zones and to predict antibiotic effectiveness based on concentration., Results: The results revealed a significant prevalence of K. pneumoniae in the lettuce samples, highlighting the risks associated with poor hygiene, transportation, storage, and contaminated irrigation water. The isolated strains exhibited high susceptibility to gentamicin but demonstrated notable resistance to doxycycline, vancomycin, and ticarcillin. Multidrug-resistant (MDR) strains were identified. ANOVA showed significant differences in inhibition zones, and the linear regression model predicted a Zone of Inhibition based on antibiotic concentration (β 0 = 10.6667, β 1 = 0.4556)., Discussion: The identification of MDR strains of K. pneumoniae underscores the urgent need for enhanced antibiotic stewardship and food safety protocols to manage foodborne pathogens. Improved hygiene practices throughout the food production and supply chain are critical to mitigate health risks and address the challenge of growing antibiotic resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khan, Wali, Khan, Munir, Pari, Yousuf and Almutawif.)

Background and Aim: Brucellosis is a highly contagious, neglected zoonotic disease of major importance worldwide. The disease is endemic in many countries, burdening healthcare systems and the livestock industry and representing a persistent public health concern in these countries. Brucellosis is considered an important occupational hazard for livestock workers. Limited studies have investigated human brucellosis in Saudi Arabia. Therefore, this study aimed to estimate the prevalence of brucellosis among employees of high-risk brucellosis professions, including veterinarians, animal herders, and abattoir workers in Madinah, Saudi Arabia, and to determine the associated risk factors., Materials and Methods: A cross-sectional study was conducted in Madinah, Saudi Arabia, during the period of January-March 2023. Ninety blood samples were collected from individuals occupationally at risk of exposure to Brucella infections. Serum samples were examined for immunoglobulins (Ig)M and IgG antibodies against Brucella using an indirect enzyme-linked immunosorbent assay. Before sample collection, a predesigned online questionnaire was used to collect the participants' sociodemographic characteristics and the probable risk factors for human brucellosis. A Chi-square test was used to compare the differences among groups; p < 0.05 were considered statistically significant., Results: Among the 90 participants among the high-risk individuals, Brucella IgM and IgG seropositivity were found in 8 (8.8%) and 11 (12.12%) cases, respectively. IgM mono antibody positivity was observed in 4 (4.44%) and 7 (7.77%) of the study population who tested positive for IgG only. Dual positivity for IgM and IgG antibodies was observed in 4 (4.44%) participants. No significant association was determined between seropositivity and age, urbanicity, education, occupation, and duration of exposure (p > 0.05)., Conclusion: Brucellosis is a high-risk occupational disease among workers with close contact with livestock. This study demonstrates that the seroprevalence of brucellosis among occupationally high-risk individuals in Madinah, Saudi Arabia, is relatively low compared to other countries in the region. Nevertheless, educational programs should be implemented to improve knowledge regarding brucellosis, particularly among high-risk individuals., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Najim, et al.)

In response to the escalating threat of drug-resistant fungi to human health, there is an urgent need for innovative strategies. Our focus is on addressing this challenge by exploring a previously untapped target, yeast casein kinase (Yck2), as a potential space for antifungal development. To identify promising antifungal candidates, we conducted a thorough screening of the diverse-lib drug-like molecule library, comprising 99,288 molecules. Five notable drug-like compounds with diverse-lib IDs 24334243, 24342416, 17516746, 17407455, and 24360740 were selected based on their binding energy scores surpassing 11 Kcal/mol. Our investigation delved into the interaction studies and dynamic stability of these compounds. Remarkably, all selected molecules demonstrated acceptable RMSD values during the 200 ns simulation, indicating their stable nature. Further analysis through Principal Component Analysis (PCA)-based Free Energy Landscape (FEL) revealed minimal energy transitions for most compounds, signifying dynamic stability. Notably, the two compounds exhibited slightly different behaviour in terms of energy transitions. These findings mark a significant breakthrough in the realm of antifungal drugs against C. albicans by targeting the Yck2 protein. However, it is crucial to note that additional experimental validation is imperative to assess the efficacy of these molecules as potential antifungal candidates. This study serves as a promising starting point for further exploration and development in the quest for effective antifungal solutions.Communicated by Ramaswamy H. Sarma.

Background and Aim: Hepatocellular carcinoma (HCC) is a significant complication of hepatitis B and still poses a global public health concern. This systematic review and meta-analysis provide adequate details on the prevalence of HCC in the HBV population within Southeast Asian countries., Method: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, a thorough search for literature discussing the prevalence of HCC in the HBV population within southeast Asia was performed. Eligible studies were subjected to a meta-analysis utilising a DerSimonian and Laird approach and a random effect model. A protocol was registered with PROSPERO (CRD42023423953)., Result: Our study meticulously recovered 41 articles from seven countries in Southeast Asia, namely Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. A total of 39,050 HBV patients and 7479 HCC cases in southeast Asia were analysed. The pooled prevalence of HCC in HBV cases within southeast Asia was 45.8% (95% CI, 34.3-57.8%, I 2 = 99.51%, p < 0.001). Singapore (62.5%, CI: 42.4-79.1) had the highest pooled prevalence of HCC in the HBV population compared to Vietnam, with the lowest estimate (22.4%, CI: 9.9-44.9). There was a drop in the pooled prevalence of HCC in HBV from 2016 until now (37.6%, CI: 19.2-60.5)., Conclusion: The findings of this review reveal a high pooled prevalence of HCC in the HBV population and therefore stir the need for routine screening, management, and surveillance.

Oxysterols (OXY) are oxidized derivatives of cholesterol associated with oxidation and can increase the risk of cardiovascular diseases. The aim of the current study is to examine the relationships between OXY profile, lipids, lipoprotein(a) [Lp(a)] and paraoxonase1 (PON1) with coronary heart disease (CHD) in patients with diabetes mellitus type1 (T1DM) and type2 (T2DM). 120 diabetic patients (T1DM=40, T2DM=80) and 60 healthy subjects were recruited in the study. OXY profile (7-KChol, 7β-OHChol and Chol-triol) was measured using liquid chromatography-mass spectrometry. The clinical profile of the study participants was also collected. 7-KChol, 7β-OHChol and Chol-triol and Lp(a), FBG and glycation parameters were higher in diabetic patients compared to controls (p>0.01), whereas PON1 was lower in patients compared to controls (p>0.01). Within the T2DM group, 7-KChol and 7β-OHChol levels were associated with CHD, obesity, and smoking (p<0.05). In addition, KChol, 7β-OHChol and Chol-triol levels were associated with smoking in T1DM (p>0.05). In both diabetic types, 7-KChol, 7β-OHChol and Chol-triol were significantly correlated with TC, LDL, ApoB and Lp(a), glycation parameters and inversely with PON1 (p>0.05). OXY profile in diabetic patients can be used as a reliable biomarker of CHD, particularly in T2DM.

Background: There is a growing interest in medicinal plants in recent years due to their many therapeutic benefits and low side effects. Among the medicinal plants is the African Adansonia digitata (baobab) that has edible fruit. In the current study, the effect of A. digitata juice consumption on the lipid profile was investigated. In addition, inhibition of the oxidation of low-density lipoprotein cholesterol (LDL-C) in-vitro by A. digitata essential oil (EO) was also investigated., Methods: In this cohort study, a total of 70 subjects of A. digitata users (AD group, 42 male and 28 female) and 70 non A. digitata users (Non-AD group, 44 male and 26 female) were recruited to participate in this study. We evaluated lipid profile, HbA1c, liver/kidney functions, and phytosterol contents in fasting blood samples of all participants., Results: The present findings illustrated significantly lower levels of total cholesterol, triglycerides, and LDL in the AD group compared to Non-AD (p < 0.01). In addition, essential oil of A. digitata inhibited LDL oxidation in-vitro as shown by the significant decreases in the formation of malonaldehyde (MDA), protein carbonyl (PC), and lipid hydroperoxide (LHP) (P<0.05). No significant changes in fasting blood glucose, HbA1c, HDL, kidney function, and liver function enzymes between the two groups were detected (P>0.05)., Conclusion: The juice of A. digitata has hypolipidemic and antioxidative effects and might be beneficial for the management of lipid levels in the body., Competing Interests: None., (© 2022 The College of Medicine and the Medical Association of Malawi.)

Objectives: To study the genotype and allele frequency of the fat mass and obesity-associated (FTO) rs8050136 A>C genetic variant and investigate its association with type 2 diabetes mekkitus (T2DM) parameters., Methods: This study was carried out on 118 diabetic patients and 106 healthy individuals (control) from Prince Mohammed bin Abdulaziz Hospital, Al Madinah Al Munawarah, Saudi Arabia. The TaqMan single-nucleotide polymorphism (SNP)genotyping assay was used for rs8050136 genotyping., Results: The frequency of the genotype AA was the same among T2DM and healthy control groups (21%). However, the frequency of genotype CC was 19.5% in T2DM patients and 24.5% in control individuals. There was no significant association between FTO SNP rs8050136 and an increased risk of T2DM. Furthermore, there was no association between the risk AA genotype and fasting blood glucose ( p =0.092), glycated hemoglobin ( p =0.177), or body mass index ( p =0.561)., Conclusion: Our findings show that the FTO rs8050136 A>C variant is not associated with T2DM in the Saudi population., (Copyright: © Saudi Medical Journal.)

Background: The interaction of T cells with infected macrophages depends on the interplay of cytokines produced in each cell, and this mechanism is a key to protective immunity against Mycobacterium tuberculosis. Extensive research has been devoted to studying the changes in systemic cytokine levels in patients with tuberculosis (TB), but the results are inconclusive. Determine Th1 and Th2 cytokine immune response levels among new TB patients compared to follow-up and healthy control., . Design: Cross-sectional laboratory-based study., Setting: Immunology Laboratory, National Center for Research., Methods: Blood samples (n = 145) were collected from confirmed new TB cases, follow-up TB cases, and from healthy controls. Participants were initially diagnosed by microcopy using Ziehl-Neelsen smear method and confirmed by polymerase chain reaction using IS6110. Cytokine levels (interleukin-10 [IL-10], tumor necrosis factor alpha [TNF-α], and Interferon-gamma [IFN-γ]) were measured directly from plasma using sandwich enzyme-linked immunosorbent assay., Main Outcome Measures: Measuring Th1 cytokines (IFN-γ and TNF-α) and Th2 cytokine (IL-10). One hundred and forty-five cases (new TB cases, 85; follow-up, 25; and healthy control, 35) were included in this study., Results: The study population were mainly males (70.3%) compared to females (29.7%) and 87.5% aged between 21 to 60 year. The plasma IFN-γ levels were found significantly higher in new TB cases (mean 35.38 pg/m; confidence interval: 29.32-41.43) than in the follow-up patients and the healthy control (P = 0.000). There were no significant differences in TNF-α and IL-10 levels among the new TB cases and the follow-up and healthy control (P = 0.852 and P = 0.340, respectively)., Conclusions: Direct plasma IFN-γ level can be used in TB patient follow-up as a recovery marker as it correlated well with the appearance of the disease and treatment response., Competing Interests: None

Objective: This study aimed to highlight the importance of mutations within Proteus mirabilis genome that are related to fluoroquinolone resistance., Methods: This is a cross sectional study performed in different teaching hospitals in Khartoum State from June 2016 to May 2017. A total of (120) P mirabilis isolates from patients with symptoms of UTIs attending different hospitals in Khartoum State were examined. First, modified Kurby Bauer method was performed for phenotypical detection of resistant isolates. Then polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing were applied for detection of mutations in GyrA , GyrB , ParC and ParE genes of isolates., Results: P. mirabilis showed 30% resistance to ciprofloxacin. All samples revealed mutation at (serine 83) of GyrA and (serine 84) of ParC by Hinf1 restriction endonuclease digestion. Sequencing was performed for 12 samples. For each gene, two resistant and one susceptible strains were randomly selected. The mutations associated with ciprofloxacin resistant P. mirabilis were as follows; (1/3) GyrA (Ser 83 to Ile) and (2/3) ParC (Ser 81 to Ile). Also it revealed silent mutations at codons of GyrB 474 leucine (3/3), 585 valine (2/3), 612 histidine (1/3) and 639 asparagine (1/3) and ParE 469 isoleucine (2/3), 531 aspartic (2/3) and 533 glycine (1/3)., Conclusions: Ciprofloxacin resistance in P. mirabilis could be monitored through detection of mutations within DNA gyrase (encoded by gyrA and gyrB) and topoisomerase IV (encoded by parC and parE)., Competing Interests: Conflict of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Background: Aedes aegypti is a vector for the (re-)emerging human pathogens dengue, chikungunya, yellow fever and Zika viruses. Almost half of the Ae. aegypti genome is comprised of transposable elements (TEs). Transposons have been linked to diverse cellular processes, including the establishment of viral persistence in insects, an essential step in the transmission of vector-borne viruses. However, up until now it has not been possible to study the overall proteome derived from an organism's mobile genetic elements, partly due to the highly divergent nature of TEs. Furthermore, as for many non-model organisms, incomplete genome annotation has hampered proteomic studies on Ae. aegypti., Results: We analysed the Ae. aegypti proteome using our new proteomics informed by transcriptomics (PIT) technique, which bypasses the need for genome annotation by identifying proteins through matched transcriptomic (rather than genomic) data. Our data vastly increase the number of experimentally confirmed Ae. aegypti proteins. The PIT analysis also identified hotspots of incomplete genome annotation, and showed that poor sequence and assembly quality do not explain all annotation gaps. Finally, in a proof-of-principle study, we developed criteria for the characterisation of proteomically active TEs. Protein expression did not correlate with a TE's genomic abundance at different levels of classification. Most notably, long terminal repeat (LTR) retrotransposons were markedly enriched compared to other elements. PIT was superior to 'conventional' proteomic approaches in both our transposon and genome annotation analyses., Conclusions: We present the first proteomic characterisation of an organism's repertoire of mobile genetic elements, which will open new avenues of research into the function of transposon proteins in health and disease. Furthermore, our study provides a proof-of-concept that PIT can be used to evaluate a genome's annotation to guide annotation efforts which has the potential to improve the efficiency of annotation projects in non-model organisms. PIT therefore represents a valuable new tool to study the biology of the important vector species Ae. aegypti, including its role in transmitting emerging viruses of global public health concern.

The development of live viral vaccines relies on empirically derived phenotypic criteria, especially small plaque sizes, to indicate attenuation. However, while some candidate vaccines successfully translated into licensed applications, others have failed safety trials, placing vaccine development on a hit-or-miss trajectory. We examined the determinants of small plaque phenotype in two dengue virus (DENV) vaccine candidates, DENV-3 PGMK30FRhL3, which produced acute febrile illness in vaccine recipients, and DENV-2 PDK53, which has a good clinical safety profile. The reasons behind the failure of PGMK30FRhL3 during phase 1 clinical trial, despite meeting the empirically derived criteria of attenuation, have never been systematically investigated. Using in vitro, in vivo and functional genomics approaches, we examined infections by the vaccine and wild-type DENVs, in order to ascertain the different determinants of plaque size. We show that PGMK30FRhL3 produces small plaques on BHK-21 cells due to its slow in vitro growth rate. In contrast, PDK53 replicates rapidly, but is unable to evade antiviral responses that constrain its spread hence also giving rise to small plaques. Therefore, at least two different molecular mechanisms govern the plaque phenotype; determining which mechanism operates to constrain plaque size may be more informative on the safety of live-attenuated vaccines.

The four serotypes of dengue virus (DENV-1 to -4) cause the most important arthropod-borne viral disease of humans. DENV non-structural protein 5 (NS5) contains enzymatic activities required for capping and replication of the viral RNA genome that occurs in the host cytoplasm. However, previous studies have shown that DENV-2 NS5 accumulates in the nucleus during infection. In this study, we examined the nuclear localization of NS5 for all four DENV serotypes. We demonstrate for the first time that there are serotypic differences in NS5 nuclear localization. Whereas the DENV-2 and -3 proteins accumulate in the nucleus, DENV-1 and -4 NS5 are predominantly if not exclusively localized to the cytoplasm. Comparative studies on the DENV-2 and -4 NS5 proteins revealed that the difference in DENV-4 NS5 nuclear localization was not due to rapid nuclear export but rather the lack of a functional nuclear localization sequence. Interaction studies using DENV-2 and -4 NS5 and human importin-α isoforms failed to identify an interaction that supported the differential nuclear localization of NS5. siRNA knockdown of the human importin-α isoform KPNA2, corresponding to the murine importin-α isoform previously shown to bind to DENV-2 NS5, did not substantially affect DENV-2 NS5 nuclear localization, whereas knockdown of importin-β did. The serotypic differences in NS5 nuclear localization did not correlate with differences in IL-8 gene expression. The results show that NS5 nuclear localization is not strictly required for virus replication but is more likely to have an auxiliary function in the life cycle of specific DENV serotypes.