Resistance to aminoglycoside and quinolone drugs among Klebsiella pneumoniae clinical isolates from northern Jordan.

This study aimed to identify phenotypic and genotypic aminoglycoside and quinolone non-susceptibility and the prevalence of aminoglycoside-modifying enzymes and plasmid-mediated quinolone resistance genes among K. pneumoniae clinical isolates from northern Jordan. K. pneumoniae isolates (n = 183) were tested for antimicrobial susceptibility using the Kirby-Bauer disk diffusion method. The double-disk synergy test was used for the detection of the extended-spectrum beta-lactamase phenotype. Polymerase chain reaction was used to detect genes encoding aminoglycoside-modifying enzyme (aac (3')-II, aac (6')-II, aac (6')-Ib, ant (3″)-I, aph (3')-VI, armA, and rmtB), and plasmid-mediated quinolone resistance (qnrA, qnrB, qnrC, qnrD, qnrS, acc(6')-Ib-cr, qepA, and oqxAB) genes. Multi-locus sequence typing was used to elucidate the genetic diversity of selected isolates. The non-susceptibility percentages to aminoglycosides and quinolones were 65.0 % and 61.7 %, respectively. The most frequent aminoglycoside-modifying enzyme gene was ant (3″)-I at 73.8 %, followed by aac (6')-Ib at 25.1 %, aac (3')-II at 17.5 %, aph (3')-VI at 12.0 %, armA at 9.8 %, and rmtB at 0.5 %. Aac (6')-II was not detected among the isolates. The most frequent plasmid-mediated quinolone resistance gene was oqxAB at 31.7 %, followed by qnrS at 26.2 %, qnrB at 25.7 %, and aac(6')-Ib-cr at 25.7 %. QnrA, qnrD, qebA, and qnrC were not detected among the isolates. Aac (3')-II, aac (6')-Ib, aph (3')-VI, armA, qnrB, qnrS, and acc(6')-Ib-cr were significantly associated with non-susceptibility to aminoglycosides, quinolones, and beta-lactams. Among 27 randomly selected K. pneumoniae isolates, the most common sequence type was ST2096, followed by ST348 and ST1207. Overall, 19 sequence types were observed, confirming a high level of genetic diversity among the isolates. High percentages of non-susceptibility to the studied antimicrobials were found and were associated with the presence of several resistance genes. Similar studies should be periodically carried out to monitor changes in the prevalence of resistance phenotypes and genotypes of isolates.

Transfusion transmitted virus and dengue virus among healthy blood donors: A prevalence report from Jordan.

Transfusion transmitted virus (TTV) is thought to contribute to non-A non-E hepatitis and other diseases. Dengue virus (DENV) is a serious mosquito-borne pathogen. Reports on TTV and DENV in Jordan and the Middle East and North Africa region are limited. Herein, the prevalence of TTV antigen and anti-DENV IgG antibodies among apparently healthy blood donors from Northern Jordan and the Northern Agwar region of Jordan was investigated using an enzyme-linked immunosorbent assay. Chi-square test and binary logistic regression were used to correlate positivity with possible infection risk factors (age, sex, residence location, and occupation). One hundred ninety apparently healthy blood donors were included in the study (age 18 - 54 years). TTV antigen was detected in 17.9% of the samples. Lower antigen positivity was observed among Agwar residents than non-residents (7.1% vs 24.5%; chi-square test P < 0.001), which was confirmed by regression analysis (odds ratio 0.262 [95% confidence interval 0.086-0.805]; P = 0.019). Antigen positivity did not differ by age, sex, or occupation. Seropositivity for anti-DENV IgG was 17.9%. Seropositivity did not differ by age, sex, or occupation. Higher seropositivity was observed among Agwar residents than non-residents (36.1% vs 9.4%; chi-square test P < 0.001), which was confirmed by regression analysis (odds ratio 5.420 [95% confidence interval 2.377-12.359]; P < 0.001). Overall, low TTV antigen prevalence and DENV seroprevalence were found among blood donors from Northern Jordan and the Northern Agwar region of Jordan.

Sources of SARS-CoV-2 transmission in Jordan: Self-reported approach.

Background: Understanding the dynamics of virus transmission is essential for controlling the COVID-19 pandemic. Demographic factors could influence transmission of the virus in different communities. Herein, the sources of COVID-19 infection in Jordan were explored. In addition, the effects of demographic factors and the adherence to preventive measures on household transmission were investigated. Methods: The study recruited Jordanian adults who recovered from COVID-19 from March to July 2021. Using a questionnaire, information about participants' demographics, level of adherence to personal protective measures, and their perceived source of COVID-19 infection were collected. Crosstabs were used to test for differences in household transmission ratios between different demographic variables. Logistic regression analysis was used to predict risk factors for household transmission. Results: The study recruited a total of 2313 participants. Household transmission was the most frequently reported source of infection (44.9%). Other sources of transmission were work/education related (16.0%), friends (8.6%), healthcare facilities (4.8%), social/event gathering (3.1%), shopping activities (2.2%), and public transport (1.6%). Significantly higher ratios of household transmission were reported by older adults (>60 years), college/university students, and female participants. No significant difference in household transmission was found between low-income and medium-high income groups. A significant increase in household transmission ratios was found with increased adherence to mask-wearing and social distancing. This could be a reflection of the reduced risk of community transmission with increased adherence to these preventive measures, coupled with the difficulty in adhering to these measures within the household setting. In multivariate logistic regression, females, young adults (18-30 years), older adults (>60 years), and those who adhere to mask-wearing most of the time were associated with an increased risk of infection in the household setting. Conclusion: The results reported in the current study provided an insight into the transmission dynamics of the virus in Jordan, as an example of the MENA region. These findings could be invaluable for the future design of public health policies to control COVID-19 and possibly future pandemics.

Effect of natural products use prior to infection with COVID-19 on disease severity and hospitalization: A self-reported cross-sectional survey study.

Background: Managing coronavirus disease 2019 (COVID-19) using available resources is essential to reduce the health burden of disease. The severity of COVID-19 is affected by nutritional status. In this study the effect of natural product use prior to infection with COVID-19 on disease severity and hospitalization was explored. Methods: This was a cross-sectional study. Between March and July 2021, a self-administered survey was conducted in Jordan. Individuals who recovered from COVID-19 and were ≥18 years old were the study population. Study measures included the use of natural products, COVID-19 severity, and hospitalization status. A multivariate regression model was used for statistical analysis. Results: The mean age (mean ± SD) of the study sample (n=2,148) was 40.25 ± 15.58 years old. Multivariate logistic regression showed that the regular intake of carnation (OR [0.56], CI [0.37-0.85]), onion (OR [0.69], CI [0.52-0.92]), lemon (OR [0.68], CI [0.51-0.90]), and citrus fruits (OR [0.66], CI [0.50-0.89]) before infection were associated with a substantial reduction in COVID-19 severity (P<0.01). Also, the consumption of carnation (OR [0.55], CI [0.34-0.88]), lemon (OR [0.57], CI [0.42-0.78]), and citrus fruits (OR [0.61], CI [0.44-0.84]) were associated with a significant decrease in the frequency of COVID-19-induced hospitalization (P<0.01). Conclusions: Regular consumption of carnation, lemon, and citrus fruits before infection was associated with better outcomes for COVID-19. Studies on other populations are required to confirm these findings.

Predictors of COVID-19 severity and hospitalization: A survey-based study from Jordan.

Objectives: To explore the possible predictors of severe illness and hospitalization due to COVID-19 among Jordanians. Method: The study was cross-sectional, survey-based and was conducted from March to July of 2021. Individuals who had recovered from COVID-19 (n = 2148) were recruited in the study. Participants were categorized according to the severity of COVID-19 infection and hospitalization. The study sample was stratified according to age, gender, body mass index (BMI), comorbidities, family income, smoking status, and ABO blood groups. Risk factors were investigated using the Chi-square test and multivariate logistic regression analyses. Results: Severe illness and hospitalization were associated with older age, males, individuals with comorbidities, higher BMI, and lower-income. No significant differences were found in the incidence of severe illness or hospitalization frequency between the ABO groups or between smokers and non-smokers. Multivariate logistic regression analyses predicted male gender, being older than 40, having a BMI of over 30, having 3 or more comorbidities, and low family income as risk factors for severe COVID-19 outcomes. Conclusion: Age was the strongest predictor for severe COVID-19 outcome, followed by having 3 or more comorbidities and to a lesser extent male gender and obesity. These results could help target at-risk groups with infection prevention measures including prioritizing primary COVID-19 vaccines, as well as booster doses.

The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization.

The COVID-19 pandemic has caused a global public health emergency. Nutritional status is suggested to be related to the severity of COVID-19 infection. Herein, we aimed to explore the impact of using vitamin and mineral supplements prior to COVID-19 infection on disease severity and hospitalization. In addition, the prior use of aspirin as an anticoagulant on the disease severity was investigated. A cross-sectional, self-administered survey was conducted between March and July 2021. Recovered COVID-19 individuals (age ≥ 18 years, n = 2148) were recruited in the study. A multivariate logistic regression was used to evaluate the associations of supplements and aspirin use with COVID-19 disease severity and hospitalization status. Among the participants, 12.1% reported symptoms consistent with severe COVID-19, and 10.2% were hospitalized due to COVID-19. After adjustment for confounding variables (age, gender, BMI, cigarette smoking status, and the number of comorbidities), the multivariate logistic regression model showed that the consumption of vitamin D supplements prior to COVID-19 infection was associated with a significant decrease in disease severity (OR = 0.68, 95% CI 0.50 - 0.92; P = 0.01), and a lower risk of hospitalization (OR = 0.64, 95% CI 0.45 - 0.89; P = 0.01). On the other hand, there were no significant differences in the frequencies of severe illness and hospitalizations with the consumption of vitamin A, folic acid, vitamin B12, vitamin B complex, vitamin C, zinc, iron, selenium, calcium, magnesium, omega 3, and aspirin before COVID-19 infection. Among the investigated nutrients, the use of vitamin D prior to COVID-19 infection was associated with reduced disease severity and hospitalization. However, more studies are required to confirm this finding.

Seroprevalence of herpes simplex virus types 1 and 2 and correlates of infection in Jordan.

BACKGROUND: Herpes infections are common infections among populations. Herein, a cross-sectional study was used to determine the seroprevalence of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) IgG antibodies and their association with potential infection risk factors among Jordanians. METHODS: A total of 759 serum samples were collected (January to February 2020) and analyzed for HSV-1 and HSV-2 IgG antibodies by enzyme-linked immunosorbent assay. Estimates for population seropositivity were determined by weighting the age-specific seroprevalence by the size of the population in each age stratum. RESULTS: The population estimate for HSV-1 seroprevalence was 75.3%. After adjustment for possible confounders, regression analysis revealed higher seroprevalence with increase in age (p < 0.005) and low household income (p = 0.002). The population estimate for HSV-2 seroprevalence was 2.9%. No significant differences in HSV-2 seroprevalence were observed in association with age, gender, family size, educational level, and socioeconomic status, likely due to low seropositivity. CONCLUSIONS: Jordanians have high HSV-1 and low HSV-2 seroprevalence. Periodical studies might be needed to evaluate changes in HSV-1 and HSV-2 seroprevalence over time. This study provides essential epidemiological data for Jordan and the Middle East and North Africa region.

Correlates of SARS-CoV-2 Variants on Deaths, Case Incidence and Case Fatality Ratio among the Continents for the Period of 1 December 2020 to 15 March 2021.

The outbreak of coronavirus disease 2019 (COVID-19), by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly developed into a worldwide pandemic. Mutations in the SARS-CoV-2 genome may affect various aspects of the disease including fatality ratio. In this study, 553,518 SARS-CoV-2 genome sequences isolated from patients from continents for the period 1 December 2020 to 15 March 2021 were comprehensively analyzed and a total of 82 mutations were identified concerning the reference sequence. In addition, associations between the mutations and the case fatality ratio (CFR), cases per million and deaths per million, were examined. The mutations having the highest frequencies among different continents were Spike_D614G and NSP12_P323L. Among the identified mutations, NSP2_T153M, NSP14_I42V and Spike_L18F mutations showed a positive correlation to CFR. While the NSP13_Y541C, NSP3_T73I and NSP3_Q180H mutations demonstrated a negative correlation to CFR. The Spike_D614G and NSP12_P323L mutations showed a positive correlation to deaths per million. The NSP3_T1198K, NS8_L84S and NSP12_A97V mutations showed a significant negative correlation to deaths per million. The NSP12_P323L and Spike_D614G mutations showed a positive correlation to the number of cases per million. In contrast, NS8_L84S and NSP12_A97V mutations showed a negative correlation to the number of cases per million. In addition, among the identified clades, none showed a significant correlation to CFR. The G, GR, GV, S clades showed a significant positive correlation to deaths per million. The GR and S clades showed a positive correlation to number of cases per million. The clades having the highest frequencies among continents were G, followed by GH and GR. These findings should be taken into consideration during epidemiological surveys of the virus and vaccine development.

Increased Adherence to Infection Control Practices Among Medical Laboratory Technicians During the COVID-19 Pandemic: A Self-Reported Survey Study.

Background: The adherence of medical laboratory technicians (MLT) to infection control guidelines is essential for reducing the risk of exposure to infectious agents. This study explored the adherence of MLT towards infection control practices during the COVID-19 pandemic. Method: The study population consisted of MLT (n = 444) who worked in private and government health sectors in Jordan. A self-reported survey was used to collect data from participants. Findings: More than 87% of the participants reported adherence to hand-washing guidelines and using personal protective equipment (PPE) when interacting with patients (74.5%), and handling clinical samples (70.0%). Besides, 88.1%, 48.2%, and 7.7% reported wearing of lab coats, face masks, and goggles, at all times, respectively. The majority reported increased adherence to infection control practices during the COVID-19 pandemic. This includes increased PPE use at the workplace (94.2%), increased frequency of disinfection of laboratory surfaces (92.4%) and laboratory equipment (86.7%), and increased frequency of handwashing/use of antiseptics (94.6%). Having a graduate degree was significantly associated with increased adherence of participants to the daily use of goggles/eye protection (p = 0.002), and the use of PPE while handling clinical samples (p = 0.011). Having work experience of >10 years was associated with increased adherence to the use of PPE while handling clinical samples (p = 0.001). Conclusion: MLT reported very good adherence with most assessed infection control practices. In addition, they reported increased conformity with infection control guidelines during the COVID-19 pandemic.

Association between tumor necrosis factor alpha and lymphotoxin alpha gene polymorphisms and migraine occurrence among Jordanians.

Inflammatory reactions in the body have been shown to contribute to migraine development. Therefore, genes involved in the inflammatory pathways might play a role in the susceptibility and development of migraine. In this study, polymorphisms in tumor necrosis factor alpha (TNFα) and lymphotoxin alpha (LTA) genes were tested for association with migraine. A total of 398 participants (198 migraine patients and 200 controls) were recruited in the study. Serum TNF level was measured using a sandwich ELISA kit. Lymphocytes' and monocytes' counts were obtained from a differential complete blood count profile. Participants' DNA was extracted and genotyped for rs1800629 and rs1799724 in TNFα, and rs909253 in LTA. Controls had a significantly higher mean lymphocyte count (P = 0.018), while the mean monocyte count and serum TNFα levels did not differ between the two groups (P > 0.05). With respect to gene polymorphisms, the rs1800629 and rs1799724 variants showed significant association with migraine in all subjects, and in males and females when analyzed separately (P < 0.001). The rs909253 did not show any statistical difference in frequencies among the two groups (P > 0.05). Having the A allele in rs1800629 was associated with a higher risk of migraine in both male (OR, 95%; CI, G/A = 3.79 [1.87-7.69]; A/A = 14.22 [1.67-121.14]; P < 0.01) and female (OR, 95%; G/A = 2.54 [1.47-4.38]; A/A = 2.52 [1.12-5.69]; P < 0.001) subjects. In conclusion, rs1800629 and rs1799724 in TNFα showed significant association with migraine among the Jordanian population.

Biosynthesis of Silver Nanoparticles from Citrobacter freundii as Antibiofilm Agents with their Cytotoxic Effects on Human Cells.

BACKGROUND: Nanomaterials have recently been identified for their potential benefits in the areas of medicine and pharmaceuticals. Among these nanomaterials, silver nanoparticles (Ag-NPs) have been widely utilized in the fields of diagnostics, antimicrobials, and catalysis. OBJECTIVE: To investigate the potential utility of Citrobacter freundii in the synthesis of silver Nanoparticles (Ag-NPs), and to determine the antimicrobial activities of the Ag-NPs produced. METHODS: Aqueous Ag+ ions were reduced when exposed to C. freundii extract and sunlight, leading to the formation of Ag-NPs. Qualitative microanalysis for the synthesized Ag-NPs was done using UVvis spectrometry, Energy Dispersive X-ray analysis (EDX), and scanning and transmission electron microscopy. The hydrodynamic size and stability of the particles were detected using Dynamic Light Scattering (DLS) analysis. The Ag-NPs' anti-planktonic and anti-biofilm activities against Staphylococcus aureus and Pseudomonas aeruginosa, which are two important skin and wound pathogens, were investigated. The cytotoxicity on human dermal fibroblast cell line was also determined. RESULTS: Ag-NPs were spherical with a size range between 15 to 30 nm. Furthermore, Ag-NPs displayed potent bactericidal activities against both S. aureus and P. aeruginosa and showed noticeable anti-biofilm activity against S. aureus biofilms. Ag-NPs induced minor cytotoxic effects on human cells as indicated by a reduction in cell viability, a disruption of plasma membrane integrity, and apoptosis induction. CONCLUSION: Ag-NPs generated in this study might be a future potential alternative to be used as antimicrobial agents in pharmaceutical applications for wound and skin related infections.

Graduate students reported practices regarding the issue of informed consent and maintaining of data confidentiality in a developing country.

Research involving human subjects requires strict adherence to ethical principles, including informed consent and assuring data confidentiality. Herein, a questionnaire was utilized to assess compliance of graduate students who conduct research involving human subjects in Jordan with proper practices related to informed consent and maintaining of data confidentiality. Among the 251 respondents, 55.4% were from health-related fields, 61.4% undertook research involving humans, and 48.6% did research requiring institutional review board approval. Only 37.1% of respondents reported exposure to research ethics education during their graduate study. Satisfactory adherence to informed consent practices was reported at rates of 56.0%-67.5%. Satisfactory adherence to practices related to data confidentiality and study participants' anonymity was reported at rates of 67.3%-74.7%. Sharing of data or samples with others was reported at a rate of 24.3%. The rates of adherence to proper informed consent practices and practices that maintain data confidentiality were less than ideal. Significant policy changes need to be implemented to address these issues.

The impact of exome sequencing on the diagnostic yield of muscular dystrophies in consanguineous families.

Muscular dystrophies (MDs) are a heterogeneous group of inherited disorders that are characterized by progressive skeletal muscle weakness and dystrophic changes on muscle biopsy. The broad genetic and clinical heterogeneity of MDs make the accurate diagnosis difficult via conventional approaches. This study investigated 23 patients from eight unrelated consanguineous families with MDs. Previous clinical assessments did not accurately clarify the type of their MD and/or misdiagnose them with another disease. Exome sequencing (ES) is an efficient, time-saving, and cost-effective tool, enabling disease-causing variant (DCV) detection in affected individuals. We investigated the use of ES to diagnose MD and discover the underlying genetic etiology. We achieved a remarkable diagnostic success rate of 87.5% (7 out of 8 families) which is the highest rate reported thus far compared to previous studies. We identified two novel pathogenic variants in DYSF gene (c.4179delG, c.1149+3G > C). The latter variant impacts the splicing machinery of DYSF mRNA. Moreover, we further assessed the pathogenicity of four recurrent variants ((DYSF, c.4076T > C), (GMPPB, c.458C > T), (SGCA, c.739G > A) (TTN, c.7331G > A), designated their neurological impact and added new phenotypes in patients with these variants. To our knowledge, this is the first study applying an ES-based comprehensive molecular diagnosis to Jordanian cohort with MDs. Our findings confirmed that ES is a powerful approach for the diagnosis of MD patients. This efficient method of molecular diagnosis is crucial for guiding patient clinical care, genetic counseling, and most importantly, paving the way for gene therapy which is currently in clinical trials.

Synergism of cationic antimicrobial peptide WLBU2 with antibacterial agents against biofilms of multi-drug resistant Acinetobacter baumannii and Klebsiella pneumoniae.

PURPOSE: The activity of the cationic antimicrobial peptide WLBU2 was evaluated against planktonic cells and biofilms of multi-drug resistant (MDR) Acinetobacter baumannii and Klebsiella pneumoniae, alone and in combination with classical antimicrobial agents. METHODS: Control American Type Culture Collection (ATCC) strains and MDR clinical isolates of A. baumannii and K. pneumoniae were utilized. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of WLBU2 alone and in combination with antimicrobials were determined by classical methods. The Calgary biofilm device was used to determine the minimum biofilm eradication concentration (MBEC). The MTT assay was used to determine the cytotoxicity of agents on eukaryotic cells. The electrophoretic mobility shift assay was used to evaluate the ability of WLBU2 to bind bacterial DNA. RESULTS: The WLBU2 MIC and MBC values were identical indicating bactericidal activity. The MIC/MBC values ranged from 1.5625 to 12.5 µM. At these concentrations, Vero cells and human skin fibroblasts were viable. The MBEC of WLBU2 ranged from 25 to 200 µM. A significant loss of eukaryotic cell viability was observed at the MBEC range. The combination of sub-inhibitory concentrations of WLBU2 with amoxicillin-clavulanate or ciprofloxacin for K. pneumoniae, and with tobramycin or imipenem for A. baumannii, demonstrated synergism, leading to a significant decrease in MIC and MBEC values for some isolates and ATCC strains. However, all combinations were associated with considerable loss in eukaryotic cells' viability. WLBU2 did not demonstrate the ability to bind bacterial plasmid DNA. CONCLUSION: WLBU2 in combination with antimicrobials holds promise in eradication of MDR pathogens.

Antimicrobial Resistance, Virulence Factors, and Pathotypes of Escherichia coli Isolated from Drinking Water Sources in Jordan.

The study investigated the prevalence of potentially pathogenic and drug resistant Escherichia coli among drinking water sources in Jordan. A total of 109 confirmed E. coli isolates were analyzed. Antimicrobial susceptibility testing was done using the Kirby Bauer disk diffusion method. Phenotypic identification of extended spectrum beta-lactamase (ESBL) and carbapenemase production was done using the double disk synergy test and the modified Hodge test, respectively. Isolates' plasmid profiles were determined by gel electrophoresis. PCR was used for detection of virulence and resistance genes. Overall, 22.0% of the isolates were potentially intestinal pathogenic E. coli (IPEC); namely enteroaggregative E. coli (16.5%), enteropathogenic E. coli (2.8%), enteroinvasive E. coli (1.8%), and enterohemorrhagic E. coli (0.9%). A third of the isolates were multi-drug resistant. The highest rates of antimicrobials resistance were observed against ampicillin (93.6%) and sulfamethoxazole/trimethoprim (41.3%). All isolates were susceptible to imipenem, meropenem, doripenem and tigecycline. The prevalence of ESBL and carbapenemase producers was 54.1% and 2.8%, respectively. BlaVIM was the most prevalent resistance gene (68.8%), followed by blaCTX (50.5%), blaTEM (45.9%), blaNDM (11%), blaKPC (4.6%), and blaSHV (0.9%). Fifty-eight (53.2%) isolates contained one or more plasmid ranging from 1.0 to 8.0 kbp. Overall, high prevalence of potentially pathogenic and resistant isolates was observed.

Increased incidence of BK virus viraemia among patients undergoing chronic haemodialysis: a case-control study.

AIMS: Incidence of BK virus (BKV) viraemia, a major risk factor for nephropathy, among patients undergoing chronic haemodialysis remains poorly investigated. This case-control study evaluated the risk of infection by BKV, in addition to hepatitis C virus (HCV) among haemodialysis subjects (n=100), compared with age-matched controls (n=100). METHODS: Subjects' blood plasma samples were subjected to nucleic acid extraction, followed by real-time PCR to evaluate viraemia by BKV and HCV, while sera samples were subjected to ELISA, to identify IgG seropositivity for HCV. RESULTS: Mean age±SD was 47.8±20.4 and 48.9±17.6 years for the haemodialysis and control groups, respectively. BKV and HCV viraemia was observed among 19% versus 8% (OR 2.38, 95% CI 1.09 to 5.18; p=0.023) and 3% versus 0% (p=0.081) of the haemodialysis and control groups, respectively. Mean BK viral load±SD did not vary significantly among the two groups; 914.8±2868 versus 44.30±74.04 copies/mL for the haemodialysis and control groups, respectively (p=0.4041). HCV seropositivity rates were 6% versus 2% (p=0.149), among the haemodialysis and control groups, respectively. CONCLUSIONS: Subjects on haemodialysis may be at increased risk of nephropathy due to increased incidence of BK virus reactivations and may require optimisation of immunosuppressive therapy.

Pomegranate and type 2 diabetes.

Over the last decade, various studies have linked pomegranate (Punica granatum Linn), a fruit native to the Middle East, with type 2 diabetes prevention and treatment. This review focuses on current laboratory and clinical research related to the effects of pomegranate fractions (peels, flowers, and seeds) and some of their active components on biochemical and metabolic variables associated with the pathologic markers of type 2 diabetes. This review systematically presents findings from cell culture and animal studies as well as clinical human research. One key mechanism by which pomegranate fractions affect the type 2 diabetic condition is by reducing oxidative stress and lipid peroxidation. This reduction may occur by directly neutralizing the generated reactive oxygen species, increasing certain antioxidant enzyme activities, inducing metal chelation activity, reducing resistin formation, and inhibiting or activating certain transcriptional factors, such as nuclear factor κB and peroxisome proliferator-activated receptor γ. Fasting blood glucose levels were decreased significantly by punicic acid, methanolic seed extract, and pomegranate peel extract. Known compounds in pomegranate, such as punicalagin and ellagic, gallic, oleanolic, ursolic, and uallic acids, have been identified as having anti-diabetic actions. Furthermore, the juice sugar fraction was found to have unique antioxidant polyphenols (tannins and anthocyanins), which could be beneficial to control conditions in type 2 diabetes. These findings provide evidence for the anti-diabetic activity of pomegranate fruit; however, before pomegranate or any of its extracts can be medically recommended for the management of type 2 diabetes, controlled, clinical studies, are needed.

Multiple functional domains and complexes of the two nonstructural proteins of human respiratory syncytial virus contribute to interferon suppression and cellular location.

Human respiratory syncytial virus (RSV), a major cause of severe respiratory diseases, efficiently suppresses cellular innate immunity, represented by type I interferon (IFN), using its two unique nonstructural proteins, NS1 and NS2. In a search for their mechanism, NS1 was previously shown to decrease levels of TRAF3 and IKKε, whereas NS2 interacted with RIG-I and decreased TRAF3 and STAT2. Here, we report on the interaction, cellular localization, and functional domains of these two proteins. We show that recombinant NS1 and NS2, expressed in lung epithelial A549 cells, can form homo- as well as heteromers. Interestingly, when expressed alone, substantial amounts of NS1 and NS2 localized to the nuclei and to the mitochondria, respectively. However, when coexpressed with NS2, as in RSV infection, NS1 could be detected in the mitochondria as well, suggesting that the NS1-NS2 heteromer localizes to the mitochondria. The C-terminal tetrapeptide sequence, DLNP, common to both NS1 and NS2, was required for some functions, but not all, whereas only the NS1 N-terminal region was important for IKKε reduction. Finally, NS1 and NS2 both interacted specifically with host microtubule-associated protein 1B (MAP1B). The contribution of MAP1B in NS1 function was not tested, but in NS2 it was essential for STAT2 destruction, suggesting a role of the novel DLNP motif in protein-protein interaction and IFN suppression.

Extended Spectrum beta-Lactamases among Gram-Negative Bacterial Isolates from Clinical Specimens in Three Major Hospitals in Northern Jordan.

Background and Objectives. Extended spectrum beta-lactamase (ESBL) production is increasing all over the world, and organisms other than E. coli and K. pneumoniae are acquiring this character. ESBL production is detectable by automation, E-test, double disk diffusion (DDD), and PCR. This study aimed to determine the prevalence of ESBL production among clinical isolates of gram-negative rods, and to evaluate the effectiveness of augmentation of clavunate with Cefotaxime, Ceftazoxime, Aztreonam, Ceftriaxone, and Cefpodoxime in detecting ESBL production. Methods. 472 clinical gram-negative isolates identified by standard methods were tested for ESBL-production by (DDD) method using six cephalosporins and amoxicillin-clavulinate discs. Results. 108/472 (22.9%) of the isolates were ESBL producers, and were prevalent in tertiary care hospitals. 88.2% of E. cloacae, 71.4% of K. pneumoniae, 28.6% of K. oxytoca, 12.5% of C. freundii, 11.1% of A. calcoacceticus, and 10.8% of E. coli were ESBL producers. The DDD test demonstrated some variations in the efficacy of the different cephalosporins in detecting all the ESBL producers. The inclusion of ceftizoxime discs increased the efficacy of the test. It is concluded that ESBL-producing bacteria were prevalent among our hospitalized patients, and involved genera other than Klebsiella and Escherichia, and the inclusion of ceftizoxime increased the efficacy of ESBL detection by the DDD test.

Respiratory syncytial virus nonstructural proteins decrease levels of multiple members of the cellular interferon pathways.

Viruses of the Paramyxoviridae family, such as the respiratory syncytial virus (RSV), suppress cellular innate immunity represented by type I interferon (IFN) for optimal growth in their hosts. The two unique nonstructural (NS) proteins, NS1 and NS2, of RSV suppress IFN synthesis, as well as IFN function, but their exact targets are still uncharacterized. Here, we investigate if either or both of the NS proteins affect the steady-state levels of key members of the IFN pathway. We found that both NS1 and NS2 decreased the levels of TRAF3, a strategic integrator of multiple IFN-inducing signals, although NS1 was more efficient. Only NS1 reduced IKKepsilon, a key protein kinase that specifically phosphorylates and activates IFN regulatory factor 3. Loss of the TRAF3 and IKKepsilon proteins appeared to involve a nonproteasomal mechanism. Interestingly, NS2 modestly increased IKKepsilon levels. In the IFN response pathway, NS2 decreased the levels of STAT2, the essential transcription factor for IFN-inducible antiviral genes. Preliminary mapping revealed that the C-terminal 10 residues of NS1 were essential for reducing IKKepsilon levels and the C-terminal 10 residues of NS2 were essential for increasing and reducing IKKepsilon and STAT2, respectively. In contrast, deletion of up to 20 residues of the C termini of NS1 and NS2 did not diminish their TRAF3-reducing activity. Coimmunoprecipitation studies revealed that NS1 and NS2 form a heterodimer. Clearly, the NS proteins of RSV, working individually and together, regulate key signaling molecules of both the IFN activation and response pathways.