New Approaches for Competing Microbial Resistance and Virulence

The spread of multidrug-resistant pathogens together with the development of fatal cases of infectious microorganisms is on the rise. Therefore, there must be new approaches for combating pathogenic microorganisms, either by overcoming antibiotic resistance or via inhibiting their virulence factors. Several virulence factors extremely increase the antimicrobial resistance of various species of pathogens; as a result, the screening of antivirulence agents has gained more and more attention recently. In this aspect, non-traditional strategies that are considered promising in overcoming virulence and pathogenicity of microorganisms will be discussed including; quorum sensing inhibition, antibiofilm, control of the global regulators, bacteriocins and bacteriophages. Applying these methods could provide innovative approaches for competing microbial resistance and virulence

Anti-quorum sensing activity of some medicinal plants

Background: Quorum sensing is the key regulator of virulence factors of Pseudomonas aeruginosa such as biofilm formation, motility, productions of proteases, hemolysin, pyocyanin, and toxins. The aim of this study was to explore the effect of the extracts from some medicinal plants on quorum sensing and related virulence factors of P. aeruginosa.Material and Methods: Quorum sensing inhibitory (OSI) effect of the alcohol extracts of 20 medicinal plants was evaluated by Chromobacterium violaceum reporter using agar cup diffusion method. The efficient QSI extracts were tested for their activity against biofilm synthesis, motility, and synthesis of pyocyanin from P. aeruginosa PA14Results: The extracts of Citrus sinensis, Laurus nobilis, Elettaria cardamomum, Allium cepa, and Coriandrum sativum exhibited potent quorum quenching effect. On the other hand, Psidium guajava and Mentha longifolia extracts showed lower QSI activity. These extracts exhibited significant elimination of pyocyanin formation and biofilm development of Pseudomonas aeruginosa PA14. In addition, they significantly inhibited twitching and swimming motilities of P. aeruginosa PA14.Conclusion: This study illustrated, for the first time, the importance of C. sinensis, L. nobilis, E. cardamomum, A. cepa, and C. sativum as quorum sensing inhibitors and virulence suppressors of P. aeruginosa. Thus, these plants could provide a natural source for the elimination of Pseudomonas pathogenesis.Keywords: Quorum sensing inhibitory activity, P. aeruginosa, Chromobacterium violaceum, virulence factor

Quorum sensing inhibitory activity of sub-inhibitory concentrations of β-lactams

Introduction: The virulence factors of Pseudomonas aeruginosa are under the control of quorum sensing (QS) signals. Hence, interference with QS prevents its pathogenesis.Objective: The aim of the present research is to assess the influence of some β-lactam antibiotics on cell communication and the release of different virulence factors.Methods: The minimal inhibitory concentrations of ceftazidime, cefepime and imipenem were evaluated by microbroth dilution method. The effect of sub-inhibitory concentration of the tested antibiotics on QS signals was investigated using reporter strain assay. In addition, different virulence factors (elastase, protease, pyocyanin and hemolysin) were estimated in the presence of their sub-inhibitory concentrations.Results: Low concentrations of ceftazidime, cefepime and imipenem caused significant elimination of the QS signals 3OHC12- HSL and C4-HSL up to 1/20 MIC. Furthermore, low concentrations of the tested antimicrobials suppressed virulence factors elastase and hemolysin. Moreover, 1/20 of their MICs reduced elastase, protease, pyocyanin and hemolysin.Conclusion: Utilization of β-lactam antibiotics at low concentrations could be an effective approach for prevention and treatment of P. aeruginosa infection.Keywords: Quorum sensing inhibition, β-lactams, Pseudomonas aeruginos

Assessment of Ceruloplasmin, Hemopexin, and Haptoglobin in Asthmatic Children

BACKGROUND: Ceruloplasmin (Cp), haptoglobin, and hemopexin play a role in iron homeostasis and may function to modulate the systemic inflammatory response and be involved in tissue repair. We hypothesized that these proteins could be biological markers for bronchial asthma that reflect the involvement of iron oxidative stress in asthma pathogenesis. AIM: Evaluation of serum levels of proteins involved in iron homeostasis (Cp, hemopexin, and haptoglobin) in asthmatic children and their correlation to pulmonary functions. MATERIALS AND METHODS: Sixty moderate to severe persistent asthmatic children aged 6–13 years were included (30 during attacks and 30 in-between attacks). Thirty healthy matched controls were also recruited. All children were subjected to history taking, clinical evaluation and assessment of complete blood picture, serum levels of Cp, haptoglobin, hemopexin, and total IgE. Pulmonary function tests were assessed for all patients. RESULTS: Serum Cp and haptoglobin were significantly elevated in asthmatic children between attacks (448.04 ± 386.79), (993.33 ± 554.56) compared to controls (168.42 ± 13.46), (473.33 ± 350.3), (p = 0.0002, p < 0.0001) and to asthmatics during exacerbations (288.8 ± 219.6), (620 ± 467.86), (p = 0.014, p = 0.006). Serum hemopexin was significantly higher in asthmatics between attacks (509.33 ± 341.51) compared to controls (296.67 ± 158.38) (p < 0.003) but no significant difference compared to acute exacerbations (477.33 ± 396.6). No significant correlations were found between any of the assessed protein levels and pulmonary functions. Hemoglobin concentration was significantly higher among stable asthmatics compared to acute exacerbation and control groups. CONCLUSION: Cp, haptoglobin, and hemopexin can be used as a panel of non-invasive biomarkers that reflect the involvement of iron oxidative stress in asthma pathogenesis

Quorum sensing inhibitory activity of sub-inhibitory concentrations of \u3b2-lactams

Introduction: The virulence factors of Pseudomonas aeruginosa are under the control of quorum sensing (QS) signals. Hence, interference with QS prevents its pathogenesis. Objective: The aim of the present research is to assess the influence of some \u3b2-lactam antibiotics on cell communication and the release of different virulence factors. Methods: The minimal inhibitory concentrations of ceftazidime, cefepime and imipenem were evaluated by microbroth dilution method. The effect of sub-inhibitory concentration of the tested antibiotics on QS signals was investigated using reporter strain assay. In addition, different virulence factors (elastase, protease, pyocyanin and hemolysin) were estimated in the presence of their sub-inhibitory concentrations. Results: Low concentrations of ceftazidime, cefepime and imipenem caused significant elimination of the QS signals 3OHC12-HSL and C4-HSL up to 1/20 MIC. Furthermore, low concentrations of the tested antimicrobials suppressed virulence factors elastase and hemolysin. Moreover, 1/20 of their MICs reduced elastase, protease, pyocyanin and hemolysin. Conclusion: Utilization of \u3b2-lactam antibiotics at low concentrations could be an effective approach for prevention and treatment of P. aeruginosa infection

The correlation between Aflatoxin B1 and Placental Apoptosis in Pregnant women with Intrauterine Growth Restriction

Objective:To explore the effect of Aflatoxin B1 toxicity as a risk factor of intrauterine growth restriction (IUGR) and to determine the role of placental apoptotic indices in the pathogenesis of IUGR and their association with maternal risk factors including residency, working and exposure to smoking. Materials and Methods:A case-control study was done at Women Health Hospital; Assiut University, Egypt. Sixty pregnant women with asymmetrical IUGR and a control group of 40 normal pregnancies were selected. Maternal urine samples were obtained for Aflatoxin B1 level measurement by layer chromatography. Quantitative determination of human placental Bcl-2 and caspase-3 using a monoclonal antibody-based enzyme-linked immunosorbent assay kits were performed. Results:The results showed that aflatoxin B1 positive cases in the IUGR group had significantly higher placental caspase-3 and lower placental Bcl-2 concentrations than those which were aflatoxin B1 negative (p<0.01). The levels of placental apoptotic indices were higher in working women who lived in urban areas and those exposed to cigarette smoke than non-working women who lived in rural areas and non-smokers. Conclusions: Aflatoxin B1 may affect the fetal growth by increasing the placental apoptosis. These results may highlight the importance of aflatoxin B1 which may contribute to the complex etiology of IUGR. Placental apoptotic indices levels were significantly affected by maternal residence, working and exposure to smoking in pregnancies complicated with IUGR

Potential Risk Factors of Developmental Cognitive Delay in the First Two Years of Life

BACKGROUND: The first two years of life constitute a critical period of rapid change. The events during this phase prepare the child for subsequent developmental competency.AIM: To determine the potential risk factors that affect an infant’s cognitive development in the first two years of life in a sample of Egyptian infantsSUBJECTS AND METHODS: A cross-sectional comparative study included 655 male and female infants. Their age ranged from 3 – 24 months. Bayley Scales of Infant and Toddler Development (Bayley III) were used for cognitive assessment. Perinatal and nutritional data were recorded. Levels of serum Zinc, Copper, Iron, vitamin B12 and complete blood count (CBC) were assessed in a subsample of 193 infants.RESULTS: Infants having below the average cognitive composite score (CCS) represented 38.47% of the whole sample. The risk of having a low average (CCS) was determined by multiple factors. Poor maternal education and low family income were the most significant social risk factors (OR = 2.19, p = 0.0003; OR = 1.64, p = 0.002 respectively). Prematurity and complicated labor represented significant perinatal risks (OR = 1.22, p = 0.005; OR = 2.39, p =0.001respectively). Bottle feeding versus breastfeeding in the first six months of life was the most significant nutritional predictor of low average (CCS) (OR = 1.79, p = 0.001). Infants with low average (CCS) had significantly lower levels of serum zinc and vitamin B12 than those with average scores. CONCLUSION: Multiple factors appear to interact affecting the early cognitive development of Egyptian infants. Prematurity, complicated labour, poor maternal education, low family income and micronutrient deficiency are the main risk factors. Studying these factors is of great value in directing governmental intervention efforts

The Interaction of Social, Physical and Nutritive Factors in Triggering Early Developmental Language Delay in a Sample of Egyptian Children

BACKGROUND: Language acquisition and child development during the early years of life depend on multiple interacting factors. AIM: To explore potential factors that can impact language development in 2 groups of Egyptian children, one with normal language development and the second with delayed development. Also, to explore to what extent can the involvement of impaired motor development potentiate the risk of developmental language delay. METHODS: This cross-sectional case-control study involved Egyptian children belonging to the middle socioeconomic class between 18 and 36 months of age. Children were classified according to their performance on language domain of Bayley Scales of Infant and Toddler Development (Bayley-III) into two groups, infants with the average or above score (control group) and those having below-average scores (cases). Motor development was assessed on the same scale. Factors affecting language development were tested, including socio-demographic, obstetric, and maternal medical factors in addition to Infant Feeding Practices. RESULTS: The independent factors lowering the language scores were early introduction of complementary food, low family income, history of delivery problems, pregnancy-related diseases of the mother, and maternal education. Impaired motor development appears as a further highly significant risk factor to the previously mentioned factors CONCLUSION: In Egyptian children, delayed language development is severely affected by the interaction of medical, social and nutritional factors. Providing adequate maternal health care during pregnancy and childbirth, regular developmental monitoring at each child visit, and screening for such risk factors, can reduce size of the problem and promote child’s social and psychological development

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely