Types and Mechanisms of Efflux Pump Systems and the Potential of Efflux Pump Inhibitors in the Restoration of Antimicrobial Susceptibility, with a Special Reference to Acinetobacter baumannii.

Bacteria express a plethora of efflux pumps that can transport structurally varied molecules, including antimicrobial agents and antibiotics, out of cells. Thus, efflux pump systems participate in lowering intracellular concentrations of antibiotics, which allows phenotypic multidrug-resistant (MDR) bacteria to survive effectively amid higher concentrations of antibiotics. Acinetobacter baumannii is one of the classic examples of pathogens that can carry multiple efflux pump systems, which allows these bacteria to be MDR-to-pan-drug resistant and is now considered a public health threat. Therefore, efflux pumps in A. baumannii have gained major attention worldwide, and there has been increased interest in studying their mechanism of action, substrates, and potential efflux pump inhibitors (EPIs). Efflux pump inhibitors are molecules that can inhibit efflux pumps, rendering pathogens susceptible to antimicrobial agents, and are thus considered potential therapeutic agents for use in conjunction with antibiotics. This review focuses on the types of various efflux pumps detected in A. baumannii, their molecular mechanisms of action, the substrates they transport, and the challenges in developing EPIs that can be clinically useful in reference to A. baumannii.

Cell Phone Social Media Use and Psychological Well-Being in Young Adults: Implications for Internet-Related Disorders.

Internet-related disorders are on the rise and increasing cell phone social media use may be one of the reasons for these disorders. To better understand internet-related disorders, we aim to explore the psychological and social aspects of cell phone social media behaviors. We hypothesized that, according to humanistic theories of positive functioning, cell phone social media connectedness to self (engagement, interest, pleasure, sense of enjoyment, meaningfulness, purposefulness, optimism, acceptance, and feeling accomplished) would relate positively to psychological well-being of undergraduate students. We also hypothesized that, according to Maslow's hierarchy of needs, cell phone social media connectedness to others (affiliation, feeling rewarded, being liked by others, and contributions to the well-being of others) would relate positively to the psychological well-being of undergraduate students. During the fall of 2019, 523 (75.4% female) undergraduate students from a large public university participated in this study by completing validated quantitative surveys on their cell phone use and psychological well-being. Spearman's rho and ordinal logistics were implemented to analyze the findings. Correlational data showed that cell phone social media connectedness to self and cell phone social media connectedness to others were positively associated with the psychological well-being of undergraduate students. Ordinal logistics showed higher odds of psychological well-being occurring with cell phone social media connectedness to self and cell phone social media connectedness to others. Cell phone social media connectedness to self significantly predicted psychological well-being with the medium effect, whereas cell phone social media connectedness to others was not a significant predictor of the psychological well-being of undergraduate students. An increase in cell phone social media connectedness to self and an increase in cell phone social media connectedness to others of undergraduate students helped them improve their psychological well-being. Cell phone social media connectedness to self significantly predicted but cell phone social media connectedness to others did not predict the psychological well-being of undergraduate students, which may have implications for the research pertaining to behavioral addiction and may help better understand internet-related disorders.

Cell phone use distracts young adults from academic work with limited benefit to self-regulatory behavior.

We aim to uncover theoretical mechanisms associated with potential negative (i.e., multitasking) and positive (i.e., self-regulation) aspects of cell phone use (CPU) for academic performance in young adults. We hypothesized that, according to the Switch-Load Theory, repeated CPU during academic activities (CPU_Multitasking) would relate negatively, whereas, according to Zimmerman's Theory of Self-Regulated Learning, CPU for self-regulated learning behaviors (CPU_SRLBehavior) would relate positively to the academic performance of undergraduate students. 525 (75.4% female) undergraduate students from a large public university participated in this study during fall 2019 by completing validated quantitative surveys accessing their CPU and academic performance. Spearman's rho was used to compute the correlations and hierarchical regression was used to analyze the variance. Spearman rank-order coefficient showed that CPU_Multitasking relates negatively, but CPU_SRLBehavior is unrelated to the college GPA of undergraduate students. Hierarchical regression showed that CPU_Multitasking was not a significant predictor of academic performance. Young adults who switch to their cell phones during class or study-related activities are more likely to have lower performance in exams as CPU_Multitasking costs time and efficiency (Switch Load Theory). Young adults who use their cell phones for self-regulated learning behavior are less likely to have an impact on their academic performance as CPU_SRLBehavior helps regulate habits but not learning processes. With the known theoretical mechanisms for CPU multitasking and SRL Behavior, this study provides a guiding document for educational computing system practitioners to explore more theory-driven empirical approaches in the field of CPU and academic success.

Sleep latency and sleep disturbances mediates the association between nighttime cell phone use and psychological well-being in college students.

To examine sleep latency and sleep disturbance as mediators between nighttime cell phone use variables (cell phone use for unstructured leisure activities and for accessing emotionally charged media content before sleep: CPU_BeforeBed and CPU_Arousal) and psychological well-being (PWB) of college students. 521 (74% female) undergraduate students from a large public university were surveyed using a validated self-report quantitative questionnaire assessing CPU variables, sleep quality, and PWB. Pearson correlation analyses were used to compute the correlation between CPU_BeforeBed, CPU_Arousal, sleep latency, and sleep disturbance. Ordinary least-squares regressions were conducted to assess the estimates of the relationships within the models. One-way ANOVA was used to see the difference between the groups. The partial eta squared was used to determine the effect size between the groups. The PROCESS method was used to perform mediation analyses. The sample consisted of undergraduate students between 18 and 29 years old, with an average age of 20 years (SD = 3.18). The sample was diverse in terms of ethnicity (49% Caucasian, 24% Latinx, 19% Asian, 3% African American, 1% Native American, 3% identified as "other") and the number of years the participants had been attending a 2 year or 4 year higher institution (38% incoming freshman, 19% sophomore, 17% junior, 14% senior, and 13% returning senior). The correlation between CPU_BeforeBed and PWB (α = - 0.044, p = 0.615), and the correlation between CPU_Arousal and PWB (α = - 0.061, p = 0.228) were not statistically significant. However, the correlation between sleep latency and PWB (α = - 0.140, p = 0.001), and the correlation between sleep disturbance and PWB (α = - 0.121, p = 0.005) were statistically significant. The mediation effect of sleep latency on the association between CPU_BeforeBed and PWB (Effect = - 0.0325, SE = 0.0145, p < 0.05), and the mediation effect of sleep disturbance on the association between CPU_Arousal and PWB (Effect = - 0.0214, SE = 0.0086, p < 0.05) were statistically significant. Sleep latency and sleep disturbance act as a mediator on the association between CPU_BeforeBed and PWB, and the association between CPU_Arousal and PWB. However, CPU_BeforeBed and CPU_Arousal did not have a direct impact on their PWB. These findings may help college students in regulating CPU habits before going to bed. These findings may also help medical practitioners make informed decisions about the use of cell phones for patients with sleep-related disorders. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00388-3.

Nighttime cell phone use and sleep quality in young adults.

Young adults are particularly vulnerable to sleep disturbances related to their cell phone use (CPU). The purpose of this study was to test Sleep Displacement and Psychological Arousal theories of CPU-led sleep disruption in relation in a sample of university students. CPU for unstructured leisure activities before sleep (CPU_BeforeBed), as well as CPU for accessing explicit or emotionally charged media content before sleep (CPU_Arousal), were both measured. 525 (75% female) undergraduate students from a large public institution participated in this study during fall 2019. The data were collected using a battery of validated self-report questionnaires. Questionnaires included the Pittsburgh Sleep Quality Index scale, which was used to measure sleep latency and sleep difficulty, and a contemporary questionnaire developed to measure CPU_BeforeBed and CPU_Arousal. A crude odds ratio analysis was implemented to analyze findings. Sleep Displacement data showed higher odds of sleep latency occurring with CPU_BeforeBed [Exp (B) = 1.091, p < 0.001]. Psychological Arousal data showed higher odds of sleep difficulty occurring with CPU_Arousal [Exp (B) = 1.065, p < 0.001]. CPU_BeforeBed significantly predicted sleep latency [Exp (B) = 1.062, p < 0.01], and CPU_Arousal significantly predicted the sleep difficulty [Exp (B) = 1.069, p < 0.001] of undergraduate students. Young adults who used cell phones before sleep and access emotionally charged content before going to bed were more likely to report trouble sleeping. They took more time to fall asleep at night as their sleep hours were compressed due to CPU. These findings support the Sleep Displacement and Arousal theories of sleep disruption and provide further insight into possible mechanisms for sleep disturbance in young adults.

An Association of Pathogens and Biofilms with Alzheimer's Disease.

As one of the leading causes of dementia, Alzheimer's disease (AD) is a condition in which individuals experience progressive cognitive decline. Although it is known that beta-amyloid (Aß) deposits and neurofibrillary tangles (NFT) of tau fibrils are hallmark characteristics of AD, the exact causes of these pathologies are still mostly unknown. Evidence that infectious diseases may cause AD pathology has been accumulating for decades. The association between microbial pathogens and AD is widely studied, and there are noticeable correlations between some bacterial species and AD pathologies, especially spirochetes and some of the oral microbes. Borrelia burgdorferi has been seen to correlate with Aß plaques and NFTs in infected cells. Because of the evidence of spirochetes in AD patients, Treponema pallidum and other oral treponemes are speculated to be a potential cause of AD. T. pallidum has been seen to form aggregates in the brain when the disease disseminates to the brain that closely resemble the Aß plaques of AD patients. This review examines the evidence as to whether pathogens could be the cause of AD and its pathology. It offers novel speculations that treponemes may be able to induce or correlate with Alzheimer's disease.

Acute hemodynamics of cardiac sympathetic denervation.

INTRODUCTION: We aimed to study the immediate hemodynamic effects of thoracoscopic bilateral cardiac sympathetic denervation (CSD) for recurrent ventricular tachycardia (VT) or VT storm. METHOD: We studied a group of 18 adults who underwent bilateral thoracoscopic CSD; the blood pressure (BP) and Heart Rate (HR) were continuously monitored during the surgery and up to 6 h post-operatively. RESULTS: Immediately on removal of the sympathetic ganglia, the patients had a drop in both the systolic (110 mm Hg to 95.8 mm Hg, p < 0.001) and diastolic BP (69.4 mm Hg to65 mm Hg, p = 0.007) along with a drop in the HR (81.6 bpm to 61.2 bpm, p < 0.001).At 6 h after CSD, the systolic and diastolic BP did not recover significantly, while there was recovery in HR (61.2 bpm to 66 bpm, p = 0.02). There was no significant difference between those with and without left ventricular (LV) systolic dysfunction. CONCLUSION: The acute hemodynamic changes during the perioperative period of CSD are significant but not serious. Awareness of this is useful for peri-operative management.

Rapid, label-free genetic detection of enteropathogens in stool without genetic isolation or amplification.

Current genetic detection methods require gene isolation, gene amplification and detection with a fluorescent-tagged probe. They typically require sophisticated equipment and expensive fluorescent probes, rendering them not widely available for rapid acute infection diagnoses at the point of care to ensure timely treatment of the diseases. Here we report a rapid genetic detection method that can detect the bacterial gene directly from patient stools using a piezoelectric plate sensor (PEPS) in conjunction with a continuous flow system with two temperature zones. With stools spiked with sodium dodecyl sulfate (SDS) in situ bacteria lysing and DNA denaturation occurred in the high-temperature zone whereas in situ specific detection of the denatured DNA by the PEPS occurred in the lower-temperature zone. The outcome was a rapid genetic detection method that directly detected bacterial genes from stool in < 40 min without the need of gene isolation, gene amplification, or expensive fluorescent tag but with polymerase chain reaction (PCR) sensitivity. In 40 blinded patient stools, it detected the toxin B gene of Clostridium difficile with 95% sensitivity and 95% specificity. The all-electrical, label-free nature of the detection further supports its potential as a low-cost genetic test that can be used at the point of care.

Tobacco smoking between immigrants and non-immigrants in Australia: A longitudinal investigation of the effect of nativity, duration of residence and age at arrival.

ISSUE ADDRESSED: Earlier research evidence suggests that there is a difference and over time change in the prevalence of tobacco smoking between immigrants and native-born population. This study investigates the differences in smoking among immigrants from English speaking (ESC) and non-English speaking (NESC) countries relative to native-born (NB) Australians, and how those differences change with duration of residence (DoR) and age at arrival (AA). METHODS: Information on 12 634 individuals from the first twelve waves (2001-2012) of Household, Income and Labour Dynamics in Australia (HILDA) longitudinal survey was analysed using multilevel group-mean-centred mixed logistic regression models. Smoking status as an outcome was dichotomized as current vs non-current smokers. RESULTS: After adjusting for covariates, relative to native-born respondents, there was no difference in the odds of smoking for English speaking countries immigrants, while immigrants from non-English speaking countries had lower odds of smoking. The smoking prevalence of immigrants from non-English speaking countries converged towards the native-born after 20 years of residence in Australia. The association between duration of residence and smoking was modified by age at arrival, with immigrants (combined ESC and NESC) who arrived as children or adolescents and had lived 20 years or longer were significantly more likely to smoke than native-born Australians. CONCLUSION: The results suggest that the initially lower smoking prevalence among non-English speaking countries immigrants converges with that of native-born Australians after twenty years of residence, and immigrants (combined ESC and NESC) who arrived as children or adolescents more than 20 years ago were more likely to be smokers. SO WHAT?: Current health promotion and anti-smoking programs should ensure that immigrants from non-English speaking background have access to education and information about the hazards of tobacco consumptions and are aware of the available smoking cessation services. Efforts to prevent smoking uptake among NESC immigrants and those who arrive as children or adolescents and live longer than 20 years is especially important for tobacco control interventions.

Cardiac magnetic resonance imaging, myocardial scar and coronary flow pattern in anomalous origin of left coronary artery from the pulmonary artery.

BACKGROUND: Anomalous origin of left coronary artery from pulmonary artery (ALCAPA) is a very rare congenital heart defect characterized by myocardial ischemia and ultimately scaring. The scar burden will determine eventual recovery of left ventricular function after corrective surgery. MATERIAL METHOD: All patients with proven diagnosis of ALCAPA and who underwent treatment at present centre were included. Detail echocardiography and cardiac magnetic resonance imaging (CMR) (delayed Gadolinium enhancement) was performed before and after surgery. RESULTS: There were 4 patients (3 females, age group 3 months to 3 yr, follow up 6 months to 20 months.) There was no peri operative mortality. All patients had significant improvement in symptom class and LVEF (increase of more than 10%) when evaluated at last follow up. Three patients had pre operative CMR and 3 post operative CMR. All patients had improvement in post operative LVEF, but >50% was observed only in one patient who had less than half thickness delayed gadolinium enhancement. The right coronary flow pattern were unique to disease. The left coronary flow pattern were had significant variation and could predict extent of scared myocardium. CONCLUSION: Ischemia in ALCAPA can lead to myocardial scarring even in early infancy. The recovery in left ventricular function is a closely related to scar burden. Coronary flow patterns are unique and give useful insight into disease process and natural history.

Molecular characterization of ß-lactamase genes in clinical isolates of carbapenem-resistant Acinetobacter baumannii.

BACKGROUND: Acinetobacter baumannii is a nosocomial pathogen which is establishing as a major cause of morbidity and mortality within the healthcare community. The success of this pathogen is largely due to its ability to rapidly gain resistance to antimicrobial therapies and its capability to persist in an abiotic environment through the production of a biofilm. Our tertiary-care hospital has showed high incidence of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. METHODS: In this study we explore both genotypic and phenotypic properties of 26 CRAB isolates: 16 isolates were collected from January 2010 to March 2011, and 10 were collected between February and May 2015. RESULTS: We determined that all 26 CRAB isolates possessed multiple ß-lactamase genes, including genes from Groups A, C, and D. Specifically, 42% of the isolates possesses the potentially plasmid-borne genes of OXA-23-like or OXA-40-like ß-lactamase. The presence of mobile gene element integron cassettes and/or integrases in 88% of the isolates suggests a possible mechanism of dissemination of antibiotic resistance genes. Additionally, the location of insertion sequence (IS) ISAba1 in promotor region of of the OXA-51-like, ADC-7, and ampC genes was confirmed. Multilocus sequence typing (MLST) demonstrated that all 26 CRAB isolates were either sequence type (ST)-229 or ST-2. Interestingly, ST-2 went from being the minority CRAB strain in the 2010-2011 isolates to the predominant strain in the 2015 isolates (from 32 to 90%). We show that the ST-2 strains have an enhanced ability to produce biofilms in comparison to the ST-229 strains, and this fact has potentially led to more successful colonization of the clinical environment over time. CONCLUSIONS: This study provides a longitudinal genetic and phenotypic survey of two CRAB sequence types, and suggests how their differing phenotypes may interact with the selective pressures of a hospital setting effecting strain dominance over a 5-year period.

Involvement of multiple stressors induced by non-thermal plasma-charged aerosols during inactivation of airborne bacteria.

A lab-scale, tunable, single-filament, point-to-point nonthermal dieletric-barrier discharge (DBD) plasma device was built to study the mechanisms of inactivation of aerosolized bacterial pathogens. The system inactivates airborne antibiotic-resistant pathogens efficiently. Nebulization mediated pre-optimized (4 log and 7 log) bacterial loads were challenged to plasma-charged aerosols, and lethal and sublethal doses determined using colony assay, and cell viability assay; and the loss of membrane potential and cellular respiration were determined using cell membrane potential assay and XTT assay. Using the strategies of Escherichia coli wildtype, over-expression mutant, deletion mutants, and peroxide and heat stress scavenging, we analyzed activation of intracellular reactive oxygen species (ROS) and heat shock protein (hsp) chaperons. Superoxide dismutase deletion mutants (ΔsodA, ΔsodB, ΔsodAΔsodB) and catalase mutants ΔkatG and ΔkatEΔkatG did not show significant difference from wildtype strain, and ΔkatE and ΔahpC was found significantly more susceptible to cell death than wildtype. The oxyR regulon was found to mediate plasma-charged aerosol-induced oxidative stress in bacteria. Hsp deficient E. coli (ΔhtpG, ΔgroEL, ΔclpX, ΔgrpE) showed complete inactivation of cells at ambient temperature, and the treatment at cold temperature (4°C) significantly protected hsp deletion mutants and wildtype cells, and indicate a direct involvement of hsp in plasma-charged aerosol mediated E. coli cell death.

Bypassing the Pump.

We present a six-year follow-up of an infant who underwent a left subclavian artery to left anterior descending artery anastomosis for anomalous origin of the left coronary artery from the pulmonary artery, without the use of cardiopulmonary bypass. The clinical status, echocardiography, angiography, and exercise tolerance with treadmill test were found to be normal. This technique could be a viable alternative to the more established coronary translocation, with lesser morbidity, shorter hospital stay, and lower economic burden, especially in the developing world.

Unmasking the culprit: MAPCA masquerading as RV failure in post surgical correction of TOF.

Pulmonary regurgitation and right ventricular dilatation are major determinants of long-term follow up of surgically corrected tetralogy of Fallot. Occasionally, there are undiagnosed associated anomalies, which can exaggerate pulmonary regurgitation. The present report describes long-term effect of major aorto pulmonary collateral on right ventricular volume also a result of successful intervention. .

Are Immigrants More Physically Active Than Native-Born Australians and Does it Changes Over Time? Evidence From a Nationally Representative Longitudinal Survey.

BACKGROUND: We investigated the differences and over time changes in recommended physical activity among foreign-born (FB) from English speaking countries (ESC) and non-English speaking countries (NESC) relative to native-born (NB) Australians, and whether the association between nativity and duration of residence (DoR) and physical activity is mediated by English language proficiency, socioeconomic status and social engagement/membership. METHODS: This study applies multilevel group-meancentered mixed (hybrid) logistic regression models to 12 waves of longitudinal data (12,634 individuals) from the Household, Income and Labor Dynamics in Australia survey with engagement in physical activities for more than 3 times a week as the outcome variable. RESULTS: Immigrants from ESC had higher odds of physical activity, while immigrants from NESC had significantly lower odds of physical activity than NB Australians, after adjusting for covariates. There was no evidence that these differences changed by DoR among immigrants from NESC, whereas ESC immigrants had higher odds of physical activity when their DoR was more than 20 years. We also found a mediating role of English language proficiency on immigrants physical activities. CONCLUSION: Appropriate health promotion interventions should be implemented to foster physical activities among NESC immigrants, considering English language proficiency as an important factor in designing interventions.

Very early onset traumatic hemolysis following mitral valve repair in a pediatric patient.

Hemolytic anemia following a mitral valve repair is a very rare complication, with only 70 cases reported worldwide. We present a case of an 8-year-old girl who presented with a very early onset hemolytic anemia following a mitral valve repair with ring annuloplasty, which necessitated a reoperation. The report also discusses the various mechanisms of traumatic hemolysis associated with valve repair and probable lessons learnt and ways to avoid this complication.

An experience with off pump technique for repair of anomalous left coronary artery from pulmonary artery (ALCAPA).

BACKGROUND: Anomalous origin of left coronary artery from pulmonary artery is a very rare disease with incidence of one every 300,000 live births. It has a high mortality of 80% in the first year of life. This observational study summarized our experience using the technique of subclavian arterial bypass without the use of cardiopulmonary bypass (CPB) for treatment of this coronary anomaly in pediatric population. The study aims to revive an earlier technique, with modifications, as an alternative to the existing coronary translocation. METHODS: From 2009 till 2015, six consecutive infants were operated by a single surgeon using subclavian artery to left coronary artery bypass done off pump, to establish a two coronary circulation. RESULTS: Five patients had an improvement in their LV ejection fractions at the time of the last follow-up. Angiography done in two cases after 2 and 6 years after surgery revealed good flow in the left coronary artery and good growth in the length of subclavian artery. There was one surgical mortality in this series. CONCLUSIONS: The technique of off pump subclavian arterial bypass for anomalous origin of the left coronary artery from the pulmonary artery is a viable alternative to the existing standard technique of coronary translocation. It essentially eliminates extracorporeal circulatory support or a left heart bypass that may be needed after coronary translocation. Also, the advantage of avoiding CPB, both in economic terms and also the adverse effects related to use of bypass in this very sick hearts, cannot be disregarded.

Color Doppler and pulse wave assessment of flow in anomalous origin of left coronary artery from pulmonary artery: Pre- and post-surgery.

Changes in left coronary artery flow pattern in anomalous left coronary from pulmonary artery can provide valuable insight into pathology and natural history of disease. We wish to discuss a case with pre and post operative left coronary flow pattern with mid term follow up.

Chemical Changes in Nonthermal Plasma-Treated N-Acetylcysteine (NAC) Solution and Their Contribution to Bacterial Inactivation.

In continuation of our previous reports on the broad-spectrum antimicrobial activity of atmospheric non-thermal dielectric barrier discharge (DBD) plasma treated N-Acetylcysteine (NAC) solution against planktonic and biofilm forms of different multidrug resistant microorganisms, we present here the chemical changes that mediate inactivation of Escherichia coli. In this study, the mechanism and products of the chemical reactions in plasma-treated NAC solution are shown. UV-visible spectrometry, FT-IR, NMR, and colorimetric assays were utilized for chemical characterization of plasma treated NAC solution. The characterization results were correlated with the antimicrobial assays using determined chemical species in solution in order to confirm the major species that are responsible for antimicrobial inactivation. Our results have revealed that plasma treatment of NAC solution creates predominantly reactive nitrogen species versus reactive oxygen species, and the generated peroxynitrite is responsible for significant bacterial inactivation.