Ebola Virus-Specific Neutralizing Antibody Persists at High Levels in Survivors 2 Years After Resolution of Disease in a Sierra Leonean Cohort.

Ebola virus (EBOV) infection results in Ebola virus disease (EVD), an often severe disease with a nonspecific presentation. Since its recognition, periodic outbreaks of EVD continue to occur in sub-Saharan Africa. The 2013-2016 West African EVD outbreak was the largest recorded, resulting in a substantial cohort of EVD survivors with persistent health complaints and variable immune responses. In this study, we characterize humoral immune responses in EVD survivors and their contacts in Eastern Sierra Leone. We found high levels of EBOV IgG in EVD survivors and lower yet substantial antibody levels in household contacts, suggesting subclinical transmission. Neutralizing antibody function was prevalent but variable in EVD survivors, raising questions about the durability of immune responses from natural infection with EBOV. Additionally, we found that certain discrete symptoms-ophthalmologic and auditory-are associated with EBOV IgG seropositivity, while an array of symptoms are associated with the presence of neutralizing antibody.

Role of biomarkers in the diagnosis and management of HCC.

For many cancers, biomarkers have served as an important tool across the cancer care continuum from risk stratification and early detection to diagnosis and treatment. Alpha-fetoprotein (AFP) remains one of the few validated biomarkers for patients with HCC. Although AFP has shown potential for each of these steps, its performance, when used alone, has often been suboptimal. There continue to be discordant recommendations about AFP's value when combined with ultrasound for surveillance, as well as its role in diagnostic algorithms. Conversely, high AFP levels are associated with aggressive tumor biology and survival, so it remains a key factor for the selection of candidates for liver transplant. There have been immense efforts to identify and validate additional biomarkers for each of these steps in the HCC care continuum. Indeed, biomarker panels have shown promising data for HCC risk stratification and surveillance among patients with cirrhosis, as well as prognostication and detection of minimal residual disease in patients undergoing HCC treatment. Several large prospective studies are currently ongoing to evaluate the role of these emerging biomarkers in clinical practice.

Incidence and predictors of complications in Gram-negative bloodstream infection.

BACKGROUND: The incidence of metastatic complications in Gram-negative bloodstream infection (GN-BSI) remains undefined. This retrospective cohort study examines the incidence and predictors of complications within 90 days of GN-BSI. METHODS: Patients with GN-BSIs hospitalized at two Prisma Health-Midlands hospitals in Columbia, South Carolina, USA from 1 January 2012 through 30 June 2015 were included. Complications of GN-BSI included endocarditis, septic arthritis, osteomyelitis, spinal infections, deep-seated abscesses, and recurrent GN-BSI. Kaplan-Meier analysis and multivariate Cox proportional hazards regression were used to examine incidence and risk factors of complications, respectively. RESULTS: Among 752 patients with GN-BSI, median age was 66 years and 380 (50.5%) were women. The urinary tract was the most common source of GN-BSI (378; 50.3%) and Escherichia coli was the most common bacteria (375; 49.9%). Overall, 13.9% of patients developed complications within 90 days of GN-BSI. The median time to identification of these complications was 5.2 days from initial GN-BSI. Independent risk factors for complications were presence of indwelling prosthetic material (hazards ratio [HR] 1.73, 95% confidence intervals [CI] 1.08-2.78), injection drug use (HR 6.84, 95% CI 1.63-28.74), non-urinary source (HR 1.98, 95% CI 1.18-3.23), BSI due to S. marcescens, P. mirabilis or P. aeruginosa (HR 1.78, 95% CI 1.05-3.03), early clinical failure criteria (HR 1.19 per point, 95% CI 1.03-1.36), and persistent GN-BSI (HR 2.97, 95% CI 1.26-6.99). CONCLUSIONS: Complications of GN-BSI are relatively common and may be predicted based on initial clinical response to antimicrobial therapy, follow-up blood culture results, and other host and microbiological factors.

Surgical Tips for Robotic Assisted Laparoscopic Abdominal Cerclage: A Minimally Invasive Approach.

Preterm birth is the leading cause of perinatal and neonatal morbidity and mortality in the developed world. An important cause of preterm birth is cervical insufficiency, leading to membrane prolapse, premature rupture of membranes, and mid-trimester pregnancy loss. A cerclage can be placed vaginally or abdominally to treat cervical insufficiency. In cases of failed prior transvaginal cerclage (TVC), transabdominal cerclage (TAC) is the alternative. The procedure can be completed via laparoscopy or open approach. The suture is placed at the internal os giving greater structural support.1 In this article, we review the definition of cervical incompetence, we present the indications for TAC, we discuss the outcomes of minimally invasive TAC compared to open approach, and we review surgical tips and tricks for robotic assisted (RA) TAC placement that can be used prior to pregnancy or in early gestation. The included images delineate the surgical technique for safe placement of robotic assisted laparoscopic abdominal cerclage in the management of cervical insufficiency.

The impact of sociodemographic, health status and resources, macroeconomic, and environmental factors on infant mortality rates in Qatar, Kingdom of Saudi Arabia, and the United Arab Emirates.

OBJECTIVES: This study aims to study the impact of sociodemographic (SD), health status and resources (HSR), macroeconomic (ME), and Environmental (EV) factors on the infant mortality rate (IMR) in Qatar, Kingdom of Saudi Arabia (KSA), and the United Arab Emirates (UAE) and from 1990 to 2022. DESIGN: A retrospective time-series study employing yearly data was conducted. A generalized least squares model was utilized to construct an exploratory model of IMR determinants for each country. RESULTS: In SD, the risk of IMR may be increased with a higher crude birth rate, adolescent fertility rate, and married women percentage. In HSR, immunization coverage shows a significant effect in preventing neonatal diseases and reducing IMR. In ME, the effect of parents' employment seems contradicted among the three countries. In EV, greenhouse emissions have also had contradictory effects among the three countries, suggesting a complex relationship with IMR. Some were consistent with global findings, whereas others contradicted the prevailing narrative. CONCLUSIONS: This study highlights the need for tailored public health interventions addressing socio-demographic, healthcare, and environmental contexts to effectively reduce IMR and enhance infant health outcomes.

Evaluation of early clinical failure criteria in Enterococcus species bloodstream infection.

PURPOSE: Early clinical failure criteria (ECFC) were recently introduced to predict unfavorable outcomes in patients with Gram-negative bloodstream infections (BSI). ECFC include hypotension, tachycardia, tachypnea or mechanical ventilation, altered mental status, and leukocytosis evaluated at 72-96 h after BSI. The aim of this retrospective cohort study was to assess performance of ECFC in predicting 28-day mortality in Enterococcus species BSI. METHODS: Hospitalized adults with Enterococcus species BSI at Prisma Health hospitals from 1 January 2015 to 31 July 2018 were identified. Multivariate logistic regression was used to determine the association between ECFC and 28-day mortality. Area under the receiver operating characteristic (AUROC) curve was used to measure model discrimination. RESULTS: Among 157 patients, 28 (18%) died within 28 days of BSI. After adjustments in multivariate model, the risk of 28-day mortality increased in the presence of each additional ECFC (OR 1.6, 95% CI 1.2-2.3, p = 0.005). Infective endocarditis (OR 3.9, 95% CI 1.4-10.7, p = 0.01) was independently associated with 28-day mortality. AUROC curve of ECFC model in predicting 28-day mortality was 0.74 with ECFC of 2 identified as the best breakpoint. Mortality was 8% in patients with ECFC < 2 compared to 33% in those with ECFC ≥ 2 (p < 0.001). CONCLUSION: ECFC had good discrimination in predicting 28-day mortality in patients with Enterococcus species BSI. These criteria may have utility in future clinical investigations.

Isolation insult during COVID-19 pandemic on the psychological status of medical students.

BACKGROUND: COVID-19 is a newly discovered infectious disease that spread and caused a global health problem. Medical students, especially those in clinical stages are among groups exposed to the disease. The study aimed to show the impact of social distancing on the mental health of Iraqi medical students. METHOD: A convenient sampling technique involved 105 participants was obtained through a questionnaire. The participants were from all stages of College Of Medicine. Questions were regarding the mental health status of the students, which included sleeping hours, nightmares, eating habits, weight problems, relationship with the family, starting to have bad habits, memory loss, attention problems, irritability, and study rank affect. RESULTS: Of about 105 participants, 64 (60.9%) of them were females and 41 (39.1%) were males. The mean age of the participants was (21.26 ± 1.065) ranging from 19 to 24 years. Feeling stressful when hearing news about COVID-19″ found in 82 (78.1%) of the participants. A high statistical significant difference (p = 0.035) among feeling isolated. About 77 (73.3%) of the participants had become easily irritable and angry. About 82 (78.1%) student started for having calculation problems. The stress with sleeping hours (p = 0.019), sleeping disturbance (p = 0.022), eating habit (p = 0.015), weight problems (p = 0.002), fear of familiar places (p = 0.004), recent memory loss (p = 0.034) and being easily irritable or angry (p = 0.0001), revealed a statistical significant association, respectively. CONCLUSION: COVID-19 news and social distancing had made medical students more stressed and irritable, affecting their sleeping hours and pattern with a general tendency for weight gain and recent memory loss in stressful students.

Post-Ebola Syndrome Presents With Multiple Overlapping Symptom Clusters: Evidence From an Ongoing Cohort Study in Eastern Sierra Leone.

BACKGROUND: Following the 2013-2016 West African Ebola outbreak, distinct, persistent health complaints were recognized in Ebola virus disease (EVD) survivors. Here we provide an in-depth characterization of post-Ebola syndrome >2.5 years after resolution of disease. Additionally, we report subphenotypes of post-Ebola syndrome with overlapping symptom clusters in survivors from Eastern Sierra Leone. METHODS: Participants in Eastern Sierra Leone were identified by the Sierra Leone Association of Ebola survivors. Survivors and their contacts were administered a questionnaire assessing self-reported symptoms and a physical examination. Comparisons between survivors and contacts were conducted using conditional logistic regression. Symptom groupings were identified using hierarchical clustering approaches. Simplified presentation of incredibly complex evaluations (SPICE), correlation analysis, logistic regression, and principal component analysis (PCA) were performed to explore the relationships between symptom clusters. RESULTS: Three hundred seventy-five EVD survivors and 1040 contacts were enrolled into the study. At enrollment, EVD survivors reported significantly more symptoms than their contacts in all categories (P < .001). Symptom clusters representing distinct organ systems were identified. Correlation and logistic regression analysis identified relationships between symptom clusters, including stronger relationships between clusters including musculoskeletal symptoms (r = 0.63, P < .001; and P < .001 for correlation and logistic regression, respectively). SPICE and PCA further highlighted subphenotypes with or without musculoskeletal symptoms. CONCLUSIONS: This study presents an in-depth characterization of post-Ebola syndrome in Sierra Leonean survivors >2.5 years after disease. The interrelationship between symptom clusters indicates that post-Ebola syndrome is a heterogeneous disease. The distinct musculoskeletal and non-musculoskeletal phenotypes identified likely require targeted therapies to optimize long-term treatment for EVD survivors.

Snapshot of narcotic drugs and psychoactive substances in Kuwait: analysis of illicit drugs use in Kuwait from 2015 to 2018.

BACKGROUND: The misuse of illicit substances is associated with increased morbidity and mortality; thus, substance abuse is a global health concern. The Arabian Gulf region is considered a crossing point and a consumer of illicit drugs. However, a lack of laboratory-based research has limited the scientific assessment of drug misuse in the Arabian Gulf region. Thus, an up-to-date analytical representation of the drug situation is warranted. METHODS: We investigated the type and quantity of detained narcotic drugs and psychotropic substances from 2015 to 2018, representing a population of approximately 4 million people, in addition to the number of abusers and mortality among abusers. In total, 6220 cases from the Narcotic and Psychotropic Laboratory and 17,755 cases from the Forensic Toxicology Laboratory were reviewed and analyzed. Substances were identified and documented using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. RESULTS: Cannabis, including marijuana, was the most seized substance, followed by heroin, opium, and cocaine. Amphetamines, including methamphetamine, in the form of powder or pills, were seized in larger quantities than other psychoactive substances. The most consumed substances were, in order, amphetamines (including methamphetamine), benzodiazepines, cannabis, and heroin. We identify the common drugs in postmortem specimens, according to sex, from suspected drug-related deaths. The most common single drug identified were heroin, benzodiazepines, and methamphetamine. Similarly, the multiple-drug cocktail of heroin-benzodiazepines, cannabis-benzodiazepines, and cannabis-amphetamines, were detected frequently. CONCLUSIONS: The data shows that cannabis is the leading type of illicit substance seized. Deaths resulting from benzodiazepines and heroin abuse were the highest in the single drug category, while heroin-benzodiazepines combination deaths were the highest in the multiple-drug category. Methamphetamine was the most abused illicit drug in Kuwait. These findings revealed the illicit drug abuse situation in the State of Kuwait, in a region that suffers from the scarcity of information regarding illicit substances. Thus, providing valuable information for drug enforcement, forensic analyst, health workers on national and international levels.

Enhanced tunable plasmonic resonance in crumpled graphene resonators loaded with gate tunable metamaterials.

Graphene devices have been widely explored for photonic applications, as they serve as promising candidates for controlling light interactions resulting in extreme confinement and tunability of graphene plasmons. The ubiquitous presence of surface crumples in graphene, very less is known on how the crumples in graphene can affect surface plasmon resonance and its absorption properties. In this article, a novel approach based on the crumpled graphene is investigated to realize broadband tunability of plasmonic resonance through the mechanical reconfiguration of crumpled graphene resonators. The mechanical reconfiguration of graphene crumples combined with dual electrostatic gating (i.e. raising the Fermi level from 0.2-0.4 eV) of graphene serves as a tuning knob enabling broad spectral tunability of plasmonic resonance in the wavelength range of 14-24 µm. The crumpled region in the resonators exhibits an effective trapping potential where it extremely confines the surface plasmonic field on the surfaces of crumples providing localized surface plasmon resonance at the apices of these crumples. Finally, to achieve near-unity absorption >99% at the resonance wavelengths (17 µm and 22 µm) crumpled graphene resonators are loaded with four ring shaped metamaterials which result in the enhanced near-field intensity of ≈1.4×106. This study delivers insight into the tunability of crumpled graphene and their coupling mechanism by providing a new platform for the flexible and gate tunable graphene sensors at the infrared region.

Burden of community-associated Clostridioides difficile infection in southeastern United States: a population-based study.

OBJECTIVES: This cross-sectional population-based study aims to determine overall incidence rate of Clostridioides difficile infection (CDI) in the State of South Carolina and provide an estimated cost of hospitalization due to community-associated CDI (CA-CDI). METHODS: All CDI cases in South Carolina were identified through National Healthcare Safety Network (NHSN) and the South Carolina Infectious Disease and Outbreak Network (SCION) from January 1, 2015 to June 30, 2016, excluding infants < 1 year of age. RESULTS: During the 18-month study period, 10,254 CDI events were identified in South Carolina residents with an overall incidence rate of 139/100,000 person-years. Over one-half of CDI cases were CA-CDI (5192; 51%) with an incidence rate of 71/100,000 person-years. Among patients with CA-CDI, 2127 (41%) required hospitalization with a median length of stay of 5 days. The annual burden of CA-CDI in South Carolina was estimated to be 9282 hospital days and $16,217,295 in hospitalization costs. CONCLUSION: The incidence rate of CA-CDI in South Carolina has surpassed both community-onset healthcare facility associated and hospital-onset CDI combined. The heavy burden of CA-CDI justifies dedication of public health resources to combat CDI in ambulatory settings, through antimicrobial stewardship initiatives.

Threat, Coping, and Social Distance Adherence During COVID-19: Cross-Continental Comparison Using an Online Cross-Sectional Survey.

BACKGROUND: Social distancing is an effective preventative policy for COVID-19 that is enforced by governments worldwide. However, significant variations are observed in adherence to social distancing across individuals and countries. Due to the lack of treatment, rapid spread, and prevalence of COVID-19, panic and fear associated with the disease causes great stress. Subsequent effects will be a variation around the coping and mitigation strategies for different individuals following different paths to manage the situation. OBJECTIVE: This study aims to explore how threat and coping appraisal processes work as mechanisms between information and citizens' adherence to COVID-19-related recommendations (ie, how the information sources and social media influence threat and coping appraisal processes with COVID-19 and how the threat and coping appraisal processes influence adherence to policy guidelines). In addition, this study aims to explore how citizens in three different countries (the United States, Kuwait, and South Korea), randomly sampled, are effectively using the mechanisms. METHODS: Randomly sampled online survey data collected by a global firm in May 2020 from 162 citizens of the United States, 185 of Kuwait, and 71 of South Korea were analyzed, resulting in a total sample size of 418. A seemingly unrelated regression model, controlling for several counterfactuals, was used for analysis. The study's focal estimated effects were compared across the three countries using the weighted distance between the parameter estimates. RESULTS: The seemingly unrelated regression model estimation results suggested that, overall, the intensity of information source use for the COVID-19 pandemic positively influenced the threat appraisal for the disease (P<.001). Furthermore, the intensity of social media use for the COVID-19 pandemic positively influenced the coping appraisal for the disease (P<.001). Higher COVID-19 threat appraisal had a positive effect on social distancing adherence (P<.001). Higher COVID-19 coping appraisal had a positive effect on social distancing adherence (P<.001). Higher intensity of COVID-19 knowledge positively influenced social distancing adherence (P<.001). There were country-level variations. Broadly, we found that the United States had better results than South Korea and Kuwait in leveraging the information to threat and coping appraisal to the adherence process, indicating that individuals in countries like the United States and South Korea may be more pragmatic to appraise the situation before making any decisions. CONCLUSIONS: This study's findings suggest that the mediation of threat and coping strategies are essential, in varying effects, to shape the information and social media strategies for adherence outcomes. Accordingly, coordinating public service announcements along with information source outlets such as mainstream media (eg, TV and newspaper) as well as social media (eg, Facebook and Twitter) to inform citizens and, at the same time, deliver balanced messages about the threat and coping appraisal is critical in implementing a staggered social distancing and sheltering strategy.

Citizens' Adherence to COVID-19 Mitigation Recommendations by the Government: A 3-Country Comparative Evaluation Using Web-Based Cross-Sectional Survey Data.

BACKGROUND: Social distancing is an effective preventative policy for the coronavirus disease (COVID-19) that is enforced by governments worldwide. However, significant variations are observed in following the policy across individuals and countries. Arguably, differences in citizens' adherence actions will be influenced by their perceptions about government's plans and the information available to guide their behaviors-more so in the digital age in the realm of mass influence of social media on citizens. Insights into the underlying factors and dynamics involved with citizens' adherence process will inform the policy makers to follow appropriate communication and messaging approaches to influence citizens' willingness to adhere to the recommendations. OBJECTIVE: The aim of this study is a comparative evaluation of citizens' adherence process to COVID-19-relevant recommendations by the government. The focus is on how three different countries' (United States, Kuwait, and South Korea) citizens, randomly sampled, respond to governments' pandemic guidance efforts. We draw insights into two categories of perceived government roles in managing the pandemic: (1) citizens' perceptions of government's role in responding to the pandemic and (2) citizens' perceptions of government's business reopening efforts. Undoubtedly, the internet and social media have burgeoned, with differing effects on shaping individuals' views and assessments of the COVID-19 situation; we argue and test for the effects of information sources, social media use, and knowledge on the adherence actions. METHODS: We randomly sampled web-based survey data collected by a global firm in May 2020 from citizens of the United States, Kuwait, and South Korea. A nonlinear ordered probit regression, controlling for several counterfactuals, was used for analysis. The focal estimated effects of the study were compared across countries using the weighted distance between the parameter estimates. RESULTS: The total sample size was 482 respondents, of which 207 (43%) lived in the United States, 181 (38%) lived in Kuwait, and 94 (20%) lived in South Korea. The ordered probit estimation results suggest that overall, perception of government response efforts positively influenced self-adherence (P<.001) and others' adherence (P<.001) to social distancing and sheltering. Perception of government business reopening efforts positively influenced others' adherence (P<.001). A higher intensity of general health information source for COVID-19 had a positive effect on self-adherence (P=.003). A higher intensity of social media source use for COVID-19 positively influenced others' adherence (P=.002). A higher intensity of knowledge on COVID-19 positively influenced self-adherence (P=.008) and negatively influenced others' adherence (P<.001). There were country-level variations-broadly, the United States and Kuwait had better effects than South Korea. CONCLUSIONS: As the COVID-19 global pandemic continues to grow and governmental restrictions are ongoing, it is critical to understand people's frustration to reduce panic and promote social distancing to facilitate the control of the pandemic. This study finds that the government plays a central role in terms of adherence to restrictions. Governments need to enhance their efforts on publicizing information on the pandemic, as well as employ strategies for improved communication management to citizens through social media as well as mainstream information sources.

Role of Early De-escalation of Antimicrobial Therapy on Risk of Clostridioides difficile Infection Following Enterobacteriaceae Bloodstream Infections.

BACKGROUND: There is a paucity of data on the effect of early de-escalation of antimicrobial therapy on rates of Clostridioides difficile infection (CDI). This retrospective cohort study evaluated impact of de-escalation from antipseudomonal ß-lactam (APBL) therapy within 48 hours of Enterobacteriaceae bloodstream infections (BSIs) on 90-day risk of CDI. METHODS: Adult patients hospitalized for >48 hours for treatment of Enterobacteriaceae BSI at Palmetto Health hospitals in Columbia, South Carolina, from 1 January 2011 through 30 June 2015 were identified. Multivariable Cox proportional hazards regression was used to examine time to CDI in patients who received >48 hours or ≤48 hours of APBL for empirical therapy of Enterobacteriaceae BSI after adjustment for the propensity to receive >48 hours of APBL. RESULTS: Among 808 patients with Enterobacteriaceae BSI, 414 and 394 received >48 and ≤48 hours of APBL, respectively. Incidence of CDI was higher in patients who received >48 hours than those who received ≤48 hours of APBL (7.0% vs 1.8%; log-rank P = .002). After adjustment for propensity to receive >48 hours of APBL and other variables in the multivariable model, receipt of >48 hours of APBL (hazard ratio [HR], 3.56 [95% confidence interval {CI}, 1.48-9.92]; P = .004) and end-stage renal disease (HR, 4.27 [95% CI, 1.89-9.11]; P = .001) were independently associated with higher risk of CDI. CONCLUSIONS: The empirical use of APBL for >48 hours was an independent risk factor for CDI. Early de-escalation of APBL using clinical risk assessment tools or rapid diagnostic testing may reduce the incidence of CDI in hospitalized adults with Enterobacteriaceae BSIs.

Derivation of a quick Pitt bacteremia score to predict mortality in patients with Gram-negative bloodstream infection.

PURPOSE: This retrospective cohort study derived a "quick" version of the Pitt bacteremia score (qPitt) using binary variables in patients with Gram-negative bloodstream infections (BSI). The qPitt discrimination was then compared to quick sepsis-related organ failure assessment (qSOFA) and systemic inflammatory response syndrome (SIRS). METHODS: Hospitalized adults with Gram-negative BSI at Palmetto Health hospitals in Columbia, SC, USA from 2010 to 2013 were identified. Multivariate Cox proportional hazards regression was used to determine variables associated with 14-day mortality. RESULTS: Among 832 patients with Gram-negative BSI, median age was 65 years and 449 (54%) were women. After adjustments for age and Charleston comorbidity score, all five components of qPitt were independently associated with mortality: temperature < 36 °C [hazard ratio (HR) 3.02, 95% confidence interval (CI) 1.95-4.62], systolic blood pressure < 90 mmHg or vasopressor use (HR 2.40, 95% CI 1.37-4.13), respiratory rate ≥ 25/min or mechanical ventilation (HR 3.01, 95% CI 1.81-5.14), cardiac arrest (HR 5.35, 95% CI 2.81-9.43), and altered mental status (HR 3.99, 95% CI 2.44-6.80). The qPitt had higher discrimination to predict mortality [area under receiver operating characteristic curve (AUROC) 0.85] than both qSOFA (AUROC 0.77, p < 0.001) and SIRS (AUROC 0.63, p < 0.001). There was a significant difference in mortality between appropriate and inappropriate empirical antimicrobial therapy in patients with qPitt ≥ 2 (24% vs. 49%, p < 0.001), but not in those with qPitt < 2 (3% vs. 5%, p = 0.36). CONCLUSIONS: The qPitt had good discrimination in predicting mortality following Gram-negative BSI and identifying opportunities for improved survival with appropriate empirical antimicrobial therapy.

Nicotinic Acetylcholine Receptor Agonists for the Treatment of Alzheimer's Dementia: An Update.

A significant portion of the clinical phenotype observed in Alzheimer's disease (AD) occurs through nicotinic acetylcholine receptors (nAChRs). Degeneration of cholinergic neurons, combined with aberrant nAChR expression and activation partially through amyloid-beta peptide (Aß)-nAChR leads to upregulation of pro-inflammatory pathways and subsequently the progressive cognitive decline of AD. Interestingly, the cholinergic anti-inflammatory pathway is also mediated through nAChR particularly α7 nAChR. Thus, agonists of these receptors will likely exert pro-cognitive benefits through multiple mechanisms including stimulating the cholinergic pathway, modulating inflammation, and buffering the effects of amyloid. Despite this promising theoretical use, trials thus far have been complicated by adverse effects or minimal improvement. This review will provide an update on several pharmacological nAChR agonists tested in clinical trials and reasons that further investigation of nAChR agonists is merited. IMPLICATIONS: nAChRs have consistently presented a promising theoretical use in the treatment of AD; however, trials thus far have been complicated by adverse effects or minimal improvement. This review will provide an update on several pharmacological nAChR agonists trialed and reasons that further investigation of nAChR agonists is merited.

Risk factors for pneumonia due to beta-lactam-susceptible and beta-lactam-resistant Pseudomonas aeruginosa: a case-case-control study.

PURPOSE: This case-case-control study aims to identify clinical predictors for pneumonia due to Pseudomonas aeruginosa (PA) which is (1) susceptible to all routinely tested antipseudomonal beta-lactams (APBL-S) and (2) resistant to at least one antipseudomonal beta-lactam (APBL-R). METHODS: Hospitalized adults with acute bacterial pneumonia at Palmetto Health hospitals in Columbia, SC, USA from January 1, 2012 to April 15, 2014 were identified. Multivariate logistic regression was used to determine risk factors for pneumonia due to APBL-S PA and APBL-R PA. RESULTS: Among 326 unique patients, 119 had pneumonia due to APBL-S PA (cases), 44 due to APBL-R PA (cases) and 163 due to ceftriaxone-susceptible bacteria (controls). Bronchiectasis [odds ratio (OR) 5.7, 95% confidence intervals (CI) 1.3-39.2], interstitial lung disease (OR 6.2, 95% CI 1.5-42.6), prior airway colonization with APBL-S PA (OR 7.2, 95% CI 1.1-139.4) and recent exposure to both antipseudomonal beta-lactam (APBL; OR 2.2, 95% CI 1.1-4.5) and nonpseudomonal beta-lactams (OR 2.6, 95% CI 1.0-6.8) were independently associated with increased risk of APBL-S PA pneumonia. Bronchiectasis (OR 8.3, 95% CI 1.7-46.6), prior airway colonization with APBL-R PA (OR 14.9, 95% CI 2.0-312.9) and recent use of only APBL (OR 7.7, 95% CI 3.4-17.9) were predictors for APBL-R PA pneumonia. CONCLUSIONS: Stratification of hospitalized patients with pneumonia based on structural lung disease, prior airway colonization and recent antimicrobial exposure may improve empirical antimicrobial selection. Expansion of antimicrobial regimen from ceftriaxone to APBL or combination therapy is suggested in patients with risk factors for APBL-S or APBL-R PA, respectively.

Salivary beta amyloid protein levels are detectable and differentiate patients with Alzheimer's disease dementia from normal controls: preliminary findings.

BACKGROUND: Peripheral diagnostics for Alzheimer's disease (AD) continue to be developed. Diagnostics capable of detecting AD before the onset of symptoms are particularly desirable, and, given the fact that early detection is imperative for alleviating long-term symptoms of the disease, methods which enable detection in the earliest stages are urgently needed. Saliva testing is non-invasive, and saliva is easy to acquire. A simple, non-invasive saliva test can potentially be used as an adjunct to diagnose AD during its earliest stages. METHODS: Salivary levels of beta amyloid 42 (Aß42) were quantitated with enzyme-linked immunosorbent-type assays. Fifteen AD patients (7 men, mean age 77.8 ± 1.8 years, mean Mini-Mental State Examination [MMSE] score 19.0 ± 1.3) and 7 normal controls (2 men, mean age 60.4 ± 4.7 years, mean MMSE 29.0 ± 0.4) were enrolled. RESULTS: Salivary Aß42 levels were significantly higher in AD patients than in controls (51.7 ± 1.6 pg/mL for AD and 21.1 ± 0.3 pg/mL for controls, p < 0.001). Based on these results, saliva testing appears to be a promising method for detecting AD during its critical early stages.

Impact of endocrine disrupting compounds in sewage impacted coastal area on seabream.

The pollution of coastal regions worldwide has been of a great concern due to the presence of endocrine disrupting chemicals (EDCs). These chemicals find their way to the marine environment via the sewage treatment plants (STPs). Hence, this study was designed to investigate the status and sources of EDCs and their effect on fish in Kuwait's coastal areas, from the chemical and biological perspectives. The assessment of three STPs indicated the presence of significant levels of phthalates (19 and 31µg/l), alkylphenols (85 and 159ng/l), and estrogens (30 and 368ng/l) in both inflow and outflow samples. The analysis of samples from field exposure sites revealed significant levels of EDCs in seawater (phthalates: 2.1-4.6µg/l; alkylphenols: 1.2-16.4ng/l; estrogens: 0-36.2ng/l) and sediment (phthalates: 2.1-15.7mg/kg dry wt; alkyphenols: 2.5-15.1µg/kg dry wt.; estrogens: 4.1-214.2µg/kg dry wt.) samples. The biological perspective investigated through the exposure of fish to sewage outlets at five sites. The hepatosomatic index (HSI) revealed a higher level in winter samples 0.48-0.79%) in comparison to summer samples 1-1.5%). Histological observation of hepatic tissue of fish exposed during winter months in all sites, showed much less necrotic changes and hepatic vacuolation in the hepatic tissue of summer exposed fish. Imunnohistochemistry evidences revealed a significant level of positive signals and Vtg localization in the hepatic tissue as the results support the histopathological alterations observed. Results of enzyme-linked immunosorbent assay (ELISA) showed no significant difference between the plasma protein content of winter and summer samples. Overall, the study suggest that there is possible local source or a chronic input of untreated and/or partially treated water due to the significant levels of phthalates, alkyphenols, and estrogens detected in the Kuwait Bay. These levels were enough to initiate alteration in the hepatic tissue of fish exposed to the sewage outlets in Kuwait for two weeks.

Application of Fluoroquinolone Resistance Score in Management of Complicated Urinary Tract Infections.

The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived from patients with bloodstream infections caused by Gram-negative bacteria and is based on fluoroquinolone use within the past 6 months, among other clinical and health care exposure criteria. This study aims to examine the utility of the FQRS in patients with complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA, from 1 April 2015 through 31 July 2015 were prospectively identified. Multivariate logistic regression was used to examine the association between prior fluoroquinolone use and resistance. Among 238 patients, 54 (23%) had cUTI due to fluoroquinolone-resistant bacteria. Overall, the median age was 66 years, 162 (68%) patients were women, and 137 (58%) patients had cUTI due to Escherichia coli Prior exposure to fluoroquinolones within 3 months (adjusted odds ratio [aOR], 23.4; 95% confidence interval [CI], 8.2 to 76.8; P < 0.001) and within 3 to 12 months (aOR, 13.2; 95% CI, 3.1 to 68.4; P < 0.001) was independently associated with fluoroquinolone resistance compared to no prior use. The area under the receiver operating characteristic curve for the FQRS increased from 0.73 to 0.80 when prior fluoroquinolone use was extended from 6 to 12 months. FQRSs of ≥2 and ≥3 had negative predictive values of 91% and 90%, respectively. The modified FQRS stratifies patients with cUTI on the basis of the predicted probability of fluoroquinolone resistance with very good discrimination. Application of the modified FQRS may improve antimicrobial utilization in patients with acute pyelonephritis.