Stabilization of Copper-Based Biochips with Alumina for Biosensing Application.

Surface plasmon resonance devices typically rely on the use of gold-coated surfaces, but the use of more abundant metals is desirable for the long-term development of plasmonic biochips. As a substitute for gold, thin copper films have been deposited on glass coverslips by thermal evaporation. As expected, these films immersed in a water solution initially exhibit an intense plasmonic resonance comparable to gold. However, without protection, an angle-resolved optical analysis shows a rapid degradation of the copper, characterized by a continuous angular shift of the plasmonic resonance curve. We show that copper films protected with a thin layer of aluminum oxide of a few nanometers can limit the oxidation rate for a sufficient time to perform some standard measurements. As the process is simple and compatible with the current biochip production technique, such an approach could pave the way for the production of alternative and more sustainable biochips.

Clinical Features and Treatment Outcomes of Pulmonary Mycobacterium avium-intracellulare Complex With and Without Coinfections.

Coinfections are more common in patients with cystic fibrosis and bronchiectasis. Infiltrates on imaging studies are seen more commonly in patients with coinfections, but coinfections did not affect treatment outcomes of pulmonary Mycobacterium avium complex.

Heart Failure in Chronic Infectious and Inflammatory Conditions: Mechanistic Insights from Clinical Heterogeneity.

PURPOSE OF REVIEW: The balance between inflammation and its resolution plays an important and increasingly appreciated role in heart failure (HF) pathogenesis. In humans, different chronic inflammatory conditions and immune-inflammatory responses to infection can lead to diverse HF manifestations. Reviewing the phenotypic and mechanistic diversity of these HF presentations offers useful clinical and scientific insights. RECENT FINDINGS: HF risk is increased in patients with chronic inflammatory and autoimmune disorders and relates to disease severity. Inflammatory condition-specific HF manifestations exist and underlying pathophysiologic causes may differ across conditions. Although inflammatory disease-specific presentations of HF differ, chronic excess in inflammation and auto-inflammation relative to resolution of this inflammation is a common underlying contributor to HF. Further studies are needed to phenotypically refine inflammatory condition-specific HF pathophysiologies and prognoses, as well as potential targets for intervention.

Enhanced Photocatalytic Activity and Photoluminescence of ZnO Nano-Wires Coupled with Aluminum Nanostructures.

In this study, we fabricated a hybrid plasmonic/semiconductor material by combining the chemical bath deposition of zinc oxide nanowires (ZnONWs) with the physical vapor deposition of aluminum nanostructures (AlNSs) under controlled temperature and atmosphere. The morphological and the optical properties of the ZnONWs/AlNSs hybrid material fabricated at different temperatures (250, 350, and 450 °C) and thicknesses (5, 7, and 9 nm) of Al layers were investigated. By adjusting the deposition and annealing parameters, it was possible to tune the size distribution of the AlNSs. The resonant coupling between the plasmonic AlNSs and ZnONWs leads to an enhanced photoluminescence response. The photocatalytic activity was studied through photodegradation under UV-light irradiation of methylene blue (MB) adsorbed at the surface of ZnO. The MB photodegradation experiment reveals that the ZnONWs covered with 7 nm aluminum film and annealed at 450 °C exhibit the highest degradation efficiency. The comparison between ZnONws and ZnONws/AlNSs shows a photoluminescence enhancement factor of 1.7 and an increase in the kinetics constant of photodegradation with a factor of 4.

Cardiovascular Implications of Immune Disorders in Women.

Immune responses differ between men and women, with women at higher risk of developing chronic autoimmune diseases and having more robust immune responses to many viruses, including HIV and hepatitis C virus. Although immune dysregulation plays a prominent role in chronic systemic inflammation, a key driver in the development of atherosclerotic cardiovascular disease (ASCVD), standard ASCVD risk prediction scores underestimate risk in populations with immune disorders, particularly women. This review focuses on the ASCVD implications of immune dysregulation due to disorders with varying global prevalence by sex: autoimmune disorders (female predominant), HIV (male-female equivalent), and hepatitis C virus (male predominant). Factors contributing to ASCVD in women with immune disorders, including traditional risk factors, dysregulated innate and adaptive immunity, sex hormones, and treatment modalities, are discussed. Finally, the need to develop new ASCVD risk stratification tools that incorporate variables specific to populations with chronic immune disorders, particularly in women, is emphasized.

Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum.

BACKGROUND: Genogroup II noroviruses are the most common cause of acute infectious gastroenteritis. We evaluated the use of a new GII.2 inoculum in a human challenge. METHODS: Forty-four healthy adults (36 secretor-positive and 8 secretor-negative for histo-blood group antigens) were challenged with ascending doses of a new safety-tested Snow Mountain virus (SMV) GII.2 norovirus inoculum (1.2 × 104 to 1.2 × 107 genome equivalent copies [GEC]; n = 38) or placebo (n = 6). Illness was defined as diarrhea and/or vomiting postchallenge in subjects with evidence of infection (defined as GII.2 norovirus RNA detection in stool and/or anti-SMV immunoglobulin G [IgG] seroconversion). RESULTS: The highest dose was associated with SMV infection in 90%, and illness in 70% of subjects with 10 of 12 secretor-positive (83%) and 4 of 8 secretor-negative (50%) becoming ill. There was no association between prechallenge anti-SMV serum IgG concentration, carbohydrate-binding blockade antibody, or salivary immunoglobulin A and infection. The median infectious dose (ID50) was 5.1 × 105 GEC. CONCLUSIONS: High rates of infection and illness were observed in both secretor-positive and secretor-negative subjects in this challenge study. However, a high dose will be required to achieve the target of 75% illness to make this an efficient model for evaluating potential norovirus vaccines and therapeutics. CLINICAL TRIALS REGISTRATION: NCT02473224.

Association of physical activity with arterial stiffness among Black adults.

Arterial stiffness is a precursor for the development of hypertension and premature cardiovascular disease (CVD). Physical activity has been associated with lower arterial stiffness among largely White populations, but the types of activity required and whether these findings apply to Black adults remain unknown. We examined whether physical activity levels were associated with arterial stiffness among Black adults in two independent cohorts. In the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity, 378 Black adults (age 52.8 ± 10.3, 39.7% male) without known CVD living in Atlanta, GA were recruited. Arterial stiffness was measured as pulse wave velocity (PWV). Total and domain-specific physical activity were assessed by self-report. Multiple linear regression models were used to investigate differences across physical activity levels after adjusting for age, sex, CVD risk factors, and socioeconomic status. Findings were validated in an independent cohort of Black adults (n = 55, age 50.4 ± 9.2, 23.6% male). After adjustment for covariates, lower arterial stiffness was associated with higher self-reported levels of sport/exercise (6.92 ± 1.13 vs 7.75 ± 1.14, p < 0.001, highest vs lowest quartile) and home/life activities (7.34 ± 1.24 vs 7.73 ± 1.07, p = 0.04, highest vs lowest quartile), but not work, active living, or the overall physical activity scores. These findings were replicated in the independent cohort where higher levels of sport/exercise remained associated with lower arterial stiffness (6.66 ± 0.57 vs 8.21 ± 0.66, p < 0.001, highest vs lowest quartile). Higher levels of sport/exercise and home/life-related physical activities (in comparison to occupational physical activity) are associated with lower arterial stiffness in Black adults.

Usefulness of Restless Legs Symptoms to Predict Adverse Cardiovascular Outcomes in Men With Coronary Artery Disease.

The relationship between restless legs syndrome (RLS) and cardiovascular disease remains enigmatic in the general population, and its prognostic value in patients with coronary artery disease (CAD) is unknown. In this study, the frequency of RLS-like symptoms was assessed using a validated instrument in 3,266 patients undergoing cardiac catheterization (mean age 64 years, 62% male, 23% Black, and 74% with obstructive CAD). Patients were followed for primary end points of cardiovascular death or incident myocardial infarction. Fine and Gray hazard models explored the association between RLS and incident events after adjustment for demographic and clinical risk factors. In the total cohort, 29% of patients reported mild (rare or sometimes) symptoms, and 15% of patients had moderate/severe (often to almost always) symptoms of RLS. Female sex (odds ratio [OR] 2.11, 95% confidence interval (CI), 1.68 to 2.57), body mass index (OR 1.12 per 5 kg/m2, 95% CI, 1.04 to 1.22), diabetes (OR 1.43, 95%,1.15 to 1.79), and ß-blocker use (OR 1.35, 95% CI, 1.07 to 1.72) were independently associated with moderate/severe symptoms of RLS compared with no symptoms. Over a 5-year follow-up period, 991 patients suffered an adverse event. Compared with those with no symptoms, patients with moderate/severe RLS had significantly higher risk of the primary end point (hazard ratio [HR] = 1.33, 95%),CI 1.01 to 1.76) after adjustment for demographic and clinical risk factors. The association was more significant in men than women, HR 1.98, 95% CI, 1.41 to 2.78 versus HR 0.99 (,95% CI, 0.64 to 1.52, p interaction= 0.013. In conclusion, among men with CAD, moderate-to-severe symptoms of RLS are associated with significantly higher risk of adverse cardiovascular outcomes, independent of traditional risk factors.

Infection- and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant.

The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies. We compared antibody binding and live virus neutralization of sera from naturally infected and Moderna-vaccinated individuals against two SARS-CoV-2 variants: B.1 containing the spike mutation D614G and the emerging B.1.351 variant containing additional spike mutations and deletions. Sera from acutely infected and convalescent COVID-19 patients exhibited a 3-fold reduction in binding antibody titers to the B.1.351 variant receptor-binding domain of the spike protein and a 3.5-fold reduction in neutralizing antibody titers against SARS-CoV-2 B.1.351 variant compared to the B.1 variant. Similar results were seen with sera from Moderna-vaccinated individuals. Despite reduced antibody titers against the B.1.351 variant, sera from infected and vaccinated individuals containing polyclonal antibodies to the spike protein could still neutralize SARS-CoV-2 B.1.351, suggesting that protective humoral immunity may be retained against this variant.

Reduced binding and neutralization of infection- and vaccine-induced antibodies to the B.1.351 (South African) SARS-CoV-2 variant.

The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies to neutralize these variants. We compared antibody binding and live virus neutralization of sera from naturally infected and spike mRNA vaccinated individuals against a circulating SARS-CoV-2 B.1 variant and the emerging B.1.351 variant. In acutely-infected (5-19 days post-symptom onset), convalescent COVID-19 individuals (through 8 months post-symptom onset) and mRNA-1273 vaccinated individuals (day 14 post-second dose), we observed an average 4.3-fold reduction in antibody titers to the B.1.351-derived receptor binding domain of the spike protein and an average 3.5-fold reduction in neutralizing antibody titers to the SARS-CoV-2 B.1.351 variant as compared to the B.1 variant (spike D614G). However, most acute and convalescent sera from infected and all vaccinated individuals neutralize the SARS-CoV-2 B.1.351 variant, suggesting that protective immunity is retained against COVID-19.

Variability in the Management of Adults With Pulmonary Nontuberculous Mycobacterial Disease.

BACKGROUND: The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States. METHODS: We conducted a 10-year (2005-2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. RESULTS: Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0-10.4; P < .001). Overall mortality was 15.7%. CONCLUSIONS: Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.

A Retrospective Chart Review on the Role of Suppressive Therapy in the Management of Spinal Infections Involving Hardware.

BACKGROUND: One percent to 8% of patients undergoing spinal instrumentation surgeries develop infections. There is no consensus on the medical and surgical management of these infections. METHODS: We conducted a retrospective chart review based on International Classification of Diseases, Ninth Revision, and Common Procedural Terminology codes relevant to spinal infections with hardware within Emory Healthcare over a 10-year period. Extracted data included patient demographics, clinical presentation, laboratory and microbiologic results, and surgical and medical management including choice and duration of suppressive therapy. Multivariable logistic regression was used to assess the association of length of use of suppressive antibiotics with treatment success and to identify predictors of use of suppressive antibiotics. RESULTS: Of 869 records, 124 met inclusion criteria. Fifty patients (40.3%) had an infection that occurred after hardware placement, mostly within 3 months postsurgery, while the remainder had vertebral osteomyelitis that required hardware placement. After initial intravenous antibiotic treatment for ≥4 weeks, 72 patients (64.5%) were given suppressive antibiotics. The overall treatment success rate was 78.2%. In spinal infections involving hardware with gram-negative rods, patients were less likely to receive suppressive antibiotics, less likely to have hardware removed, and less likely to have treatment success compared with patients with infections with Staphylococcus species. CONCLUSIONS: Management of spinal infections involving hardware should be tailored to the timing of onset of infection and causative organism. Further studies are needed to determine best management practices, particularly for gram-negative rod infections where the role of further suppressive antibiotics and hardware removal may be warranted.