Showing papers by "University of Alabama at Birmingham published in 2022"

Liver Transplantation Outcomes From Controlled Circulatory Death Donors

Abstract: Objective: To compare the outcomes of livers donated after circulatory death (DCD) and undergoing either in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) with livers undergoing static cold storage (SCS). Summary of Background Data: DCD livers are associated with increased risk of primary nonfunction, poor function, and nonanastomotic strictures (NAS), leading to underutilization. Methods: A single center, retrospective analysis of prospectively collected data on 233 DCD liver transplants performed using SCS, NRP, or NMP between January 2013 and October 2020. Results: Ninety-seven SCS, 69 NRP, and 67 NMP DCD liver transplants were performed, with 6-month and 3-year transplant survival (graft survival non-censored for death) rates of 87%, 94%, 90%, and 76%, 90%, and 76%, respectively. NRP livers had a lower 6-month risk-adjusted Cox proportional hazard for transplant failure compared to SCS (hazard ratio 0.30, 95% Confidence Interval 0.08–1.05, P = 0.06). NRP and NMP livers had a risk-adjusted estimated reduction in the mean model for early allograft function score of 1.52 (P < 0.0001) and 1.19 (P < 0.001) respectively compared to SCS. Acute kidney injury was more common with SCS (55% vs 39% NRP vs 40% NMP; P = 0.08), with a lower risk-adjusted peak-to-baseline creatinine ratio in the NRP (P = 0.02). No NRP liver had clinically significant NAS in contrast to SCS (14%) and NMP (11%, P = 0.009), with lower risk-adjusted odds of overall NAS development compared to SCS (odds ratio = 0.2, 95%CI 0.06–0.72, P = 0.01). Conclusion: NRP and NMP were associated with better early liver function compared to SCS, whereas NRP was associated with superior preservation of the biliary system.

Ribosome Biogenesis: A Central Player in Cancer Metastasis and Therapeutic Resistance

Abstract: Abstract Ribosomes are a complex ensemble of rRNA and ribosomal proteins that function as mRNA translation machines. Ribosome biogenesis is a multistep process that begins in the nucleolus and concludes in the cytoplasm. The process is tightly controlled by multiple checkpoint and surveillance pathways. Perturbations in these checkpoints and pathways can lead to hyperactivation of ribosome biogenesis. Emerging evidence suggests that cancer cells harbor a specialized class of ribosomes (onco-ribosomes) that facilitates the oncogenic translation program, modulates cellular functions, and promotes metabolic rewiring. Mutations in ribosomal proteins, rRNA processing, and ribosome assembly factors result in ribosomopathies that are associated with an increased risk of developing malignancies. Recent studies have linked mutations in ribosomal proteins and aberrant ribosomes with poor prognosis, highlighting ribosome-targeted therapy as a promising approach for treating patients with cancer. Here, we summarize various aspects of dysregulation of ribosome biogenesis and the impact of resultant onco-ribosomes on malignant tumor behavior, therapeutic resistance, and clinical outcome. Ribosome biogenesis is a promising therapeutic target, and understanding the important determinants of this process will allow for improved and perhaps selective therapeutic strategies to target ribosome biosynthesis.

Willingness to Get a COVID-19 Vaccine and Reasons for Hesitancy Among Medicare Beneficiaries: Results From a National Survey.

Abstract: Objectives To assess (1) the willingness to get a COVID-19 vaccine among Medicare beneficiaries, (2) the associated factors, and (3) the reasons for vaccine hesitancy. Methods Data were taken from the Medicare Current Beneficiary Survey (MCBS) 2020 Fall COVID-19 Supplement, conducted October-November 2020. Willingness to get a COVID-19 vaccine was measured by respondents' answer to whether they would get a COVID-19 vaccine when available. We classified responses of "definitely" and "probably" as "willing to get," and responses "probably not," "definitely not," and "not sure" as "vaccine hesitancy." Reasons for vaccine hesitancy were assessed by a series of yes/no questions focusing on 10 potential reasons. The analytical sample included 6715 adults 65 years and older. We conducted a logistic regression model to assess demographic factors and other factors associated with the willingness to get a COVID-19 vaccine. All analyses were conducted in Stata 14 and accounted for the complex survey design of MCBS. Results Overall, 61.0% (95% confidence interval [CI], 59.1-63.0) of Medicare beneficiaries would be willing to get a vaccine when available. Among those who were hesitant, more than 40% reported that mistrust of the government and side effects as the main reasons. Logistic regression model results showed that non-Hispanic Blacks (adjusted odds ratio [AOR] = 0.33; 95% CI, 0.24-0.44) and Hispanics (AOR = 0.60; 95% CI, 0.47-0.77) were less willing to get a vaccine than non-Hispanic Whites; beneficiaries with an income of less than $25 000 (AOR = 0.71; 95% CI, 0.62-0.81) were less willing to get the vaccine than those with an income of $25 000 or more; those who did not think that the COVID-19 virus was more contagious (AOR = 0.53; 95% CI, 0.41-0.69) or more deadly (AOR = 0.51; 95% CI, 0.41-0.65) were also less willing to get the vaccine than those who thought that the virus was more contagious or more deadly than the influenza virus. Conclusions The 2020 MCBS survey data showed that close to 40% of Medicare beneficiaries were hesitant about getting a COVID-19 vaccine, and the hesitancy was greater in racial/ethnic minorities. Medicare beneficiaries were concerned about the safety of the vaccine, and some appeared to be misinformed. Evidence-based educational and policy-level interventions need to be implemented to further promote COVID-19 vaccination.

Galactose-Deficient IgA1 B cells in the Circulation of IgA Nephropathy Patients Carry Preferentially Lambda Light Chains and Mucosal Homing Receptors

Abstract: IgA nephropathy (IgAN) primary glomerulonephritis is characterized by the deposition of circulating immune complexes composed of polymeric IgA1 molecules with altered O-glycans (Gd-IgA1) and anti-glycan antibodies in the kidney mesangium. The mesangial IgA deposits and serum IgA1 contain predominantly λ light (L) chains, but the nature and origin of such IgA remains enigmatic.We analyzed λ L chain expression in peripheral blood B cells of 30 IgAN patients, 30 healthy controls (HCs), and 18 membranous nephropathy patients selected as disease controls (non-IgAN).In comparison to HCs and non-IgAN patients, peripheral blood surface/membrane bound (mb)-Gd-IgA1+ cells from IgAN patients express predominantly λ L chains. In contrast, total mb-IgA+, mb-IgG+, and mb-IgM+ cells were preferentially positive for kappa (κ) L chains, in all analyzed groups. Although minor in comparison to κ L chains, λ L chain subsets of mb-IgG+, mb-IgM+, and mb-IgA+ cells were significantly enriched in IgAN patients in comparison to non-IgAN patients and/or HCs. In contrast to HCs, the peripheral blood of IgAN patients was enriched with λ+ mb-Gd-IgA1+, CCR10+, and CCR9+ cells, which preferentially home to the upper respiratory and digestive tracts. Furthermore, we observed that mb-Gd-IgA1+ cell populations comprise more CD138+ cells and plasmablasts (CD38+) in comparison to total mb-IgA+ cells.Peripheral blood of IgAN patients is enriched with migratory λ+ mb-Gd-IgA1+ B cells, with the potential to home to mucosal sites where Gd-IgA1 could be produced during local respiratory or digestive tract infections.

Enzyme nomenclature and classification: the state of the art

Abstract: The IUBMB enzyme classification system, available at the IUBMB ExplorEnz website, uses a four-component number (the EC number) that identifies an enzyme in terms of reaction catalysed. There were originally six recognized groups of enzymes: Oxidoreductases (EC 1), Transferases (EC 2), Hydrolases (EC 3), Lyases (EC 4), Isomerases (EC 5) and Ligases (EC 6). Of these, the lyases, which are defined as ‘enzymes that cleave C-C, C-O, C-N and other bonds by means other than by hydrolysis or oxidation’, present particular recognition and classification problems. Recently, a new class, the Translocases (EC 7), has been added, which incorporates enzymes that catalyse the movement of ions or molecules across membranes or their separation within membranes. A new subclass of the isomerases has also been included for those enzymes that alter the conformations of proteins and nucleic acids. Newly reported enzymes are being regularly added to the list after validation and where new information affects the classification of an existing entry, a new EC number is created, but the old one is not reused.

Preventing Parkinson’s Disease: An Environmental Agenda

Abstract: Fueled by aging populations and continued environmental contamination, the global burden of Parkinson’s disease (PD) is increasing. The disease, or more appropriately diseases, have multiple environmental and genetic influences but no approved disease modifying therapy. Additionally, efforts to prevent this debilitating disease have been limited. As numerous environmental contaminants (e.g., pesticides, metals, industrial chemicals) are implicated in PD, disease prevention is possible. To reduce the burden of PD, we have compiled preclinical and clinical research priorities that highlight both disease prediction and primary prevention. Though not exhaustive, the “PD prevention agenda” builds upon many years of research by our colleagues and proposes next steps through the lens of modifiable risk factors. The agenda identifies ten specific areas of further inquiry and considers the funding and policy changes that will be necessary to help prevent the world’s fastest growing brain disease.

Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes

Abstract: Semaglutide, a glucagon like peptide-1 (GLP-1) receptor agonist, is available as monotherapy in both subcutaneous as well as oral dosage form (first approved oral GLP-1 receptor agonist). It has been approved as a second line treatment option for better glycaemic control in type 2 diabetes and currently under scrutiny for anti-obesity purpose. Semaglutide has been proved to be safe in adults and elderly patients with renal or hepatic disorders demanding no dose modification. Cardiovascular (CV) outcome trials established that it can reduce various CV risk factors in patients with established CV disorders. Semaglutide is well tolerated with no risk of hypoglycaemia in monotherapy but suffers from gastrointestinal adverse effects. A large population affected with COVID-19 infection were diabetic; therefore use of semaglutide in diabetes as well as CV patients would be very much supportive in maintaining health care system during this pandemic situation. Hence, this peptidic drug can be truly considered as a quintessential of GLP-1 agonists for management of type 2 diabetes.

Aurora Borealis in dentistry: The applications of cold plasma in biomedicine

Abstract: Plasma is regularly alluded to as the fourth form of matter. Its bounty presence in nature along with its potential antibacterial properties has made it a widely utilized disinfectant in clinical sciences. Thermal plasma and non-thermal (or cold atmospheric) plasma (NTP) are two types of plasma. Atoms and heavy particles are both available at the same temperature in thermal plasma. Cold atmospheric plasma (CAP) is intended to be non-thermal since its electrons are hotter than the heavier particles at ambient temperature. Direct barrier discharge (DBD), atmospheric plasma pressure jet (APPJ), etc. methods can be used to produce plasma, however, all follow a basic concept in their generation. This review focuses on the anticipated uses of cold atmospheric plasma in dentistry, such as its effectiveness in sterilizing dental instruments by eradicating bacteria, its advantage in dental cavity decontamination over conventional methods, root canal disinfection, its effects on tooth whitening, the benefits of plasma treatment on the success of dental implant placement, and so forth. Moreover, the limitations and probable solutions has also been anticipated. These conceivable outcomes thus have proclaimed the improvement of more up-to-date gadgets, for example, the plasma needle and plasma pen, which are efficient in treating the small areas like root canal bleaching, biofilm disruption, requiring treatment in dentistry.

Mucus, commensals, and the immune system

Abstract: The immune system in the large intestine is separated from commensal microbes and comparatively rare enteric pathogens by a monolayer of diverse epithelial cells overlaid with a compact and adherent inner mucus layer and a looser outer mucus layer. Microorganisms, collectively referred to as the mucus-associated (MA) microbiota, physically inhabit this mucus barrier, resulting in a dynamic and incessant dialog to maintain both spatial segregation and immune tolerance. Recent major findings reveal novel features of the crosstalk between the immune system and mucus-associated bacteria in health and disease, as well as disease-related peripheral immune signatures indicative of host responses to these organisms. In this brief review, we integrate these novel observations into our overall understanding of host-microbiota mutualism at the colonic mucosal border and speculate on the significance of this emerging knowledge for our understanding of the prevention, development, and progression of chronic intestinal inflammation.

Cellular and humoral immune response to SARS-CoV-2 mRNA vaccines in patients treated with either Ibrutinib or Rituximab

Abstract: Patients treated with B-cell-targeting therapies like Rituximab or Ibrutinib have decreased serological response to various vaccines. In this study, we tested serological and cellular response to SARS-CoV-2 mRNA vaccines in 16 patients treated with Ibrutinib, 16 treated with maintenance Rituximab, 18 patients with chronic lymphocytic leukaemia (CLL) with watch and wait status and 21 healthy volunteers. In comparison with the healthy volunteers, where serological response was achieved by 100% subjects, patients on B-cell-targeting therapy (Ibrutinib and Rituximab) had their response dramatically impaired. The serological response was achieved in 0% of Rituximab treated, 18% of Ibrutinib treated and 50% of untreated CLL patients. Cell-mediated immunity analysed by the whole blood Interferon-γ Release immune Assay developed in 80% of healthy controls, 62% of Rituximab treated, 75% of Ibrutinib treated and 55% of untreated CLL patients. The probability of cell-mediated immune response development negatively correlates with disease burden mainly in CLL patients. Our study shows that even though the serological response to SARS-CoV-2 vaccine is severely impaired in patients treated with B-cell-targeting therapy, the majority of these patients develop sufficient cell-mediated immunity. The vaccination of these patients therefore might be meaningful in terms of protection against SARS-CoV-2 infection.

Sexually transmitted infections and female reproductive health

Abstract: Women are disproportionately affected by sexually transmitted infections (STIs) throughout life. In addition to their high prevalence in women, STIs have debilitating effects on female reproductive health due to female urogenital anatomy, socio-cultural and economic factors. In this Review, we discuss the prevalence and impact of non-HIV bacterial, viral and parasitic STIs on the reproductive and sexual health of cisgender women worldwide. We analyse factors affecting STI prevalence among transgender women and women in low-income settings, and describe the specific challenges and barriers to improved sexual health faced by these population groups. We also synthesize the latest advances in diagnosis, treatment and prevention of STIs. Women are more affected by sexually transmitted infections than men. This Review examines the impact of non-HIV STIs on women’s health, and discusses recent advances and current challenges in the treatment and prevention of STIs.

An Improved Virtual Inertia Control Strategy for Low Voltage AC Microgrids with Hybrid Energy Storage Systems

Abstract: This paper proposes a novel virtual inertia control (VIC) method based on a feedforward decoupling strategy to address the low inertia issue of power-converter-interfaced microgrids. The feedforward control scheme is employed to eliminate the coupling between active and reactive power caused by line impedance. The active power-voltage droop can be applied to the battery converter in the hybrid energy storage system (HESS). A novel VIC method is developed for the supercapacitor (SC) converter of HESS to increase the inertia of the microgrid. Detailed small-signal modeling of the SC converter with the proposed VIC was conducted, and the transfer function model was obtained. Parameter analysis of the virtual inertia and virtual damping was carried out with the pole-zero map method, and the step response characteristic of output voltage amplitude with power variation was analyzed in detail, deriving the parameter design principle. The simulation study verifies the effectiveness and validity of the proposed control strategy. The proposed feedforward decoupling method and VIC can be widely applied in microgrids to enhance inertia and improve their power quality.

Encapsulation of miRNA and siRNA into Nanomaterials for Cancer Therapeutics

Abstract: Globally, cancer is amongst the most deadly diseases due to the low efficiency of the conventional and obsolete chemotherapeutic methodologies and their many downsides. The poor aqueous solubility of most anticancer medications and their low biocompatibility make them ineligible candidates for the design of delivery systems. A significant drawback associated with chemotherapy is that there are no advanced solutions to multidrug resistance, which poses a major obstacle in cancer management. Since RNA interference (RNAi) can repress the expression of genes, it is viewed as a novel tool for advanced drug delivery. this is being explored as a promising drug targeting strategy for the treatment of multiple diseases, including cancer. However, there are many obstructions that hinder the clinical uses of siRNA drugs due to their low permeation into cells, off-target impacts, and possible unwanted immune responses under physiological circumstances. Thus, in this article, we review the design measures for siRNA conveyance frameworks and potential siRNA and miRNA drug delivery systems for malignant growth treatment, including the use of liposomes, dendrimers, and micelle-based nanovectors and functional polymer-drug delivery systems. This article sums up the advancements and challenges in the use of nanocarriers for siRNA delivery and remarkably centers around the most critical modification strategies for nanocarriers to build multifunctional siRNA and miRNA delivery vectors. In short, we hope this review will throw light on the dark areas of RNA interference, which will further open novel research arenas in the development of RNAi drugs for cancer.

Nurse Burnout Syndrome and Work Environment Impact Patient Safety Grade

Abstract: BACKGROUND Burnout impacts nurses' health as well as brain structures and functions including cognitive function, which could lead to work performance and patient safety issues. Yet, few organization-level factors related to patient safety have been identified. PURPOSE This study examined nurse-reported patient safety grade and its relationship to both burnout and the nursing work environment. METHODS A cross-sectional electronic survey was conducted among nurses (N = 928) in acute care Alabama hospitals. RESULTS In multilevel ordinal mixed-effects models with nurses nested within hospitals, all burnout dimensions of the Copenhagen Burnout Inventory (OR for +1 SD ranging 0.63-0.78; P < .05) and work environment (OR for +1 SD ranging 4.35-4.89; P < .001) were related to the outcome of patient safety grade after controlling for nurse characteristics. CONCLUSIONS Results indicate that health care organizations may reduce negative patient safety ratings by reducing nurse burnout and improving the work environment at the organization level.