Nevin Manimala

Biosens Bioelectron. 2021 Oct 30;196:113743. doi: 10.1016/j.bios.2021.113743. Online ahead of print.

ABSTRACT

Lipoproteins are composed of lipid and apolipoproteins in conjunction with noncovalent bonds. Different lipoprotein categories, particularly Low-Density Lipoprotein (LDL), High-Density Lipoprotein (HDL) and Very Low-Density Lipoprotein (VLDL) disagree in roles for the occurrence and development of cardiovascular disease, and their exact discrimination are critically required. Herein, a multiplexed sensor platform combined with an encoder system is introduced for accurate analysis of multiple lipoproteins in complex matrix. Three encoders, i.e., bare AuNPs, AuNPs-anti-LDL aptamer (AuNPs-apt) and AuNPs-non-aptamer DNA (AuNPs-n), facilitate precise discrimination for lipoprotein subclasses at a fairly low level of 0.490 nM. The binding of single-stranded DNA (ssDNA) with AuNPs prevents them from gathering in a relatively higher level of salt. In targets stimuli, the weaker binding between ssDNA and AuNPs is destroyed to certain degrees depending on the differential affinities among DNA, AuNPs, and multifarious proteins. It results in distinct aggregation states of encoders to cause diverse ultraviolet absorption, which may be statistically characterized to achieve highly facile and precise identification for lipoprotein subclasses. Remarkably, LDL at 0.05-37.5 μg/mL could be identified by the encoder system. 11 typical proteins including three lipoprotein subclasses in human serum were also precisely discriminated. Furthermore, the accurate identification of lipoprotein subclasses with different molar ratios from real clinical serum samples were obtained.

PMID:34740115 | DOI:10.1016/j.bios.2021.113743

Pharmacol Res Perspect. 2021 Dec;9(6):e00875. doi: 10.1002/prp2.875.

ABSTRACT

We aimed to summarize and describe the burden of serious adverse drug reactions (ADRs) in sub-Saharan Africa (SSA) in the era of antiretroviral therapy. We searched Medline, CINAHL, Africa-Wide Information, Scopus, and Web of Science, without language restriction up to March 2021. We hand-searched reference lists, conference abstracts, and dissertation databases. We included studies reporting proportions of admissions attributed to ADRs, admissions prolonged by ADRs, or in-hospital deaths attributed to ADRs. Two reviewers independently screened the studies, reviewed the study quality using a previously published tool, and extracted the data. We tested for heterogeneity using I² -statistics and summarized the study results using medians and interquartile ranges. Subgroup analyses summarized the results by study quality, setting, methodology, and population. From 1005 unique references identified, we included 15 studies. Median study quality was 7/10; heterogeneity was very high. Median [IQR] proportion of admissions attributed to ADRs was 4.8% [1.5% to 7.0%] (14 studies) and 6.4% [4.0% to 8.4%] in nine active surveillance studies in adults. Two pediatric studies reported the proportion of admissions prolonged by ADRs (0.29% and 0.99%). Three studies reported the proportion of in-hospital deaths attributed to ADRs (2.5%, 13%, and 16%). Antiretroviral and antituberculosis drugs were often implicated in serious ADRs. Evidence of the burden of serious ADRs in SSA is patchy and heterogeneous. A few high-quality studies suggest that the burden is considerable, and that it reflects the regional impact of the HIV pandemic. Further characterization of this burden is required, ideally in studies of standardized methodology.

PMID:34738728 | DOI:10.1002/prp2.875

Luminescence. 2021 Nov 5. doi: 10.1002/bio.4154. Online ahead of print.

ABSTRACT

In this paper, two simple, rapid and highly sensitive spectrofluorimetric methods were developed and validated for nystatin determination in its pure form and pharmaceutical dosage form (oral suspension). The first method is based on measuring of nystatin native fluorescence after dilution with isopropyl alcohol at 407 nm (excitation 303 nm). The floursence intensity is linered dependant on the nystatin concentrartion within the specified range 50-500 ngmL^-1 . The second is based on micellar enhancement of nystatin fluoescence by using sodium dodecyl sulphate (SDS). In the presence of 2% w/v SDS, about 1.9 -fold enhancement can be achieved in the relative fluorescence intensity (RFI) of nystatin. The linear range for the second method was 20-100 ngmL^-1 . The limit of quantification and detection were found to be 43.23 ngmL^-1 and 14.27 ngmL^-1 (method I), 6.08 ngmL^-1 and 2.0 ngmL^-1 (method II). According to percentage recoveries and relative standard deviations (RSDs) obtained, the proposed methods are precise (RSDs were less than 2%), reproducible, and accurate and could be successfully applied for quantitative estimation of nystatin in its dosage form. The statistical results of this method were compared with that of the reported method and showed excellent agreement in respect for accuracy and precision.

PMID:34738720 | DOI:10.1002/bio.4154

Pediatr Transplant. 2021 Nov 5:e14182. doi: 10.1111/petr.14182. Online ahead of print.

ABSTRACT

BACKGROUND: Delayed time to listing (TTL) for pediatric transplant patients is associated with increased risks of mortality and morbidity. The full range of health disparities, sociodemographic factors, and other barriers associated with delays in listing in the pediatric transplant candidate evaluation process has not been fully examined.

METHODS: Retrospective chart reviews were conducted for 183 kidney, liver, and heart transplant candidates ages 0-18 who were referred for evaluation during 2012-2015. Demographic information and potential barriers (e g., social/medical factors, financial concerns) were gathered from pre-transplant evaluations and included in a comprehensive model to evaluate mechanisms that explain differences in TTL. Descriptive statistics, logistic regression models, Cox proportional hazards models, and path analysis were used for analyses.

RESULTS: Candidates included 26.8% heart, 33.3% liver, and 39.9% kidney patients. The most common barrier to listing was financial (71.6%), followed by caregiver psychological or substance use (57.9%), and medical problems (49.7%). Higher age, kidney, and liver organ type (relative to the heart), and presence of social, medical, administrative/motivation, and financial barriers were all directly associated with longer TTL. Public insurance was indirectly associated with TTL through social, administrative/motivation, and financial barriers. Organ type was indirectly associated with TTL through financial barriers.

CONCLUSIONS: Results suggest social problems, administrative issues, and financial issues act as mechanisms through which insurance type and liver transplant candidates face increased risk of delays in transplant listing time. There are numerous clinical implications and interventions that are warranted to reduce TTL among pediatric transplant candidates with co-occurring barriers.

PMID:34738706 | DOI:10.1111/petr.14182

Diabetes Obes Metab. 2021 Nov 5. doi: 10.1111/dom.14598. Online ahead of print.

ABSTRACT

AIMS: To assess the comparative cardiovascular and renal effectiveness of SGLT2 inhibitors vs GLP-1-receptor-agonists in routine clinical practice.

MATERIALS AND METHODS: Cohort study of nationwide registers from Sweden, Denmark and Norway, 2013-2018, including 87525 new users of SGLT2 inhibitors and 63921 new users of GLP-1-receptor-agonists, analyzed intention-to-treat. Coprimary outcomes, analyzed intention to treat, were major adverse cardiovascular events (MACE; myocardial infarction/stroke/cardiovascular death), heart failure (hospitalization for heart failure/heart failure death) and serious renal events (renal replacement therapy/hospitalization for renal events/death from renal causes).

RESULTS: Use of SGLT2 inhibitors vs GLP-1-receptor-agonists, was associated with higher risk of MACE (adjusted incidence rate: 15.2 vs 14.4 events per 1000 person-years; HR 1.07 [95% CI 1.01-1.15]), similar risk of heart failure (6.0 vs 6.0 events per 1000 person-years; HR 1.02 [0.92-1.12]) and lower risk of serious renal events (2.9 vs 4.0 events per 1000 person-years; HR 0.76 [0.66-0.87]). In as-treated analyses, the HR (95% CI) was 1.11 (1.00-1.24) for MACE, 0.88 (0.74-1.04) for heart failure and 0.60 (0.47-0.77) for serious renal events. In secondary outcome analyses, use of SGLT2 inhibitors vs GLP-1-receptor-agonists was not associated with statistically significant differences in risk of myocardial infarction (HR 1.09 [95% CI 1.00-1.19]), cardiovascular death (HR 0.97 [95% CI 0.84-1.12]), death from renal causes (HR 0.75 [95% CI 0.41-1.35]) or any cause death (HR 1.01 [95% CI 0.94-1.09]) while risk of stroke was higher (HR 1.14 [95% CI 1.03-1.26]) and risk of renal replacement therapy (HR 0.74 [95% CI 0.56-0.97]) and hospitalization for renal events (HR 0.75 [95% CI 0.65-0.88]) was lower among users of SGLT2 inhibitors.

CONCLUSIONS: Use of SGLT2 inhibitors vs GLP-1-receptor-agonists was associated with a similar risk of heart failure and lower risk of serious renal events while use of GLP-1-receptor-agonists vs SGLT2 inhibitors was associated with a slightly lower risk of MACE. In as-treated analyses, the associations with MACE and serious renal events increased in magnitude and the HR for heart failure tended towards a protective association for SGLT2 inhibitors. This article is protected by copyright. All rights reserved.

PMID:34738703 | DOI:10.1111/dom.14598

NMR Biomed. 2021 Nov 5:e4638. doi: 10.1002/nbm.4638. Online ahead of print.

ABSTRACT

Nuclear magnetic resonance (NMR) spectroscopy allows for simultaneous detection of a wide range of metabolites and lipids. As metabolites act together in complex metabolic networks, they are often highly correlated, and optimal biological insight is achieved when using methods that take the correlation into account. For this reason, latent-variable-based methods, such as principal component analysis and partial least-squares discriminant analysis, are widely used in metabolomic studies. However, with increasing availability of larger population cohorts, and a shift from analysis of spectral data to using quantified metabolite levels, both more traditional statistical approaches and alternative machine learning methods have become more widely used. This review aims at providing an overview of the current state-of-the-art multivariate methods for the analysis of NMR-based metabolomic data as well as alternative methods, highlighting their strengths and limitations.

PMID:34738674 | DOI:10.1002/nbm.4638

Adv Mater. 2021 Nov 5:e2106674. doi: 10.1002/adma.202106674. Online ahead of print.

ABSTRACT

Defects are ubiquitous in 2D materials and can not only affect the structure and properties of the materials but can also introduce new functionalities. Methods to adjust the structure and density of defects during bottom-up synthesis are required to control the growth of 2D materials with tailored optical and electronic properties. In this paper, w e present a Au-assisted chemical vapor deposition approach to selectively form S_W and S2_W antisite defects, whereby one or two sulfur atoms substitute for a tungsten atom in WS₂ monolayers. Guided by first-principles calculations, w e describe a new method that can maintain tungsten-poor growth conditions relative to sulfur via the low solubility of W atoms in a gold/W alloy, thereby significantly reducing the formation energy of the antisite defects during the growth of monolayer WS₂ . The atomic structure and composition of the antisite defects are unambiguously identified as S_W and S2_W by Z-contrast scanning transmission electron microscopy and electron energy-loss spectroscopy, and their total concentration is statistically determined, with levels observed up to ∼5.0%. Scanning tunneling microscopy/spectroscopy measurements and first-principles calculations further verified these antisite defects and revealed the localized defect states in the bandgap of WS₂ monolayers that are candidates for single photon emitters. This bottom-up synthesis method to form antisite defects should apply in the synthesis of other 2D transition metal dichalcogenides. This article is protected by copyright. All rights reserved.

PMID:34738669 | DOI:10.1002/adma.202106674

Eur J Neurosci. 2021 Nov 5. doi: 10.1111/ejn.15512. Online ahead of print.

ABSTRACT

Lesch-Nyhan disease is a rare, sex-linked, genetic neurodevelopmental disorder that is characterized by hyperuricemia, dystonia, cognitive impairment, and recurrent self-injury. We previously found reduced brain white matter volume in patients with Lesch-Nyhan disease compared to healthy adults using voxel-based morphometry. Here we address the structural integrity of white matter via diffusion tensor imaging. We hypothesized that white matter integrity would be decreased in men with Lesch-Nyhan disease and to a lesser extent in men with a milder variant of the disease (Lesch-Nyhan variant) relative to healthy men. After acquiring diffusion-weighted brain images from Lesch-Nyhan disease (n = 5), Lesch-Nyhan variant (n = 6), and healthy participants (n = 10), we used both Tract-Based Spatial Statistics and a regions of interest approach to analyze between-group fractional anisotropy differences. We first replicated earlier findings of reduced intracranial, gray matter, and white matter volumes in patients. We then discovered marked reductions of fractional anisotropy relative to the healthy control group. The Lesch-Nyhan disease group showed more pronounced reductions in white matter integrity than the Lesch-Nyhan variant group. In addition to whole brain fractional anisotropy group differences, reductions in white matter integrity were observed in the corpus callosum, corona radiata, cingulum, internal capsule, and superior longitudinal fasciculus. Moreover, the variant group had attenuated dystonia severity symptoms and cognitive deficits. These findings highlight the need to better understand the role of white matter in Lesch-Nyhan disease.

PMID:34738666 | DOI:10.1111/ejn.15512

J Bone Miner Res. 2021 Nov 5. doi: 10.1002/jbmr.4465. Online ahead of print.

ABSTRACT

Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analysed the data from a study collecting lumbar CT spine scans at enrolment and 12 months post-treatment with romosozumab (210 mg SC QM, n = 17), open-label daily teriparatide (20 ug SC, n = 19) or placebo (SC QM, n = 20). For each of the 56 women, cortical thickness (CtTh), endocortical thickness (EcTh), cortical BMD (CtBMD), cancellous BMD (CnBMD) and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, colour maps of the changes in the lumbar vertebrae structure were statistically analysed and then visualised on the bone surface. At 12 months Romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral CtTh increase of 10.3% versus 4.3% for teriparatide, an EcTh increase of 137.6% versus 47.5% for teriparatide, a CtBMD increase of 2.1% versus a – 0.2% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated CnBMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared to the change in the placebo group (-4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment, and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. This article is protected by copyright. All rights reserved.

PMID:34738660 | DOI:10.1002/jbmr.4465

Child Care Health Dev. 2021 Nov 5. doi: 10.1111/cch.12922. Online ahead of print.

ABSTRACT

BACKGROUND: Medical rehabilitation plays an important role in the health care of chronically ill children and adolescents. During medical rehabilitation, supporting illness-related self-regulation is a central goal. Beliefs about illness and beliefs about treatment are core elements of patients’ self-regulation, and there is evidence, that these beliefs are relevant predictors of different health- and treatment-related outcomes such as adherence. However, little is known about adolescents’ beliefs about rehabilitation. This study therefore explores adolescents’ treatment beliefs in the context of inpatient medical rehabilitation.

METHODS: A qualitative study was conducted in a German rehabilitation clinic for children and adolescents. Using a purposive sampling method, thirteen adolescents (12-16 years old) were recruited. Semi-structured, audiotaped interviews were conducted and analysed using content analysis.

RESULTS: Results demonstrate that adolescents have differentiated rehabilitation-related treatment beliefs. Twelve themes, with various subthemes, emerged which include access to and knowledge about rehabilitation, the rehabilitation-related individual position and normative aspects, expectations of oneself, as well as in respect of the social context (fellow patients, contact with family and friends), expectations of the structure, process and outcome of rehabilitation, concerns and barriers, and emotional aspects.

CONCLUSIONS: Our explorative study revealed a broad range of rehabilitation-related treatment beliefs in adolescents, indicating parallels, but also differences, to research results with adults. Treatment beliefs are assumed to be an influencing factor for various health- and treatment-related outcomes. Thus, implications of our findings for clinical practice and further research are discussed.

PMID:34738647 | DOI:10.1111/cch.12922