Nevin Manimala

J Clin Lab Anal. 2022 Jan 26:e24251. doi: 10.1002/jcla.24251. Online ahead of print.

ABSTRACT

OBJECTIVES: To explore the immune-related genetic susceptibility of human leukocyte antigen (HLA) alleles and their correlation with panel reactive antibody (PRA) generation during end-stage renal disease (ESRD) progression.

MATERIALS AND METHODS: Data of the expression patterns of HLA-A, -B, and -DR alleles and PRAs of 347 ESRD patients awaiting renal transplantation in Hunan Province from 2015 to 2019 were retrospectively studied. The polymerase chain reaction with sequence-specific primers was used for HLA genotyping and the enzyme-linked immunosorbent assay for PRA detection. SPSS 21.0 software was used for all allele frequency and statistical analyses.

RESULTS: Thirteen HLA-A, 25 HLA-B, and 13 HLA-DR alleles were expressed. The allele frequencies of HLA-A2, -B48, -B52, and -B55 were significantly higher in the case group than in the control group (p < 0.05), whereas that of HLA-B60 was significantly higher in the control group (p < 0.05). The frequency of HLA alleles in the PRA-positive group was significantly higher in females than in males (p < 0.05). The allele frequencies of HLA-A2, -B38, and -B46 were significantly higher in the PRA-positive group than in the PRA-negative one (p < 0.05), whereas that of HLA-60 was significantly higher in the PRA-negative group (p < 0.05).

CONCLUSION: HLA-A2, -B48, -B52, and -B55 may be the ESRD susceptibility alleles in Han Chinese patients in Hunan Province, whereas HLA-B60 may be the protective allele. Patients carrying HLA-A2, -B38, and -B46 are more likely to develop PRA positivity, whereas the opposite is true for those with HLA-B60.

PMID:35083784 | DOI:10.1002/jcla.24251

Stat Med. 2022 Jan 26. doi: 10.1002/sim.9305. Online ahead of print.

ABSTRACT

While the serotypes of Streptococcus pneumoniae are known to compete during colonization in human hosts, our knowledge of how competition occurs is still incomplete. New insights of pneumococcal between-type competition could be generated from carriage data obtained by molecular-based detection methods, which record more complete sets of serotypes involved in co-carriage than when detection is done by culture. Here, we develop a Bayesian estimation method for inferring between-type interactions from longitudinal data recording the presence/absence of the types at discrete observation times. It allows inference from data containing co-carriage of two or more serotypes, which is often the case when pneumococcal presence is determined by molecular-based methods. The computational burden posed by the increased number of types detected in co-carriage is addressed by approximating the likelihood under a multi-state model with the likelihood of only those trajectories with minimum number of acquisition and clearance events between observation times. The proposed method’s performance was validated on simulated data. The estimates of the interaction parameters of acquisition and clearance were unbiased in settings with short sampling intervals between observation times. With less frequent sampling, the estimates of the interaction parameters became more biased, but their ratio, which summarizes the total interaction, remained unbiased. Confounding due to unobserved heterogeneity in exposure could be corrected by including individual-level random effects. In an application to empirical data about pneumococcal carriage in infants, we found new evidence for between-serotype competition in clearance, although the effect size was small.

PMID:35083763 | DOI:10.1002/sim.9305

Biomed Chromatogr. 2022 Jan 26. doi: 10.1002/bmc.5348. Online ahead of print.

ABSTRACT

Chinese hamster ovary (CHO) cells have been widely used in the biopharmaceutical industry for production of therapeutic proteins. CHO cells in fed-batch cultures produce various amino acid-derived intermediate metabolites. These small molecule metabolic byproducts have proven to be critical to cell growth, culture performance, and more interestingly antibody drug productivity. Herein, we developed a liquid chromatography – high resolution mass spectrometry (LC-HRMS) based targeted metabolomics approach for comprehensive quantification of total 21 growth inhibition related metabolites generated from 14 different amino acids in CHO cell fed-batch cultures. High throughput derivatization procedures, matrix-matched calibration curves, stable isotope-labeled internal standards, and accurate mass Full MS scan were utilized in order to achieve our goal for wide scope of metabolite screening as well as validity and reliability of metabolite quantification. We further present a novel analytical strategy for extending the assay’s dynamic range by utilizing naturally occurring isotope M+1 ion as a quantification analogue in the circumstances where the principal M ion is beyond its calibration range. The integrated method was qualified for selectivity, sensitivity, linearity, accuracy, precision, isotope analysis and other analytical aspects to demonstrate assay robustness. We then applied this metabolomics approach to characterize metabolites of interest in a CHO cell based monoclonal antibody (mAb) production process with fed-batch bioreactor culture mode. Absolute quantification combined with multivariate statistical analysis illustrated that our target analytes derived from amino acids, especially from branched-chain amino acids, closely correlated with cell viability and significantly differentiated cellular stages in production process.

PMID:35083760 | DOI:10.1002/bmc.5348

Br J Soc Psychol. 2022 Jan 27. doi: 10.1111/bjso.12518. Online ahead of print.

ABSTRACT

A substantial minority of the public express belief in conspiracy theories. A robust phenomenon in this area is that people who believe one conspiracy theory are more likely to believe in others. But the reason for this “positive manifold” of belief in conspiracy theories is unclear. One possibility is that a single underlying latent factor (e.g. “conspiracism”) causes variation in belief in specific conspiracy theories. Another possibility is that beliefs in various conspiracy theories support one another in a mutually reinforcing network of beliefs (the “monological belief system” theory). While the monological theory has been influential in the literature, the fact that it can be operationalised as a statistical network model has not previously been recognised. In this study, we therefore tested both the unidimensional factor model and a network model. Participants were 1553 American adults recruited via Prolific. Belief in conspiracies was measured using an adapted version of the Belief in Conspiracy Theories Inventory. The fit of the two competing models was evaluated both by using van Bork et al.’s (Psychometrika, 83, 2018, 443, Multivariate Behavioral Research, 56, 2019, 175) method for testing network versus unidimensional factor models, as well as by evaluating goodness of fit to the sample covariance matrix. In both cases, evaluation of fit according to our pre-registered inferential criteria favoured the network model.

PMID:35083755 | DOI:10.1111/bjso.12518

Br J Dermatol. 2022 Jan 26. doi: 10.1111/bjd.21032. Online ahead of print.

ABSTRACT

OBJECTIVES: Prurigo nodularis is a debilitating skin condition that is classified as rare by the Genetic and Rare Diseases Information Center (GARD) and National Organization for Rare Diseases (NORD). There are no estimates of the prevalence of prurigo nodularis in England. We aimed to address this data gap by describing the epidemiology of prurigo nodularis in a representative dataset derived from the English National Health Service.

METHODS: The study utilised data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics inpatient data. Patients with a diagnosis of prurigo nodularis were selected by clinical code in the primary care or inpatient datasets. Case definition was based on a minimum of two distinct diagnoses to maximize specificity. Point prevalence was calculated for the midpoint of 2018 and incidence rates from 2008-2018 presented. For those classified as incident cases, demographic and clinical characteristics were reported. In sensitivity analyses the case definition was modified to relax the multiple diagnosis criteria and to restrict cases to those diagnosed within a maximum of four or ten years of the midpoint prevalence date.

RESULTS: 11,656 patients within the dataset had at least one prurigo nodularis diagnosis. Following application of the relevant inclusion criteria 2,743 patients formed the point prevalent cohort; an estimated prevalence of 3.27 patients per 10,000 (95% CI 3.15-3.40). In sensitivity analyses the estimated prevalence ranged from 2.24 (2.14-2.34) to 6.98 (6.8-7.16). Incidence over the study period was 2.88 per 100,000 patient years. Comorbidity was relatively high in this population notably for atopic dermatitis (52.2%), depression (41.1%) and anxiety (35.4%).

CONCLUSION: This study supports the NORD/GARD classification of prurigo nodularis as a rare disease with a prevalence of 3.27 patients per 10,000 equating to 18,471 patients living with the disease in England in 2018. The relatively high prevalence of comorbidity observed for these patients may increase the complexity of management.

PMID:35083742 | DOI:10.1111/bjd.21032

Anaesthesia. 2022 Jan 27. doi: 10.1111/anae.15650. Online ahead of print.

ABSTRACT

Tramadol is a bitter atypical opioid analgesic drug and is prescribed to treat postoperative pain in children. However, in many countries there is no licensed paediatric tramadol formulation available. We have formulated a novel chewable chocolate-based drug delivery system for the administration of tramadol to children. This pilot, single-centre, open-label, randomised clinical study assessed the taste tolerability and comparative population pharmacokinetics of the novel tramadol chewable tablet against a compounded tramadol hydrochloride oral liquid, at a dose of 1 mg.kg^-1 . A 5-point facial hedonic scale was used by the children, parents and nurses to assess tolerability. One hundred and forty-one children aged 3-16 years were given tramadol 30 min before general anaesthesia. Blood samples were taken following the induction of anaesthesia and for up to 5 h following tramadol administration. Tramadol and its active metabolite O-desmethyltramadol were analysed using reversed-phase high-performance liquid chromatography. A population pharmacokinetic model was built using non-linear mixed effects modelling. The relative bioavailability for the tablet was 1.25 times higher (95%CI 1.16-1.35) than for tramadol hydrochloride oral liquid, while the absorption rate constant for the tablet was significantly lower (1.97 h^-1 vs. 3.34 h^-1 , p < 0.001). Larger inter-individual variability in absorption rates were observed with the liquid tramadol. The tramadol chewable tablet was more acceptable in taste to children when assessed by the children, parents and nurses (all p < 0.001). We conclude that the novel tramadol chewable tablet has favourable acceptability and more reliable relative bioavailability in children compared with tramadol hydrochloride oral liquid.

PMID:35083739 | DOI:10.1111/anae.15650

J Med Toxicol. 2022 Jan 27. doi: 10.1007/s13181-021-00868-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Cardiotoxicity represents the primary cause of death in acute aluminum phosphide (AlP) poisoning. Prompt supportive care can improve patient survival. This study assessed the role of echocardiography in estimating the survival probability of AlP-poisoned patients admitted to the intensive care unit.

METHODS: A prospective cohort study of symptomatic acute AlP poisoned patients was conducted between September 2019 and December 2020. Patients were subjected to history taking, clinical examination, To be included, patient evaluation needed to include electrocardiographic (ECG) and echocardiographic studies. The statistical analysis assessed the association between patient survival and relevant factors. Survival analysis was performed using the Kaplan-Meier survival curve and Cox proportional hazard regression.

RESULTS: A total of 90 patients met inclusion criteria. Electrocardiographic abnormalities were detected in 38.1% of survivors and 82.6% of non-survivors (p < 0.001). Survivors had a higher mean left ventricle ejection fraction (LVEF) (50.86 ± 6.30% vs. 26.52 ± 7.64%, respectively, p < 0.001) and a lower percentage of global LV hypokinesia (4.8% vs. 94.2%, p < 0.001). The mean survival time was higher among patients with LVEF ≥ 50% than those with LVEF = 41-49% and ≤ 40% (p = 0.014 and 0.001, respectively). The hazard of death was 4.42 and 5.40 times greater in patients with LVEF ≤ 40% or with global LV hypokinesia, respectively. Regression revealed that the global LV hypokinesia, ECG abnormalities, and decreased LVEF and oxygen saturation were significantly associated with the risk of death (hazard ratios: 4.382, 3.348, 0.957, and 0.971, respectively).

CONCLUSIONS: Echocardiography represents a valuable diagnostic tool to assess cardiac function in acute AlP poisoning. Both LVEF and global LV hypokinesia significantly impact the survival of AlP-poisoned patients. Echocardiography was superior to ECG changes in terms of accuracy for the prediction of mortality.

PMID:35083735 | DOI:10.1007/s13181-021-00868-x

Environ Sci Pollut Res Int. 2022 Jan 27. doi: 10.1007/s11356-021-18082-1. Online ahead of print.

ABSTRACT

Anthropogenic pollution plays an important part in deteriorating the water quality of rivers all over the world, especially in urban areas of Africa where water quality monitoring is still seriously constrained by the limited test facility and capability. In this study, for evaluating the impact of urbanization on the river water quality, we investigated four typical urban rivers of Tanzania through the upper-urban-down gradient assessment approach and analyzed by water quality index (WQI) and statistical methods. The physicochemical indices monitored in these rivers revealed that the contents of those indicators of TN, TP, PO₄^3-, NH₄⁺, COD_Mn, and NO₃^– were accumulated significantly in the lower reaches of the cities, which indicated the life-type pollution characteristics in such urban rivers of Africa. The following main conclusions are achieved from this study. The water quality of 30% of the investigated river sections is in the medium to good status based on the subjective WQI with sensory factors included. Moreover, the sections with obvious water quality decline are mainly limited to the river segments within the urban central area, and severe pollution of water bodies is closely related to large cities, indicating an increasing pollution tendency with the quickly growing population. Therefore, to help formulate water pollution control policies in response to the rapid urban expansion in African countries, it is necessary to adopt an economical and feasible method to carry out early monitoring of surface water quality timely.

PMID:35083687 | DOI:10.1007/s11356-021-18082-1

Environ Sci Pollut Res Int. 2022 Jan 27. doi: 10.1007/s11356-021-18247-y. Online ahead of print.

ABSTRACT

Up to now, information about biogeochemistry of many trace elements is scarce. Meanwhile, all the elements are always present in soil and plants. It may be suggested that the trace elements also play certain role in the biogeochemical processes. The aim of the research was to study bioaccumulation of poorly investigated trace elements (scandium, cerium, europium, hafnium, and tantalum) and well-known elements (chromium, iron, cobalt, zinc, and arsenic) in two crops, oats and barley, and examine how these elements interact with each other as they absorbed by plants. The plants were grown in the soils that differed in their parameters and in level of contamination. Although oats and barley are botanically similar and were grown under the same conditions, the plants differed in the ability to accumulate many elements. The uptake of the elements by the plants also depended on type of soil. For example, concentrations of Cr, Fe, Co, As, Sc, Ce, Eu, Hf, and Ta in roots of the oats grown in slightly contaminated soil were much higher as compared to the concentrations of the elements in roots of the barley grown in the same soil. In leaves of the oats grown in moderately contaminated soil, the concentrations of Cr, As, Ce, Eu, and Ta were statistically significantly higher than those in leaves of the barley grown in the soil. In soils and in plants, relationships between elements were both similar and different. A statistically significant correlation was found between the poorly investigated trace elements and well-studied elements.

PMID:35083671 | DOI:10.1007/s11356-021-18247-y

Environ Sci Pollut Res Int. 2022 Jan 27. doi: 10.1007/s11356-021-18196-6. Online ahead of print.

ABSTRACT

Epidemiological studies found that exposure to air pollution increases cardiovascular hospitalizations. However, studies on rural-urban differences in associations between hospitalizations for cardiovascular diseases and air pollution are limited. The generalized linear model (GLM) was applied to investigate the associations between cardiovascular hospitalizations and air pollution (SO₂, NO₂, PM_2.5, PM₁₀, CO, and O₃) in Guangxi, southwest China, in 2015 (January 1-December 31). The relative risk of pollutants (SO₂, NO₂) on cardiovascular hospital admissions was significantly different between urban and rural areas. The effect of SO₂ on cardiovascular hospitalizations was higher in urban areas than in rural areas at lag0 to lag3 and cumulative lag01 to lag03. In urban areas, there were positive associations between NO₂ and cardiovascular hospitalizations at lag0, lag1 and cumulative lag01, lag02. In contrast, the effect of NO₂ on cardiovascular hospitalizations was not significant in rural areas. Urban residents were more sensitive than rural residents to SO₂ and NO₂. Subgroup analyses showed statistically significant differences between rural and urban areas in the association between SO₂ and NO₂ and cardiovascular hospitalizations for males. For age groups, people aged ≥ 65 years appeared to be more vulnerable to SO₂ and NO₂ in urban areas. The effects of PM_2.5 PM₁₀, CO, and O₃ on cardiovascular hospitalizations were consistently negative for all groups. Our findings indicated that there were rural-urban differences in associations between cardiovascular hospitalizations and air pollutants. In rural areas, the risk of cardiovascular hospitalizations was mainly influenced by SO₂. Therefore, we expect to pay attention to protecting people from air pollution, particularly for those aged ≥ 65 years in urban areas.

PMID:35083669 | DOI:10.1007/s11356-021-18196-6