Nevin Manimala

J Subst Abuse Treat. 2021 Jun 3;130:108521. doi: 10.1016/j.jsat.2021.108521. Online ahead of print.

ABSTRACT

BACKGROUND: Methadone use for the management of opioid dependency during pregnancy is commonplace. Methadone levels are altered during pregnancy due to changes in maternal physiology. Despite this, a paucity of data exist regarding the most appropriate optimal dosing regimens during pregnancy.

METHODS: This study applied a pharmacokinetic modeling approach to examine gestational changes in R- and S-methadone concentrations in maternal plasma and fetal (cord) blood. This study did so to derive a theoretical optimal dosing regimen during pregnancy, and to identify the impact of Cytochromes P450 (CYP) 2B6 and 2C19 polymorphisms on methadone maternal and fetal pharmacokinetics.

RESULTS: The study noted significant decreases in maternal R- and S-methadone plasma concentrations during gestation, with concomitant increases in fetal levels. At a dose of 90 mg once daily, 75% (R-) and 94% (S-) of maternal methadone trough levels were below the lower therapeutic window at term (week 40). The developed optimal dosing regimen escalated doses to 110 mg by week 5, followed by 10 mg increments every 5 weeks up to a maximum of 180 mg once daily near term. This increase resulted in 27% (R-) and 11% (S-) of subjects with trough levels below the lower therapeutic window at term. CYP2B6 poor metabolizers (PM) and either CYP2C19 extensive metabolizers (EM), PM, or ultra-rapid (UM) metabolizer phenotypes demonstrated statistically significant increases in concentrations when compared to their matched CYP2B6 EM counterparts.

CONCLUSIONS: Specific and gestation-dependent dose titrations are required during pregnancy to reduce the risks associated with illicit drug use and to maintain fetal safety.

PMID:34118695 | DOI:10.1016/j.jsat.2021.108521

J Neurol Sci. 2021 Jun 1;427:117518. doi: 10.1016/j.jns.2021.117518. Online ahead of print.

ABSTRACT

BACKGROUND: Age-related white matter lesions (WML) are common, impact neuronal connectivity, and affect motor function and cognition. In addition to pathological nigrostriatal losses, WML are also common co-morbidities in Parkinson’s disease (PD) that affect postural stability and gait. Automated brain volume measures are increasingly incorporated into the clinical reporting workflow to facilitate precision in medicine. Recently, multi-modal segmentation algorithms have been developed to overcome challenges with WML quantification based on single-modality input.

OBJECTIVE: We evaluated WML volumes and their distribution in a case-control cohort of PD patients to predict the domain-specific clinical severity using a fully automated multi-modal segmentation algorithm.

METHODS: Fifty-five subjects comprising of twenty PD patients and thirty-five age- and gender-matched control subjects underwent standardized motor/gait and cognitive assessments and brain MRI. Spatially differentiated WML obtained using automated segmentation algorithms on multi-modal MPRAGE and FLAIR images were used to predict domain-specific clinical severity. Preliminary statistical analysis focused on describing the relationship between WML and clinical scores, and the distribution of WML by brain regions. Subsequent stepwise regressions were performed to predict each clinical score using WML volumes in different brain regions, while controlling for age.

RESULTS: WML volume strongly correlates with both motor and cognitive dysfunctions in PD patients (p < 0.05), with differential impact in the frontal lobe and periventricular regions on cognitive domains (p < 0.01) and severity of motor deficits (p < 0.01), respectively.

CONCLUSION: Automated multi-modal segmentation algorithms may facilitate precision medicine through regional WML load quantification, which show potential as imaging biomarkers for predicting domain-specific disease severity in PD.

PMID:34118693 | DOI:10.1016/j.jns.2021.117518

Soc Sci Med. 2021 May 31;281:114090. doi: 10.1016/j.socscimed.2021.114090. Online ahead of print.

ABSTRACT

BACKGROUND: Promoting good hand hygiene in older children is an important measure to reduce the burden of common diseases such as diarrhoea and acute respiratory infections. The evidence around what works to change this behaviour, however, is unclear.

OBJECTIVES: To aid future intervention design and effective use of resources, this review aims to identify the individual components used in hand hygiene interventions and assesses their contribution to intended behavioural change.

METHODS: We systematically searched seven databases for experimental studies evaluating hand hygiene interventions targeting children (age 5-12) and quantitively reporting hand hygiene behaviour. Interventions in each study were categorised as ‘promising’, or ‘non-promising’ according to whether they led to a positive change in the targeted behaviour. Behaviour change techniques (BCTs) were identified across interventions using a standard taxonomy and a novel promise ratio calculated for each (the ratio of promising to non-promising interventions featuring the BCT). ‘Promising’ BCTs were those with a promise ratio of ≥2. BCTs were ranked from most to least promising.

RESULTS: Our final analysis included 19 studies reporting 22 interventions across which 32 unique BCTs were identified. The most frequently used were ‘demonstration of the behaviour’, ‘instruction on how to perform the behaviour’ and ‘adding objects to the environment’. Eight BCTs had a promise ratio of ≥2 and the five most promising were ‘demonstration of the behaviour’, ‘information about social and environmental consequences’, ‘salience of consequences’, ‘adding objects to the environment’, and ‘instruction on how to perform the behaviour’.

CONCLUSIONS: Our findings suggest that hand hygiene interventions targeting older children should employ a combination of promising BCTs that ensure children understand the behaviour and the consequences of their hand hygiene habits, appropriate hardware is available, and social support is provided. Researchers are encouraged to consistently and transparently describe evaluated interventions to allow promising components to be identified and replicated.

PMID:34118686 | DOI:10.1016/j.socscimed.2021.114090

Sci Total Environ. 2021 May 29;791:148101. doi: 10.1016/j.scitotenv.2021.148101. Online ahead of print.

ABSTRACT

The assessment of pasture quality in permanent grasslands is essential for their conservation and management, as it can contribute to making real-time decisions for livestock management. In this study, we assessed the potential of Sentinel-2 configuration to predict forage quality in high diverse Mediterranean permanent grasslands of open woodlands. We evaluated the performance of Partial Least Squares Regression (PLS) models to predict crude protein (CP), neutral detergent fibre (NDF), acid detergent fibre (ADF) and enzyme digestibility of organic matter (EDOM) by using three different reflectance datasets: (i) laboratory measurements of reflectance of dry and ground pasture samples re-sampled to Sentinel-2 configuration (Spec-lab) (ii) field in-situ measurements of grasslands canopy reflectance resampled to Sentinel-2 configuration (Spec-field); (iii) and Bottom Of Atmosphere Sentinel-2 imagery. For the three reflectance datasets, the models to predict CP content showed moderate performance and predictive ability. Mean R²_test = 0.68 were obtained using Spec-lab data, mean R²_test decreased by 0.11 with Spec-field and by 0.18 when Sentinel-2 reflectance was used. Statistics for NDF showed worse predictions than those obtained for CP: predictions produced with Spec-lab showed mean R²_test = 0.64 and mean RPD_test = 1.73. The mean values of R²_test = 0.50 and RPD_test = 1.54 using Sentinel-2 BOA reflectance were marginally better than the values obtained with Spec-field (mean R²_test = 0.48, mean RPD_test = 1.43). For ADF and EDOM, only predictions made with Spec-lab produced acceptable results. Bands from the red-edge region, especially band 5, and the SWIR regions showed the highest contribution to estimating CP and NDF. Bands 2, blue and 4, red also seem to be important. The implementation of field spectroscopy in combination with Sentinel-2 imagery proved to be feasible to produce forage quality maps and to develop larger datasets. This study contributes to increasing knowledge of the potential and applicability of Sentinel-2 to predict the quality of Mediterranean permanent grasslands in open woodlands.

PMID:34118678 | DOI:10.1016/j.scitotenv.2021.148101

Sci Total Environ. 2021 Jun 3;791:148127. doi: 10.1016/j.scitotenv.2021.148127. Online ahead of print.

ABSTRACT

In order to trace the sources of sediment materials and trace metals in the Weser River system (Germany), and the riverine input to the North Sea, Sr, Nd and Pb isotopes, together with multi-elemental compositions, were measured for sediments collected over the entire Weser River Basin, from headwaters to the estuary. Mass fractions of metals, including Ag, Cd, and Pb, and of one metalloid, Sb, higher than their crustal abundance, were observed within the entire Weser Basin. Isotope-amount ratio n(⁸⁷Sr)/n(⁸⁶Sr) and ε_Nd ranged from 0.71182 ± 0.00005 to 0.72880 ± 0.00009 and -11.3 ± 0.3 to -21.0 ± 0.3, respectively. n(²⁰⁶Pb)/n(²⁰⁴Pb), n(²⁰⁷Pb)/n(²⁰⁴Pb), and n(²⁰⁸Pb)/n(²⁰⁴Pb) ranged from 18.226 ± 0.008 to 18.703 ± 0.012, 15.613 ± 0.007 to 15.653 ± 0.012 and 38.14 ± 0.02 to 38.84 ± 0.02, respectively. Sr and Nd isotope compositions reflected primarily a mixture of natural materials derived from the Weser Basin. Pb isotope signatures indicated strong anthropogenic influences in the middle-lower Weser region. Pb isotopic compositions in the sediments from the Aller (tributary of the Weser) and its tributary suggested influence from historical Pb-Zn ore mining in the Harz Mountains that might contribute to the observed elevated mass fractions of Ag, Cd, Sb and Pb in that region. K-means cluster and principal component analysis of the Sr, Nd, and Pb isotope data yielded results consistent with their isotope systematics, supporting statistical analysis as an unsupervised tool in isotope fingerprinting studies. Sr, Nd, and Pb isotopic signatures in the sediments of the Weser were distinctively different from those of another major river discharging into the North Sea, the Elbe. This suggested that this Sr, Nd, and Pb isotope dataset can be used to distinguish riverine input of sediment materials and metals between the two rivers, thereby assessing their individual contribution to materials transported into the North Sea.

PMID:34118659 | DOI:10.1016/j.scitotenv.2021.148127

Environ Int. 2021 Jun 9;155:106678. doi: 10.1016/j.envint.2021.106678. Online ahead of print.

ABSTRACT

Ten years of nationally representative biomonitoring data collected between 2007 and 2017 are available from the Canadian Health Measures Survey (CHMS). These data establish baseline environmental chemical concentrations in the general population. Here we sought to evaluate temporal trends in environmental chemical exposures in the Canadian population by quantifying changes in biomarker concentrations measured in the first five two-year cycles of the CHMS. We identified 39 chemicals that were measured in blood or urine in at least three cycles and had detection rates over 50% in the Canadian population. We calculated geometric mean concentrations for each cycle using the survey weights provided. We then conducted analyses of variance to test for linear trends over all cycles. We also calculated the percent difference in geometric means between the first and most recent cycle measured. Of the 39 chemicals examined, we found statistically significant trends across cycles for 21 chemicals. Trends were decreasing for 19 chemicals from diverse chemical groups, including metals and trace elements, phenols and parabens, organophosphate pesticides, per- and polyfluoroalkyl substances, and plasticizers. Significant reductions in chemical concentrations included di-2-ethylhexyl phthalate (DEHP; 75% decrease), perfluorooctane sulfate (PFOS; 61% decrease), perfluorooctanoic acid (PFOA; 58% decrease), dimethylphosphate (DMP; 40% decrease), lead (33% decrease), and bisphenol A (BPA; 32% decrease). Trends were increasing for two pyrethroid pesticide metabolites, including a 110% increase between 2007 and 2017 for 3-phenoxybenzoic acid (3-PBA). No significant trends were observed for the remaining 18 chemicals that included arsenic, mercury, fluoride, acrylamide, volatile organic compounds, and polycyclic aromatic hydrocarbons. National biomonitoring data indicate that concentrations, and therefore exposures, have decreased for many priority chemicals in the Canadian population. Concentrations for other chemical groups have not changed or have increased, although average concentrations remain below thresholds of concern derived from human exposure guidance values. Continued collection of national biomonitoring data is necessary to monitor trends in exposures over time.

PMID:34118655 | DOI:10.1016/j.envint.2021.106678

Parkinsonism Relat Disord. 2021 Jun 1;88:46-50. doi: 10.1016/j.parkreldis.2021.05.022. Online ahead of print.

ABSTRACT

OBJECTIVE: In the present work, we aimed to investigate the expression of microRNAs (miRNAs) in routine colonic biopsies obtained from patients with idiopathic Parkinson’s disease (PD) and to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression.

METHODS: Patients with PD (n = 13) and healthy controls (n = 17) were prospectively recruited to undergo routine colonic biopsies for cancer screening. Total RNA was extracted from the biopsy material and the expression of miRNAs was quantified by Illumina High-Throughput Sequencing.

RESULTS: Statistical analysis revealed a significant submucosal enrichment of the miRNA hsa-miR-486-5p in colonic biopsies from PD patients compared to the control subjects. The expression of miR-486-5p correlated with age and disease severity as measured by the UPDRS and Hoehn & Yahr scale. miRNA gene target analysis identified 301 gene targets that are affected by miR-486-5p. A follow-up associated target identification and pathway enrichment analysis further determined their role in distinct biological processes in the enteric nervous system (ENS).

INTERPRETATION: Our work demonstrates an enrichment of submucosal miR-486-5p in routine colonic biopsies from PD patients. Our results will support the examination of miR-486-5p as a PD biomarker and help to understand the significance of the miR-486-5p gene targets for PD onset and progression. In addition, our data will support the investigation of the molecular and cellular mechanisms of GI dysfunction in PD.

PMID:34118643 | DOI:10.1016/j.parkreldis.2021.05.022

Chemosphere. 2021 Jun 4;282:131104. doi: 10.1016/j.chemosphere.2021.131104. Online ahead of print.

ABSTRACT

River biofilm communities are the first ones to be exposed to all toxic discharges received via run off from agricultural fields. Hence, changes in river biofilm community structure and growth pattern are considered as indicator of overall health of lotic ecosystem. Toxicants have effect on biofilm biomass, photosynthetic efficiency and chlorophyll a concentrations. Mathematical models may be applied to estimate the overall vigor of riverine ecosystems considering biofilms as indicators. Herein, previous empirical data of Ricart et al. (2009) on long term effects of environmentally relevant concentrations of diuron on biofilm communities of the River Llobregat, Spain was considered as our model inputs. Our objective is to understand the influence of diuron, chlorophyll a concentrations and photosynthetic efficiency on biovolume using a statistical model. The non-linear relationships between biovolume (dependent variable) and diuron, chlorophyll a concentrations and photosynthetic efficiency (independent variables) were represented by constructing three separate basis functions based on day 8 empirical data. Biovolume, due to nonlinear influence as yielded by the basis functions were used in a multiple linear regression model to estimate the net biovolume. Model validation was done based on day 29 empirical data. The experimentally determined biovolume and our model estimated biovolume showed similar trends. Also, diuron and photosynthetic efficiency had significant (p < 0.05) influence on biovolume. Since, the predominance of diatoms as biofilms within periphytic layers is very common in lotic systems, estimation of changes in diatom biovolume will be significant to assess the effect of herbicides. Diatom biovolume of any day (for example day 22) mentioned in the experimental study may be determined by this model, without the requirement of tedious manual biovolume calculation. Our model will be useful in numerous other studies undertaken on the toxic effect of pollutants on biofilms to quickly and accurately estimate the biofilm biovolume.

PMID:34118626 | DOI:10.1016/j.chemosphere.2021.131104

Knee. 2021 Jun 9;31:64-76. doi: 10.1016/j.knee.2021.05.009. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of the present study was to compare the accuracy of prosthetic alignment with three-dimensional computed tomography (3DCT) measurements following total knee arthroplasty (TKA) performed using a robotic-assisted surgical technique versus a conventional TKA.

METHODS: 41 TKAs were performed with a handheld robotic-assisted surgical procedure (Robot group) between 2019 and 2020. Another 41 patients underwent TKA with a conventional manual surgical procedure (Manual group) using the same prosthesis. The operation durations between both groups were investigated. 3DCT scans of the entire lower extremities were taken before and after the surgery and femoral and tibial alignments in the coronal, sagittal, and axial planes were measured using computer software. The differences in prosthetic alignment and translation between the preoperative 3DCT plan and postoperative 3DCT image were also measured.

RESULTS: There were no statistically significant differences in the post-operative outliers of the femorotibial angle between the groups. In the tibial-axial plane, the mean of prosthetic alignment in the anteroposterior plane was 4.0° in the Robot group and 6.7° in the Manual group (p < 0.01). The rate of outliers for tibial-axial alignment in the Robot group was significantly less than in the Manual group (p < 0.01). There were no statistically significant differences in prosthetic translation in the proximal-distal, anterior-posterior and medial-lateral orientations between the groups.

CONCLUSIONS: In a radiologic study using 3DCT, robotic-assisted TKA reduced the outliers for rotational alignment of the tibial prosthesis in comparison to conventional TKA, which can lead to improved tracking of the femoral-tibial bearing surfaces.

PMID:34118583 | DOI:10.1016/j.knee.2021.05.009

Mult Scler Relat Disord. 2021 May 7;52:103003. doi: 10.1016/j.msard.2021.103003. Online ahead of print.

ABSTRACT

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is an autoimmune disorder of the central nervous system. Dimethyl Fumarate is a disease-modifying medication used to treat RRMS patients that can induce lymphopenia. We aimed to immunophenotype peripheral blood mononuclear cells (PBMC) in RRMS patients cross-sectionally and examine the characteristics and modifications of lymphopenia over time.

METHODS: Characterization of PBMC was done by multiparametric flow cytometry. Patients had been on treatment for up to 4 years and were grouped into lymphopenic (DMF-L) and non-lymphopenic (DMF-N) patients.

RESULTS: Lymphopenia affected the cell population changes over time, with other patient characteristics (gender, age, and previous treatment status) also having significant effects. In both lymphopenic and non-lymphopenic patients, PBMC percentages were reduced over time. While overall T and B cells frequencies were not affected, males, older patients and untreated patients had significant changes in B cell subpopulations over time. CD4⁺ to CD8⁺T cell ratio increased significantly in lymphopenic patients over time. CD4^–CD8^–T cell population was similarly reduced in both lymphopenic and non-lymphopenic patients, over time. While the monocyte and NK overall populations were not changed, non-classical monocyte subpopulation decreased over time in lymphopenic patients. We also found CD56^–CD16⁺ and CD56^–CD16^– NK cells frequencies changed over time in lymphopenic patients. Immune populations showed correlations with clinical outcomes measured by EDSS and relapse rate. Analysis of the overall immunophenotype showed that, while groups divided by other patient characteristics showed differences, the lymphopenia status overrode these differences, resulting in similar immunophenotype within DMF-L.

CONCLUSIONS: Our data provide evidence that under the same therapy, lymphopenia affects how the immunophenotype changes over time and can override the differences associated with other patient characteristics and possibly mask other significant changes in the immune profile of patients.

PMID:34118574 | DOI:10.1016/j.msard.2021.103003