Nevin Manimala

J Pain Palliat Care Pharmacother. 2023 Dec 18:1-8. doi: 10.1080/15360288.2023.2288093. Online ahead of print.

ABSTRACT

Treating palliative cancer patients with antithrombotics is challenging because of the higher risk for both venous thromboembolism and major bleeding. There is a lack of available guidelines on deprescribing potentially inappropriate antithrombotics. We have therefore created an antithrombotics scheme to aid in (de)prescribing antithrombotics. A retrospective single-center clinical cohort observational study was performed to evaluate it. Patients with solid tumors with a life expectancy of less than 3 months seen by the palliative team were included. Comparisons were made between patients who were treated according to the antithrombotics scheme and those who were not. 47.6% of patients used antithrombotics. One hundred and eleven patients were included for analysis. Most patients used antithrombotics according to the scheme (n = 80, 72.1%). Eleven patients experienced a clinical event, seven patients in the scheme adherence group (9.9%) and four in the no scheme adherence group (13.8%), which was not statistically significant (p = 0.726). The higher frequency of clinical events in the group without scheme adherence suggests that (de)prescribing antithrombotics according to the antithrombotics scheme is safe. The results of this study suggest that the antithrombotics scheme could aid healthcare professionals identifying possible inappropriate antithrombotics in palliative cancer patients. Further prospective research is needed to investigate this tool.

PMID:38109061 | DOI:10.1080/15360288.2023.2288093

Chem Biodivers. 2023 Dec 18:e202301213. doi: 10.1002/cbdv.202301213. Online ahead of print.

ABSTRACT

Ecotoxicological risk assessments form the foundation of regulatory decisions for industrial chemicals used in various sectors. In this study, a multi-target-QSAR model established by a backpropagation neural network trained with the Levenberg-Marquardt (LM) algorithm was used to construct a statistically robust and easily interpretable Mt-QSAR model with high external predictability for the simultaneous prediction of the environmental fate in form of octanol-water partition coefficient (LogP), (BCF) and acute oral toxicity in mammals and birds (LD_50rat ) and (LD_50bird ) for a wide range of chemical structural classes of insecticides. Principal component analysis was performed on descriptors selected by the SW-MLR method, and the selected PCs were used for constructing the SW-MLR-PCA-ANN model. The developed well-trained model (RMSE=0.83, MPE=0.004, CCC=0.82, IIC=0.78, R² =0.69) was statistically robust as indicated by the external validation parameters (RMSE=0.93, MPE=0.008, CCC=0.77, IIC=0.68, R² =0.61). The AD of the developed Mt-QSAR model was also defined to identify the most reliable predictions. Finally, the missing values in the dataset for the aforementioned targets were predicted using the constructed Mt-QSAR model. The proposed approach can be used for simultaneous prediction of the environmental fate of new insecticides, especially ones that haven’t been tested yet.

PMID:38109053 | DOI:10.1002/cbdv.202301213

J Autism Dev Disord. 2023 Dec 18. doi: 10.1007/s10803-023-06209-x. Online ahead of print.

ABSTRACT

PURPOSE: This article aims to determine the oral health status, the dental treatment, the behavioral management techniques, and the follow-up of pediatric autistic spectrum disorder (ASD) patients treated at the Clinic for Pediatric Patients with Disabilities (CPPD) at a public university in Brazil.

METHODS: The medical records of all the patients seen between 1990 and 2020 were evaluated. Data were collected on the autistic patients’ medical and dental conditions, treatments, behavior during dental visits, behavioral management techniques used, and the entire follow-up period at the clinic. The Student’s t-test and chi-square tests were used to perform the statistical analysis (α = 0.05%).

RESULTS: Sixty-six records of ASD children were analyzed from a total of 656 dental records. The majority were male (80.3%). The mean age was 7.39 ± 2.75 years. All the children had a cognitive deficit, and 62.5% used medication. Most of the children arrived with caries lesions (56.1%), and the mean number of decayed, missed and filled teeth in both the deciduous (dmft-d) and permanent dentition (DMFT) was 2.45 ± 3.13 and 0.87 ± 1.51, respectively. The restorative technique was the most commonly used procedure (54.5%), and protective stabilization was the most frequently used behavioral management technique (18.2%). Of the children who sought treatment, 86.4% were discharged, and 15.2% abandoned the procedure. The majority (those discharged) continued to undergo regular follow-up at the clinic (86%), and the incidence of new caries lesions observed was 33.33% Conclusions: Although our ASD patients had a high frequency of caries and dental treatment needs, we observed good adherence to the treatment, with a low dropout rate, and high discharge rate.

PMID:38109033 | DOI:10.1007/s10803-023-06209-x

Behav Genet. 2023 Dec 18. doi: 10.1007/s10519-023-10170-x. Online ahead of print.

ABSTRACT

Contemporary genome-wide association study (GWAS) methods typically do not account for variability in genetic effects throughout development. We applied genomic structural equation modeling to combine developmentally-informative phenotype data and GWAS to create polygenic scores (PGS) for alcohol use frequency that are specific to developmental stage. Longitudinal cohort studies targeted for gene-identification analyses include the Collaborative Study on the Genetics of Alcoholism (adolescence n = 1,118, early adulthood n = 2,762, adulthood n = 5,255), the National Longitudinal Study of Adolescent to Adult Health (adolescence n = 3,089, early adulthood n = 3,993, adulthood n = 5,149), and the Avon Longitudinal Study of Parents and Children (ALSPAC; adolescence n = 5,382, early adulthood n = 3,613). PGS validation analyses were conducted in the COGA sample using an alternate version of the discovery analysis with COGA removed. Results suggest that genetic liability for alcohol use frequency in adolescence may be distinct from genetic liability for alcohol use frequency later in developmental periods. The age-specific PGS predicts an increase of 4 drinking days per year per PGS standard deviation when modeled separately from the common factor PGS in adulthood. The current work was underpowered at all steps of the analysis plan. Though small sample sizes and low statistical power limit the substantive conclusions that can be drawn regarding these research questions, this work provides a foundation for future genetic studies of developmental variability in the genetic underpinnings of alcohol use behaviors and genetically-informed, age-matched phenotype prediction.

PMID:38108996 | DOI:10.1007/s10519-023-10170-x

Oral Radiol. 2023 Dec 18. doi: 10.1007/s11282-023-00728-0. Online ahead of print.

ABSTRACT

OBJECTIVES: Low-dose-rate brachytherapy (LDR-BT) with ¹⁹⁸Au grains and ¹⁹²Ir pins is an essential treatment option for oral cancer due to its high rate of local control and low invasiveness. However, the radiation exposure of medical radiation workers is concerning. Thus, we aimed to determine the radiation dose delivered to medical radiation workers during LDR-BT using ¹⁹⁸Au grains and ¹⁹²Ir pins for oral cancer.

METHODS: Thirty-two patients with oral cancer underwent ¹⁹⁸Au grain interstitial LDR-BT between June 2016 and May 2023, and 23 patients with tongue cancer underwent ¹⁹²Ir pin interstitial LDR-BT between March 2015 and November 2017 at our hospital. Dosimetry was performed by attaching a dosimeter to the chest pocket of the operator and assistant during ¹⁹⁸Au grain or ¹⁹²Ir pin LDR-BT. Since the operator also loads ¹⁹⁸Au grains into the implantation device, the operator’s radiation dose includes the dose received during this preparation.

RESULTS: Mean radiation doses of the operators with ¹⁹⁸Au grain and ¹⁹²Ir pin LDR-BT were 165.8 and 211.2 μSv, respectively. Statistically significant differences between the radioactive sources of ¹⁹⁸Au grain and ¹⁹²Ir pin LDR-BT were observed (p = 0.0459). The mean radiation doses of the assistants with ¹⁹⁸Au grain and ¹⁹²Ir pin LDR-BT were 92.0 and 162.0 μSv, respectively. Statistically significant differences were observed between the radioactive sources of ¹⁹⁸Au grains and ¹⁹²Ir pin LDR-BT (p = 0.0003).

CONCLUSIONS: Regarding radioactive source differences, ¹⁹²Ir pin LDR-BT resulted in higher doses delivered to medical radiation workers than ¹⁹⁸Au grain LDR-BT.

PMID:38108954 | DOI:10.1007/s11282-023-00728-0

Prev Sci. 2023 Dec 18. doi: 10.1007/s11121-023-01601-6. Online ahead of print.

ABSTRACT

Exposure to certain chemicals prenatally and in childhood can impact development and may increase risk for attention-deficit/hyperactivity disorder (ADHD). Leveraging a larger set of literature searches conducted to synthesize results from longitudinal studies of potentially modifiable risk factors for childhood ADHD, we present meta-analytic results from 66 studies that examined the associations between early chemical exposures and later ADHD diagnosis or symptoms. Studies were eligible for inclusion if the chemical exposure occurred at least 6 months prior to measurement of ADHD diagnosis or symptomatology. Included papers were published between 1975 and 2019 on exposure to anesthetics (n = 5), cadmium (n = 3), hexachlorobenzene (n = 4), lead (n = 22), mercury (n = 12), organophosphates (n = 7), and polychlorinated biphenyls (n = 13). Analyses are presented for each chemical exposure by type of ADHD outcome reported (categorical vs. continuous), type of ADHD measurement (overall measures of ADHD, ADHD symptoms only, ADHD diagnosis only, inattention only, hyperactivity/impulsivity only), and timing of exposure (prenatal vs. childhood vs. cumulative), whenever at least 3 relevant effect sizes were available. Childhood lead exposure was positively associated with ADHD diagnosis and symptoms in all analyses except for the prenatal analyses (odds ratios (ORs) ranging from 1.60 to 2.62, correlation coefficients (CCs) ranging from 0.14 to 0.16). Other statistically significant associations were limited to organophosphates (CC = 0.11, 95% confidence interval (CI): 0.03-0.19 for continuous measures of ADHD outcomes overall), polychlorinated biphenyls (CC = 0.08, 95% CI: 0.02-0.14 for continuous measures of inattention as the outcome), and both prenatal and childhood mercury exposure (CC = 0.02, 95% CI: 0.00-0.04 for continuous measures of ADHD outcomes overall for either exposure window). Our findings provide further support for negative impacts of prenatal and/or childhood exposure to certain chemicals and raise the possibility that primary prevention and targeted screening could prevent or mitigate ADHD symptomatology. Furthermore, these findings support the need for regular review of regulations as our scientific understanding of the risks posed by these chemicals evolves.

PMID:38108946 | DOI:10.1007/s11121-023-01601-6

J Clin Monit Comput. 2023 Dec 18. doi: 10.1007/s10877-023-01104-3. Online ahead of print.

ABSTRACT

Intensive care unit (ICU) nurses frequently manually titrate norepinephrine to maintain a predefined mean arterial pressure (MAP) target after high-risk surgery. However, achieving this task is often suboptimal. We have developed a closed-loop vasopressor (CLV) controller to better maintain MAP within a narrow range. After ethical committee approval, fifty-three patients admitted to the ICU following high-risk abdominal surgery were randomized to CLV or manual norepinephrine titration. In both groups, the aim was to maintain MAP in the predefined target of 80-90 mmHg. Fluid administration was standardized in the two groups using an advanced hemodynamic monitoring device. The primary outcome of our study was the percentage of time patients were in the MAP target. Over the 2-hour study period, the percentage of time with MAP in target was greater in the CLV group than in the control group (median: IQR_25-75: 80 [68-88]% vs. 42 [22-65]%), difference 37.2, 95% CI (23.0-49.2); p < 0.001). Percentage time with MAP under 80 mmHg (1 [0-5]% vs. 26 [16-75]%, p < 0.001) and MAP under 65 mmHg (0 [0-0]% vs. 0 [0-4]%, p = 0.017) were both lower in the CLV group than in the control group. The percentage of time with a MAP > 90 mmHg was not statistically different between groups. In patients admitted to the ICU after high-risk abdominal surgery, closed-loop control of norepinephrine infusion better maintained a MAP target of 80 to 90 mmHg and significantly decreased postoperative hypotensive when compared to manual norepinephrine titration.

PMID:38108944 | DOI:10.1007/s10877-023-01104-3

Biochem Genet. 2023 Dec 18. doi: 10.1007/s10528-023-10574-8. Online ahead of print.

ABSTRACT

Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment.

METHODS: 554 UCEC tumor samples and 23 normal samples’ RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes’ expression patterns were confirmed.

RESULTS: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks’ respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated.

CONCLUSIONS: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic.

PMID:38108937 | DOI:10.1007/s10528-023-10574-8

J Neurol. 2023 Dec 18. doi: 10.1007/s00415-023-12136-9. Online ahead of print.

ABSTRACT

BACKGROUND: Postural instability (PI) is a common disabling symptom in Parkinson’s disease (PD), but little is known on its pathophysiological basis.

OBJECTIVE: In this study, we aimed to identify the brain structures associated with PI in PD patients, using different MRI approaches.

METHODS: We consecutively enrolled 142 PD patients and 45 control subjects. PI was assessed using the MDS-UPDRS-III pull-test item (PT). A whole-brain regression analysis identified brain areas where grey matter (GM) volume correlated with the PT score in PD patients. Voxel-based morphometry (VBM) and Tract-Based Spatial Statistics (TBSS) were also used to compare unsteady (PT ≥ 1) and steady (PT = 0) PD patients. Associations between GM volume in regions of interest (ROI) and several clinical features were then investigated using LASSO regression analysis.

RESULTS: PI was present in 44.4% of PD patients. The whole-brain approach identified the bilateral inferior frontal gyrus (IFG) and superior temporal gyrus (STG) as the only regions associated with the presence of postural instability. VBM analysis showed reduced GM volume in fronto-temporal areas (superior, middle, medial and inferior frontal gyrus, and STG) in unsteady compared with steady PD patients, and the GM volume of these regions was selectively associated with the PT score and not with any other motor or non-motor symptom.

CONCLUSIONS: This study demonstrates a significant atrophy of fronto-temporal regions in unsteady PD patients, suggesting that these brain areas may play a role in the pathophysiological mechanisms underlying postural instability in PD. This result paves the way for further studies on postural instability in Parkinsonism.

PMID:38108896 | DOI:10.1007/s00415-023-12136-9

Mikrochim Acta. 2023 Dec 18;191(1):36. doi: 10.1007/s00604-023-06120-3.

ABSTRACT

A highly sensitive colorimetric method (glycan-based nano(e)zyme) was developed for sensitive and rapid detection of the SARS-CoV-2 virus based on N-acetyl neuraminic acid (sialic acid)-functionalized gold nanoparticles (SA-Au NZs). A number of techniques were used to characterize the prepared nanomaterials including XRD, FT-IR, UV-vis, DLS, and TEM. DLS analysis indicates an average hydrodynamic size of 34 nm, whereas TEM analysis indicates an average particle size of 15.78 nm. This observation confirms that water interacts with nanoparticle surfaces, resulting in a large hydrodynamic diameter. The peroxidase-like activity of SA-Au NZs was examined with SARS-CoV-2 and influenza viruses (influenza A (H1N1), influenza A (H3N2), and influenza B). UV-visible spectroscopy was used to monitor and record the results, as well as naked eye detection (photographs). SA-Au NZs exhibit a change in color from light red to purple when SARS-CoV-2 is present, and they exhibit a redshift in their spectrum. N-acetyl neuraminic acid interacts with SARS-CoV-2 spike glycoprotein, confirming its ability to bind glycans. As a result, SA-Au NZs can detect COVID-19 with sensitivity and specificity of over 95% and 98%, respectively. This method was approved by testing saliva samples from 533 suspected individuals at Ghaem Hospital of Mashhad, Mashhad, Iran. Sensitivity and specificity were calculated by comparing the results with the definitive results. The positive results were accompanied by a color change from bright red to purple within five minutes. Statistical analysis was performed based on variables such as age, gender, smoking, diabetes, hypertension, and lung involvement. In clinical trials, it was demonstrated that this method can be used to diagnose SARS-CoV-2 in a variety of places, such as medical centers, hospitals, airports, universities, and schools.

PMID:38108890 | DOI:10.1007/s00604-023-06120-3