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Blood Metabolomic Signatures to Identify Bacterial Infection in Patients with Decompensated Cirrhosis

J Gastrointestin Liver Dis. 2022 Mar 19;31(1):40-47. doi: 10.15403/jgld-4034.

ABSTRACT

BACKGROUND AND AIMS: Bacterial infections are associated with high mortality rates in patients with decompensated cirrhosis. Early diagnosis with the available diagnostic tools is challenging. Metabolomics is a novel technique with a widespread application in hepatology. The aims of our study were to find new biomarkers for decompensated cirrhosis and for those with overlapping bacterial infections.

METHODS: 43 patients with compensated and 54 patients with decompensated cirrhosis were enrolled in the study. In patients with decompensation, a complete infectious workup was performed at admission. Blood and ascitic fluid were collected and stored at -80° C until performing the metabolomic analysis. Statistical analysis was performed using the Metaboanalyst 4.0 software.

RESULTS: 36 patients (66%) in the decompensated group were infected. Among them, 15 had multiple infections; thus, finally, 52 infections were diagnosed. The main metabolic pathways affected in patients with decompensated cirrhosis were those related to lipid metabolism, involving acylcarnitines, stearic acid derivatives, and 12/15 HETE-GABA. N-oleoyl ethanolamine was the most promising biomarker for bacterial infection diagnosis. Moreover, prostaglandin E2/D2/H2 and N-oleoyl alanine levels were higher in Gram- positive infections and ceramides (d16:2/18:0), in Gram-negative infections, respectively. L-phenylalanine (m/z=166.09) and lysophosphatidylethanolamine (18:3/0:0) were the two most relevant identified ascitic biomarkers for spontaneous bacterial peritonitis diagnosis.

CONCLUSIONS: The lipid and energetic metabolic pathways were the most affected in patients with decompensated cirrhosis and those with overlapping infections.

PMID:35306561 | DOI:10.15403/jgld-4034

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Clinical Relevance of Anti-Gliadin Seropositivity in the Ageing Population: A Long-term Follow-up Study

J Gastrointestin Liver Dis. 2022 Mar 19;31(1):11-17. doi: 10.15403/jgld-4025.

ABSTRACT

AIMS: To explore if anti-gliadin antibody (AGA) positivity is associated with overall mortality or morbidity and especially with the development of coeliac disease during long-term gluten exposure.

METHODS: The study population comprised 130 persistently AGA-positive but transglutaminase-2 (anti- TG2) -negative and 52 persistently AGA- and anti-TG2 -negative subjects aged 64-88 years. HLA-typing for DQ2 and DQ8 (coeliac-type HLA) was performed on the AGA-positives. The medical records of the study population were reviewed to compare mortality and morbidity during a long-term follow-up of 12-13 years since the initial antibody analysis.

RESULTS: Mortality or cumulative prevalence of gastroenterological, autoimmune, psychiatric, cardiovascular or any malignant diseases did not differ statistically between the AGA-positives and the AGA-negatives. Neurological diseases were more common in the AGA-negative group (p=0.017), but there was no statistical difference between the prevalence of any particular neurological diseases. Coeliac-type HLA in AGA-positive subjects did not influence mortality or morbidity. However, during the last six to seven years the incidence of immunological diseases was more common in the AGA-positive subjects without coeliac-type HLA than in those with coeliac-type HLA, or in the AGA-negative group (p=0.020). None of the persistently AGA-positive subjects developed clinically diagnosed coeliac disease.

CONCLUSIONS: Gliadin antibody positivity without coeliac disease does not predict mortality or morbidity in the ageing population continuing to consume gluten for over ten years.

PMID:35306543 | DOI:10.15403/jgld-4025

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A systematic review and meta-analysis of toxicity and treatment outcomes with pharmacogenetic-guided dosing compared to standard of care BSA-based fluoropyrimidine dosing

Br J Cancer. 2022 Mar 19. doi: 10.1038/s41416-022-01779-6. Online ahead of print.

ABSTRACT

BACKGROUND: Serious and potentially life-threatening toxicities can occur following 5-fluorouracil/capecitabine exposure. Patients carrying Dihydropyrimidine Dehydrogenase (DPYD) variant alleles associated with decreased enzymatic function are at a greater risk of early/severe 5-fluorouracil/capecitabine toxicity. The objective of this systematic review/meta-analysis was to evaluate treatment outcomes between Pharmacogenetics Guided Dosing (PGD) versus non-PGD and within PGD (DPYD variant allele carriers versus wild type).

METHODS: A systematic review/meta-analysis of original publications indexed in Ovid Medline, Ovid Embase, and the Cochrane CENTRAL (Wiley) library from inception to 7-Dec-2020. Eligible studies evaluated at least one pre-defined treatment outcome measures (toxicity/hospitalisations/survival/overall response/quality of life).

RESULTS: Of 1090 identified publications, 17 met predefined eligibility criteria. The meta-analysis observed reduced incidence of grade 3/4 overall toxicity (Risk Ratio [RR] 0.32 [95% Cl 0.27-0.39], p < 0.00001) and grade 3/4 diarrhoea (RR 0.38 [95% Cl 0.24-0.61], p < 0.0001) among PGD versus non-PGD cohorts. Within PGD cohorts, there was no statistical differences for overall response rates (complete/partial) (RR 1.31 [95% Cl 0.93-1.85], p = 0.12). Similar results were found with stable disease (RR 1.27 [95% Cl 0.66-2.44], p = 0.47).

CONCLUSION: PGD improves patient outcomes in terms of grade 3/4 toxicity, in particular overall toxicity and diarrhoea, without impacting on treatment response.

REGISTRATION NUMBER: The study is registered with PROSPERO, registration number CRD42020223768.

PMID:35306539 | DOI:10.1038/s41416-022-01779-6

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Nevin Manimala Statistics

Parameters from site classification to harmonize MRI clinical studies: Application to a multi-site Parkinson’s disease dataset

Hum Brain Mapp. 2022 Mar 19. doi: 10.1002/hbm.25838. Online ahead of print.

ABSTRACT

Multi-site MRI datasets are crucial for big data research. However, neuroimaging studies must face the batch effect. Here, we propose an approach that uses the predictive probabilities provided by Gaussian processes (GPs) to harmonize clinical-based studies. A multi-site dataset of 216 Parkinson’s disease (PD) patients and 87 healthy subjects (HS) was used. We performed a site GP classification using MRI data. The outcomes estimated from this classification, redefined like Weighted HARMonization PArameters (WHARMPA), were used as regressors in two different clinical studies: A PD versus HS machine learning classification using GP, and a VBM comparison (FWE-p < .05, k = 100). Same studies were also conducted using conventional Boolean site covariates, and without information about site belonging. The results from site GP classification provided high scores, balanced accuracy (BAC) was 98.39% for grey matter images. PD versus HS classification performed better when the WHARMPA were used to harmonize (BAC = 78.60%; AUC = 0.90) than when using the Boolean site information (BAC = 56.31%; AUC = 0.71) and without it (BAC = 57.22%; AUC = 0.73). The VBM analysis harmonized using WHARMPA provided larger and more statistically robust clusters in regions previously reported in PD than when the Boolean site covariates or no corrections were added to the model. In conclusion, WHARMPA might encode global site-effects quantitatively and allow the harmonization of data. This method is user-friendly and provides a powerful solution, without complex implementations, to clean the analyses by removing variability associated with the differences between sites.

PMID:35305545 | DOI:10.1002/hbm.25838

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Advancement in the contemporary clinical diagnosis and treatment strategies of insomnia disorder

Sleep Med. 2022 Mar 1;91:124-140. doi: 10.1016/j.sleep.2022.02.018. Online ahead of print.

ABSTRACT

This review is intended to provide an updated summary of, but not limited to, classification, etiopathogenesis, diagnosis, and treatment strategies for insomnia disorder. The severity of insomnia symptoms irrespective of co-existing primary medical condition/s in the studied patients classified insomnia as ‘insomnia disorder’ to prioritize the clinical attention on insomnia (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). The frequency and duration of symptoms further divided insomnia into chronic, short-term, and other insomnia disorder (International Classification of Sleep Disorders, Third Edition). This disorder is a phenomenal state of hyperarousal developed and perpetuated by environmental, behavioral, cognitive, genetic, socioeconomic, preexisting medical factors. Overarching physiological, cortical, behavioral, and cognition changes in hyperarousal manifest insomnia disorder. It, sometimes, leads to the co-occurrence of other chronic medical condition/s. The contemporary diagnosis of insomnia disorder needs to consider modified diagnostic criteria, growing evidence on insomnia disorder symptoms, associated factors, co-existing medical condition/s (if any) to identify the subjective severity of insomnia disorder and design a treatment plan. The recommended treatment strategies include cognitive-behavioral therapy for insomnia (CBTI) and pharmacotherapy. However, CBTI lacks accessibility, qualified facilitators, and pharmacotherapy has limitations like side effects, physiological tolerance/dependence. The investigation of phytocompounds subdued these drawbacks of existing treatments as some compounds showed anti-insomniac potential. Furthermore, complementary alternative medicines (CAMs) like mindfulness-based practices, acupuncture, listening to music, Yogasanas, Pranayama, digital cognitive behavioral therapy for insomnia (dCBTI) during bedtime proved supportive in insomnia disorder treatment.

PMID:35305527 | DOI:10.1016/j.sleep.2022.02.018

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Longitudinal analysis of aging in place at TigerPlace: Resident function and well-being

Geriatr Nurs. 2022 Mar 16;45:47-54. doi: 10.1016/j.gerinurse.2022.02.030. Online ahead of print.

ABSTRACT

This paper reports on a longitudinal eight-year analysis (2011-2019) of trajectory of function and well-being residents of TigerPlace Aging in Place (AIP) model of care. Residents were routinely assessed using standard health assessment instruments. Average scores from each measure were examined for changes or trends in resident function; decline over time was calculated. Scores for depression, mental health subscale Short Form Health Survey-12 (SF-12) remained stable over time. Mini Mental State Exam declined to mild dementia range (21-24). Physical measures SF-12 physical health subscale, ADLs, and IADLs declined slightly, while fall risk increased over time. When yearly trends in AIP were modeled with a referent group there was no significant worsening of functioning. The length of stay for TigerPlace residents continued to remain stable at nearly 30 months. Residents maintained function in the environment of their choice longer at cost less than nursing homes, and just above residential care cost.

PMID:35305514 | DOI:10.1016/j.gerinurse.2022.02.030

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Evaluation of pulmonary function and exercise capacity after COVID-19 pneumonia

Heart Lung. 2022 Mar 11;54:1-6. doi: 10.1016/j.hrtlng.2022.03.004. Online ahead of print.

ABSTRACT

BACKGROUND: Individuals who suffer from coronavirus disease 2019 (COVID-19) pneumonia may experience pulmonary dysfunction during the chronic period due to pulmonary parenchymal damage after acute disease.

OBJECTIVES: The aim of the present study was to evaluate the pulmonary function and exercise capacity of patients treated for COVID 19 pneumonia after discharge.

METHODS: In this cross-sectional study, 79 people who were hospitalized with COVID-19 between March and October 2020 were evaluated at least two months after discharge. A pulmonary function test and a six-minute walk test were administered to the individuals included in the study.

RESULTS: Restrictive-type disorder was detected in 21.5% of the individuals who were evaluated at least two months after discharge. The forced expiratory volume in the first second (FEV1) and the forced vital capacity (FVC) values of the pulmonary function tests were significantly lower in the individuals with severe/critical clinical disease compared to those with moderate disease (p = 0.004 and p = 0.001, respectively). Although the six-minute walk test (6MWT) distances were lower in the severe/critical group than in the moderate group, the difference was not statistically significant (p > 0.05).

CONCLUSIONS: Individuals who are discharged after hospitalization for COVID-19 pneumonia may develop a restrictive type of pulmonary dysfunction. Therefore, survivors of COVID-19 pneumonia should be evaluated for pulmonary function and rehabilitation needs and should be provided with treatment as required.

PMID:35305515 | DOI:10.1016/j.hrtlng.2022.03.004

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Hippocampal and auditory contributions to speech segmentation

Cortex. 2022 Feb 23;150:1-11. doi: 10.1016/j.cortex.2022.01.017. Online ahead of print.

ABSTRACT

Statistical learning has been proposed as a mechanism to structure and segment the continuous flow of information in several sensory modalities. Previous studies proposed that the medial temporal lobe, and in particular the hippocampus, may be crucial to parse the stream in the visual modality. However, the involvement of the hippocampus in auditory statistical learning, and specifically in speech segmentation is less clear. To explore the role of the hippocampus in speech segmentation based on statistical learning, we exposed seven pharmaco-resistant temporal lobe epilepsy patients to a continuous stream of trisyllabic pseudowords and recorded intracranial stereotaxic electro-encephalography (sEEG). We used frequency-tagging analysis to quantify neuronal synchronization of the hippocampus and auditory regions to the temporal structure of words and syllables of the learning stream. We also analyzed the event-related potentials (ERPs) of the test to evaluate the role of both regions in the recognition of newly segmented words. Results show that while auditory regions highly respond to syllable frequency, the hippocampus responds mostly to word frequency. Moreover, ERPs collected in the hippocampus show clear sensitivity to the familiarity of the items. These findings provide direct evidence of the involvement of the hippocampus in the speech segmentation process and suggest a hierarchical organization of auditory information during speech processing.

PMID:35305505 | DOI:10.1016/j.cortex.2022.01.017

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Amalgamation of comparative protein modeling with quantitative structure-retention relationship for prediction of the chromatographic behavior of peptides

J Chromatogr A. 2022 Mar 12;1669:462967. doi: 10.1016/j.chroma.2022.462967. Online ahead of print.

ABSTRACT

Peptide therapeutics plays a prominent role in medical practice. Both peptides and proteins have been used in several disease conditions like diabetes, cancer, bacterial infections etc. The optimization of a peptide library is a time consuming and expensive chore. The tools of computational chemistry offer a way to optimize the properties of peptides. Quantitative Structure Retention (Chromatographic) Relationships (QSRR) is a powerful tool which statistically derives relationships between chromatographic parameters and descriptors that characterize the molecular structure of analytes. In this paper, we show how Comparative Protein ModelingQuantitative Structure Retention Relationship (acronym ComProM-QSRR) can be used to predict the retention time of peptide sequences. This formalism is founded on our earlier published QSAR methodology HomoSAR. ComProM-QSRR can recognize and distinguish the contribution of amino acids at specific positions in the peptide sequences to the retention phenomena through their related physicochemical properties. This study firmly establishes the fact that this approach can be pragmatically used to predict the retention time to all classes of peptides regardless of size or sequence.

PMID:35305457 | DOI:10.1016/j.chroma.2022.462967

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Isomeric cross sections of the (n, α) reactions on the 90Zr, 93Nb and 92Mo isotopes measured for 13.73 MeV-14.77 MeV and estimated for 10 MeV-20 MeV neutron energies

Appl Radiat Isot. 2022 Mar 11;184:110192. doi: 10.1016/j.apradiso.2022.110192. Online ahead of print.

ABSTRACT

Isomeric cross sections for the 90Zr(n, α)87Srm, 93Nb(n, α)90Ym and 92Mo(n, α)89Zrm reactions were measured at five neutron energies over the range 13.73 MeV-14.77 MeV using the activation technique in combination with high resolution γ-ray spectrometry. In the present work, the cross sections are measured for the 90Zr(n, α)87Srm and 93Nb(n, α)90Ym reactions are referenced to the 27Al(n, α)24Na standard reaction cross section whereas those measured for 92Mo(n, α)89Zrm reaction are referenced to the 56Fe(n, p)56Mn standard reaction cross section. The cross sections for these reactions were also theoretically estimated using the EMPIRE-3.2 and TALYS 1.8 codes over the neutrons energy range of 10 MeV-20 MeV and matched with the experimental cross sections by making a proper choice of the model parameters. A minimum eight different sets of these statistical model calculations were performed by using the consistent sets of model parameters along with the pre-equilibrium mechanism in addition to the direct-reaction and the statistical Hauser-Feshbach (HF) compound nucleus ones. The measured cross sections for these three reactions increase with the increase in neutron energy from 13.73 MeV to 14.77 MeV. As the proton number increased by one when we go from zirconium to niobium or from niobium to molybdenum, the probability of alpha particle emission also increases at each corresponding neutron energy. The present results indicate that the measured cross section at each neutron energy for the 92Mo(n, α)89Zrm reaction is found to be the highest as compared to the other two reactions whereas, for the 90Zr(n, α)87Srm reaction, the measured cross section is found to be the lowest as compared to the other two reactions studied. The results obtained from the present measurement are found to be in good agreement with the calculated reaction cross section based on theoretical models and also with the work reported by earlier authors.

PMID:35305484 | DOI:10.1016/j.apradiso.2022.110192