Category: Nevin Manimala

Infect Dis Poverty. 2021 May 17;10(1):69. doi: 10.1186/s40249-021-00836-1.

ABSTRACT

BACKGROUND: COVID-19 can lead to increased psychological symptoms such as post-traumatic stress disorder (PTSD), depression, and anxiety among patients with COVID-19. Based on the previous mindfulness-based interventions proved to be effective, this protocol reports a design of a randomized controlled trial aiming to explore the efficacy and possible mechanism of a mindful living with challenge (MLWC) intervention developed for COVID-19 survivors in alleviating their psychological problems caused by both the disease and the pandemic.

METHODS: In April 2021, more than 1600 eligible participants from Hubei Province of China will be assigned 1:1 to an online MLWC intervention group or a waitlist control group. All participants will be asked to complete online questionnaires at baseline, post-program, and 3-month follow-up. The differences of mental health status (e.g. PTSD) and physical symptoms including fatigue and sleeplessness between the COVID-19 survivors who receiving the online MLWC intervention and the control group will be assessed. In addition, the possible mediators and moderators of the link between the MLWC intervention and target outcomes will be evaluated by related verified scales, such as the Five Facets Mindfulness Questionnaire. Data will be analyzed based on an intention-to-treat approach, and SPSS software will be used to perform statistical analysis.

DISCUSSION: The efficacy and potential mechanism of MLWC intervention in improving the quality of life and psychological status of COVID-19 survivors in China are expected to be reported. Findings from this study will shed light on a novel and feasible model in improving the psychological well-being of people during such public health emergencies. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000037524; Registered on August 29, 2020, http://www.chictr.org.cn/showproj.aspx?proj=60034 .

PMID:34001277 | DOI:10.1186/s40249-021-00836-1

Neurol Res Pract. 2021 May 17;3(1):27. doi: 10.1186/s42466-021-00125-0.

ABSTRACT

BACKGROUND: Emergency intubation is an inherent risk of procedural sedation regimens for endovascular treatment (EVT) of acute ischemic stroke. We aimed to characterize the subgroup of patients, who had to be emergently intubated, to identify predictors of the need for intubation and assess their outcomes.

METHODS: This is a retrospective analysis of the single-center study KEEP SIMPLEST, which evaluated a new in-house SOP for EVT under primary procedural sedation. We used descriptive statistics and regression models to examine predictors and functional outcome of emergently intubated patients.

RESULTS: Twenty of 160 (12.5%) patients were emergently intubated. National Institutes of Health Stroke Scale (NIHSS) on admission, premorbid modified Rankin scale (mRS), Alberta Stroke Program Early CT Score, age and side of occlusion were not associated with need for emergency intubation. Emergency intubation was associated with a lower rate of successful reperfusion (OR, 0.174; 95%-CI, 0.045 to 0.663; p = 0.01). Emergently intubated patients had higher in-house mortality (30% vs 6.4%; p = 0.001) and a lower rate of mRS 0-2 at 3 months was observed in those patients (10.5% vs 37%, p = 0.024).

CONCLUSIONS: Emergency intubation during a primary procedural sedation regimen for EVT was associated with lower rate of successful reperfusion. Less favorable outcome was observed in the subgroup of emergently intubated patients. More research is required to find practical predictors of intubation need and to determine, whether emergency intubation is safe under strict primary procedural sedation regimens for EVT.

PMID:34001285 | DOI:10.1186/s42466-021-00125-0

Parasit Vectors. 2021 May 17;14(1):259. doi: 10.1186/s13071-021-04746-x.

ABSTRACT

BACKGROUND: The direct toxicological impact of insecticides on vector mosquitoes has been well emphasized; however, behavioural responses such as excito-repellency and physical avoidance as a result of insecticide exposure have not been much studied. We have demonstrated the excito-repellency and behavioural avoidance in certain vector mosquito species on exposure to a slow-release insecticidal paint (SRIP) formulation in addition to direct toxicity.

METHODS: A SRIP formulation developed by the Defence Research and Development Establishment, Gwalior, contains chlorpyriphos, deltamethrin and pyriproxyfen as active insecticides. Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti mosquitoes were used to study the excito-repellency response of the formulation. The experiments were performed in a specially designed dual-choice exposure and escape chamber made of transparent polymethyl methacrylate. For the experiments, the SRIP formulation was applied undiluted at a rate of 8 m² per kg on 15 cm² metallic surfaces. Mosquitoes were introduced into the exposure chamber, and observations of the movement of mosquitoes into the escape chamber through the exit portal were taken at 1-min intervals for up to 30 min.

RESULTS: The evaluated formulation displayed strong excito-repellency against all three tested vector mosquito species. Results showed that the ET₅₀ (escape time 50%) for Ae. aegypti, An. stephensi and Cx. quinquefasciatus was 20.9 min, 14.5 min and 17.9 min for contact exposure (CE) respectively. Altogether in CE, the escape rates were stronger in An. stephensi mosquitoes at different time intervals compared to Ae. aegypti and Cx. quinquefasciatus mosquitoes. The probit analysis revealed that the determined ET did not deviate from linearity for both non-contact exposure (NCE) and placebo exposure (PE) (χ² ≤ 7.9; p = 1.0) for Ae. aegypti mosquitoes and for NCE (χ² = 8.3; p = 1.0) and PE (χ² = 1.7; p = 1.0) treatments in Cx. quinquefasciatus. Mortality (24 h) was found to be statistically higher (F = 6.4; p = 0.02) in An. stephensi for CE but did not vary for NCE (p ≥ 0.3) and PE (p = 0.6) treatments among the tested mosquito species. Survival probability response suggested that all the three tested species displayed similar survival responses for similar exposures (χ² ≤ 2.3; p ≥ 0.1).

CONCLUSION: The study demonstrates the toxicity and strong behavioural avoidance in known vector mosquito species on exposure to an insecticide-based paint formulation. The combination of insecticides in the present formulation will broaden the overall impact spectrum for protecting users from mosquito bites. The efficacy data generated in the study provide crucial information on the effectiveness of the tested formulation and could be useful in reducing the transmission intensity and disease risk in endemic countries.

PMID:34001242 | DOI:10.1186/s13071-021-04746-x

Borderline Personal Disord Emot Dysregul. 2021 May 17;8(1):17. doi: 10.1186/s40479-021-00157-7.

ABSTRACT

BACKGROUND: Previous studies revealed an association between traumatic childhood experiences and emotional dysregulation in patients with borderline personality disorder (BPD). However, possible mediating pathways are still not fully understood. The aim of the present study was to investigate the potential mediating role of body connection, describing the awareness of the relationship of bodily and mental states, for the association between a history of traumatic childhood experiences and BPD core symptomatology.

METHODS: One-hundred-twelve adult female individuals with BPD and 96 healthy female controls (HC) were included. Impaired emotion regulation, traumatic childhood experiences, and BPD symptomatology were assessed with self-report questionnaires. The Scale of Body Connection was used to assess two dimensions of body connection, that is body awareness, describing attendance to bodily information in daily life and noticing bodily responses to emotions and/or environment and body dissociation, describing a sense of separation from one’s own body, due to avoidance or emotional disconnection. Mann-Whitney U tests were employed to test for group differences (BPD vs. HC) on the two SBC subscales and associations with clinical symptoms were analyzed with Spearman correlations. We performed mediation analyses in the BPD group to test the assumption that body connection could act as a mediator between a history of traumatic childhood experiences and emotion dysregulation.

RESULTS: Individuals with BPD reported significantly lower levels of body awareness and significantly higher levels of body dissociation compared to HC. Body dissociation, traumatic childhood experiences, and emotion dysregulation were significantly positively associated. Further analyses revealed that body dissociation, but not body awareness, significantly and fully mediated the positive relationship between traumatic childhood experiences and impaired emotion regulation in the BPD sample. This mediation survived when trait dissociation, i.e., general dissociative experiences not necessarily related to the body, was statistically controlled for.

CONCLUSION: Certain dimensions of body connection seem to be disturbed in BPD patients, with body dissociation being an important feature linking a history of traumatic childhood experiences to current deficits in emotion regulation.

PMID:34001243 | DOI:10.1186/s40479-021-00157-7

Genome Med. 2021 May 17;13(1):83. doi: 10.1186/s13073-021-00904-z.

ABSTRACT

BACKGROUND: While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods are needed to systematically bridge this crucial gap to facilitate experimental testing of hypotheses and translation to clinical utility.

RESULTS: Here, we leveraged cross-phenotype associations to identify traits with shared genetic architecture, using linkage disequilibrium (LD) information to accurately capture shared SNPs by proxy, and calculate significance of enrichment. This shared genetic architecture was examined across differing biological scales through incorporating data from catalogs of clinical, cellular, and molecular GWAS. We have created an interactive web database (interactive Cross-Phenotype Analysis of GWAS database (iCPAGdb)) to facilitate exploration and allow rapid analysis of user-uploaded GWAS summary statistics. This database revealed well-known relationships among phenotypes, as well as the generation of novel hypotheses to explain the pathophysiology of common diseases. Application of iCPAGdb to a recent GWAS of severe COVID-19 demonstrated unexpected overlap of GWAS signals between COVID-19 and human diseases, including with idiopathic pulmonary fibrosis driven by the DPP9 locus. Transcriptomics from peripheral blood of COVID-19 patients demonstrated that DPP9 was induced in SARS-CoV-2 compared to healthy controls or those with bacterial infection. Further investigation of cross-phenotype SNPs associated with both severe COVID-19 and other human traits demonstrated colocalization of the GWAS signal at the ABO locus with plasma protein levels of a reported receptor of SARS-CoV-2, CD209 (DC-SIGN). This finding points to a possible mechanism whereby glycosylation of CD209 by ABO may regulate COVID-19 disease severity.

CONCLUSIONS: Thus, connecting genetically related traits across phenotypic scales links human diseases to molecular and cellular measurements that can reveal mechanisms and lead to novel biomarkers and therapeutic approaches. The iCPAGdb web portal is accessible at http://cpag.oit.duke.edu and the software code at https://github.com/tbalmat/iCPAGdb .

PMID:34001247 | DOI:10.1186/s13073-021-00904-z

Clin Epigenetics. 2021 May 17;13(1):111. doi: 10.1186/s13148-021-01095-5.

ABSTRACT

Worldwide, colorectal cancer (CRC) is a deadly disease whose death rate ranks second among cancers though its incidence ranks third. Early CRC detection is key and is associated with improved survival outcomes. However, existing tests for CRC diagnosis have several weaknesses thus rendering them inefficient. Moreover, reliable prognostic tests that can predict the overall cancer outcome and recurrence of the disease as well as predictive markers that can assess effectiveness of therapy are still lacking. Thus, shifting to noninvasive liquid biopsy or blood-based biomarkers is vital to improving CRC diagnosis, prognosis, and prediction. Methylated circulating tumor DNA (ctDNA) has gained increased attention as a type of liquid biopsy that is tumor-derived fragmented DNA with epigenetic alterations. Methylated ctDNA are more consistently present in blood of cancer patients as compared to mutated ctDNA. Hence, methylated ctDNA serves as a potential biomarker for CRC that is worth investigating. In this review, we explore what has been reported about methylated ctDNA as a biomarker for CRC diagnosis that can distinguish between CRC patients or those having adenoma and healthy controls as validated specifically through ROC curves. We also examine methylated ctDNA as a biomarker for CRC prognosis and prediction as confirmed through robust statistical analyses. Finally, we discuss the major technical challenges that limits the use of methylated ctDNA for clinical application and suggest possible recommendations to enhance its usage.

PMID:34001239 | DOI:10.1186/s13148-021-01095-5

Genome Med. 2021 May 17;13(1):85. doi: 10.1186/s13073-021-00902-1.

ABSTRACT

BACKGROUND: Single liquid biopsy analytes (LBAs) have been utilized for therapy selection in metastatic breast cancer (MBC). We performed integrative statistical analyses to examine the clinical relevance of using multiple LBAs: matched circulating tumor cell (CTC) mRNA, CTC genomic DNA (gDNA), extracellular vesicle (EV) mRNA, and cell-free DNA (cfDNA).

METHODS: Blood was drawn from 26 hormone receptor-positive, HER2-negative MBC patients. CTC mRNA and EV mRNA were analyzed using a multi-marker qPCR. Plasma from CTC-depleted blood was utilized for cfDNA isolation. gDNA from CTCs was isolated from mRNA-depleted CTC lysates. CTC gDNA and cfDNA were analyzed by targeted sequencing. Hierarchical clustering was performed within each analyte, and its results were combined into a score termed Evaluation of multiple Liquid biopsy analytes In Metastatic breast cancer patients All from one blood sample (ELIMA.score), which calculates the contribution of each analyte to the overall survival prediction. Singular value decomposition (SVD), mutual information calculation, k-means clustering, and graph-theoretic analysis were conducted to elucidate the dependence between individual analytes.

RESULTS: A combination of two/three/four LBAs increased the prevalence of patients with actionable signals. Aggregating the results of hierarchical clustering of individual LBAs into the ELIMA.score resulted in a highly significant correlation with overall survival, thereby bolstering evidence for the additive value of using multiple LBAs. Computation of mutual information indicated that none of the LBAs is independent of the others, but the ability of a single LBA to describe the others is rather limited-only CTC gDNA could partially describe the other three LBAs. SVD revealed that the strongest singular vectors originate from all four LBAs, but a majority originated from CTC gDNA. After k-means clustering of patients based on parameters of all four LBAs, the graph-theoretic analysis revealed CTC ERBB2 variants only in patients belonging to one particular cluster.

CONCLUSIONS: The additional benefits of using all four LBAs were objectively demonstrated in this pilot study, which also indicated a relative dominance of CTC gDNA over the other LBAs. Consequently, a multi-parametric liquid biopsy approach deconvolutes the genomic and transcriptomic complexity and should be considered in clinical practice.

PMID:34001236 | DOI:10.1186/s13073-021-00902-1

Stem Cell Res Ther. 2021 May 17;12(1):289. doi: 10.1186/s13287-021-02305-w.

ABSTRACT

BACKGROUND: Recent studies demonstrated that autologous mitochondria derived from bone marrow mesenchymal stem cells (BMSCs) might be valuable in the treatment of spinal cord injury (SCI). However, the mechanisms of mitochondrial transfer from BMSCs to injured neurons are not fully understood.

METHODS: We modified BMSCs by CD157, a cell surface molecule as a potential regulator mitochondria transfer, then transplanted to SCI rats and co-cultured with OGD injured VSC4.1 motor neuron. We detected extracellular mitochondrial particles derived from BMSCs by transmission electron microscope and measured the CD157/cyclic ADP-ribose signaling pathway-related protein expression by immunohistochemistry and Western blotting assay. The CD157 ADPR-cyclase activity and Fluo-4 AM was used to detect the Ca²⁺ signal. All data were expressed as mean ± SEM. Statistical analysis was analyzed by GraphPad Prism 6 software. Unpaired t-test was used for the analysis of two groups. Multiple comparisons were evaluated by one-way ANOVA or two-way ANOVA.

RESULTS: CD157 on BMSCs was upregulated when co-cultured with injured VSC4.1 motor neurons. Upregulation of CD157 on BMSCs could raise the transfer extracellular mitochondria particles to VSC4.1 motor neurons, gradually regenerate the axon of VSC4.1 motor neuron and reduce the cell apoptosis. Transplantation of CD157-modified BMSCs at the injured sites could significantly improve the functional recovery, axon regeneration, and neuron apoptosis in SCI rats. The level of Ca²⁺ in CD157-modified BMSCs dramatically increased when objected to high concentration cADPR, ATP content, and MMP of BMSCs also increased.

CONCLUSION: The present results suggested that CD157 can regulate the production and transfer of BMSC-derived extracellular mitochondrial particles, enriching the mechanism of the extracellular mitochondrial transfer in BMSCs transplantation and providing a novel strategy to improve the stem cell treatment on SCI.

PMID:34001228 | DOI:10.1186/s13287-021-02305-w

BMC Res Notes. 2021 May 17;14(1):186. doi: 10.1186/s13104-021-05598-5.

ABSTRACT

OBJECTIVE: African ancestry seems to be a risk factor for hypertension; however, few genetic studies have addressed this issue. This study aimed to investigate the prevalence of polymorphisms NOS3; rs1799983, IGFBP3; rs11977526 and TCF7L2; rs7903146 in Brazilian women of African descent and their association with hypertension.

RESULTS: The prevalences of the less frequent genotypes were 26.5% TT genotype of NOS3; rs1799983, 16.7% AA genotype of IGFBP3; rs11977526, and 18.3% TT genotype of TCF7L2; rs7903146. For these conditions, the prevalence of hypertension and PR (adjusted) relatively to the ancestral genotype were, respectively: 52.0% vs 24.5% (PR = 1.54; p < 0.001), 62.0% vs 24.1% (PR = 1.59; p < 0.001), and 38.9% vs 27.9% (PR = 0.86; p = 0.166). Associations with hypertension were statistically significant, except for the TCF7L2; rs7903146 polymorphism, after adjusted analysis. Brazilian Afro-descendant women with the TT genotype for the NOS3 gene and the AA genotype for the IGFBP3 gene are more susceptible to hypertension. The understanding of underlying mechanisms involving the pathogenesis of hypertension can motivate research for the development of new therapeutic targets related to nitric oxide metabolism and the management of oxidative stress.

PMID:34001234 | DOI:10.1186/s13104-021-05598-5

Trials. 2021 May 17;22(1):346. doi: 10.1186/s13063-021-05293-7.

ABSTRACT

BACKGROUND: Up to three quarters of surgical patients receive inadequate pain relief, with 40% of patients reporting severe pain following knee replacement, which may indicate the current pain relief strategies using opiate-based analgesia cannot achieve patient satisfaction. Liposomal bupivacaine is liposome-encapsulated bupivacaine which has been reported to be effective for up to 72 h. The study of Peri-Articular Anaesthetic for Replacement of the Knee (SPAARK) trial has been designed to assess the effectiveness of peri-articular liposomal bupivacaine and bupivacaine hydrochloride compared with peri-articular bupivacaine hydrochloride alone in the management of post-operative pain following knee replacement.

METHODS/DESIGN: The SPAARK trial is a multi-centre, patient-blinded, randomised controlled trial. The co-primary outcomes are post-operative recovery assessed by global QoR-40 scores at 72 h and cumulative pain VAS score from 6 to 72 h following surgery. Longer-term measures of the co-primary outcomes are collected at 6 weeks and 6 and 12 months post randomisation, together with secondary outcomes, i.e. the Oxford Knee Score, and the American Knee Society Score. Cumulative opiate use and fitness for discharge are measured up to 72 h post-surgery. The analysis approaches for the primary and secondary outcomes are described here, as are the descriptive statistics which will be reported. The full SPAARK protocol has already been published.

RESULTS: The co-primary outcomes will be analysed using multivariate linear regression adjusting for stratification factors and other important prognostic variables, including baseline scores in the case of the QoR-40. The adjusted mean difference between the two groups together with 97.5% confidence intervals will be reported for each of the primary outcomes. Other continuous variables will be assessed using the same method. Binary outcomes will be assessed using chi-squared tests.

DISCUSSION: The paper provides details of the planned statistical analyses for the SPAARK trial and aims to reduce the risk of outcome reporting bias from prior data knowledge. Any changes or deviations from this statistical analysis plan will be described and justified in the final study report.

TRIAL REGISTRATION: ISRCTN54191675 . Registered on 13 November 2017.

PMID:34001205 | DOI:10.1186/s13063-021-05293-7