Nevin Manimala

J Food Biochem. 2021 Mar 29:e13719. doi: 10.1111/jfbc.13719. Online ahead of print.

ABSTRACT

Apoptotic effects of secoisolariciresinol diglucoside (SDG) in 2D and 3D cultures of SW480 cells were investigated. 40-200 μM SDG was used and IC50 values were determined for three different time intervals as 24, 48, or 72 hr for further experiments. BrdU, TUNEL, AIF, and caspase-3 stainings were used. SDG inhibited cell proliferation almost half and half for all time intervals in 2D and 3D cultures and also, induced apoptosis. Apoptotic cell percentages in the control group for 24, 48, and 72 hr were 27.00%, 29.00%, and 28.00%, respectively, while in the SDG treatment group were 59.00%, 61.00%, and 62.00%, respectively. In the spheroid cell culture, apoptotic cell percentages in the control group for 24, 48, and 72 hr were 6.90%, 7.20%, and 7.10%, respectively, while in the SDG treatment group were 19.50%, 19.50%, and 20.70%, respectively. Caspase-3 and AIF antibodies were used to indicate caspase-dependent and -independent apoptotic pathways. Significant increases were seen in both AIF and caspase-3 stainings when compared to the control group but caspase-3 staining results were significantly greater when compared to the AIF staining at all time intervals (p < .05). To prove this, CASP3 gene expression was evaluated by RT-qPCR. Unlike staining results, there was no statistically significant change at 24 hr in 2D and 3D cultures. But, significant upregulation at 48 (2.32-fold in 2D and 2.46-fold in 3D) and 72 hr (5.04-fold in 2D and 6.45-fold in 3D) were seen. PRACTICAL APPLICATIONS: Colon cancer is one of the most prevalent cancer in the developed countries and its etiology is complex. Although the underlying mechanisms are mostly unknown, the link between diet and colon cancer is known and dietary habits can promote cancer or protect against it. In recent years, flaxseed is accepted as a significant functional food ingredient and feeding with it could help in to prevent cancer. Secoisolariciresinol diglucoside is a flaxseed lignan and is metabolized to mammalian lignans by the gut. In the present study, SDG was evaluated for its apoptotic effects in colon carcinoma cell line via monolayer and spheroid cultures using immunohistochemical and gene expression techniques. Findings of this study suggest that SDG may protect against cancers and in particularly against colon cancer and further investigations has to be carried out for detailed underlying mechanisms.

PMID:33778961 | DOI:10.1111/jfbc.13719

Folia Morphol (Warsz). 2021 Mar 29. doi: 10.5603/FM.a2021.0032. Online ahead of print.

ABSTRACT

We aimed to use the “SomnoMed MAS” device, which brings the mandible forward in Obstructive Sleep Apnea Syndrome patients due to mandibular retrognathia, and to examine its effects on facial soft tissues by stereophotogrammetry (3dMD) method. Thirty-one patients with a mean age of 44 years and 6 months were included in the study. SomnoMed MAS, one of the splint appliances that position the mandible in front, was applied to all patients and the changes in facial soft tissues were examined by overlapping the images taken at different times with the 3dMD Face system. The obtained data were analyzed statistically and the level of statistical significance was determined as p≤0.05.Mouth width decreased statistically during T0-T1 period. In T0-T2 period, while crista philtri and labiale inferius points moved backwards, Mouth width, nose width decreased and nasal base width increased. In the T0-T3 period, nasal base width increased statistically, the philtrum width and the mouth width decreased, and the soft tissue nasion point came to the fore.Splint treatment, which positions the mandible in front in adult OSAS patients, affected the middle and lower facial soft tissues with the forward and downward translational movement of the lower jaw.

PMID:33778939 | DOI:10.5603/FM.a2021.0032

J Cancer Res Clin Oncol. 2021 Mar 28. doi: 10.1007/s00432-021-03603-9. Online ahead of print.

ABSTRACT

PURPOSE: Treatment response following transarterial chemoembolization (TACE) is frequently evaluated with Liver Imaging Reporting and Data System Treatment Response (LR-TR) algorithm, but its association with patients’ outcomes is not supported in the literature. The purpose of this study was to provide such data.

METHODS: A retrospective analysis of 99 TACE patients with stage A/B hepatocellular carcinoma according to Barcelona-Clinic Liver Cancer staging system was performed. Two radiologists assessed LR-TR, while a third radiologist re-assessed divergent results. Overall survival (OS) and time to disease progression (TTP) were the primary endpoints of the study, while the Cox proportional hazard model was used for outcome analyses.

RESULTS: Interobserver agreement was substantial between the two readers with κ = 0.69 (95% CI 0.58-0.81). The median OS in viable, equivocal, and non-viable groups were 27, 27, and 73 months, respectively (p < 0.001). However, after adjustment for confounding factors, there was no significant association between initial viable response and OS (HR 0.98 [95% CI 0.37-2.63], p = 0.97), while equivocal response remained statistically significant (HR 3.52. [95% CI 1.27-9.71], p = 0.015). No significant association was noted when viable and equivocal groups were analyzed in aggregate (HR 1.03 [95% CI 0.4-2.4], p = 0.96). The median TTP did not differ between non-viable and viable groups (23 vs 18 months, respectively; p = 0.98). None of the analyzed predictors was associated with TTP.

CONCLUSION: Initial LR-TR response was not an independent predictor for OS nor TTP. The preliminary results suggest the necessity for more aggressive management of equivocal patients.

PMID:33778924 | DOI:10.1007/s00432-021-03603-9

Mol Biol Rep. 2021 Mar 28. doi: 10.1007/s11033-021-06293-1. Online ahead of print.

ABSTRACT

Fanconi anemia (FA) occurs due to genomic instability with predisposition to bone marrow failure, phenotypic abnormalities and cancers. Though mutations in 22 genes leading to DNA repair defect have been identified, the cellular factor such as oxidative stress has also shown to be associated with FA. Nitrosative Stress (NS) is biochemically correlated to many oxidative stress related disorders and the NS as a pathological hallmark in FA has been so far overlooked. We carried out the study first time in Indian patients with FA with an objective to understand the role of NS in the pathogenesis of FA. The study was carried out in 70 FA subjects. The FA subjects were diagnosed by chromosomal breakage analysis. Molecular study was carried out by Next Generation Sequencing and Sanger sequencing. The 3-nitrotyrosine [3-NT] levels were estimated through enzyme-linked immuno-sorbent assay (ELISA) and the nitric oxide synthase genes- NOS1 (c.-420-34221G>A (rs1879417), c.-420-10205C>T (rs499776), c.4286+720G>C (rs81631)) and NOS2 (c.1823C>T (p. Ser608Leu) (rs2297518)) polymorphism were studied by direct sequencing. Chromosomal breakage analysis revealed a high frequency of chromosomal breaks (Mean chromosomal breakage-4.13 ± 1.5 breaks/metaphase) in 70 FA patients as compared to the control. Molecular studies revealed FANCA (58.34%), FANCG (18.34%) and FANCL (16.6%) complementation groups. The 3-nitrotyrosine [3-NT] levels showed to be significantly (p < 0.05) elevated in FA subjects when compared to the age match controls. Genotyping of the NOS2 gene c.1823C>T (p. Ser608Leu) (rs2297518), showed statistically significant (P < 0.05) association with FA. Elevated level of 3-NT is one of the cause of NS and NOS2 gene polymorphism associated with FA is an important target in the treatment regimen.

PMID:33778919 | DOI:10.1007/s11033-021-06293-1

Ann Surg Oncol. 2021 Mar 28. doi: 10.1245/s10434-021-09863-6. Online ahead of print.

ABSTRACT

BACKGROUND: Intraoperative blood cell salvage and autotransfusion (IBSA) during liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial for concern regarding adversely impacting oncologic outcomes.

OBJECTIVE: We aimed to evaluate the long-term oncologic outcomes of patients who underwent LT with incidentally discovered HCC who received IBSA compared with those who did not receive IBSA.

METHODS: Patients undergoing LT (January 2001-October 2018) with incidental HCC on explant pathology were retrospectively identified. A 1:1 propensity score matching (PSM) was performed. HCC recurrence and patient survival were compared. Kaplan-Meier survival analyses were performed, and univariable Cox proportional hazard analyses were performed for risks of recurrence and death.

RESULTS: Overall, 110 patients were identified (IBSA, n = 76 [69.1%]; non-IBSA, n = 34 [30.9%]). Before matching, the groups were similar in terms of demographics, transplant, and tumor characteristics. Overall survival was similar for IBSA and non-IBSA at 1, 3, and 5 years (96.0%, 88.4%, 83.0% vs. 97.1%, 91.1%, 87.8%, respectively; p = 0.79). Similarly, the recurrence rate at 1, 3, and 5 years was not statistically different (IBSA 0%, 1.8%, 1.8% vs. non-IBSA 0%, 3.2%, 3.2%, respectively; p = 0.55). After 1:1 matching (26 IBSA, 26 non-IBSA), Cox proportional hazard analysis demonstrated similar risk of death and recurrence between the groups (IBSA hazard ratio [HR] of death 1.26, 95% confidence interval [CI] 0.52-3.05, p = 0.61; and HR of recurrence 2.64, 95% CI 0.28-25.30, p = 0.40).

CONCLUSIONS: IBSA does not appear to adversely impact oncologic outcomes in patients undergoing LT with incidental HCC. This evidence further supports the need for randomized trials evaluating the impact of IBSA use in LT for HCC.

PMID:33778907 | DOI:10.1245/s10434-021-09863-6

J Rehabil Med. 2021 Mar 29. doi: 10.2340/16501977-2821. Online ahead of print.

ABSTRACT

OBJECTIVE: To perform a European survey of the evidence needs and training demands of insurance medicine professionals related to professional tasks and evidence-based practice.

DESIGN: International survey.

SUBJECTS: Professionals working in insurance medicine.

METHODS: Experts designed an online questionnaire including 26 questions related to 4 themes: evidence needs; training demands; evidence-seeking behaviour; and attitudes towards evidence-based medicine. Descriptive statistics were presented by country/conference and the total sample.

RESULTS: A total of 782 participants responded. Half of participants experienced evidence needs at least once a week, related to mental disorders (79%), musculoskeletal disorders (67%) and occupational health (65%). Guidelines (76%) and systematic reviews (60%) were the preferred types of evidence and were requested for assessment of work capacity (64%) and prognosis of return-to-work (51%). Evidence-based medicine was thought to facilitate decision-making in insurance medicine (95%). Fifty-two percent of participants felt comfortable finding, reading, interpreting, and applying evidence. Countries expressed similar needs for reviews on typical topics.

CONCLUSION: This study reveals evidence gaps in key areas of insurance medicine, supporting the need for further research, guidelines and training in evidence-based insurance medicine. Importantly, insurance medicine professionals should recognize that evidence-based practice is crucial in producing high-quality assessments.

PMID:33778897 | DOI:10.2340/16501977-2821

Europace. 2021 Mar 29:euab013. doi: 10.1093/europace/euab013. Online ahead of print.

ABSTRACT

AIMS : The COVID-19 pandemic has led to a decline in hospitalizations for non-COVID-19-related conditions. We explored the impact of the COVID-19 pandemic on cardiac operations and interventions undertaken in England.

METHODS AND RESULTS : An administrative database covering hospital activity for England, the Health Episodes Statistics, was used to assess a total of 286 697 hospitalizations for cardiac operations and interventions, as well as 227 257 hospitalizations for myocardial infarction (MI) and 453 799 for heart failure (HF) from 7 January 2019 to 26 July 2020. Over the 3 months of ‘lockdown’, total numbers and mean reductions in weekly rates [n (-%)], compared with the same time period in 2019, were: coronary artery bypass grafting [-2507 (-64%)]; percutaneous coronary intervention [-5245 (-28%)]; surgical [-1324 (-41%)] and transcatheter [-284 (-21%)] aortic valve replacement; mitral valve replacement; implantation of pacemakers [-6450 (-44%)], cardiac resynchronization therapy with [-356 (-42%)] or without [-491 (-46%)] defibrillation devices, and implantable cardioverter-defibrillators [-501 (-45%)]; atrial fibrillation ablation [-1902 (-83%)], and other ablations [-1712 (-64%)] (all P < 0.001). Over this period, there were 21 038 fewer procedures than in the reference period in 2019 (P < 0.001). These changes paralleled reductions in hospitalizations for MI [-10 794 (-27%)] and HF [-63 058 (-28%)] (both P < 0.001).

CONCLUSIONS : The COVID-19 pandemic has led to substantial reductions in the number of cardiac operations and interventions undertaken. An alternative strategy for healthcare delivery to patients with cardiac conditions during the COVID-19 pandemic is urgently needed.

PMID:33778881 | DOI:10.1093/europace/euab013

J Appl Lab Med. 2021 Mar 29:jfab004. doi: 10.1093/jalm/jfab004. Online ahead of print.

ABSTRACT

BACKGROUND: Traumatic brain injury (TBI) is a significant public health issue affecting nearly 69 million patients worldwide per year. Reliable diagnostic biomarkers are urgently needed to aid in disease diagnosis and prognosis and to guide patient aftercare. Blood biomarkers represent an attractive modality to quickly, cheaply, and objectively evaluate clinical status. We hypothesize that deep and quantitative plasma proteomic profiling with a novel technology, proximity extension assay, may lead to the discovery of diagnostic and/or prognostic biomarkers of TBI.

METHODS: We used high-throughput proximity extension assays (PEA) to quantify the relative abundance of over 1000 unique proteins in plasma. PEA is a highly sensitive multiplex immunoassay capable of detecting very low-abundance proteins (down to fg/mL) in complex biological matrices. Our patient cohort consisted of severe TBI (sTBI) patients, matched healthy controls, and another non-TBI group that was included in the analysis to validate the specificity of the candidates during the selection process. The obtained protein quantification data was then filtered to identify candidate biomarkers through statistical analysis, literature searches, and comparison to our reference control groups.

RESULTS: Overall, we identified 6 novel candidate TBI biomarkers. Candidates exhibit a significant increase in plasma protein abundance in sTBI when comparing between healthy controls and sTBI patients. Candidates generally had low expression in our reference groups compared with the sTBI group.

CONCLUSIONS: Our preliminary findings represent a starting point for future validation. These biomarkers, either alone or in combination, may have significant clinical utility in aiding in TBI diagnosis, prognosis, and/or management.

PMID:33778875 | DOI:10.1093/jalm/jfab004

Alcohol Alcohol. 2021 Mar 29:agab016. doi: 10.1093/alcalc/agab016. Online ahead of print.

ABSTRACT

AIMS: This meta-analysis reviewed 15 clinical trials (18 study sites/arms), examining the efficacy of an integrated cognitive-behavioral intervention (CBI) delivered to individuals with an alcohol or other drug use disorder and a co-occurring mental health disorder (AOD/MHD). Outcomes were alcohol or other drug use and mental health symptoms at post-treatment through follow-up.

METHODS: The inverse-variance weighted effect size was calculated for each study and pooled under random effects assumptions.

RESULTS: Integrated CBI showed a small effect size for AOD (g = 0.188, P = 0.061; I2 = 86%, τ2 = 0.126, k = 18) and MHD (g = 0.169, P = 0.024; I2 = 58%, τ2 = 0.052, k = 18) outcomes, although only MHD outcomes were statistically significant. Analysis by subgroup suggested that effect magnitude varied by type of contrast condition (integrated CBI + usual care vs. usual care only; integrated CBI vs. a single-disorder intervention), follow-up time point (post-treatment vs. 3-6 months) and primary AOD/MHD diagnosis, although these sub-groups often contained significant residual heterogeneity. In a series of mixed effects, meta-regression models, demographic factors were non-significant predictors of between-study heterogeneity. For AOD outcomes, greater effects were observed in higher quality studies, but study quality was not related to effect size variability for MHD outcomes.

CONCLUSIONS: The current meta-analysis shows a small and variable effect for integrated CBI with the most promising effect sizes observed for integrated CBI compared with a single disorder intervention (typically an AOD-only intervention) for follow-up outcomes, and for interventions targeting alcohol use and/or post-traumatic stress disorder. Given the clinical and methodological variability within the sample, results should be considered a preliminary, but important step forward in our understanding of treatment for co-occurring AOD/MHD.

PMID:33778869 | DOI:10.1093/alcalc/agab016

Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Mar 25:S2451-9022(21)00086-0. doi: 10.1016/j.bpsc.2021.03.009. Online ahead of print.

ABSTRACT

BACKGROUND: Stressful life events (SLEs) is an important causal factor in depression, the mechanism of which, however, remains unclear. Recent studies suggested that white matter (WM) micro-structures might be a potential mediator between SLEs and depression. Hence, we intended to investigate the concrete correspondence among them using the mediation effect models.

METHODS: WM micro-structures of 194 participants with SLEs experience prospectively recruited from 6 residential communities were detected with diffusion tensor imaging (DTI). The relationship with each other among SLEs, WM micro-structures and depression were respectively explored with multiple linear regression models and logistic regression models. Furthermore, the influence of WM micro-structures on the association between SLEs and depression was tested with the mediation effect models.

RESULTS: The successfully established mediation effect models showed the specific influence of fractional anisotropy (FA) of the corpus callosum and left uncinate fasciculus on the association between SLEs and depression onset (ab path = 0.032; ab path = 0.026) and depressive severity (ab path = 0.052; ab path = 0.067). The significantly total mediation effects on the association between SLEs and depression onset (ab path = 0.031) and severity (ab path = 0.075) through FA of the corpus callosum and left uncinate fasciculus also were found.

CONCLUSIONS: WM micro-structures alterations imposed a substantial mediation effect on the association between SLEs and depression, which suggested the changes in the WM micro-structures integrity might increase the risk of depression onset and unfavorable disease courses induced by the SLEs.

PMID:33775928 | DOI:10.1016/j.bpsc.2021.03.009