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Nevin Manimala Statistics

Genetics, not the uterine environment, drive the formation of trophoblast inclusions: Insights from a twin study

Placenta. 2021 Apr 18:S0143-4004(21)00128-4. doi: 10.1016/j.placenta.2021.04.010. Online ahead of print.

ABSTRACT

INTRODUCTION: Trophoblast inclusions (TIs) are associated with aneuploidy and pregnancy loss and have thus been considered to be a marker of genetic abnormality. However, to date, no study has specifically explored whether TIs are a manifestation of fetal genetics or, rather, the result of the intrauterine environment. The goal of this study was to compare the frequency of TIs in the placentas of monozygotic (MZ) and dizygotic (DZ) twin pairs in order to determine whether the formation of TIs is genetically driven or not.

METHODS: We performed a retrospective case series of placentas from 48 twin pairs. The placentas were grouped based on zygosity: MZ, DZ, or unknown (UZ). The average number of total TIs per slide was calculated for each twin individual and the mean absolute difference in the total TIs per slide between the twin pairs was calculated for each zygosity group and compared.

RESULTS: The mean difference in the total TIs per slide for DZ twins was significantly greater than the mean difference in the total TIs per slide for MZ twins (p = 0.003). The mean difference in the total TIs per slide for the UZ group was also significantly greater than the mean difference in total TIs per slide between MZ twin pairs (p = 0.028).

DISCUSSION: Our finding that MZ twins were significantly more concordant than DZ twins for the average number of TIs per slide supports the conclusion that TIs are intrinsic to the genetics of the fetus, not the uterine environment.

PMID:33941390 | DOI:10.1016/j.placenta.2021.04.010

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Combined Effect of a Polygenic Risk Score and Rare Genetic Variants on Prostate Cancer Risk

Eur Urol. 2021 May 1:S0302-2838(21)00253-0. doi: 10.1016/j.eururo.2021.04.013. Online ahead of print.

ABSTRACT

Although prostate cancer is known to have a strong genetic basis and is influenced by both common and rare variants, the ability to investigate the combined effect of such genetic risk factors has been limited to date. We conducted an investigation of 81 094 men from the UK Biobank, including 3568 prostate cancer cases, to examine the combined effect of rare pathogenic/likely pathogenic/deleterious (P/LP/D) germline variants and common prostate cancer risk variants, measured using a polygenic risk score (PRS), on prostate cancer risk. The absolute risk of prostate cancer for HOXB13, BRCA2, ATM, and CHEK2 P/LP/D carriers ranged from 9% to 56%, and the absolute risk in noncarriers ranged from 2% to 31%, by age 85 yr, for men in the lowest and highest PRS decile, respectively. The high-penetrant HOXB13 G84E prostate cancer risk variant was most common in cases in the lowest PRS quintile (4.4%) and least common in cases in the highest PRS quintile (0.5%; p = 0.005), whereas there was no statistically significant difference in frequencies by PRS in controls. While rare and common variants strongly and distinctly influence prostate cancer onset, consideration of rare and common variants in conjunction will lead to more precise estimates of a man’s lifetime risk of prostate cancer. PATIENT SUMMARY: We found that the risk of prostate cancer conveyed by rare variants could vary depending on an individual’s genetic profile of common risk variants. This implies that in order to comprehensively assess genetic risk of prostate cancer, it is important to consider both rare and common variants.

PMID:33941403 | DOI:10.1016/j.eururo.2021.04.013

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The regression of the bovine tuberculin reaction: Results from the Reactor Quality Assurance study in Northern Ireland

Vet J. 2021 Jun;272:105664. doi: 10.1016/j.tvjl.2021.105664. Epub 2021 Mar 26.

ABSTRACT

Tuberculin skin tests remain widely used in the control of bovine tuberculosis (bTB) in cattle. Little is known about the rate of regression of tuberculin reactions after the comparative intradermal cervical test (CICT) in cattle. This study aimed to collect data to describe tuberculin regression in reactors following the CICT at 72 ± 4 h post injection. Reactors were also tested using the interferon gamma (IFN-γ) assay to establish if any pattern existed between these results and the CICT reaction regression. The data were derived from 108 herds, 112 herd-level CICTs and 1008 animals. A multivariable linear mixed model was built to explore the regression of the bovine tuberculin reaction over time and the influence of potential predictors. The results confirmed a proportional decline in the bovine tuberculin reaction occurred over time. The predictors in the final model demonstrated that regression of the tuberculin reaction differed between reactors according to their IFN-γ test results and whether visible lesions were present at slaughter. Follow-up measurement of tuberculin reactions and the serial use of the IFN-γ assay in large breakdowns has the potential to provide both a mechanism for quality assurance of the current CICT bTB surveillance and the identification of atypical breakdowns or reactors requiring further investigation.

PMID:33941331 | DOI:10.1016/j.tvjl.2021.105664

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68Ga-PSMA-11 PET, 18F-PSMA-1007 PET, and MRI for Gross Tumor Volume Delineation in Primary Prostate Cancer: Intermodality and Intertracer Variability

Pract Radiat Oncol. 2021 May-Jun;11(3):202-211. doi: 10.1016/j.prro.2020.11.006.

ABSTRACT

PURPOSE: To assess the intermodality and intertracer variability of gallium-68 (68Ga)- or fluorine-18 (18F)-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and biparametric magnetic resonance imaging (bpMRI)-based gross tumor volume (GTV) delineation for focal boosting in primary prostate cancer.

METHODS: Nineteen prospectively enrolled patients with prostate cancer underwent a PSMA PET/MRI scan, divided into a 1:1 ratio between 68Ga-PSMA-11 and 18F-PSMA-1007, before radical prostatectomy (IWT140193). Four delineation teams performed manual contouring of the GTV based on bpMRI and PSMA PET imaging, separately. Index lesion coverage (overlap%) and interobserver variability were assessed. Furthermore, the distribution of the voxelwise normalized standardized uptake values (SUV%) was determined for the majority-voted (>50%) GTV (GTVmajority) and whole prostate gland to investigate intertracer variability. The median patientwise SUV% contrast ratio (SUV%-CR, calculated as median GTVmajority SUV% / median prostate gland without GTVmajority SUV%) was calculated according to the tracer used.

RESULTS: A significant difference in overlap% favoring PSMA PET compared with bpMRI was found in the 18F subgroup (median, 63.0% vs 53.1%; P = .004) but was not present in the 68Ga subgroup (32.5% vs 50.6%; P = .100). Regarding interobserver variability, measured Sørensen-Dice coefficients (0.58 vs 0.72) and calculated mean distances to agreement (2.44 mm vs 1.22 mm) were statistically significantly lower and higher, respectively, for the 18F cohort compared with the 68Ga cohort. For the bpMRI-based delineations, the median Sørensen-Dice coefficient and mean distance to agreement were 0.63 and 1.76 mm, respectively. Median patientwise SUV%-CRs of 1.8 (interquartile range [IQR], 1.6-2.7) for 18F-PSMA and 3.3 (IQR, 2.7-5.9) for 68Ga-PSMA PET images were found.

CONCLUSIONS: Both MRI and PSMA PET provided consistent intraprostatic GTV lesion detection. However, the PSMA tracer seems to have a major influence on the contour characteristics, owing to an apparent difference in SUV% distribution in the prostate gland.

PMID:33941347 | DOI:10.1016/j.prro.2020.11.006

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Study on the independent effect of thyroid hormone based on uric acid level on NAFLD

J Health Popul Nutr. 2021 May 3;40(1):21. doi: 10.1186/s41043-021-00247-w.

ABSTRACT

OBJECTIVE: This study aims to explain the correlation among non-alcoholic fatty liver disease (NAFLD), hyperuricemia, and thyroid function and to find independent risk factors for each other.

METHODS: Data were obtained from subjects who underwent health examination in the Health Promotion Centre of Sir Run Run Shaw Hospital of Zhejiang University from January 2017 to February 2019. The diagnosis of NAFLD was according to the clinical diagnosis of the guidelines. Serum uric acid (SUA) > 360 μmol/L (female) and SUA > 420 μmol/L (male) were enrolled in the hyperuricemia group. R software was used for statistical analysis.

RESULTS: 55,449 subjects were included in the analysis. 34.27% of patients were classified as NAFLD group (N=19004), and 65.73% of patients were classified as non-NAFLD group (N=36445). The levels of gender ratio, age, BMI, waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), HbA1c, triglyceride (TG), high-density lipoprotein (HDLC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), creatinine (CR), FT3, FT4, and TSH were significantly different between the non-NAFLD group and NAFLD group. Age, BMI, waist circumference, DBP, fFBG, HbA1c, total cholesterol (TC), low-density lipoprotein (LDLC), AST, and UA were all independent risk factors for NAFLD. In the normal uric acid group, variables other than SBP and TSH were independent factors of NAFLD. In the hyperuricemia group, all variables except SBP, FT4, and TSH were independent factors of NAFLD.

CONCLUSION: The level of uric acid is related to the occurrence of NAFLD. Hyperuricemia is one of the independent risk factors of NAFLD. TSH level is not related to the occurrence of NAFLD, while FT3 and FT4 may be related to NAFLD.

PMID:33941292 | DOI:10.1186/s41043-021-00247-w

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Clinical, biochemical, and echocardiographic evaluation of neonates with vitamin D deficiency due to maternal vitamin D deficiency

Cardiol Young. 2021 May 4:1-6. doi: 10.1017/S1047951121001633. Online ahead of print.

ABSTRACT

OBJECTIVE: There are a few number of case reports and small-scale case series reporting dilated cardiomyopathy due to vitamin D-deficient rickets. The present study evaluates the clinical, biochemical, and echocardiographic features of neonates with vitamin D deficiency.

PATIENTS AND METHODS: In this prospective single-arm observational study, echocardiographic evaluation was performed on all patients before vitamin D3 and calcium replacement. Following remission of biochemical features of vitamin D deficiency, control echocardiography was performed. Biochemical and echocardiographic characteristics of the present cohort were compared with those of 27 previously published cases with dilated cardiomyopathy due to vitamin D deficiency.

RESULTS: The study included 148 cases (95 males). In the echocardiographic evaluation, none of the patients had dilated cardiomyopathy. All of the mothers were also vitamin D deficient and treated accordingly. Comparison of patients with normocalcaemia and hypocalcaemia at presentation revealed no statistically significant difference between the ejection fraction and shortening fraction, while left ventricle end-diastolic diameter and left ventricle end-systolic diameter were higher in patients with hypocalcaemia. Previously published historical cases were older and had more severe biochemical features of vitamin D deficiency.

CONCLUSION: To the best of our knowledge, in this first and largest cohort of neonates with vitamin D deficiency, we did not detect dilated cardiomyopathy. Early recognition and detection before developing actual rickets and preventing prolonged hypocalcaemia are critically important to alleviate cardiac complications.

PMID:33941295 | DOI:10.1017/S1047951121001633

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The association between residual neuromuscular blockade (RNMB) and critical respiratory events: a prospective cohort study

Perioper Med (Lond). 2021 May 4;10(1):14. doi: 10.1186/s13741-021-00183-7.

ABSTRACT

BACKGROUND: Inadequate neuromuscular recovery might impair pulmonary function among adult patients who undergo general anaesthesia and might thus contribute to critical respiratory events in the post-anaesthesia care unit (PACU). The pilot study aims to understand the baseline incidence of residual neuromuscular blockade (RNMB) and postoperative critical respiratory events (CREs), which are described in a modified Murphy’s criteria in the PACU.

METHOD: This is a prospective cohort study from January to March 2017 from a tertiary hospital in Saudi Arabia with thirty adult patients over 18 years old scheduled for elective surgery under general anaesthesia with neuromuscular blocking drugs (NMBDs) who were enrolled in the study. The Mann-Whitney U tests, chi-square tests and independent-samples T tests were used. The train-of-four (TOF) ratios were measured upon arrival in the PACU by using acceleromyography with TOF-Scan. Subjects’ demographics, perioperative data and the occurrence of postoperative CREs in the PACU were recorded.

RESULTS: Twenty-six (86.7%) patients out of thirty in the study have received rocuronium as NMBDs whilst neostigmine as a reversal drug with only 23 (76.7%). The incidence of RNMB (TOF ratio < 0.9) was in 16 patients (53.3%). The incidence of RNMB was significantly higher in female patients (p = 0.033), in patients who had not undergone quantitative neuromuscular monitoring before extubation (p = 0.046) and in patients with a shorter duration of surgery (p = 0.001). Postoperative CREs occurred in twenty patients (66.7%), and there were significantly more of these CREs among patients with RNMB (p = 0.001). In addition, a statistically significant difference was observed in the occurrence of CREs according to body mass index (p = 0.047).

CONCLUSION: This research showed that RNMB is a significant contributing factor to the development of critical respiratory events during PACU stay. Therefore, routine quantitative neuromuscular monitoring is recommended to reduce the incidence of RNMB.

PMID:33941287 | DOI:10.1186/s13741-021-00183-7

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Maladaptive behaviours in adolescence and their associations with personality traits, emotion dysregulation and other clinical features in a sample of Italian students: a cross-sectional study

Borderline Personal Disord Emot Dysregul. 2021 May 4;8(1):14. doi: 10.1186/s40479-021-00154-w.

ABSTRACT

BACKGROUND: Emotion Dysregulation (ED), childhood trauma and personality are linked to the occurrence of maladaptive behaviours in adolescence which, in turn, may be related to increased risk for psychopathology in the life course. We sought to explore the relationship among the occurrence of different clusters of maladaptive behaviours and ED, clinical features (i.e. impulsivity, childhood maltreatment, anxiety, depressive symptoms) and personality traits that have been found to be associated to Borderline Personality Disorder (BPD), in a sample of 179 adolescent students.

METHODS: Multiple Correspondence Analysis (MCA) was applied to detect clustered types of maladaptive behaviours and groups of students were defined as individuals engaging in these clustered behaviours (non-suicidal self-injury-NSSI, binge eating, binge drinking, cannabis use, and sexual risk behaviours). Logistic models were used to evaluate the association among clinical scales, and student groups. Mediation analysis was used to evaluate whether clinical features affected the association between personality traits and student groups.

RESULTS: MCA analysis allowed to identify three student groups: NSSI/binge eating (NSSI-BE) behaviours, other maladaptive behaviours and “none”. Higher scores in ED, impulsivity, childhood maltreatment, anxiety and depressive symptoms increased the risk of belonging to the cluster of NSSI-BE behaviours compared to the other two groups. ED, depression and anxiety symptoms were found to be mediators of the relationship between specific personality traits, mainly pertaining to the negative affectivity construct, and NSSI/BE.

CONCLUSIONS: Individuals engaging in NSSI-BE behaviours represent a vulnerable adolescent population. ED, depression and anxiety were mediators of the relationship between a variety of personality traits related to BPD and NSSI and binge eating behaviours. Findings have important clinical implications in terms of prevention and interventions among adolescents engaging in self-damaging behaviours.

PMID:33941285 | DOI:10.1186/s40479-021-00154-w

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Biaxial flexural strength of various CAD-CAM glass-ceramic materials

Am J Dent. 2021 Apr;34(2):91-96.

ABSTRACT

PURPOSE: To evaluate and compare the flexural strength of three CAD-CAM glass-ceramic materials and to investigate the effect of various surface treatments on their flexural strength.

METHODS: 120 rectangular specimens were fabricated from three different types of CAD-CAM ceramic blocks and were divided into three groups: zirconia-reinforced lithium silicate (Celtra Duo, Group 1), leucite-reinforced glass-ceramic (IPS Empress CAD, Group 2), and lithium disilicate ceramic (IPS e.max CAD, Group 3). Dimensions of the specimens were standardized to 14.5×12.5 mm and 1.5 mm thickness. Specimens in each group were randomized into four subgroups. The first subgroup (NS) did not undergo any surface treatment; the second subgroup (P) underwent polishing only; the third subgroup (G) underwent glazing only; and the fourth subgroup (PG) underwent both polishing and glazing surface treatments. Biaxial flexural strength (FS) testing was performed until fracture occurred; FS was calculated in MPa. All analyses were performed using SPSS version 24.

RESULTS: Group NS2 showed the lowest FS (89.34 ± 25.30 MPa). Group PG3 showed a significantly higher FS (365.38 ± 52.52 MPa) than Group P3 (268.15 ± 48.34). There was a statistically significant difference among the material groups for each surface treatment: IPS e.max CAD showed the highest FS, which was significantly greater than that of both Celtra Duo and IPS Empress CAD. The combination of polishing and glazing surface treatment resulted in significantly higher flexural strength than polishing alone for all three materials tested. For each material, no significant difference was found between the following surface treatments: control and polishing-only surface treatments; glazing-alone and the combination of polishing and glazing surface treatments. For each surface treatment, Celtra Duo showed significantly lower flexural strength than IPS e.max CAD. However, it displayed higher flexural strength than IPS Empress CAD, although the difference was only significant for glazing and the combination of polishing and glazing.

CLINICAL SIGNIFICANCE: This study provides the clinician with an estimate of the flexural strength of glass-ceramic materials and shows how various surface treatments affect their strength.

PMID:33940666

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Reliability of magnetic resonance imaging on detecting degenerative bone changes of the temporomandibular joint

Am J Dent. 2021 Apr;34(2):101-104.

ABSTRACT

PURPOSE: To evaluate and describe the most frequent TMJ degenerative bone alterations on MRI and CT and to determine the accuracy, sensitivity, and specificity of MRI.

METHODS: Images of 80 subjects were selected and evaluated from a database and 57 were selected. The subjects were submitted to CT and MRI exams (each subject on the same day). The joints were evaluated in the sagittal and coronal planes under closed mouth position. Each individual parameter was scored as absent or present. Absolute and relative frequencies were obtained and the Kappa concordance index test and equality of two proportions were used. To correlate the presence of bone alterations, the Chi-Square test was performed. A significance level of 0.05 (5%) was defined, with 95% of statistical confidence interval.

RESULTS: Of the 57 subjects, (47 female, 10 male), the ages ranged from 18-83 years (mean 43 years). The intra and inter-rater agreement tests demonstrated reliability among the examiners for all variables analyzed on MRI and CT.

CLINICAL SIGNIFICANCE: MRI is a reliable and valid method for observing bone changes in the TMJ, with the advantage of non-exposure to radiation and cost-effectiveness due to the use of only one exam.

PMID:33940668