Nevin Manimala

Complement Ther Clin Pract. 2022 Apr 12;48:101590. doi: 10.1016/j.ctcp.2022.101590. Online ahead of print.

ABSTRACT

The objective of this study was to investigate the day-to-day experiences of positive and negative emotions among partners of veterans assigned service dogs for posttraumatic stress disorder (PTSD). As part of a larger clinical trial, a total of N = 87 partners of post-9/11 veterans with PTSD were recruited from a nonprofit service dog provider and participated in an ecological momentary assessment (EMA) protocol. The sample included partners of veterans who received a PTSD service dog after baseline (n = 48, treatment group) and partners of veterans on the waitlist for a service dog (n = 39, control group). Data were collected twice daily for two weeks at baseline and again at follow-up three months later, for approximately 56 assessments per participant (28 at baseline, 28 at follow up). Participants completed an average of 84% of questionnaires at baseline (n = 23.6) and 86% (n = 24.1) at follow-up. A total of 3780 EMA questionnaires were collected among partners for this analysis. Data were analyzed using a generalized linear mixed model. Three months following baseline, partners of veterans with service dogs reported statistically significant higher levels of positive emotions than the control partners (p = .01, d = 0.39) with small-to-medium effect sizes for each individual positive emotion. No statistically significant differences were reported for negative emotions (p = .77, d = 0.21). This study quantitatively identifies higher levels of positive emotion in partners who are cohabitating with a PTSD service dog compared to those partners who remained on the waitlist. Given the influence that positive emotions have on well-being and coping, findings suggest that the influence of service dogs may go beyond veterans to influence their cohabitating partners.

PMID:35439705 | DOI:10.1016/j.ctcp.2022.101590

J Clin Virol. 2022 Apr 12;150-151:105161. doi: 10.1016/j.jcv.2022.105161. Online ahead of print.

ABSTRACT

BACKGROUND: Booster doses for COVID-19 vaccinations are currently recommended and approved in many countries. However, we need more evidence on the immune response of individuals to booster doses of inactivated vaccines and the neutralizing effect against the variants of concerns of SARS-CoV-2.

OBJECTIVE: To compare the fold reduction in antibody titers against the variants of concerns of SARS-CoV-2 between the primary doses and booster dose vaccine cohorts of inactivated BBIBP-CorV vaccine.

STUDY DESIGN: In this observational study Plaque Reduction Neutralization Test (PRNT) assay was done on pooled serum samples of the recipients of primary two doses of inactivated BBIBP-CorV and on the pooled serum samples of recipients of a booster dose of inactive BBIBP-CorV. The neutralizing antibody titers against the wild (Wuhan) strain and the variants of concern (alpha, beta and delta) were compared.

RESULTS: The serum sample pool from the booster cohort had high neutralizing antibody titers against the SARS-CoV-2 variants compared to the pooled serum samples of the recipients of primary two doses of inactivated BBIBP-CorV and the difference was statistically significant. The observed fold reduction in antibody titers from the serum pool of recipients of two doses of BBIBP-CorV vaccine were 3.7-fold, 14.6-fold and 10.4-fold compared to 1.8 -fold, 6.5-fold and 3.8-fold reduction against the alpha, beta and delta lineages respectively in the serum pool of recipient of a booster dose (three doses of BBIBP-CorV).

CONCLUSION: Booster doses of inactive BBIBP-CORV offered better protection against the variants of concern of SARS-CoV-2.

PMID:35439702 | DOI:10.1016/j.jcv.2022.105161

J Magn Reson. 2022 Apr 9;339:107218. doi: 10.1016/j.jmr.2022.107218. Online ahead of print.

ABSTRACT

Dipolar electron paramagnetic resonance (EPR) experiments, such as double electron-electron resonance (DEER), measure distributions of nanometer-scale distances between paramagnetic centers, which are valuable for structural characterization of proteins and other macromolecular systems. One challenge in the least-squares fitting analysis of dipolar EPR data is the separation of the inter-molecular contribution (background) and the intra-molecular contribution. For noisy experimental traces of insufficient length, this separation is not unique, leading to identifiability problems for the background model parameters and the long-distance region of the intra-molecular distance distribution. Here, we introduce a regularization approach that mitigates this by including an additional penalty term in the objective function that is proportional to the variance of the distance distribution and thereby penalizes non-compact distributions. We examine the reliability of this approach statistically on a large set of synthetic data and illustrate it with an experimental example. The results show that the introduction of compactness can improve identifiability.

PMID:35439683 | DOI:10.1016/j.jmr.2022.107218

Eur J Cancer. 2022 Apr 16;168:51-55. doi: 10.1016/j.ejca.2022.03.013. Online ahead of print.

ABSTRACT

AIM: Patients with cancer are at an increased risk for severe coronavirus disease of 2019. We previously reported initial findings from a single centre prospective study evaluating antibody response after BNT162b2 vaccine, showing that adequate antibody response was achieved after two doses, but not after one, in patients with cancer vaccinated during anticancer therapy. Herein, we report a follow-up study, evaluating antibody response six months after the second vaccine dose.

METHODS: The study included patients with solid tumours undergoing anticancer treatment, and immunocompetent health-care workers serving as controls. Serum titres of the receptor-binding domain (RBD) IgG and neutralising antibodies (Nabs) were measured approximately six months after the second vaccine dose. Complete blood count values were collected and evaluated as predictors for antibody response.

RESULTS: The analysis included 93 patients with cancer (66.7% metastatic). Six months after the second vaccine dose (mean 176 ± 20 days), seropositivity rate among patients and controls was 83.9% versus 96.3% (p = 0.0001), respectively. Median RBD-IgG titre was lower among patients compared with controls (2.3 versus 3.2, p = 0.0002). Among seropositive individuals, median Nabs titre was similar between patients with cancer and controls (p = 0.566). Among patients with cancer, lymphocyte and neutrophil counts were not correlated with either RBD-IgG or Nabs titres.

CONCLUSIONS: Seropositivity rates and RBD-IgG titre at six months after second BNT162b2 vaccine dose are lower among patients with cancer compared with healthy controls. However, Nabs titre is similar, suggesting a comparable protection among seropositive individuals. Lymphocyte count is not predictive of antibody response.

PMID:35439660 | DOI:10.1016/j.ejca.2022.03.013

Am J Otolaryngol. 2022 Apr 11;43(3):103451. doi: 10.1016/j.amjoto.2022.103451. Online ahead of print.

ABSTRACT

INTRODUCTION: Dysthyroid optic neuropathy (DON) is the most severe complication of Graves’ orbitopathy (GO) and its management may require decompression surgery. Clear recommendations do not exist about which surgery should be performed and how extended the decompression should be. In this paper we present our experience regarding the management of DON via 3 different surgical protocols: a modified extended orbital apex decompression, a 2 walls decompression (inferior and lateral) and a 3 walls decompression (inferior, lateral and medial) and evaluate the functional outcomes.

METHODS: Retrospective evaluation of subjects affected by DON not responding to medical therapy has been performed. All patients were submitted to pre- and post-operative ophthalmologic evaluations and orbital and sinuses CT scan in order to evaluate functional and surgical outcomes.

RESULTS: 27 patients were enrolled in the study. Surgical procedures were performed on 42 orbits. A statistically significant post-operative improvement was recorded in visual acuity, proptosis, color vision and fundus oculi evaluation for all groups. No patient developed major or minor complications after surgery.

CONCLUSIONS: Extended endonasal approach and 3 walls decompression have been proved effective in the management of DON. The choice between them is done according to degree of proptosis, general status and eye-surface damages.

PMID:35439657 | DOI:10.1016/j.amjoto.2022.103451

Comput Methods Programs Biomed. 2022 Apr 10;220:106805. doi: 10.1016/j.cmpb.2022.106805. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Modeling the size and shape of human skull and scalp is essential for head injury assessment, design of helmets and head-borne equipment, and many other safety applications. Finite element (FE) head models are important tools to assess injury risks and design personal protective equipment. However, current FE head models are mainly developed based on the midsize male, failing to account for the significant morphological variation that exists in the skull and brain. The objective of this study was to develop a statistical head geometry model that accounts for size and shape variations among the adolescent and young adult population.

METHODS: To represent subject-specific geometry using a homologous mesh, threshold-based segmentation of head CT scans of 101 subjects between 14 and 25 years of age was performed, followed by landmarking, mesh morphing, and projection. Skull and scalp statistical geometry models were then developed as functions of age, sex, stature, BMI, head length, head breadth, and tragion-to-top of head using generalized Procrustes analysis (GPA), principal component analysis (PCA) and multivariate regression analysis.

RESULTS: The statistical geometry models account for a high percentage of morphological variations in scalp geometry (R²=0.63), outer skull geometry (R²=0.66), inner skull geometry (R²=0.55), and skull thickness (error < 1 mm) CONCLUSIONS: Skull and scalp statistical geometry models accounts for size and shape variations among the adolescent and young adult population were developed as functions of subject covariates. These models may serve as the geometric basis to develop individualized head FE models for injury assessment and design of head-borne equipment.

PMID:35439654 | DOI:10.1016/j.cmpb.2022.106805

Contemp Clin Trials. 2022 Apr 16:106761. doi: 10.1016/j.cct.2022.106761. Online ahead of print.

ABSTRACT

BACKGROUND: The MEL-SELF trial is a randomised controlled trial of patient-led surveillance compared to clinician-led surveillance in people treated for localised cutaneous melanoma (stage 0, I, II). The primary trial aim is to determine if patient led-surveillance compared to clinician-led surveillance increases the proportion of participants who are diagnosed with a new primary or recurrent melanoma at a fast-tracked unscheduled clinic visit. The secondary outcomes include time to diagnosis of any skin cancer, psychosocial outcomes, acceptability, and resource use.

OBJECTIVE: The objective of this report is to outline and publish the pre-determined statistical analysis plan before the database lock and the start of analysis.

METHODS/DESIGN: The statistical analysis plan describes the overall analysis principles, including how participants will be included in each analysis, the presentation of the results, adjustments for covariates, the primary and secondary outcomes, and their respective analyses. In addition, we present the planned sensitivity and subgroup analyses. A separate analysis plan will be published for health economic outcomes.

RESULTS: The MEL-SELF statistical analysis plan has been designed to minimize bias in estimating effects of the intervention on primary and secondary outcomes. By pre-specifying analyses, we ensure the study’s integrity and believability while enabling the reproducibility of the final analysis.

CONCLUSION: This detailed statistical analysis plan will help to ensure transparency of reporting of results from the MEL-SELF trial.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000176864. Registered 18 February 2021, https://www.anzctr.org.au/ACTRN12621000176864.aspx.

PMID:35439647 | DOI:10.1016/j.cct.2022.106761

World Neurosurg. 2022 Apr 16:S1878-8750(22)00496-X. doi: 10.1016/j.wneu.2022.04.048. Online ahead of print.

ABSTRACT

BACKGROUND: It has been proposed in the most recent 2021 World Health Organization (WHO) Classification of brain tumors that the loss of trimethylation at histone 3 lysine site 27 (H3K27me3) may prognosticate meningioma outcomes. However to date the emerging literature remains diffuse in its stance on this. Correspondingly, the aim of this study was to determine the prognostic relevance of H3K27me3 loss in meningiomas METHODS: Searches of 7 electronic databases from inception to October 2021 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Outcomes were pooled by random-effects meta-analyses of proportions where possible.

RESULTS: A total of 7 retrospective cohort studies satisfied all criteria. There were 2180 meningioma patients overall, with 1291 (59%) male patients, and a mean age of 56 years old. Across all 7 studies, the pooled incidence of H3K27me3 loss was estimated to be 15% (95% CI 8-24%). Across 6 studies the pooled multivariate-derived HR estimate for recurrence was 1.77 (95% CI 1.23-2.31, P<0.01). Overall survival by univariate analysis was significantly shorter with H3K27me3 loss in 2/4 (50%) studies, and 2 studies described significant association between H3K27me3 loss and shorter overall survival by means of multivariate analysis.

CONCLUSION: The contemporary metadata favors greater recurrence of meningioma based independently on H3K27me3 loss that is statistically significant. It is possible that these effects are more pronounced in Grade 2 meningiomas, but more robust data and analysis is needed to augment this position.

PMID:35439620 | DOI:10.1016/j.wneu.2022.04.048

Environ Pollut. 2022 Apr 16:119319. doi: 10.1016/j.envpol.2022.119319. Online ahead of print.

ABSTRACT

Acrylamide (AA) is an organic contaminant that naturally forms in starchy foods during high-temperature cooking under low-moisture conditions. It is mainly produced from the sugars and amino acids present in food by the Maillard reaction. When humans are exposed to AA, AA is eliminated in the urine as mercapturic acid conjugates, primarily including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA3), and N-acetyl-3-[(3-amino-3-oxopropyl)sulfinyl]-L-alanine (AAMA-Sul), which are used as exposure biomarkers of AA in human biomonitoring studies. Although the carcinogenic effects of AA on humans have not been demonstrated yet, some studies have shown that AA may negatively affect children’s health. The main objective of this study was to evaluate the exposure of Spanish children (n = 612) to AA. For this purpose, the levels of AAMA, AAMA-Sul, and GAMA3 in first-morning urine samples were analyzed by “dilute and shoot” and liquid chromatography coupled to tandem mass spectrometry. The three metabolites were detected in all the children involved in this study in the following order (geometric mean (GM)): AAMA (79 ng ml^-1) > AAMA-Sul (28 ng ml^-1) > GAMA3 (18 ng ml^-1). Statistical analysis suggested that the intake of fried potato products and biscuits could be associated with higher levels of AA metabolites in urine. Estimated daily intakes of AA in the children under study were in the range of 1.2-1.5 μg AA·kg-body weight^-1·day^-1 (GM). Risk assessment calculations indicate that the health risk of AA exposure cannot be overlooked and the exposure of Spanish children to AA should be closely monitored.

PMID:35439595 | DOI:10.1016/j.envpol.2022.119319

Horm Mol Biol Clin Investig. 2022 Apr 20. doi: 10.1515/hmbci-2021-0044. Online ahead of print.

ABSTRACT

OBJECTIVES: PCOS is the most common endocrinological disorder amongst women of reproductive age. The consequences of PCOS extend beyond the reproductive axis and may lead to the development of metabolic syndrome leading to a high risk for hypertension and cardiovascular disease. Therefore, a more comprehensive evaluation of biochemical markers that reflect the cardiovascular risk is required for further understanding of pathophysiologic mechanisms, diagnosis and management.

METHODS: In this case-control study, women diagnosed with PCOS (n=100) in the age group (18-35 years) years were taken as cases and age matched healthy controls (n=100) were enrolled. Estimations of fasting plasma Glucose, serum total cholesterol (TC), triglycerides (TG) and High-density lipoprotein (HDL) concentrations were assayed while Low-density lipoprotein (LDL) was calculated by using Fredrickson Friedwald’s formula. Serum Lipoprotein-a (Lp-a) was estimated using ELISA (Enzyme Linked Immunosorbent Assay). The quantitative data were expressed as Mean ± Standard Deviation (SD). Unpaired Student’s t-test was used to compare the values (PCOS vs Controls) and Pearson’s correlation coefficient was used to elucidate the relationship between the variables.

RESULTS: FBS and all lipid parameters were significantly increased in PCOS patients compared to control subjects. On the other hand, HDL-C was significantly decreased as compared to the control subjects. The hormones TSH, LH, FSH, PRL and LH/FSH ratio were significantly increased in PCOS patients compared to control subjects. Lipoprotein-a and PAI-1 was significantly increased in PCOS patients compared to the control subjects. Upon bivariate correlation analysis, Lp(a) had significant correlations with PAI-1 (r=0.35, p=0.000), WHR (r=0.25, p=0.000), LDL (r=0.52, p=0.000) and TSH (r=0.24, p=0.000). While the correlations with FBS (r=-0.008, p=0.91) and LH/FSH ratio (r=-0.004, p=0.95) were statistically insignificant.

CONCLUSIONS: The evaluation of serum biomarkers such as Lp-a, PAI-1 and lipid profile routinely in PCOS patients may have diagnostic role in the early detection of metabolic abnormalities and endocrine derangements and timely management of comorbid Diabetes and Cardiovascular disease in PCOS females.

PMID:35439403 | DOI:10.1515/hmbci-2021-0044