Tag: pubmed

Biometrics. 2021 Apr 9. doi: 10.1111/biom.13467. Online ahead of print.

ABSTRACT

The presence of protein aggregates in cells is a known feature of many human age-related diseases, such as Huntington’s disease. Simulations using fixed parameter values in a model of the dynamic evolution of expanded polyglutaime (PolyQ) proteins in cells have been used to gain a better understanding of the biological system. However, there is considerable uncertainty about the values of some of the parameters governing the system. Currently, appropriate values are chosen by ad-hoc attempts to tune the parameters so that the model output matches experimental data. The problem is further complicated by the fact that the data only offer a partial insight into the underlying biological process: the data consist only of the proportions of cell death and of cells with inclusion bodies at a few time points, corrupted by measurement error. Developing inference procedures to estimate the model parameters in this scenario is a significant task. The model probabilities corresponding to the observed proportions cannot be evaluated exactly and so they are estimated within the inference algorithm by repeatedly simulating realisations from the model. In general such an approach is computationally very expensive and we therefore construct Gaussian process emulators for the key quantities and reformulate our algorithm around these fast stochastic approximations. We conclude by highlighting appropriate values of the model parameters leading to new insights into the underlying biological processes. This article is protected by copyright. All rights reserved.

PMID:33837525 | DOI:10.1111/biom.13467

Ann Biomed Eng. 2021 Apr 9. doi: 10.1007/s10439-021-02772-5. Online ahead of print.

ABSTRACT

Ischemic mitral regurgitation (IMR) is a prevalent cardiac disease associated with substantial morbidity and mortality. Contemporary surgical treatments continue to have limited long-term success, in part due to the complex and multi-factorial nature of IMR. There is thus a need to better understand IMR etiology to guide optimal patient specific treatments. Herein, we applied our finite element-based shape-matching technique to non-invasively estimate peak systolic leaflet strains in human mitral valves (MVs) from in-vivo 3D echocardiographic images taken immediately prior to and post-annuloplasty repair. From a total of 21 MVs, we found statistically significant differences in pre-surgical MV size, shape, and deformation patterns between the with and without IMR recurrence patient groups at 6 months post-surgery. Recurrent MVs had significantly less compressive circumferential strains in the anterior commissure region compared to the recurrent MVs (p = 0.0223) and were significantly larger. A logistic regression analysis revealed that average pre-surgical circumferential leaflet strain in the Carpentier A1 region independently predicted 6-month recurrence of IMR (optimal cutoff value – 18%, p = 0.0362). Collectively, these results suggest greater disease progression in the recurrent group and underscore the highly patient-specific nature of IMR. Importantly, the ability to identify such factors pre-surgically could be used to guide optimal treatment methods to reduce post-surgical IMR recurrence.

PMID:33837494 | DOI:10.1007/s10439-021-02772-5

Ann Biomed Eng. 2021 Apr 9. doi: 10.1007/s10439-021-02771-6. Online ahead of print.

ABSTRACT

Surgical repair of Tetralogy of Fallot (TOF) involves a series of steps to remove right ventricular outflow tract and pulmonary artery obstruction. However, the large degree of anatomic variability among preoperative TOF patients may impact the effectiveness of different repair strategies and, subsequently, different geometric modifications for different patients. This study investigates the relationships between geometric and hemodynamic parameters and mechanical energy efficiency for a patient-specific dataset of 16 postoperative TOF repairs, using morphometric and statistical shape analyses, as well as computational fluid dynamics simulations with physiologically-relevant inlet and outlet boundary conditions. Quantitatively, negative correlations were found between the right and left pulmonary artery centerline tract cumulative torsion and energy efficiency (r = – 0.65, p = 0.01, for both). A positive correlation was also found for a statistical shape mode associated with skewing of the geometric sub-regions (r = 0.61, p = 0.01). Qualitatively, medium- and low-efficiency geometries exhibit disturbed flow and much more proximal vortex formation as compared to a high-efficiency geometry. Thus, it is recommended, as much as possible, to both relieve and avoid the introduction of torsion into the patient’s anatomy during surgical repair of TOF.

PMID:33837495 | DOI:10.1007/s10439-021-02771-6

Acta Neurol Belg. 2021 Apr 9. doi: 10.1007/s13760-021-01647-9. Online ahead of print.

ABSTRACT

Inflammation in a myelinated portion of the nervous system is the mainstay of multiple sclerosis (MS). Elevation of inflammatory markers such as procalcitonin, ESR and hs-CRP is suspected to occur in MS patients. However, their prognostic role and their relationship with the severity of clinical symptoms of MS and MRI evidences has remained unnoticed in the literature. Hence, we aim to evaluate the serum level of inflammatory markers in the acute attack of MS patients and demonstrate the potential prognostic role of these inflammatory markers. This study was carried on case and control groups of definite MS patients. The cases were patients with active MS and were further allocated into four subgroups, while as control group included patients with non-active MS. Furthermore, all the participants underwent brain and cervical magnetic resonance imaging (MRI) using a contrast agent. A significant difference was detected in hs-CRP level (p = 0.009) across the subgroups of the cases. The highest level of hs-CRP was reported in patients with cerebellar and brain stem symptoms (mean = 6998.13 ± 3501.16), while the lowest in patients with pyramidal and urinary incontinence symptoms (mean = 1958.91 ± 2662.16). Moreover, correlation coefficient between values of MRI contrast-enhanced lesions and ESR level was statistically significant (Rs = 0.503 and p = 0.001). Elevation of ESR serum level positively correlates with disease activity evidenced by values of contrast-enhanced plaques of MRI in relapsing-remitting MS patients which may predict the disease activity. In addition, MS relapse with cerebellar and brain stem symptoms is associated with a high concentration of hs-CRP plasma level.

PMID:33837496 | DOI:10.1007/s13760-021-01647-9

Eur Arch Otorhinolaryngol. 2021 Apr 9. doi: 10.1007/s00405-021-06798-2. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) with the clinical and pathological parameters of 118 laryngeal cancer patients, as well as their effects on the survival of the disease.

METHODS: For the calculation of SII, PLR, and NLR, hemogram tests were conducted before treatment. Receiver-operating characteristic (ROC) analysis was used to calculate the cut-off value of SII, NLR, and PLR for overall survival (OS) and disease-free survival (DFS).

RESULTS: A statistically significant relationship was found between SII and lymphovascular invasion and between NLR and local recurrence, and lymphovascular invasion. In a univariate analysis, SII (p < 0.001) and NLR (p = 0.001) for OS and SII (p < 0.001), PLR (p = 0.043), and NLR (p < 0.001) for DFS were detected as prognostic factors. In a multivariate analysis for OS, SII (HR = 10.54, 95% CI 1.28-86.77; p = 0.029) and extracapsular extension (HR = 3.08, 95% CI 1.15-8.21; p = 0.024) were identified as independent prognostic factors. In a multivariate analysis for DFS, only an extracapsular extension presence (HR = 3.32, 95% CI 1.37-8.08; p = 0.008) was detected as an independent prognostic factor.

CONCLUSION: In laryngeal cancer, high SII values were determined as poor independent prognostic factors for OS. High SII, NLR, and PRL have been identified as poor prognostic factors in DFS. A correlation was found between NLR and local recurrence, and lymphovascular invasion and between SII with lymphovascular invasion positivity.

PMID:33837464 | DOI:10.1007/s00405-021-06798-2

Int J Eat Disord. 2021 Apr 9. doi: 10.1002/eat.23516. Online ahead of print.

ABSTRACT

OBJECTIVE: This study sought to determine whether gastric symptoms are associated with later eating disorder (ED) symptoms during early adolescence, and whether this relationship is moderated by parental warmth/acceptance and/or the child’s sex.

METHOD: Longitudinal data from the Adolescent Brain Cognitive Development^SM Study were utilized. Participants ages 9-10 years old (N = 4,950; 2,370 female) completed measures at baseline and 1 year later (Y1). At baseline, gastric symptoms were measured by parent-reported items from the Child Behavior Checklist (CBCL), and perceived parental acceptance was measured by youth report on the Children’s Report of Parent Behavior Inventory (CRPBI) Acceptance subscale separately for mothers and fathers. ED symptoms at Y1 were assessed by parent report on a computerized version of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Linear mixed-effects models were conducted separately for maternal and paternal acceptance to test relationships among variables.

RESULTS: A three-way interaction between baseline gastric symptoms, sex, and maternal acceptance predicted Y1 ED symptoms (𝛽 = 0.08; p < .01). Post-hoc analyses revealed that the interaction between gastric symptoms and maternal acceptance was significant for girls only (𝛽 = -0.06, p < .01), such that low maternal acceptance was associated with a stronger relationship between baseline gastric symptoms and Y1 ED symptoms. No statistically significant main effects or interactions were found in the model for paternal acceptance.

DISCUSSION: Gastric symptoms and low perceived maternal acceptance may interact to result in heightened risk for EDs in young adolescent girls.

PMID:33836108 | DOI:10.1002/eat.23516

PLoS One. 2021 Apr 9;16(4):e0249477. doi: 10.1371/journal.pone.0249477. eCollection 2021.

ABSTRACT

BACKGROUND: The search for immune correlates of protection against Mycobacterium tuberculosis (MTB) infection in humans is limited by the focus on peripheral blood measures. Bronchoalveolar lavage (BAL) can safely be done and provides insight into cellular function in the lung where infection is first established. In this study, blood and lung samples were assayed to determine if heavily MTB exposed persons who resist development of latent MTB infection (RSTR) vs those who develop latent MTB infection (LTBI), differ in the make-up of resident BAL innate and adaptive immune cells.

METHODS: Bronchoscopy was performed on 21 healthy long-term Ugandan RSTR and 25 LTBI participants. Immune cell distributions in BAL and peripheral blood were compared by differential cell counting and flow cytometry.

RESULTS: The bronchoscopy procedure was well tolerated with few adverse reactions. Differential macrophage and lymphocyte frequencies in BAL differed between RSTR and LTBI. When corrected for age, this difference lost statistical significance. BAL CD4+ and CD8+ T cells were almost entirely composed of effector memory T cells in contrast to PBMC, and did not differ between RSTR and LTBI. BAL NKT, γδ T cells and NK cells also did not differ between RTSR and LTBI participants. There was a marginally significant increase (p = 0.034) in CD8 T effector memory cells re-expressing CD45RA (TEMRA) in PBMC of LTBI vs RSTR participants.

CONCLUSION: This observational case-control study comparing unstimulated BAL from RSTR vs LTBI, did not find evidence of large differences in the distribution of baseline BAL immune cells. PBMC TEMRA cell percentage was higher in LTBI relative to RSTR suggesting a role in the maintenance of latent MTB infection. Functional immune studies are required to determine if and how RSTR and LTBI BAL immune cells differ in response to MTB.

PMID:33836031 | DOI:10.1371/journal.pone.0249477

Arch Pathol Lab Med. 2021 Apr 9. doi: 10.5858/arpa.2020-0572-OA. Online ahead of print.

ABSTRACT

CONTEXT.—: Genomic molecular testing practices in a pediatric tertiary care institution.

OBJECTIVE.—: To evaluate exome sequencing (ES) ordering practices and the effects of applying criteria to support ES stewardship. Exome sequencing can provide molecular diagnostic information for patients with known or suspected genetic diseases, but it is relatively expensive, and the cost is often borne by patients, institutions, and payers.

DESIGN.—: We examined ordering patterns of ES approved by board-certified geneticists at our tertiary pediatric care center, as well as preauthorization outcomes for ES requests. We compared positivity rates among patients by patient phenotype, composite insurance coverage criteria, and insurance preauthorization outcome.

RESULTS.—: Patients who met composite coverage criteria were more likely to receive a positive result from ES compared to patients who did not meet composite coverage criteria, though this trend was not statistically significant. There was no significant difference in ES results between patients who were denied or not denied preauthorization by insurance payers.

CONCLUSIONS.—: Insurance payers should consider implementing and/or expanding coverage criteria for ES and institutions should implement stewardship programs to support appropriate ES practices.

PMID:33836053 | DOI:10.5858/arpa.2020-0572-OA

J Food Prot. 2021 Apr 9. doi: 10.4315/JFP-20-490. Online ahead of print.

ABSTRACT

The growth and hemolysin production of two V. alginolyticus strains (HY9901 and ATCC17749T) at 30 °C in briny tilapia, shrimp, scallop, oyster, pork, chicken, freshwater fish and egg fried rice were investigated. Bacterial counts were enumerated by plate counting. Hemolysin production was evaluated by blood agar and hemolytic titer tests. The two V. alginolyticus strains displayed similar growth and hemolysin production patterns in the foods. Based on the goodness of fit primary model statistics (R 2 , MSE, BF, AF), the modified Gompertz model was a better fit to V. alginolyticus growth in foods than the logistic model. Growth kinetic parameters of V. alginolyticus displayed a higher μ max and shorter λ in briny tilapia > shrimp > freshwater fish > egg fried rice > scallop > oyster > chicken > pork. It was notable that the V. alginolyticus counts were similar at the stationary phase, with no significant growth behavior difference between raw and cooked foods. Significantly higher (p < 0.05) thermostable direct hemolysin (TDH) activity was produced by V. alginolyticus in briny tilapia > freshwater fish > shrimp > chicken > egg fried rice > scallop > oyster > pork. But the hemolytic titer was not consistent with the TDH activity, being significantly higher (p < 0.05) in briny tilapia > egg fried rice > shrimp > freshwater fish > chicken > scallop > oyster > pork. Contrary to current belief, V. alginolyticus displayed a higher hemolysin production in some non-seafoods (freshwater fish, egg fried rice and chicken) than in scallop or oyster. This is the first report of growth and toxicity of V. alginolyticus in different food matrices and confirmation that some non-seafood contaminated with V. alginolyticus can be even more pathogenic. This study will enhance the awareness of non-seafood safety and improve the V. alginolyticus risk assessment accuracy.

PMID:33836066 | DOI:10.4315/JFP-20-490

J Surg Oncol. 2021 Apr 9. doi: 10.1002/jso.26479. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: This study aimed to evaluate the safety and efficacy of robot-assisted laparoscopic tumor enucleation (RAE) for the treatment of renal hilar tumors and to describe our experience with renorrhaphy-related surgical techniques.

METHODS: Retrospective data were collected from 173 consecutive patients who underwent RAE for localized renal tumors (cT1-cT2N0M0) at our hospital between September 2014 and November 2019.

RESULTS: Seventy-five patients had renal hilar tumors and 98 patients had nonhilar tumors. There were no statistical differences between the hilar and nonhilar groups in operation time (190 [115-390] vs. 190 [110-390] min, p = 0.889), warm ischemia time (26 [12-60] vs. 27 [17-41] min, p = 0.257), hospital stay duration (8 [3-16] vs. 7.5 [4-18] days, p = 0.386), renal function (estimated glomerular filtration rate, 102.5 [29.4-144] vs. 101.3 [64.2-134.7] ml/min/1.73 m² , p = 0.631); creatinine level, (76 [43-169] vs. 78.5 [50-281.3] µmol/L, p = 0.673), perioperative complications rate, or surgical margin status. However, patients with hilar tumors lost significantly more blood than did those with nonhilar tumors (250 [50-1500] vs. 200 [20-1200] ml, p = 0.007). During the follow-up period (median, 30 months), three patients in each group experienced recurrence. The 5-year recurrence-free rates were 93.0% and 95.4% in the hilar and nonhilar tumor groups, respectively (p = 0.640).

CONCLUSIONS: For experienced robot laparoscopists, RAE is a safe, effective, and feasible procedure for renal hilar tumors, without increased risk of positive surgical margins or worse midterm oncologic outcomes compared with nonhilar tumors.

PMID:33836093 | DOI:10.1002/jso.26479