Author: Nevin Manimala

Med Phys. 2021 Apr 10. doi: 10.1002/mp.14878. Online ahead of print.

ABSTRACT

PURPOSE: To show that intrinsic radiosensitivity varies greatly for protons and carbon (C) ions in addition to photons, and that DNA repair capacity remains important in governing this variability.

METHODS: We measured or obtained from the literature clonogenic survival data for a number of human cancer cell lines exposed to photons, protons (9.9 keV/μm), and C-ions (13.3-77.1 keV/μm). We characterized their intrinsic radiosensitivity by the dose for 10% or 50% survival (D_10% or D_50% ), and quantified the variability at each radiation quality by the coefficient of variation (COV) in D_10% and D_50% . We also treated cells with DNA repair inhibitors prior to irradiation to assess how DNA repair capacity affects their variability.

RESULTS: We found no statistically significant differences in the COVs of D_10% or D_50% between any of the radiation qualities investigated. The same was true regardless of whether the cells were treated with DNA repair inhibitors, or whether they were stratified into histologic subsets. Even within histologic subsets, we found remarkable differences in radiosensitivity for high LET C-ions that were often greater than the variations in RBE, with brain cancer cells varying in D_10% (D_50% ) up to 100% (131%) for 77.1 keV/μm C-ions, and non-small cell lung cancer and pancreatic cancer cell lines varying up to 55% (76%) and 51% (78%), respectively, for 60.5 keV/μm C-ions. The cell lines with modulated DNA repair capacity had greater variability in intrinsic radiosensitivity across all radiation qualities.

CONCLUSIONS: Even for cell lines of the same histologic type, there are remarkable variations in intrinsic radiosensitivity, and these variations do not differ significantly between photon, proton or C-ion radiation. The importance of DNA repair capacity in governing the variability in intrinsic radiosensitivity is not significantly diminished for higher LET radiation.

PMID:33837540 | DOI:10.1002/mp.14878

J Am Geriatr Soc. 2021 Apr 10. doi: 10.1111/jgs.17155. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVES: Certified nursing assistants (CNAs) who work in nursing homes (NHs) face significant work and personal stress. Self-compassion training has been shown to decrease stress postintervention in previous studies among healthcare providers and those in helping professions. This study examines the feasibility, acceptability, and preliminary outcomes of self-compassion training to address CNA stress and well-being.

DESIGN: Pre-post intervention.

SETTING: Three mid-size, nonprofit NHs in North Carolina.

PARTICIPANTS: Thirty CNAs, with a mean age of 49, 96% of whom were female, and 83% black/African American.

INTERVENTION: In one NH, participants received an 8-week, 2.5-h/session (20 h total) group intervention. At the time of recruitment for NHs 2 and 3, a briefer format (6-week, 1-h/session; 6 h total) became available and was preferred by CNAs, thus both NHs 2 and 3 participants received a 6-h group intervention. All interventions occurred in meeting rooms within participating NHs during shift changes.

MEASUREMENTS: Intervention attendance, retention, and acceptability; self-compassion, stress, burnout, depression, and attitudes toward residents with dementia, and job satisfaction pre-, post-, 3-month post-, and 6-month postintervention were assessed.

RESULTS: Attendance and program satisfaction were high, and attrition was low for both training formats. Self-compassion was significantly improved at all time periods (p < 0.001), and stress and depression improved significantly through 3 months (p < 0.05), but not 6 months. No statistically significant change in job satisfaction was noted.

CONCLUSION: Self-compassion interventions are feasible and acceptable for CNAs working in NHs and show promise for managing stress and improving well-being and compassion toward residents. The briefer 6-h format may maximize participation, while still providing benefits.

PMID:33837539 | DOI:10.1111/jgs.17155

Contact Dermatitis. 2021 Apr 9. doi: 10.1111/cod.13856. Online ahead of print.

ABSTRACT

BACKGROUND: Data regarding teledermatology for patch testing are limited.

OBJECTIVES: Compare patch test readings and final interpretation by 2 in-person dermatologists (IPDs) with 8 teledermatologists (TDs).

METHODS: Patch tested patients had photographs taken of 70 screening series allergens at 48-hour (48H) and second (2nd) readings. 8 TDs reviewed photos and graded reactions (negative, irritant, doubtful, +, ++, +++) at 48H and 2nd readings; in addition, they coded a final interpretation (allergic, indeterminant, irritant, negative) for each reaction. TDs rated overall image quality and confidence level for each patient and patch test reaction, respectively. Percentage of TD-IPD agreement based on clinical significance (success, indeterminate, and failure) were calculated. Primary outcome was agreement at 2^nd reading.

RESULTS: Data were available for 99, 101, and 66 participants at 48H, 2^nd reading, and final interpretation, respectively. Pooled failure (+/++/+++ vs negative) at 2^nd reading was 13.6% (range 7.9-20.4%). Pooled failure at 48H and final interpretation was 5.4% (range 2.9-6.8%) and 24.6% (range 10.2-36.8%). Confidence in readings was statistically correlated to quality of images and disagreement.

CONCLUSION: For patch testing, teledermatology has significant limitations including clinically significant pooled failure percentages of 13.6% for 2^nd readings and 24.6% for final interpretation. This article is protected by copyright. All rights reserved.

PMID:33837533 | DOI:10.1111/cod.13856

J Anim Ecol. 2021 Apr 10. doi: 10.1111/1365-2656.13492. Online ahead of print.

ABSTRACT

1. Neonicotinoid insecticides are the most widely used class of insecticides in the world and can have both lethal and sub-lethal effects on non-target organisms in agricultural areas. Monarch butterflies (Danaus plexippus) have experienced dramatic declines in recent decades and, given that a large proportion of milkweed on the landscape grows in agricultural areas, there is concern about the negative effects of neonicotinoids on this non-target insect. 2. In the field, we exposed common milkweed (Asclepias syriaca), an obligate host plant of monarch butterflies, to agriculturally-realistic levels of clothianidin, a widely used neonicotinoid insecticide. We tested whether this treatment influenced the number of eggs laid and larval survival over two years. 3. Milkweeds were transplanted into 60 experimental plots alongside a corn crop planted with a clothianidin seed-coat and 60 control plots alongside an untreated corn crop. The number of eggs, larvae at each stage (first-fifth instar), and presence of other arthropods were recorded weekly from June to the end of August and survival from egg to fifth instar was estimated using a Bayesian state-space statistical model. 4. We counted more eggs in treated plots compared to control plots, suggesting a preference for treated milkweed. The number of plots with arthropods did not differ between treatments, but within treated plots, there was a greater decrease in the number of arthropods throughout the season. There was no evidence that monarchs selected plots with fewer arthropods for oviposition. Larval survival was lower in clothianidin-treated plots compared to control plots. 5. Our results suggest milkweed near clothianidin-treated crops can reduce larval survival of monarch butterflies. While we provide some evidence that clothianidin could also act as an ecological trap for this species, further work is needed to identify additional components of fitness, including individual egg-laying rates and survival beyond the pupal stage. Our findings add to a growing body of evidence that neonicotinoids can negatively affect non-target organisms.

PMID:33837530 | DOI:10.1111/1365-2656.13492

Int J Gynaecol Obstet. 2021 Apr 10. doi: 10.1002/ijgo.13702. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the influence of cancer on ovarian response and oocyte quality in controlled ovarian hyperstimulation (COH).

METHODS: This prospective study conducted at the Physiopathology of Reproduction and Andrology Unit of Sandro Pertini Hospital enrolled 82 cancer patients undergoing controlled ovarian stimulation (COH) cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization (IVF) for male-factor infertility from June 2016 to November 2019. The interventions performed were COH, oocyte retrieval, and quality evaluation. Main outcome measures were maximal estradiol levels on the day of human chorionic gonadotropin administration, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, and rates of metaphase 2 oocytes and abnormal oocytes. All data were analyzed using the Statistical Package for the Social Sciences (SPSS) 22.0 – SPSS Chicago, IL, USA.

RESULTS: Intergroup comparisons (82 cancer patients and 180 patients in control group) showed a significant difference in ovarian response, especially for a significant higher number of abnormal oocytes in cancer patients (P < 0.0001). Regression analysis to assess the influence of the neoplastic process, regardless of the type, on ovarian response showed an effect on the main outcome measured due to cancer itself.

CONCLUSION: Cancer influences the ovarian response, particularly the oocyte quality, during COH performed for fertility preservation.

PMID:33837528 | DOI:10.1002/ijgo.13702

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

Cancer Causes Control. 2021 Apr 9. doi: 10.1007/s10552-021-01422-4. Online ahead of print.

ABSTRACT

PURPOSE: Racial disparities in acute myeloid leukemia (AML) have been reported but the relative contribution of disease versus patient-specific factors including comorbidities and access to care is unclear.

METHODS: We conducted a retrospective analysis of patient characteristics, treatment patterns and outcomes in a racially diverse patient cohort controlling for cytogenetic risk group. Patients were classified into four groups: non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic and Other.

RESULTS: We evaluated 106 patients from 84 zipcodes incorporating demographics, clinicopathologic features, treatment patterns and outcomes. We identified significant differences in BMI and geographic poverty based on ethnoracial group, while prognostic mutations in NPM1 and FLT3 did not differ significantly. Utilization of intensive chemotherapy and transplant rate did not differ by ethnoracial group. However, there was a significantly higher use of alternate donor transplants in minority populations. There was a notably increased rate of clinical trial enrollment in NHW patients compared to other groups. In log-rank analysis, NHW patients had increased overall survival (OS) compared to NHB, Hispanic and Other patients (31.6 months vs. 16.7 months vs. 14.3 months, vs 18.1 months, p = 0.021). In bivariate analysis, overall survival was negatively influenced by advanced age and race. Obesity and zip code poverty levels approached statistical significance in predicting OS. In multivariate analysis, the only factors independently influencing OS were race and allogeneic stem cell transplant.

CONCLUSION: These results suggest that race impacts survival in intermediate-risk AML, highlighting the need to dissect biologic and nonbiologic factors that contribute to this disparity.

PMID:33837498 | DOI:10.1007/s10552-021-01422-4

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

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

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