Predictors of Invasiveness in Adenocarcinoma of Lung with Lepidic Growth Pattern.

Lung adenocarcinoma with lepidic growth pattern (LPA) is characterized by tumor cell proliferation along intact alveolar walls, and further classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive lepidic predominant adenocarcinoma (iLPA). Accurate diagnosis of lepidic lesions is critical for appropriate prognostication and management as five-year survival in patients with iLPA is lower than in those with AIS and MIA. We aimed to evaluate the accuracy of CT-guided core needle lung biopsy classifying LPA lesions and identify clinical and radiologic predictors of invasive disease in biopsied lesions. Thirty-four cases of adenocarcinoma with non-invasive lepidic growth pattern on core biopsy pathology that subsequently were resected between 2011 and 2018 were identified. Invasive LPA vs. non-invasive LPA (AIS or MIA) was defined based on explant pathology. Histopathology of core biopsy and resected tumor specimens was compared for concordance, and clinical, radiologic and pathologic variables were analyzed to assess for correlation with invasive disease. The majority of explanted tumors (70.6%) revealed invasive disease. Asian race (p = 0.03), history of extrathoracic malignancy (p = 0.02) and absence of smoking history (p = 0.03) were associated with invasive disease. CT-measured tumor size was not associated with invasiveness (p = 0.15). CT appearance of density (p = 0.61), shape (p = 0.78), and margin (p = 0.24) did not demonstrate a significant difference between the two subgroups. Invasiveness of tumors with lepidic growth patterns can be underestimated on transthoracic core needle biopsies. Asian race, absence of smoking, and history of extrathoracic malignancy were associated with invasive disease.

Phosphorylated S6 ribosomal protein expression by immunohistochemistry correlates with de novo donor-specific HLA antibodies in lung allograft recipients.

BACKGROUND: Per the ISHLT 2016 definition, a C4d-positive lung biopsy is required to meet criteria for definite antibody-mediated rejection (AMR). Unfortunately, C4d has poor sensitivity and specificity, and low inter-rater reliability. Phosphorylated S6 ribosomal protein (p-S6RP) expressed via the mTOR pathway has been shown to be a biomarker of AMR and correlates with donor-specific antibodies (DSA) in heart allografts. However, p-S6RP immunohistochemistry (IHC) in the setting of pulmonary AMR has yet to be evaluated. We sought to determine whether p-S6RP IHC performed on lung biopsies correlates with de novo DSA. METHODS: IHC for p-S6RP performed on 26 biopsies from lung transplant recipients with de novo HLA DSA (DSA+) and 28 biopsies from patients with no DSA (DSA-) were evaluated by 3 pathologists who independently scored the degree of alveolar macrophage and pneumocyte staining. Staining in ≥50% of the biopsy as determined by at least 2 pathologists was considered positive. RESULTS: Twenty-one (81%) DSA+ biopsies stained positive for p-S6RP in pneumocytes and 21 (81%) in macrophages. Six DSA- biopsies (21%) stained positive for p-S6RP in pneumocytes, 6 (21%) were positive in macrophages. Pneumocyte p-S6RP staining was 81% sensitive and 79% specific for DSA. Macrophage staining showed the same sensitivity and specificity but with lower inter-rater agreement (κ = 0.53 vs 0.68). CONCLUSIONS: This study demonstrates a positive relationship between de novo DSA and p-S6RP expression in pneumocytes and macrophages using IHC. p-S6RP is relatively sensitive and specific, and has superior inter-rater reliability compared to C4d.

Postural control development from late childhood through young adulthood.

BACKGROUND: The development of stable postural control is characterized by changes in sway variability and periods of rapid reorganization of motor system components. RESEARCH QUESTION: The current study examined whether changing biomechanical and perceptual demands influences the postural control behavior during development. METHOD: The center of pressure (COP) was assessed via a cross-sectional design. Data were collected from 48 females in three age groups (late childhood, mid-adolescence, and young adulthood) during four quiet stance conditions: (1) eyes open with feet apart, (2) eyes open with feet together, (3) eyes closed with feet apart, and (4) eyes closed with feet together. Linear measures included total path length of the COP and the mean/standard deviation of the overall COP position and speed. To characterize the sway patterns via nonlinear analyses, the speed and two-dimensional positional time series were submitted to sample entropy and Renyi entropy, respectively. RESULTS: The linear results indicated that the late childhood group displayed longer COP trajectories (p < .001) and faster and more variable COP speed (p's < .001). These results held for both the feet apart and feet together conditions, independent of vision. The nonlinear results indicated that the late childhood group exhibited less regularity, overall, in their COP sway position (i.e., Renyi entropy) compared to the two older groups in the feet apart condition (p's ≤ .041), and to the young adults in the feet together condition, independent of vision (p < .001). However, the mid-adolescent group demonstrated greater regularity in their COP speed (i.e., sample entropy) when their eyes were closed compared to the other two groups, independent of stance (p's < .05). SIGNIFICANCE: The linear results support previous findings, while the nonlinear measures indicate sway characteristics that may provide a window into the development of underlying control processes that regulate quiet standing.

Sex-Specific Dependence of Linear and Nonlinear Postural Control Metrics on Anthropometrics During Clinical Balance Tests in Healthy Young Adults.

CONTEXT: Previous work suggests that balance behavior is a sex-dependent, complex process that can be characterized by linear and nonlinear metrics. Although a certain degree of center of pressure variability may be expected based on sexual dimorphism, there is evidence to suggest that these effects are obscured by potential interactions between sex and anthropometric factors. To date, no study has accounted for such interactive effects using both linear and nonlinear measures. OBJECTIVE: This investigation sought to analyze interactive models featuring sex, height, and weight as predictors of linear and nonlinear aspects of postural control. DESIGN: Cross-sectional study. SETTING: Controlled laboratory. PARTICIPANTS: A total of 26 males (23.80 [3.44] y, 177.87 [6.44] cm, 81.70 [10.80] kg) and 28 females (21.14 [2.03] y, 169.57 [8.80] cm, 64.48 [8.86] kg) were sampled from a healthy university population. MAIN OUTCOME MEASURES: Linear (range [RNG], velocity [VEL], and SD) and nonlinear (detrended fluctuation analysis scaling exponent, multivariate multiscale sample entropy [MMSECI]) summary metrics of center of pressure time series. PROCEDURE: Participants stood on a force plate for 20 seconds in 3 conditions: double (D), single (S), and tandem (T) stance. Data for each stance condition were analyzed using regression models with interaction terms for sex × height and sex × weight. In D, weight had a positive, significant main effect on VELy, MMSECId, and MMSECIv. In men, height was observed to have a positive effect on SDy (S), RNGy (S), and RNGx (T) and a negative effect on MMSECIv (T). In women, weight was observed to have a positive effect on SDy and VELx (both T). CONCLUSIONS: Our findings suggest that men and women differ with respect to certain linear and nonlinear aspects of balance behavior, and that these differences may reflect sex-specific behavioral patterns in addition to effects related to sexual dimorphism.

Aldehyde dehydrogenase isoforms and inflammatory cell populations are differentially expressed in term human placentas affected by intrauterine growth restriction.

OBJECTIVE: Intrauterine growth restriction (IUGR) is a complication of pregnancy that has both short- and long-term sequelae for affected mothers and offspring. The pathophysiology of disease stems from poor nutrient and oxygen provision to the fetus, resulting in increased oxidative stress within the placenta. As the milieu within the local microenvironment alters macrophage differentiation, we hypothesized that macrophage plasticity may be altered in placentas associated with IUGR, and that macrophages would show hallmarks of lipid peroxidation including altered aldehyde metabolism. METHODS: In human placentas taken from normal pregnancies resulting in appropriate-for-gestational-age (AGA) newborns and placentas associated with IUGR, placental macrophages were evaluated by immunohistochemistry and shown in IUGR to resemble pro-inflammatory activated M1-type macrophages. To link oxidative stress to macrophages, the expression of aldehyde dehydrogenase (ALDHs) isozymes ALDH1, ALDH2, and ALDH3 was assessed. RESULTS: All three isozymes displayed preferential staining for distinct cellular populations within the term human placenta. ALDH1 and ALDH2 were strongly expressed in placental Hofbauer and decidual stromal cells. ALDH3, in contrast, was present in extravillous trophoblasts. Comparing AGA and IUGR-associated placentas, ALDH1 and ALDH2 trended to have greater expression in macrophage populations but lower expression in decidual cell populations in IUGR-associated placentas. ALDH3 had higher expression in IUGR-associated placentas but localized specifically to extravillous trophoblast populations. CONCLUSION: Therefore, we speculate that specific ALDH isozymes have cell-specific functions related to differentiation, inflammation, or oxidative stress responses that are altered in IUGR-associated term human placentas. This family of isozymes may be a novel method to identify human placentas affected by placental insufficiency/IUGR.

Relationship between changes in vestibular sensory reweighting and postural control complexity.

Complexity measures have become increasingly prominent in the postural control literature. Several studies have found associations between clinical balance improvements and complexity, but the relationship between sensory reweighting and complexity changes has remained unobserved. The purpose of this study was to determine the relationship between sensory reweighting via Wii Fit balance training and complexity. Twenty healthy adults completed 6 weeks of training. Participants completed the sensory organization test (SOT) before and after the sessions. Complexity of postural control was analyzed through sample entropy of the center-of-pressure velocity time series in the resultant, anterior-posterior (AP), and medial-lateral directions, and compared to SOT summary score changes. Significant differences were found between pre- and post-training for the condition five (p < .001, d = .525) and vestibular summary scores (p < .001, d = .611). Similarly, changes in complexity were observed from pre- to post-training in the resultant (p = .040, d = .427) direction. While the AP velocity was not significant (p = .07, d = .355), its effect size was moderate. A moderate correlation was revealed in the posttest between AP complexity and condition 5 (r = .442, p = .05), as well as between AP complexity and the vestibular summary score (r = .351, p = .13). The results of this study show that a moderate relationship exists between postural control complexity and the vestibular system, suggesting that complexity may reflect the neurosensory organization used to maintain upright stance.

Wii Fit exer-game training improves sensory weighting and dynamic balance in healthy young adults.

The Nintendo Wii Fit is a balance training tool that is growing in popularity due to its ease of access and cost-effectiveness. While considerable evidence now exists demonstrating the efficacy of the Wii Fit, no study to date has determined the specific mechanism underlying Wii Fit balance improvement. This paucity of knowledge was addressed in the present study using the NeuroCom Balance Manager's Sensory Organization Test (SOT) and Limits of Stability (LOS) test. These well-recognized posturography assessments, respectively, measure sensory weighting and dynamic stability mechanisms of balance. Forty healthy, young participants were recruited into two groups: Wii Fit Balance Intervention (WFBI) (n=20) and Control (CON) (n=20). Balance training consisted of seven Wii Fit exer-games played over the course of six consecutive weeks (2-4×/week, 30-45min/day). The WFBI group performed Neurocom testing before and after the intervention, while the CON group was tested along a similar timeline with no intervention. Mixed-design ANOVAs found significant interactions for testing time point and condition 5 of the SOT (p<0.02), endpoint excursion (p<0.01), movement velocity (p<0.02), and response time (p<0.01). These effects were such that greater improvements were seen for the WFBI group following Wii Fit training. These findings suggest that individuals with known issues regarding the processing of multiple sources of sensory information and/or who have limited functional bases of support may benefit most from Wii Fit balance training.

Using the Wii Fit as a tool for balance assessment and neurorehabilitation: the first half decade of "Wii-search".

The Nintendo Wii Fit was released just over five years ago as a means of improving basic fitness and overall well-being. Despite this broad mission, the Wii Fit has generated specific interest in the domain of neurorehabilitation as a biobehavioral measurement and training device for balance ability. Growing interest in Wii Fit technology is likely due to the ubiquitous nature of poor balance and catastrophic falls, which are commonly seen in older adults and various disability conditions. The present review provides the first comprehensive summary of Wii Fit balance research, giving specific insight into the system's use for the assessment and training of balance. Overall, at the time of the fifth anniversary, work in the field showed that custom applications using the Wii Balance Board as a proxy for a force platform have great promise as a low cost and portable way to assess balance. On the other hand, use of Wii Fit software-based balance metrics has been far less effective in determining balance status. As an intervention tool, positive balance outcomes have typically been obtained using Wii Fit balance games, advocating their use for neurorehabilitative training. Despite this, limited sample sizes and few randomized control designs indicate that research regarding use of the Wii Fit system for balance intervention remains subject to improvement. Future work aimed at conducting studies with larger scale randomized control designs and a greater mechanistic focus is recommended to further advance the efficacy of this impactful neurorehabilitation tool.