A cross-sectional study of differences in 6-min walk distance in healthy adults residing at high altitude versus sea level

BACKGROUND: We sought to determine if adult residents living at high altitude have developed sufficient adaptation to a hypoxic environment to match the functional capacity of a similar population at sea level. To test this hypothesis, we compared the 6-min walk test distance (6MWD) in 334 residents living at sea level vs. at high altitude. METHODS: We enrolled 168 healthy adults aged ≥35 years residing at sea level in Lima and 166 individuals residing at 3,825 m above sea level in Puno, Peru. Participants completed a 6-min walk test, answered a sociodemographics and clinical questionnaire, underwent spirometry, and a blood test. RESULTS: Average age was 54.0 vs. 53.8 years, 48% vs. 43% were male, average height was 155 vs. 158 cm, average blood oxygen saturation was 98% vs. 90%, and average resting heart rate was 67 vs. 72 beats/min in Lima vs. Puno. In multivariable regression, participants in Puno walked 47.6 m less (95% CI -81.7 to -13.6 m; p < 0.01) than those in Lima. Other variables besides age and height that were associated with 6MWD include change in heart rate (4.0 m per beats/min increase above resting heart rate; p < 0.001) and percent body fat (-1.4 m per % increase; p = 0.02). CONCLUSIONS: The 6-min walk test predicted a lowered functional capacity among Andean high altitude vs. sea level natives at their altitude of residence, which could be explained by an incomplete adaptation or a protective mechanism favoring neuro- and cardioprotection over psychomotor activity

NavWell: A simplified virtual-reality platform for spatial navigation and memory experiments

Being able to navigate, recall important locations, and find the way home are critical skills, essential for survival for both humans and animals. These skills can be examined in the laboratory using the Morris water maze, often considered the gold standard test of animal navigation. In this task, animals are required to locate and recall the location of an escape platform hidden in a pool filled with water. Because animals can not see the platform directly, they must use various landmarks in the environment to escape. With recent advances in technology and virtual reality (VR), many tasks originally used in the animal literature can now be translated for human studies. The virtual water maze task is no exception. However, a number of issues are associated with these mazes, including cost, lack of flexibility, and lack of standardization in terms of experimental designs and procedures. Here we present a virtual water maze system (NavWell) that is readily downloadable and free to use. The system allows for the easy design of experiments and the testing of participants on a desktop computer or fully immersive VR environment. The data from four independent experiments are presented in order to validate the software. From these experiments, a set of procedures for use with a number of well-known memory tests is suggested. This potentially can help with the standardization of navigational research and with navigational testing in the clinic or in an educational environment. Finally, we discuss the limitations of the software and plans for its development and future use

Prognostic Significance of Deregulated Dicer Expression in Breast Cancer

<div><p>Background</p><p>Dicer, an RNase III-type endonuclease, is the key enzyme involved in RNA interference and microRNA pathways. Aberrant expression of Dicer is reported in several human cancers. Our aim was to assess the prognostic role of Dicer in breast cancer.</p><p>Methods</p><p>The entire series comprised 666 invasive breast cancers (IBCs), 480 DCIS cases (397 associated with IBC and 83 pure DCIS) and 305 lymph node metastases. Cytoplasmic Dicer expression by immunohistochemistry was scored as negative (no staining) and positive (weak, moderate or strong staining).</p><p>Results</p><p>Dicer staining was assessable in 446 IBC, 128 DCIS and 101 lymph node metastases. Expression of Dicer was observed in 33% (145/446) of IBCs, 34% (44/128) of DCIS and 57% (58/101) of lymph node metastases. Dicer expression was increased in nodal metastases compared to primary tumours (p<0.001); and was associated with ER negativity (p<0.001), HER2 positivity (p<0.001), high Ki67 labeling index (p<0.001) and expression of basal-like biomarkers (p = 0.002). Dicer positivity was more frequent in the HER2 overexpressing (p<0.001) and basal-like (p = 0.002) subtypes compared to luminal A subtype. Dicer expression was associated with reduced overall survival (OS) on univariate analysis (p = 0.058) and remained an independent predictor of OS on multivariate analysis (HR 2.84, 95% CI 1.43–5.62, p = 0.003), with nodal status (HR 2.61, 95% CI 1.18–5.80, p = 0.018) and PR (HR 0.28, 95% CI 0.13–0.59, p = 0.001). Further, moderate or strong expression of Dicer was associated with improved disease-free survival in the HER2-overexpressing subtype compared to negative or weak expression (p = 0.038).</p><p>Conclusion</p><p>Deregulated Dicer expression is associated with aggressive tumour characteristics and is an independent prognostic factor for OS. Our findings suggest that Dicer is an important prognostic marker in breast cancer and that its prognostic role may be subtype specific.</p></div

Dicer expression by IHC in normal breast tissue.

<p>Representative images of Dicer staining (A) without blocking peptide and (B) with blocking peptide are shown. Panel A is representative of Dicer staining in normal breast tissue.</p

Clinico-pathological features and biomarker profile of the series.

<p>^a no. of cases for which data is available.</p><p>^b whole tumour measurement is given in cases if it differs from the size of the IBC.</p><p>LR: locoregional.</p

Kaplan-Meier curves for OS (A) and DFS (B) in IBC categorised according to Dicer expression in the entire series.

<p>Dicer expression is categorised as negative (intensity score 0) and positive (intensity score 1, 2 or 3).</p

Dicer expression in DCIS.

<p>Representative images of the spectrum of the staining intensity observed for Dicer in DCIS where 0 = negative (A), 1 = weak (B), 2 = moderate (C) and 3 = strong (D).</p

Kaplan-Meier curves for DFS (A, B) and OS (C) in the HER2 overexpressing subtype of IBC categorized according to Dicer expression.

<p>(A, C) Dicer expression is categorised as negative (intensity score 0) and positive (intensity scores 1, 2 and 3). (B) Dicer expression is categorised as negative (intensity score 0), low (intensity score 1) and high (intensity score 2 and 3).</p

Dicer expression scores in invasive carcinoma, DCIS and lymph node metastasis.

<p>^a number of cases for which Dicer expression data was available.</p><p>^b includes 108 DCIS cases associated with DCIS and 20 pure DCIS cases.</p

Multivariate analysis of Dicer expression for OS.

<p>^a HR: Hazard ratio.</p