Reproducibility of Brain Morphometry from Short-Term Repeat Clinical MRI Examinations: A Retrospective Study

Purpose

To assess the inter session reproducibility of automatic segmented MRI-derived measures by FreeSurfer in a group of subjects with normal-appearing MR images.

Materials and Methods

After retrospectively reviewing a brain MRI database from our institute consisting of 14,758 adults, those subjects who had repeat scans and had no history of neurodegenerative disorders were selected for morphometry analysis using FreeSurfer. A total of 34 subjects were grouped by MRI scanner model. After automatic segmentation using FreeSurfer, label-wise comparison (involving area, thickness, and volume) was performed on all segmented results. An intraclass correlation coefficient was used to estimate the agreement between sessions. Wilcoxon signed rank test was used to assess the population mean rank differences across sessions. Mean-difference analysis was used to evaluate the difference intervals across scanners. Absolute percent difference was used to estimate the reproducibility errors across the MRI models. Kruskal-Wallis test was used to determine the across-scanner effect.

Results

The agreement in segmentation results for area, volume, and thickness measurements of all segmented anatomical labels was generally higher in Signa Excite and Verio models when compared with Sonata and TrioTim models. There were significant rank differences found across sessions in some labels of different measures. Smaller difference intervals in global volume measurements were noted on images acquired by Signa Excite and Verio models. For some brain regions, significant MRI model effects were observed on certain segmentation results.

Conclusions

Short-term scan-rescan reliability of automatic brain MRI morphometry is feasible in the clinical setting. However, since repeatability of software performance is contingent on the reproducibility of the scanner performance, the scanner performance must be calibrated before conducting such studies or before using such software for retrospective reviewing.     

Short-Term Intensified Cycle Training Alters Acute and Chronic Responses of PGC1α and Cytochrome C Oxidase IV to Exercise in Human Skeletal Muscle

Reduced activation of exercise responsive signalling pathways have been reported in response to acute exercise after training; however little is known about the adaptive responses of the mitochondria. Accordingly, we investigated changes in mitochondrial gene expression and protein abundance in response to the same acute exercise before and after 10-d of intensive cycle training. Nine untrained, healthy participants (mean±SD; VO_2peak 44.1±17.6 ml/kg/min) performed a 60 min bout of cycling exercise at 164±18 W (72% of pre-training VO_2peak). Muscle biopsies were obtained from the vastus lateralis muscle at rest, immediately and 3 h after exercise. The participants then underwent 10-d of cycle training which included four high-intensity interval training sessions (6×5 min; 90–100% VO_2peak) and six prolonged moderate-intensity sessions (45–90 min; 75% VO_2peak). Participants repeated the pre-training exercise trial at the same absolute work load (64% of pre-training VO_2peak). Muscle PGC1-α mRNA expression was attenuated as it increased by 11- and 4- fold (P<0.001) after exercise pre- and post-training, respectively. PGC1-α protein expression increased 1.5 fold (P<0.05) in response to exercise pre-training with no further increases after the post-training exercise bout. RIP140 protein abundance was responsive to acute exercise only (P<0.01). COXIV mRNA (1.6 fold; P<0.01) and COXIV protein expression (1.5 fold; P<0.05) were increased by training but COXIV protein expression was decreased (20%; P<0.01) by acute exercise pre- and post-training. These findings demonstrate that short-term intensified training promotes increased mitochondrial gene expression and protein abundance. Furthermore, acute indicators of exercise-induced mitochondrial adaptation appear to be blunted in response to exercise at the same absolute intensity following short-term training.     

Photosynthetic Responses of Tropical Trees to Short-Term Exposure to Ozone

Saplings of the tropical trees Tibouchina pulchra (Cham.) Cogn., Caesalpinia echinata Lam., and Psidium guajava L. cv. Paluma were exposed in open-top chambers with charcoal filtered air and measurements of gas exchange and chlorophyll fluorescence were made before (t₁) and after exposure to non-filtered air plus O₃ (t₂), simulating 6-h peaks of O₃ similar to those observed in São Paulo city (SE Brazil, reaching an AOT40 of 641 nmol mol^–1). After the fumigation, the net photosynthetic rate, stomatal conductance, transpiration rate, and F_v/F_m were reduced (p<0.05) for the three species. C. echinata was the most sensitive species and P. guajava cv. Paluma the most resistant.     

Impact of Individual and Environmental Socioeconomic Status on Peritoneal Dialysis Outcomes: A Retrospective Multicenter Cohort Study

Objectives

We aimed to explore the impacts of individual and environmental socioeconomic status (SES) on the outcome of peritoneal dialysis (PD) in regions with significant SES disparity, through a retrospective multicenter cohort in China.

Methods

Overall, 2,171 incident patients from seven PD centers were included. Individual SES was evaluated from yearly household income per person and education level. Environmental SES was represented by regional gross domestic product (GDP) per capita and medical resources. Undeveloped regions were defined as those with regional GDP lower than the median. All-cause and cardiovascular death and initial peritonitis were recorded as outcome events.

Results

Poorer PD patients or those who lived in undeveloped areas were younger and less-educated and bore a heavier burden of medical expenses. They had lower hemoglobin and serum albumin at baseline. Low income independently predicted the highest risks for all-cause or cardiovascular death and initial peritonitis compared with medium and high income. The interaction effect between individual education and regional GDP was determined. In undeveloped regions, patients with an elementary school education or lower were at significantly higher risk for all-cause death but not cardiovascular death or initial peritonitis compared with those who attended high school or had a higher diploma. Regional GDP was not associated with any outcome events.

Conclusion

Low personal income independently influenced all-cause and cardiovascular death, and initial peritonitis in PD patients. Education level predicted all-cause death only for patients in undeveloped regions. For PD patients in these high risk situations, integrated care before dialysis and well-constructed PD training programs might be helpful.     

Association of Individual Non-Steroidal Anti-Inflammatory Drugs and Chronic Kidney Disease: A Population-Based Case Control Study

Background

Non-steroidal anti-inflammatory agents (NSAIDs) are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD), specifically, across various NSAIDs.

Aim

The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.

Methods

A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID). Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID), with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.

Results

Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44) and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44), meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87) and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21).

Conclusions

The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.     

Effects of Interval and Continuous Exercise Training on CD4 Lymphocyte Apoptotic and Autophagic Responses to Hypoxic Stress in Sedentary Men

Exercise is linked with the type/intensity-dependent adaptive immune responses, whereas hypoxic stress facilitates the programmed death of CD4 lymphocytes. This study investigated how high intensity-interval (HIT) and moderate intensity-continuous (MCT) exercise training influence hypoxia-induced apoptosis and autophagy of CD4 lymphocytes in sedentary men. Thirty healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO_2max, n=10) or MCT (sustained 60%VO_2max, n=10) for 30 minutes/day, 5 days/week for 5 weeks, or to a control group that did not received exercise intervention (CTL, n=10). CD4 lymphocyte apoptotic and autophagic responses to hypoxic exercise (HE, 100W under 12%O₂ for 30 minutes) were determined before and after various regimens. The results demonstrated that HIT exhibited higher enhancements of pulmonary ventilation, cardiac output, and VO₂ at ventilatory threshold and peak performance than MCT did. Before the intervention, HE significantly down-regulated autophagy by decreased beclin-1, Atg-1, LC3-II, Atg-12, and LAMP-2 expressions and acridine orange staining, and simultaneously enhanced apoptosis by increased phospho-Bcl-2 and active caspase-9/-3 levels and phosphotidylserine exposure in CD4 lymphocytes. However, five weeks of HIT and MCT, but not CTL, reduced the extents of declined autophagy and potentiated apoptosis in CD4 lymphocytes caused by HE. Furthermore, both HIT and MCT regimens manifestly lowered plasma myeloperoxidase and interleukin-4 levels and elevated the ratio of interleukin-4 to interferon-γ at rest and following HE. Therefore, we conclude that HIT is superior to MCT for enhancing aerobic fitness. Moreover, either HIT or MCT effectively depresses apoptosis and promotes autophagy in CD4 lymphocytes and is accompanied by increased interleukin-4/interferon-γ ratio and decreased peroxide production during HE.     

Distinct Transcriptional Responses across Tissue-Resident Macrophages to Short-Term and Long-Term Metabolic Challenge

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Evaluating Intervention Fidelity: An Example from a High-Intensity Interval Training Study

Aim

Intervention fidelity refers to the degree to which an experimental manipulation has been implemented as intended, but simple, robust methods for quantifying fidelity have not been well documented. Therefore, we aim to illustrate a rigorous quantitative evaluation of intervention fidelity, using data collected during a high-intensity interval training intervention.

Design

Single-group measurement study.

Methods

Seventeen adolescents (mean age ± standard deviation [SD] 14.0 ± 0.3 years) attended a 10-week high-intensity interval training intervention, comprising two exercise sessions per week. Sessions consisted of 4-7 45-s maximal effort repetitions, interspersed with 90-s rest. We collected heart rate data at 5-s intervals and recorded the peak heart rate for each repetition. The high-intensity exercise criterion was ≥90% of individual maximal heart rate. For each participant, we calculated the proportion of total exercise repetitions exceeding this threshold. A linear mixed model was applied to properly separate the variability in peak heart rate between- and within-subjects. Results are presented both as intention to treat (including missed sessions) and per protocol (only participants with 100% attendance; n=8).

Results

For intention to treat, the median (interquartile range) proportion of repetitions meeting the high-intensity criterion was 58% (42% to 68%). The mean peak heart rate was 85% of maximal, with a between-subject SD of 7.8 (95% confidence interval 5.4 to 11.3) percentage points and a within-subject SD of 15.1 (14.6 to 15.6) percentage points. For the per protocol analysis, the median proportion of high-intensity repetitions was 68% (47% to 86%). The mean peak heart rate was 91% of maximal, with between- and within-subject SDs of 3.1 (-1.3 to 4.6) and 3.4 (3.2 to 3.6) percentage points, respectively.

Conclusions

Synthesising information on exercise session attendance and compliance (exercise intensity) quantifies the intervention dose and informs evaluations of treatment fidelity.     

Chronic Arsenic Exposure and Risk of Post Kala-azar Dermal Leishmaniasis Development in India: A Retrospective Cohort Study

BackgroundVisceral leishmaniasis (VL), with the squeal of Post-kala-azar dermal leishmaniasis (PKDL), is a global threat for health. Studies have shown sodium stibogluconate (SSG) resistance in VL patients with chronic arsenic exposure. Here, we assessed the association between arsenic exposure and risk of developing PKDL in treated VL patients.MethodsIn this retrospective study, PKDL patients (n = 139), earlier treated with SSG or any other drug during VL, were selected from the study cohort. Trained physicians, unaware of arsenic exposure, interviewed them and collected relevant data in a questionnaire format. All probable water sources were identified around the patient’s house and water was collected for evaluation of arsenic concentration. A GIS-based village-level digital database of PKDL cases and arsenic concentration in groundwater was developed and individual point location of PKDL cases were overlaid on an integrated GIS map. We used multivariate logistic regression analysis to assess odds ratios (ORs) for association between arsenic exposure and PKDL development.ResultsOut of the 429 water samples tested, 403 had arsenic content of over 10 μg/L, with highest level of 432 μg/L among the seven study villages. Multivariate adjusted ORs for risk of PKDL development in comparison of arsenic concentrations of 10.1–200 μg/L and 200.1–432.0 μg/L were 1.85 (1.13–3.03) and 2.31 (1.39–3.8) respectively. Interestingly, similar results were found for daily dose of arsenic and total arsenic concentration in urine sample of the individual. The multivariate-adjusted OR for comparison of high baseline arsenic exposure to low baseline arsenic exposure of the individuals in the study cohort was 1.66 (95% CI 1.02–2.7; p = 0.04).ConclusionOur findings indicate the need to consider environmental factors, like long time arsenic exposure, as an additional influence on treated VL patients towards risk of PKDL development in Bihar.     

Prey Responses to Predator's Sounds: A Review and Empirical Study

Many animals assess their risk of predation by listening to and evaluating predators' vocalizations. We reviewed the literature to draw generalizations about predator discrimination abilities, the retention of these abilities over evolutionary time, and the potential underlying proximate mechanisms responsible for discrimination. Broadly, we found that some prey possess an ability to respond to a predator after having been evolutionarily isolated from a specific predator (i.e., predators are allopatric) and that some prey are predisposed to respond to certain types of predators that they coevolved with but without having ecological experience. However, these types of studies are lacking, and relatively, few studies have examined predator discrimination abilities in ungulates. To begin addressing these knowledge gaps, we performed field experiments on Mule deer (Odocoileus hemionus) in which we investigated the ability of deer to discriminate among familiar predators [coyotes (Canis latrans) and mountain lions (Puma concolor)] and an evolutionary relevant predator with which deer have had no recent exposure [locally extinct wolves (Canis lupus)]. We found that Mule deer respond to and discriminate among predators based on predator vocalizations and have retained an ability to respond to wolves that have been extinct from the study area since the early 20th century. Previous playback studies have shown that responses vary among human‐habituated and non‐habituated populations and differ according to human proximity. Deer greater than 0.5 km from human residences allocated more time to heightened responses both before and after stimulus playback. Our findings may help predict how prey–predator interactions may change as a result of the recovering wolf population with a basis in ecological and evolutionary experience in predator discrimination and desensitization.     

Proteome Dynamics and Physiological Responses to Short-Term Salt Stress in Brassica napus Leaves

Salt stress limits plant growth and crop productivity and is an increasing threat to agriculture worldwide. In this study, proteomic and physiological responses of Brassica napus leaves under salt stress were investigated. Seedlings under salt treatment showed growth inhibition and photosynthesis reduction. A comparative proteomic analysis of seedling leaves exposed to 200 mM NaCl for 24 h, 48 h and 72 h was conducted. Forty-four protein spots were differentially accumulated upon NaCl treatment and 42 of them were identified, including several novel salt-responsive proteins. To determine the functional roles of these proteins in salt adaptation, their dynamic changes in abundance were analyzed. The results suggested that the up-accumulated proteins, which were associated with protein metabolism, damage repair and defense response, might contribute to the alleviation of the deleterious effect of salt stress on chlorophyll biosynthesis, photosynthesis, energy synthesis and respiration in Brassica napus leaves. This study will lead to a better understanding of the molecular basis of salt stress adaptation in Brassica napus and provides a basis for genetic engineering of plants with improved salt tolerance in the future.     

Sensitivity Analysis of Individual Responses of Plants to Global Change

Today research on global change is becoming one of the three vital topics in ecology. Within this field, simulating an individual plant’s physiological responses to global change, especially the combined effects of CO2 enrichment and the climatic change it caused, is a useful model in predicting the changes of either natural vegetation or agricultural crops, in that the physiological basis of the responses are mostly understood and the results of simulation can be checked with experi ments at any level or step when needed. Since the scenarios of the global changes often differ with different GCM’s, and will change as the GCM’s are being improved, even though, the simulation programs can still be used to for new predictions. In this study, based on the physiological mechanisms, a systematic dynamic model of plant individual growth was established, which included a weather generator and a growth module. The combined effects of enriched CO2 and climatic change on the main physiological processes, such as photosynthesis, respiration, etc., and seasonal dynamics of biomass were considered in the model. The data sets of the long-term weather records of Beijing Meteorological Station and the observed values of many ecophysiological quantities, obtained in a CO2 enrichment experiment of soybean, were used to parameterize and to validate the model. The results showed that data obtained from the simulation were quite compatible with those from the observation. When the CO2 concentration was doubled, the peak values of the total biomass and green biomass were increased approximately by 70% and 56% respectively. Furthermore, the responses of the total net assimilation and the average specific dark respiration rate within the growth season explained the internal mechanism of the biomass responses. The result indicated that the total net assimilation increased, while the average specific dark respiration rate decreased. Thus, it can be deduced that the increase of biomass was brought about not only by the increase of the net assimilation, but also by 'the decrease of the specific dark respiration rate. Sensitivity analysis was used to the soybean individual responses to global change. The seasonal dynamics of the total biomass to the combined effects of different levels of CO2, temperature and precipitation were simulated. CO2 concentration and precipitation have positive, while temperature has negative effect on total biomass. The positive effect of precipitation became weaker with increasing temperatures, while the negative effect of temperature was strengthened by the increased precipitation. The positive effect of CO2 concentration became stronger with the increasing temperatures, but weaker under enhancing precipitations. The positive effect of precipitation and the negative effect of temperature were weakened by doubling the CO2 concentration. These are partly due to the enhanced water use efficiency caused by CO2 enrichment, which in turn renders the plant individual more resistant and adaptable to the environmental change.     

Introduction to “Coping with Environmental Risk and Uncertainty: Individual and Cultural Responses”

The papers in this special issue of Human Nature collectively consider societal and individual responses to a wide variety of environmental and social risks. The first paper considers societal level effects of pathogen risk on collectivism and conformity, avoidance of outsiders, and in-group loyalty in a worldwide cross-cultural sample. The second deals with societal-level effects of resource unpredictability on the nature and conduct of warfare in eastern Africa. The third deals with effects of volcanic eruptions and earthquakes and mediating factors on individual perceptions of risk in Mexico and Ecuador. The final paper deals with effects of various types of father absence on women’s reproductive life histories in Bangladesh.     

Exploring Responses to Art in Adolescence: A Behavioral and Eye-Tracking Study

Adolescence is a peculiar age mainly characterized by physical and psychological changes that may affect the perception of one''s own and others'' body. This perceptual peculiarity may influence the way in which bottom-up and top-down processes interact and, consequently, the perception and evaluation of art. This study is aimed at investigating, by means of the eye-tracking technique, the visual explorative behavior of adolescents while looking at paintings. Sixteen color paintings, categorized as dynamic and static, were presented to twenty adolescents; half of the images represented natural environments and half human individuals; all stimuli were displayed under aesthetic and movement judgment tasks. Participants'' ratings revealed that, generally, nature images are explicitly evaluated as more appealing than human images. Eye movement data, on the other hand, showed that the human body exerts a strong power in orienting and attracting visual attention and that, in adolescence, it plays a fundamental role during aesthetic experience. In particular, adolescents seem to approach human-content images by giving priority to elements calling forth movement and action, supporting the embodiment theory of aesthetic perception.     

Effects of High Intensity Interval Training and Strength Training on Metabolic,Cardiovascular and Hormonal Outcomes in Women with Polycystic Ovary Syndrome: A Pilot Study

Background

Polycystic ovary syndrome is a common endocrinopathy in reproductive-age women, and associates with insulin resistance. Exercise is advocated in this disorder, but little knowledge exists on the optimal exercise regimes. We assessed the effects of high intensity interval training and strength training on metabolic, cardiovascular, and hormonal outcomes in women with polycystic ovary syndrome.

Materials and Methods

Three-arm parallel randomized controlled trial. Thirty-one women with polycystic ovary syndrome (age 27.2 ± 5.5 years; body mass index 26.7 ± 6.0 kg/m²) were randomly assigned to high intensity interval training, strength training, or a control group. The exercise groups exercised three times weekly for 10 weeks.

Results

The main outcome measure was change in homeostatic assessment of insulin resistance (HOMA-IR). HOMA-IR improved significantly only after high intensity interval training, by -0.83 (95% confidence interval [CI], -1.45, -0.20), equal to 17%, with between-group difference (p = 0.014). After high intensity interval training, high-density lipoprotein cholesterol increased by 0.2 (95% CI, 0.02, 0.5) mmol/L, with between group difference (p = 0.04). Endothelial function, measured as flow-mediated dilatation of the brachial artery, increased significantly after high intensity interval training, by 2.0 (95% CI, 0.1, 4.0) %, between-group difference (p = 0.08). Fat percentage decreased significantly after both exercise regimes, without changes in body weight. After strength training, anti-Müllarian hormone was significantly reduced, by -14.8 (95% CI, -21.2, -8.4) pmol/L, between-group difference (p = 0.04). There were no significant changes in high-sensitivity C-reactive protein, adiponectin or leptin in any group.

Conclusions

High intensity interval training for ten weeks improved insulin resistance, without weight loss, in women with polycystic ovary syndrome. Body composition improved significantly after both strength training and high intensity interval training. This pilot study indicates that exercise training can improve the cardiometabolic profile in polycystic ovary syndrome in the absence of weight loss.

Trial Registration

ClinicalTrial.gov NCT01919281     

Oral Contraceptives and Breast Neoplasia: A Retrospective Study

Between 1 December 1968 and 31 December 1971 345 women aged 16-39 years with a lump in the breast (90 malignant and 255 benign) were interviewed at five London teaching hospitals together with 347 matched controls suffering from acute medical or surgical conditions or admitted to hospital for routine elective surgery. Questions were asked about each patient''s medical, obstetric, menstrual, contraceptive, and social histories.The data do not suggest that the use of oral contraceptives is related in any way to the risk of breast cancer but provide some evidence that the preparations may actually protect against benign breast disease. This protective effect is largely confined to women who continue to use oral contraceptives and have used them altogether for more than two years. Such women appear to have only about 25% as great a risk of being admitted to hospital for a breast biopsy as women who have never used oral contraceptives at all.     

Short-Term and Long-Term Responses of Crassulacean Acid Metabolism Plants to Elevated CO(2)

For the leaf succulent Agave deserti and the stem succulent Ferocactus acanthodes, increasing the ambient CO₂ level from 350 microliters per liter to 650 microliters per liter immediately increased daytime net CO₂ uptake about 30% while leaving nighttime net CO₂ uptake of these Crassulacean acid metabolism (CAM) plants approximately unchanged. A similar enhancement of about 30% was found in dry weight gain over 1 year when the plants were grown at 650 microliters CO₂ per liter compared with 350 microliters per liter. Based on these results plus those at 500 microliters per liter, net CO₂ uptake over 24-hour periods and dry weight productivity of these two CAM succulents is predicted to increase an average of about 1% for each 10 microliters per liter rise in ambient CO₂ level up to 650 microliters per liter.     

Bisphosphonates and Osteonecrosis of the Jaw: A Retrospective Study

ObjectiveTo assess the prevalence of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonate therapy and in those who were bisphosphonate naïve.MethodsWe undertook a retrospective review of medical records of patients at the New York Harbor Health Care System from 1999 through 2004. Charts were selected for review if patients had a Current Procedural Terminology (CPT) code suggestive of ONJ or if they had ever received bisphosphonate therapy.ResultsAmong 1,951 medical records reviewed, we identified 2 patients with ONJ who had received bisphos-phonates and 2 patients with ONJ who were bisphospho-nate naïve. Both patients treated with bisphosphonates had multiple myeloma and were receiving monthly infusions. They had initially received pamidronate before treatment was changed to zoledronic acid. In each case, ONJ was precipitated by a routine dental extraction. The prevalence of ONJ in our patient population receiving intravenously administered bisphosphonates was 1 in 71.5. Of the 2 cases of ONJ in bisphosphonate-naïve patients, osteora-dionecrosis was clearly incriminated in 1 patient and potentially the causative factor in the other patient as well. No patients receiving orally administered bisphosphonates had ONJ, nor did this complication occur in any patients receiving parenteral bisphosphonate therapy for disorders such as osteoporosis or Paget’s disease of bone.ConclusionBisphosphonates remain an important option for management of metabolic bone disease and complications of malignant disease. The overall prevalence of ONJ in patients receiving bisphosphonates seems to be very low; however, patients receiving intense parenteral therapy for an underlying malignant condition appear to have a uniquely elevated risk for the development of this complication. A causal relationship between bisphosphonates and ONJ remains to be proved and merits further investigation. (Endocr Pract. 2007;13:232-238)