Active-Duty Physicians' Perceptions and Satisfaction with Humanitarian Assistance and Disaster Relief Missions: Implications for the Field

Background

The United States Department of Defense participates in more than 500 missions every year, including humanitarian assistance and disaster relief, as part of medical stability operations. This study assessed perceptions of active-duty physicians regarding these activities and related these findings to the retention and overall satisfaction of healthcare professionals.

Methods and Findings

An Internet-based survey was developed and validated. Of the 667 physicians who responded to the survey, 47% had participated in at least one mission. On a 7-point, Likert-type response scale, physicians reported favorable overall satisfaction with their participation in these missions (mean  = 5.74). Perceived benefit was greatest for the United States (mean  = 5.56) and self (mean  = 5.39) compared to the target population (mean  = 4.82). These perceptions were related to participants'' intentions to extend their military medical service (total model R ²  = .37), with the strongest predictors being perceived benefit to self (β = .21, p<.01), the U.S. (β = .19, p<.01), and satisfaction (β = .18, p<.05). In addition, Air Force physicians reported higher levels of satisfaction (mean  = 6.10) than either Army (mean  = 5.27, Cohen''s d = 0.75, p<.001) or Navy (mean  = 5.60, Cohen''s d  = 0.46, p<.01) physicians.

Conclusions

Military physicians are largely satisfied with humanitarian missions, reporting the greatest benefit of such activities for themselves and the United States. Elucidation of factors that may increase the perceived benefit to the target populations is warranted. Satisfaction and perceived benefits of humanitarian missions were positively correlated with intentions to extend time in service. These findings could inform the larger humanitarian community as well as military medical practices for both recruiting and retaining medical professionals.     

Task-specific performance fatigability and the bilateral deficit during isokinetic leg extensions

Objectives:The purpose of the present study was to compare the fatigue-induced changes in performance fatigability, bilateral deficit, and patterns of responses for the electromyographic (EMG) and mechanomyographic (MMG) amplitude (AMP) and mean power frequency (MPF), during unilateral and bilateral maximal, fatiguing leg extensions.Methods:Nine men (Mean±SD; age =21.9±2.4 yrs; height =181.8±11.9 cm; body mass =85.8±6.2 kg) volunteered to perform 50 consecutive maximal, bilateral (BL), unilateral dominant (DL), and unilateral non-dominant (NL) isokinetic leg extensions at 180°·s^-1, on 3 separate days. Electromyographic and MMG signals from both vastus lateralis (VL) muscles were recorded. Repeated measures ANOVAs were utilized to examine mean differences in normalized force, EMG AMP, EMG MPF, MMG AMP, MMG MPF and the bilateral deficit.Results:The results demonstrated a Condition × Repetition interaction for normalized force (p=0.004, η²_p=0.222) and EMG MPF (p=0.034, η²_p=0.214) and main effects for Repetition for EMG AMP (p=0.019, η²_p=0.231), MMG AMP (p<0.001, η²_p=0.8550), MMG MPF (p=0.009, η²_p=0.252), and the bilateral deficit (p<0.001, η²_p=0.366).Conclusions:The findings demonstrated less performance fatigability during the BL than the unilateral tasks, likely due to a reduced relative intensity via interhemispheric inhibition that attenuated the development of excitation-contraction coupling failure during the BL task.     

Gender-specific genetic associations of polymorphisms in ACE,AKR1C2, FTO and MMP2 with weight gain over a 10-year period

Weight gain, when it leads to overweight or obesity, is nowadays one of the major health problems. ACE, FTO, AKR1C2, TIMP4 and MMP2 genes have been implicated in previous studies on weight regulation. This study investigated the contribution of polymorphisms in these five candidate genes to the risk of weight gain over a 10-year time period. Two groups were selected from participants of the Doetinchem cohort study who were followed over a 10-year period: A stable weight group (±2 kg/10 year; n = 259) and a weight gainers group who increased their body weight by roughly 10 % (>8 kg/10 year; n = 237). Starting BMI was between 20 and 35 kg/m² and baseline age between 20 and 45 years. Selected SNPs and insert/deletion in candidate genes were measured in each group. In men, the allelic distribution of FTO rs9939609 (χ²p = 0.005), ACE rs4340 (χ²p = 0.006) and AKR1C2 rs12249281 (χ²p = 0.019) differed between the weight stable and weight gainers group. Interaction between FTO rs9939609 and ACE rs4340 was observed. In women, the allelic distribution of MMP2 rs1132896 differed between the weight stable and weight gainers group (χ²p = 0.00001). The A-allele of FTO was associated with a 1.99× higher risk of gaining weight in men (OR 1.99, p = 0.020), while in women, the C-allele of MMP2 was associated with a 2.50× higher risk of weight gain (OR 2.50, p = 0.001) over the 10-year period. We found that FTO in men and MMP2 in women are associated with weight gain over a 10-year follow-up period.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0434-2) contains supplementary material, which is available to authorized users.     

High Prevalence of HIV,HCV and Tuberculosis and Associated Risk Behaviours among New Entrants of Methadone Maintenance Treatment Clinics in Guangdong Province,China

Background

Methadone maintenance treatment (MMT) has been available in Guangdong province, China since 2006. This study aims to estimate the prevalence levels of HIV, Hepatitis C (HCV), Tuberculosis (TB) and their co-infections and associated demographic and risk behaviours among MMT entrants.

Method

A total of 2296 drug users at the time of their MMT enrolment were recruited from four clinics during 2006-2011. Participants’ demographic characteristics, infection status and self-reported high-risk drug-use and sexual behaviours were surveyed. Log-linear contingency analysis was employed to investigate the demographic and behavioural differences between gender and drug-user type, while multivariate regression analysis was used to identify the associated factors of HIV, HCV and TB infections.

Results

Female drug users demonstrate significantly higher frequency of daily drug consumption (Log-linear contingency analysis, G²=10.86, p=0.013) and higher proportion of having had sex in the past three months (G²=30.22, p<0.001) than their male counterparts. Among injecting drug users, females also inject (χ²=16.15, p=0.001) and share syringes (χ²=13.24, p=0.004) more frequently than males. Prevalence of HIV, HCV and TB among MMT entrants are 6.3%, 78.7% and 4.4% respectively. Co-infections of HIV/HCV, HIV/TB, HCV/TB and HIV/HCV/TB reportedly infect 5.6%, 0.5%, 3.8% and 0.3% of study participants. Infection risks of HIV, HCV and TB are consistently associated with increasing length of drug use, injecting drugs, financial dependence and reduced sexual activities.

Conclusion

Injecting drug use is the major contributing factor in prevalence levels of HIV, HCV and TB among MMT entrants. Female drug users are more disadvantaged in their social status and risk-taking in their drug use behaviours than males.     

Worst case scenario match analysis and contextual variables in professional soccer players: a longitudinal study

This study aimed to describe the worst-case scenarios (WCS) of professional soccer players by playing position in different durations and analyse WCS considering different contextual variables (match half, match location and match outcome). A longitudinal study was conducted in a professional soccer team. Data were collected from different WCS durations in the total distance (TD), high-speed running distance (HSRD), and sprinting distance (SPD). A mixed analysis of variance was performed to compare different WCS durations between playing positions and contextual variables, making pairwise comparisons by Bonferroni post hoc test. Positional differences were found for TD (p < 0.01, ω_p² = 0.02), HSRD (p < 0.01, ω_p² = 0.01) and SPD (p < 0.01, ω_p² = 0.02). There was a significant interaction when comparing WCS by match half in TD (F = 6.1, p < 0.01, ω_p² = 0.07) but no significant differences in HSRD (p = 0.403, ω_p² = 0) or SPD (p = 0.376, ω_p² = 0). A significant interaction was identified when comparing WCS by match location in TD (F = 51.5, p < 0.01, ω_p² = 0.14), HSRD (F = 19.15, p < 0.01, ω_p² = 0.05) and SPD (F = 8.95, p < 0.01, ω_p² = 0.01) as well as WCS by match outcome in TD (F = 36.4, p < 0.01, ω_p² = 0.08), HSRD (F = 13.6, p < 0.01, ω_p² = 0.04) and SPD (F = 7.4, p < 0.01, ω_p² = 0.02). Positional differences exist in TD, HSRD, and SPD in match-play WCS, and contextual variables such as match half, match location and match outcome have a significant impact on the WCS of professional soccer players.     

Incidence and Characteristics of Injuries during the 2010 FELDA/FAM National Futsal League in Malaysia

Objective

In Malaysia, futsal is a popular sport played by individuals across all ages and genders. Despite its popularity, information on futsal related injury in Malaysia is not available. The purpose of this study is to examine the injury incidence and injury patterns among amateur men and women futsal players in Malaysia.

Methods

Players reported injury to the tournament medical team during the FELDA/FAM National Futsal League 2010 were interviewed and assessed by a Sports Medicine registrar. Player''s socio-demographic profiles and information about the injury were documented in the injury report form adapted from medical report form used by FIFA: Medical Assessment and Research Centre (F-Marc).

Results

A total of 86 injuries were reported from 141 matches, equivalent to an incidence of 91.5 injuries per 1000 player hours (95% CI 72.2 to 110.8), or 61.0 injuries per 1000 player matches (95% CI 48.1 to 73.9). Most were minor injuries resulted from contact with another player. Injuries often involved the lower extremity (44%) followed by the trunk (14%) and the upper limb (13%). Ankle (n = 7; 39%) and knee (n = 6; 33%) sprains were the most prevalent diagnoses of time-loss injuries. A significant association between time-loss and type of injury was found χ ² (1,N = 86) = 3.99, p = 0.04. In addition, time-loss injury was significantly associated with playing surface χ ² (1,N = 86) = 10.11, p = 0.018.

Conclusion

The injury rate during the FELDA/FAM National Amateur Futsal Men''s League in Malaysia was lower compared with previous Futsal World Cups competition. Most injuries resulted from contact with another player were minor and did not lead to time-loss from participation. Time-loss injury was significantly associated with type of injury and playing surface.     

Meningiomas of the Cerebellopontine Angle: Radiological Differences in Tumors with Internal Auditory Canal Involvement and Their Influence on Surgical Outcome

This study explored the clinical, radiological, and pathological characteristics of cerebellopontine angle (CPA) meningiomas with internal auditory canal (IAC) involvement. The pre- and postoperative MR images of 193 consecutive patients with pathologically diagnosed meningioma centered around the IAC were analyzed, focusing on changes in the IAC, maximal axial tumor volume, peritumoral brain edema, and postoperative residual tumor. Patient age, sex, tumor volume, postoperative residual tumor, and pathological subtype were compared in patients with and without IAC involvement by the tumor and among the different types of IAC involvement. The results showed that the 71 patients (36.8%) with IAC involvement had a higher ratio of peritumoral edema (χ²=5.922, P=0.015), postoperative residual tumor (χ²=22.183, P< 0.001), and a predominance of the meningothelial subtype (χ²=5.89, P=0 .015). Peritumoral edema was a risk factor for IAC involvement (P=0.016, OR=2.186). Radiologically, IAC involvement could be distinguished as intruding (31%, 22/71), filled (29.6%, 21/71), and dilated (39.4%, 28/71). Patients with intruding IAC were significantly older (54.5±9.54 years, P=0.021) and had the lowest postoperative residual tumor values (42%, χ²=7.865, P= 0.005), while those with filled IAC were more likely to be female (95%, χ²=9.404, P=0.009).Our observations provide the basis for a morphological classification of IAC involvement by CPA meningiomas and further insight into the clinical features of these tumors.     

Genotypes and Transmitted Drug Resistance among Treatment-Naive HIV-1-Infected Patients in a Northwestern Province,China: Trends from 2003 to 2013

Background

Transmitted drug resistance (TDR) reduces the efficacy of initial antiretroviral treatment and has become a public health concern. Little information is available regarding the genetic diversity of HIV-1 and the prevalence of TDR among treatment-naïve patients in a northwestern province of China since the implementation of national free antiretroviral therapy (ART).

Methods

Blood samples from 372 HIV-1 treatment-naive patients were collected between 2003 and 2013 in Shaanxi province. Viral RNA was extracted for nested PCR, and phylogenetic reconstruction and recombination analyses were performed to characterize patterns of the HIV-1 subtypes. Genotypic drug resistance testing was performed using an in-house assay to determine trends in the prevalence of HIV-1 transmitted drug resistance.

Results

Multiple genotypes were identified among the patients in Shaanxi, including B (25.0%), C (0.3%), G (0.3%), and CRF01_AE (39.2%), CRF07_BC (32.7%), CRF08_BC (0.8%), CRF55_01B (1.1%), and URFs (0.6%). The subtypes were associated with the transmission routes (χ² = 77.113, p<0.01). In this study, a low baseline CD4⁺ T cell count and a high viral load were found among CRF01_AE-infected patients compared with patients who were infected with non-CRF01_AE (p<0.01) through sexual transmission; however, the CRF01_AE subtype was not associated with a low baseline CD4⁺ T cell count or a high viral load in Chinese patients infected through blood transmission (p = 0.249). The overall TDR rate in this population was 4.4% between 2003 and 2013. A univariate logistic regression model revealed that a low CD4 T cell count (≤100 cells/µL) was associated with the development of drug-resistant strains.

Conclusion

Our work revealed diverse HIV-1 subtype distributions in Shaanxi province. We identified a low and stable TDR time trend among ART-naive patients. These findings enhance our understanding of HIV-1 genetic diversity and provide some guidelines for the improvement and implementation of a comprehensive public health strategy of HIV-1 TDR prevention.     

Common Variants of FTO Are Associated with Childhood Obesity in a Cross-Sectional Study of 3,126 Urban Indian Children

Background

FTO variants are robustly associated with obesity and related traits in many population and shown to have variable impact during life course. Although studies have shown association of FTO variants with adiposity in adult Indian, its association in Indian children is yet to be confirmed.

Methods

Here we examined association of FTO variants (rs9939609 and rs8050136) with obesity and related anthropometric and biochemical traits in 3,126 Indian children (aged 11–17 years) including 2,230 normal-weight and 896 over-weight/obese children. We also compared effects observed in the present study with that observed in previous studies on South Asian adults and children of other ethnic groups.

Results

The variant rs9939609 showed significant association with risk of obesity [OR = 1.21, P = 2.5×10⁻³] and its measures BMI, weight, waist circumference and hip circumference [β range = 0.11 to 0.14 Z-score units; P range = 1.3×10⁻⁴ to 1.6×10⁻⁷] in children. The observed effect sizes in Indian children were similar to those reported for European children. Variant rs9939609 explained 0.88% of BMI variance in Indian children. The effect sizes of rs9939609 on BMI and WC were ∼2 fold higher in children than adults. Interestingly rs9939609 was also associated with serum levels of thyroid stimulating hormone (TSH) [β = 0.10 Z-score, P = 5.8×10⁻³]. The other variant rs8050136 was in strong linkage disequilibrium with rs9939609 (r² = 0.97) and provided similar association results.

Conclusion

The study provides first report of association of FTO variants with obesity and related anthropometric traits in Indian children with higher impact in children compared to adults. We also demonstrated association of FTO variant with serum levels of TSH, indicating putative influence of FTO in hypothalamic-pituitary-thyroid axis.     

Fasting Enhances TRAIL-Mediated Liver Natural Killer Cell Activity via HSP70 Upregulation

Acute starvation, which is frequently observed in clinical practice, sometimes augments the cytolytic activity of natural killer cells against neoplastic cells. In this study, we investigated the molecular mechanisms underlying the enhancement of natural killer cell function by fasting in mice. The total number of liver resident natural killer cells in a unit weight of liver tissue obtained from C57BL/6J mice did not change after a 3-day fast, while the proportions of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)⁺ and CD69⁺ natural killer cells were significantly elevated (n = 7, p <0.01), as determined by flow cytometric analysis. Furthermore, we found that TRAIL⁻ natural killer cells that were adoptively transferred into Rag-2^−/− γ chain^−/− mice could convert into TRAIL⁺ natural killer cells in fasted mice at a higher proportion than in fed mice. Liver natural killer cells also showed high TRAIL-mediated antitumor function in response to 3-day fasting. Since these fasted mice highly expressed heat shock protein 70 (n = 7, p <0.05) in liver tissues, as determined by western blot, the role of this protein in natural killer cell activation was investigated. Treatment of liver lymphocytes with 50 µg/mL of recombinant heat shock protein 70 led to the upregulation of both TRAIL and CD69 in liver natural killer cells (n = 6, p <0.05). In addition, HSP70 neutralization by intraperitoneally injecting an anti- heat shock protein 70 monoclonal antibody into mice prior to fasting led to the downregulation of TRAIL expression (n = 6, p <0.05). These findings indicate that acute fasting enhances TRAIL-mediated liver natural killer cell activity against neoplastic cells through upregulation of heat shock protein 70.     

Visual vs Fully Automatic Histogram-Based Assessment of Idiopathic Pulmonary Fibrosis (IPF) Progression Using Sequential Multidetector Computed Tomography (MDCT)

Objectives

To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector computed tomography (MDCT) assessed by semi-quantitative visual scores (VSs) and fully automatic histogram-based quantitative evaluation and to test the relationship between these two methods of quantification.

Methods

Forty IPF patients (median age: 70 y, interquartile: 62-75 years; M:F, 33:7) that underwent 2 MDCT at different time points with a median interval of 13 months (interquartile: 10-17 months) were retrospectively evaluated. In-house software YACTA quantified automatically lung density histogram (10^th-90^th percentile in 5^th percentile steps). Longitudinal changes in VSs and in the percentiles of attenuation histogram were obtained in 20 untreated patients and 20 patients treated with pirfenidone. Pearson correlation analysis was used to test the relationship between VSs and selected percentiles.

Results

In follow-up MDCT, visual overall extent of parenchymal abnormalities (OE) increased in median by 5 %/year (interquartile: 0 %/y; +11 %/y). Substantial difference was found between treated and untreated patients in HU changes of the 40th and of the 80th percentiles of density histogram. Correlation analysis between VSs and selected percentiles showed higher correlation between the changes (Δ) in OE and Δ 40^th percentile (r=0.69; p<0.001) as compared to Δ 80^th percentile (r=0.58; p<0.001); closer correlation was found between Δ ground-glass extent and Δ 40^th percentile (r=0.66, p<0.001) as compared to Δ 80^th percentile (r=0.47, p=0.002), while the Δ reticulations correlated better with the Δ 80^th percentile (r=0.56, p<0.001) in comparison to Δ 40^th percentile (r=0.43, p=0.003).

Conclusions

There is a relevant and fully automatically measurable difference at MDCT in VSs and in histogram analysis at one year follow-up of IPF patients, whether treated or untreated: Δ 40^th percentile might reflect the change in overall extent of lung abnormalities, notably of ground-glass pattern; furthermore Δ 80^th percentile might reveal the course of reticular opacities.     

Serum levels of appetite-regulating hormones and pro-inflammatory cytokines are ameliorated by a CLA diet and endurance exercise in rats fed a high-fat diet

[Purpose]

This study examined whether conjugated linoleic acid (CLA) supplementation and endurance exercise affect appetite-regulating hormones and pro-inflammatory cytokines in rats.

[Methods]

Seven-week-old male Sprague-Dawley rats were divided randomly into the high-fat diet sedentary group (HS, n=8), the 1.0% CLA supplemented high-fat diet sedentary group (CS, n=8), and the 1.0% CLA supplemented high-fat diet exercise group (CE, n=8). Rats in the CE group swam 60 min/day, 5 days/week for 4 weeks.

[Results]

Leptin and insulin levels in the CS and CE groups were significantly lower than those in the HS group (p<0.001), whereas leptin (p<0.01) and insulin (p<0.05) levels decreased significantly in the CE compared to those in the CS group. Interleukin (IL)-1β (p<0.001) and IL-6 (p<0.01) levels in the CS and CE groups decreased significantly compared to those in the HS group. Leptin (IL-1β: r=0.835, p<0.001), IL-6 (r=0.607, p<0.05), insulin (IL-1β: r=0.797, p<0.01), and IL-6 (r=0.827, p<0.01) levels were positively related with pro-inflammatory cytokine levels.

[Conclusion]

Endurance exercise may play an important role during CLA supplementation of rats on a high-fat diet.     

Mildly Elevated Serum Bilirubin Levels Are Negatively Associated with Carotid Atherosclerosis among Elderly Persons

Serum bilirubin may have a beneficial role in preventing oxidative changes in atherosclerosis. Limited information is available on whether serum total bilirubin is an independent confounding factor for carotid atherosclerosis {for example, intima-media thickness (IMT), plaque} measured noninvasively by B-mode ultrasonography only among elderly persons. The study subjects were 325 men aged 79±8 (mean ± standard deviation) years and 509 women aged 81±8 years that were enrolled consecutively from patients aged ≥60 years in the medical department. Carotid IMT and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that in men age (β = 0.199, p = 0.002), smoking status (β = 0.154, p = 0.006), GGT (β = -0.139, p = 0.039), and GGT (β = -0.133, p = 0.022) were significantly and independently associated with carotid IMT, and in women age (β = 0.186, p<0.001), systolic blood pressure (β = 0.104, p = 0.046), diastolic blood pressure (β = -0.148, p = 0.004), prevalence of antihypertensive medication (β = 0.126, p = 0.004), fasting plasma glucose (β = 0.135, p = 0.003), GGT (β = -0.104, p = 0.032), estimated glomerular filtration rate, serum bilirubin (β = -0.119, p = 0.006), and prevalence of cardiovascular disease (CVD) (β = 0.103, p = 0.017) were also independently associated with carotid IMT. The odds ratios (ORs) {95% confidence interval (CI)} of increasing serum bilirubin category were negatively associated with carotid IMT ≥1.0 mm and plaque in both genders. Compared to subjects with a serum bilirubin of Quartile-1, the multivariate-OR (95% CI) of carotid plaque was 0.25 (0.11–0.57) in the Quartile-4 male group, and 0.41 (0.21–0.78) in the Quartile-2 female group, 0.51 (0.26–0.98) in the Quartile-3 female group, and 0.46 (0.24–0.89) in the Quartile-4 female group. Our data demonstrated an independently negative association between serum bilirubin and carotid atherosclerosis in both genders.     

Optic Nerve Magnetisation Transfer Ratio after Acute Optic Neuritis Predicts Axonal and Visual Outcomes

Magnetisation transfer ratio (MTR) can reveal the degree of proton exchange between free water and macromolecules and was suggested to be pathological informative. We aimed to investigate changes in optic nerve MTR over 12 months following acute optic neuritis (ON) and to determine whether MTR measurements can predict clinical and paraclinical outcomes at 6 and 12 months. Thirty-seven patients with acute ON were studied within 2 weeks of presentation and at 1, 3, 6 and 12 months. Assessments included optic nerve MTR, retinal nerve fibre layer (RNFL) thickness, multifocal visual evoked potential (mfVEP) amplitude and latency and high (100%) and low (2.5%) contrast letter acuity. Eleven healthy controls were scanned twice four weeks apart for comparison with patients. Patient unaffected optic nerve MTR did not significantly differ from controls at any time-point. Compared to the unaffected nerve, affected optic nerve MTR was significantly reduced at 3 months (mean percentage interocular difference = −9.24%, p = 0.01), 6 months (mean = −12.48%, p<0.0001) and 12 months (mean = −7.61%, p = 0.003). Greater reduction in MTR at 3 months in patients was associated with subsequent loss of high contrast letter acuity at 6 (ρ = 0.60, p = 0.0003) and 12 (ρ = 0.44, p = 0.009) months, low contrast letter acuity at 6 (ρ = 0.35, p = 0.047) months, and RNFL thinning at 12 (ρ = 0.35, p = 0.044) months. Stratification of individual patient MTR time courses based on flux over 12 months (stable, putative remyelination and putative degeneration) predicted RNFL thinning at 12 months (F _2,32 = 3.59, p = 0.02). In conclusion, these findings indicate that MTR flux after acute ON is predictive of axonal degeneration and visual disability outcomes.     

High b Value (2,000 s/mm2) Diffusion-Weighted Magnetic Resonance Imaging in Prostate Cancer at 3 Tesla: Comparison with 1,000 s/mm2 for Tumor Conspicuity and Discrimination of Aggressiveness

Objective

The objective of our study was to investigate tumor conspicuity and the discrimination potential for tumor aggressiveness on diffusion-weighted magnetic resonance imaging (DW-MRI) with high b value at 3-T.

Materials and Methods

The institutional review board approved this study and waived the requirement for informed consent. A total of 50 patients with prostate cancer (69 cancer foci; 48 in the PZ, 20 in the TZ, and one in whole prostate) who underwent multiparametric prostate MRI including DW-MRI (b values: 0, 1000 s/mm² and 0, 2000 s/mm²) on a 3-T system were included. Lesion conspicuity score (LCS) using visual assessment (1 = invisible for surrounding normal site; 2 = slightly high intensity; 3 = moderately high; and 4 = very high) and tumor-normal signal intensity ratio (TNR) were assessed, and apparent diffusion coefficient (ADC, ×10⁻³ mm²/s) of the tumor regions and normal regions were measured.

Results

Mean LCS and TNR at 0, 2000 s/mm² was significantly higher than those at 0, 1000 s/mm² (p<0.001 for both). In addition, ADC at both 0, 1000 and 0, 2000 s/mm² was found to distinguish intermediate or high risk cancer with Gleason score ≥7 from low risk cancer with Gleason score ≤6 (p<0.001 for both). Furthermore, ADC of tumor regions correlated with Gleason score at both 0, 1000 s/mm² (ρ = −0.602; p<0.001) and 0, 2000 s/mm² (ρ = −0.645; p<0.001).

Conclusions

For tumor conspicuity and characterization of prostate cancer on DW-MRI of 3-T MRI, b = 0, 2000 s/mm² is more useful than b = 0, 1000 s/mm².     

COPS5 Protein Overexpression Increases Amyloid Plaque Burden,Decreases Spinophilin-immunoreactive Puncta,and Exacerbates Learning and Memory Deficits in the Mouse Brain

Brain accumulation of neurotoxic amyloid β (Aβ) peptide because of increased processing of amyloid precursor protein (APP), resulting in loss of synapses and neurodegeneration, is central to the pathogenesis of Alzheimer disease (AD). Therefore, the identification of molecules that regulate Aβ generation and those that cause synaptic damage is crucial for future therapeutic approaches for AD. We demonstrated previously that COPS5 regulates Aβ generation in neuronal cell lines in a RanBP9-dependent manner. Consistent with the data from cell lines, even by 6 months, COPS5 overexpression in APΔE9 mice (APΔE9/COPS5-Tg) significantly increased Aβ40 levels by 32% (p < 0.01) in the cortex and by 28% (p < 0.01) in the hippocampus, whereas the increases for Aβ42 were 37% (p < 0.05) and 34% (p < 0.05), respectively. By 12 months, the increase was even more robust. Aβ40 levels increased by 63% (p < 0.001) in the cortex and by 65% (p < 0.001) in the hippocampus. Similarly, Aβ42 levels were increased by 69% (p < 0.001) in the cortex and by 71% (p < 0.011) in the hippocampus. Increased Aβ levels were translated into an increased amyloid plaque burden both in the cortex (54%, p < 0.01) and hippocampus (64%, p < 0.01). Interestingly, COPS5 overexpression increased RanBP9 levels in the brain, which, in turn, led to increased amyloidogenic processing of APP, as reflected by increased levels of sAPPβ and decreased levels of sAPPα. Furthermore, COPS5 overexpression reduced spinophilin in both the cortex (19%, p < 0.05) and the hippocampus (20%, p < 0.05), leading to significant deficits in learning and memory skills. Therefore, like RanBP9, COPS5 also plays a pivotal role in amyloid pathology in vivo.     

The Challenge of Living On: Psychopathology and Its Mediating Influence on the Readjustment of Former Child Soldiers

Current civil wars are characterized by the increasing involvement of civilian populations and the systematic employment of child soldiers. An example of such wars was the conflict in Northern Uganda, where the war-affected population is still challenged by the reintegration of formerly abducted children and youths. A cross-sectional, population-based survey, using a multistage cluster sampling approach of 1,113 Northern Ugandans aged between 12 and 25 in camps for internally displaced persons and locally validated instruments was conducted to assess symptoms and diagnoses of Posttraumatic Stress Disorder (PTSD) and probable Depression in war-affected, as well as formerly abducted individuals. Further objectives were to determine predictors of psychopathology and to relate indicators of maladjustment (i.e., impairments in daily and community functioning, somatic complaints, suicidality, aggressiveness and discrimination) to abduction, level of exposure to violence and psychopathology. 43% of the sample reported abduction by the rebel army. Exposure to violence among this group was higher than for non-abducted youths (t = 28.05; p<.001). PTSD point prevalence rates were 25% among former child soldiers and 7% among the comparison group. High suicidal ideation was present in 16% and 6% respectively. A higher amount of experienced and witnessed event-types (β = . 32. p<.001), loss of first-degree relatives (β = .13. p<.001) and the number of event-types involving forced perpetration (β = .23. p<.001) were identified as risk factors of PTSD symptoms in former child soldiers. The associations between abductee-status and indicators of maladjustment were fully mediated by level of trauma exposure and psychopathology. Results show that child soldiering and its psychological sequelae affect a substantial proportion of children and youths. After release or flight, their readjustment depends at least partly on their level of mental traumatization.     

Angiotensin II Stimulates Thick Ascending Limb Superoxide Production via Protein Kinase Cα-dependent NADPH Oxidase Activation

Angiotensin II (Ang II) stimulates thick ascending limb (TAL) O production, but the receptor(s) and signaling mechanism(s) involved are unknown. The effect of Ang II on O is generally attributed to the AT₁ receptor. In some cells, Ang II stimulates protein kinase C (PKC), whose α isoform (PKCα) can activate NADPH oxidase. We hypothesized that in TALs, Ang II stimulates O via AT₁ and PKCα-dependent NADPH oxidase activation. In rat TALs, 1 nm Ang II stimulated O from 0.76 ± 0.17 to 1.97 ± 0.21 nmol/min/mg (p < 0.001). An AT₁ antagonist blocked the stimulatory effect of Ang II on O (0.87 ± 0.25 nmol/min/mg; p < 0.006), whereas an AT₂ antagonist had no effect (2.16 ± 0.133 nmol/min/mg; p < 0.05 versus vehicle). Apocynin, an NADPH oxidase inhibitor, blocked Ang II-stimulated O by 90% (p < 0.01). Ang II failed to stimulate O in TALs from p47^phox−/− mice (p < 0.02). Monitored by fluorescence resonance energy transfer, Ang II increased PKC activity from 0.02 ± 0.03 to 0.13 ± 0.02 arbitrary units (p < 0.03). A general PKC inhibitor, GF109203X, blocked the effect of Ang II on O (1.47 ± 0.21 versus 2.72 ± 0.47 nmol/min/mg with Ang II alone; p < 0.03). A PKCα- and β-selective inhibitor, Gö6976, also blocked the stimulatory effect of Ang II on O (0.59 ± 0.15 versus 2.05 ± 0.28 nmol/min/mg with Ang II alone; p < 0.001). To distinguish between PKCα and PKCβ, we used tubules expressing dominant-negative PKCα or -β. In control TALs, Ang II stimulated O by 2.17 ± 0.44 nmol/min/mg (p < 0.011). In tubules expressing dominant-negative PKCα, Ang II failed to stimulate O (change: −0.30 ± 0.27 nmol/min/mg). In tubules expressing dominant-negative PKCβ1, Ang II stimulated O by 2.08 ± 0.69 nmol/min/mg (p < 0.002). We conclude that Ang II stimulates TAL O production via activation of AT₁ receptors and PKCα-dependent NADPH oxidase.     

Clinicopathological Characteristics of Gynecological Cancer Associated with Hypoxia-Inducible Factor 1α Expression: A Meta-Analysis Including 6,612 Subjects

BackgroundGynecological cancer is characterized by tumor hypoxia. However, the role of hypoxia-inducible factor 1α (HIF-1α) in gynecological cancer remains unclear.MethodElectronic databases including Cochrane Library, PUBMED, Web of Knowledge and clinical trial registries were searched from inception through October 2014 for published, case-control studies assessing the association between HIF-1α and the clinicopathological characteristics of gynecological cancer. We pooled results from 59 studies using fixed or random-effects models and present results as odds ratios (ORs) following the PRISMA guidelines.ResultsOur meta-analysis, which included 6,612 women, demonstrated that the expression of HIF-1α was associated with the clinicopathological characteristics of gynecological cancer. The expression of HIF-1α in cancer or borderline tissue was significantly higher than that in normal tissue (cancer vs. normal: odds ratio (OR) =9.59, 95% confidence interval (CI): 5.97, 15.39, p<0.00001; borderline vs. normal: OR=4.13, 95% (CI): 2.43, 7.02, p<0.00001; cancer vs. borderline: OR=2.70, 95% (CI): 1.69, 4.31, p<0.0001). The expression of HIF-1α in III‒IV stage or lymph node metastasis was significantly higher than that in I‒II stage or that without lymph node metastasis, respectively (OR=2.66, 95% (CI): 1.87,3.79, p<0.00001; OR= 3.98, 95% (CI): 2.10,12.89, p<0.0001). HIF-1α was associated with histological grade of cancer (Grade 3 vs. Grade 1: OR=3.77, 95% (CI): 2.76,5.16, p<0.00001; Grade 3 vs. Grade 2: OR=1.62, 95% (CI): 1.20,2.19, p=0.002; Grade 2 vs. Grade 1: OR=2.34, 95% (CI): 1.82,3.00, p<0.00001),5-years disease free survival (DFS) rates (OR=2.93, 95% (CI):1.43,6.01, p=0.001) and 5-years overall survival (OS) rates (OR=5.53, 95% (CI): 2.48,12.31, p<0.0001).ConclusionHIF-1α is associated with the malignant degree, FIGO stage, histological grade, lymph node metastasis, 5-years survival rate and recurrence rate of gynecological cancer. It may play an important role in clinical treatment and prognostic evaluation.     

Total gene deletions and mutant frequency of the HPRT gene as indicators of radiation exposure in Chernobyl liquidators

This study was conducted to determine the utility of deletion spectrum and mutant frequency (MF) of the hypoxanthine phosphoribosyl transferase gene (HPRT) as indicators of radiation exposure in Russian Liquidators who served in 1986 or 1987 in the clean up effort following the nuclear power plant accident at Chernobyl. HPRT MF was determined using the cloning assay for 117 Russian Controls and 122 Liquidators whose blood samples were obtained between 1991 and 1998. Only subjects from whom mutants were obtained for deletion analysis are included. Multiplex PCR analysis was performed on cell extracts of 1080 thioguanine resistant clones from Controls and 944 clones from Liquidators. Although the deletion spectra of Liquidators and Controls were similar overall, the Liquidator deletion spectrum was heterogeneous over time. Most notable, the proportion of total gene deletions was higher in 1991–1992 Liquidators than in Russian Controls (χ²=10.5, p=0.001) and in 1993–1994 Liquidators (χ²=8.3, p=0.004), and was marginally elevated relative to 1995–1996 Liquidators (χ²=3.3, p=0.07). This type of mutation has been highly associated with radiation exposure. Total gene deletions were not increased after 1992. Band shift mutations were also increased in the 1991–1992 Liquidators but were associated with increased MF of both Liquidators and Controls (p=0.009), not with increased MF in 1991–1992 Liquidators (p=0.7), and hence are not believed to be associated with radiation exposure. Regression analysis demonstrated that relative to Russian Controls HPRT MF was elevated in Liquidators overall when adjusted for age and smoking status (37%, p=0.0001), and also was elevated in Liquidators sampled in 1991–1992 (72%, p=0.0076), 1993–1994 (22%, p=0.037), and 1995–1996 (62%, p=0.0001). In summary, HPRT MF was found to be the more sensitive and persistent indicator of radiation exposure, but the specificity of total gene deletions led to detection of probable heterogeneity of radiation exposure within the exposed population.