Background Intestinal 18F-FDG Uptake Is Related to Serum Lipid Profile and Obesity in Breast Cancer Patients

Background

This study investigated the relationships between background intestinal uptake on ¹⁸F–FDG PET and cardio-metabolic risk (CMR) factors.

Methods

A total of 326 female patients that underwent ¹⁸F–FDG PET to determine the initial stage of breast cancer were enrolled. None of the patients had history of diabetes or hypertension. The background intestinal uptake on PET was visually graded (low vs. high uptake group) and quantitatively measured using the maximal standardized uptake value (SUV_max). SUV_max of 7 bowel segments (duodenum, jejunum, ileum, cecum, hepatic flexure, splenic flexure, and descending colon-sigmoid junction) were averaged for the total bowel (TB SUV_max). Age, body mass index (BMI), fasting blood glucose level (BST), triglyceride (TG), cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) were the considered CMR factors. The relationships between background intestinal ¹⁸F–FDG uptake on PET and diverse CMR factors were analyzed.

Results

The visual grades based on background intestinal ¹⁸F–FDG uptake classified 100 (30.7%) patients into the low uptake group, while 226 (69.3%) were classified into the high uptake group. Among CMR factors, age (p = 0.004), BMI (p<0.001), and TG (p<0.001) were significantly different according to visual grade of background intestinal ¹⁸F–FDG uptake. Quantitative TB SUV_max showed significant positive correlation with age (r = 0.203, p<0.001), BMI (r = 0.373, p<0.001), TG (r = 0.338, p<0.001), cholesterol (r = 0.148, p = 0.008), and LDL (r = 0.143, p = 0.024) and significant negative correlation with HDL (r = -0.147, p = 0.022). Multivariate analysis indicated that BMI and TG were independent factors in both visually graded background intestinal ¹⁸F–FDG uptake (p = 0.027 and p = 0.023, respectively) and quantitatively measured TB SUV_max (p = 0.006 and p = 0.004, respectively).

Conclusion

Increased background intestinal ¹⁸F–FDG uptake on PET may suggest alteration of lipid metabolism and risk of cardio-metabolic disease in non-diabetic and non-hypertensive breast cancer patients.     

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health

Background

Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment.

Purpose

To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO_2max), cardio-metabolic risk and psychological health which are comparable to MICT.

Methods

Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m^-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15–60 seconds, >90% HR_max) interspersed with periods of recovery cycling (≤25 min.session^-1, 3 sessions.week^-1). MICT participants performed continuous cycling (~70% HR_max, 30–45 min.session^-1, 5 sessions.week^-1). VO_2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention.

Results

Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO_2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables.

Conclusions

HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity.     

Noninvasive Evaluation of Metabolic Tumor Volume in Lewis Lung Carcinoma Tumor-Bearing C57BL/6 Mice with Micro-PET and the Radiotracers 18F-Alfatide and 18F-FDG: A Comparative Analysis

Purpose

To explore the value of a new simple lyophilized kit for labeling PRGD₂ peptide (¹⁸F-ALF-NOTA-PRGD₂, denoted as ¹⁸F-alfatide) in the determination of metabolic tumor volume (MTV) with micro-PET in lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice verified by pathologic examination and compared with those using ¹⁸F-fluorodeoxyglucose (FDG) PET.

Methods

All LLC tumor-bearing C57BL/6 mice underwent two attenuation-corrected whole-body micro-PET scans with the radiotracers ¹⁸F-alfatide and ¹⁸F-FDG within two days. ¹⁸F-alfatide metabolic tumor volume (V_RGD) and ¹⁸F-FDG metabolic tumor volume (V_FDG) were manually delineated slice by slice on PET images. Pathologic tumor volume (V_Path) was measured in vitro after the xenografts were removed.

Results

A total of 37 mice with NSCLC xenografts were enrolled and 33 of them underwent ¹⁸F-alfatide PET, and 35 of them underwent ¹⁸F-FDG PET and all underwent pathological examination. The mean ± standard deviation of V_Path, V_RGD, and V_FDG were 0.59±0.32 cm³ (range,0.13~1.64 cm³), 0.61±0.37 cm³ (range,0.15~1.86 cm³), and 1.24±0.53 cm³ (range,0.17~2.20 cm³), respectively. V_Path vs. V_RGD, V_Path vs. V_FDG, and V_RGD vs. V_FDG comparisons were t = -0.145, P = 0.885, t = -6.239, P<0.001, and t = -5.661, P<0.001, respectively. No significant difference was found between V_Path and V_RGD. V_FDG was much larger than V_RGD and V_Path. V_RGD seemed more approximate to the pathologic gross tumor volume. Furthermore, V_Path was more strongly correlated with V_RGD (R = 0.964,P<0.001) than with V_FDG (R = 0.584,P<0.001).

Conclusions

¹⁸F-alfatide PET provided a better estimation of gross tumor volume than ¹⁸F-FDG PET in LLC tumor-bearing C57BL/6 mice.     

Expectant Mothers Maximizing Opportunities: Maternal Characteristics Moderate Multifactorial Prenatal Stress in the Prediction of Birth Weight in a Sample of Children Adopted at Birth

Background

Mothers’ stress in pregnancy is considered an environmental risk factor in child development. Multiple stressors may combine to increase risk, and maternal personal characteristics may offset the effects of stress. This study aimed to test the effect of 1) multifactorial prenatal stress, integrating objective “stressors” and subjective “distress” and 2) the moderating effects of maternal characteristics (perceived social support, self-esteem and specific personality traits) on infant birthweight.

Method

Hierarchical regression modeling was used to examine cross-sectional data on 403 birth mothers and their newborns from an adoption study.

Results

Distress during pregnancy showed a statistically significant association with birthweight (R² = 0.032, F _{(2, 398)} = 6.782, p = .001). The hierarchical regression model revealed an almost two-fold increase in variance of birthweight predicted by stressors as compared with distress measures (R² Δ = 0.049, F _{(4, 394)} = 5.339, p < .001). Further, maternal characteristics moderated this association (R² Δ = 0.031, F _{(4, 389)} = 3.413, p = .009). Specifically, the expected benefit to birthweight as a function of higher SES was observed only for mothers with lower levels of harm-avoidance and higher levels of perceived social support. Importantly, the results were not better explained by prematurity, pregnancy complications, exposure to drugs, alcohol or environmental toxins.

Conclusions

The findings support multidimensional theoretical models of prenatal stress. Although both objective stressors and subjectively measured distress predict birthweight, they should be considered distinct and cumulative components of stress. This study further highlights that jointly considering risk factors and protective factors in pregnancy improves the ability to predict birthweight.     

Effects of Heavy Strength Training on Running Performance and Determinants of Running Performance in Female Endurance Athletes

Purpose

The purpose of the current study was to investigate the effects of adding strength training to normal endurance training on running performance and running economy in well-trained female athletes. We hypothesized that the added strength training would improve performance and running economy through altered stiffness of the muscle-tendon complex of leg extensors.

Methods

Nineteen female endurance athletes [maximal oxygen consumption (VO_2max): 53±3 ml∙kg^-1∙min^-1, 5.8 h weekly endurance training] were randomly assigned to either normal endurance training (E, n = 8) or normal endurance training combined with strength training (E+S, n = 11). The strength training consisted of four leg exercises [3 x 4–10 repetition maximum (RM)], twice a week for 11 weeks. Muscle strength, 40 min all-out running distance, running performance determinants and patellar tendon stiffness were measured before and after the intervention.

Results

E+S increased 1RM in leg exercises (40 ± 15%) and maximal jumping height in counter movement jump (6 ± 6%) and squat jump (9 ± 7%, p < 0.05). This was accompanied by increased muscle fiber cross sectional area of both fiber type I (13 ± 7%) and fiber type II (31 ± 20%) in m. vastus lateralis (p < 0.05), with no change in capillary density in m. vastus lateralis or the stiffness of the patellar tendon. Neither E+S nor E changed running economy, fractional utilization of VO_2max or VO_2max. There were also no change in running distance during a 40 min all-out running test in neither of the groups.

Conclusion

Adding heavy strength training to endurance training did not affect 40 min all-out running performance or running economy compared to endurance training only.     

H-Index Is Important for Postural Control for People with Impaired Foot Sole Sensation

Introduction

People with Peripheral Neuropathy (PN), especially those with impaired sensory inputs through the small-afferent fiber (type II afferent fibers) reflex loop (SAF), might depend more on the large-afferent fiber (type I afferent fibers) reflex loop (LAF) for postural control.

Purpose

To examine whether the function of the LAF reflex loop, reflected by the H-reflex and ankle joint proprioception, influences postural control when the SAF reflex loop is impaired, as indicated by reduced foot sole cutaneous sensation.

Methods

Thirteen participants (8 women, 5 men) diagnosed with PN and 12 age-matched controls (7 women, 5 men) completed the testing protocol. Measures of interest included the H-index, active (AAP) and passive (PAP) ankle proprioception, plantar pressure sensitivity (PPS), average sway velocity (V_AVG) and area (A₉₅) during 30 seconds eyes-closed standing, 6-minute walk distance (6MWD) and timed up-and-go duration (TUG).

Results

Statistically significant group-dependent regression was observed between V_AVG and H-index. Compared to the control group, the PN group demonstrated reduced PPS (2.0 ± 1.9 vs. 4.2 ± 1.2, P < .05) and H-index (63.6 ± 10.9 vs. 76.4 ± 16.0, P < .05), greater V_AVG (3.5 ± 2.1 vs. 1.6 ± 0.6cm/s, P < .05) and A₉₅ (10.0 ± 10.1 vs. 2.5 ± 1.5cm², P < .05), shorter 6MWD (442.2 ± 93.0 vs. 525.3 ± 68.2m, P < .05), and longer TUG (9.4 ± 1.6 vs. 6.5 ± 1.3s, P < .05). Within the PN group, but not the control group, the H-index was correlated with V_AVG (r = -.56, P < .05). Moreover, within the PN group only, PAP scores were correlated with 6MWD (r = -.68, P < .05) and TUG (r = -.59, P < .05) performance. No other statistically significant group difference, correlation or group-dependent regression was observed.

Conclusion

V_AVG, 6MWD, and TUG correlated with LAF reflex loop function observed among those with impaired functioning of the SAF reflex loop. This observation suggests that the LAF reflex loop may be critical to the control of balance in those individuals suffering from small-fiber PN.     

Different Prognostic Values of Plasma Epstein-Barr Virus DNA and Maximal Standardized Uptake Value of 18F-FDG PET/CT for Nasopharyngeal Carcinoma Patients with Recurrence

Purpose

To evaluate and compare the prognostic value of Epstein-Barr virus (EBV) DNA and maximal standard uptake values (SUV_max ) of ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography (¹⁸F-FDG-PET) in subgroups of nasopharyngeal carcinoma (NPC) patients with locoregional or distant recurrence.

Patients and Methods

A total of 194 patients with recurrent NPC (locoregional recurrence: 107, distant recurrence: 87) were enrolled. Patients took evidence of recurrence performed with ¹⁸F-FDG-PET and an EBV DNA test before salvage treatment. Clinical parameters, the status of EBV DNA and the value of SUV_max were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards regression model.

Results

In the subgroup of patients with locoregional recurrence, patients with SUV_max<8.65 had significantly better overall survival (OS) (P=0.005) compared with the patients with SUV_max ≥8.65. However, both elevated EBV DNA load (≥21,100 copies/ml) and distant SUV_max (≥13.55) were significantly associated with worse OS compared with the patients with EBV DNA <21,100 copies/ml or distant SUV_max <13.55 for the subgroup with distant recurrence (P=0.015 and P=0.006, respectively). The predictive ability of EBV DNA was superior to that of SUV_max (P=0.062). Multivariate analysis showed that SUV_max was only an independent prognostic factor for OS in patients with locoregional recurrence (P=0.042), whereas EBV DNA independently predicted OS for the patients with distant recurrence (P=0.007). For those patients with undetectable EBV DNA, SUV_max<8.65 was still an independent favorable prognostic factor (P=0.038).

Conclusions

SUV_max is a useful biomarker for predicting OS in nasopharyngeal carcinoma patients with locoregional recurrence or with undetectable EBV DNA. Both distant SUV_max and EBV DNA appear to be independent predictors of OS in patients with distant recurrence; however, the predictive ability of EBV DNA was superior to that of SUV_max.     

Abdominal Functional Electrical Stimulation to Assist Ventilator Weaning in Acute Tetraplegia: A Cohort Study

Background

Severe impairment of the major respiratory muscles resulting from tetraplegia reduces respiratory function, causing many people with tetraplegia to require mechanical ventilation during the acute stage of injury. Abdominal Functional Electrical Stimulation (AFES) can improve respiratory function in non-ventilated patients with sub-acute and chronic tetraplegia. The aim of this study was to investigate the clinical feasibility of using an AFES training program to improve respiratory function and assist ventilator weaning in acute tetraplegia.

Methods

AFES was applied for between 20 and 40 minutes per day, five times per week on four alternate weeks, with 10 acute ventilator dependent tetraplegic participants. Each participant was matched retrospectively with a ventilator dependent tetraplegic control, based on injury level, age and sex. Tidal Volume (V_T) and Vital Capacity (V_C) were measured weekly, with weaning progress compared to the controls.

Results

Compliance to training sessions was 96.7%. Stimulated V_T was significantly greater than unstimulated V_T. V_T and V_C increased throughout the study, with mean V_C increasing significantly (V_T: 6.2 mL/kg to 7.8 mL/kg V_C: 12.6 mL/kg to 18.7 mL/kg). Intervention participants weaned from mechanical ventilation on average 11 (sd: ± 23) days faster than their matched controls.

Conclusion

The results of this study indicate that AFES is a clinically feasible technique for acute ventilator dependent tetraplegic patients and that this intervention may improve respiratory function and enable faster weaning from mechanical ventilation.

Trial Registration

ClinicalTrials.gov NCT02200393     

Comparative Study for Efficacy and Safety of Adenoidectomy according to the Surgical Method: A Prospective Multicenter Study

Background/Objective

There have been several operative techniques for adenoidectomy and their efficacy and morbidity are different according to the technique. This prospective multicenter study was aimed to compare the efficacy and morbidity of coblation adenoidectomy (CA) with those of power-assisted adenoidectomy.

Study Design

Prospective multi-institutional study.

Methods

Children who underwent CA, power-assisted adenoidectomy with cauterization (PAA+C) or without cauterization (PAA-C) due to adenoid hypertrophy were enrolled from 13 hospitals between July 2013 and June 2014. Mean operation time, degree of intraoperative bleeding and postoperative bleeding rate were evaluated.

Results

A total of 388 children (mean age ± standard deviation = 6.6 ± 2.5 years; 245 males and 143 females) were included. According to the adenoidectomy technique, the children were classified into 3 groups: (1) CA (n = 116); (2) PAA+C (n = 153); and (3) PAA-C (n = 119). Significant differences were not found in age and sex among three groups. In the CA group, mean operation time was significantly shorter (P < 0.001) and degree of intraoperative bleeding was significantly less (P < 0.001) compared to PAA+C or PAA-C group. Delayed postoperative bleeding rate of PAA-C group was significantly higher than that of CA or PAA+C group (P = 0.016).

Conclusions

This prospective multicenter study showed that CA was superior to PAA in terms of mean operation time and degree of intraoperative bleeding.     

Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy

Background

To find prognostic biomarkers in pretreatment dynamic contrast-enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy.

Methods

Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two compartment exchange, adiabatic approximation to tissue homogeneity (WX-AATH), and distributed parameter (WX-DP) models. The total hepatic blood flow, arterial flow fraction (γ), arterial blood flow (BF _A), portal blood flow, blood volume, mean transit time, permeability-surface area product, fractional interstitial volume (v _I), extraction fraction, mean intracellular water molecule lifetime (τ _C), and fractional intracellular volume (v _C) were calculated. After receiver operating characteristic analysis with leave-one-out cross-validation, individual parameters for each model were assessed in terms of 1-year-survival (1YS) discrimination using Kaplan-Meier analysis, and association with overall survival (OS) using univariate Cox regression analysis with permutation testing.

Results

The WX-TK-model-derived γ (P = 0.022) and v _I (P = 0.010), and WX-ETK-model-derived τ _C (P = 0.023) and v _C (P = 0.042) were statistically significant prognostic biomarkers for 1YS. Increase in the WX-DP-model-derived BF _A (P = 0.025) and decrease in the WX-TK, WX-ETK, WX-AATH, and WX-DP-model-derived v _C (P = 0.034, P = 0.038, P = 0.028, P = 0.041, respectively) were significantly associated with an increase in OS.

Conclusions

The WX-ETK-model-derived v _C was an effective prognostic biomarker for advanced HCC treated with sunitinib.     

Effects of Thiazolidinedione Therapy on Inflammatory Markers of Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

Background

Inflammation is a common feature in patients with type 2 diabetes mellitus (T₂DM). This meta-analysis aimed to assess the influence of thiazolidinedione (TZD) therapy on the circulating levels of inflammatory markers in patients with T₂DM.

Methods and Results

We searched the databases Medline, Embase, ScienceDirect, Web of Science, SpringerLink, and the Cochrane Library for randomized controlled trials (RCTs) that examined the effects of thiazolidinedione vs. a placebo on patients with T₂DM. The main outcomes were absolute changes in levels of circulating inflammatory markers. Twenty-seven RCTs were included and data were analyzed using a fixed-effect model or a random-effect model based on heterogeneity. Pooled results indicated that circulating levels of high-sensitivity C reactive protein (hsCRP; SMD = –0.65, 95% CI = –0.98 to –0.32, p < 0.01), monocyte chemoattractant protein-1 (MCP-1; WMD = –54.19, 95% CI = –73.86 to –34.52, p < 0.01), von Willebrand factor% (vWF%; WMD = –8.18, 95% CI = –13.54 to –2.81, p 0.01), fibrinogen (SMD = –0.26, 95% CI = –0.41 to –0.11, p < 0.01) and E-selectin(WMD = –3.57, 95% CI = –5.59 to -1.54, p <0.01) were significantly decreased after TZD therapy. However, interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand, plasminogen activator inhibitor 1 (PAI-1) and intercellular adhesion molecule (ICAM-1) were not significantly affected. Subgroup analyses of PAI-1, vWF% and fibrinogen in terms of trial drugs showed significant reductions for rosiglitazone (all p valuses< 0.05), but not pioglitazone treatment. Conversely, the E-selectin (p < 0.01) lowering effect only existed in the pioglitazone group. Further, rosiglitazone and pioglitazone treatment reduced serum hsCRP and MCP-1 but had no marked effects on MMP-9, IL-6 and ICAM-1.

Conclusions

Limited evidence suggested that TZD therapy had anti-inflammatory property that might contribute to its beneficial effect on inflammatory state in patients with type 2 diabetes.     

Clinical characteristics of OGTT-derived hepatic- and muscle insulin resistance in healthy young men

[Purpose]

Insulin inhibits glucose release in the liver but increases glucose absorption in muscles. When insulin cannot properly control glucose, it negatively affects glucose metabolism and, furthermore, contributes to the onset of metabolic syndrome and chronic disease. Therefore, this study''s goal is to understand the clinical characteristics of hepatic insulin resistance and muscle insulin sensitivity in healthy young men.

[Methods]

Twenty-eight healthy young men (age 23.3 ± 0.5; mean ± SE) participated in this study. Liver function and blood lipids were measured by blood sampling from brachial vein after participants fasted the previous day. Hepatic insulin resistance and muscle insulin sensitivity were evaluated using two-hour OGTT along with surrogate index related to insulin sensitivity. The VO_2max was evaluated using cycle ergometer. Systemic insulin sensitivity was evaluated using two-hour euglycemic hyperinsulinemic clamp method.

[Results]

Hepatic insulin resistance showed a significant correlation with body fat (r = 0.609, p < 0.05). Also, hepatic insulin resistance showed a significant correlation with GOT (r = 0.467), GPT (r = 0.434), and γ-GTP (r = 0.375), reflecting liver functions, as well as showing a significant correlation with hs-CRP (r = 0.492, p < 0.05). On the other hand, muscle insulin sensitivity had no correlation with neither body fat nor liver function index (p > 0.05), and among surrogate indexes, it showed a significant correlation with Avignon (r = -0.493) and Matsuda index (r = -0.577). Glucose infusion rate, using the clamp method, showed a significant correlation with muscle insulin sensitivity (r = 0.448, p < 0.05). The VO_2max had a significant correlation with hepatic insulin resistance (r = -0.435, p < 0.05) and muscle insulin sensitivity (r = 0.474, p < 0.05), respectively.

[Conclusion]

For young men in their 20''s, the OGTT-based hepatic insulin sensitivity was an indicator of hepatic function and body fat but muscle insulin sensitivity was related to peripheral insulin sensitivity. Also, for young men, higher VO_2max indicated lower hepatic insulin resistance and higher muscle insulin sensitivity.     

Quantification of Calcium Amount in a New Experimental Model: A Comparison between Ultrasound and Computed Tomography

Purpose

Calcification is an important prognostic factor in aortic valve stenosis. However, there is no ultrasound (US) method available to accurately quantify calcification in this setting to date. We aimed to validate a new US method for measuring the amount of calcium in an in vitro model, and compare it to computed tomography (CT), the current imaging gold standard.

Materials and Methods

An agar phantom (2% agar) was made, containing 9 different amounts of calcium-hydroxyapatite Ca₅(PO₄)₃OH (2 to 50mg). The phantoms were imaged with micro-CT and US (10 MHz probe). The calcium area (area_calcium) and its maximum pixel value (PV_max) were obtained. These values were summed to calculate CT and US calcium scores (∑(area_calcium × PV_max)) and volumes (∑area_calcium). Both US- and CT-calcium scores were compared with the calcium amounts, and with each other.

Results

Both calcium scores correlated significantly with the calcium amount (R² = 0.9788, p<0.0001 and R² = 0.8154, p<0.0001 for CT and US respectively). Furthermore, there was a significant correlation between US and CT for calcium volumes (R² = 0.7392, p<0.0001) and scores (R² = 0.7391, p<0.0001).

Conclusion

We developed a new US method that accurately quantifies the amount of calcium in an in vitro model. Moreover it is strongly correlated with CT.     

Monitoring HIV Drug Resistance Early Warning Indicators in Cameroon: A Study Following the Revised World Health Organization Recommendations

Background

The majority (>95%) of new HIV infection occurs in resource-limited settings, and Cameroon is still experiencing a generalized epidemic with ~122,638 patients receiving antiretroviral therapy (ART). A detrimental outcome in scaling-up ART is the emergence HIV drug resistance (HIVDR), suggesting the need for pragmatic approaches in sustaining a successful ART performance.

Methods

A survey was conducted in 15 ART sites of the Centre and Littoral regions of Cameroon in 2013 (10 urban versus 05 rural settings; 8 at tertiary/secondary versus 7 at primary healthcare levels), evaluating HIVDR-early warning indicators (EWIs) as-per the 2012 revised World Health Organization’s guidelines: EWI₁ (on-time pill pick-up), EWI₂ (retention in care), EWI₃ (no pharmacy stock-outs), EWI₄ (dispensing practices), EWI₅ (virological suppression). Poor performance was interpreted as potential HIVDR.

Results

Only 33.3% (4/12) of sites reached the desirable performance for “on-time pill pick-up” (57.1% urban versus 0% rural; p<0.0001) besides 25% (3/12) with fair performance. 69.2% (9/13) reached the desirable performance for “retention in care” (77.8% urban versus 50% rural; p=0.01) beside 7.7% (1/13) with fair performance. Only 14.4% (2/13) reached the desirable performance of “no pharmacy stock-outs” (11.1% urban versus 25% rural; p=0.02). All 15 sites reached the desirable performance of 0% “dispensing mono- or dual-therapy”. Data were unavailable to evaluate “virological suppression” due to limited access to viral load testing (min-max: <1%-15%). Potential HIVDR was higher in rural (57.9%) compared to urban (27.8%) settings, p=0.02; and at primary (57.9%) compared to secondary/tertiary (33.3%) healthcare levels, p=0.09.

Conclusions

Delayed pill pick-up and pharmacy stock-outs are major factors favoring HIVDR emergence, with higher risks in rural settings and at primary healthcare. Retention in care appears acceptable in general while ART dispensing practices are standard. There is need to support patient-adherence to pharmacy appointments while reinforcing the national drug supply system.     

Peripheral Blood Mononuclear Cells HIV DNA Levels Impact Intermittently on Neurocognition

Objectives

To determine the contribution of peripheral blood mononuclear cells’ (PBMCs) HIV DNA levels to HIV-associated dementia (HAD) and non-demented HIV-associated neurocognitive disorders (HAND) in chronically HIV-infected adults with long-term viral suppression on combined antiretroviral treatment (cART).

Methods

Eighty adults with chronic HIV infection on cART (>97% with plasma and CSF HIV RNA <50 copies/mL) were enrolled into a prospective observational cohort and underwent assessments of neurocognition and pre-morbid cognitive ability at two visits 18 months apart. HIV DNA in PBMCs was measured by real-time PCR at the same time-points.

Results

At baseline, 46% had non-demented HAND; 7.5% had HAD. Neurocognitive decline occurred in 14% and was more likely in those with HAD (p<.03). Low pre-morbid cognitive ability was uniquely associated with HAD (p<.05). Log₁₀ HIV DNA copies were stable between study visits (2.26 vs. 2.22 per 10⁶ PBMC). Baseline HIV DNA levels were higher in those with lower pre-morbid cognitive ability (p<.04), and higher in those with no ART treatment during HIV infection 1st year (p = .03). Baseline HIV DNA was not associated with overall neurocognition. However, % ln HIV DNA change was associated with decline in semantic fluency in unadjusted and adjusted analyses (p = .01-.03), and motor-coordination (p = .02-.12) to a lesser extent.

Conclusions

PBMC HIV DNA plays a role in HAD pathogenesis, and this is moderated by pre-morbid cognitive ability in the context of long-term viral suppression. While the HIV DNA levels in PBMC are not associated with current non-demented HAND, increasing HIV DNA levels were associated with a decline in neurocognitive functions associated with HAND progression.     

Cognitive and Typing Outcomes Measured Simultaneously with Slow Treadmill Walking or Sitting: Implications for Treadmill Desks

Purpose

This study compared cognitive (attention, learning, and memory) and typing outcomes during slow treadmill walking or sitting. Seventy-five healthy individuals were randomly assigned to a treadmill walking group (n=37; 23 female) or sitting group (n=38; 17 female).

Methods

The treadmill walking group completed a series of tests while walking at 1.5 mph. The sitting group performed the same tests while sitting at a standard desk. Tests performed by both groups included: the Rey Auditory Verbal Learning Test and a modified version of the Paced Auditory Serial Attention Test. In addition, typing performance was evaluated.

Results

Participants in the treadmill walking group performed worse on the Rey Auditory Verbal Learning Test for total learning than the sitting group; the main effect was significant (F(1,73)=4.75, p=0.03, η _p ²=0.06); however, short- and long-delay recall performance did not differ between groups (p>0.05). For the Paced Auditory Serial Attention Test, total number of correct responses was lower in the treadmill walking group relative to the sitting group; the main effect was significant (F(1,73)=4.97, p=0.03, η _p ²=0.06). The performance of both groups followed the same learning slope (Group x Trial interactions were not significant) for the Rey Auditory Verbal Learning Test and Paced Auditory Serial Attention Test. Individuals in the treadmill walking group performed significantly worse for all measures of typing (p<0.05).

Conclusion

Walking on a treadmill desk may result in a modest difference in total learning and typing outcomes relative to sitting, but those declines may not outweigh the benefit of the physical activity gains from walking on a treadmill.     

Characterization of Neutral Lipase BT-1 Isolated from the Labial Gland of Bombus terrestris Males

Background

In addition to their general role in the hydrolysis of storage lipids, bumblebee lipases can participate in the biosynthesis of fatty acids that serve as precursors of pheromones used for sexual communication.

Results

We studied the temporal dynamics of lipolytic activity in crude extracts from the cephalic part of Bombus terrestris labial glands. Extracts from 3-day-old males displayed the highest lipolytic activity. The highest lipase gene expression level was observed in freshly emerged bumblebees, and both gene expression and lipase activity were lower in bumblebees older than 3 days. Lipase was purified from labial glands, further characterized and named as BT-1. The B. terrestris orthologue shares 88% sequence identity with B. impatiens lipase HA. The molecular weight of B. terrestris lipase BT-1 was approximately 30 kDa, the pH optimum was 8.3, and the temperature optimum was 50°C. Lipase BT-1 showed a notable preference for C8-C10 p-nitrophenyl esters, with the highest activity toward p-nitrophenyl caprylate (C8). The Michaelis constant (K_m) and maximum reaction rate (V_max) for p-nitrophenyl laurate hydrolysis were K_m = 0.0011 mM and V_max = 0.15 U/mg.

Conclusion

This is the first report describing neutral lipase from the labial gland of B. terrestris. Our findings help increase understanding of its possible function in the labial gland.     

Simultaneous [18F]FDG-PET/MRI: Correlation of Apparent Diffusion Coefficient (ADC) and Standardized Uptake Value (SUV) in Primary and Recurrent Cervical Cancer

Objectives

Previous non–simultaneous PET/MR studies have shown heterogeneous results about the correlation between standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs). The aim of this study was to investigate correlations in patients with primary and recurrent tumors using a simultaneous PET/MRI system which could lead to a better understanding of tumor biology and might play a role in early response assessment.

Methods

We included 31 patients with histologically confirmed primary (n = 14) or recurrent cervical cancer (n = 17) who underwent simultaneous whole-body ¹⁸F-FDG-PET/MRI comprising DWI. Image analysis was performed by a radiologist and a nuclear physician who identified tumor margins and quantified ADC and SUV. Pearson correlations were calculated to investigate the association between ADC and SUV.

Results

92 lesions were detected. We found a significant inverse correlation between SUV_max and ADC_min (r = -0.532, p = 0.05) in primary tumors as well as in primary metastases (r = -0.362, p = 0.05) and between SUV_mean and ADC_min (r = -0.403, p = 0.03). In recurrent local tumors we found correlations for SUV_max and ADC_min (r = -0.747, p = 0.002) and SUV_mean and ADC_min (r = -0.773, p = 0.001). Associations for recurrent metastases were not significant (p>0.05).

Conclusions

Our study demonstrates the feasibility of fast and reliable measurement of SUV and ADC with simultaneous PET/MRI. In patients with cervical cancer we found significant inverse correlations for SUV and ADC which could play a major role for further tumor characterization and therapy decisions.

Key Point 1

This study investigates the correlation of functional parameters in a simultaneous PET/MRI.

Key Point 2

We found significant inverse correlations between ADC and SUV in cervical carcinoma which could increase knowledge about tumor biology.     

Mapping and Congenic Dissection of Genetic Loci Contributing to Hyperglycemia and Dyslipidemia in Mice

Background

Patients with dyslipidemia have an increased risk of developing type 2 diabetes, and diabetic patients often have dyslipidemia. Potential genetic connections of fasting plasma glucose with plasma lipid profile were evaluated using hyperlipidemic mice.

Methods

225 male F₂ mice were generated from BALB/cJ (BALB) and SM/J(SM) Apoe-deficient (Apoe^−/−) mice and fed a Western diet for 5 weeks. Fasting plasma glucose and lipid levels of F₂ mice were measured before and after 5 weeks of Western diet and quantitative trait locus (QTL) analysis was performed using data collected from these two time points. 144 SNP(single nucleotide polymorphism) markers across the entire genome were typed.

Results

One major QTL (logarithm of odds ratio (LOD): 6.46) peaked at 12.7 cM on chromosome 9,Bglu16, and 3 suggestive QTLs on chromosomes 15, 18 and X were identified for fasting glucose, and over 10 loci identified for lipid traits. Bglu16 was adjacent to a major QTL, Hdlq17, for high-density lipoprotein (HDL) cholesterol (LOD: 6.31, peak: 19.1 cM). A congenic strain with a donor chromosomal region harboring Bglu16 and Hdlq17 on the Apoe^−/− background showed elevations in plasma glucose and HDL levels. Fasting glucose levels were significantly correlated with non-HDL cholesterol and triglyceride levels, especially on the Western diet, but only marginally correlated with HDL levels in F₂ mice.

Conclusions

We have demonstrated a correlative relationship between fasting glucose and plasma lipids in a segregating F₂ population under hyperlipidemic conditions, and this correlation is partially due to genetic linkage between the two disorders.     

Criterion-Related Validity of the Distance- and Time-Based Walk/Run Field Tests for Estimating Cardiorespiratory Fitness: A Systematic Review and Meta-Analysis

Objectives

The main purpose of the present meta-analysis was to examine the criterion-related validity of the distance- and time-based walk/run tests for estimating cardiorespiratory fitness among apparently healthy children and adults.

Materials and Methods

Relevant studies were searched from seven electronic bibliographic databases up to August 2015 and through other sources. The Hunter-Schmidt’s psychometric meta-analysis approach was conducted to estimate the population criterion-related validity of the following walk/run tests: 5,000 m, 3 miles, 2 miles, 3,000 m, 1.5 miles, 1 mile, 1,000 m, ½ mile, 600 m, 600 yd, ¼ mile, 15 min, 12 min, 9 min, and 6 min.

Results

From the 123 included studies, a total of 200 correlation values were analyzed. The overall results showed that the criterion-related validity of the walk/run tests for estimating maximum oxygen uptake ranged from low to moderate (r_p = 0.42–0.79), with the 1.5 mile (r_p = 0.79, 0.73–0.85) and 12 min walk/run tests (r_p = 0.78, 0.72–0.83) having the higher criterion-related validity for distance- and time-based field tests, respectively. The present meta-analysis also showed that sex, age and maximum oxygen uptake level do not seem to affect the criterion-related validity of the walk/run tests.

Conclusions

When the evaluation of an individual’s maximum oxygen uptake attained during a laboratory test is not feasible, the 1.5 mile and 12 min walk/run tests represent useful alternatives for estimating cardiorespiratory fitness. As in the assessment with any physical fitness field test, evaluators must be aware that the performance score of the walk/run field tests is simply an estimation and not a direct measure of cardiorespiratory fitness.