The Temporal Trend of Influenza-Associated Morbidity and the Impact of Early Appearance of Antigenic Drifted Strains in a Southeast Asian Country

Globally, influenza infection is a major cause of morbidity and mortality in the elderly, who are suggested to be the major target group for trivalent influenza vaccine (TIV) vaccination by World Health Organization. In spite of an increasing trend in vaccine coverage rates in many countries, the effect of vaccination among the elderly in reducing hospitalization and mortality remains controversial. In this study, we conducted a historical cohort study to evaluate the temporal pattern of influenza-associated morbidity among persons older than 64 years over a decade. The temporal patterns of influenza-associated morbidity rates among the elderly older than 64 years indicated that Taiwan''s elderly P&I outpatient visits have been decreasing since the beginning of the 1999–2000 influenza season; however, hospitalization has been increasing despite significant increases in vaccine coverage. The propensity score logistic regression model was implemented to evaluate the source of bias and it was found that the TIV-receiving group had a higher propensity score than the non-receiving group (P<0.0001). In order to investigate the major factors affecting the temporal pattern of influenza-associated morbidity, we then used the propensity score as a summary confounder in a multivariate Poisson regression model based on the trimmed data. Our final models suggested that the factors affected the temporal pattern of morbidity differently. The variables including co-morbidity, vaccination rate, influenza virus type A and B isolation rate were associated with increased outpatient visits and hospitalization (p<0.05). In contrast, variables including high propensity score, increased 1°C in temperature, matching vaccine strains of type A/H1N1 and type B were associated with decreased outpatient visits and hospitalization (p<0.05). Finally, we assessed the impact of early appearance of antigenic-drifted strains and concluded that an excess influenza-associated morbidity substantial trends toward higher P&I hospitalization, but not outpatient visits, during the influenza season with early appearance of antigenic-drifted strains.     

Treating and Preventing Influenza in Aged Care Facilities: A Cluster Randomised Controlled Trial

Background

Influenza is an important cause of morbidity and mortality for frail older people. Whilst the antiviral drug oseltamivir (a neuraminidase inhibitor) is approved for treatment and prophylaxis of influenza during outbreaks, there have been no trials comparing treatment only (T) versus treatment and prophylaxis (T&P) in Aged Care Facilities (ACFs). Our objective was to compare a policy of T versus T&P for influenza outbreaks in ACFs.

Methods and Findings

We performed a cluster randomised controlled trial in 16 ACFs, that followed a policy of either “T”—oseltamivir treatment (75 mg twice a day for 5 days)—or “T&P”—treatment and prophylaxis (75 mg once a day for 10 days) for influenza outbreaks over three years, in addition to enhanced surveillance. The primary outcome measure was the attack rate of influenza. Secondary outcomes measures were deaths, hospitalisation, pneumonia and adverse events. Laboratory testing was performed to identify the viral cause of influenza-like illness (ILI) outbreaks. The study period 30 June 2006 to 23 December 2008 included three southern hemisphere winters. During that time, influenza was confirmed as the cause of nine of the 23 ILI outbreaks that occurred amongst the 16 ACFs. The policy of T&P resulted in a significant reduction in the influenza attack rate amongst residents: 93/255 (36%) in residents in T facilities versus 91/397 (23%) in T&P facilities (p = 0.002). We observed a non-significant reduction in staff: 46/216 (21%) in T facilities versus 47/350 (13%) in T&P facilities (p = 0.5). There was a significant reduction in mean duration of outbreaks (T = 24 days, T&P = 11 days, p = 0.04). Deaths, hospitalisations and pneumonia were non-significantly reduced in the T&P allocated facilities. Drug adverse events were common but tolerated.

Conclusion

Our trial lacked power but these results provide some support for a policy of “treatment and prophylaxis” with oseltamivir in controlling influenza outbreaks in ACFs.

Trail Registration

Australian Clinical Trials Registry ACTRN12606000278538     

Fatty Acid- and Cholesterol Transporter Protein Expression along the Human Intestinal Tract

Background

Protein distribution profiles along the human intestinal tract of transporters involved in the absorption of cholesterol and long-chain fatty acids (LCFA) have been scarcely evaluated.

Methodology/Principal Findings

In post-mortem samples from 11 subjects, intestinal transporter distribution profiles were determined via Western Blot. Differences in transporter protein levels were statistically tested using ANOVA and Tukey''s Post Hoc comparisons. Levels in all segments were expressed relative to those in duodenum. Except for ABCG5 and FATP4, levels (mean±SEM) were the highest in the ileum. For ABCA1, ileal levels (1.80±0.26) differed significantly from those in duodenum (P = 0.049) and proximal colon (0.92±0.14; P = 0.029). ABCG8 levels in ileum (1.91±0.30) differed from those in duodenum (P = 0.041) and distal colon (0.84±0.22; P = 0.010) and jejunum (1.64±0.26) tended to be higher than distal colon (0.84±0.22; P = 0.087). Ileal NPC1L1 levels (2.56±0.51) differed from duodenum levels (P = 0.019) and from distal colon (1.09±0.22; P = 0.030). There was also a trend (P = 0.098) for higher jejunal (2.23±0.37) than duodenal NPC1L1 levels. The levels of ABCG5 did not correlate with those of ABCG8. FAT/CD36 levels in ileum (2.03±0.42) differed from those in duodenum (P = 0.017), and proximal and distal colon (0.89±0.13 and 0.97±0.15 respectively; P = 0.011 and P = 0.014). FABPpm levels in ileum (1.04±0.13) differed from proximal (0.64±0.07; P = 0.026) and distal colon (0.66±0.09; P = 0.037).

Conclusions/Significance

The distribution profiles showed a bell-shape pattern along the GI-tract with the highest levels in ileum for ABCA1, ABCG8, NPC1L1, FATCD36 and FABPm, suggesting a prominent role for ileum in transporter-mediated uptake of cholesterol and LCFAs.     

De Novo Lipogenesis and Cholesterol Synthesis in Humans with Long-Standing Type 1 Diabetes Are Comparable to Non-Diabetic Individuals

Background

Synthesis of lipid species, including fatty acids (FA) and cholesterol, can contribute to pathological disease. The purpose of this study was to investigate FA and cholesterol synthesis in individuals with type 1 diabetes, a group at elevated risk for vascular disease, using stable isotope analysis.

Methods

Individuals with type 1 diabetes (n = 9) and age-, sex-, and BMI-matched non-diabetic subjects (n = 9) were recruited. On testing day, meals were provided to standardize food intake and elicit typical feeding responses. Blood samples were analyzed at fasting (0 and 24 h) and postprandial (2, 4, 6, and 8 hours after breakfast) time points. FA was isolated from VLDL to estimate hepatic FA synthesis, whereas free cholesterol (FC) and cholesteryl ester (CE) was isolated from plasma and VLDL to estimate whole-body and hepatic cholesterol synthesis, respectively. Lipid synthesis was measured using deuterium incorporation and isotope ratio mass spectrometry.

Results

Fasting total hepatic lipogenesis (3.91±0.90% vs. 5.30±1.22%; P = 0.41) was not significantly different between diabetic and control groups, respectively, nor was synthesis of myristic (28.60±4.90% vs. 26.66±4.57%; P = 0.76), palmitic (12.52±2.75% vs. 13.71±2.64%; P = 0.65), palmitoleic (3.86±0.91% vs. 4.80±1.22%; P = 0.65), stearic (5.55±1.04% vs. 6.96±0.97%; P = 0.29), and oleic acid (1.45±0.28% vs. 2.10±0.51%; P = 0.21). Postprandial lipogenesis was also not different between groups (P = 0.38). Similarly, fasting synthesis of whole-body FC (8.2±1.3% vs. 7.3±0.8%/day; P = 0.88) and CE (1.9±0.4% vs. 2.0±0.3%/day; P = 0.96) and hepatic FC (8.2±2.0% vs. 8.1±0.8%/day; P = 0.72) was not significantly different between diabetic and control subjects.

Conclusions

Despite long-standing disease, lipogenesis and cholesterol synthesis was not different in individuals with type 1 diabetes compared to healthy non-diabetic humans.     

Technical Performance Reduces during the Extra-Time Period of Professional Soccer Match-Play

Despite the importance of extra-time in determining progression in specific soccer tournament matches, few studies have profiled the demands of 120-minutes of soccer match-play. With a specific focus on the extra-time period, and using a within-match approach, we examined the influence of prolonged durations of professional soccer match-play on markers of technical (i.e., skilled) performance. In 18 matches involving professional European teams played between 2010 and 2014, this retrospective study quantified the technical actions observed during eight 15-minute epochs (E1: 00∶00–14∶59 min, E2: 15∶00–29∶59 min, E3: 30∶00–44∶59 min, E4: 45∶00–59∶59 min, E5: 60∶00–74∶59 min, E6: 75∶00–89∶59 min, E7: 90∶00–104∶59 min, E8: 105∶00–119∶59 min). Analysis of players who completed the demands of the full 120 min of match-play revealed that the cumulative number of successful passes observed during E8 (61±23) was lower than E1–4 (E1: 88±23, P = 0.001; E2: 77±21, P = 0.005; E3: 79±18, P = 0.001; E4: 80±21, P = 0.001) and E7 (73±20, P = 0.002). Similarly, the total number of passes made in E8 (71±25) was reduced when compared to E1 (102±22, P = 0.001), E3 (91±19, P = 0.002), E4 (93±22, P≤0.0005) and E7 (84±20, P = 0.001). The cumulative number of successful dribbles reduced in E8 (9±4) when compared to E1 (14±4, P = 0.001) and E3 (12±4, P≤0.0005) and the total time the ball was in play was less in E8 (504±61 s) compared to E1 (598±70 s, P≤0.0005). These results demonstrate that match-specific factors reduced particular indices of technical performance in the second half of extra-time. Interventions that seek to maintain skilled performance throughout extra-time warrant further investigation.     

Impact of Untreated Obstructive Sleep Apnea on Left and Right Ventricular Myocardial Function and Effects of CPAP Therapy

Background

Obstructive sleep apnea (OSA) has deteriorating effect on LV function, whereas its impact on RV function is controversial. We aimed to determine the effect of OSA and continuous positive airway pressure (CPAP) treatment on left and right ventricular (LV, RV) function using transthoracic echocardiography (TTE) and 2 dimensional speckle tracking (2D ST) analysis of RV deformation capability.

Methods and Results

82 patients with OSA and need for CPAP therapy were prospectively enrolled and underwent TTE at study inclusion and after 6 months of follow up (FU). Multivariate regression analysis revealed an independent association between baseline apical right ventricular longitudinal strain (RV-Sl), BMI and the severity of OSA (apical RV-Sl: P = 0.0002, BMI: P = 0.02). After CPAP therapy, LV functional parameters (LVEF: P<0.0001, LV performance index: P = 0.03, stroke volume: P = 0.042), and apical RV-Sl (P = 0.001) improved significantly. The effect of CPAP therapy was related to severity of OSA (LVEF: AHI 5–14, 66.4±8.8%, 68.5±10.6% [P = ns]; AHI 15–30∶59.8±7.7%, 68.6±9.3% [P = 0.002]; AHI>30∶54.1±12.4%, 68.2±13.6%[P<0.0001]; apical RV-Sl: AHI 5–14: −17.3±8.7%, −16.0±10.8% [P = ns], AHI 15–30: −9.8±6.0%, −15.4±10.9% [P = 0.028], AHI>30: −6.3±5.7%, −17.9±11.2% [P<0.0001]).

Conclusions

OSA seems to have deteriorating effect on LV and RV function. We found a beneficial effect of CPAP on LV and RV functional parameters predominately in patients with severe OSA. 2D speckle tracking might be of value to determine early changes in global and regional right ventricular function.     

Impact of Gout on Left Atrial Function: A Prospective Speckle-Tracking Echocardiographic Study

The purpose of our study was to evaluate the left ventricular (LV) and left atrial (LA) function in patients with gout. A total of 173 patients underwent a comprehensive Doppler-echocardiography examination. Participants were divided into four groups–Stage 0: control (n = 35), Stage I: asymptomatic hyperuricemia (n = 30), Stage II: gouty arthritis without tophi (n = 58), and Stage III: tophaceous gout (n = 50). Serum uric acid levels were not significantly different between stage I, II and III. Stage III patients demonstrated a higher ratio of the transmitral and myocardial peak early diastolic velocities (E/Em) (10.50±3.18 vs. 8.58±2.07; P = 0.008), and larger maximal LA volume index (LAVi) (29.60±9.89 vs. 20.07±4.76 ml/m²; P<0.001) compared with controls. Stage III patients had decreased LV global longitudinal systolic strain (LVε) compared with controls (−20.2±3.06 vs. −21.79±2.27; P = 0.002). Stage III patients also had decreased peak atrial longitudinal strain rate during ventricular systole (ALSR_syst), peak atrial longitudinal strain rate during ventricular early diastole (ALSR_early), and peak atrial longitudinal strain rate during ventricular late diastole (ALSR_late) compared with controls (1.73±0.48 vs. 2.05±0.55 1/s, −1.44±0.53 vs. −2.07±0.84 1/s, −2.07±0.7 vs. −2.66±0.91 1/s, respectively; all P<0.005). Multiple regression analysis revealed severity of gout had an independent negative impact on LA pump function (ALSR_late). In conclusion, gout caused LV diastolic dysfunction, LV subclinical systolic dysfunction and LA reservoir, conduit, and booster pump dysfunction.     

Soluble Tumor Necrosis Factor Related Apoptosis Inducing Ligand Level as a Predictor of Severity of Sepsis and the Risk of Mortality in Septic Patients

Background

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) as a member of the TNF gene superfamily induces apoptosis primarily in tumor cells. TRAIL also plays an important role in the modulation of inflammatory responses, especially in the process of immune paralysis. The aim of the present study was to examine soluble TRAIL (sTRAIL) levels in septic patients in an attempt to explore the association between sTRAIL level and the risk of mortality.

Methods

Plasma sTRAIL levels were detected by ELISA in 50 septic patients and 20 healthy volunteers. HLA-DR expression in monocytes was detected by flow cytometry. Selective biochemical parameters were recorded, and patients were monitored in a 28-day period for mortality.

Results

The mean plasma sTRAIL level in septic patients was significantly lower than that in healthy controls (16.9±8.3 vs. 68.3±8.6 pg/ml, P<0.01), and was significantly higher in 28-day survivors than those in non-survivors (19.4±9.8 vs. 13.9±4.7 pg/ml, P<0.05). Univariate analysis indicated that plasma sTRAIL level was positively correlated with monocyte and lymphocyte counts and HLA-DR expression level (r = 0.5, P<0.01; r = 0.3, P<0.05; r = 0.43, P<0.01, respectively). STRAIL level was negatively correlated with APACHE II score, BUN and age (r = −0.48, P<0.01; r = −0.29, P<0.05; r = −0.45, P<0.01, respectively). Multiple linear regression analysis indicated that the predictor of plasma soluble TRAIL level was HLA-DR expression (P<0.01).

Conclusion

Low plasma sTRAIL levels were associated with immune paralysis and a high risk of mortality in patients with septic shock. sTRAIL may prove to be a potential biomarker of immune function and predict the survival of septic patients.     

Coagulation and Fibrinolysis Index Profile in Patients with ANCA-Associated Vasculitis

Background

Previous studies observed the high prevalence of venous thromboembolism in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study analyzed the coagulation and fibrinolysis index profile in AAV patients.

Methods

The current study recruited 321 AAV patients in active stage and 78 AAV patients in quiescent stage. Coagulation and fibrinolysis index profiles in these AAV patients were analysed, and their associations with various clinical and pathological parameters were further investigated.

Results

The circulating levels of D-dimer, fibrin degradation products and platelet count were significantly higher in AAV patients in active stage compared with those in remission [0.8 (0.4, 1.5) mg/L vs. 0.28 (0.2, 0.55) mg/L, P<0.05; 5.6 (5.0, 10.0) mg/L vs. 1.9 (1.2, 2.8) mg/L, P<0.05; 269±127×10⁹/L vs. 227±80×10⁹/L, P<0.05, respectively]. Among the 321 AAV patients in active stage, compared with patients with normal levels of D-dimer, patients with elevated D-dimer levels had significantly higher levels of initial serum creatinine, erythrocyte sedimentation rate, C reactive protein and the Birmingham Vasculitis Activity Scores (P = 0.014, P<0.001, P<0.001, P = 0.002, respectively). Moreover, correlation analysis showed that the levels of D-dimer correlated with erythrocyte sedimentation rate and C reactive protein levels (r = 0.384, P<0.001; r = 0.380, P<0.001, respectively).

Conclusion

Patients with active AAV are in hypercoagulable states, and circulating levels of D-dimer are associated with disease activity of AAV.     

Genome Wide Analysis of Narcolepsy in China Implicates Novel Immune Loci and Reveals Changes in Association Prior to Versus After the 2009 H1N1 Influenza Pandemic

Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7×10⁻⁹ OR 0.77), ZNF365 (rs10995245 max P = 1.2×10⁻¹¹ OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2×10⁻⁹ OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10⁻⁹ beta −1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8×10⁻¹⁰ OR 0.57). These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.     

Alterations of Neuromuscular Function after the World's Most Challenging Mountain Ultra-Marathon

We investigated the physiological consequences of the most challenging mountain ultra-marathon (MUM) in the world: a 330-km trail run with 24000 m of positive and negative elevation change. Neuromuscular fatigue (NMF) was assessed before (Pre-), during (Mid-) and after (Post-) the MUM in experienced ultra-marathon runners (n = 15; finish time  = 122.43 hours ±17.21 hours) and in Pre- and Post- in a control group with a similar level of sleep deprivation (n = 8). Blood markers of muscle inflammation and damage were analyzed at Pre- and Post-. Mean ± SD maximal voluntary contraction force declined significantly at Mid- (−13±17% and −10±16%, P<0.05 for knee extensor, KE, and plantar flexor muscles, PF, respectively), and further decreased at Post- (−24±13% and −26±19%, P<0.01) with alteration of the central activation ratio (−24±24% and −28±34% between Pre- and Post-, P<0.05) in runners whereas these parameters did not change in the control group. Peripheral NMF markers such as 100 Hz doublet (KE: −18±18% and PF: −20±15%, P<0.01) and peak twitch (KE: −33±12%, P<0.001 and PF: −19±14%, P<0.01) were also altered in runners but not in controls. Post-MUM blood concentrations of creatine kinase (3719±3045 Ul·¹), lactate dehydrogenase (1145±511 UI·L⁻¹), C-Reactive Protein (13.1±7.5 mg·L⁻¹) and myoglobin (449.3±338.2 µg·L⁻¹) were higher (P<0.001) than at Pre- in runners but not in controls. Our findings revealed less neuromuscular fatigue, muscle damage and inflammation than in shorter MUMs. In conclusion, paradoxically, such extreme exercise seems to induce a relative muscle preservation process due likely to a protective anticipatory pacing strategy during the first half of MUM and sleep deprivation in the second half.     

Magnetic Resonance Imaging Determined Visceral Fat Reduction Associates with Enhanced IL-10 Plasma Levels in Calorie Restricted Obese Subjects

Background

Obesity is characterized by a low grade chronic inflammation state. Indeed circulating pro-inflammatory cytokines, such as TNF-α and IL-6, are elevated in obese subjects, while anti-inflammatory cytokines, such as IL-10, appear to be reduced. Cytokines profile improves after weight loss, but how visceral or subcutaneous fat loss respectively affect pro- or anti-inflammatory cytokines plasma levels has not been precisely assessed. Therefore in the present study we correlated changes in circulating cytokine profile with quantitative changes in visceral and subcutaneous adipose tissue depots measured by an ad hoc Magnetic Resonance Imaging (MRI) protocol before and after weight loss.

Materials and Methods

In 14 obese subjects, MRI determination of visceral and subcutaneous fat and plasma glucose, insulin, TNF-α IL-6, and IL-10 measurements were performed before and after a caloric restriction induced weight loss of at least 5% of the original body weight.

Results

Weight loss improved insulin sensitivity (QUICKI Index: 0.35±0.03 vs 0.37±0.04; P<0.05), increased IL-10 (3.4±1.9 vs 4.6±1.0 pg/mL; P<0.03), and reduced TNF-α and IL-6 plasma levels (2.5±1.3 vs 1.6±1.5 pg/mL, P<0.0015, 2.3±0.4 vs 1.6±0.6 pg/mL, P<0.02 respectively). A significant correlation was observed between the amount of visceral fat loss and the percentage reduction in both TNF-α (r = 0.56, p<0.05) and IL-6 (r = 0.19 p<0.05) plasma levels. In a multiple regression analysis, the amount of visceral fat loss independently correlated with the increase in IL-10 plasma levels.

Conclusion

The reduction in visceral adipose tissue is the main driver of the improved inflammatory profile induced by weight loss.     

Effects of 12 Weeks High-Intensity & Reduced-Volume Training in Elite Athletes

It was investigated if high-intensity interval training (HIT) at the expense of total training volume improves performance, maximal oxygen uptake and swimming economy. 41 elite swimmers were randomly allocated to a control (CON) or HIT group. For 12 weeks both groups trained ∼12 h per week. HIT comprised ∼5 h vs. 1 h and total distance was ∼17 km vs. 35 km per week for HIT and CON, respectively. HIT was performed as 6-10×10-30 s maximal effort interspersed by 2–4 minutes of rest. Performance of 100 m all-out freestyle and 200 m freestyle was similar before and after the intervention in both HIT (60.4±4.0 vs. 60.3±4.0 s; n = 13 and 133.2±6.4 vs. 132.6±7.7 s; n = 14) and CON (60.2±3.7 vs. 60.6±3.8 s; n = 15 and 133.5±7.0 vs. 133.3±7.6 s; n = 15). Maximal oxygen uptake during swimming was similar before and after the intervention in both the HIT (4.0±0.9 vs. 3.8±1.0 l O₂×min⁻¹; n = 14) and CON (3.8±0.7 vs. 3.8±0.7 l O₂×min⁻¹; n = 11) group. Oxygen uptake determined at fixed submaximal speed was not significantly affected in either group by the intervention. Body fat % tended to increase (P = 0.09) in the HIT group (15.4±1.6% vs. 16.3±1.6%; P = 0.09; n = 16) and increased (P<0.05) in the CON group (13.9±1.5% vs. 14.9±1.5%; n = 17). A distance reduction of 50% and a more than doubled HIT amount for 12 weeks did neither improve nor compromise performance or physiological capacity in elite swimmers.     

Acoustic Radiation Force Impulse Imaging for Noninvasive Evaluation of Renal Parenchyma Elasticity: Preliminary Findings

Objective

To evaluate the diagnostic value of acoustic radiation force impulse (ARFI) to test the elasticity of renal parenchyma by measuring the shear wave velocity (SWV) which might be used to detect chronic kidney disease (CKD).

Methods

327 healthy volunteers and 64 CKD patients were enrolled in the study. The potential influencing factors and measurement reproducibility were evaluated in the healthy volunteers. Correlations between SWV and laboratory tests were analyzed in CKD patients.?Receiver-operating characteristic curve (ROC) analyses were performed to assess the diagnostic performance of ARFI.

Results

The SWV of healthy volunteers correlated significantly to age (r = −0.22, P<0.001, n = 327) and differed significantly between men and women (2.06±0.48 m/s vs. 2.2±0.52 m/s, P = 0.018, n = 327). However, it did not correlate significantly to height, weight, body mass index, waistline, kidney dimension and the depth for SWV measurement (n = 30). Inter- and intraobserver agreement expressed as intraclass coefficient correlation were 0.64 (95% CI: 0.13 to 0.82, P = 0.011) and 0.6 (95% CI: 0.31 to 0.81, P = 0.001) (n = 40). The mean SWV in healthy volunteers was 2.15±0.51 m/s, while was 1.81±0.43 m/s, 1.79±0.29 m/s, 1.81±0.44 m/s, 1.64±0.55 m/s, and 1.36±0.17 m/s for stage 1, 2, 3, 4 and 5 in CKD patients respectively. The SWV was significantly higher for healthy volunteers compared with each stage in CKD patients. ARFI could not predict the different stages of CKD except stage 5. In CKD patients, SWV correlated to e-GFR (r = 0.3, P = 0.018), to urea nitrogen (r =  −0.3, P = 0.016), and to creatinine (r =  −0.41, P = 0.001). ROC analyses indicated that the area under the ROC curve was 0.752 (95% CI: 0.704 to 0.797) (P<0.001). The cut-off value for predicting CKD was 1.88 m/s (sensitivity 71.87% and specificity 69.69%).

Conclusion

ARFI may be a potentially useful tool in detecting CKD.     

Neuroprotective Efficacy of Methylene Blue in Ischemic Stroke: An MRI Study

Methylene blue (MB) has unique energy-enhancing and antioxidant properties and is FDA-approved drug to treat methemoglobinemia and cyanide poisoning. This study evaluated the efficacy of MB to treat ischemic stroke in rats using longitudinal MRI and behavioral measures. Rats were subjected to 60-minute middle-cerebral-artery occlusion. In a randomized double-blinded design, vehicle or MB was administered after reperfusion. The initial lesion volumes at 30 minutes post-ischemia were not significantly different between the two groups (P = 0.92). The final infarct volumes two days after stroke increased in the vehicle group but decreased in the MB group, yielding a 30% difference in infarct volume (P = 0.03). Tracking tissue fate on a pixel-by-pixel basis showed that MB salvaged more initial core pixels compared to controls (22±3% versus 11±3%, P = 0.03), and more mismatch pixels compared to controls (83±3% versus 61±8%, P = 0.02). This study demonstrates MB treatment minimizes ischemic brain injury and improves functional outcomes.     

Excess Mortality Associated with Influenza among Tuberculosis Deaths in South Africa, 1999–2009

Background

Published data on the interaction between influenza and pulmonary tuberculosis (PTB) are limited. We aimed to estimate the influenza-associated mortality among individuals with PTB in South Africa from 1999–2009.

Methods

We modelled the excess influenza-associated mortality by applying Poisson regression models to monthly PTB and non-tuberculosis respiratory deaths, using laboratory-confirmed influenza as a covariate.

Results

PTB deaths increased each winter, coinciding with influenza virus circulation. Among individuals of any age, mean annual influenza-associated PTB mortality rate was 164/100,000 person-years (n = 439). The rate of non-tuberculosis respiratory deaths was 27/100,000 (n = 1125) for HIV-infected and 5/100,000 (n = 2367) for HIV-uninfected individuals of all ages. Among individuals aged <65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-infected (relative risk (RR): 5.2; 95% CI: 4.6–5.9) and HIV-uninfected individuals (RR: 61.0; CI: 41.4–91.0). Among individuals aged ≥65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-uninfected individuals (RR: 13.0; 95% CI: 12.0–14.0).

Conclusion

We observed an increased risk of influenza-associated mortality in persons with PTB compared to non-tuberculosis respiratory deaths. If confirmed in other settings, our findings may support recommendations for active inclusion of patients with TB for influenza vaccination and empiric influenza anti-viral treatment of patients with TB during influenza epidemics.     

Association between Oestrogens Receptor Expressions in Breast Cancer and Comorbidities: A Cross-Sectional,Population-Based Study

Background

Breast cancer with oestrogen receptor expression is common in older women. Several factors, such as age and reproductive hormone exposure, have been associated with oestrogen receptor expression in breast cancer. However, the association between comorbidities and the oestrogen receptor expression has been poorly studied. We hypothesized that there was an association between burden comorbidity and breast cancer with oestrogen receptor expression in older women.

Objective

To determine whether oestrogen receptor expression in breast cancer was associated with burden comorbidity in community-dwelling women.

Methods

A total of 1,707 women with breast cancer registered on the list of a breast cancer registry were included. The recorded data included: age, Charlson Comorbidity Index score≥1, breast cancer characteristics (coded according to the International Classification of Diseases for Oncology), and breast cancer pathological stage (the pathological-tumour-node-metastasis, Scarff Bloom Richardson, and hormonal status of oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor).

Results

Breast cancer with oestrogen receptor expression was identified in 1,378 patients (80·7%). The fully-adjusted logistic regression showed that oestrogen receptor expression was associated with Charlson Comorbidity Index score≥1 (odds ratio [OR] = 1·91,95%confidence interval [CI] = [1.01–3.61], P = 0·048), progesterone receptor expression (OR = 16·64, 95%CI = [11.62–23.81], P<0·001), human epidermal growth factor receptor (OR = 0·54, 95%CI = [0.34–0.84], P = 0·007), age (OR = 1.02, 95%CI = [1.00–1.03], P = 0.008), Scarff Bloom Richardson grade II and grade III (OR = 0·21with 95%CI = [0.10–0.44] and OR = 0·06 with 95%CI = [0.03–0.12], P<0·001).

Conclusion

Our findings provide new data showing an independent positive association between burden comorbidity and breast cancer with oestrogen receptor expression. This result confirms that evaluation of oestrogen receptor expression in breast cancer should not be limited to hormonal factors stratified by age.     

Improved Clinical Outcomes of High Risk β Thalassemia Major Patients Undergoing a HLA Matched Related Allogeneic Stem Cell Transplant with a Treosulfan Based Conditioning Regimen and Peripheral Blood Stem Cell Grafts

Improving clinical outcomes among high risk Class III β thalassemia major patients (Class IIIHR) receiving an allogeneic SCT remains a challenge. From October, 2009 a treosulfan based regimen (TreoFluT) was used for all consecutive Class III patients (n = 50). The clinical outcomes were compared with the historical conventional busulfan (BuCy) based regimen (n = 139). Use of TreoFluT was associated with a significantly reduced incidence of sinusoidal obstruction syndrome (SOS) among Class IIIHR cases (78% to 30%; P = 0.000) and early TRM (46% to 13%; p = 0.005). There was also a trend towards better engraftment in the Class IIIHR subset (P = 0.055). However, the use of bone marrow (BM) as source of stem cells along with the TreoFluT regimen was associated with 50% early mixed chimerism which reduced to 8.5% with the use of a peripheral blood stem cell graft (PBSC). Use of a PBSC graft was not associated with a significant increase in the incidence of acute or chronic graft versus host disease (GVHD). The overall and event free survival was significantly better among the Class IIIHR subset with the use of TreoFluT Vs. BuCy (86.6±7.3 Vs. 39.4±6.8%; P = 0.002 and 77.8±8.8 Vs. 32.4±6.5%; P = 0.003 respectively). A TreoFluT conditioning regimen with a PBSC graft can significantly improve clinical outcomes of Class IIIHR patients.     

The Impact of Estradiol and 1,25(OH)2D3 on Metabolic Syndrome in Middle-Aged Taiwanese Males

In addition to adipocytokines, estradiol (E2) and vitamin D have been reported to affect insulin sensitivity, glucose homeostasis and body weight. However, studies about the impact of E2 and vitamin D on metabolic syndrome (MetS) are still limited. The aim of this study is to clarify the roles of circulating E2 and vitamin D on the risk of MetS in middle-aged Taiwanese males. A total of 655 male volunteers, including 243 subjects with MetS (mean age: 56.7±5.8 years) and 412 normal controls (mean age: 55.1±3.6 years), were evaluated. Subjects with MetS had significantly lower circulating E2, 1,25(OH)₂D₃, and adiponectin, and higher leptin than those without MetS (P<0.001 for all comparisons). E2 and 1,25(OH)₂D₃ were significantly associated with 4 individual components of MetS; more than adiponectin and leptin that were only associated with 3 individual components. In multivariate regression analysis, E2 (beta = −0.216, P<0.001) and 1,25(OH)₂D₃ (beta = 0.067, P = 0.045) were still significant predictors of MetS independent of adiponectin and leptin. Further large studies are needed to confirm our preliminary results and elucidate the possible mechanism.     

Inhibin Alpha-Subunit (INHA) Expression in Adrenocortical Cancer Is Linked to Genetic and Epigenetic INHA Promoter Variation

Adrenocortical carcinoma (ACC) is a rare, but highly malignant tumor of unknown origin. Inhibin α-subunit (Inha) knockout mice develop ACCs following gonadectomy. In man, INHA expression varies widely within ACC tissues and its circulating peptide inhibin pro-αC has been described as a novel tumor marker for ACC. We investigated whether genetic and epigenetic changes of the INHA gene in human ACC cause loss or variation of INHA expression. To this end, analyses of INHA sequence, promoter methylation and mRNA expression were performed in human adrenocortical tissues. Serum inhibin pro-αC levels were also measured in ACC patients. INHA genetic analysis in 37 unique ACCs revealed 10 novel, heterozygous rare variants. Of the 3 coding bases affected, one variant was synonymous and two were missense variants: S72F and S184F. The minor allele of rs11893842 at −124 bp was observed at a low frequency (24%) in ACC samples and was associated with decreased INHA mRNA levels: 4.7±1.9 arbitrary units for AA, compared to 26±11 for AG/GG genotypes (P = 0.034). The methylation of four proximal INHA promoter CpGs was aberrantly increased in five ACCs (47.7±3.9%), compared to normal adrenals (18.4±0.6%, P = 0.0052), whereas the other 14 ACCs studied showed diminished promoter methylation (9.8±1.1%, P = 0.020). CpG methylation was inversely correlated to INHA mRNA levels in ACCs (r = −0.701, p = 0.0036), but not associated with serum inhibin pro-αC levels. In conclusion, aberrant methylation and common genetic variation in the INHA promoter occur in human ACCs and are associated with decreased INHA expression.