Re-examine the transfusion transmitted risk of SARS-CoV-2 virus during a major COVID-19 outbreak in 2022.

INTRODUCTION: Although no case of COVID-19 transmission through transfusion has been reported, blood transfusion service (BTS) continues to implement pre-donation and post-donation measures to minimise the risk. In year 2022, when local healthcare system was badly impacted by a major outbreak, it opened an opportunity to re-examine the viraemia risk in these asymptomatic donors. MATERIALS AND METHODS: Records were retrieved from blood donors who reported COVID-19 after donation and follow-up was also made for recipients who received their blood. Blood samples at donation were tested for SARS-CoV-2 viraemia by single-tube nested real-time RT-PCR assay designed to detect most SARS-CoV-2 variants including the prevailing delta and omicron variants. RESULTS: From 1 January to 15 August 2022, the city with 7.4 M inhabitants recorded 1 187 844 COVID-19 positive cases and 125 936 successful blood donations were received. 781 donors reported to the BTS after donation with 701 being COVID-19 related (including close contact and symptoms respiratory tract infection). 525 COVID-19 were positive at the time of call back or follow-up. Of the 701 donations, they were processed into 1480 components with 1073 discarded upon donors' call back. For remaining 407 components, no recipient was found to have adverse event or COVID-19 positive. 510 samples from the above 525 COVID-19 positive donors were available and all tested negative for SARS-CoV-2 RNA. DISCUSSION: With the negative SARS-CoV-2 RNA in blood donation samples and follow up data in transfusion recipients, the risk of transfusion transmitted COVID-19 appears negligible. However, current measures remains important in securing blood safety with ongoing surveillance of their effectiveness.

Effect of upadacitinib on atopic hand eczema in patients with moderate-to-severe atopic dermatitis: Results from two randomized phase 3 trials.

BACKGROUND: Approximately 60% of patients with atopic dermatitis have involvement of the hands adding to the burden of disease. OBJECTIVE: This analysis aims to evaluate the effect of upadacitinib monotherapy on atopic hand eczema in patients with moderate-to-severe AD over 16 weeks in the Measure Up 1 and 2 studies. METHODS: Data from patients (ages 12-75) randomized 1:1:1 to receive upadacitinib 15 mg, 30 mg, or placebo once daily in the Measure Up 1 and 2 studies were analysed for impact on atopic hand eczema assessed using the Hand Eczema Severity Index (HECSI). The percent change from baseline in HECSI score was a prespecified additional endpoint at all visits. The proportion of patients with at least a 75% improvement in HECSI score (HECSI 75) was evaluated post hoc. RESULTS: Patients treated with upadacitinib 15 mg or 30 mg experienced greater improvement in HECSI score compared with placebo as early as Week 1, which was maintained through Week 16. At Week 16, the mean change from baseline in HECSI score for patients receiving upadacitinib 15 mg, 30 mg, and placebo was -68%, -74%, and -15% in Measure Up 1 and -68%, -74% and +21% (positive change indicates worsening for placebo) in Measure Up 2, respectively. A greater proportion of upadacitinib-treated patients achieved HECSI 75 compared with placebo at all timepoints beginning at Week 1 through Week 16. CONCLUSIONS: Upadacitinib 15 mg and 30 mg monotherapy provided rapid and sustained improvement in atopic hand eczema compared with placebo through Week 16 in patients with moderate-to-severe AD. At Week 16, the observed mean improvements in HECSI score in upadacitinib-treated patients were clinically meaningful based on previous interpretability studies. These results suggest that upadacitinib may be an effective treatment option for atopic hand eczema in patients with moderate-to-severe AD.

US Evaluation of Axillary Lymphadenopathy Following COVID-19 Vaccination: A Prospective Longitudinal Study.

Background Both temporal changes in imaging characteristics of lymphadenopathy on US scans after COVID-19 vaccination and expected duration of radiologically evident lymphadenopathy remain uncertain. Purpose To longitudinally evaluate COVID-19 vaccine-associated lymphadenopathy on axillary US scans at various time intervals in both messenger (mRNA) and vector vaccine recipients. Materials and Methods This prospective cohort study was conducted between March 2021 and January 2022. The participants were asymptomatic women without breast cancer who had received COVID-19 vaccination. Serial follow-up US was performed in women with lymphadenopathy. The following variables were assessed: cortical thickness, number of lymph nodes, morphologic characteristics, and Doppler signal. Temporal changes in cortical thickness and number of lymph nodes during follow-up were assessed using a linear mixed model. Results Ninety-one women with lymphadenopathy in the vaccinated arm had undergone a total of 215 serial US examinations (mean age, 44 years ± 13 [SD]). Fifty-one participants had received a vector vaccine (ChAdOx1 nCoV-19 vaccine) and 40 had received an mRNA vaccine (BNT162b2 vaccine [n = 37] and mRNA-1273 vaccine [n = 3]). Three of the 91 women were lost to follow-up; thus, 88 women underwent serial US. Complete resolution of axillary lymphadenopathy was observed at a median of 6 weeks after vaccination (range, 4-7 weeks) in 26% of women (23 of 88). Among 49 women with follow-up US at a median of 12 weeks after vaccination (range, 8-14 weeks), persistent lymphadenopathy was observed in 25 (51%). During the follow-up period, the cortical thickness gradually decreased (P < .001) over time regardless of vaccine type; however, values were higher in recipients of the mRNA vaccine than in recipients of the vector vaccine (P = .02). Conclusion COVID-19 vaccine-associated axillary lymphadenopathy frequently persisted for more than 6 weeks on US scans. Lymphadenopathy should be interpreted considering vaccine type and time elapsed since vaccination. Follow-up US examination at least 12 weeks after vaccination may be reasonable, particularly for recipients of the messenger RNA vaccine. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Moy and Kim in this issue.

COVID-19's U.S. Temperature Response Profile.

We estimate the U.S. temperature response profile (TRP) for COVID-19 and show it is highly sensitive to temperature variation. Replacing the erratic daily death counts U.S. states initially reported with counts based on death certificate date, we build a week-ahead statistical forecasting model that explains most of their daily variation (R2 = 0.97) and isolates COVID-19's TRP (p < 0.001). These counts, normalized at 31 °C (U.S. mid-summer average), scale up to 160% at 5 °C in the static case where the infection pool is held constant. Positive case counts are substantially more temperature sensitive. When temperatures are declining, dynamic feedback through a growing infection pool can substantially amplify these temperature effects. Our estimated TRP can be incorporated into COVID-related planning exercises and used as an input to SEIR models employed for longer run forecasting. For the former, we show how our TRP is predictive of the realized pattern of growth rates in per capita positive cases across states five months after the end of our sample period. For the latter, we show the variation in herd immunity levels implied by temperature-driven, time-varying R0 series for the Alpha and Delta variants of COVID-19 for several representative states. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10640-021-00603-8.

Efficient Ground-State Cooling of Large Trapped-Ion Chains with an Electromagnetically-Induced-Transparency Tripod Scheme.

We report the electromagnetically-induced-transparency (EIT) cooling of a large trapped ^{171}Yb^{+} ion chain to the quantum ground state. Unlike conventional EIT cooling, we engage a four-level tripod structure and achieve fast sub-Doppler cooling over all motional modes. We observe simultaneous ground-state cooling across the complete transverse mode spectrum of up to 40 ions, occupying a bandwidth of over 3 MHz. The cooling time is observed to be less than 300 µs, independent of the number of ions. Such efficient cooling across the entire spectrum is essential for high-fidelity quantum operations using trapped ion crystals for quantum simulators or quantum computers.

Inter-relationships among psychopathology, premorbid adjustment, cognition and psychosocial functioning in first-episode psychosis: a network analysis approach.

BACKGROUND: Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP. METHOD: This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses. RESULTS: Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength. CONCLUSION: Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.

Abnormal cognitive effort allocation and its association with amotivation in first-episode psychosis.

BACKGROUND: Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP). METHOD: Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants' willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored. RESULTS: Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits. CONCLUSION: This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.

[Feasibility and efficacy of percutaneous pulmonary vein stenting for the treatment of patients with severe pulmonary vein stenosis due to fibrosing mediastinitis].

Objective: To evaluate the feasibility and safety percutaneous pulmonary vein intervention in patients with severe pulmonary vein stenosis (PVS) caused by fibrosing mediastinitis(FM). Methods: This retrospective analysis included 5 FM patients (2 male, 3 female, 54-77 years old) confirmed by clinical presentation and chest computed tomography (CT) scan from January to June 2018 who were from Gansu Provincial Hospital and Shanghai Chest Hospital. CT pulmonary angiography (CTPA) further revealed severe PVS caused by fibrotic tissue compression in mediastinum. After selective pulmonary vein angiography, gradually balloon angioplasty was used to expand the pulmonary vein and then stents were implanted in the pre-dilated stenotic pulmonary veins. Evaluation of therapeutic effect was made at 6 months after the procedure. Results: All of 11 serious compression PVS were treated with stent implantation (diameter: 7-10 mm, length: 17-27 mm). After stenting, degree of pulmonary vein stenosis decreased from (83±16)% to (12±4)% (P<0.01). The minimal diameter of the stenotic pulmonary vein was significantly increased from (0.8±0.5)mm to (7.5±0.8)mm (P<0.01). Trans-stenotic gradient decreased from (27.0±15.1)mmHg (1 mmHg=0.133 kPa) to (2.50±0.58)mmHg (P<0.05). Mean pulmonary pressure measured by cardiac catheter decreased from (45.0±9.0)mmHg to (38.7±8.4)mmHg (P<0.05). One patient experienced cardiac arrest due to vagal nerve reflex during big sizing balloon stent dilation and recovered after cardiopulmonary resuscitation. There were no other serious procedure related complications. During the follow-up, severe stenosis at end of proximal stent was evidenced in 1 patient due to fibrotic compression, and another patient developed in-stent thrombosis due to discontinuation of prescribed anticoagulant. Conclusion: Percutaneous intervention for severe pulmonary vein stenosis caused by FM is feasible and safe, and can improve hemodynamic caused by the compression of mediastinal vascular structures in these carefully selected patients.

Self-reported domain-specific and accelerometer-based physical activity and sedentary behaviour in relation to psychological distress among an urban Asian population.

BACKGROUND: The interpretation of previous studies on the association of physical activity and sedentary behaviour with psychological health is limited by the use of mostly self-reported physical activity and sedentary behaviour, and a focus on Western populations. We aimed to explore the association of self-reported and devise-based measures of physical activity and sedentary behaviour domains on psychological distress in an urban multi-ethnic Asian population. METHODS: From a population-based cross-sectional study of adults aged 18-79 years, data were used from an overall sample (n = 2653) with complete self-reported total physical activity/sedentary behaviour and domain-specific physical activity data, and a subsample (n = 703) with self-reported domain-specific sedentary behaviour and accelerometry data. Physical activity and sedentary behaviour data were collected using the Global Physical Activity Questionnaire (GPAQ), a domain-specific sedentary behaviour questionnaire and accelerometers. The Kessler Screening Scale (K6) and General Health Questionnaire (GHQ-12) were used to assess psychological distress. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals, adjusted for socio-demographic and lifestyle characteristics. RESULTS: The sample comprised 45.0% men (median age = 45.0 years). The prevalence of psychological distress based on the K6 and GHQ-12 was 8.4% and 21.7%, respectively. In the adjusted model, higher levels of self-reported moderate-to-vigorous physical activity (MVPA) were associated with significantly higher odds for K6 (OR = 1.47 [1.03-2.10]; p-trend = 0.03) but not GHQ-12 (OR = 0.97 [0.77-1.23]; p-trend = 0.79), when comparing the highest with the lowest tertile. Accelerometry-assessed MVPA was not significantly associated with K6 (p-trend = 0.50) nor GHQ-12 (p-trend = 0.74). The highest tertile of leisure-time physical activity, but not work- or transport-domain activity, was associated with less psychological distress using K6 (OR = 0.65 [0.43-0.97]; p-trend = 0.02) and GHQ-12 (OR = 0.72 [0.55-0.93]; p-trend = 0.01). Self-reported sedentary behaviour was not associated with K6 (p-trend = 0.90) and GHQ-12 (p-trend = 0.33). The highest tertile of accelerometry-assessed sedentary behaviour was associated with significantly higher odds for K6 (OR = 1.93 [1.00-3.75]; p-trend = 0.04), but not GHQ-12 (OR = 1.34 [0.86-2.08]; p-trend = 0.18). CONCLUSIONS: Higher levels of leisure-time physical activity and lower levels of accelerometer-based sedentary behaviour were associated with lower psychological distress. This study underscores the importance of assessing accelerometer-based and domain-specific activity in relation to mental health, instead of solely focusing on total volume of activity.

Diagnostic performances of supplemental breast ultrasound screening in women with personal history of breast cancer.

Background Supplemental breast ultrasonography (US) has been used as a surveillance imaging method in women with personal history of breast cancer (PHBC). However, there have been limited data regarding diagnostic performances. Purpose To evaluate diagnostic performances of supplemental breast US screening for women with PHBC and to compare with those for women without PHBC. Material and Methods Between 2011 and 2012, 12,230 supplemental US exams were performed in 12,230 women with negative mammograms: 6584 women with PHBC and 5646 women without PHBC. Cancer detection rate, interval cancer rate, abnormal interpretation rate, positive predictive values (PPVs), sensitivity, and specificity were calculated and compared. Results Overall cancer detection rate and first-year interval cancer rate were 1.80/1000 exams and 0.91/1000 negative exams, both of which were higher in women with PHBC than in women without PHBC (2.88 vs. 0.53 per 1000, P = 0.003; 1.50 vs. 0.20 per 1000, P = 0.027). Abnormal interpretation rate was lower in the women with PHBC than in women without PHBC (9.1% vs. 12.1%, P < 0.001). Sensitivity was not different (67.9% vs. 75.0%, P = 1.000), whereas specificity and PPV3 were higher in women with PHBC than in women without PHBC (91.2% vs. 88.0%, P < 0.001; 22.6% vs. 3.1%, P < 0.001). The majority of detected cancers in women with PHBC (78.9%, 15/19) were stage 0 or 1. Conclusion Supplemental breast US screening increases early stage second breast cancers with high specificity and PPV3 in women with PHBC, however, high interval cancer rate in younger women with PHBC should be noted.

The influences of peritumoral lymphatic invasion and vascular invasion on the survival and recurrence according to the molecular subtypes of breast cancer.

PURPOSE: We aimed to compare the influences of lymphatic invasion (LI) and vascular invasion (VI) on survival and recurrence according to the molecular subtypes of breast cancer. METHODS: We retrospectively analyzed data on 820 breast cancer patients and assessed overall survival (OS) and disease-free survival (DFS) according to LI and VI using the Kaplan-Meier estimator and the Cox proportional hazards model. RESULTS: Both positive LI and positive VI showed inferior OS and DFS compared with negative LI and negative VI (all p < 0.001). Both positive LI and positive VI showed higher local, regional, and distant recurrence rates (p = 0.002 for regional recurrence of VI, p < 0.001 for all the others). Although LI was a significant independent predictor of OS (hazard ratio [HR] 1.927; 95% confidence interval [CI] 1.046-3.553) and DFS (HR 1.815; 95% CI 1.063-3.096), VI was not in the multivariate analyses. Regarding OS, both positive LI and positive VI showed worse survival rates in the luminal A (p = 0.016 and p = 0.024, respectively) and triple negative subtypes (both p < 0.001). Regarding DFS, LI was a significant prognosticator in the luminal A and triple negative (both p < 0.001) subtypes. VI was a significant prognosticator across all molecular subtypes, although the prognostic impact was most prominent in the luminal A subtype (p < 0.001). CONCLUSIONS: Both LI and VI were significant, unfavorable prognostic factors of OS and DFS, especially in the luminal A and triple negative breast cancer subtypes. Although LI was a significant independent predictor of OS and DFS, VI was not after the multivariate analyses.

Diagnostic performance of tomosynthesis and breast ultrasonography in women with dense breasts: a prospective comparison study.

PURPOSE: To compare the diagnostic performances of tomosynthesis and ultrasonography as adjunctives to digital mammography in women with dense breasts. METHODS: A total of 778 women with dense breasts underwent digital mammography with tomosynthesis and ultrasonography for screening and diagnostic purposes. The findings of tomosynthesis and ultrasonography were evaluated independently. The primary endpoint was overall diagnostic accuracy determined by area under the receiver operating characteristic curve (AUC). Secondary endpoints included sensitivity, specificity, and predictive values. RESULTS: Of the 778 participants, 698 women (140 breast cancers) were included in the analysis. Based on the AUC findings, the non-inferiority of tomosynthesis to ultrasonography was established in the overall group as well as in all subgroups except for that comprising women with extremely dense breast composition. There were no significant differences in AUC between tomosynthesis and ultrasonography among asymptomatic participants and participants who underwent imaging for screening (0.912 vs. 0.934 [P = 0.403] and 0.987 vs. 0.950 [P = 0.270], respectively). Tomosynthesis exhibited lower sensitivity (91.4 vs. 96.4%; P = 0.039), and higher specificity (83.9 vs. 70.4%; P < 0.001) and positive predictive value (58.7 vs. 45.0%; P < 0.001) than ultrasonography. CONCLUSIONS: Tomosynthesis exhibits comparable performance to ultrasonography as an adjunct to mammography for diagnosis of breast cancer, except among women with extremely dense breasts.

Preoperative MR Imaging in Women with Breast Cancer Detected at Screening US.

Purpose To determine additional cancer yield of magnetic resonance (MR) imaging in women with breast cancer detected at screening ultrasonography (US) and to identify a subgroup of women who are likely to benefit from preoperative MR imaging. Materials and Methods This study was approved by the institutional review board, and the requirement for informed consent was waived. A retrospective review of 374 women (median age, 48 years; age range, 30-74 years) with breast cancer detected at screening US (invasive, n = 321) who underwent preoperative breast MR imaging between 2007 and 2013 was performed. Cancer yield and positive predictive value of biopsy were calculated. Multivariate logistic regression analysis was performed to identify clinical-pathologic features associated with additional cancer detected at MR imaging. Results Of 374 women, 21 (5.6%; 95% confidence interval [CI]: 3.5%, 8.5%) were diagnosed with additional cancer (positive predictive value of biopsy, 42.0% [21 of 50 women]; 95% CI: 28%, 57%). Index invasive lobular cancer (ILC) histologic type was significantly associated with additional cancer detected at MR imaging (odds ratio, 4.0; 95% CI: 1.2, 13.6; P = .03). In women with index invasive cancer, premenopausal status (odds ratio, 5.7; 95% CI: 1.2, 35.8; P = .03) and lobular histologic type (odds ratio, 3.9; 95% CI: 1.1, 12.3; P = .03) were factors associated with additional cancer detected at MR imaging. Conclusion Preoperative MR imaging helped to detect additional sites of cancer in 5.6% of women with breast cancer detected at screening US. Women with index ILC and premenopausal women are more likely to benefit from preoperative MR imaging. © RSNA, 2016 Online supplemental material is available for this article.

Evaluation of Screening US-detected Breast Masses by Combined Use of Elastography and Color Doppler US with B-Mode US in Women with Dense Breasts: A Multicenter Prospective Study.

Purpose To investigate the value of the combined use of elastography and color Doppler ultrasonography (US) with B-mode US for evaluation of screening US-detected breast masses in women with dense breasts. Materials and Methods This prospective, multicenter study included asymptomatic women with dense breasts who were referred for screening US between November 2013 and December 2014. Eligible women had a newly detected breast mass at conventional B-mode US screening, for which elastography and color Doppler US were performed. The following outcome measures were compared between B-mode US and the combination of B-mode US, elastography, and color Doppler US: area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and the number of false-positive findings at screening US. Results Among 1021 breast masses (mean size, 1.0 cm; range, 0.3-3.0 cm) in 1021 women (median age, 45 years), 68 were malignant (56 invasive). Addition of elastography and color Doppler US to B-mode US increased the AUC from 0.87 (95% confidence interval [CI]: 0.82, 0.91) to 0.96 (95% CI: 0.95, 0.98; P < .001); specificity from 27.0% (95% CI: 24.2%, 29.9%) to 76.4% (95% CI: 73.6%, 79.1%; P < .001) without loss in sensitivity (95% CI: -1.5%, 1.5%; P > .999); and PPV from 8.9% (95% CI: 7.0%, 11.2%) to 23.2% (95% CI: 18.5%, 28.5%; P < .001), while avoiding 67.7% (471 of 696) of unnecessary biopsies for nonmalignant lesions. Conclusion Addition of elastography and color Doppler US to B-mode US can increase the PPV of screening US in women with dense breasts while reducing the number of false-positive findings without missing cancers. © RSNA, 2017 Online supplemental material is available for this article.

Long non-codingRNA (lncRNA) TUG1 and the prognosis of cancer: a meta-analysis.

Some studies assessed the association between lncRNA taurine-upregulated gene 1 (TUG1) and the survival in cancer. However, the results were inconclusive.  Therefore, we performed a meta-analysis to determine this association. We used the following electronic databases to search for eligible literature: PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang. We used ORs and 95% CIs to measure the association between TUG1 and the survival of cancer. There was no significant association between TUG1 and OS of cancer (HR=1.26, 95% CI=0.97-1.64). In the subgroup analysis by cancer type, significant association could be find in osteosarcoma (HR=1.72, 95% CI=1.27-2.32) and digestive system's tumors (HR=1.66, 95% CI=1.04-2.66). In conclusion, this meta-analysis study indicated that TUG1 might associate with the OS of osteosarcoma and digestive system's tumors.

Low birth weight is associated with adiposity, impaired skeletal muscle energetics and weight loss resistance in mice.

BACKGROUND: In utero undernutrition is associated with obesity and insulin resistance, although its effects on skeletal muscle remain poorly defined. Therefore, in the current study we explored the effects of in utero food restriction on muscle energy metabolism in mice. METHODS: We used an experimental mouse model system of maternal undernutrition during late pregnancy to examine offspring from undernourished dams (U) and control offspring from ad libitum-fed dams (C). Weight loss of 10-week-old offspring on a 4-week 40% calorie-restricted diet was also followed. Experimental approaches included bioenergetic analyses in isolated mitochondria, intact (permeabilized) muscle and at the whole body level. RESULTS: U have increased adiposity and decreased glucose tolerance compared to C. Strikingly, when U are put on a 40% calorie-restricted diet they lose half as much weight as calorie-restricted controls. Mitochondria from muscle overall from U had decreased coupled (state 3) and uncoupled (state 4) respiration and increased maximal respiration compared to C. Mitochondrial yield was lower in U than C. In permeabilized fiber preparations from mixed fiber-type muscle, U had decreased mitochondrial content and decreased adenylate-free leak respiration, fatty acid oxidative capacity and state 3 respiratory capacity through complex I. Fiber maximal oxidative phosphorylation capacity did not differ between U and C but was decreased with calorie restriction. CONCLUSIONS: Our results reveal that in utero undernutrition alters metabolic physiology through a profound effect on skeletal muscle energetics and blunts response to a hypocaloric diet in adulthood. We propose that mitochondrial dysfunction links undernutrition in utero with metabolic disease in adulthood.

A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study.

OBJECTIVE: To evaluate the efficacy and safety of subcutaneous blisibimod, an inhibitor of B cell activating factor, in patients with systemic lupus erythematosus (SLE) in a dose-ranging Phase 2b clinical trial. METHODS: 547 patients with SLE with anti-double stranded DNA or antinuclear antibodies and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥6 at baseline were randomised to receive placebo or blisibimod at one of 3 dose levels. The primary end point, measured at Week 24, was the SLE Responder Index-5 (SRI-5, meeting established SRI criteria but with ≥5 point improvement in SELENA-SLEDAI). RESULTS: Although SRI-5 response rates were not significantly improved in the pooled blisibimod groups compared with placebo, they were higher in subjects randomised to the highest dose of blisibimod (200 mg once-weekly (QW)) compared with pooled placebo, from Week 16 to Week 24, reaching statistical significance at Week 20 (p=0.02). SRI response rates compared with placebo were higher still in subjects who attained SELENA-SLEDAI improvements of ≥8, and in a subgroup of patients with severe disease (SELENA-SLEDAI ≥10 and receiving corticosteroids at baseline). In subjects with protein:creatine ratios of 1-6 at baseline, significant reductions in proteinuria were observed with blisibimod. Significant (p<0.01) changes in anti-double stranded DNA antibodies, complement C3 and C4, and reductions in B cells were observed with blisibimod.No imbalances in serious adverse events or infections (4/280 and 3/266), deaths (4/280 and 3/266) and malignancies (2/280 and 2/266) were reported for blisibimod compared with placebo. CONCLUSIONS: This study successfully identified a safe, effective and convenient dose, study population and end point for evaluation of blisibimod effect in Phase 3. TRIAL REGISTRATION NUMBER: NCT01162681.

Expression of mTOR and its inhibitory effect on cell proliferation and apoptosis of breast cancer cells.

The aim of this study is to investigate the expression of mTOR in breast cancer and observe the effect of CCI-779 on proliferation and apoptosis of MDA-MB-231 cells. Immunohistochemical staining was used to detect the expression of mTOR protein in breast cancer tissues and MDA-MB-231 cells. MTT assay was used to assess the effect of CCI-779 on proliferation of MDA-MB-231 cells. Annex-inV-FITC/ PI assay was utilized to evaluate the effect of CCI-779 on apoptosis of MDA-MB-231 cells. Among the 71 cases of breast cancer tissues, 54.9% were mTOR-positive that exhibited significantly higher expression than the 32 cases of normal tissues (21.9%); mTOR protein was also found to be expressed in MDA-MB-231 cells. The mTOR inhibitor CCI-779 significantly inhibited the proliferation of MDA-MB-231 cells that was dose- and time-dependent. However, CCI-779 was unable to induce apoptosis of MDA-MB-231 cells as demonstrated with AnnexinV-FITC/PI assay. mTOR plays a key role in the initiation and development of breast cancer, and its inhibitor CCI-779 exerts a strong suppressive activity against MDA-MB-231 cells, suggesting its therapeutic potential to treat breast cancer.

Quality of end-of-life cancer care in Canada: a retrospective four-province study using administrative health care data.

BACKGROUND: The quality of data comparing care at the end of life (eol) in cancer patients across Canada is poor. This project used identical cohorts and definitions to evaluate quality indicators for eol care in British Columbia, Alberta, Ontario, and Nova Scotia. METHODS: This retrospective cohort study of cancer decedents during fiscal years 2004-2009 used administrative health care data to examine health service quality indicators commonly used and previously identified as important to quality eol care: emergency department use, hospitalizations, intensive care unit admissions, chemotherapy, physician house calls, and home care visits near the eol, as well as death in hospital. Crude and standardized rates were calculated. In each province, two separate multivariable logistic regression models examined factors associated with receiving aggressive or supportive care. RESULTS: Overall, among the identified 200,285 cancer patients who died of their disease, 54% died in a hospital, with British Columbia having the lowest standardized rate of such deaths (50.2%). Emergency department use at eol ranged from 30.7% in Nova Scotia to 47.9% in Ontario. Of all patients, 8.7% received aggressive care (similar across all provinces), and 46.3% received supportive care (range: 41.2% in Nova Scotia to 61.8% in British Columbia). Lower neighbourhood income was consistently associated with a decreased likelihood of supportive care receipt. INTERPRETATION: We successfully used administrative health care data from four Canadian provinces to create identical cohorts with commonly defined indicators. This work is an important step toward maturing the field of eol care in Canada. Future work in this arena would be facilitated by national-level data-sharing arrangements.

Added value of shear-wave elastography for evaluation of breast masses detected with screening US imaging.

PURPOSE: To evaluate the additional value of shear-wave elastography (SWE) to B-mode ultrasonography (US) and to determine an appropriate guideline for the combined assessment of screening US-detected breast masses. MATERIALS AND METHODS: This study was conducted with institutional review board approval, and written informed consent was obtained. From March 2010 to February 2012, B-mode US and SWE were performed in 159 US-detected breast masses before biopsy. For each lesion, Breast Imaging Reporting and Data System (BI-RADS) category on B-mode US images and the maximum stiffness color and elasticity values on SWE images were assessed. A guideline for adding SWE data to B-mode US was developed with the retrospective cohort to improve diagnostic performance in sensitivity and specificity and was validated in a distinct prospective cohort of 207 women prior to biopsy. RESULTS: Twenty-one of 159 masses in the development cohort and 12 of 207 breast masses in the validation cohort were malignant. In the development cohort, when BI-RADS category 4a masses showing a dark blue color or a maximum elasticity value of 30 kPa or less on SWE images were downgraded to category 3, specificity increased from 9.4% (13 of 138) to 59.4% (82 of 138) and 57.2% (79 of 138) (P < .001), respectively, without loss in sensitivity (100% [21 of 21]). In the validation cohort, specificity increased from 17.4% (34 of 195) to 62.1% (121 of 195) and 53.3% (104 of 195) (P < .001) respectively, without loss in sensitivity (91.7% [11 of 12]). CONCLUSION: The addition of SWE to B-mode US improved diagnostic performance with increased specificity for screening US-detected breast masses. BI-RADS category 4a masses detected at US screening that showed a dark blue color or a maximum elasticity value of 30 kPa or less on SWE images can be safely followed up instead of performing biopsy.