The accuracy of simple, feasible alternatives to polysomnography for assessing sleep in intensive care: An observational study.

BACKGROUND: Sleep disturbance is common in intensive care patients. Understanding the accuracy of simple, feasible sleep measurement techniques is essential to informing their possible role in usual clinical care. OBJECTIVE: The aim of the study was to investigate whether sleep monitoring techniques such as actigraphy (ACTG), behavioural assessments, and patient surveys are comparable with polysomnography (PSG) in accurately reporting sleep quantity and quality among conscious, intensive care patients. METHODS: An observational study was conducted in 20 patients admitted to the intensive care unit (ICU) for a minimum duration of 24 h, who underwent concurrent sleep monitoring via PSG, ACTG, nursing-based observations, and self-reported assessment using the Richards-Campbell Sleep Questionnaire. RESULTS: The reported total sleep time (TST) for the 20 participants measured by PSG was 328.2 min (±106 min) compared with ACTG (362.4 min [±62.1 min]; mean difference = 34.22 min [±129 min]). Bland-Altman analysis indicated that PSG and ACTG demonstrated clinical agreement and did not perform differently across a number of sleep variables including TST, awakening, sleep-onset latency, and sleep efficiency. Nursing observations overestimated sleep duration compared to PSG TST (mean difference = 9.95 ± 136.3 min, p > 0.05), and patient-reported TST was underestimated compared to PSG TST (mean difference = -51.81 ± 144.1 7, p > 0.05). CONCLUSIONS: Amongst conscious patients treated in the ICU, sleep characteristics measured by ACTG were similar to those measured by PSG. ACTG may provide a clinically feasible and acceptable proxy approach to sleep monitoring in conscious ICU patients.

Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy - an ancillary study of the SAKK 09/10 randomized clinical trial.

BACKGROUND: The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. PATIENTS AND METHODS: A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. RESULTS: The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P < 0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores. CONCLUSIONS: This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.

Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial.

BACKGROUND: The phase III CHAARTED trial established upfront androgen-deprivation therapy (ADT) plus docetaxel (D) as a standard for metastatic hormone-sensitive prostate cancer (mHSPC) based on meaningful improvement in overall survival (OS). Biological prognostic markers of outcomes and predictors of chemotherapy benefit are undefined. PATIENTS AND METHODS: Whole transcriptomic profiling was performed on primary PC tissue obtained from patients enrolled in CHAARTED prior to systemic therapy. We adopted an a priori analytical plan to test defined RNA signatures and their associations with HSPC clinical phenotypes and outcomes. Multivariable analyses (MVAs) were adjusted for age, Eastern Cooperative Oncology Group status, de novo metastasis presentation, volume of disease, and treatment arm. The primary endpoint was OS; the secondary endpoint was time to castration-resistant PC. RESULTS: The analytic cohort of 160 patients demonstrated marked differences in transcriptional profile compared with localized PC, with a predominance of luminal B (50%) and basal (48%) subtypes, lower androgen receptor activity (AR-A), and high Decipher risk disease. Luminal B subtype was associated with poorer prognosis on ADT alone but benefited significantly from ADT + D [OS: hazard ratio (HR) 0.45; P = 0.007], in contrast to basal subtype which showed no OS benefit (HR 0.85; P = 0.58), even in those with high-volume disease. Higher Decipher risk and lower AR-A were significantly associated with poorer OS in MVA. In addition, higher Decipher risk showed greater improvements in OS with ADT + D (HR 0.41; P = 0.015). CONCLUSION: This study demonstrates the utility of transcriptomic subtyping to guide prognostication in mHSPC and potential selection of patients for chemohormonal therapy, and provides proof of concept for the possibility of biomarker-guided selection of established combination therapies in mHSPC.

The feasibility and reliability of actigraphy to monitor sleep in intensive care patients: an observational study.

BACKGROUND: Sleep amongst intensive care patients is reduced and highly fragmented which may adversely impact on recovery. The current challenge for Intensive Care clinicians is identifying feasible and accurate assessments of sleep that can be widely implemented. The objective of this study was to investigate the feasibility and reliability of a minimally invasive sleep monitoring technique compared to the gold standard, polysomnography, for sleep monitoring. METHODS: Prospective observational study employing a within subject design in adult patients admitted to an Intensive Care Unit. Sleep monitoring was undertaken amongst minimally sedated patients via concurrent polysomnography and actigraphy monitoring over a 24-h duration to assess agreement between the two methods; total sleep time and wake time. RESULTS: We recruited 80 patients who were mechanically ventilated (24%) and non-ventilated (76%) within the intensive care unit. Sleep was found to be highly fragmented, composed of numerous sleep bouts and characterized by abnormal sleep architecture. Actigraphy was found to have a moderate level of overall agreement in identifying sleep and wake states with polysomnography (69.4%; K = 0.386, p < 0.05) in an epoch by epoch analysis, with a moderate level of sensitivity (65.5%) and specificity (76.1%). Monitoring accuracy via actigraphy was improved amongst non-ventilated patients (specificity 83.7%; sensitivity 56.7%). Actigraphy was found to have a moderate correlation with polysomnography reported total sleep time (r = 0.359, p < 0.05) and wakefulness (r = 0.371, p < 0.05). Bland-Altman plots indicated that sleep was underestimated by actigraphy, with wakeful states overestimated. CONCLUSIONS: Actigraphy was easy and safe to use, provided moderate level of agreement with polysomnography in distinguishing between sleep and wakeful states, and may be a reasonable alternative to measure sleep in intensive care patients. Clinical Trial Registration number ACTRN12615000945527 (Registered 9/9/2015).

A case of GNE myopathy mimicking hereditary motor neuropathy.

A 36-year-old woman who presented with upper limb distal weakness since the age of 15 years, with gradual progression to the lower limbs, is reported. Hereditary motor neuropathy was initially suspected based on distal weakness and hyporeflexia; however, whole exome sequencing accidentally revealed a compound heterozygous variant in the GNE gene, and ultrasound revealed increased homogeneous echogenicity in the involved muscles, which is characteristic of myopathic changes. Muscle magnetic resonance imaging revealed fatty infiltration in all limb muscles, sparing the triceps brachii, vastus lateralis and vastus medialis. Muscle biopsy revealed intracytoplasmic rimmed vacuole, supporting the diagnosis of GNE myopathy.

Fracture liaison services for osteoporosis in the Asia-Pacific region: current unmet needs and systematic literature review.

The analysis aimed to identify the treatment gaps in current fracture liaison services (FLS) and to provide recommendations for best practice establishment of future FLS across the Asia-Pacific region. The findings emphasize the unmet need for the implementation of new programs and provide recommendations for the refinement of existing ones. The study's objectives were to evaluate fracture liaison service (FLS) programs in the Asia-Pacific region and provide recommendations for establishment of future FLS programs. A systematic literature review (SLR) of Medline, PubMed, EMBASE, and Cochrane Library (2000-2017 inclusive) was performed using the following keywords: osteoporosis, fractures, liaison, and service. Inclusion criteria included the following: patients ≥ 50 years with osteoporosis-related fractures; randomized controlled trials or observational studies with control groups (prospective or retrospective), pre-post, cross-sectional and economic evaluation studies. Success of direct or indirect interventions was assessed based on patients' understanding of risk, bone mineral density assessment, calcium intake, osteoporosis treatment, re-fracture rates, adherence, and mortality, in addition to cost-effectiveness. Overall, 5663 unique citations were identified and the SLR identified 159 publications, reporting 37 studies in Asia-Pacific. These studies revealed the unmet need for public health education, adequate funding, and staff resourcing, along with greater cooperation between departments and physicians. These actions can help to overcome therapeutic inertia with sufficient follow-up to ensure adherence to recommendations and compliance with treatment. The findings also emphasize the importance of primary care physicians continuing to prescribe treatment and ensure service remains convenient. These findings highlight the limited evidence supporting FLS across the Asia-Pacific region, emphasizing the unmet need for new programs and/or refinement of existing ones to improve outcomes. With the continued increase in burden of fractures in Asia-Pacific, establishment of new FLS and assessment of existing services are warranted to determine the impact of FLS for healthcare professionals, patients, family/caregivers, and society.

[Clinical research about needle-tract assisted standard percutaneous nephrolithotomy for the treatment of complicated upper urinary tract calculi].

Objective: To investigate the safety and efficacy of needle-tract assisted standard percutaneous nephrolithotomy (PCNL) for the treatment of complicated upper urinary tract calculi. Methods: The clinical data of 1 562 patients with complicated upper urinary calculi who received standard PCNL from December 2013 to December 2017 at Department of Urology, the First Affiliated Hospital of Xiamen University were retrospectively analyzed. There were large residual stones in 256 patients through B-ultrasound exploration after standard PCNL, could't be detected with nephoscope in standard PCNL tracts. 16 F mini PCNL tract were established in 120 cases for treatment of residual stones, while needle-tract were established in order to guide nephroscope to find residual stones in 126 cases. Needle-tract were transferred to 16 F mini PCNL tract for treatment of residual stones in 10 patients if these residual stones could't be detected through needle-tract. Operation time, change of hemoglobin level after operation, incidence of postoperative complications, time of hospitalization and rate of stone clearance were measured in two groups. The statistical methods used included t test, Wilcoxon rank sum test, and χ2 test. Results: There were 1 to 3 mini tracts (M(QR): 1(1)) established in the mini tracts group and 1 to 7 needle-tracts (M(QR): 3(2)) established in the needle-tract group (Z=-10.57, P=0.000). Compared with mini tract group, the operation time ((62.0±18.0) minutes vs. (84.0±15.5) minutes, t=10.242, P=0.000), hospitalization time ((4.40±0.86) days vs. (5.20±0.81) days, t=7.570, P=0.049), hemoglobin dropped ((1.31±0.47) g/L vs. (2.74±0.63) g/L, t=20.12, P=0.000), and incidence of postoperative complications (7.9% (10/126) vs. 19.2% (23/120), χ2=6.674, P=0.01) of needle-tract group were lower, while postoperative stone clearance rate was higher (89.7% vs. 76.7%, χ2=7.497, P=0.006). No perioperative severe complications such as pleural injury, pneumatothorax, perforation of renal, trauma of abdominal organ occurred in two groups. Conclusion: Needle-tract assisted standard PCNL for the treatment of complicated upper urinary calculi can significantly improve stone clearance rate, reduce operation time, decrease risk of kidney and surrounding organs damage.

The upper-limb volumetric changes in breast cancer survivors with axillary web syndrome.

Whether upper-limb swelling is associated with axillary web syndrome (AWS) is unknown. We recruited unilateral breast cancer (BC) patients who were scheduled for surgical intervention and lymph node dissection. The pre-operative assessment and post-operative assessment 3-4 weeks after surgery evaluated the upper-limb circumferential measurements, segmental limb volume, pain scores, grasp, shoulder range of motion (ROM), shoulder muscle power and quality-of-life scores. In the control group, the peri-elbow volume and upper-arm volume were significantly higher post-operatively than pre-operatively. In the AWS group, no significant difference was found. In comparison with the control group, the AWS group had significantly more pain, less active ROM in shoulder abduction and a lower upper-limb volume at 0-10 cm proximal to the lateral epicondyle. The incidence of lymphedema was 9.9% and was not associated with AWS. AWS is a common morbidity of lymph node dissection and causes significant pain and restricted shoulder abduction in the affected limb in BC survivors. This study is the first to investigate post-operative upper-limb volumetric changes in BC survivors with and without AWS. Our findings are of great value for the clinical effect of AWS in BC survivors, for patient education, and for developing diagnostic tools for detecting AWS.

[The surgical treatment of ovarian cancer metastasis between liver and diaphragm: a report of 83 cases].

Objective: To explore the safety and feasibility of associating diaphragm resection and liver-diaphragmatic metastasis lesions resection for patients with advanced ovarian cancer. Methods: Retrospectively analysis 83 cases(98 times) of advanced ovarian cancer with liver-diaphragmatic metastasis between January 2012 and December 2016 at Department of Liver Surgery, Peking Union Medical College Hospital.The patients were aged from 19 to 75 years.Surgical procedure included metastatic lesions resection(43 times) and stripping(55 times). Operation status, post-operative complications, pathology results and follow-up of the patients were analyzed. Results: Fifteen patients received twice surgical treatment and 68 patients received one time surgical treatment. Postoperative hemorrhage in chest and between liver and diaphragm was not occurred in all cases.Dyspnea and low oxygen saturation were occurred in two cases of stripping patients and 1 case of metastatic lesions resection patients.Results of CT examination indicated that there was medium to large amount of ascites in right chests.The symptoms were relieved after placing thoracic closed drainage.Other patients were recovered smoothly.All patients were diagnosed as ovarian cancer by pathological examination. Conclusion: Associating diaphragm resection is safe and feasible for liver-diaphragmatic metastasis lesions from ovarian cancer.

[Visual impact of sub-tenon's anesthesia during surgery for retinal detachment].

Objective: To investigate the visual impact and influence factors of sub-Tenon's anesthesia in retinal detachment patients during pars plana vitrectomy (PPV) or combined phacoemulsification and PPV surgery. Methods: In this prospective case series study, 104 consecutive patients who underwent PPV or combined phacoemulsification and PPV under sub-Tenon's anesthesia between October 2012 and December 2013 were enrolled. Intraoperatively, the patients were asked whether they could see the light of the operating microscope or not at 5 minutes after sub-Tenon's anesthesia, and at the end of phacoemulsification, core vitreous removal, peripheral vitreous removal and the whole surgery, with their contralateral eyes being covered tightly and no photobleaching. The best corrected visual acuity and visual evoked potentials were examined and compared with each other preoperatively and at 1.5 months and 3 months postoperatively. Chi-square test was used to compare the detection rate of amaurosis between different modus operandi and whether covered contra-lateral eye. Student-t test was used to compare the difference of age and preoperative BCVA between the patients with or without experienced amaurois. Lastly, BCVA between different times were tested by one-way ANOVA analysis. Results: Without covering the contralateral eyes, the incidence of no light perception in various surgical steps was 0%, while it was 72.1%(75/104), 93.8%(75/80), 96.2%(100/104), 96.2%(100/104) and 86.5%(90/104) at the five timepoints, respectively, when the contralateral eyes were covered tightly. The incidence was 51.9%(54/104), 85.0%(68/80), 85. 6%(89/104), 84.6%(69/104) and 66.3%(88/104), respectively, after photobleaching was excluded. Approximately 95.2%(99/104) of patients reported no light perception at least once, 54.5%(54/99) reported no light perception 5 minutes after sub-Tenon's anesthesia, and 30.3%(30/99) recovered light perception when the surgery was finished. All eyes recovered to at least light perception on the first postoperative day. The best corrected visual acuity and visual evoked potentials at 1.5 months and 3 months postoperatively were significantly better than those before surgery. The BCVA was 1.75±0.78 preoperative, 0.96±0.63 1.5 months after operation, and 0.92±0.57 3 months after operation. There was a significant statistical difference between preoperative BCVA and postoperative BCVA (F=50.61, P<0.01) . In patients without waveform detection preoperatively, PVEP waveform could be found in 43.6% and 61.4% of the pactients at 1.5 months and 3 months after operation respectively. In those had certain waveform preoperatively, PVEP amplitudes rise significantly after surgery (t(1.5)=-2.69, t(3)=-2.97, P<0.05) . Conclusions: No light perception was detected in various surgical steps of vitrectomy under sub-Tenon's anesthesia in most patients. The blocking of optic nerve conduction may be caused by sub-Tenon' s anesthesia. Photobleaching can also have some effect. The incidence of no light perception during the surgery was not correlated with preoperative visual acuity, age and gender. Moreover, the effect was transient and harmless to visual function.(Chin J Ophthalmol, 2017, 53: 332-337).

Bacteria killing nanotechnology Bio-Kil effectively reduces bacterial burden in intensive care units.

A contaminated hospital environment has been identified as an important reservoir of pathogens causing healthcare-associated infections. This study is to evaluate the efficacy of bacteria killing nanotechnology Bio-Kil on reducing bacterial counts in an intensive care unit (ICU). Two single-bed rooms (S-19 and S-20) in the ICU were selected from 7 April to 27 May 2011. Ten sets of new textiles (pillow cases, bed sheets, duvet cover, and patient clothing) used by patients in the two single-bed rooms were provided by the sponsors. In the room S-20, the 10 sets of new textiles were washed with Bio-Kil; the room walls, ceiling, and air-conditioning filters were treated with Bio-Kil; and the surfaces of instruments (respirator, telephone, and computer) were covered with Bio-Kil-embedded silicon pads. Room S-19 served as the control. We compared the bacterial count on textiles and environment surfaces as well as air samples between the two rooms. A total of 1,364 samples from 22 different sites in each room were collected. The mean bacterial count on textiles and environmental surfaces in room S-20 was significantly lower than that in room S-19 (10.4 vs 49.6 colony-forming units [CFU]/100 cm(2); P < 0.001). Room S-20 had lower bacterial counts in air samples than room S-19 (33.4-37.6 vs 21.6-25.7 CFU/hour/plate; P < 0.001). The density of microbial isolations was significantly greater among patients admitted to room S-19 than those to room S-20 (9.15 vs 5.88 isolates per 100 patient-days, P < 0.05). Bio-Kil can significantly reduce bacterial burden in the environment of the ICU.

Development of a Semiselective Medium for Detection of Nalanthamala psidii, Causal Agent of Wilt of Guava.

Guava wilt, caused by Nalanthamala psidii, has become an important disease of guava (Psidium guajava) in Taiwan since the 1970s. This study was conducted to develop a semiselective medium for detecting N. psidii in soil and in tissues of diseased guava trees. Among 9 carbon and 21 nitrogen compounds tested in a modified Czapek-Dox medium, the most effective carbon and nitrogen sources for mycelial growth of N. psidii were sucrose and glycine, respectively. Among eight fungicides tested, iprodione at 5 µg ml-1 and azoxystrobin at 1 µg ml-1 were the most effective fungicides for detection of N. psidii in artificially infested soil or in naturally infected guava debris. Based on the requirement for carbon and nitrogen sources and response to fungicides, a semiselective medium designated as modified sucrose-glycine semiselective medium (mSGSSM) was developed for isolation of N. psidii, using the modified Czapek-Dox medium containing 3% sucrose, 0.3% glycine, iprodione at 5 µg ml-1, azoxystrobin at 1 µg ml-1, streptomycin at 200 µg ml-1, and neomycin at 200 µg ml-1. Colonies of N. psidii on mSGSSM at 30°C for 5 to 10 days were white to orange with sparse aerial hyphae. N. psidii was detected more accurately and efficiently on mSGSSM than on other media, including potato dextrose agar, modified Nash-Snyder medium, and modified Czapek-Dox medium. This semiselective medium is effective in detection of N. psidii from various parts of diseased guava trees and in soil; therefore, it would be a useful medium for etiological, ecological, and epidemiological studies of guava wilt.

II. Novel HCV NS5B polymerase inhibitors: discovery of indole C2 acyl sulfonamides.

Development of SAR at the C2 position of indole lead 1, a palm site inhibitor of HCV NS5B polymerase (NS5B IC(50)=0.053µM, replicon EC(50)=4.8µM), is described. Initial screening identified an acyl sulfonamide moiety as an isostere for the C2 carboxylic acid group. Further SAR investigation resulted in identification of acyl sufonamide analog 7q (NS5B IC(50)=0.039µM, replicon EC(50)=0.011µM) with >100-fold improved replicon activity.

I. Novel HCV NS5B polymerase inhibitors: discovery of indole 2-carboxylic acids with C3-heterocycles.

SAR development of indole-based palm site inhibitors of HCV NS5B polymerase exemplified by initial indole lead 1 (NS5B IC(50)=0.9 µM, replicon EC(50)>100 µM) is described. Structure-based drug design led to the incorporation of novel heterocyclic moieties at the indole C3-position which formed a bidentate interaction with the protein backbone. SAR development resulted in leads 7q (NS5B IC(50)=0.032 µM, replicon EC(50)=1.4 µM) and 7r (NS5B IC(50)=0.017 µM, replicon EC(50)=0.3 µM) with improved enzyme and replicon activity.

Control of postharvest Botrytis fruit rot of strawberry by volatile organic compounds of Candida intermedia.

A study was conducted to identify volatile organic compounds or volatiles produced by Candida intermedia strain C410 using gas chromatography-mass spectrometry, and to determine efficacy of the volatiles of C. intermedia in suppression of conidial germination and mycelial growth of Botrytis cinerea and control of Botrytis fruit rot of strawberry. Results showed that, among 49 volatiles (esters, alcohols, alkenes, alkanes, alkynes, organic acids, ketones, and aldehydes) identified from C. intermedia cultures on yeast extract peptone dextrose agar, two compounds, 1,3,5,7-cyclooctatetraene and 3-methyl-1-butanol, were the most abundant. Synthetic chemicals of 1,3,5,7-cyclooctatetraene; 3-methyl-1-butanol; 2-nonanone; pentanoic acid, 4-methyl-, ethyl ester; 3-methyl-1-butanol, acetate; acetic acid, pentyl ester; and hexanoic acid, ethyl ester were highly inhibitory to conidial germination and mycelial growth of B. cinerea. Inhibition of conidial germination and mycelial growth of B. cinerea by volatiles of C. intermedia was also observed. Meanwhile, results showed that incidence and severity of Botrytis fruit rot of strawberry was significantly (P < 0.01) reduced by exposure of the strawberry fruit to the volatiles from C. intermedia cultures or C. intermedia-infested strawberry fruit. These results suggest that the volatiles of C. intermedia C410 are promising biofumigants for control of Botrytis fruit rot of strawberry.

MicroRNA-21 expression in neonatal blood associated with antenatal immunoglobulin E production and development of allergic rhinitis.

BACKGROUND: The prevalence of allergic diseases has increased in the past decades. It is unknown whether expression of certain microRNAs (miRNAs) in neonatal leucocytes is correlated to IgE production and/or allergic diseases. OBJECTIVE: This study investigated the association of miRNA expression in neonatal leucocytes with cord blood IgE (CBIgE) elevation and development of allergic disease. METHODS: We screened for the expression of a panel of 157 miRNAs in mononuclear leucocytes from human umbilical cord blood (CB) samples with elevated CBIgE and tracked the association of down-regulated miRNA expression to the miRNA-targeted gene expression and to children with allergic rhinitis (AR). RESULTS: Among the initial screen of 10 CB samples with elevated CBIgE, expression of eight of the 157 miRNAs was low. Of these eight down-expressed miRNAs, three remained down-regulation in a validation with other 20 CB samples, and two of the three miRNAs, miR-21 and miR-126, were significantly lower in monocytes from AR children. Further analysis of mRNA expression of the miR-21-targeted genes identified that TGFBR2 expression on monocytes was significantly up-regulated in CB with elevated CBIgE, and in AR patients. Transfection of miR-21 precursor into monocytes from patients with AR increased miR-21 expression and decreased TGFBR2 expression. CONCLUSION: This study demonstrated the first in the literature that lower miR-21 expression in CB and increased TGFBR2 expression is associated with antenatal IgE production and development of AR.

Inhibitors of hepatitis C virus polymerase: synthesis and characterization of novel 2-oxy-6-fluoro-N-((S)-1-hydroxy-3-phenylpropan-2-yl)-benzamides.

SAR exploration from an initial hit, (S)-N-(2-cyclohexenylethyl)-2-fluoro-6-(2-(1-hydroxy-3-phenylpropan-2-ylamino)-2-oxoethoxy)benzamide (1), identified using our proprietary automated ligand identification system (ALIS),(1) has led to a novel series of selective hepatitis C virus (HCV) NS5B polymerase inhibitors with improved in vitro potency as exemplified by (S)-2-fluoro-6-(2-(1-hydroxy-3-phenylpropan-2-ylamino)-2-oxoethoxy)-N-isopentyl-N-methylbenzamidecarboxamide (41) (IC(50)=0.5 microM). The crystal structure of an analogue (44) was solved and provided rationalization of the SAR of this series, which binds in a distinct manner in the palm domain of NS5B, consistent with biochemical analysis using enzyme mutant variants. These data warrant further lead optimization efforts on this novel series of non-nucleoside inhibitors targeting the HCV polymerase.

Assessment of the clinical outcomes and cost-effectiveness of the management of systolic heart failure in Chinese patients using a home-based intervention.

This study was designed to assess the clinical effect of a home-based telephone intervention in Chinese heart failure patients. A total of 550 Chinese heart failure patients were enrolled into either (i) a group that received the usual standard of care (UC group); or (ii) a group that received a home-based heart failure centre management programme using nursing specialist-led telephone consultations (HFC group). The impact of the home-based intervention on admission rate, admission length and medical costs over 6 months was measured. Although the mean left ventricular ejection fraction in HFC patients was 29.3% compared with 34.8% in UC patients, the home-based intervention resulted in a significantly lower all-cause admission rate per person (HFC 0.60 +/- 0.77 times/person; UC 0.96 +/- 0.85 times/person), a shorter all-cause hospital stay (reduced by 8 days per person) and lower total 6-month medical costs (reduced by US$2682 per patient). These results suggest that the home-based intervention with nursing specialist-led telephone consultations may improve the clinical outcome and provide cost-savings for Chinese patients with heart failure.