Baseline Blood Levels of Mucin-1 Are Associated with Crucial On-Treatment Adverse Outcomes in Patients with Idiopathic Pulmonary Fibrosis Receiving Antifibrotic Pirfenidone.

Mucin-1 is a multi-functional glycoprotein expressed by type II alveolocytes and may be detectable in the circulation following pulmonary fibrosis. The prognostic utility of baseline pre-treatment blood levels of mucin-1 in patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotics has not yet been fully established. We retrospectively studied a cohort of patients (from two hospitals) with IPF who were receiving pirfenidone for >12 weeks. Baseline blood mucin-1 levels were measured via sandwich enzyme-linked immunosorbent assays. We investigated the performance of mucin-1 levels in longitudinally predicting the risks of acute exacerbation of IPF (AE-IPF) and severe adverse outcomes (SAO), including lung transplantation and death. Seventy patients were included; 20 developed AE-IPF; and 31 had SAO during the follow-up period. Patients with baseline mucin-1 levels ≥2.5 ng/mL had enhanced risks of AE-IPF (adjusted hazard ratio [aHR], 14.07; 95% confidence interval [CI], 4.26-46.49) and SAO within 2 years (aHR, 7.87; 95% CI, 2.86-21.70) and anytime during the follow-up (aHR, 4.68; 95% CI, 2.11-10.39). The risks increased across subgroups with increasing mucin-1 levels. Patients in the "mucin-1 ≥ 2.5" group also exhibited an accelerated decline in DLCO. This study supports baseline blood mucin-1 levels as a biomarker for IPF that predicts adverse outcomes during pirfenidone treatment.

Enhanced risk of traumatic brain injury in patients with chronic obstructive pulmonary disease.

This study tests our hypothesis that patients with chronic obstructive pulmonary disease (COPD) have an increased risk of traumatic brain injury (TBI).In this nationwide retrospective cohort study, we used a subset of Taiwan's National Health Insurance Research Database, involving 1 million randomly selected beneficiaries. Patients with newly diagnosed COPD between 2000 and 2008 were identified. They were subgrouped as 'COPDAE+' (if they had severe acute exacerbation of COPD during the follow-ups) or 'COPDAE-' (if they had no acute exacerbation), and were frequency matched with randomly selected subjects without COPD (the 'non-COPD' group). Baseline differences were balanced by the inverse probability of treatment weighting based on the propensity score. For each patient, the risk of TBI during the subsequent 5 years was determined. The competing risk of death was controlled.We identified 3734 patients in 'COPDAE+', and frequency matched them with 11,202 patients in 'COPDAE-' and 11,202 subjects in 'non-COPD'. Compared with those in 'non-COPD', patients in 'COPDAE+' and 'COPDAE-' had an increased risk of TBI: the adjusted HR for 'COPDAE+' was 1.50, 95% CI 1.31 to 1.73, and that for 'COPDAE-' was 1.21, 95% CI 1.09 to 1.34. The highest risk was observed in the 'COPDAE+' group that aged <65 (the adjusted HR was 1.92; 95% CI 1.39 to 2.64).COPD has been linked to complications beyond the respiratory system. In this study we showed that COPD is associated with an increased risk of TBI.

Antiproliferation effect and apoptosis mechanism of prostate cancer cell PC-3 by flavonoids and saponins prepared from Gynostemma pentaphyllum.

The objectives of this study were to investigate the antiproliferation and apoptosis mechanism of saponin and flavonoid fractions from Gynostemma pentaphyllum (Thunb.) Makino on prostate cancer cell PC-3. Both flavonoid and saponin fractions were isolated by a column chromatographic method with Cosmosil 75C(18)-OPN as adsorbent and elution solvents of ethanol-water (30:70, v/v) for the former and 100% ethanol for the latter, followed by high-performance liquid chromatography-tandem mass spectrometry analysis. On the basis of the MTT assay, the saponin and flavonoid fraction were comparably effective in inhibiting the growth of PC-3 cells, with the IC(50) being 39.3 and 33.3 µg/mL, respectively. Additionally, both fractions induced an arrest of PC-3 cell cycle at both S and G2/M phases, with both early and late apoptotic cell populations showing a dose-dependent rise. The Western blot assay indicated that the incorporation of flavonoid or saponin fraction could modulate the expression of G2 and M checkpoint regulators, cyclins A and B, and the antiapoptotic proteins Bcl-2 and Bcl-xl and pro-apoptotic proteins Bad and Bax. The expression of the caspase-3 and its activated downstream substrate effectors, DFF45 and poly (ADP-ribose) polymerase-1 (PARP-1), was also increased and followed a dose-dependent manner. All of these findings suggest that the apoptosis of PC-3 cells may proceed through the intrinsic mitochondria pathway.

Micro package of short term wireless implantable microfabricated systems.

Package is a critical part in biomedical implantable systems. Many factors affecting the host body and the life time of implantable systems need to be considered. Package becomes more critical for microfabricated systems with wireless charging and communication. This paper presents the first phase study on micro package techniques for short term (30 to 90 days) implantable systems. A MEMS implantable telemetry model system was designed for packaging evaluation. The transmitter was custom designed and fabricated using MOSIS processes and an external receiver was designed and built for data collection. For short term implantable systems, medical grade silicone outer coating is used for "tissue compatibility"; while multilayer polymeric and nanometer-thin metal or ceramic films were used for inner coatings to provide mechanical strength and to block vapor and moisture penetration. The total coating thickness is less than 0.6 mm. The electrical performances (leakage resistance) of test board and model devices coated with various package materials and processes are evaluated in 40 degrees C saline. This paper presents: the model system; the evaluation methods and analysis of failure modes of polymeric coating on test boards; the solution to the failures and suggested coating techniques of polymeric materials; and the evaluation of model systems packaged with multi-layer coatings in 40 degrees C saline. The expected performance of developed packaging method was verified by experiments. Implantable wireless MEMS system can be packaged with thin multilayer materials to have an expected life time greater than 30 days.