BackgroundAcute respiratory distress syndrome (ARDS) due to severe influenza A H1N1 pneumonitis would result in impaired pulmonary functions and health‐related quality of life (HRQoL) after hospital discharge.ObjectivesThe recovery of pulmonary functions, exercise capacity, and HRQoL in the survivors of ARDS due to 2009 pandemic influenza A H1N1 pneumonitis (H1N1‐ARDS) was evaluated in a tertiary teaching hospital in northern Taiwan between May 2010 and June 2011.Patients and MethodsData of spirometry, total lung capacity (TLC), diffusing capacity of carbon monoxide (DLCO), and 6‐minute walk distance (6MWD) in the patients survived from H1N1‐ARDS were collected 1, 3, and 6 months post‐hospital discharge. HRQoL was evaluated with St. George respiratory questionnaire (SGRQ).ResultsNine survivors of H1N1‐ARDS in the study period were included. All these patients received 2 months’ pulmonary rehabilitation program. Pulmonary functions and exercise capacity included TLC, forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1), DLCO, and 6MWD improved from 1 to 3 months post‐hospital discharge. Only TLC had further significant improvement from 3 to 6 months. HRQoL represented as the total score of SGRQ had no significant improvement in the first 3 months but improved significantly from 3 to 6 months post‐discharge.ConclusionThe impaired pulmonary functions and exercise capacity in the survivors of H1N1‐ARDS improved soon at 3 months after hospital discharge. Their quality of life had keeping improved at 6 months even though there was no further improvement of their pulmonary functions and exercise capacity.

Tumor cells transform into endothelial cells by epithelial-to-mesenchymal transition, which is characterized by vasculogenic mimicry (VM). VM not only accelerates tumor progression but also increases drug-induced resistance. However, very little is currently known about the molecular determinants that enable VM. Targeting VM might bring a new breakthrough in cancer treatment. Thrombin is the key enzyme of the blood coagulation system and could contribute to tumor progression. Nevertheless, the association between thrombin and VM formation remains largely unknown. We found that VM was associated with the overall survival of non-small-cell lung cancer (NSCLC) patients, and that thrombin expression was closely related to VM formation. This research revealed that thrombin induced VM formation via PAR-1-mediated NF-κB signaling cascades. The novel thrombin inhibitors r-hirudin and DTIP inhibited VM formation and spontaneous metastases in subcutaneous tumors. Clinical pathological analysis confirmed that NSCLC patients with thrombin-positive/PAR-1-high expression had the poorest prognosis and were the most likely to form VM. The promotional activity of thrombin in VM formation and tumor metastasis was abolished in PAR-1deficient NSCLC cells. The EGFR inhibitor gefitinib had no effect on VM and increased VEGF expression in tumors. The combination therapy of DTIP and gefitinib achieved a better therapeutic effect than either agent alone. This study is the first to illustrate that thrombin substantially contributes, together with PAR-1, to VM formation and to illustrate that VM might be a target of r-hirudin and DTIP to suppress tumor progression. The anticoagulants r-hirudin and DTIP could be employed for antitumor therapy. Combination therapy with DTIP with an EGFR inhibitor might achieve superior therapeutic effects.

Misfolding, aggregation, and cerebral accumulation of tau deposits are hallmark features of Alzheimer’s disease. Positron emission tomography study of tau can facilitate the development of anti-tau treatment. Here, we investigated a novel tau tracer 18F-PM-PBB3 (18F-APN-1607) in a mouse model of tauopathy. Dynamic PET scans were collected in groups of rTg4510 transgenic mice at 2–11 months of age. Associations between distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) with cerebellum reference were used to determine the optimal scanning time and uptake pattern for each age. Immunohistochemistry staining of neurofibrillary tangles and autoradiography study was performed for ex vivo validation. An SUVR 40–70 min was most consistently correlated with DVR and was used in further analyses. Significant increased 18F-PM-PBB3 uptake in the brain cortex was found in six-month-old mice (+28.9%, p < 0.05), and increased further in the nine-month-old group (+38.8%, p < 0.01). The trend of increased SUVR value remained evident in the hippocampus and striatum regions except for cortex where uptake becomes slightly reduced in 11-month-old animals (+37.3%, p < 0.05). Radioactivity distributions from autoradiography correlate well to the presence of human tau (HT7 antibody) and hyperphosphorylated tau (antibody AT8) from the immunohistochemistry study of the adjacent brain sections. These findings supported that the 40–70 min 18F-PM-PBB3 PET scan with SUVR measurement can detect significantly increased tau deposits in a living rTg4510 transgenic mouse models as early as six-months-old. The result exhibited promising dynamic imaging capability of this novel tau tracer, and the above image characteristics should be considered in the design of longitudinal preclinical tau image studies.

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Cytoplasmic polyadenylation element binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein that downregulates translation of multiple plasticity-related proteins (PRPs) at the glutamatergic synapses. Activity-induced synthesis of PRPs maintains long-lasting synaptic changes that are critical for memory consolidation and chronic pain manifestation. CPEB3-knockout (KO) mice show aberrant hippocampus-related plasticity and memory, so we investigated whether CPEB3 might have a role in nociception-associated plasticity. CPEB3 is widely expressed in the brain and peripheral afferent sensory neurons. CPEB3-KO mice with normal mechanosensation showed hypersensitivity to noxious heat. In the complete Freund's adjuvant (CFA)-induced inflammatory pain model, CPEB3-KO animals showed normal thermal hyperalgesia and transiently enhanced mechanical hyperalgesia. Translation of transient receptor potential vanilloid 1 (TRPV1) RNA was suppressed by CPEB3 in dorsal root ganglia (DRG), whereas CFA-induced inflammation reversed this inhibition. Moreover, CPEB3/TRPV1 double-KO mice behaved like TRPV1-KO mice, with severely impaired thermosensation and thermal hyperalgesia. An enhanced thermal response was recapitulated in non-inflamed but not inflamed conditional-KO mice, with cpeb3 gene ablated mostly but not completely, in small-diameter nociceptive DRG neurons. CPEB3-regulated translation of TRPV1 RNA may play a role in fine-tuning thermal sensitivity of nociceptors.