Real-time bioprocess and automated feed control with in-line Raman sensor

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Intra-articular injections of sodium hyaluronate (Hyalgan®) in osteoarthritis of the knee. a randomized, controlled, double-blind, multicenter trial in the asian population

<p>Abstract</p> <p>Background</p> <p>The efficacy and tolerability of 500-730 kDa sodium hyaluronate (Hyalgan^®) for treatment of osteoarthritis (OA) pain has been established in clinical trials, but few data are available in the Asian population. We conducted a randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and tolerability of this preparation in a Taiwanese population.</p> <p>Methods</p> <p>Two hundred patients with mild to moderate OA of the knee were randomized to receive five weekly intra-articular injections of sodium hyaluronate or placebo. The primary efficacy outcome was the change from baseline to Week 25 in patients' evaluation of pain using a 100-mm visual analog scale (VAS) during the 50-foot walking test. Additional outcomes included Western Ontario and McMaster Universities (WOMAC) scores, time on the 50-foot walking test, patient's and investigator's subjective assessment of effectiveness, acetaminophen consumption, and the amounts of synovial fluid.</p> <p>Results</p> <p>The Hyalgan^®treatment group showed a significantly greater improvement from baseline to Week 25 in VAS pain on the 50-foot walking test than the placebo group (p = 0.0020). The Hyalgan^®group revealed significant improvements from baseline to week 25 in WOMAC pain and function score than the placebo group (p = 0.005 and 0.0038, respectively) Other outcomes, such as time on the 50-foot walking test and subjective assessment of effectiveness, did not show any significant difference between groups. Both groups were safe and well tolerated.</p> <p>Conclusions</p> <p>The present study suggests that five weekly intra-articular injections of sodium hyaluronate are well tolerated, can provide sustained relief of pain, and can improve function in Asian patients with osteoarthritis of the knee.</p> <p>Level of Evidence</p> <p>Therapeutic study, Level I-1a (randomized controlled trial with a significant difference).</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01319461">NCT01319461</a></p

MR Imaging of Pregnancy Luteoma: a Case Report and Correlation with the Clinical Features

We report here on a 26-year-old pregnant female who developed hirsutism and virilization during her third trimester along with a significantly elevated serum testosterone level. Abdominal US and MR imaging studies were performed, and they showed unique imaging features that may suggest the diagnosis of pregnancy luteoma in the clinical context. After the delivery, the serum testosterone level continued to decrease, and it returned to normal three weeks postpartum. The follow-up imaging findings were closely correlated with the clinical presentation

Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways

Antrodia cinnamomea (AC) is a medicinal fungal species that has been widely used traditionally in Taiwan for the treatment of diverse health-related conditions including cancer. It possesses potent anti-inflammatory and antioxidant properties in addition to its ability to promote cancer cell death in several human tumors. Our aim was to improve the anticancer activity of AC in hepatocellular carcinoma (HCC) through its cocultivation with ginger aiming at tuning the active ingredients. HCC cell lines, Huh-7 and HepG2 were used to study the in vitro anticancer activity of the ethanolic extracts of AC (EAC) alone or after the cocultivation in presence of ginger (EACG). The results indicated that the cocultivation of AC with ginger significantly induced the production of important triterpenoids and EACG was significantly more potent than EAC in targeting HCC cell lines. EACG effectively inhibited cancer cells growth via the induction of cell cycle arrest at G2/M phase and induction of apoptosis in Huh-7 and HepG2 cells as indicated by MTT assay, cell cycle analysis, Annexin V assay, and the activation of caspase-3. In addition, EACG modulated cyclin proteins expression and mitogen-activated protein kinase (MAPK) signaling pathways in favor of the inhibition of cancer cell survival. Taken together, the current study highlights an evidence that EACG is superior to EAC in targeting cancer cell survival and inducing apoptotic cell death in HCC. These findings support that EACG formula can serve as a potential candidate for HCC adjuvant therapy

Characterization of CRISPR-Cas Systems in Clinical Klebsiella pneumoniae Isolates Uncovers Its Potential Association With Antibiotic Susceptibility

Prokaryotic CRISPR-Cas systems limit the acquisition of genetic elements and provide immunity against invasive bacteriophage. The characteristics of CRISPR-Cas systems in clinical Klebsiella pneumoniae isolates are still unknown. Here, 97 K. pneumoniae genomes retrieved from the Integrated Microbial Genomes &amp; Microbiomes genome database and 176 clinical isolates obtained from patients with bloodstream (BSI, n = 87) or urinary tract infections (UTI, n = 89) in Taiwan, were used for analysis. Forty out of ninety-seven genomes (41.2%) had CRISPR-Cas systems identified by the combination of CRISPRFinder and cas1 gene sequence alignment. The phylogenetic trees revealed that CRISPR-Cas systems in K. pneumoniae were divided into two types (type I-E, 23; subtype I-E∗, 17) based on the sequences of Cas1 and Cas3 proteins and their location in the chromosome. The distribution of type I-E and I-E∗ CRISPR-Cas systems was associated with the multilocus sequence typing and the pulsed-field gel electrophoresis results. Importantly, no CRISPR-Cas system was identified in published genomes of clonal complex 258 isolates (ST11 and ST258), which comprise the largest multi-drug resistant K. pneumoniae clonal group worldwide. PCR with cas-specific primers showed that 30.7% (54/176) of the clinical isolates had a CRISPR-Cas system. Among clinical isolates, more type I-E CRISPR-Cas systems were found in UTI isolates (BSI, 5.7%; UTI, 11.2%), and subtype I-E∗ CRISPR-Cas systems were dominant in BSI isolates (BSI, 28.7%; UTI, 15.7%) (p = 0.042). Isolates which had subtype I-E∗ CRISPR-Cas system were more susceptible to ampicillin-sulbactam (p = 0.009), cefazolin (p = 0.016), cefuroxime (p = 0.039), and gentamicin (p = 0.012), compared to the CRISPR-negative isolates. The strains containing subtype I-E∗ CRISPR-Cas systems had decreased numbers of plasmids, prophage regions, and acquired antibiotic resistance genes in their published genomes. Here, we first revealed subtype I-E∗ CRISPR-Cas system in K. pneumoniae potentially interfering with the acquisition of phages and plasmids harboring antibiotic resistance determinants, and thus maintained these isolates susceptible to antibiotics

Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake

Serum Levels of Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor 1 Are Associated With Autonomic Dysfunction and Impaired Cerebral Autoregulation in Patients With Epilepsy

Background: Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) may regulate the autonomic nervous system (ANS) in epilepsy. The present study investigated the role of IGF-1 and BDNF in the regulation of autonomic functions and cerebral autoregulation in patients with epilepsy.Methods: A total of 57 patients with focal epilepsy and 35 healthy controls were evaluated and their sudomotor, cardiovagal, and adrenergic functions were assessed using a battery of ANS function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial doppler during the breath-holding test and the Valsalva maneuver. Interictal serum levels of BDNF and IGF-1 were measured with enzyme-linked immunosorbent assay kits.Results: During interictal period, reduced serum levels of BDNF and IGF-1, impaired autonomic functions, and decreased cerebral autoregulation were noted in patients with epilepsy compared with healthy controls. Reduced serum levels of BDNF correlated with age, adrenergic and sudomotor function, overall autonomic dysfunction, and the autoregulation index calculated in Phase II of the Valsalva maneuver, and showed associations with focal to bilateral tonic-clonic seizures. Reduced serum levels of IGF-1 were found to correlate with age and cardiovagal function, a parameter of cerebral autoregulation (the breath-hold index). Patients with a longer history of epilepsy, higher seizure frequency, and temporal lobe epilepsy had lower serum levels of IGF-1.Conclusions: Long-term epilepsy and severe epilepsy, particularly temporal lobe epilepsy, may perturb BDNF and IGF-1 signaling in the central autonomic system, contributing to the autonomic dysfunction and impaired cerebral autoregulation observed in patients with focal epilepsy

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

The Risk of Stroke after Percutaneous Vertebroplasty for Osteoporosis: A Population-Based Cohort Study

PURPOSE: To investigate the incidence and risk of stroke after percutaneous vertebroplasty in patients with osteoporosis. METHODS: A group of 334 patients with osteoporosis, and who underwent percutaneous vertebroplasty during the study period, was compared to 1,655 age-, sex- and propensity score-matched patients who did not undergo vertebroplasty. All demographic covariates and co-morbidities were deliberately matched between the two groups to avoid selection bias. Every subject was followed-up for up to five years for stroke. Adjustments using a Cox regression model and Kaplan-Meier analyses were conducted. RESULTS: A total of 1,989 osteoporotic patients were followed up for 3,760.13 person-years. Overall, the incidence rates of any stroke, hemorrhagic stroke and ischemic stroke were 22.6, 4.2 and 19.6 per 1,000 person-years, respectively. Patients who underwent vertebroplasty were not more likely to have any stroke (crude hazard ratio = 1.13, p = 0.693), hemorrhagic stroke (HR = 2.21, p = 0.170), or ischemic stroke (HR = 0.96, p = 0.90). After adjusting for demographics, co-morbidities and medications, the vertebroplasty group had no significant difference with the comparison group in terms of any, hemorrhagic and ischemic strokes (adjusted HR = 1.22, 3.17, and 0.96, p = 0.518, 0.055, and 0.91, respectively). CONCLUSIONS: Osteoporotic patients who undergo percutaneous vertebroplasty are not at higher risk of any stroke in the next five years after the procedure