Lipoprotein(a) [Lp(a)] is a unique lipoprotein with controversial functions. Lp(a) contains apolipoprotein(a) [apo(a)] covalently attached to apolipoprotein B on the low-density lipoprotein (LDL) particle. The distribution of blood Lp(a) concentrations in several populations have been found to be skewed with Lp(a) being mostly present at low level (0 – 200 mg/L). A high Lp(a) concentration (greater than 200 mg/L) in blood increases the risk of various vascular diseases including chronic heart disease, acute myocardial infarction and cerebral thrombosis. With Lp(a) potentially having such deleterious effects, there is a need to ask what are the evolutionary benefit(s) of Lp(a) to humans and other mammals that have it. Lp(a) has been reported to offer a number of benefits such as providing protection from LDL cholesterol and providing a source of cholesterol in wound tissue. Furthermore, some evidence is emerging that Lp(a) has anti-tumor properties. Other surveys have indicated that Lp(a) is advantageous because it promotes longevity. Lp(a) is only found in humans, old world monkeys and hedgehogs. Individuals who do not express Lp(a) do not show any disease symptoms, which indicates that Lp(a) is not essential for human life. It still remains unclear why mysterious Lp(a) has evolved and is present in humans.

Much progress has been made in gene therapy, but significant challenges remain. One is development of a range of different tools that can be used for different therapeutic purposes. Another is site-specific gene targeting for safe and faithful therapeutic gene expression. Viruses have long been considered the most promising tools for human gene therapy. However, fatal side effects associated with viral vectors have hampered their clinical application. DNA transposons, widely utilized for decades as genetic tools in plants and insects, are now emerging as viable vectors for gene therapy. In this article, we will give a brief review of the adverse effects associated with virus-based gene therapy followed by a glimpse of the adeno-associated virus vector system, which is currently the most promising viral vector for gene therapy. The development of DNA transposon-based gene delivery systems and the advantages and limits of the most commonly used DNA transposon systems, Sleeping Beauty, Tol2, and piggyBac, will be extensively discussed Finally, we will focus on the most promising transposon system for gene therapy, piggyBac. Challenges and considerations for advancing piggyBac for therapeutic application will be critically addressed.

Background: In recent years, there has been a rapid worldwide emergence of multidrugresistant (MDR) pathogens, especially in cases of nosocomial infections. This study assesses the in vitro activities of ampicillin/sulbactam, cefpirome, colistin, daptomycin, ertapenem, meropenem, teicoplanin, tigecycline and vancomycin against 208 aerobic bacterial pathogens that caused 197 nosocomial infections in 184 patients. Methods: Antimicrobial susceptibility was evaluated by Etest. Broth dilution method was utilized in tigecycline susceptibility testing. Results: Most (140/208, 67%) of the isolates were facultative Gram-negative bacilli. Of the 31 oxacillin-resistant S. aureus (ORSA) isolates, 16 were susceptible to daptomycin (16/31, 51.6%) according to the breakpoint ± 1 μg/ml. All 31 ORSA isolates were susceptible to teicoplanin, and vancomycin but MICs of vancomycin for all 31 ORSA isolates were ± 1 μg/ml. Of the 21 isolates of A. baumannii that were multiple-drug-resistant, 19 isolates (19/21, 90%) were susceptible to colistin and 18 isolates (18/21, 86%) sensitive to tigecycline. Of the 22 isolates of E. coli with extended-spectrum beta-lactamase (ESBL), the most susceptible antimicrobial agent were colistin (20/22, 91%), ertapenem (21/22, 96%), meropenem and tigecycline (22/22, 100%). Of the 11 isolates of P. aeruginosa, 6 isolates were susceptible to colistin (6/11, 55%) and all isolates were susceptible to meropenem (11/11, 100%). Conclusion: For nosocomial infections caused by MDR-Acinetobacter baumannii, colistin and tigecycline are usually susceptible according to the result of this study. For nosocomial infections caused by ORSA, ORSA has reduced susceptibility to vancomycin, teicoplanin and daptomycin. For MDR-P. aeruginosa, further study is needed.

Background: Gastric cancer remains one of the leading causes of cancer death worldwide. Currently, no standard secondary-line chemotherapy for locally advanced or metastatic gastric cancer is recommended. The aim of this study is to demonstrate and confirm the overall objective response rate to irinotecan plus cisplatin for previously treated patients with metastatic or locally advanced gastric cancer in Taiwan. Methods: Patients in this study had been diagnosed with gastric adenocarcinoma with evidence of advanced disease and had failure of first line chemotherapy or documented disease progression while receiving adjuvant chemotherapy. Patients had good Eastern Cooperative Oncology Group performance status and adequate hematologic, renal and liver function. Patients received irinotecan 60 mg/m2 followed by cisplatin 30 mg/m2 on days 1 and 8, every 3 weeks. Treatment was administered until disease progression, intolerable toxicity or consent withdrawal. Evaluation was conducted every two cycles using the Response Evaluation Criteria in Solid Tumors. The toxicity was recorded by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0, year 2003. Results: From January 2007 to December 2008, 24 patients were enrolled. Their median age was 54 years (range 30 to 77 years). Fifteen patients (63%) were men. Five patients (21%) achieved partial response, while ten patients (42%) remained stable. The median progression-free survival was 109 days and median overall survival was 222 days. The major grade 3/4 toxicities were neutropenia (20.9%) and diarrhea (8.3%). Conclusions: Second-line chemotherapy with irinotecan and cisplatin for advanced gastric cancer is effective and has acceptable toxicity.

Background: Monitoring hypnotic depth is used to prevent awareness during general anesthesia. We used the A-line ARX index (AAI) to assess the effect of shortterm inhalation of sevoflurane in the prevention of intubation-induced inadequate hypnotic depth during anesthetic induction. Methods: Thirty patients were randomly divided into the sevoflurane and non-sevoflurane groups, both of which were given 3 μg kg-1 fentanyl, 4 mg kg-1 thiamylal, and 0.2 mg kg-1 cis-atracurium intravenously to induce general anesthesia. The sevoflurane group then inhaled 6% sevoflurane and 4 L/min O2 for 3 minutes, whereas the non-sevoflurane group was given 4 L/min O2 alone. Both groups were intubated 3 minutes after induction. Measurements of the AAI, non-invasive blood pressure, and heart rate were performed every minute, starting 3 minutes prior to induction until 9 minutes after intubation. Results: Intubation induced a significant AAI elevation in the non-sevoflurane group (47.13 ± 20.88, 48.13 ± 20.05, 40.87 ± 15.86 and 31.27 ± 15.26 at 1, 2, 3 and 4 minutes after intubation, respectively, vs. 17.67 ± 6.44 at 3 minutes after induction; p < 0.05), whereas the AAI remained unchanged for the sevoflurane group following intubation. Moreover, the non-sevoflurane group demonstrated higher AAI values after intubation compared with the sevoflurane group. There were no significant differences in blood pressure and heart rate between the two groups throughout the study. Conclusion: Adding 6% sevoflurane with 4 L/min O2 for 3 minutes during the induction period prevented inadequate hypnotic depth caused by intubation but was not sufficient to inhibit fluctuations in hemodynamics.

Background: Tobacco use is known as a serious global public health problem, and is also an important risk factor for oral diseases. Saliva is the first biological medium encountered during inhalation of cigarette smoke. Therefore, the main aim of this study was to compare the levels of salivary antioxidants between healthy smoking and non-smoking men. Methods: Unstimulated whole saliva samples were collected from 80 men. Forty subjects were smokers with a daily consumption of 20 cigarettes for at least 10 years and 40 subjects were non-smokers. The salivary levels of uric acid, superoxide dismutase, glutathione peroxidase, and peroxidase were measured and compared between studied groups. Results: The mean levels of salivary superoxide dismutase, glutathione peroxidase, and peroxidase were significantly lower in smokers than non-smokers. There was no statistically significant difference in the salivary uric acid level between smokers and non-smokers. Conclusions: Measurement of antioxidant agents in human saliva might be useful for estimating the level of oxidative stress caused by cigarette smoke.

Background: Awareness of the anatomy and variations of the extensor tendons on the dorsum of the hand is necessary when assessing the traumatized or diseased hand and when considering tendons for repair or transfer. A complete quantitative documentation of the extensor tendons is lacking. Method: The arrangements of extensor tendons to the medial four fingers namely, the extensor digitorum communis (EDC), extensor indicis proprius (EIP) and extensor digiti minimi (EDM) on the dorsum of the hand and the intertendinous connections between them were studied in 100 upper limb specimens. The findings were photographed, tabulated and analyzed statistically. Results: In 98% of the specimens, the EIP was a single tendon with a single insertion, whereas in two right upper limbs there were two EIP tendons with two insertions. In 77% of the specimens the EDC distally had tendons to the middle three fingers (EDC index, EDC longus and EDC ring). The EDC small was present in only 34% of samples and the EDM showed normal anatomy in only 20%. The most common types of juncturae tendinum in the 2nd, 3rd and 4th intermetacarpal spaces were Type 1, 2 and 3r, respectively. Two accessory muscles were seen. One was the extenson medii proprius in 5% of samples and the other, the extensor digitorum brevis manus, was seen in 3%. Conclusion: Variations of the extensor tendons were common in this study, especially for the middle and ring fingers which showed multiple tendons of the EDC.

Background: The association between obesity and depression remains equivocal. The aims of this study were to examine the association between body mass index (BMI) and depressive symptoms in the Chinese adult population. Methods: In this study, data from the Health Promotion Knowledge, Attitudes, and Performance Survey, conducted in 2002 among 20,385 Taiwanese adults (aged 18-64 years), were used. Depressive symptoms were assessed by the Taiwanese Depression Questionnaire (cut off point 19). Weight status was categorized as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5- 23.9 kg/m2), overweight (BMI 24-26.9 kg/m2), and obese (BMI ≥ 27 kg/m2). Results: Bivariate analyses revealed that underweight men and women had higher risks of depressive symptoms than normal weight individuals. After controlling for education, income, occupation, smoking status, marital status, presence of chronic disease, exercise, and weight control measures, we found that underweight men were significantly more likely to have depressive symptoms than normal weight men (Adjusted odds ratio [AOR] 2.68, 95% confidence interval [CI] 1.85-3.88). On the contrary, obese women were significantly less likely to have depressive symptoms than normal weight women (AOR 0.62, 95% CI 0.46-0.83). Conclusion: The associations of BMI and depressive symptoms were different between genders. Underweight men ran a higher risk of depression than normal weight men, and overweight women had a lower risk than normal weight women. These findings support the "jolly fat" hypothesis among the adult population in the Chinese community.

Background: Periventricular nodular heterotopia (PNH) is a rare congenital anomaly of the brain presenting as nodular heterotopia along the paraventricular region. Ten cases of PNH complicated by aortic aneurysm have been reported in the literature, and 9 of them also had symptoms of Ehlers-Danlos syndrome (EDS). This study investigated the association of PNH and cardiovascular anomalies in Asians. Methods: Patients with a diagnosis of brain heterotopia on magnetic resonance imaging at Chang Gung Memorial Hospital between 1994 and 2010 were screened for both typical PNH and cardiovascular anomalies. The family members of the index cases were also evaluated. Results: One family (5 patients) and a sporadic case were found to have both typical PNH and cardiovascular anomalies. Two of them had aortic root aneurysm, one had aortic regurgitation, and one had minor valvular disease. Two patients had a history of seizures, but none of them had EDS. Conclusions: Clinical heterogeneity exists in the patients with PNH. Overlap in the symptoms of PNH, cardiovascular anomalies, aortic aneurysm, and EDS were reviewed. EDS is unusual in Asians with PNH. Aortic aneurysm and other valvular heart diseases are common cardiovascular anomalies in PNH patients.

Background: Extracorporeal membrane oxygenation (ECMO) has been utilized for critically ill patients such as those with life-threatening respiratory failure or post-cardiotomy cardiogenic shock. Patients on ECMO with acute renal failure have high mortality rates. This study identifies specific predictors of hospital mortality for patients receiving ECMO and continuous arteriovenous hemofiltration (CAVH). Methods: This study reviewed the medical records of 123 critically ill patients on ECMO plus CAVH at a cardiovascular surgical intensive care unit (CVSICU) at a tertiary care university hospital between March 2003 and August 2010. Patient baseline, clinical, and laboratory data were collected retrospectively as survival predicators. Results: The overall mortality rate was 85.4%. The most common conditions requiring ECMO plus CAVH were cardiogenic shock and oliguria. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and organ system failure (OSF) score both indicated good discriminative power (area under the receiver operating characteristic curve [AUROC] 0.812 ± 0.048 and 0.758 ± 0.057, respectively). Multiple logistic regression analysis indicated that age, mean arterial pressure, and OSF score on day 1 of ECMO plus CAVH were independent risk factors for hospital mortality. Cumulative survival rates at the 6-month follow-up differed significantly (p < 0.001) between those with an OSF score ≤ 4 vs. those with an OSF score > 4. Conclusions: During ECMO plus CAVH support, both the OSF and APACHE II scores showed good discriminative power in predicting hospital mortality for these patients.

Both moclobemide and fluoxetine are used in the treatment of depression, and have been shown to produce fewer side effects than conventional tricyclic antidepressants. A combination of moclobemide and fluoxetine has been used in refractory depression, however there is potential for severe serotonin toxicity. We describe a lethal case of serotonin toxicity in a 36 year-old woman after she ingested multiple drugs, including moclobemide 4500 mg, fluoxetine 200 mg, propranolol 300 mg and several benzodiazepines. The clinical features included coma, mydriasis, hyperthermia, tremor, hyperreflexia, rhabdomyolysis, renal failure and respiratory insufficiency. Eventually, the patient died of disseminated intravascular coagulation and circulatory collapse at 22.5 h postingestion. Toxicological analysis of the patient's blood confirmed high levels of moclobemide 150 μg/mL (therapeutic 1-3 μg/mL), fluoxetine 3750 ng/mL (therapeutic 47-469 ng/mL) and several benzodiazepines. In conclusion, a combination of moclobemide and fluoxetine should be avoided in depressed patients with high suicidal tendencies. Moreover, early recognition and aggressive intervention are the mainstays in the management of potentially life-threatening serotonin toxicity.

We report 2 boys, 11 and 7 years old, whose Tourette's disorder improved significantly after a period of repeated, sustained practice of activities requiring reflexive responses One boy engaged in physical exercise including hand-eye co-ordination (table tennis for 6 hours every weekday) and the other learned foreign languages (5 languages within 3 years). Tics may be thought of as a kind of overflow of energy, and excessive energy consumption with physical or mental exercise may improve the motor disorder and associated comorbidities. However, the exercise may require a quick, reflexive response to visual or verbal stimuli.