Scientific and Regulatory Perspective on Monoclonal Antibody Biosimilars

Similar biotherapeutic products (SBPs), also called biosimilars, exhibit similar biological and clinical properties to authorized reference products. Biosimilars, including small molecules like erythropoietin and complex macromolecules like monoclonal antibodies (mAbs), have been used extensively in disease treatment. Monoclonal antibody biosimilars have gradually become a dominant development in the global pharmaceutical industry since their patents or data protection have been expired or nearing expiration. Since the mAb biosimilars are complex biological macromolecules with various post-translation modifications, it is important to evaluate whether these tiny differences significantly affect the quality. From a regulatory perspective, the comparability study needs to be performed to demonstrate that the quality, safety, and efficacy are similar to the biological reference. Based on these comprehensive comparative results, the indicated extrapolation might be acceptable. Post-market surveillance is also required because of unexpected biological variation caused by slightly different manufacturing processes. This chapter presents the scientific and regulatory considerations for monoclonal antibody biosimilar products for manufactures and for the regulatory authorities to administrate wisely and comprehensively

The association between problematic cellular phone use and risky behaviors and low self-esteem among Taiwanese adolescents

<p>Abstract</p> <p>Background</p> <p>Cellular phone use (CPU) is an important part of life for many adolescents. However, problematic CPU may complicate physiological and psychological problems. The aim of our study was to examine the associations between problematic CPU and a series of risky behaviors and low self-esteem in Taiwanese adolescents.</p> <p>Methods</p> <p>A total of 11,111 adolescent students in Southern Taiwan were randomly selected into this study. We used the Problematic Cellular Phone Use Questionnaire to identify the adolescents with problematic CPU. Meanwhile, a series of risky behaviors and self-esteem were evaluated. Multilevel logistic regression analyses were employed to examine the associations between problematic CPU and risky behaviors and low self-esteem regarding gender and age.</p> <p>Results</p> <p>The results indicated that positive associations were found between problematic CPU and aggression, insomnia, smoking cigarettes, suicidal tendencies, and low self-esteem in all groups with different sexes and ages. However, gender and age differences existed in the associations between problematic CPU and suspension from school, criminal records, tattooing, short nocturnal sleep duration, unprotected sex, illicit drugs use, drinking alcohol and chewing betel nuts.</p> <p>Conclusions</p> <p>There were positive associations between problematic CPU and a series of risky behaviors and low self-esteem in Taiwanese adolescents. It is worthy for parents and mental health professionals to pay attention to adolescents' problematic CPU.</p

Social science studies of the environment in Taiwan: what can the international community learn from work published within Taiwan?

This Translations contribution synthesises critical environmental social science research produced in Taiwan and published largely in Chinese. Taiwan is distinctive in east Asia in that it has had, over several decades, a relatively large and prolific community of scholars engaged with environmental justice and sustainability. This research tradition is linked to the emergence of grassroots environmentalism in response to environmental issues faced during Taiwan’s rapid industrialisation, and to the democratisation of Taiwanese society from the 1980s onwards. Fuller understanding of research produced and published within in Taiwan hence yields insights for the role of social science within newly industrialising and democratising nations. Although the story of Taiwanese society’s relation to environmentalism is to an extent understood in English-language literature, less prevalent are the diverse ways Taiwanese social scientists have engaged with environmental issues, the empirical case studies which have shaped their thinking, and the influences of Western environmental sociology and science and technology studies (STS) within Taiwan. By synthesising Chinese-language environmental social science literature from Taiwan, we characterise three strands of scholarship: activism and social movements; environmental controversies; and environmental governance, policy and institutions. We identify (a) the ability of communities and civil societies to affect change from within extant governance processes and (b) the local-level implications of national sustainable development rhetoric as two areas where Taiwanese scholarship may make particularly valuable contributions to work at the sustainability-environmental justice interface

Antimicrobial Susceptibility and Multiplex PCR Screening of AmpC Genes From Isolates of Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens

Background/PurposeThe emergence of multiple drug resistance in Enterobacteriaceae is of particular concern. The aim of this study was to evaluate the antimicrobial susceptibility and screen for the ampC gene in three members of the Enterobacteriaceae family (Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens) found at Taichung Veterans General Hospital during the past 5 years using multiplex polymerase chain reaction (PCR).MethodsThe susceptibility of thirty isolates from each of the three Enterobacteriaceae family members to five antimicrobial agents (ceftazidime, flomoxef, imipenem, moxifloxacin, and colistin) was assessed. The susceptibility was analyzed by disk diffusion, screening and confirmatory tests for extended-spectrum β-lactamases (ESBL) and minimum inhibitory concentration tests according to the recommendations of the Clinical and Laboratory Standards Institute. The detection of ampC genes (3 families, including DHA, EBC and CIT) was performed by multiplex PCR. To detect the coexistence of ESBL genes, PCR was performed using five primer pairs: TEM, SHV, SHV-5, CTX-M-3, and CTX-M-14.ResultsOf the 90 isolates, 53 (58.9%) were positive in the screening test for ESBL. Resistance genes were detected in 12 (22.6%) of these isolates: ampC gene of DHA type in one E. cloacae isolate and EBC type in three E. cloacae isolates; ampC gene of CIT type in four C. freundii isolates; CTX-M-3-like in one C. freundii isolate and one S. marcescens isolate; TEM in three E. cloacae isolates, three C. freundii isolates and two S. marcescens isolates; SHV in one C. freundii isolate.ConclusionAntibiotic phenotypes cannot accurately distinguish the resistance mechanisms caused by ampC or ESBL, and especially in ESBL-ampC combinations. However, PCR is a useful technique for the identification of the different types of resistance genes

Clinical Outcome of Mycobacterium abscessus Infection and Antimicrobial Susceptibility Testing

Background/PurposeMycobacterium abscessus is the most resistant and rapidly growing mycobacterium and causes a wide range of clinical infectious diseases. The relationship between antimicrobial susceptibility and clinical outcome needs to be further evaluated.MethodsForty M. abscessus isolates were obtained from clinical specimens of 40 patients at the Taichung Veterans General Hospital from January 2006 to December 2008. Antimicrobial susceptibility testing was performed using the broth microdilution method according to the recommendations of the National Committee for Clinical Laboratory Standards. The clinical manifestations and outcomes were reviewed from medical records.ResultsTwenty-two patients were diagnosed with M. abscessus infection. Cough (86.3%), hemoptysis (31.8%) and fever (18.1%) were the most common symptoms. The radiographic findings included reticulonodular opacities (50.0%), consolidation (31.8%) and cavitary lesions (18.1%). The 40 isolates were susceptible to amikacin (95.0%), cefoxitin (32.5%), ciprofloxacin (10.0%), clarithromycin (92.5%), doxycycline (7.5%), imipenem (12.5%), moxifloxacin (22.5%), sulfamethoxazole (7.5%) and tigecycline (100%). The rate of treatment failure was 27.3% at the end of the 12th month after the start of treatment, although these patients were treated with a combination of clarithromycin and other antimicrobial agents.ConclusionM. abscessus is naturally susceptible to clarithromycin and amikacin, variably susceptible to cefoxitin and imipenem, and resistant to most other antimicrobial drugs. Combination therapy with clarithromycin, amikacin and other active antimicrobial agents may lead to clinical improvement; however, the rate of treatment failure is still high

Single-incision thoracoscopic surgery for primary spontaneous pneumothorax

<p>Abstract</p> <p>Objective</p> <p>Single-incision laparoscopic surgery had been proven effective for appendectomy, cholecystectomy, and inguinal hernia repair. However, single-incision thoracoscopic surgery (SITS) in primary spontaneous pneumothorax (PSP) has not been reported.</p> <p>Methods</p> <p>We prospectively enrolled 30 PSP patients who received thoracoscopic surgery in the division of Thoracic Surgery of China Medical University Hospital. Ten patients received SITS and 20 patients received traditional three-port thoracoscopic surgery. The operative time, blood loss, wound size, visual analog scale (VAS) pain score, and patient satisfaction score were compared.</p> <p>Results</p> <p>There was no significant difference in the operative time and blood loss between the two groups. However, the VAS pain scores were significantly better in the SITS group in first 24 hours after surgery. Patient satisfaction scores in the SITS group were also significantly better in the first 24 and 48 hours after operation.</p> <p>Conclusion</p> <p>Although three-port thoracoscopic surgery for PSP is well established, SITS results in better patient satisfaction and decreased postoperative pain in the treatment of PSP.</p

Renal Protection for Coronary Angiography in Advanced Renal Failure Patients by Prophylactic Hemodialysis A Randomized Controlled Trial

ObjectivesWe performed a study to determine whether prophylactic hemodialysis reduces contrast nephropathy (CN) after coronary angiography in advanced renal failure patients.BackgroundPre-existing renal failure is the greatest risk factor for CN. Hemodialysis can effectively remove contrast media, but its effect upon preventing CN is still uncertain.MethodsEighty-two patients with chronic renal failure, referred for coronary angiography, were assigned randomly to receive either normal saline intravenously and prophylactic hemodialysis (dialysis group; n = 42) or fluid supplement only (control group; n = 40).ResultsProphylactic hemodialysis lessened the decrease in creatinine clearance within 72 h in the dialysis group (0.4 ± 0.9 ml/min/1.73 m2vs. 2.2 ± 2.8 ml/min/1.73 m2; p < 0.001). Compared with the dialysis group, the serum creatinine concentrations in the control group were significantly higher at day 4 (6.3 ± 2.3 mg/dl vs. 5.1 ± 1.3 mg/dl; p = 0.010) and at peak level (6.7 ± 2.7 mg/dl vs. 5.3 ± 1.5 mg/dl; p = 0.005). Temporary renal replacement therapy was required in 35% of the control patients and in 2% of the dialysis group (p < 0.001). Thirteen percent of the control patients, but none of the dialysis patients, required long-term dialysis after discharge (p = 0.018). For the patients not requiring chronic dialysis, 13 patients in the control group (37%) and 2 in the dialysis group (5%) had an increase in serum creatinine concentration at discharge of more than 1 mg/dl from baseline (p < 0.001).ConclusionsProphylactic hemodialysis is effective in improving renal outcome in chronic renal failure patients undergoing coronary angiography

Schwann Cell Migration Induced by Earthworm Extract via Activation of PAs and MMP2/9 Mediated through ERK1/2 and p38

The earthworm, which has stasis removal and wound-healing functions, is a widely used Chinese herbal medicine in China. Schwann cell migration is critical for the regeneration of injured nerves. Schwann cells provide an essentially supportive activity for neuron regeneration. However, the molecular migration mechanisms induced by earthworms in Schwann cells remain unclear. Here, we investigate the roles of MAPK (ERK1/2, JNK and p38) pathways for earthworm-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in Schwann cells. Moreover, earthworm induced phosphorylation of ERK1/2 and p38, but not JNK, activate the downstream signaling expression of PAs and MMPs in a time-dependent manner. Earthworm-stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with U0126 and SB203580, resulting in migration and uPA-related signal pathway inhibition. The results were confirmed using small interfering ERK1/2 and p38 RNA. These results demonstrated that earthworms can stimulate Schwann cell migration and up-regulate PAs and MMP2/9 expression mediated through the MAPK pathways, ERK1/2 and p38. Taken together, our data suggests the MAPKs (ERK1/2, p38)-, PAs (uPA, tPA)-, MMP (MMP2, MMP9) signaling pathway of Schwann cells regulated by earthworms might play a major role in Schwann cell migration and nerve regeneration

Seismic Stratigraphic Features of the Late Miocene-Present Unconformities and Related Seismic Units, Northern Offshore Taiwan

We investigate the seismic stratigraphic features offshore northern Taiwan by using newly collected multichannel seismic data. Two significant regional unconformities U1 and U2 have been identified, which further subdivide the sedimentary sequence into three seismic units as SU I, SU II, and SU III. The lowermost seismic unit SU I is a pre-late Miocene sequence, while the middle and upper seismic unit SU II and SU III result from the interactions between the rapid fault-controlled subsidence and the stable thermal-controlled subsidence. We consider that the present-day offshore northern Taiwan is under a post-collisional state and the unconformities U1 and U2 represent a response to the mountain collapse and to the cessation of the regional volcano-tectonic activities. It is not until 1.5 Ma that northern offshore Taiwan became a post-collisional basin and started to receive sediments, with a rapid fault-controlled subsidence. Afterward, the basin became dominated by a stable thermal-controlled subsidence at 0.2 Ma. Although the main volcano-tectonic activities in the northern offshore Taiwan are ceased, modern geophysical and geochemical investigations have suggested that the tectonism and the volcanism are still active and represent potential threatening geohazard