Facile synthesis of insulin fusion derivatives through sortase A ligation

Insulin derivatives such as insulin detemir and insulin degludec are U.S. Food and Drug Administration (FDA)-approved long-acting insulin currently used by millions of people with diabetes. These derivatives are modified in C-terminal B29 lysine to retain insulin bioactivity. New and efficient methods for facile synthesis of insulin derivatives may lead to new discovery of therapeutic insulin. Herein, we report a new method using sortase A (SrtA)-mediated ligation for the synthesis of insulin derivatives with high efficiency and functional group tolerance in the C-terminal B chain. This new insulin molecule (Ins-SA) with an SrtA-recognizing motif can be conjugated to diverse groups with N-terminal oligoglycines to generate new insulin derivatives. We further demonstrated that a new insulin derivative synthesized by this SrtA-mediated ligation shows strong cellular and

Preventing early-onset group B streptococcal sepsis: clinical risk factor-based screening or culture-based screening?

INTRODUCTION@#Two strategies are available for prevention of early-onset group B streptococcal (GBS) sepsis - clinical risk factor-based screening and routine culture-based screening of pregnant women for GBS colonisation. In our hospital, we switched from the former to the latter approach in 2014.@*METHODS@#We compared the incidence of early-onset GBS sepsis during 2001-2015 between infants born to pregnant women who were screened for GBS colonisation and those born to women who were not screened.@*RESULTS@#Among 41,143 live births, there were nine cases of early-onset GBS sepsis. All infants with GBS sepsis were born to pregnant women who were not screened for GBS colonisation. The incidence of early-onset GBS sepsis among infants of women who were not screened was 0.41 per 1,000 live births (95% confidence interval [CI] 0.19-0.77) when compared to infants of women who were screened, for whom the sepsis incidence was zero per 1,000 live births (95% CI 0-0.19; p = 0.005).@*CONCLUSION@#Our data suggests that routine culture-based screening of pregnant women for GBS colonisation is a better preventive strategy for early-onset GBS sepsis in neonates when compared to clinical risk factor-based screening.

Discussion on Application Practice and Improvement Program of Outpatient Pharmacy Automation System in Our Hospital / 中国药房

OBJECTIVE:To improve automatic outpatient pharmacy drug delivery system in our hospital,and to promote the efficiency of automatic drug delivery. METHODS:The outpatient pharmacy automation system of our hospital was introduced in terms of main structure,working process and application. The work efficiency,safety and error were compared between automatic drug delivery mode and manual drug delivery mode. Drug delivery machine was improved to increase the rate of drug delivery. RE-SULTS:The outpatient pharmacy automation system of our hospital included 2 boxed drug delivery machine and 1 drug dispensing machine,etc. Compared with manual drug delivery mode,automatic drug delivery mode improved drug delivery efficiency,health security and use security,and reduced drug delivery error. Through adjusting the time setting and step of drug delivery of gearing in drug delivery machine,idle time of transmission equipment was utilized effectively,and the quantity of delivered prescriptions was increased,increasing from 220 to 320 each hour. CONCLUSIONS:The reasonable improvement of outpatient pharmacy auto-mation system makes outpatient pharmacy automation system play a bigger role,and further optimize resources.

Clinical significance of HPV E6/E7 mRNA test combining TCT test to detect early cervical dysplasia / 实用医学杂志

Objective To investigate the value of HPV E6/E7 mRNA test combining liquid-based cytology test in cervical cancer screening. Methods A total of 377 samples from Wenzhou People's Hospital from June 2014 to September 2015 were collected and screened by HPV E6/E7 mRNA test combining with liquid-based cytology test , and the results was compared with the findings from the gold criteria of histology and pathology. Results The combination of HPV E6/E7 mRNA test and liquid-based cytology test can enhance the testing sensitivity and specificity. The sensitivity of the combination of HPV E6/E7 mRNA test and liquid-based cytology test for the diagnosis of LSIL was 94.41%, and that for the diagnosis of HSIL was 96.36%. Based on the gold criteria of histology and pathology , the sensitivity , specificity , positive-predictive value and negative predictive value of HPV E6/E7 mRNA test for the diagnosis of HSIL was 90%, 60.67%, 48.53% and 92.49%respectively. The sensitivity, specificity, positive-predictive value and negative- predictive value of liquid-based cytology test for the diagnosis of HSIL was 72.73%, 75.28%, 54.79% and 87.01% respectively. Conclusions The sensitivity of HPV E6/E7 mRNA test is superior to that of liquid-based cytology test , while the specificity of HPV E6/E7 mRNA test is inferior to that of liquid-based cytology test. The negative predictive value of HPV E6/E7 mRNA test is more meaningful than that of liquid-based cytology test. The combination of HPV E6/E7 mRNA test and liquid-based cytology test can enhance the testing sensitivity , but it does not increase the specificity.

A large symptomatic jejunal subepithelial tumor treated with endoloop-assisted polypectomy using spiral enteroscopy

No abstract available.

Competency-based Radiology Residency: A Survey of Expectations from Singapore's Perspective

In response to the demands of an ageing nation, the postgraduate medical education in Singapore is currently in the early stage of transition into the American-styled residency programme. This study assessed the expectations of both radiology trainees and faculty on their ideal clinical learning environment (CLE) which facilitates the programme development. A modified 23-item questionnaire was administered to both trainees and faculty at a local training hospital. All items were scored according to their envisioned level of importance and categorised into 5 main CLE domains-supervision, formal training programme, work-based learning, social atmosphere and workload. 'Supervision' was identified as the most important domain of the CLE by both trainees and faculty, followed by 'formal training programmes', 'work-based learning' and 'social atmosphere'. 'Workload' was rated as the least important domain. For all domains, the reported expectation between both trainees and faculty respondents did not differ significantly. Intragroup comparison also showed no significant difference within each group of respondents. This study has provided valuable insights on both respondents' expectations on their ideal CLE that can best train competency in future radiologists. Various approaches to address these concerns were also discussed. The similarities in findings between ours and previous studies suggest that the 'supervision', 'formal training programmes' and 'work-based learning' domains are crucial for the success of a postgraduate medical training and should be emphasised in future curriculum. 'Workload' remains a challenge in postgraduate medical training, but attempts to address this will have an impact in future radiology training.

Medullary Sponge Kidney on Retrograde Pyelography / 전남의대학술지

A woman aged 31 had recurrent urinary tract infection with bloody urine. A series image of medullary sponge kidney presented by intravenous urography (IVU) was detected dynamically by retrograde pyelography (RP). Other than ultrasonography and IVU, RP is also a reliable method to detect medullary sponge kidney.

Medullary Sponge Kidney on Retrograde Pyelography / 전남의대학술지

A woman aged 31 had recurrent urinary tract infection with bloody urine. A series image of medullary sponge kidney presented by intravenous urography (IVU) was detected dynamically by retrograde pyelography (RP). Other than ultrasonography and IVU, RP is also a reliable method to detect medullary sponge kidney.

Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study

BACKGROUND/AIMS: Only moderate to severe Crohn's Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria. METHODS: A retrospective analysis was conducted in nine medical centers in Taiwan and we collected the results of CD patients receiving adalimumab from Sep 2009 to Mar 2014. The clinical characteristics, response measured by CDAI (Crohn's Disease Activity Index), adverse events and survival status were recorded and analyzed. CR-70, CR-100, and CR-150 were defined as attaining a CDAI decrease of 70, 100 or 150 points compared with baseline. RESULTS: A total of 103 CD patient records were used in this study. Sixty percent of these patients received combination therapy of adalimumab together with immunomodulators. CR-70 was 68.7%, 74.5% and 88.4% after week 4, 8 and 12 of treatment, respectively. The steroid-free rate, complications and survival were 47.6%, 9.7% and 99% of patients, respectively. In considering the mucosal healing, only 25% patients achieve mucosal healing after treatment for 6 to12 months. Surgery was still needed in 16.5% of patients. Combination treatment of adalimumab with immunomodulators further decreased the level of CDAI at week 8 when compared with the monotherapy. CONCLUSIONS: Even under the stringent criteria for using adalimumab, the response rate was comparable to those without stringent criteria.

Clinics in diagnostic imaging (140). Iatrogenic sciatic nerve injury secondary to intramuscular injection

A 77-year-old Chinese female patient presented with acute onset of left lower limb paraesthesia and weakness after she received an intramuscular injection for pain relief in the gluteal region. Magnetic resonance (MR) imaging of her lumbosacral spine and sacral plexus was performed. The MR imaging findings are reviewed and discussed.

Successful treatment of biphasic metaplastic sarcomatoid carcinoma of the breast by evaluation of immunohistochemical markers

Biphasic metaplastic sarcomatoid carcinoma [MSC] of the breast is rare and aggressive. Patients with metaplastic breast carcinomas tend to have poor outcomes with a high risk of recurrence following primary surgery. Most reports have shown that systemic therapy appears to be less effective. We report a case of a 42-year-old female who presented with a large [14 cm] cauliflower breast mass. Biopsy revealed a poorly differentiated sarcoma. Initially, neo-adjuvant concurrent chemoradiotherapy with a sarcoma regimen was prescribed, and the tumor regressed to a large ulcer. Subsequent biopsy showed invasive ductal carcinoma [estrogen receptor, progesterone receptor stained weakly, 5%, Her2:2+] and disappearance of the sarcomatous component. Second-line neoadjuvant therapy was designed according to the histologic features of infiltrating ductal carcinoma, which led to nearly a complete response. A modified radical mastectomy of the right breast and axillary dissection was performed followed by monoclonal antibody [trastuzumab] therapy for 6 months due to the surgical specimen showing Her2:3+. The treatment course went smoothly with a good response. The patient had no evidence of disease at 18 months

Temporally shifted hemodynamic response model helps to extract acupuncture-induced functional magnetic resonance imaging blood oxygenation-level dependent activities / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The onsets of needling sensation introduced by acupuncture stimulus can vary widely from subject to subject. This should be explicitly accounted for by the model blood oxygenation-level dependent (BOLD) time course used in general linear model (GLM) analysis to obtain more consistent across-subject group results. However, in standard GLM analysis, the model BOLD time course obtained by convolving a canonical hemodynamic response function with an experimental paradigm time course is assumed identical across subjects. Although some added-on properties to the model BOLD time course, such as temporal and dispersion derivatives, may be used to account for different BOLD response onsets, they can only account for the BOLD onset deviations to the extent of less than one repetition time (TR).</p><p><b>METHODS</b>In this study, we explicitly manipulated the onsets of model BOLD time course by shifting it with -2, -1, or 1 TR and used these temporally shifted BOLD model to analyze the functional magnetic resonance imaging (fMRI) data obtained from three acupuncture fMRI experiments with GLM analysis. One involved acupuncture stimulus on left ST42 acupoint and the other two on left GB40 and left BL64 acupoints.</p><p><b>RESULTS</b>The model BOLD time course with temporal shifts, in addition to temporal and dispersion derivatives, could result in better statistical power of the data analysis in terms of the average correlation coefficients between the used BOLD models and extracted BOLD responses from individual subject data and the T-values of the activation clusters in the grouped random effects.</p><p><b>CONCLUSIONS</b>The GLM analysis with ordinary BOLD model failed to catch the large variability of the onsets of the BOLD responses associated with the acupuncture needling sensation. Shifts in time with more than a TR on model BOLD time course might be required to better extract the acupuncture stimulus-induced BOLD activities from individual fMRI data.</p>

The C-terminal variable domain of LigB from Leptospira mediates binding to fibronectin

Adhesion through microbial surface components that recognize adhesive matrix molecules is an essential step in infection for most pathogenic bacteria. In this study, we report that LigB interacts with fibronectin (Fn) through its variable region. A possible role for LigB in bacterial attachment to host cells during the course of infection is supported by the following observations: (i) binding of the variable region of LigB to Madin-Darby canine kidney (MDCK) cells in a dose-dependent manner reduces the adhesion of Leptospira, (ii) inhibition of leptospiral attachment to Fn by the variable region of LigB, and (iii) decrease in binding of the variable region of LigB to the MDCK cells in the presence of Fn. Furthermore, we found a significant reduction in binding of the variable region of LigB to Fn using small interfering RNA (siRNA). Finally, the isothermal titration calorimetric results confirmed the interaction between the variable region of LigB and Fn. This is the first report to demonstrate that LigB binds to MDCK cells. In addition, the reduction of Fn expression in the MDCK cells, by siRNA, reduced the binding of LigB. Taken together, the data from the present study showed that LigB is a Fn-binding protein of pathogenic Leptospira spp. and may play a pivotal role in Leptospira-host interaction during the initial stage of infection.