IP Group Research Articles

Longitudinal Analysis of Long-Term Safety and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIFc) in Adults/Adolescents with Severe Hemophilia a

Longitudinal Analysis of Long-Term Safety and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIFc) in Adults/Adolescents with Severe Hemophilia a

Longitudinal Analysis of Long-Term Safety and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Children with Severe Hemophilia a

Longitudinal Analysis of Long-Term Safety and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Children with Severe Hemophilia a

Long Term Safety and Efficacy of Recombinant Factor IX Fc Fusion Protein (rFIXFc) Prophylaxis in Children with Hemophilia B: Interim Results of the B-Yond Extension Study

Introduction: The phase 3 Kids B-LONG study (NCT01440946) demonstrated the safety, efficacy, and pharmacokinetics of prophylactic recombinant factor IX Fc fusion protein (rFIXFc) for the prevention and treatment of bleeding episodes in children with severe hemophilia B. The ongoing rFIXFc extension study B-YOND (NCT01425723) is evaluating long-term safety and efficacy of rFIXFc in children and adults with hemophilia B. The safety and efficacy data for pediatric subjects from the second B-YOND interim data cut (11 Sep 2015) are reported here. Methods: The Kids B-LONG study enrolled males aged Results: At the time of the second B-YOND interim data cut, 27 subjects had completed Kids B-LONG and enrolled in B-YOND ( Conclusion: These data confirm the long-term safety of rFIXFc with maintenance of low ABRs and extended-interval prophylaxis in children with hemophilia B. This research was funded by Biogen and Sobi. Biogen and Sobi reviewed and provided feedback on the abstract. The authors had full editorial control of the abstract and provided their final approval of all content. Disclosures Ducore:Octapharama: Membership on an entity9s Board of Directors or advisory committees; Baxalta (Shire): Membership on an entity9s Board of Directors or advisory committees; LFB: Membership on an entity9s Board of Directors or advisory committees; Bayer: Membership on an entity9s Board of Directors or advisory committees; Pfizer: Membership on an entity9s Board of Directors or advisory committees; CSL Behring: Membership on an entity9s Board of Directors or advisory committees; Biogen: Membership on an entity9s Board of Directors or advisory committees. Fischer:Baxter: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Speakers Bureau; Biogen: Consultancy; Biotest: Consultancy, Speakers Bureau; Baxalta/Baxter: Consultancy, Research Funding, Speakers Bureau; Wyeth: Research Funding; Pfizer: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Freeline: Consultancy. Kulkarni:Kedrion: Membership on an entity9s Board of Directors or advisory committees; BPL: Membership on an entity9s Board of Directors or advisory committees; Biogen: Research Funding, Speakers Bureau; Pfizer: Membership on an entity9s Board of Directors or advisory committees; Novo Nordisk: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Baxter: Membership on an entity9s Board of Directors or advisory committees, Research Funding. Nolan:Sobi: Research Funding; Biogen: Research Funding. Perry:Biogen: Consultancy, Honoraria; Novo Nordisk: Consultancy, Membership on an entity9s Board of Directors or advisory committees. Yuan:Biogen: Employment, Equity Ownership. Ramirez-Santiago:Biogen: Employment, Equity Ownership. Ferrante:Sobi: Employment. Lethagen:Sobi: Employment.

Clinical Outcomes in Adults/Adolescents with Hemophilia B Treated Long Term with Recombinant Factor IX Fc Fusion Protein (rFIXFc) Prophylaxis: Interim Results of the B-Yond Extension Study

Clinical Outcomes in Adults/Adolescents with Hemophilia B Treated Long Term with Recombinant Factor IX Fc Fusion Protein (rFIXFc) Prophylaxis: Interim Results of the B-Yond Extension Study

Outcome of oral infection in mice inoculated with Trypanosoma cruzi IV of the Western Brazilian Amazon

A new epidemiological view of American trypanosomiasis or Chagas disease has been formulated in recent decades. Oral transmission of the etiological agent of Chagas disease, Trypanosoma cruzi, has been the most common form of transmission. The T. cruzi discrete typing units TcI and TcIV have been involved in tens outbreaks of acute cases of Chagas disease in the Brazilian Amazon region. We investigated the intensity of infection in mice that were orally inoculated (OR group) with four strains of TcIV that were isolated from two outbreaks of acute Chagas disease that was orally acquired in the state of Amazonas, Brazil. We compared the OR group with mice that were intraperitoneally inoculated (IP group). Blood samples were analyzed by fresh blood examination, hemoculture, and conventional and qualitative real-time polymerase chain reaction (PCR). Samples of different tissues were analyzed by quantitative real-time PCR. The OR group exhibited a higher maximum peak of parasitemia, greater rates of positivity, and higher parasite loads in different tissues during acute infection compared with the IP group, indicating a greater intensity of orally acquired infection. Mice that were orally inoculated with TcIV strains that were obtained from two outbreaks of orally acquired Chagas disease in Amazonas, Brazil, exhibited a more intense course of infection compared with intraperitoneally inoculated mice, reflected by higher levels of parasitemia and parasite loads.

Microfloral diversity in the lower respiratory tracts of neonates with bacterial infectious pneumonia combined with ventilator‑associated pneumonia.

Bacterial infectious pneumonia is one of the major causes of mortality in neonates, particularly when the neonates suffer from ventilator‑associated pneumonia (VAP). However, the causes of pneumonia are difficult to define. Thus, the present study focused on understanding the diversity of microflora in the lower respiratory tract to elucidate the causes. The experimental groups comprised newborns who suffered from infectious pneumonia with or without VAP (IVAP and IP groups, respectively), whereas the control group comprised newborns who suffered from respiratory distress syndrome (RDS) without VAP (RDS group). Following 1, 3 and 5days of ventilation, sputum samples were collected and the DNA was extracted. The DNA was amplified and separated, and the 16S rDNA was then sequenced and analyzed for diversity. The results of the diversity and Shannon‑Wiener indices were ordered as follows: IVAP group<IP group<RDSgroup. The percentages of Streptococcus sp., Serratia sp. and Achromobacter sp. in the IP and IVAP groups were higher, compared with those in the RDS group, whereas the percentages of Klebsiella sp. and Acinetobacter sp. were lower on day1. The percentages of Klebsiella sp. and Streptococcus sp. on days1 and3 were ordered as follows: IVAP group>IPgroup> RDS group, and the percentages of Serratia sp., Acinetobacter sp. and Achromobacter sp. were ordered as follows: IVAP group<IPgroup<RDS group. After 3‑5days, the percentages of Klebsiella sp., Acinetobacter sp., Streptococcus sp., Serratia sp. and Achromobacter sp. in the IVAP group were lower, compared with those in the RDS and IP groups. It was concluded that the decreased microfloral diversity, increased constituent ratios of Klebsiella sp. and Streptococcus sp., and decreased ratios of Serratia sp. and Acinetobacter sp. in the lower respiratory tract of neonates suffering from pneumonia may be indicators of VAP.

Effect of isoflurane preconditioning on autophagy during focal cerebral ischemia-reperfusion injury in rats

Objective To evaluate the effect of isoflurane preconditioning on autophagy during focal cerebral ischemia-reperfusion(I/R)injury in rats. Methods Thirty-six healthy male Sprague-Dawley rats, weighing 250-280 g, aged 7-8 weeks, were divided into 3 groups(n=12 each)using a random number table: sham operation group(group S), cerebral I/R group(group I/R)and isoflurane preconditioning group(group IP). Focal cerebral I/R was induced by 2 h middle cerebral artery occlusion followed by 24 reperfusion.Group IP inhaled 1.5% isoflurane for 1 h per day for 5 consecutive days, the other two groups only inhaled 30% oxygen, and focal cerebral I/R was induced at 24 h after the last inhalation.At 24 h of reperfusion, neurologic deficit was assessed and scored, the rats were then sacrificed, and brains were removed for determination of cerebral infarct size(using triphenyl tetrazolium chloride staining)and expression of microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)and Beclin-1(by Western blot). Results Compared with group S, the neurologic deficit scores and cerebral infarct size were significantly increased, and the expression of hippocampal LC3-Ⅱ and Beclin-1 was significantly up-regulated in I/R and IP groups(P<0.05). Compared with group I/R, the neurologic deficit scores and cerebral infarct size were significantly decreased, and the expression of hippocampal LC3-Ⅱ and Beclin-1 was significantly up-regulated in group IP(P<0.05). Conclusion The mechanism by which isoflurane preconditioning ameliorates focal cerebral I/R injury is related to enhancement of autophagy in the rats. Key words: Isoflurane; Ischemic preconditioning; Brain; Reperfusion injury; Autophagy

Patient-Reported Outcomes Measurement Information System Physical Function Item Bank, Version 1.0: Physical Function Assessment for Athletic Patient Populations.

The Patient-Reported Outcomes Measurement Information System (PROMIS) item banks have been validated for general populations, but their application to high-functioning patient populations remains speculative. To examine the measurement properties of the PROMIS physical function item bank, version 1.0, when applied to individuals representing high levels of physical ability. Cross-sectional study. National Collegiate Athletic Association Division I and III collegiate athletic training rooms and intramural events. A heterogeneous sample of 215 adults from Division I or Division III collegiate or recreational sports volunteered for this study. Participants were divided into 4 groups depending on sport activity and injury status: healthy collegiate (HC; 33 men, 37 women; age = 19.7 ± 1.1 years), injured and currently active in sport (IP; 21 men, 29 women; age = 19.9 ± 1.2 years), injured and currently not active in sport (INP; 12 men, 18 women; age = 19.7 ± 1.3 years), and healthy recreational (HR; 47 men, 18 women; age = 20.1 ± 1.4 years). Participants completed 2 assessments: (1) an injury-history questionnaire and (2) the PROMIS physical function item bank, version 1.0, in computer-adaptive form. Mean PROMIS physical function scores were determined for each group. The PROMIS physical function score for the HC group (61.7 ± 6.0) was higher than for the IP (54.9 ± 7.5) and INP (44.1 ± 8.2) groups (P < .001). The IP group had a higher score than the INP group (P < .001). Mean PROMIS scores were not different between the HC and HR participants (mean difference = 1.9, P = .10). The computer-adaptive PROMIS physical function item bank, version 1.0, accurately distinguished injury status in elite-level athletes on a physical function latent trait continuum. Although it was unable to distinguish HC athletes from HR athletes, exposing a possible ceiling effect, it offers potential for use as an outcome instrument for athletic trainers and other sports medicine clinicians.

Laparoscopic management of ectopic pregnancies: a comparison between interstitial and "more distal" tubal pregnancies.

Laparoscopy is an established, safe, and feasible management option for tubal pregnancies, even in women with significant hemoperitoneum. In case of interstitial pregnancy, however, a laparoscopic surgical approach is still a matter of debate. The objective of this study is to evaluate the safety and feasibility of a laparoscopic approach to interstitial pregnancies. A total of 92 women with ectopic pregnancy who underwent a surgical management from April 2009 to August 2015 were reviewed. Clinical and surgical outcomes of confirmed interstitial pregnancies (n=10) (IP group) were compared with those of "more distal" tubal pregnancies (n=79) (TP group). Although there were no differences between the two groups in gestational age, ß-hCG values were significantly higher in the IP group (p=0.005). All patients with IP were treated by laparoscopic wedge resection. The rate of surgical complications (p=0.413) and subsequent MTX treatment (p=0.531) were not significantly different between groups. Operating room (OR) time (p=0.007) was higher in the IP than in the TP group. After stratification for the presence of hemoperitoneum this difference remained, with patients in the IP group having longer OR time (p=0.034) and additionally higher intra-operative blood loss (EBL) (p=0.013). On the other hand, in the absence of hemoperitoneum no differences between the two groups were observed. In experienced hands, the laparoscopic management of interstitial pregnancies seems to be as safe and feasible as that of other tubal pregnancies. However, it could be technically more challenging, especially in case of hemoperitoneum.

Effect of intrathecal cell-penetrating peptide Tat-FynP on inflammatory pain in rats

Objective To evaluate the effect of intrathecal cell-penetrating peptide Tat-FynP on inflammatory pain in rats. Methods Eighty healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 180-220 g, were randomly divided into 5 groups(n=16 each)using a random number table: control group(group C), inflammatory pain group(group IP), group FynP, group Tat-FynP and group mTat-FynP.Inflammatory pain was induced by injecting complete Freund′s adjuvant 100 μl into the plantar surface of the right hindpaw in IP, FynP, Tat-FynP, and mTat-FynP groups, while the equal volume of normal saline was given in group C. At 1 day after establishment of the model, FynP, Tat-FynP and mTat-FynP 15 μl(20 μg/kg)were injected intrathecally in FynP, Tat-FynP, and mTat-FynP groups, respectively.Ten rats in each group were randomly selected, and the mechanical paw withdrawal threshold(MWT)and thermal paw withdrawal latency(TWL)were measured before establishment of the model and at 1, 3, 5, 7, 10 and 14 days after establishment of the model.The left 6 rats were selected from each group at 1 day after intrathecal administration, and the lumbar enlargement segments of the spinal cord were removed for determination of phosphorylated 2B subunit-containing NMDA receptor(p-NR2B)expression by Western blot. Results Compared with group C, the MWT was significantly decreased, and the TWL was significantly shortened at each time point after establishment of the model, and the expression of p-NR2B was significantly up-regulated in IP, FynP, Tat-FynP and mTat-FynP groups(P 0.05). Conclusion Intrathecal cell-penetrating peptide Tat-FynP can reduce inflammatory pain in rats. Key words: Cell-penetrating peptides; Injections, spinal; Inflammation; Pain

Intranasal Administration of Interleukin-1 Receptor Antagonist in a Transient Focal Cerebral Ischemia Rat Model

The interleukin-1 receptor antagonist (IL-1RA) is a potential stroke treatment candidate. Intranasal delivery is a novel method thereby a therapeutic protein can be penetrated into the brain parenchyma by bypassing the blood-brain barrier. Thus, this study tested whether intranasal IL-1RA can provide neuroprotection and brain penetration in transient cerebral ischemia. In male Sprague-Dawley rats, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1 h. The rats simultaneously received 50 mg/kg human IL-1RA through the intranasal (IN group) or intraperitoneal route (IP group). The other rats were given 0.5 mL/kg normal saline (EC group). Neurobehavioral function, infarct size, and the concentration of the administered human IL-1RA in the brain tissue were assessed. In addition, the cellular distribution of intranasal IL-1RA in the brain and its effect on proinflammatory cytokines expression were evaluated. Intranasal IL-1RA improved neurological deficit and reduced infarct size until 7 days after MCAO (p<0.05). The concentrations of the human IL-1RA in the brain tissue 24 h after MCAO were significantly greater in the IN group than in the IP group (p<0.05). The human IL-1RA was confirmed to be co-localized with neuron and microglia. Furthermore, the IN group had lower expression of interleukin-1β and tumor necrosis factor-α at 6 h after MCAO than the EC group (p<0.05). These results suggest that intranasal IL-1RA can reach the brain parenchyma more efficiently and provide superior neuroprotection in the transient focal cerebral ischemia.

Protective effect and mechanism of ischemic postconditioning in rats underwent myocardial ischemia/ reperfusion injury

This study is designed to observe the effect of ischemic postconditioning in rats underwent acute myocardial ischemia/reperfusion injury and to investigate the related mechanism. A total of 30 SD rats were randomly divided into sham operation group (control group, n=10), ischemia/reperfusion group (IR group, n=10) and ischemic postconditioning group (PC group, n=10) based on random number table. Rats in IR group underwent 30 minutes myocardial ischemia by occlusion of the proximal portion of left anterior descending (LAD) coronary artery followed by 2 hours reperfusion. In control group, there was no IR intervention. In PC group, at the start of reperfusion, three cycles of 30 seconds reperfusion and 30 seconds LAD reocclusion preceded the 2 hours of reperfusion. The hemodynamic values were measured via a cannula inserted into the right common carotid artery.The area at risk was assessed by Evans blue staining and the infarct size as measured by TTC staining.Western blot and Real time PCR were respectively used to assess the expression of predicted target gene Bim and microRNA-214(miR-214) in the area at risk at the end of 2 hours reperfusion. (1) The hemodynamic monitoring in different groups: the left ventricular systolic pressure (LVSP), ±dp/dtmax, and heart rate of IR group and PC group were lower than those of control group, but left ventricular end-diastolic pressure (LVEDP) was higher than that of control group (all P<0.05). The LVSP and ±dp/dtmax of PC group were higher than those of IR group, and LVEDP was lower than that of IR group (all P<0.05). (2) Myocardial ischemia area and infarction range in different groups: there was no statistically difference in the proportion of area at risk (AAR) in left ventricle (LV) (AAR/LV) between PC group and IP group ((27.00 + 7.55) % vs. (26.67 + 11.68) %, P>0.05). The proportion of infarct size in the area at risk(IS/AAR) of PC group was lower than that of IR group((30.67±3.51)% vs. (48.67±4.62)%, P<0.05). (3) The expression of Bim protein in rats ischemic myocardial tissue in different groups: the expression of Bim protein in ischemic myocardial tissue of IR group was higher than that of control group (2.34±0.15 vs. 0.75±0.05, P<0.05), and that of PC group was lower than IR group (1.25±0.14 vs. 2.34±0.15, P<0.05). (4) The expression of of miR-214 in rats ischemic myocardial tissue in different groups: the expression of miR-214 of IR group was lower than that of control group(0.20±0.04 vs. 1.00, P<0.01), and that of PC group was higer than that of IR group (0.85±0.20 vs. 0.20±0.04, P<0.01). There was no statistically difference between PC group and control group (P>0.05). Postconditioning could significantly decrease the ischemia/reperfusion injury by reducing the infarct size and improve cardiac function in this in vivo rat model. The expression of Bim in postconditioning group is significantly depressed, which may play an important role in the protection process of postconditioning, and the downregulation of Bim might be mediated with the increase of miR-214 expression.

The Interactive-GIS-Tutor (IGIST): an option for GIS teaching in resource-poor South African schools

This paper reports findings from a study that examined geographic information system (GIS) knowledge development after the introduction of an Interactive-GIS-Tutor (IGIST) as a multimedia teaching tool. Although GIS has been included in the curriculum over the past decade, the majority of teachers continue to lack formal GIS training, resources, and support. As a potential solution to this problem, the IGIST offers teachers the option of using either a computer connected to a digital projector or a computer laboratory within the same application. Nine classes of grade 11 geography learners (n = 215) were selected and separated into three groups: a projector group (IP), a computer group (IC) and a textbook group (C), which also acted as the control group. After the IGIST intervention, the IP group revealed a statistically significant effect with regard to knowledge development, whereas the IC group demonstrated a significant practical effect. Participant interviews confirmed that the use of IGIST in combination with a digital projector, or within a computer laboratory, is a workable GIS teaching and learning option. Future IGIST development recommendations include providing multi-language options and more video clips with exploratory activities in Quantum GIS. This work provides a foundation upon which to expand dialogue among GIS developers, academia, teachers and the Department of Basic Education on the development of workable GIS teaching options.

Abstract 4754: Overexpression of TSH and ERBB2 (HER2) receptors is associated with sharply decreased survival in high grade serous ovarian cancer

Abstract Objective. To test if hormone or growth factor receptor expression is associated with survival among patients with high grade serous ovarian cancer (HGS OvCa) we analyzed tumor mRNA expression microarray and clinical data from The Cancer Genome Atlas (TCGA). Methods. HGS OvCa patients were surgically staged prior to treatment with IP (n = 90) or IV-only (n = 398) chemotherapy. Multivariate Cox proportional-hazards regression tested associations of expression of 9 hormone or growth factor receptors with progression free survival (PFS) and overall survival (OS). Hazard ratios are hazard per each one standard deviation increase in gene expression. Expression was analyzed as a continuous variable by restricted mean survival analysis. Mean PFS or OS were compared between IP and IV groups by permutation testing stratified by expression. P-values were two-tailed. Results. Expression of ESR1, PGR, FSHR, LHCGR, MET, and EGFR were not associated with PFS or OS. TSHR expression was associated with decreased OS (HR 1.22 (1.06-1.41), p = 0.005) and PFS (HR 1.18 (1.05-1.33), p = 0.006) among IV-only treated patients. ERBB2 expression was associated with decreased OS (HR 1.48 (1.05-2.10), p = 0.027) among patients who received IP chemotherapy. Using multigene (ESR2, PGR, TSHR, and ERBB2) analysis, among the IP group, ERBB2 (HR 1.76 (1.11-2.79), p = 0.015) and ESR2 (HR 0.28 (0.08-0.93), p = 0.037) were associated with OS. Only TSHR expression was associated with decreased OS (HR 1.22 (1.06-1.41), p = 0.005) and decreased PFS (HR 1.18 (1.05-1.33), p = 0.007) on multigene analysis of IV-only treated patients. OS and PFS decreased steeply at high expression of TSHR and ERBB2. Among patients with upper 10th percentile TSHR expression, no significant difference in mean OS or PFS was observed between patients treated with IP versus IV-only chemotherapy. Patients with lower TSHR expression (&amp;lt; 90% percentile) experienced a mean 13.7-month increased OS and 16.4-month increased PFS associated with IP chemotherapy (p &amp;lt; 0.0001). Conclusions. Among HGS OvCa patients treated with IV-only chemotherapy, increased tumor TSHR expression was associated with decreased OS and PFS. High TSHR expression characterized patients who did not benefit from IP chemotherapy. Citation Format: Brandon-Luke L. Seagle, Monica Dandapani, Chen Hui Luo, Claire Hoppenot, Robert Samuelson, Kevin H. Eng, Kunle Odunsi, Shohreh Shahabi. Overexpression of TSH and ERBB2 (HER2) receptors is associated with sharply decreased survival in high grade serous ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4754.

Morbidity and mortality after total splenectomy for lymphoid neoplasms

BackgroundSplenectomy is indicated for selected patients with lymphoid neoplasms. We examined surgical morbidity and mortality in this high-risk patient population using a contemporary national cohort, with attention to hospitalization status before surgery. Materials and methodsThe American College of Surgeons National Surgical Quality Improvement Program database (2005-2013) was queried for patients with lymphoid malignancies undergoing splenectomy. Stepwise statistical analyses were performed to identify factors associated with increased risk of death and serious morbidity (DSM). A risk scoring system was developed to predict DSM. ResultsIn 456 patients, morbidity rate was 24.1%, and mortality rate was 2.4%. Albumin <3 g/dL (odds ratio [OR] = 2.6, P = 0.005), hematocrit <30% (OR = 2.8, P < 0.0001), and a history of chronic obstructive pulmonary disease (OR = 3.4 P = 0.009) were independent predictors of DSM. Rates of DSM were stratified by these risk factors (RFs): 13.5% (0 RF), 34.4% (1 RF), and 58.5% (2-3 RF), P < 0.0001. Patients admitted before surgery (IP) were more likely to have RF compared with those undergoing surgery on the day of admission (SDS); 74.6 versus 26.4%, P < 0.001. Morbidity (39.7% versus 18.2%, P < 0.0001) and mortality (7.1% versus 0.6%, P < 0.0001) were significantly increased in the IP group. ConclusionsSplenectomy for lymphoid neoplasm in hospitalized patients is associated with substantial morbidity and mortality. Risk stratification in this group may aid in perioperative management to mitigate DSM.

Effectiveness of an interprofessional workshop on pain management for medical and nursing students

ABSTRACTInterprofessional (IP) care is critical for effective pain management, but evidence is lacking about the best way to teach pain management skills to medical and nursing students using IP strategies. In 2013 and 2014, 307 medical and 169 nursing students participated in an IP case-based pain management workshop. The aims of this study were to determine (1) if students who participate in IP case-based learning groups will have improved pain management skills compared to students who participate in uniprofessional case-based learning groups, and (2) if students mentored by faculty with IP training will have improved pain management skills compared to students who are not mentored by IP-trained faculty. Student learning was assessed and compared using scored checklists for each group’s pain management plans. Findings show that IP mentorship and IP group participation improved medical students’ pain management skills but did not have the same effect on nursing student performance. Continued work is needed to develop, refine, and integrate innovative and tailored IP strategies into the curricula of medical and nursing schools to advance the pain management competencies of students before they enter clinical practice.

Role of autophagy in development of inflammatory pain in rats

Objective To evaluate the role of autophagy in the development of inflammatory pain in the rats. Methods Twenty-four healthy adult male Sprague-Dawley rats, weighing 180-240 g, were randomly divided into 4 groups (n=6 each) by using a random number table: control group (group C), inflammatory pain group (group IP), dimethyl sulfoxide (DMSO) group (group D), and rapamycin (autophagy inducer) group (group R). Inflammatory pain was produced by injecting 50 μl bee venom into the plantar surface of the left hindpaw.In group C, 0.9% normal saline was injected into the plantar surface of the left hindpaw.In group D, 2% DMSO was injected through a gastric tube into the stomach 1 ml per day for 3 consecutive days, and the model was established at 1 h after injection on 3rd day.In group R, rapamycin 10 mg/kg (in 2% DMSO) was injected through a gastric tube into stomach 1 ml per day for 3 consecutive days, and the model was established at 1 h after injection on 3rd day.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 2 h after the model was established.After measurement of the pain threshold, the dorsal horn of the spinal cord was removed for determination of the expression of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ), Beclin-1 and p62 by Western blot. Results Compared with group C, the MWT was significantly decreased, the TWL was significantly shortened in IP and D groups, and the expression of LC3Ⅱ, Beclin-1 and p62 in the dorsal horn of the spinal cord was significantly up-regulated in IP, D and R groups (P 0.05). Conclusion Autophagy disorders are involved in the development of inflammatory pain in the rats. Key words: Autophagy; Inflammatory; Pain

Dynamic Analysis of Changes of Protein Levels and Selected Biochemical Indices in Rat Serum in the Course of Experimental Pleurisy.

A significant role is played in inflammation by the liver, which, stimulated by inflammatory mediators, synthetizes plasma proteins with various dynamics. The purpose of these studies is to generate a detailed dynamic analysis of changes to concentrations of plasma and serum protein fractions and selected acute-phase proteins as well as nonspecific biochemical indices during the course of an induced pleurisy. The studies were conducted on female inbred Buffalo rats, which were divided into two groups: a control group (C) and an experimental group (IP) in which pleurisy was induced. In the IP group, significant changes in biochemical indices were observed between the 48th and 96th hours of pleurisy. A reduction of albumin, transferrin, urea, and creatinine concentrations was observed, while concentrations of the complement components C3 and C4, haptoglobin, and fibrinogen increased. An early increase of IL-1 was observed, while increases of IL-6 and TNF were noted in the later period. The maximum intensity of the processes described above occurred between the 72nd and 96th hours of pleurisy.

Hardware complications and failure of three‐unit zirconia‐based and porcelain‐fused‐metal implant‐supported fixed dental prostheses: a retrospective cohort study with up to 8 years

The aim of the present study was to assess the hardware complications and survival of three-unit implant-supported zirconia-based fixed dental prostheses (IZ) and implant-supported porcelain-fused-metal fixed dental prostheses (IP). The study is a retrospective cohort study with up to 8years (mean 4.8years) follow-up. Patients with conventional three-unit implant-supported fixed dental prostheses (without cantilever) in posterior area were reviewed. Hardware complications and survival rate were evaluated. Chi-Square test was used to test the difference between IZ and IP groups. Two hundred and thirty-seven patents (IZ:112, IP:125) with 279 three-unit restorations (IZ:127, IP:152) participated in the study. The overall survival rate was 95.3% in IZ group and 94.7% in IP group at implant-level and 94.6% in IZ group and 94.4% in IP group at subject-level. Veneer chipping was the most frequently seen complication (20.1%). Significant higher minor veneer chipping rate (Grade 1) was found in IZ group (P=0.04). No significant difference of veneer chipping rate (Grade 2 and Grade 3) was found between the two groups. The overall hardware complication rates of IZ were significantly higher than IP (33.07% and 18.42%, P=0.01). High survival rate of zirconia-base and Porcelain-fused-to-metal (PFM) restorations can be achieved with up to 8years follow-up. The zirconia-based restorations need more polishing procedures, maintenance, and professional care than PFM restorations. The number of implants supporting a fixed dental prosthesis did not influence the implant survival and hardware complications. Well-designed studies with high evidence level are still needed to further explore the hardware complications and clinical survival of IZ and IP.

Effects of brown rice on cellular growth and metabolic changes in mice

The consumption of rice, especially brown rice, is known to promote cellular growth but the underlying mechanisms and key metabolites of this process are unclear. This study investigated the effects of brown rice on cellular growth and the underlying mechanisms using a metabolomics approach in vivo. C57BL/6J male mice were fed an isocaloric diet composed of control chow, Ilpum rice (IP; Oryza sativa L. cv. Ilpum), or Ilpum brown rice (IB) for 4weeks, and then the metabolites of the liver were analyzed. The rice consumption reduced the liver enzyme levels in plasma and did not result in obesity. The plasma total-cholesterol levels were significantly reduced in the IB group compared with the IP group. The plasma concentrations of growth hormone and insulin growth factor-1 were significantly increased, along with increased thigh bone width in the IB group compared with the IP group, suggesting that the intake of brown rice promoted animal growth. Gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) was used for the metabolic profiling of liver samples obtained from IP- and IB-fed mice. The obtained data sets were subjected to multivariate statistical analysis to investigate which metabolites contributed to the differences between the IP and IB groups. GC-TOF-MS analysis revealed the presence of 31 metabolites consisting of 8 lipids, 4 sugars and sugar alcohols, 15 amino acids, and 4 organic acids. Partial least-squares regression analysis demonstrated significant correlations between the data collected from GC-TOF-MS and the levels of growth hormone. The levels of l-valine, l-glutamine, and d-mannose were significantly higher in the IB group than the control and IP groups.