Ug Group Research Articles

Exploring the implementation of stepwise inquiry-based learning in higher education

Abstract The study aims to explore the implementation of stepwise inquiry in chemistry education. The levels of inquiry used range from structured inquiry (level 1) to guided inquiry (level 2). The research design involved methods of analyzing the implementation of inquiry levels, assessing the ability to answer questions, engage in critical thinking, and gather student responses. The research sample consisted of 73 students studying biochemistry. A total of 14 groups, each containing 5–6 members, were involved in this research. The research results show that six groups (SG) successfully followed the investigation process at the inquiry steps, while eight groups were unsuccessful (UG). The average scores of the sub-skills collaboration, communication, data collection, use of equipment, and implementation of experimental design were the highest compared to other subskills. The stages of interpreting problems, observation, experimental design, formulating hypotheses, data analysis, and developing conclusions are still in progress and are classified as low. The SG group had an average N-Gain critical thinking score higher than the UG group (p < 0.05). The analysis of the ability to answer questions and think critically shows that the category of developing hypotheses and analyzing arguments had the lowest ability to respond compared to other indicators.

Mapping terrestrial mammals in China based on species richness of functional groups

Biodiversity loss is one of the most critical environmental issues globally. Functional diversity and functional groups, extending and expanding the concept of species richness, provide a more comprehensive understanding of biodiversity. By integrating mathematical indices calculation with classical geospatial statistical analysis and mapping techniques, we explored and visually illustrated the spatial patterns and regularities of functional diversity. This approach shed light on the functional diversity of China’s terrestrial mammals from a macroecological perspective. We found that in terms of overall quantity composition, underground-living mammals (UG groups) had the highest proportion (55.1%) in the vertical niche dimension, while nocturnal mammals (NO groups) dominated (58.6%) the in temporal niche dimension. Employing grid cells as fundamental units, in most grid cells, the proportion of UG and NO groups exceeded 50%, consistent with the overall quantity results. Examining the spatial distribution of functional group species richness from different perspectives reveals varying patterns. For instance, standard deviations of vertical and temporal niches showed different spatial clustering traits on either side of the Hu Huanyong Line. In a specific dimension of functional diversity, the numerical differences among functional groups are larger in grasslands with homogenous vegetation, while in forests with diverse vegetation types, these differences are minimized. Additionally, if there is a large disparity in species richness among functional groups in one dimension, there may be a smaller disparity in another. These findings offer a macroecological perspective for biodiversity research, providing insights for interdisciplinary studies in basic ecology, conservation biology, and geography, and offering scientific guidance for mammal conservation.

Evaluation of luciferase and prefusion-stabilized F protein from respiratory syncytial virus mRNA/LNPs in pre-clinical models using jet delivery compared to needle and syringe

Described here is the evaluation of a luciferase (luc) and respiratory syncytial virus (RSV) messenger RNA / lipid nanoparticle (mRNA/LNP) vaccine using a Needle-free Injection System, Tropis®, from PharmaJet® (Golden, Colorado USA). Needle-free jet delivery offers an alternative to needle/syringe. To perform this assessment, compatibility studies with Tropis were first performed with a luc mRNA/LNP and compared to needle/syringe. Although minor changes in particle size and encapsulation efficiency were observed when using Tropis on the benchtop, in vitro luciferase activity remained the same. Next, the luc mRNA/LNP was administered to rats intramuscularly using Tropis or needle/syringe and tracking of the injection and distribution was performed. Lastly, an mRNA encoding a prefusion-stabilized F protein from RSV was delivered intramuscularly using both Tropis and needle/syringe at 1 and 5 mcg mRNA. An equivalent IgG response was observed using both Tropis and needle/syringe. The cell mediated immune (CMI) response was also evaluated, and responses to RSV-F were detected from animals immunized with needle/syringe at all dose levels, and from the animals immunized with Tropis in the 5 and 25 ug groups. These results indicated that delivery of mRNA/LNPs with Tropis is a potential means of administration and an alternative to needle/syringe.

Evaluation of Lumbar Sonography as a Learning Aid for Performing Subarachnoid Block Using the Paramedian Approach by Medical Junior Resident Anaesthesiologists: A Randomized Controlled Trial.

Pre-procedural ultrasound can be used to identify the subarachnoid space in difficult spinal procedures. However, multiple punctures can result in numerous complications, including post-dural puncture headache, neural trauma, and spinal and epidural haematoma. Thus, the following hypothesis was proposed: in contrast to the conventional blind paramedian dural puncture, pre-procedural ultrasound results in a successful dural puncture on the first attempt. In this prospective, randomised controlled study, 150 consenting patients were randomly assigned to one of the two groups: ultrasound-guided paramedian (UG) and conventional blind paramedian (PG). In the UG paramedian group, pre-procedural ultrasound was performed to mark the insertion site, whereas, in the PG group, the landmark technique was used. A total of 22 different anaesthesiology residents performed all subarachnoid blocks. The time taken to perform spinal anaesthesia in the UG group was 38-49.5 s, which is shorter than the time taken in the PG group, which was 38-55 s, with a p-value < 0.046, which is statistically significant. The primary outcome of a successful dural puncture on the first attempt was not significantly higher in the UG group (49.33%) than in the PG group (34.67%), with a p-value< 0.068. The number of attempts taken for a successful spinal tap in the UG group was a median of 2.0 (1 to 2), and the PG group had a median of 2 (1 to 2.5), with a p-value <0.096, which is statistically non-significant. Ultrasound guidance showed improvement in the success rate of paramedian anaesthesia. In addition, it improves the success rate of dural puncture and the rate of puncture on the first attempt. It also shortens the time required for a dural puncture. In the general population, the pre-procedural UG paramedian group did not outperform the PG paramedian group.

Effectiveness of a Nutritional Mobile Application for Management of Hyperphosphatemia in Patients on Hemodialysis: A Multicenter Open-Label Randomized Clinical Trial.

This study aims to determine the effectiveness of a phosphate mobile app (PMA), MyKidneyDiet-Phosphate Tracker ©2019, on hemodialysis (HD) patients with hyperphosphatemia. A multicenter, open-label, randomized controlled trial design allowed randomization of patients with hyperphosphatemia to either the usual care group (UG; receiving a single dietitian-led session with an education booklet) or the PMA group (PG). Thirty-three patients in each intervention group completed the 12-week study. Post-intervention, serum phosphorus levels were reduced in both groups (PG: −0.25 ± 0.42 mmol/L, p = 0.001; UG: −0.23 ± 0.33 mmol/L, p < 0.001) without any treatment difference (p > 0.05). Patients in both groups increased their phosphate knowledge (PG: 2.18 ± 3.40, p = 0.001; UG: 2.50 ± 4.50, p = 0.003), without any treatment difference (p > 0.05). Dietary phosphorus intake of both groups was reduced (PG: −188.1 ± 161.3 mg/d, p < 0.001; UG: −266.0 ± 193.3 mg/d, p < 0.001), without any treatment difference (p > 0.05). The serum calcium levels of patients in the UG group increased significantly (0.09 ± 0.20 mmol/L, p = 0.013) but not for the PG group (−0.03 ± 0.13 mmol/L, p = 0.386), and the treatment difference was significant (p = 0.007). As per phosphate binder adherence, both groups reported a significant increase in Morisky Medication Adherence Scale scores (PG: 1.1 ± 1.2, p < 0.001; UGa: 0.8 ± 1.5, p = 0.007), without any treatment difference (p > 0.05). HD patients with hyperphosphatemia using the PMA achieved reductions in serum phosphorus levels and dietary phosphorus intakes along with improved phosphate knowledge and phosphate binder adherence that were not significantly different from a one-off dietitian intervention. However, binder dose adjustment with meal phosphate content facilitated by the PMA allowed stability of corrected calcium levels, which was not attained by UC patients whose binder dose was fixed.

Histopathological Evaluation of the Effect of Eugenol in a Model of Trinitrobenzenesulfonic Acid-Induced Colitis in Rats

Abstract Introduction: Trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis in animals is a commonly used model of inflammatory bowel disease (IBD). Eugenol (Eug) is a natural phenolic compound possessing promising antioxidant and anti-inflammatory therapeutic properties. Aim: The present study investigated the effects of Eug in a TNBS-induced rat colitis model using criteria for histopathological evaluation of the colonic damage. Materials and methods: Male Wistar rats were divided into 6 experimental groups, each of 10 rats: Control, TNBS, TNBS+Eug1, TNBS+Eug5, TNBS+Eug25, and TNBS+Eug125 group. Eug or the solvent (sunflower oil) was applied orally using an orogastric cannula. The control group and TNBS group were treated only with sunflower oil. Eug groups were treated with corresponding doses of Eug (1, 5, 25 and 125 mg/kg) dissolved in sunflower oil. Colitis was induced by the application of TNBS in the colon. The animal treatment began 6 days before the colitis induction and continued for 8 days after it. At the end of the experiment, colitis severity was evaluated histopathologically regarding epithelium injury, inflammatory cell infiltration, and formation of granulation tissue. Results: In all TNBS+Eug groups, the formation of granulation tissue was enhanced compared to TNBS. In group TNBS+Eug125 the difference was significant compared to the control group (p &lt; 0.05). No significant improvement regarding the scores of epithelium injury and inflammatory cell infiltration was observed in Eug groups compared to TNBS group. Conclusion: Eug did not improve the signs of TNBS-induced epithelial injury and inflammatory cell infiltration, but stimulated the formation of granulation tissue which might be considered as a sign of healing.

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial

Optical Coherence Tomography Angiography in Uveitic Glaucoma – A Pilot Study

ABSTRACT Purpose: To compare vessel density (VD) as measured by optical coherence tomography angiography (OCTA), in uveitic eyes with secondary glaucoma (UG) with VD in uveitic eyes without glaucoma (UV), eyes with primary open-angle glaucoma (POAG), and healthy eyes (HY). Methods: VD was measured at the following segmentation areas: radial peripapillary capillaries, superficial (SL) and deep vascular plexus (DL) and choroid. Results: The majority of the measured papillary areas showed significantly lower VD in the UG group than in the HY group. In macular area, in the superficial vascular plexus wholeVD was significantly lower than in the healthy group, as well as in four other quadrants. In DL no significant differences could be found. At choroidal level, the VD of UG group were significantly lower in two quadrants than in UV group. Conclusions: OCTA can be used to detect differences in VD in papillary and macular region of uveitis glaucoma eyes.

Abstract 3317: Discovery of novel STING agonists with robust anti-tumor activity

Abstract Introduction: Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER) membrane signaling protein, which plays a key role in the sensing of cytoplasmic DNA arising from bacterial and viral infection, as well as self-DNA. Several studies have shown that STING signaling is essential for antitumor immunity by inducing the production of type I IFN and activating both innate and adaptive immunity. Therefore, activation of STING pathway in the tumor microenvironment could be a potential effective approach for cancer immunotherapy. Here, we present the characterization of novel STING agonists in a variety of in vitro cell lines and in vivo murine models. Methods: THP-1 monocyte cells and HEK 293-derived cells transfected with STING variants were used for cellular potency evaluation. Multiple murine tumor models were used for evaluation of in vivo efficacy. Tumor cells were inoculated into C57BL/6 mice and compounds were injected intratumorally three times at every three days when tumors reached a mean volume of approximately 100 mm3. Compounds-treated mice free from tumor for 30 days were re-challenged with MC38 tumor cells in MC38 murine model. Results: Several lead compounds CS-1018, CS-1020 and CS-1010 activate mouse and human STING variants in vitro with much better potency than natural ligand cGAMP and reference compound X. CS-1018 demonstrated dose dependent robust antitumor activity in B16F10 and MC38 mouse models. 3 out of 8 mice achieve complete responses at the dose of 100 ug in B16F10, 25% or 75% of mice were tumor free when treated with 5 ug or 25 ug of compound respectively in MC38. The survival mice from 5 ug and 25 ug groups remained tumor-free after re-challenged with another inoculation of MC38 cancer cells. The antitumor activity of compound CS-1020 and CS-1010 was also demonstrated in MC38 mouse model. When CS-1020 was dosed at 5 ug or 25 ug, complete responses were observed in 63% or 88% of mice respectively. In the case of CS-1010, the dose of 5 ug provides complete responses in 100% of treated mice. Similarly, both compounds induced immune-mediated tumor rejection when re-challenged with the same cancer cells. Conclusions: We have identified several STING agonists, which demonstrated better cellular potency to mouse and human STING alleles compared to natural ligand cGAMP and reference compound. All compounds showed dose dependent antitumor activity in MC38 or B16F10 syngeneic models, in addition, tumor-free mice after treatment of compounds developed tumor specific immunologic memory response in MC38 murine model. Combination studies of identified STING agonists with other IO agents are currently ongoing. The results will be discussed. Citation Format: Anrong Li, Yuntao Song, Chen Dong, Xiaoqi Chen, Junbao Yang. Discovery of novel STING agonists with robust anti-tumor activity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3317.

Palatal volume estimation in operated unilateral and bilateral cleft lip and palate subjects using digital study models.

To quantify and compare palatal volume of operated unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) subjects. This cross-sectional study was conducted on 85 study models comprising of 40 operated UCLP subjects (UG; mean age 10.33±1.76years), 25 operated BCLP subjects (BG; mean age 10.44±1.92years) and 20 non-cleft controls (C; mean age 12.90±1.68years). The study models were scanned using 3D scanner and palatal volume assessment done using 3-matic software. Kruskal-Wallis test for palatal volume and one-way ANOVA for intercanine (IC), interpremolar (IPM) and intermolar (IM) width comparison were used. Pearson correlation was done between IM, IPM, and IC width, and palatal volume for three groups. The control group sample was evaluated by two observers to evaluate the interobserver reliability. The median palatal volume of C, UG and BG groups was 5814.31mm3 , 2452.34mm3 and 1688.39mm3 , respectively. Significantly smaller palatal volume was found in UG and BG compared to control. Significant difference was seen in IC width between three groups. The IM, IPM and IC width with palatal volume in UG and IM width with palatal volume in BG group showed significant correlation. The ICC showed excellent agreement (>0.9) between observers. Palatal volume of UG and BG groups was smaller by 57.82% and 71.1%, respectively, compared to controls. Improving IPM width in UG and IM width in BG seems to have more impact in correction of palatal volume.

201 Correlation between metaphase II oocyte cytoplasmic granulation patterns and intracytoplasmic sperm injection fertilization outcome in older patients

Cytoplasmic granulation is frequently observed in human MII oocytes in fertility clinics from women requiring early egg retrieval (also called highly individualized egg retrieval, with hCG trigger at lead follicle size 16.0-18.0mm or even less) to avoid premature luteinization. Early retrieval is mostly done for older women (≥36 years old) or younger women with premature ovarian aging. However, only limited reports have focused on detailed analysis of the patterns of cytoplasmic granulation and their correlation with the quality of human oocytes. The aim of this report was to evaluate correlation between granulation patterns of human MII oocytes from early retrieval and the corresponding fertilization rates from intracytoplasmic sperm injection (ICSI). Each MII oocyte was imaged when ICSI was performed. The granulation pattern of each oocyte was reviewed, evaluated, and categorized by the same person as non-granulation (NG, homogeneous, sandy pattern, no granulation or granulation area &amp;lt;1/8 of total cytoplasm), central granulation (CG, ring pattern, a cluster of granules in centre with size &amp;gt;1/4 of oocyte diameter), uneven granulation (UG, sandy-rocky pattern, granulation area &amp;gt;1/8 but &amp;lt;3/4 of total cytoplasm), and dispersed granulation (DG, rocky pattern, granulation area &amp;gt;3/4 of total cytoplasm). Fertilization (pronucleus count, PN) results were then extracted from medical records and matched to the granulation categories. In total, 1759 oocytes done with ICSI in year 2018 were analysed. Fertilization (&amp;lt;2PN, 2PN or &amp;gt;2PN) rates of each group (n=381, n=1222, n=156, respectively) were calculated. Student's t-test was used for group-group comparison analysis. Compared with the NG group, the UG and CG groups had lower 2PN rates (67.2% vs. 84.6%; P&amp;lt;0.001; 73.0% vs. 84.6%; P&amp;lt;0.05; respectively) and the DG group had a much lower 2PN rate (43.3% vs. 84.6%; P&amp;lt;0.001). The UG and CG groups had higher &amp;lt;2PN rates (24.8% vs. 12.1%; P&amp;lt;0.001; 24.3% vs. 12.1%; P&amp;lt;0.001; respectively), and the DG group had a much higher &amp;lt;2PN rate (41.1% vs. 12.1%; P&amp;lt;0.001) than the NG group. For &amp;gt;2PN rates, both UG and DG groups were higher than the NG group (8.0% vs. 3.3%; P&amp;lt;0.05; 15.6% vs. 3.3%; P&amp;lt;0.001; respectively), whereas the DG group was higher than the UG group (15.6% vs. 8.0%). These data demonstrated that dispersed granulation was the worst pattern for fertilization. Interestingly, many of the uneven-granulation group oocytes could become homogeneous (non-granulation) after hours or overnight IVM culture, suggesting that uneven granulation might be a sign of incomplete cytoplasmic maturity. Technically, performing ICSI through the less-granulation side was easier because of less resistance to membrane breaking and to pushing sperm out. Discovering the molecular nature of the granules and related cytoskeleton structures would extend our understanding of their existence and improve treatments by adjusting stimulation and trigger accordingly.

Selective Use of Radiation-Based Management in Localized Muscle-Invasive Bladder Cancer

Radiotherapy-based management of muscle-invasive bladder cancer (MIBC) is increasingly recognized as an alternative to radical cystectomy, however its use remains controversial. At our institution, bladder-preserving treatment is considered to have equipoise compared to radical cystectomy, particularly in cases with ‘favorable’ features such as cT2 and small (<5cm) primary tumor. We investigated outcomes of this so-called favorable group (FG) compared to a contemporaneous unfavorable cohort of patients (UG). We retrospectively reviewed patients with localized MIBC treated with curative-intent radiotherapy +/- chemotherapy (concurrent and/or neoadjuvant/adjuvant) after maximal transurethral resection of bladder tumor (TURBT) between 2003 and 2017. We examined local control (BLC), distant metastasis-free survival (DMFS), and overall survival (OS) among 1) FG, and 2) UG (either cT3/4, and/or tumor size≥ 5 cm or unknown). Outcomes were estimated using Kaplan-Meier method; and univariable and multivariable analysis were performed using Cox Proportional Hazards Model. In total, 128 patients with localized MIBC were identified; of these 105 (82%), 17 (13%), and 6 (5%) patients had cT2, cT3, and cT4 disease, respectively. Median patient age was 76.5 years (43.0-95.0). Median follow-up was 3.1 years (0.1-11.7). Median recorded tumor size (n=98 [76.6%]) was 3.0 cm (0.5-8.5). There were 71 patients (55.5%) in FG and 57 (44.5%) in UG. Thirty-three patients (19 FG, 14 UG) had no chemotherapy due to comorbidities or preference, and 23 patients (14 FG, 9 UG) were considered unfit for cystectomy. Chemotherapy delivery was: 57 concurrent, 11 neoadjuvant/adjuvant, 27 concurrent and adjuvant/adjuvant. For all patients, 3-year BLC, DMFS, and OS were 64%, 64%, and 82%. At 3 years, BLC of FG and UG were 65% and 61% at 3 years, respectively (not significant [NS]); DMFS were 71% and 57% (p= 0.044), OS were 92% and 69% (NS), respectively. In multivariable analysis cT4 was associated with worse DMFS (HR= 19.5, p<0.001) and OS (HR= 35.3, p<0.001). Similarly, cT3 was associated with worse BLC (HR= 3.2, p= 0.0036). The primary tumor size was not associated with BLC. Overall BLC rates were acceptable, despite one quarter of patients treated without chemotherapy. Bladder local control in FG patients was comparable to the UG group. FG designation was not a useful discriminator for better local outcomes, while cT stage predicted BLS, DMFS, and OS. Large primary tumor did not appear to adversely affect BLC. Further studies to incorporate other factors such as lymphovascular invasion or concurrent carcinoma in-situ will aid oncologists in selecting optimal treatment approach.

Comparison of Intra-Operative Vital Sign Changes during Total Thyroidectomy in Patients with Controlled and Uncontrolled Graves' Disease.

Thyroid storm (TS) is a life-threatening emergency endocrine condition. Thyroid hormones should be normalized before thyroidectomy is performed in patients with Graves’ disease. However, thyroid hormone levels are inevitably high in patients undergoing surgery. This study analyzed differences in vital sign changes during thyroidectomy between patients with controlled and uncontrolled Graves’ disease and assessed thyroid hormone cutoffs for TS. Preoperative levels of the thyroid hormones free T4 (FT4), T3, and thyroid stimulating hormone (TSH) were retrospectively analyzed in patients who underwent total thyroidectomy for Graves’ disease. Patients were divided into those with uncontrolled Graves’ (UG) disease, defined as preoperative TSH <0.3 µIU/mL and FT4 >1.7 ng/dL, those with controlled Graves’ (CG) disease, those with extremely uncontrolled Graves’ (EUG) disease, defined as TSH <0.3 µIU/mL and FT4 >3.4 ng/dL, and finally, those without EUG (non-EUG). The 29 patients with Graves’ disease included 12 with CG group and 17 with UG. FT4 and T3 concentrations were significantly higher in the UG group. There were no differences in vital sign and anesthetic agent. These 29 patients could also be divided into those with (n = 4) and without EUG (n = 25). The mean age was lower (21.5 vs. 40.9 years, p < 0.001) and the mean operation time was shorter (121.4 vs. 208.8 min, p = 0.003) in the EUG group. Requirements for anesthetic agents were greater in the EUG group. Mean FT4 concentration in the EUG group was 3.8 ng/dL, and there were no changes in vital signs during surgery. Vital sign change during thyroid surgery was not observed in patients with uncontrolled Graves’ disease up to the twice upper normal limit of T4 level.

A Randomized, Double-Blind, Phase 2 Study of the Effects of the Vaccine Vanutide Cridificar with QS-21 Adjuvant on Immunogenicity, Safety and Amyloid Imaging in Patients with Mild to Moderate Alzheimer's Disease.

Vanutide Cridificar (ACC-001), a novel investigational immunotherapeutic vaccine designed to elicit antibodies against the N-terminal peptide 1-7 of the amyloid-beta peptide, believed to be important in the pathogenesis of Alzheimer's disease (AD). To evaluate the immunogenicity, safety and impact of ACC-001 with Quillaja saponaria (QS-21) adjuvant on the reduction of brain fibrillar amyloid burden, assayed by positron emission tomography (PET) imaging, in patients with mild to moderate AD. Randomized, phase 2, interventional study. ClinicalTrials.gov Identifier: NCT01284387. Individuals with mild to moderate Alzheimer's disease (Mini-Mental State Examination scores 18-26; measurable amyloid burden in the expected range, on the screening 18F-florbetapir PET scan; and a Rosen modified Hachinski ischemic score ≤4). Participants were randomized to 3 μg or 10 μg ACC-001 (each in combination with 50 μg QS-21) or placebo (without QS-21). Primary endpoint was the change from baseline to week 104 in cerebral amyloid burden as measured by the global cortical average (GCA) standard value uptake ratio (SUVR) based on the brain 18F-florbetapir PET composite cortical SUVR between each ACC-001+QS-21 dose compared with placebo. Secondary endpoints included safety, immunogenicity and pharmacodynamics. Exploratory endpoints included cognitive and functional efficacy, and health outcome measures. Of 126 randomized patients (placebo: 40; ACC-001 3 µg+QS-21: 43; and ACC-001 10 µg+QS-21: 43), 125 received study treatment; 92 (73%) completed the study. Change in 18F-florbetapir PET GCA SUVR, was not significantly different between either of the two ACC-001+QS-21 treatment groups and placebo (3 μg +QS-21 vs. placebo diff=-0.03, p=0.54; 10 μg +QS-21 vs. placebo diff=-0.08, p=0.07), but the trend was numerically consistent with a dose response. The geometric mean peak anti-Aβ IgG titers were slightly higher in the 10 μg than the 3 μg group. The proportion of responders was similar in both dose groups of ACC-001+QS-21. The cerebrospinal fluid (CSF) p-tau changes from baseline in both active treatment groups were not statistically different from placebo, but were numerically consistent with a dose response (3 μg +QS-21 vs. placebo diff=-3.2, p=0.57; 10 μg +QS-21 vs. placebo diff=-7.0, p=0.19). The vMRI showed statistically significant faster treatment-related decrease in brain volume in the 10 μg group but was not significant in the 3 μg group, compared with placebo (3 μg diff =-1.3 mL/year, p=0.50; 10 μg diff=-4.2 mL/year, p=0.02). Measured plasma Aβ levels increased in parallel with peak anti-Aβ titers after each injection. Amyloid-related imaging abnormalities with edema/effusion (ARIA-E) were more frequent in patients who received ACC-001+QS-21 than placebo (6% vs. 0%) but none were symptomatic. The most common treatment-emergent adverse events in the active groups were injection reactions, and occurred more frequently in the ACC-001+QS-21 groups than the placebo (48% vs 8%), the majority of which were mild and transient. Primary biomarker efficacy endpoints were not statistically significant in either dose group. The numerical decreases in 18F-florbetapir PET GCA SUVR suggests a dose-related trend for greater reductions in fibrillar amyloid burden in the ACC-001+QS-21 10 µg group compared with placebo. Likewise, while not significant, there was a numerical trend of decreased CSF p-tau levels with ACC-001, possibly consistent with a downstream effect in the ACC-001+QS-21 group. Insufficient antibody titers or quality, insufficient power to detect a difference, or too short duration of follow up may be reasons why a statistically significant response was not observed. Brain volume measures showed faster volume loss in the 10 µg treatment group, similar to the effect seen in few earlier AD immunotherapy trials which may suggest removal of amyloid and resultant decrease in inflammation. No new, unexpected safety signals were detected.

Reproducibility of caries diagnosis in permanent teeth according to WHO, ICDAS-II and Nyvad criteria

Aim: To assess inter-examiner reproducibility in the detection of 20 occlusal caries in permanent teeth using three diagnostic codes and criteria: WHO (1997), Nyvad and ICDAS-II. Methods: Three graduate students (G) and two undergraduate dental students (UG) without previous experience in the use of Nyvad and ICDAS-II were trained by a reference examiner. Examiner validity was assessed by consensus agreement between the investigators. Two cutoff points were used for ICDAS-II and Nyvad to represent reproducibility values: the A- lesion, B- cavity lesion. Results: According to the examiners consensus, the kappa values ranged from 0.71 to 0.85 for G group and from 0.85 to 0.95 for UG group (ICDAS-II). For the Nyvad index values varied from of 0.77 to 1.00 (G) and from 0.65 to 0.74 (UG), for the WHO index, values obtained ranged from 0.66 to 1.00 (UG) and 1.00 (G). Using a cutoff A, interexaminers reproducibility (ICDAS-II) ranged from 0.73 to 0.87 (G) and 1.00 (UG). According to Nyvad criteria, the kappa value ranged from 0.78 to 1.00 (G) and from 0.70 and 0.90 (UG) when compared to the consensus. The kappa values using the cutoff point B ranged from 0.66 to 1.00 (G), 0.76-0.89 (UG) in ICDAS-II and the in Nyvad criteria varied from 0.87 to 1.00 (G) and from 0.65 to 0.88 (UG). Conclusions: Reproducibility values ranged from good to perfect. The reproducibility revealed precise answers in the occlusal caries lesions diagnosis according to the criteria used. The best use of reliability tools for examiner training was important regardless of the examiners being undergraduate or graduate students.

Efecto de un extracto hidroalcohólico de Uncaria tomentosa (uña de gato) sobre la población de células dendríticas y sus moléculas HLA-DR y CD86 ante el estimulo con lipopolisacáridos

Objective. To determine the effect of an hydro-alcoholic extract of cats claw Uncaria tomentosa (uG) over lipopolysaccharides - treated dendritic cells (DC) and HLA-DR and CD86 molecules expression of peripheral blood samples obtained from healthy individuals. Materials and methods. Peripheral blood samples were collected from healthy individuals. Peripheral Blood Mononuclear Cells (PBMC) were isolated by centrifugation over density gradient, pre-treated with and without the addition of uG, and then stimulated for 24 h with lipopolysaccharides (LPS), then the cells were labelled with specific fluorescent monoclonal antibodies to HLA-DR, Linage type 1 (Lin1), CD11c and CD86 and prepared for flow. Results. Compared to PBMC with LPS but without uG group, we found a decrease of myeloid DC (mDC) percentage (p<0.05) and a tendency to increase plasmacytoid DC (pDC) percentage, both in a dose-dependent manner. There was a decrease in media fluorescence intensity (MfI) of HLA-DR in DCp between 500 and 1000 µg/mL of CC (p<0,001), but we found a increase in MfI of CD86 at all concentrations (p<0,05). There was no effect of uG over MfI of the HLA-DR or CD86 expression in mDC. Conclusions. uG showed a tendency to increase pDC percentage and decreased mDC percentage. uG did not affect the expression of CD86 and HLA-DR from mDC. This study demonstrates that uG promotes activation/differentiation of pDC, which has a demonstrated involvement in the adaptive immune response mechanisms.