AA Groups Research Articles

Under the name of “Lua”: revisiting genetic heterogeneity and population ancestry of Austroasiatic speakers in northern Thailand through genomic analysis

BackgroundAustroasiatic (AA)-speaking populations in northern Thailand are of significant interest due to their status as indigenous descendants and their location at the crossroads of AA prehistoric distribution across Southern China, the Indian Subcontinent, and Mainland Southeast Asia. However, the complexity of ethnic identification can result in inaccuracies regarding the origin and migration history of these populations. To address this, we have conducted a genome-wide SNP analysis of 89 individuals from two Lavue and three Lwa-endonym populations. We then combined our outcomes with previously published data to elucidate the genetic diversity and clustering of AA groups in northern Thailand.ResultsOur findings align with existing linguistic classifications, revealing different genetic compositions among the three branches of the Mon-Khmer subfamily within the AA family: Monic, Khmuic, and Palaungic. Although the term “Lua” ethnicity is confusingly used to identify ethnic groups belonging to both Khmuic and Palaungic branches, our genomic data indicate that the Khmuic-speaking Lua living on the eastern side of the region are relatively distant from the Palaungic-speaking Lavue and Lwa populations living on the western side. The Lavue populations, primarily inhabiting mountainous areas, exhibit a genetic makeup unique to the AA family, with a close genetic relationship to the Karenic subgroup of the Sino-Tibetan language family. Conversely, the Lwa and Blang populations, residing in lowland river valleys, display genetic signatures resulting from admixture with Tai-Kadai-speaking ethnic groups.ConclusionUtilizing genome-wide SNP markers, our findings indicate genetic heterogeneity among the Lua, Lavue, and Lwa ethnic groups. The intricate interplay of genetics, cultural heritage, and historical influences has shaped these ethnic communities. Our study underscores the importance of accurate ethnic classifications, emphasizing the use of self-identified endonyms, names created and used by the ethnic groups themselves. This approach respects the AA communities in northern Thailand and acknowledges their significant contributions to advancing our understanding of genetic anthropology.

Effect of acupuncture on the sleep quality of hemodialysis patients in a capital city in the Northeast of Brazil

Objective: Analyze the effect of auricular acupuncture on the sleep quality of hemodialytic patients with chronic pain in a capital city in the Northeast of Brazil. Methods: This study includes double-blind, randomized in blocks and allocated at a rate of 1:1, controlled trial that was conducted in two hemodialysis clinics, with 94 chronic renal patients with chronic pain (auricular acupuncture [AA]: 47, sham acupuncture [SA]: 47). Both received 12 sessions for three months. We collected data using the Pittsburg Sleep Quality Index (PSQI). Data were analyzed using t-tests, Wilcoxon test and ANOVA. Results: Comparing the SA and AA groups, there was a statistically significant difference at baseline (p < 0.001), a significant intergroup difference, and the AA group had better sleep quality than the SA group during and at the end of the 12 sessions (< 0.001). A high magnitude of the effect of auricular acupuncture on sleep quality was found at the end of the sessions (D= -1.94). Conclusion: The auricular acupuncture intervention proved to be effective in improving the subjective sleep classification of renal patients.

Abstract A070: Real world treatment patterns and patient outcomes of neuroendocrine tumors: A single institution study

Abstract Neuroendocrine tumors (NETs) are rare and diverse, with increasing incidence but poorly understood prognostic variables. While African American or Black patients typically have poorer outcomes across various tumor types, this is not well documented for NETs. Our study aimed to investigate racial disparities in NET outcomes. Patients who had a diagnosis of neuroendocrine tumor between 2014 and 2022 were identified and analyzed in this retrospective chart analysis, with race determined as Caucasian (CA) or Black African American (BAA). Histology was stratified as high grade or those without high grade histology. Grade of tumor was identified as well differentiated, moderately or poorly differentiated, and other/unknown. Log-rank test was conducted to compare the survival curves between CA and AA groups. Cox proportional hazards model was built to adjust for potential confounders, including age at diagnosis and gender (if applicable) while comparing racial disparities. The CA vs. AA hazard ratio (HR) and p-values were calculated. Among the 655 patients analyzed, 63.4% were Caucasian (CA) and 36.6% were Black African American (BAA). The average age at diagnosis across the cohort was 61.5 years. The gender distribution was approximately equal, with 50.2% females and 49.8 % males. High-grade histology was identified in 114 patients, of whom 28.1% were BAA and 71.9% were CA. Within this subgroup, males were more prevalent than females (61.4% vs. 38.6%). Overall survival (OS) for CA patients with high-grade histology was 57.4 months, compared to 67.5 months for BAA patients (p=0.7). Additionally, no statistically significant difference in OS was observed between males and females with high-grade histology (60.8 months vs. 68.1 months, respectively; p=0.3). Analysis of tumor grade revealed that well- differentiated tumors were present in 122 patients (18.63%). Among these patients, there was no statistically significant difference in survival between BAA and CA. The primary tumor site was the colon in 89 patients (13.6%), with 77.5% being CA and 22.5% BAA. Pancreatic tumors were present in 119 patients (18.2%), with 72% being CA and 28% BAA. The next most common primary sites were the small intestine (24.9%), rectum (17.6%), and stomach (9.9%). In comparing survival outcomes between racial groups, CA patients had a significantly worse OS (76.9 months) compared to BAA patients (84.6 months) (p=0.05). Regardless of race, females demonstrated better survival (84.2 months) compared to males (75.7 months) (p=0.04). In our retrospective analysis, Caucasian (CA) patients had worse overall survival (OS) than Black African American (BAA) patients, likely due to a higher proportion of CA patients with high- grade histology and primary tumors in the colon. Females showed better OS than males across all subtypes. The reasons for the higher incidence of worse histology in CA patients are unclear. Larger studies are needed to confirm these findings, understand racial disparities, and develop strategies to mitigate them. Citation Format: Radhika Gutta, Wan-Ting su, Ruicond She, Muhammad Shahid, Gazala Khan. Real world treatment patterns and patient outcomes of neuroendocrine tumors: A single institution study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A070.

Association Study Between DRD2, DRD3 Genetic Polymorphisms and Adverse Reactions in Chinese Patients on Amisulpride Treatment.

To determine if the cardiac function and "endocrinium" of Chinese patients are associated with dopamine D2 (DRD2) (rs6276) and DRD3 (rs6280, rs963468) genetic polymorphisms when treated with amisulpride. This study enrolled 148 patients with schizophrenia who took amisulpride orally for 8 weeks. DRD2 (rs6276) and DRD3 (rs6280, rs963468) genetic polymorphisms were detected with TaqMan-MGB allelic discrimination. Analysis by multivariate covariance analysis (MANCOVA) showed that after adjusting for age, gender, and the baseline level, the increase in the level of aspartate aminotransferase (AST) and creatine kinase (CK) in the rs6276 AG group was higher than that in the AA and GG groups. Similarly, the changed estradiol (E2) level in rs6276 GG and rs963468 GG groups was higher than that in the other two groups. Adjusting for covariates, the increased triglyceride (TG) level in rs6276 GG and rs963468 GG groups was the highest among their different genotype groups. The increase in the level of "AST" in the rs6280 TT group was higher than that in the CC and CT groups upon adjusting for covariates. Similarly, MANCOVA showed that the increase in the level of "CK" in the rs6280 CT group was higher than that in the CC and CT groups. Besides, the increased level of "PRL" in the rs6280 CC group and rs963468 GG group was higher than that in their other two genotypes groups. DRD2 (rs6276) and DRD3 (rs6280, rs963468) polymorphisms can affect amisulpride tolerability since they are associated with the observed adverse reactions, including cardiac dysfunction and endocrine disorders in Chinese patients with schizophrenia.

Effects of Maternal Smoke Exposure on Endoplasmic Reticulum Stress and Autophagy in the Lungs of Offspring Mice.

Cigarette smoke (CS) induces autophagy and endoplasmic reticulum (ER) stress in the lungs. Research suggests that maternal exposure to CS during pregnancy leads to decreased lung function in offspring. However, the effects of maternal CS exposure on lung autophagy and ER stress in offspring during pregnancy remain unclear. C57BL/6J female mice were divided into the AA (air treatment during both pre-pregnancy and pregnancy), AS (air treatment during pre-pregnancy and CS treatment during pregnancy), SA (CS treatment during pre-pregnancy and air treatment during pregnancy), and SS (CS treatment during both pre-pregnancy and pregnancy) groups. The male offspring mice were selected to the study and euthanized 49 days after birth for the study. Hematoxylin and eosin (HE) staining was employed to observe pathological alterations, while transmission electron microscopy (TEM) was utilized to examine ultrastructure and autophagic vesicles. Additionally, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method was applied to identify apoptosis in lung tissues. Immunofluorescence, Real-Time PCR, and Western Blot analyses were conducted to assess the expression of ER stress and autophagy-related markers in lung tissues. The findings revealed that exposure to CS heightened the extent of pathological damage and the abundance of autophagosomes in the lungs of offspring mice. TUNEL results indicated an increased fluorescence intensity in the AS, SA and SS groups, with the most significant in AS and SS groups. Furthermore, CS exposure augmented the fluorescence intensity and expression of ER stress and autophagy-related proteins. The expression of C/EBP-homologous protein (CHOP) exhibited no discernible difference between the SA and SS groups but showed a significant increase in the AS group. Conversely, the expression levels of glucose-regulated protein 78 (GRP78), Caspase-12, Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3) exhibited no significant difference between the AS and SA groups, whereas they were significantly upregulated in the SS group. Preconceptional and gestational exposure to CS heightened ER stress and autophagy in the lungs of mouse offspring. However, in mothers who smoked, withdrawal from CS during pregnancy led to a reduction in ER stress and autophagy in the lungs of their offspring.

Adding thread-embedding acupuncture to auricular acupuncture enhances short-term weight reduction in overweight and obesity: A double-blinded, randomized, sham-controlled trial

BackgroundAuricular acupuncture (AA) has been widely used in overweight and obesity management due to its safety and effectiveness. The combination of other acupuncture therapies with thread-embedding acupuncture (TEA) has shown enhanced effects. However, there is a lack of evidence regarding AA plus TEA for overweight and obesity. This study was conducted to address this question. MethodsA randomized placebo-controlled trial was conducted involving 66 overweight or obese participants, divided into two groups: 33 received AA plus TEA, and 33 received AA plus sham TEA over eight weeks. The primary outcome was body weight (BW) reduction. Secondary outcomes included changes in body mass index (BMI) and waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), food cravings questionnaire-trait-reduced (FCQ-Tr) and food craving visual analog scale (VAS) scores. Safety outcomes were adverse events (AEs). ResultsAfter eight weeks, BW decreased by a mean (SD) of -4.45 (1.29) kg and -2.05 (1.33) kg in the AA plus TEA and AA plus sham TEA groups, respectively (MD [95 % CI]: 2.40 [1.75; 3.05]). BMI, WC, WHR, and food craving VAS score decreased significantly more in the AA plus TEA group than in the AA plus sham TEA group. No significant differences were found in FCQ-Tr and HC between groups. Seven AEs were recorded that were mild and resolved without treatment. ConclusionThe addition of TEA to AA is a safe and effective management of overweight and obesity. Further studies should incorporate dietary and lifestyle modifications and follow-up after the intervention to assess long-term effectiveness. Trial registrationThe study protocol had been registered on ClinicalTrials.gov (NCT06091761).

Impact of Perceived Racial Discrimination on Depressive Symptoms and School Outcomes Among Asian American Youth

Using two survey datasets–the Korean American Families (KAF) Project and the Cross Cultural Families (CCF) Project, this study examined how perceived racial discrimination influences depressive symptoms and school outcomes among Asian American adolescents, and what factors mediate the association between perceived discrimination and youth outcomes. The KAF Project surveyed Korean American (KA) youth in Midwest (n = 220), and the CCF Project surveyed Cambodian American (CA) youth (n = 164), and Vietnamese American (VA) youth (n = 163) in a Pacific Northwest school district. Using Structural Equation Modeling, the results revealed perceived discrimination was positively associated with depressive symptoms for KA and VA youths, but school misbehavior only for CA youth. Among KA youth, perceived discrimination was positively associated with ethnic identity, in turn positively related to social support, thereby reducing depressive symptoms. Among CA and VA youths, perceived discrimination was not associated with ethnic identity, but ethnic identity was related to social support, which in turn was associated with lower depressive symptoms, less school misbehaviors and better grades. This study offers insights into the way in which perceived racial discrimination may exert an impact on children’s mental health and school outcomes and how the mechanisms that explain this relationship vary across AA subgroups. The findings of this study highlight the need for sustained research in the future to advance research and practice for AA groups.

Real-World Evidence of FOLFIRI Combined with Anti-Angiogenesis Inhibitors or Anti-EGFR Antibodies for Patients with Early Recurrence Colorectal Cancer After Adjuvant FOLFOX/CAPOX Therapy: A Japanese Claims Database Study.

Oxaliplatin-containing adjuvant regimens (folinic acid, fluorouracil, and oxaliplatin/capecitabine and oxaliplatin [FOLFOX/CAPOX]) are used after curative resection of colorectal cancer (CRC). However, real-world evidence regarding treatment sequences and outcomes in patients with early recurrence CRC after adjuvant chemotherapy is limited. We aimed to describe the patient characteristics, treatment sequence, and overall duration of second-line (2L) therapy in patients with early recurrence CRC who received adjuvant chemotherapy (FOLFOX/CAPOX) followed by folinic acid, fluorouracil, and irinotecan (FOLFIRI) + anti-angiogenesis drugs (AA) or FOLFIRI + anti-epidermal growth factor receptor (EGFR) antibodies. This retrospective study analyzed Japanese administrative data from November 2014 to March 2023 of adult patients who underwent CRC resection surgery, started FOLFOX/CAPOX ≤3 months (mo) after surgery, and had early CRC recurrence. Early recurrence was defined as initiation of FOLFIRI+AA or FOLFIRI+anti-EGFR antibodies as 2L therapy, ≤12 mo of discontinuing adjuvant chemotherapy. Patient characteristics, treatment sequence, median time to treatment discontinuation (mTTD), i.e., duration between the start and end dates of 2L therapy (Kaplan-Meier method), and factors associated with 2L time to treatment discontinuation constituted the study outcomes (Cox regression model). Subgroup analyses were performed for timing of early CRC recurrence (≤6 mo and 6-12 mo) and tumor sidedness. Among the 832 selected patients (median age [minimum-maximum] 67 (24-86) years, 56.4% male), CAPOX (71.3%) was more commonly used than FOLFOX (28.7%) as adjuvant therapy. FOLFIRI+AA (72.5%) was used more commonly than FOLFIRI+anti-EGFR antibodies (27.5%) in 2L. AA and anti-EGFR antibodies groups had similar mTTD: 6.2 mo (95% confidence interval 5.8, 6.9) and 6.1 mo (95% confidence interval 5.2, 7.4). Age ≥70 years showed significant association with shorter 2L treatment duration (hazard ratio 1.2, 95% confidence interval 1.0, 1.4; p = 0.03). The AA cohort's mTTD was numerically shorter in the ≤6 mo recurrence subgroup compared with the 6-12 mo recurrence subgroup (6.1 mo vs 8.1 mo); the anti-EGFR antibodies cohort had similar mTTD (5.8 mo vs 6.2 mo). The AA and anti-EGFR antibodies cohorts also had similar mTTD in the left-sided CRC subgroup (6.5 mo vs 6.2 mo), but not in the right-sided subgroup (5.6 mo vs 3.9 mo). This is the first administrative data-based real-world evidence on treatment sequence and outcomes for patients with early recurrence CRC treated with FOLFIRI+AAs or FOLFIRI+ anti-EGFR antibodies after adjuvant FOLFOX/CAPOX therapy in Japan. Both regimens had similar TTD, but relapse timing and tumor sidedness may influence their efficacy.

Should I stay or should I go: an assessment of criteria for safe day of surgery discharge of displaced supracondylar humerus fractures.

Immobilization type and in-hospital observation following surgical management of displaced supracondylar fractures are subject to surgeon preference and training. Our goal was to determine criteria for immediate discharge and optimal type of immobilization. Medical records of 661 patients with type III, IV or flexion-type displaced supracondylar humerus fractures treated at a level 1 pediatric trauma center from January 2013 to September 2019 were reviewed. Patients were separated into 'admission appropriate' (AA = 113) and 'discharge appropriate' (DA = 548) sub-cohorts. Neurovascular deficit at presentation (P < 0.001), post-operative physical exam deterioration (P < 0.001), age (P < 0.001) and post-operative immobilization modality (P = 0.02) were significantly different between AA and DA groups. When comparing patients who presented with neurologic deficit to those neurovascularly intact, there was a significant difference in whether circumferential immobilization was used post-operatively (P < 0.001), IV medication need (P < 0.001), discharge or admission (P < 0.001), neurologic decline (P < 0.001), return to ED (P = 0.008) and vascular compromise (P = 0.05). Twenty-four of the 56 (43%) patients who were AA and had no neurovascular finding on presentation had their immobilization adjusted (bivalved or loosened) to accommodate for swelling overnight. Only 1 was initially maintained in a splint or bivalved cast; the other 23 were initially maintained post-operatively in circumferential immobilization (P = 0.01). Our findings suggest that patients with intact neurovascular exams at presentation are candidates for early discharge, and splinting or bivalved casting may be preferable, especially in patients who are discharged.

Optimal sequential therapy for metastatic castration-resistant prostate cancer after androgen receptor pathway inhibitors in the up-front era.

168 Background: The optimal sequential therapy for metastatic castration-resistant prostate cancer (mCRPC) following the use of up-front androgen receptor pathway inhibitors (ARPIs) for metastatic hormone-sensitive prostate cancer (mHSPC) is still unclear. Methods: A total of 220 patients who received systemic therapy for de novo mHSPC at Nagoya University Hospital and its affiliated institutions between 2014 and 2022 were included in the study. Patients who received up-front therapy with ARPI as first-line therapy for mHSPC, followed by ARPI as primary therapy for mCRPC were defined as the AA group, followed by docetaxel (DOC) as primary therapy for mCRPC were defined as the AD group. On the other hand, the vAA group was defined as patients who received androgen deprivation therapy alone or combined androgen blockade as “vintage” first-line therapy for mHSPC, followed by two consecutive ARPIs as sequential therapy for mCRPC, and the vAD group was defined as patients who received ARPI followed by DOC as sequential therapy for mCRPC. Patient characteristics and progression-free survival (PFS) of the second agent after the first ARPI were compared in each group. Results: We identified 14 patients in the AA group, 16 in the AD group, 84 in the vAA group, and 59 in the vAD group. There were no differences in patient background such as initial PSA, Gleason score, and metastatic burden between the groups, while patient age was lower in the AD and vAD groups compared to the AA and vAA groups. The PFS of the second agent in the AA group was significantly shorter than that in the vAA group (median, 6.8 vs. 1.9 months; hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.25-0.87; p=0.017). In contrast, there was no significant difference in PFS of the second agent in the vAD and AD groups (median, 7.0 vs. 4.0 months; HR, 0.63; 95%CI, 0.29-1.34; p=0.235). Conclusions: The effect of each agent after ARPI therapy in the UP-FRONT era may be poorer than that in the VINTAGE era. In the setting after up-front ARPI, sequential therapy with DOC may be more appropriate than sequential therapy with ARPI.

Early Clinical Efficacy of Small Incision Reduction and Superior Closed Pin Fixation of Goss-Ideberg Type III Glenoid Fractures using X-ray and CT Scan.

Imaging techniques such as X-rays and 3D Computed Tomography (CT) are used to diagnose and evaluate a patient's shoulder before and after surgery. Identifying the kind, location, and severity of a shoulder fracture helps surgeons choose the right treatment and surgery. The study examines the effectiveness of small incision reduction and superior closure pinning in treating Ideberg type III glenoid fractures identified by X-ray and CT scans. From October 2017 to June 2022, 40 patients with Ideberg type III glenoid fractures underwent mini-incision reduction and superior closed pinning fixation using the Anterior (AA) and Posterior (PA) approaches. Pre- and post-surgery shoulder scores and imaging data were analyzed. Outpatient review and shoulder anteroposterior radiographs were collected at 1, 3, 6, and 12 months after surgery. We assessed shoulder joint function using the American Shoulder and Elbow Society (ASES) shoulder score, VAS score, Constant-Murley Shoulder Outcome (Constant) score, and DASH score. A total of 40 patients were monitored for 14-16 months, averaging 15.2 ± 0.3 months. All fractures were healed between 14-25 weeks from X-rays, averaging 17.6 ± 5.4 weeks. Both the AA and PA groups had similar shoulder score changes. However, the AA group did better. In all cases, ASES shoulder scores were outstanding at 80%. Radiographs demonstratedno traumatic arthritis or internal fixation failure consequences like screw loosening or breakage. It was concluded that Ideberg type III glenoid fracture reduction with an anterior small incision and superior closed pinning hollow lag screw internal fixation could be successful.

Povišena srednja zapremina eritrocita u anemiji srpastih ćelija - jedna priča, previše?

Abstract: Introduction: Sickle cell disease is a hereditary blood disorder characterized by defective hemoglobin. Red cell indices are proposed as potential tools for diagnosing and managing sickle cell disorders. Materials and Methods: This study aimed to assess the utility of red cell indices as screening tools for sickle cell anemia. One hundred consenting adults of both sexes participated. Haematological parameters, including packed cell volume, hemoglobin values, hemoglobin electrphoretic patterns, and red blood cell count, were examined. Mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), and mean cell hemoglobin (MCH) were calculated. Data analysis was performed using GraphPad Prism Software Version 9, with statistical significance set at p &lt; 0.05 (95% confidence interval). Results: Haemoglobin values were significantly lower in Hb SS subjects (5.68 ± 1.7g/dl) compared to Hb AA (11.30 ± 1.5 g/dl) and Hb AS groups (11.03 ± 1.4 g/dl) (F = 32.279; p &lt; 0.00001). The pattern was consistent with PCV and RBC values. Among the red blood cell indices assessed, only MCV showed a significant elevation (95.7 ± 2.4 fl) in the HbSS group compared to other groups (F = 4.165; p = 0.0183). No statistically significant difference was observed in MCHC and MCH values between the three groups (F = 0.5373, p &gt; 0.586 for MCHC; F = 0.607, p &gt; 0.546 for MCH). The prevalence of haemoglobin variants was as follows: HbAA (77%), HbAS (19%), and HbSS (4%). Conclusion: This study highlights significant reductions in haemoglobin values in Hb SS subjects and a notable elevation in MCV values in the Hb SS blood group. Elevated MCV in sickle cell anemia, where red cells are typically microcytic, warrants further investigation for differential diagnosis.

Tooth morphology, internal fit, occlusion and proximal contacts of dental crowns designed by deep learning-based dental software: A comparative study

ObjectivesThis study compared the tooth morphology, internal fit, occlusion, and proximal contacts of dental crowns automatically generated via two deep learning (DL)-based dental software systems with those manually designed by an experienced dental technician using conventional software. MethodsThirty partial arch scans of prepared posterior teeth were used. The crowns were designed using two DL-based methods (AA and AD) and a technician-based method (NC). The crown design outcomes were three-dimensionally compared, focusing on tooth morphology, internal fit, occlusion, and proximal contacts, by calculating the geometric relationship. Statistical analysis utilized the independent t-test, Mann–Whitney test, one-way ANOVA, and Kruskal–Wallis test with post hoc pairwise comparisons (α = 0.05). ResultsThe AA and AD groups, with the NC group as a reference, exhibited no significant tooth morphology discrepancies across entire external or occlusal surfaces. The AD group exhibited higher root mean square and positive average values on the axial surface (P < .05). The AD and NC groups exhibited a better internal fit than the AA group (P < .001). The cusp angles were similar across all groups (P = .065). The NC group yielded more occlusal contact points than the AD group (P = .006). Occlusal and proximal contact intensities varied among the groups (both P < .001). ConclusionsCrowns designed by using both DL-based software programs exhibited similar morphologies on the occlusal and axial surfaces; however, they differed in internal fit, occlusion, and proximal contacts. Their overall performance was clinically comparable to that of the technician-based method in terms of the internal fit and number of occlusal contact points. Clinical significanceDL-based dental software for crown design can streamline the digital workflow in restorative dentistry, ensuring clinically-acceptable outcomes on tooth morphology, internal fit, occlusion, and proximal contacts. It can minimize the necessity of additional design optimization by dental technician.

A comparative urinary proteomic and metabolomic analysis between renal aa amyloidosis and membranous nephropathy with clinicopathologic correlations

Urinary omics has become a powerful tool for elucidating pathophysiology of glomerular diseases. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urine proteomic and metabolomic analysis between recently diagnosed renal AA amyloidosis (AA) and membranous nephropathy (MN) patients. Urine samples of 22 (8 AA, 8 MN and 6 healthy control) patients were analyzed with nLC-MS/MS and GC/MS for proteomic and metabolomic studies, respectively. Pathological specimens were scored for glomerulosclerosis and tubulointerstitial fibrosis grades. Functional enrichment analysis between AA and control groups showed enrichment in cell adhesion related sub-domains. Uromodulin (UMOD) was lower, whereas ribonuclease 1 (RNase1) and α-1-microglobulin/bikunin precursor (AMBP) were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = −0.48, p = 0.03) and AMBP-eGFR (r = −0.69, p = 0.003) variables. Metabolomic analysis showed myo-inositol and urate were higher in AA compared to MN group. A positive correlation was detected between RNase1 and urate independent of eGFR values (r = 0.63, p = 0.01). Enrichment in cell adhesion related domains suggested a possible increased urinary shear stress due to amyloid fibrils. UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be related with systemic inflammation in AA amyloidosis. SignificanceUrinary omics studies have become a standard tool for biomarker studies. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urinary omics analysis between recently diagnosed renal AA amyloidosis (AA), membranous nephropathy (MN) patients and healthy controls. Pathological specimens were scored with glomerulosclerosis (G) and tubulointerstitial fibrosis (IF) grades to consolidate the results of the omics studies and correlation analyzes. Functional enrichment analysis showed enrichment in cell adhesion related sub-domains due to downregulation of cadherins; which could be related with increased urinary shear stress due to amyloid deposition and disruption of tissue micro-architecture. In comparative proteomic analyzes UMOD was lower, whereas RNase1 and AMBP were higher in AA compared to MN group. Whereas in metabolomic analyzes; myo-inositol, urate and maltose were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = −0.48, p = 0.03), AMBP-eGFR (r = −0.69, p = 0.003) and between RNase1-Urate independent of eGFR values (r = 0.63, p = 0.01). This study is the first comprehensive urinary omics analysis focusing on renal AA Amyloidosis to the best of our knowledge. Based on physiologic roles and clinicopathologic correlations of the molecules; UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be increased with systemic inflammation and endothelial damage in AA amyloidosis.

Donor Hemoglobin Genotype Does Not Impact Outcomes Following Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease: A STAR Study

Sickle cell disease (SCD) is an inherited hemoglobin (Hb) disorder which leads to significant morbidity and early mortality. Hematopoietic cell transplantation (HCT) is the only curative treatment with long-term outcome data, demonstrating excellent symptom-free survival particularly when a matched related donor (MRD) is available. Most MRD have sickle cell trait (Hb AS), but trait donor HCT is considered acceptable by the FDA and without negative impact. Further, initial gene addition and editing approaches for SCD have resulted in a trait-like status with benefit. Sickle trait, however, is associated with complications such as papillary necrosis, bacteriuria, splenic infarction, and exercise-induced death. The primary aim of this study was to compare long-term outcomes following MRD HCT for SCD based on donor Hb genotype, to objectively describe any impact on outcomes. Retrospective data was available for this analysis on 182 SCD patients ≥1 year post MRD HCT at 10 participating Sickle Transplant Advocacy and Research (STAR) Alliance centers. Summary statistics were presented as mean (standard deviation) for continuous variables and count (%) for categorical variables. Comparisons were made between Hb AA and Hb AS donor groups using both parametric and non-parametric tests for continuous variables and Chi-square test/exact test for categorical variables, with p-value &amp;lt;0.05 set as significant. Amongst 182 patients undergoing MRD HCT, 67% (n=122) had a Hb AS donor ( Table). In the overall cohort, median age at HCT was 8.7 (4.8) years and most patients had HbSS (n=174; 96%) with a severe clinical phenotype (n=97; 54%). HCT was performed using bone marrow (n=166; 92%) with myeloablative conditioning (n=156; 86%) in the majority. Patients with a severe disease phenotype and Hb AS donor were significantly more likely to have recurrent vaso-occlusive pain crises as an indication for HCT (p=0.033), otherwise there were no differences in baseline patient or HCT characteristics between cohorts. With mean post-HCT follow up of 4.5 (3.9) and 5.1 (4.1) years in Hb AA and Hb AS donor cohorts (p=0.145), no significant differences were seen in recipient outcomes including time to neutrophil and platelet engraftment, number of or time to last platelet transfusion, myeloid or unsorted % donor chimerism, number with acute (day 100) or chronic GVHD (1 year), or time to discontinue immunosuppression (data not shown). Disease recurrence and need for 2 nd HCT were rare in both cohorts (AA: 2 [3%] and 2 [3%]; AS: 3 [3%] and 4 [3%]; p=0.665 and 1.0, respectively). Two (3%) and 5 (4%) patients died in the AA and AS cohorts, respectively (p=1.0). Aside from a statistically (but not clinically) significant difference in Hb at day 30 (p=0.044), no difference was seen in longitudinal Hb or markers of hemolysis (LDH and ARC; Figure). No significant difference was seen in median number of RBC units transfused (AA: 4.0 [2.0-6.0]; AS: 3.0 [2.0-6.0]; p=0.454) or days to last transfusion (AA: 23.0 [14.0-77.0]; AS: 22.0 [13.0-75.0]; p=0.86). SCD complications were rare post-HCT, with no difference seen between cohorts in number (%) with VOC (AA: 1 [2%; had 2 separate VOC events]; AS: 3 [3%]; p=1.0), ACS (none reported), chronic pain (AA: 0 [0%]; AS: 1 [&amp;lt;1%]; p=1.0), or other SCD-related complications (AA: 2 [3%]; AS: 9 [7%; had 11 separate other events]; p=0.456). Stroke occurred in a significantly higher proportion with an AA versus AS donor (5 [8%] and 2 [2%], respectively; p=0.04). No significant differences were seen in longitudinal (1 and 2 years and at last follow up) post-HCT cardiac (EF, SF, TRJ velocity), pulmonary (FEV1, FVC, DLCO), or renal (GFR) function between cohorts (data not shown). Our results indicate that in MRD HCT for SCD, AS and AA donors yield comparable long-term outcomes. In this retrospective and registry-based study design, detailed analyses did not show differences between the two cohorts at baseline or at any timepoint post-HCT. While there were some outcome differences between the cohorts, they were either not clinically significant or did not have a scientific rationale, and thus were likely due to chance alone (denoted by bolding in Table). Given the young age of our cohort at HCT and thus a smaller proportion with SCD-related organ dysfunction, our results may not be applicable to an older cohort with significant organ dysfunction which will require a separate analysis.

313 Effect of Dietary Trace Mineral Source on Performance, Bones Mineralization and Mineral Status in Fattening Pigs

Abstract Several papers report greater bioavailability of dietary trace mineral fed as organic in pigs compared with inorganic sources. However, only a few studies have tried to assess the variability of the trace mineral bioavailability among different organic sources. Growing barrows (n = 54; initial BW = 28.9 ± 1.3 kg) were used to determine the effects of trace mineral source on growth performance, bones mineralization and mineral status over the entire fattening period (d0-d73). Pigs were blocked by BW and randomly assigned to supplementation of trace minerals as inorganic (ITM) or one of 2 organic sources (OTM): glycine complex (GLY) or amino acids complex (AA). During the two feeding phases (growing: d0-d35; finishing: d35-d73), the experimental diets were supplemented with 5, 35 and 5 mg/kg of Cu, Zn and Mn, respectively. Pigs were fed restricted all through the experimental period. Feed intake was therefore comparable all through the experimental period for all pigs. Growth performance did not differ among the three experimental groups during the growing phase. However, Feed:Gain ratio measured during the finishing period tended to be affected by the dietary treatments (P=0.10). When grouping the GLY and AA pigs, the Feed:Gain ratio measured from d35 to d73 for the OTM pigs was significantly lower compared with ITM pigs (-0.07, P = 0.03). There was no significant effect of the dietary treatment on plasma trace mineral concentrations and alkaline phosphatase activity measured at day 34. At the end of the growing phase, plasma ceruloplasmin activity tended to be greater for the GLY and AA groups in comparison with the ITM pigs (+6.9%, P = 0.06). The zinc deposition in the proximal phalanx was significantly increased when the trace minerals were offered as organic compared with the group ITM (+10.9%, P = 0.06). Zinc content in the liver was greater for the pigs fed the OTM sources compared with the others (+6.0%, P = 0.10). The quantity of copper deposited in the liver did not differ significantly among the 3 trace mineral sources. This study indicates that the total replacement of inorganic Zn, Cu and Mn by organic sources brings benefits in terms of feed efficiency in fattening pigs. A better bioavailability as suggested by greater deposition levels in bone and liver as well as the increased circulating ceruloplasmin activity could explain the improvement of performance during the finishing period. Regardless of the variable considered, no significant differences were noticed between the two organic trace mineral sources.

Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Utility of Noninvasive Scores in Patients With Acromegaly.

Nonalcoholic fatty liver disease (NAFLD) is a metabolical disorder and can lead to liver fibrosis. Because it is commonly seen, several noninvasive scores (NS) have been validated to identify high-risk patients. Patients with NAFLD have been shown to have higher serum angiopoietin-like protein-8 (ANGPTL-8) levels. The risk of NAFLD is known insufficiently in acromegaly. Moreover, the utility of the NS and the link between NAFLD and ANGPTL-8 in acromegaly is unknown. Thirty-two patients with acromegaly (n = 15, active [AA] and n = 17, controlled acromegaly [CA]) and 19 healthy controls were included. Magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) was used to evaluate hepatic steatosis, and magnetic resonance elastography to evaluate liver stiffness measurement. ANGPTL-8 levels were measured with ELISA. Median liver MRI-PDFF and NAFLD prevalence in AA were lower than in CA (P = .026 and P < .001, respectively). Median magnetic resonance elastography-liver stiffness measurement were similar across groups. Of the NS, visceral adiposity index, fatty liver index, hepatic steatosis index, and triglyceride-glucose index (TyG) all showed positive correlation with the liver MRI-PDFF in the control group. However, only TyG significantly correlated with liver fat in the AA and CA groups. There was no correlation between traditional NAFLD risk factors (body mass index, waist circumference, C-reactive protein, homeostasis model assessment for insulin resistance, visceral adipose tissue) and liver MRI-PDFF in the AA and CA. Patients with acromegaly with NAFLD had lower GH, IGF-1, and ANGPTL-8 levels than in those without NAFLD (P = .025, P = .011, and P = .036, respectively). Active acromegaly may protect from NAFLD because of high GH. In patients with acromegaly, NAFLD risk cannot be explained with classical risk factors; hence, additional risk factors must be identified. TyG is the best score to evaluate NAFLD risk. Lower ANGPTL-8 in patients with acromegaly and NAFLD implies this hormone may be raised because of insulin resistance rather than being a cause for NAFLD.

Effectiveness of vocal fold medialization surgery on the swallowing function of patients with unilateral vocal fold paralysis.

Vocal fold medialization surgery is generally considered a phonosurgical procedure for improvement of vocal function in patients with glottic insufficiency. However, the literature describing this procedure for the management of dysphagia is limited. This study aims to assess the effects of medialization surgery on swallowing function in patients with unilateral vocal fold paralysis (UVFP). We enrolled 32 patients with UVFP undergoing vocal fold medialization surgery (medialization laryngoplasty combined with arytenoid adduction [ML + AA], 12 cases; injection laryngoplasty [IL], 20 cases). We assessed the aerodynamic vocal function including maximum phonation time and mean flow rate to evaluate glottal closure status. The Hyodo score determined by flexible endoscopic evaluation and Functional Oral Intake Scale (FOIS) were evaluated pre- and postoperatively. Almost 60% of patients with UVFP had dysphagia, and one-third were at high risk for aspiration. Aerodynamic parameters effectively improved after IL and ML + AA. With regard to swallowing, both the FOIS and total Hyodo score were significantly improved postoperatively. We found a particularly significant improvement in pharyngeal clearance. However, patients with high vagal nerve paralysis and postoperative insufficient glottal closure showed poor swallowing benefits after the interventions. In patients with recurrent laryngeal nerve palsy, there were no significant differences in postoperative swallowing function between the ML + AA and IL groups. Vocal fold medialization surgery was effective in improving swallowing function in most cases with UVFP, except for those with high vagal paralysis and insufficient postoperative glottal closure. Both IL and ML + AA showed an equivalent effect on swallowing improvement. 3b.

Inequities in Patient Access to Care Among Asian American, Native Hawaiian, and Pacific Islander Adults in Medicaid.

Despite decades of advocacy for disaggregated data collection and reporting for Asian American, Native Hawaiian, and Pacific Islander (AA and NHPI) people, significant gaps remain in our ability to understand AA and NHPI individuals' access to care. We assess inequities in access to care measures between non-Hispanic White and AA and NHPI adult Medicaid enrollees. We used the 2014-15 Nationwide Adult Medicaid Consumer Assessment of Healthcare Providers and Systems, the first-and-only nationally representative sample of Medicaid enrollees. Our main outcomes were access to needed care, access to a personal doctor, timely access to a checkup, and timely access to specialty care. Using multivariable linear probability models, we assessed the relationship between racial/ethnic group and our outcomes, both in the aggregate and disaggregated into ten racial/ethnic groups, and adjusted for enrollee-level sociodemographic characteristics, health status, and state-level Medicaid expansion status. In aggregate, AA and NHPI enrollees reported worse access to care than White enrollees on all four metrics (p < 0.001). The magnitude of disparities varied across the ten AA and NHPI ethnic groups. Disparities relative to White enrollees were particularly large in magnitude, roughly 1.5 to 2 times greater, for Chinese, Korean, and Vietnamese enrollees than for the aggregated AA and NHPI group. Despite comparable insurance coverage, there were inequities in multiple access to care metrics between non-Hispanic White and AA and NHPI Medicaid enrollees. Collection of disaggregated health data on AA and NHPI patients reveals important variation in access to care by ethnic group.

#4952 CLINICOPATHOLOGIC CORRELATIONS OF URINARY PROTEOMIC AND METABOLOMIC ANALYSIS IN PATIENTS WITH RENAL AA AMYLOIDOSIS AND MEMBRANOUS NEPHROPATHY

Abstract Background and Aims AA Amyloidosis is a multisystemic amyloidosis subtype that develops on the background of various chronic inflammatory etiologies. Urinary omics studies have become a promising tool for elucidating pathophysiology and prognosis of glomerular diseases. However, no urinary omics analysis has been performed focusing on renal AA amyloidosis in literature to the best of our knowledge. Our main aim in this study is to perform a comparative urine proteomic and metabolomic analysis of recently diagnosed renal AA amyloidosis and to investigate the correlation of bioinformatic results with clinical and pathological data. Method Urine samples of 8 recently diagnosed AA amyloidosis (AA), 8 membranous nephropathy (MN) and 6 healthy control group patients were collected before kidney biopsy procedure. Proteomic analyzes were performed with nLC/Q-TOF MS/MS and metabolomic analyzes were performed by GC/MS in all patients. Biopsy specimens were scored according to glomerulosclerosis (G), tubular atrophy (TA) and interstitial fibrosis (IF) grades by two pathologists. Raw spectroscopic data was analyzed using MaxQuant and MS-DIAL programs for proteomic and metabolomic studies, respectively. Statistical analysis of the differences in molecules between study groups were performed with ANOVA and HSD-Tukey tests. Principal component (PCA) and heatmap analyzes were made in R language, while gene ontology (GO), network and functional enrichment analysis of bioinformatic results were performed with PANTHER, STRING and MetaboAnalyst databases. Results In comparison between AA and MN groups, median eGFR values tend to be lower in the AA group (67.6 vs 112 ml/min/1.73 m2 respectively, p = 0.08). Median 24-hour urine protein levels did not show statistically significant difference (9499 vs 9512 mg/day respectively, p = 0.9). Percentage of patients with moderate/severe IF/TA was higher and G score was tend to be in AA group compared to MN group (p values 0.02 and 0.07 for IF/TA and G scores, respectively). As a result of proteomic analysis, a total of 859 proteins were determined. Statistical analysis showed 51 proteins that were significantly differ in AA group compared to the control group. GO and functional enrichment analyzes showed that statistically most significant sub-domains were mainly related with cell-cell adhesion (Figure 1 &amp; 2). In comparative analysis between AA and MN patients, uromodulin (UMOD) was lower in the AA group than in the MN group (log2FC -3.37), whereas ribonuclease 1 (RNASE1) and α-1-microglobulin/bikunin precursor protein (AMBP) were higher in the AA group (log2FC 3.41 and 3.07, respectively). In Spearman correlation analyzes, significant negative correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03) and between AMBP-eGFR (r = -0.69, p = 0.003) variables. Metabolomic analysis showed 9 metabolites that were significantly different between AA and other study groups. Myo-inositol and urate were higher in AA group compared to MN group, while D-mannitol and N-acetylglutamate were higher in AA group compared to the control group. Significant positive correlation independent of GFR was detected between RNASE1 and urate (r = 0.63, p = 0.01). Conclusion Our study is the first urinary comparative omics analysis performed on renal AA amyloidosis patients to the best of our knowledge. We demonstrated specific protein and metabolites that distinguish AA group from the control and MN groups. Enrichment and GO analyzes between AA and the control group showed a negative enrichment in cell-cell adhesion related sub-domains, suggesting a possible increased urinary shear stress resulting in downregulation of cadherins in AA amyloidosis. In comparative analysis between AA and MN groups, UMOD and AMBP proteins and myo-inositol were thought to be associated with high tubulointerstitial damage, whereas RNASE1 and urate were believed to be related with systemic inflammation and endothelial damage [1].