Genomic Insights into Edwardsiella ictaluri: Molecular Epidemiology and Antimicrobial Resistance in Striped Catfish (Pangasianodon hypophthalmus) Aquaculture in Vietnam.

Edwardsiella ictaluri is responsible for causing bacillary necrosis (BNP) in striped catfish (Pangasianodon hypophthalmus) in Vietnam. This study offers a comprehensive genomic characterization of E. ictaluri to enhance understanding of the molecular epidemiology, virulence, and antimicrobial resistance. E. ictaluri isolates were collected from diseased striped catfish in the Mekong Delta. The species was confirmed through PCR. Antimicrobial susceptibility testing was conducted using minimum inhibitory concentrations for commonly used antimicrobials. Thirty representative isolates were selected for whole genome sequencing to delineate their genomic profiles and phylogeny. All strains belonged to ST-26 and exhibited genetic relatedness, differing by a maximum of 90 single nucleotide polymorphisms. Most isolates carried multiple antimicrobial resistance genes, with the tet(A) gene present in 63% and floR in 77% of the genomes. The ESBL gene, blaCTX-M-15, was identified in 30% of the genomes. Three plasmid replicon types were identified: IncA, p0111, and IncQ1. The genomes clustered into two clades based on their virulence gene profile, one group with the T3SS genes and one without. The genetic similarity among Vietnamese isolates suggests that disease spread occurs within the Mekong region, underscoring the importance of source tracking, reservoir identification, and implementation of necessary biosecurity measures to mitigate spread of BNP.

Comparative genomic analysis of Aeromonas dhakensis and Aeromonas hydrophila from diseased striped catfish fingerlings cultured in Vietnam.

Introduction: Motile Aeromonas septicemia (MAS) is a burden for striped catfish (Pangasius hypophthalmus) farmers in Vietnam. MAS can be caused by several species of Aeromonas but Aeromonas hydrophila is seen as the leading cause of MAS in aquaculture, but recent reports suggest that A. dhakensis is also causing MAS. Methods: Here we investigated the bacterial etiology of MAS and compared the genomic features of A. hydrophila and A. dhakensis. We collected 86 isolates from diseased striped catfish fingerlings over 5 years from eight provinces in Vietnam. Species identification was done using PCR, MALDI-TOF and whole genome sequence (WGS). The MICs of commonly used antimicrobials was established. Thirty presumed A. hydrophila isolates were sequenced for species confirmation and genomic comparison. A phylogenetic analysis was conducted using publicly available sequences and sequences from this study. Results: A total of 25/30 isolates were A. dhakensis sequence type (ST) 656 and 5/30 isolates were A. hydrophila ST 251. Our isolates and all publicly available A. hydrophila isolates from Vietnam belonged to ST 251 and differed with <200 single nucleotide polymorphisms (SNP). Similarly, all A. dhakensis isolates from Vietnam belonged to ST 656 and differed with <100 SNPs. The tet(A) gene was found in 1/5 A. hydrophila and 19/25 A. dhakensis. All A. hydrophila had an MIC ≤2 mg/L while 19/25 A. dhakensis had MIC ≥8 mg/L for oxytetracycline. The floR gene was only found in A. dhakensis (14/25) which showed a MIC ≥8 mg/L for florfenicol. Key virulence genes, i.e., aerA/act, ahh1 and hlyA were present in all genomes, while ast was only present in A. dhakensis. Discussion: This study confirms previous findings where A. dhakensis was the dominating pathogen causing MAS and that the importance of A. hydrophila has likely been overestimated. The differences in antimicrobial susceptibility between the two species could indicate a need for targeted antimicrobial treatment plans. The lipopolysaccharide regions and outer membrane proteins did not significantly differ in their immunogenic potentials, but it remains to be determined with in vivo experiments whether there is a difference in the efficacy of available vaccines against A. hydrophila and A. dhakensis.

Efficient symptomatic treatment and viral load reduction for children with influenza virus infection by nasal-spraying Bacillus spore probiotics.

Influenza virus is a main cause of acute respiratory tract infections (ARTIs) in children. This is the first double-blind, randomized, and controlled clinical trial examining the efficacy of nasal-spraying probiotic LiveSpo Navax, which contains 5 billion of Bacillus subtilis and B. clausii spores in 5 mL, in supporting treatment of influenza viral infection in pediatric patients. We found that the nasal-spraying Bacillus spores significantly shortened the recovery period and overall treatment by 2 days and increased treatment effectiveness by 58% in resolving all ARTIs' symptoms. At day 2, the concentrations of influenza virus and co-infected bacteria were reduced by 417 and 1152 folds. Additionally, the levels of pro-inflammatory cytokines IL-8, TNF-α, and IL-6 in nasopharyngeal samples were reduced by 1.1, 3.7, and 53.9 folds, respectively. Compared to the standard control group, treatment regimen with LiveSpo Navax demonstrated significantly greater effectiveness, resulting in 26-fold reduction in viral load, 65-fold reduction in bacterial concentration, and 1.1-9.5-fold decrease in cytokine levels. Overall, nasal-spraying Bacillus spores can support the symptomatic treatment of influenza virus-induced ARTIs quickly, efficiently and could be used as a cost-effective supportive treatment for respiratory viral infection in general.Clinical trial registration no: NCT05378022 on 17/05/2022.

Using intersectionality to study gender and antimicrobial resistance in low- and middle-income countries.

Different sexes and genders experience differentiated risks of acquiring infections, including drug-resistant infections, and of becoming ill. Different genders also have different health-seeking behaviours that shape their likelihood of having access to and appropriately using and administering antimicrobials. Consequently, they are distinctly affected by antimicrobial resistance (AMR). As such, it is crucial to incorporate perspectives on sex and gender in the study of both AMR and antimicrobial use in order to present a full picture of AMR's drivers and impact. An intersectional approach to understanding gender and AMR can display how gender and other components 'intersect' to shape the experiences of individuals and groups affected by AMR. However, there are insufficient data on the burden of AMR disaggregated by gender and other socio-economic characteristics, and where available, it is fragmented. For example, to date, the best estimate of the global burden of bacterial AMR published in The Lancet does not consider gender or other social stratifiers in its analysis. To address this evidence gap, we undertook a scoping review to examine how sex and gender compounded by other axes of marginalization influence one's vulnerability and exposure to AMR as well as one's access to and use of antimicrobials. We undertook a gendered analysis of AMR, using intersectionality as a concept to help us understand the multiple and overlapping ways in which different people experience exposure vulnerability to AMR. This approach is crucial in informing a more nuanced view of the burden and drivers of AMR. The intersectional gender lens should be taken into account in AMR surveillance, antimicrobial stewardship, infection prevention and control and public and professional awareness efforts, both donor and government funded, as well as national and international policies and programmes tackling AMR such as through national action plans.

Internal controls driven by mindfulness toward enhanced ethical behaviors: Empirical evidence from Vietnam.

This study develops and tests a moderated mediation model regarding the effectiveness of internal control structure on organizational ethical behaviors via the mediating role of internal control effectiveness and the moderating role of organizational mindfulness in the relationship between internal control structure and internal control effectiveness. The proposed model and its hypotheses were tested using partial least squares structural equation modeling (PLS-SEM) in SmartPLS3 with survey data from 540 large Vietnamese manufacturing and service firms. This study found the following: (1) The internal control structure positively affects internal control effectiveness, which in turn promotes ethical organizational behaviors; and (2) The effect of internal control structure on internal control effectiveness is amplified by strengthening organizational mindfulness. The findings demonstrate that combining internal control systems and organizational mindfulness contributes to the ethical business practices of firms in an emerging market. Our study bridges the gap in the literature on internal control and mindfulness by providing empirical evidence on how the interaction between organizational mindfulness and internal control systems can promote ethical business practices. Additionally, our study advances the current understanding of how internal control systems can interact with organizational mindfulness to influence ethical business practices in the context of an emerging market.

Stromal Tumor-Infiltrating Lymphocytes Associated with Immunohistopathology and Molecular Subtypes of Breast Cancer in Vietnam.

OBJECTIVE: Breast cancer is a heterogeneous disease with varied symptoms and pathogenesis, as well as variable prognosis and therapeutic outcomes. Stromal tumor-infiltrating lymphocytes, one of the tumor microenvironment factors, has been recognized as an important immunological biomarker that reflected the antitumor immune response in breast cancer. METHODS: We analyzed 207 invasive breast cancer patients who had lumpectomy or mastectomy and have not received any pre-operative treatment. Clinicopathological characteristics, immunohistochemistry characteristics, molecular subtypes classification and stromal TILs evaluation were investigated. RESULT: Stromal TILs correlated with well-established prognostic markers. Tumor grade showed significantly higher sTILs percentages in high-grade tumors than in low-grade tumors (p<0.001). There was a statistically significant association between intermediate and high levels of sTILs and a high Ki-67 index (p< 0.001). ER/PR negative was significantly related to high sTILs. Mean sTILs score was significantly higher in TNBC (40.1±31.6%) compared to others, statistically significant (p<0.001). In HER2-negative breast cancer, sTILs were significantly associated with histologic grade, ER status, PR status, and Ki67 index. CONCLUSION: sTILs played an important role, associated with unfavorable factors in breast cancer. Our findings support the use of stromal sTILs to identify a more aggressive phenotype of tumors.

Advancement of cloud-based accounting effectiveness, decision-making quality, and firm performance through digital transformation and digital leadership: Empirical evidence from Vietnam.

The accounting literature is silent about how digital transformation can be transformed into outstanding business performance through cloud-based accounting effectiveness (CBAE) under the supervision of digital leaders. In the digital age, this mechanism is practically significant for emerging market firms to promote accounting practices and decision-making effectiveness. Thus, this study investigates how CBAE and decision-making quality (DMQ) mediate the impact of digital transformation on firm performance. In addition, the moderating effects of digital leadership on the relationships between digital transformation and CBAE and those between CBAE and DMQ are investigated. The proposed model and its hypotheses are evaluated using partial least squares structural equation modeling (PLS-SEM) on survey data from 252 large-sized Vietnamese firms. The study's findings are as follows: (1) digital transformation positively affects CBAE, which affects DMQ and firm performance; (2) when digital leadership is strong, the effects of digital transformation on CBAE and CBAE on DMQ are amplified. These findings demonstrate how the interaction between digital transformation and digital leadership can contribute to the success of firms in emerging markets that use cloud accounting. In addition, the current study elucidates the mechanism by which digital transformation influences the digitalization of accounting practices and contributes to our understanding of digital transformation research in accounting by introducing digital leadership as a boundary condition.

Preventing medication history errors in high-risk patients: Impact of California Senate Bill 1254.

PURPOSE: California Senate Bill (SB) 1254 (effective January 1, 2019) requires pharmacy staff at acute hospitals with more than 100 beds to obtain a medication profile for high-risk patients upon hospital admission. This multicenter study sought to evaluate the statewide impact of California SB 1254 by capturing the errors intercepted and harm prevented as a result of the passage of the bill. METHODS: This was a multicenter, prospective, observational study conducted at 11 hospitals in California for 6 consecutive weeks between January 2020 and March 2020. Participating sites captured medication history errors identified among high-risk patients using organization-specific criteria. Errors were categorized by type and ranked for severity of potential or actual harm based on the modified National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) categories. RESULTS: Study sites had an average daily census of 180 to 800 patients. Approximately 94% (n = 2,554) of medication histories conducted disclosed at least 1 error. Approximately 54% (n = 1,474) of histories disclosed at least 1 serious or potentially life-threatening error. Approximately 6 errors were identified and prevented per patient (95% CI, 5.62-6.01 errors per patient), and 1 in 4 errors (25%) was categorized as potentially serious or life-threatening. CONCLUSION: Among high-risk patients, pharmacy-led medication histories significantly reduced medication errors. If not intercepted, these errors would have likely resulted in substantial morbidity and mortality. Future research should evaluate opportunities to standardize high-risk criteria to support patient prioritization and allocation of resources.

A Multicenter Study of Clinicopathology and Immunohistochemical Distinction between Adult and Pediatric Large B-Cell Lymphoma.

Introduction: Pediatric DLBCL is considered a homogenous group and has superior outcomes compared to adults. This study investigated the clinical pathology and immunohistochemical distinction between adult and pediatric large B-cell lymphoma. Methods: A cross-sectional study of 314 NHLs with the morphology of diffuse pattern, large B-cell, and CD20 expression was investigated. Results: Of 314 cases, there were 6 cases of pleomorphic MCL (all in adults), 19 cases of Burkitt lymphoma (all in children), and 289 cases of DLBCL. Pediatric DLBCL had many striking differences: More frequency in extra-nodal sites; a higher proportion of centroblastic morphology; a predominance of GCB-type; a high proliferation rate; an infrequency of Bcl2 protein expression, and a lack of double-expresser lymphoma. Conclusions: Our study demonstrated the significant biological differences between adult and pediatric DLBCL.

Nasal-spraying Bacillus spores as an effective symptomatic treatment for children with acute respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is a leading cause of Acute Respiratory Tract Infections (ARTIs) in young children. However, there is currently no vaccine or treatment available for children. Here, we demonstrated that nasal-spraying probiotics containing 5 billion of Bacillus spores (LiveSpo Navax) is an effective symptomatic treatment in a 6-day randomized controlled clinical study for RSV-infected children (n = 40-46/group). Navax treatment resulted in 1-day faster recovery-time and 10-50% better efficacy in relieving ARTI symptoms. At day 3, RSV load and level of pro-inflammatory cytokines in nasopharyngeal samples was reduced by 630 folds and 2.7-12.7 folds respectively. This showed 53-fold and 1.8-3.6-fold more effective than those in the control-standard of care-group. In summary, nasal-spraying Bacillus spores can rapidly and effectively relieve symptoms of RSV-induced ARTIs while exhibit strong impacts in reducing viral load and inflammation. Our nasal-spraying probiotics may provide a basis for simple-to-use, low-cost, and effective treatment against viral infection in general.

The impact of internal control systems on the intensity of innovation and organizational performance of public sector organizations in Vietnam: the moderating role of transformational leadership.

Drawing on the resource-based view, new public management theory, and innovation systems theory, this study examines the relationships between internal control systems (ICSs) and organizational performance in Vietnamese public sector organizations (PSOs), with particular emphasis on the mediating role of intensity of innovation and the moderating role of transformational leadership. Data from 319 PSOs in Vietnam corroborated our hypothesis that ICSs boost the intensity of innovation, which has a beneficial effect on organizational performance. Additionally, data demonstrated that intensity of innovation fully mediated the relationships between ICSs and organizational performance, and that transformational leadership reinforced the mediating relationships. The findings have implications for our understanding of the function of leadership and ICSs in managing innovation and promoting performance in PSOs in emerging markets.

Gabapentinoid Dosing and Associated Toxicities in Patients With or Without Concomitant Opioids During Hospitalization.

Gabapentinoid drugs (gabapentin and pregabalin) are increasingly used for pain as both patients and physicians seek opioid-sparing or opioid-reducing strategies. Such widespread use for off-label pain indications is not supported by robust evidence, risking potential unintended consequences relating to adverse events. This study evaluated adult patients who were administered at least one dose of a gabapentinoid during a hospital admission between January 1, 2018 and December 31, 2018. The primary objective was to compare the difference in administered gabapentinoid total daily dose in patients with or without concomitant opioid. Secondary objectives included comparing the difference in sedation documentation, renal function, fall risk scores using the Hester Davis Fall Risk Scale, and central nervous system (CNS) related side effects between the 2 study groups. Four hundred and ninety nine patients (pregabalin n = 32 and gabapentin n = 467) were included. Due to small sample size for pregabalin, outcome results were presented for gabapentin only. The mean gabapentin total daily dose was 706 mg (SD = 614 mg) in the non-opioid group versus 860 mg (SD = 553 mg) in the opioid group (p = 0.007). There was more sedation documentation observed in the opioid group (p < 0.001). Patients in the opioid group used a significantly higher gabapentinoid total daily dose. Sedation documentation was significantly more in the opioid group despite commonly reported CNS related adverse events with gabapentinoids.

Phytochemical investigation on Vitex negundo leaves and their anti-inflammatory and analgesic activities

Abstract The phytochemical investigation on Vitex negundo leaves has led to the isolation of one new iridoid glucoside (8α-hydroxy-4-carboxyl-5ßH-9ßH-iridoid-1α-O-(6'-O-(6,7-dihydrofoliamenthonyl)-ß-ᴅ-glucopyranoside, 3), together with three known compounds, namely agnuside (1), 6'-O-E-caffeoylmussaenosidic acid (2), and 3,5-dicaffeoylquinic acid (4). The HPLC analytical study was also performed to quantify the content of agnuside (1) in dried leaves. The results indicated the very high content of 1 (3.04 ± 0.02%). The method was also validated by various parameters, including linearity (R2= 0.9999), precision (intra-day RSD ≤ 2.50%, inter-day RSD= 0.76%), and accuracy (recovery rates 96.58-101.86%). The animal testing data showed that the extract did not reduce pain at the doses of 9.6 and 28.8 g /kg (leaf weight/body weight) in the hot plates and pain measuring models but showed the pain reduction in the acetic acid-induced pain model. The extract at the dose of 5.6 g/kg (leaf weight/body weight) also had effects on the acute inflammation in the carrageenin-induced edema model. The extract at the dose 9.6 and 28.8 g/kg (leaf weight/body weight) also showed significant chronic anti-inflammation, comparable to methylprednisolone at the dose 10 mg/kg on the mouse peritoneal

Teachers' and Learners' Beliefs About Pronunciation Instruction in Tertiary English as a Foreign Language Education.

Recent studies have sought to describe and understand English as a second/foreign language (ESL/EFL) teachers' pronunciation teaching practices in different contexts, but much less research has examined how teachers and learners perceive pronunciation instruction at tertiary level, especially in EFL settings. The qualitative study reported in this paper extends this line of research by investigating the beliefs of teachers and learners with regard to pronunciation instruction in tertiary EFL education in Vietnam. Data were collected from individual semi-structured interviews with six EFL teachers and focus group interviews with 24 students (four students per group) at a Vietnamese university. The study adopted a content-based approach to qualitative data analysis. The findings show that both the teachers and students considered pronunciation instruction an important component in tertiary EFL programs, which deserves explicit and systematic delivery. The findings suggest that both groups of participants believed communicative pronunciation teaching to have the potential to improve learners' pronunciation and facilitate their general communicative purposes. The study has implications for language curriculum design and L2 pronunciation teaching and learning.

Smoking Cessation Pharmacotherapy Utilization and Costs to a Medicaid Managed Care Plan.

BACKGROUND: Medicaid coverage for smoking cessation medications has expanded; however, little research has been conducted to evaluate patient-level changes in medication use over time and its associated economic impact on health plans. OBJECTIVE: The aim of this study was to characterize trends in smoking cessation medication utilization between 2006 and 2017 within a Medicaid population and estimate per-member per-month (PMPM) costs to the health plan. METHODS: This study was a retrospective longitudinal analysis conducted among adult members of a Medicaid managed care plan in California. Pharmacy claims data from January 1, 2006 to December 31, 2017 were analyzed to estimate utilization and cost of smoking cessation medications. Additionally, data from 3164 members who filled prescription(s) for cessation medication(s) in 2017 were evaluated to quantify quit attempts and use of combination therapy. For members who had been prescribed bupropion SR, varenicline, or the nicotine patch, the extent to which the durations of therapy were consistent with the manufacturers' recommended minimum duration of therapy were also assessed. RESULTS: The average PMPM expenditures for smoking cessation medications were approximately US$0.15 in 2017, compared with US$0.01-US$0.03 between 2006 and 2013. In 2017, a total of 3164 members initiated an estimated 3850 quit attempts, most commonly using the nicotine patch (57.5%) or varenicline (32.8%). Combination therapy accounted for 2.9% of quit attempts. The median therapy duration for the nicotine patch, varenicline, and bupropion SR was 28, 30, and 33 days, respectively, and for each of these medications, fewer than half of members filled prescriptions for the minimum recommended duration of therapy. CONCLUSIONS: Pharmacy claims data suggest that despite comprehensive coverage, most beneficiaries are underutilizing smoking cessation agents and are not completing the recommended treatment durations.

A study of pathological characteristics and BRAF V600E status in Langerhans cell histiocytosis of Vietnamese children.

BACKGROUND: Langerhans cell histiocytosis (LCH) is more common in children than adults and involves many organs. In children, the BRAF V600E mutation is associated with recurrent and high-risk LCH. METHODS: We collected paraffin blocks of 94 pediatric LCH patients to detect BRAF V600E mutation by sequencing. The relationship between BRAF V600E status and clinicopathological parameters were also critically analyzed. RESULTS: BRAF V600E mutation exon 15 was detected in 45 cases (47.9%). Multiple systems LCH showed a significantly higher BRAF V600E mutation rate than a single system (p=.001). No statistical significance was evident for other clinical characteristics such as age, sex, location, risk organs involvement, and CD1a expression. CONCLUSIONS: In Vietnamese LCH children, the proportion of BRAF V600E mutational status was relatively high and related to multiple systems.

A study of pathological characteristics and BRAF V600E status in Langerhans cell histiocytosis of Vietnamese children

Background@#Langerhans cell histiocytosis (LCH) is more common in children than adults and involves many organs. In children, the BRAF V600E mutation is associated with recurrent and high-risk LCH. @*Methods@#We collected paraffin blocks of 94 pediatric LCH patients to detect BRAF V600E mutation by sequencing. The relationship between BRAF V600E status and clinicopathological parameters were also critically analyzed. @*Results@#BRAF V600E mutation exon 15 was detected in 45 cases (47.9%). Multiple systems LCH showed a significantly higher BRAF V600E mutation rate than a single system (p=.001). No statistical significance was evident for other clinical characteristics such as age, sex, location, risk organs involvement, and CD1a expression. @*Conclusions@#In Vietnamese LCH children, the proportion of BRAF V600E mutational status was relatively high and related to multiple systems.

Ethnopharmacology, Phytochemistry, and Pharmacology of Syzygium nervosum.

Syzygium nervosum, which belongs to the Myrtaceae plant family, is widely distributed and cultivated in South East Asian countries. The decoction of S. nervosum leaves and flower buds has been consumed regularly as a beverage among the Vietnamese and Chinese communities. In addition, it has also been used in traditional medicine for a variety of purposes, notably for influenza, skin diseases, and digestive conditions. To date, there has been a considerable number of publications on chemical profiling and pharmacological activities of S. nervosum crude extract and pure isolated compounds. Our analysis indicated the characteristic chemical scaffolds and potential bioactivities on cancer, diabetes, and inflammatory diseases of this plant. The review aims to summarize up-to-date past study results and suggest future research direction on this species, in order to promote clinical applications of S. nervosum.

Cassaine Diterpenoid Amide from Stem Bark of Erythrophleum fordii Suppresses Cytotoxic and Induces Apoptosis of Human Leukemia Cells.

Cassaine diterpenoids amides from the stem bark of Vietnamese Erythrophleum fordii Oliver were screened for their cytotoxic activity against human cancer cells. The cell proliferation assay results showed that, among the active compounds, 3ß-acetyl-nor-erythrophlamide (3AEP) exhibited the most potential cytotoxicity against human leukemia HL-60 and KG cells with IC50 values of 12.0 ± 1.2 and 18.1 ± 2.7 µM, respectively. Treatment of 3AEP resulted in the apoptosis of HL-60 cells via the activation of caspase 3, and poly (ADP-ribose) polymerase (PARP). Molecular docking in silico results showed that the 3AEP can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.51 and -9.63 kcal/mol respectively. These results indicated that the stem bark of Vietnamese E. fordii and its cassaine diterpenoid amides may be useful in the apoptosis induction of human leukemia cancer cells.

Assessing the therapeutic potential of Graptopetalum paraguayense on Alzheimer's disease using patient iPSC-derived neurons.

Alzheimer's disease (AD) is the most common type of dementia and also one of the leading causes of death worldwide. However, the underlying mechanisms remain unclear, and currently there is no drug treatment that can prevent or cure AD. Here, we have applied the advantages of using induced pluripotent stem cell (iPSC)-derived neurons (iNs) from AD patients, which are able to offer human-specific drug responsiveness, in order to evaluate therapeutic candidates for AD. Using approach involving an inducible neurogenin-2 transgene, we have established a robust and reproducible protocol for differentiating human iPSCs into glutamatergic neurons. The AD-iN cultures that result have mature phenotypic and physiological properties, together with AD-like biochemical features that include extracellular ß-amyloid (Aß) accumulation and Tau protein phosphorylation. By screening using a gene set enrichment analysis (GSEA) approach, Graptopetalum paraguayense (GP) has been identified as a potential therapeutic agent for AD from among a range of Chinese herbal medicines. We found that administration of a GP extract caused a significantly reduction in the AD-associated phenotypes of the iNs, including decreased levels of extracellular Aß40 and Aß42, as well as reduced Tau protein phosphorylation at positions Ser214 and Ser396. Additionally, the effect of GP was more prominent in AD-iNs compared to non-diseased controls. These findings provide valuable information that suggests moving extracts of GP toward drug development, either for treating AD or as a health supplement to prevent AD. Furthermore, our human iN-based platform promises to be a useful strategy when it is used for AD drug discovery.