Asian Subjects Research Articles

Ectopic gut colonization: a metagenomic study of the oral and gut microbiome in Crohn\u2019s disease

BackgroundThis study aims to characterize, the gut and oral microbiome in Asian subjects with Crohn’s disease (CD) using whole genome shotgun sequencing, thereby allowing for strain-level comparison.MethodsA case–control study with age, sex and ethnicity matched healthy controls was conducted. CD subjects were limited to well-controlled patients without oral manifestations. Fecal and saliva samples were collected for characterization of gut and oral microbiome respectively. Microbial DNA were extracted, libraries prepared and sequenced reads profiled. Taxonomic diversity, taxonomic association, strain typing and microbial gene pathway analyses were conducted.ResultsThe study recruited 25 subjects with CD and 25 healthy controls. The oral microbe Streptococcus salivarius was found to be enriched and of concordant strains in the gut and oral microbiome of Crohn’s disease subjects. This was more likely in CD subjects with higher Crohn’s Disease Activity Index (184.3 ± 2.9 vs 67.1 ± 82.5, p = 0.012) and active disease status (Diarrhoea/abdominal pain/blood-in-stool/fever and fatigue) (p = 0.016). Gut species found to be significantly depleted in CD compared to control (Relative abundance: Median[Range]) include: Faecalibacterium prausnitzii (0.03[0.00–4.56] vs 13.69[5.32–18.71], p = 0.010), Roseburia inulinivorans (0.00[0.00–0.03] vs 0.21[0.01–0.53], p = 0.010) and Alistipes senegalensis (0.00[0.00–0.00] vs 0.00[0.00–0.02], p = 0.029). While Clostridium nexile (0.00[0.00–0.12] vs 0.00[0.00–0.00], p = 0.038) and Ruminococcus gnavus (0.43[0.02–0.33] vs 0.00[0.00–0.13], p = 0.043) were found to be enriched. C. nexile enrichment was not found in CD subjects of European descent. Microbial arginine (Linear-discriminant-analysis: 3.162, p = 0.001) and isoprene (Linear-discriminant-analysis: 3.058, p < 0.001) pathways were found at a higher relative abundance level in gut microbiome of Crohn’s disease.ConclusionsThere was evidence of ectopic gut colonization by oral bacteria, especially during the active phase of CD. Previously studied gut microbial differences were detected, in addition to novel associations which could have resulted from geographical/ethnic differences to subjects of European descent. Differences in microbial pathways provide possible targets for microbiome modification.

The Efficacy and Safety of Dual-Frequency Ultrasound for Improving Skin Hydration and Erythema in Patients with Rosacea and Acne.

Inflammatory skin diseases, such as rosacea and acne, are major causes of facial erythema and accompanying skin barrier dysfunction. Several methods to restore the impaired skin barrier and improve facial erythema, such as medication, radiofrequency, laser, and ultrasound therapy were attempted. This study evaluated the efficacy and safety of dual-frequency ultrasound with impulse mode, for improving skin hydration and erythema in Asian subjects with rosacea and acne. Twenty-six subjects with facial erythema received an ultrasound treatment once per week, for 4 weeks, over both cheeks. The erythema index and transepidermal water loss (TEWL) were measured at each visit. Clinicians assessed the erythema improvement and patients evaluated their satisfaction level. The average decrease in TEWL and erythema index at 6 weeks was 5.37 ± 13.22 g·h−1·m−2 (p = 0.020) and 39.73 ± 44.21 (p = 0.010), respectively. The clinician’s erythema assessment and the subject satisfaction questionnaire score significantly improved at final follow-up (p < 0.001; p = 0.003, respectively). No serious adverse effects were observed during the treatment and follow-up periods. The dual-frequency ultrasound with impulse mode appears to be effective and safe for improving skin hydration and erythema in patients with rosacea and acne.

Large diameter scleral lens benefits for Asians with intractable ocular surface diseases: a prospective, single-arm clinical trial

To report the efficacy and safety of large diameter scleral lenses and determine their suitability in Asian subjects with intractable ocular surface diseases. This prospective study enrolled intractable ocular surface diseases subjects with uncorrected visual acuity > counting finger but ≥ 0.3 logMAR and best-corrected visual acuity (BCVA) ≥ 0.3 logMAR, to fit large diameter scleral lenses for 12 weeks. 21 eyes (13 subjects) consisting ten eyes (47.6%) with persistent epithelial defects, 6 (28.6%) with graft-versus-host disease, 4 (19.0%) with Stevens–Johnson syndrome and one (4.8%) with severe dry eye were ultimately enrolled. Primary outcome measures were the visual acuity, corneal and conjunctival fluorescein staining, Ocular Surface Disease Index (OSDI), and National Eye Institute 25-Item Visual Function Questionnaire (NEI-VFQ-25). At week 12 with large diameter scleral lenses, BCVA improved from 0.77 logMAR to 0.27 logMAR (P < 0.001). High-grade corneal and conjunctival fluorescein staining proportion decreased from 61.90 to 14.29% and 52.38 to 9.52%, respectively (P = 0.0036 and 0.0063, respectively). OSDI and NEI-VFQ-25 improved from 67.89 to 34.69 and 51.40 to 64.48, respectively (P < 0.001). No adverse effects were observed. In Asians with intractable ocular surface diseases, large diameter scleral lens improves visual acuity and alleviates signs and symptoms of ocular surface diseases without any significant complications.Trial registration Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Project No. HI12C0015 (A120018)). Clinical Trials.gov, NCT04535388. Registered 18 August 2020—Retrospectively registered, http://clinicaltrials.gov/ct2/show/NCT04535388.

Evaluating CO2 laser-assisted sclerectomy surgery with mitomycin C combined with or without phacoemulsification in adult Asian glaucoma subjects.

To evaluate and compare outcomes of CO2 laser-assisted sclerectomy surgery (CLASS) with mitomycin C (MMC) combined with or without phacoemulsification in adult Asian glaucoma patients. Retrospective, comparative study. Adult Asian glaucoma patients who underwent CLASS alone or combined with phacoemulsification using standardized surgery by two trained glaucoma surgeons between 2014 and 2016 were identified. The main measures of outcome were: intraocular pressure (IOP), use of supplemental medical therapy, best-corrected visual acuity (BCVA), microperforations, macroperforations, and repeated intervention(s) for glaucoma. Forty-one eyes who underwent CLASS alone (13 eyes) or combined with phacoemulsification (28 eyes) were included. Overall, BCVA improved from 0.28 ± 0.19 to 0.14 ± 0.17, and 0.17 ± 0.19, 0.22 ± 0.24, and 0.18 ± 0.23 at 6, 12, 24, and 36months, respectively. Mean IOP dropped from 17.9 ± 4.7mmHg to 14.6 ± 5.5, 13.9 ± 3.3, 14.3 ± 3.6, and 14.1 ± 3.7mmHg, and average number of medications reduced from 2.9 ± 0.9 to 0.2 ± 0.6, 0.5 ± 0.9, 1.0 ± 1.2, and 1.3 ± 1.4 at the same time points. There was no statistically significant difference in BCVA, IOP, and medication reduction between the two groups. CLASS combined with or without phacoemulsification was equally safe and effective, but yielded more modest results in our population.

A clinical evaluation of noninvasive and contactless radiofrequency technique in the treatment of abdominal fat.

There is an increasing demand for fat reduction and body contouring procedures. Noninvasive radiofrequency devices have been used to tighten skin and treat cellulite, but there are few studies confirming their efficacy for abdominal fat reduction. This study explored the effects of four noninvasive radiofrequency (RF) treatments on abdominal fat in Asian subjects, evaluating body weight, body mass index (BMI), and waist circumference. In this study, 16 patients with abdominal obesity were treated four times with a noninvasive and contactless selective RF device (VANQUISH ME™, BTL Aesthetics). Treatments were 7days apart and lasted 45min each. The BMI and circumference of the upper, middle, and lower abdomen were measured at baseline and after each treatment. There were statistically significant reductions in BMI and abdominal circumference in all 16 patients (P<.05). Most patients only experienced a slight abdominal heat sensation and minimal body sweating during the treatment, and no adverse reactions were observed after the treatment. The noninvasive and contactless selective RF technique was effective and safe in reducing fat, BMI, and abdominal circumference.

Common Variants at 21q22.3 Locus Influence &lt;i&gt;MX1&lt;/i&gt; Gene Expression and Susceptibility to Severe COVID-19

The COVID-19 disease, caused by the SARS-Cov-2, presents a heterogeneous clinical spectrum. The risk factors do not fully explain the wide spectrum of disease manifestations, so genetic factors could account for novel insights into its pathogenesis.In our previous study, we hypothesized that common variants on chromosome 21, near TMPRSS2 and MX1 genes, may be genetic risk factors associated with the different clinical manifestations of COVID-19. Here, we performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms (SNPs) within TMPRSS2 and near MX1 gene show suggestive associations (P≤1x10-5) with severe COVID-19. All five SNPs replicated the association in two independent cohorts of Asian subjects while two and one out of the 5 SNPs replicated in African and Italian populations, respectively (P≤0.05). The minor alleles of the five SNPs correlated with a reduced risk of developing severe COVID-19 and an increased level of MX1 expression in blood. One (rs12329760, V197M) of these SNPs resided in the exon 6 of TMPRSS2 and was also predicted to alter the protein conformation.Our findings provide further evidence that host genetic factors can contribute to determining the different clinical presentations of COVID-19 and that MX1, an antiviral effector of type I and III interferon pathway, could be a potential therapeutic target.Funding: This study was supported by the project "CEINGE TASK-FORCE COVID19", codeD64I200003800 by Regione Campania for the fight against Covid-19 (DGR n. 140 del 17 Marzo 2020).Conflict of Interest: Nothing to disclose.

Guardians of the Buddha's Home: Domestic Religion in Contemporary Jōdo Shinshū by Jessica Starling

Reviewed by: Guardians of the Buddha's Home: Domestic Religion in Contemporary Jōdo Shinshū by Jessica Starling Eisho Nasu (bio) Guardians of the Buddha's Home: Domestic Religion in Contemporary Jōdo Shinshū. By Jessica Starling. University of Hawai'i Press, Honolulu, 2019. xii, 186 pages. $62.00, cloth; $28.00, paper. Jessica Starling's Guardians of the Buddha's Home: Domestic Religion in Contemporary Jōdo Shinshū is a welcome addition to the small but growing literature on domestic spheres in contemporary Japanese Buddhism. The "guardians" who are the subject of Starling's study are the bōmori (temple guardians), the wives of priests of the Jōdo Shinshū tradition, one of the [End Page 136] largest forms of "domestic" Buddhism in Japan. The founder of this tradition, Shinran (1173–1262), consciously rejected monastic norms and chose marriage and family as the basis of his Buddhist practice. Using her extensive ethnographic research, Starling skillfully and conscientiously presents her informants' voices so that readers can reimagine and reevaluate the stereotypical image of Buddhist traditions dominated so far by the collective voices of male priests. Starling's work stands out for its focus on mainly nonordained, nonmonastic women. Much of the literature on women in Buddhism has justifiably centered on the lives of Buddhist nuns (whether ordained or not). Starling's study of temple wives instead opens the door to the Buddhist home, an area still underrepresented in the field of Japanese Buddhism (with Paula Arai's Bringing Zen Home: The Healing Heart of Japanese Women's Rituals being another excellent example of studies of domestic Buddhism1). While the women Starling introduces are not nuns and ordination is not required (although increasingly bōmori are obtaining ordination), they are nevertheless "domestic religious professionals" who live in temples, which perhaps still differentiates them from other laywomen. As temple wives married to temple priests/husbands, their work is defined in part by traditional gender roles and expectations. But, ironically, it is these expectations, Starling asserts, that make the temple wife into a professional: "One of the surprising discoveries of my fieldwork was that the very gender ideology that divides labor along gender lines and 'confines' women to staying at home in fact renders temple wives de facto religious professionals" (p. 16). That is, bōmori work to propagate Buddhism from within the home, for example by welcoming people into the temple with hospitality that will foster connections with the temple and Amida (pp. 44–46); furthermore, whenever the priest/husband is away from the home (or dies), the wife becomes the de facto priest, conducting rituals and services (chapter 5). Starling's work explores how women navigate these various roles, their attitudes toward their work, and the problems they face within institutions and society that still tend to devalue women's contributions to traditionally male work. In the "Introduction," Starling is careful to set out the limits of her position as a Western scholar studying Asian subjects. She draws on works by Wei-Yi Cheng and Nirmala Salgado that have pointed out the tendency of Western scholars to apply their own feminist ideas and expectations to Asian Buddhist women,2 thereby (consciously or unconsciously) making [End Page 137] a discourse of Asian women's self-empowerment, agency, resistance, and freedom that Asian women themselves may not recognize. To avoid mischaracterization, Starling tries to "enter into the everyday lives of her informants with an honest sense of humility in order to discover the categories and concepts that operate for them on a practical level" (p. 7). Overall, this is a strength of Starling's work (although I have one criticism; see below), and she listens to the actual voices of the women (and men) she interviews. She seeks to understand their lives broadly through the "intimacy and intersubjectivity" that is at the core of their many family and community relationships and that gives them relational agency (p. 11). Readers find an alternative vision of contemporary Japanese Buddhist practice in the context of domestic life, in which temple wives cultivate skills of interpersonal communication rather than scripted doctrine. Starling constructs all six chapters around her interviews with 60 women from temple families, which...

Normal acid exposure time in esophageal pH monitoring in Asian and Western populations: A systematic review and meta-analysis.

Esophageal acid exposure time (AET) during 24h pH monitoring is reproducible and predictive outcomes of treatment for gastroesophageal reflux disease. Several small Asian studies have investigated the normal range of the AET; the range may be different from that in Western populations. We evaluated its normal range in healthy Asian compared to Western subjects. We searched PubMed, Embase, Cochrane Library, and KoreaMed for studies that reported pH monitoring parameters in healthy subjects. Studies that reported the AET values of healthy subjects were eligible for the analyses. The upper limit of normal of the AET was obtained from the 95th percentile of the available raw data or calculated as the mean value +2 standard deviations. Nineteen Asian and 49 Western studies were assessed. The estimated AET values were analyzed using a bootstrapping technique, weighted according to the sample size. The mean AET was 1.1% and 2.9% in the Asian and Western populations, respectively. The upper limit of the reference range was 3.2% (95% confidence interval [CI], 2.7-3.9%) and 8.2 (95% CI, 6.7-9.9) in the Asian and Western populations, respectively. The normal AET differed between the Asian and Western populations because the CI of the two groups did not overlap. The upper limit of normal of the AET in healthy Asian subjects was 3.2% (95% CI, 2.7-3.9%), which was lower than that of healthy Western subjects.

Abundance and Associated Variations of Cytochrome P450 Drug-Metabolizing Enzymes in the Liver of East Asian Adults: A Meta-Analysis.

Cytochrome P450 (CYP) enzymes are one of the main sources of variability in drug metabolic clearance. Information on their abundance levels is therefore crucial to optimize scaling factors for in vitro-in vivo extrapolation (IVIVE) to predict metabolic clearance. This study aims to quantify the abundance data of hepatic drug-metabolizing CYP enzymes in East Asian subjects reported from various sources in the literature using meta-analysis. We conducted a meta-analysis on the abundance of drug-metabolizingCYP enzymes in the liver of East Asian adults. Eligible reports were identified based on predefined criteria-(1) individual liver microsomal samples, and (2) absolute protein abundance data from normal tissues of East Asian adult subjects. Subgroup and sensitivity analyses were also performed. Among the 11 CYP isoforms analyzed in East Asian subjects, CYP3A5 and CYP3A4 had the highest protein levels. In particular, the number of studies and the liver sample used to quantify the abundance of CYP3A4 were the largest. Of the isoforms involved, CYP2J2 and CYP2B6 had the lowest abundance level, i.e., <5 pmol/ mg of microsomal protein. For enzymes with abundance values available in both Chinese and Japanese subjects (CYP1A2, CYP2C9, CYP3A4, and CYP3A5), the abundance level of each CYP isoform appeared to be higher in Chinese than in Japanese subjects. The most distinct difference was observed in CYP3A5 abundance. The current meta-analysis shows that the abundance levels of CYP enzymes appear to vary greatly among different East Asian individuals who have similar ethnic backgrounds and food habits. The pooled data of CYP abundance can be used as preliminary reference values along with the associated variations for the projections of pharmacokinetics through physiologically based pharmacokinetic (PBPK)approaches.

Sodium-glucose co-transporter-2 inhibitors and all-cause mortality: A meta-analysis of randomized controlled trials.

The present meta-analysis is aimed at assessing the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors on all-cause mortality and differences across different trials and molecules of the class. We included all randomized clinical trials with a duration of treatment longer than 52 weeks, enrolling at least 100 patients in each arm, and comparing an SGLT2 inhibitor with any comparator or placebo. Out of 139, 235 and 145 items identified, 21 trials were selected, enrolling 39 593 and 30 771 patients in SGLT2 inhibitor and comparator arms, respectively, with a median duration of 104 weeks, and reporting 2474 and 2298 deaths for SGLT2 inhibitors and comparators, respectively. No relevant heterogeneity was found (I2 = 17%). Treatment with SGLT2 inhibitors was associated with a significant reduction in all-cause mortality (MH-OR [95% CI] 0.86 [0.81, 0.91] P < .00001). Meta-regression analyses found a significant direct association of treatment effect only with the proportion of Asian subjects enrolled, and an inverse correlation with the proportion of Caucasian patients. In conclusion, SGLT2 inhibitors reduce all-cause mortality in randomized controlled trials.

Perception and liking of yogurts with different degrees of granularity in relation to ethnicity, preferred oral processing and lingual tactile acuity

Food perception and liking depend on both product properties and consumer characteristics. The aim of this study was to investigate the effect of ethnicity, preferred oral processing and lingual tactile acuity on the consumer perception and liking of yogurt. To achieve the aim, six yogurt samples were prepared, including a homogeneous yogurt, a yogurt manufactured with micro particles, and four samples with addition of flakes or cut grains in different concentrations into homogeneous yogurt. Adults (n = 152) including seventy-five Asian Chinese subjects and seventy-seven Caucasian Danish subjects rated their perception and liking of yogurts. Subjects' preferred oral processing were identified according to how they prefer to manipulate food in their mouth ('soft processing likers' and 'firm processing likers'), and their tactile acuity was assessed by von Frey filaments. A descriptive sensory analysis of the yogurt was conducted by a trained panel consisting of 10 assessors. Results showed that ethnicity had a considerable influence on the liking of yogurts. Chinese subjects liked both yogurts containing macro particles (grains or low level of flakes) and homogeneous yogurts with no added particles, whereas Danish subjects significantly decreased their liking of yogurts with addition of particles, either micro or macro. Subjects' preferred oral processing and oral tactile acuity had a less pronounced effect on the liking of yogurts. Differences in texture perception of yogurts were negligible. The present results highlight a significant cultural effect on consumer acceptability and thus underline the importance of conducting the cross-cultural sensory research to the yogurt market.

Drug Safety of Benzodiazepines in Asian Patients With Chronic Obstructive Pulmonary Disease.

Purpose: Many comorbidities, including depression, anxiety, and insomnia, occur in patients with chronic obstructive pulmonary disease (COPD). These patients may be prescribed benzodiazepines (BZDs). However, there are some concerns that benzodiazepines increase the risk of drug overdose, hypercapnic respiratory failure, acute exacerbation and increased mortality. The aim of our study was to evaluate the drug safety of BZDs in patients with COPD. Methods: We used the National Health Insurance Research database in Taiwan from 2002 to 2016 to perform a retrospective cohort study. We enrolled patients who were exposed to the first prescription of BZDs, non-BZDs or a combination (mix user) after COPD diagnosis. We performed 1:1:1 propensity score matching in three groups. The outcomes were COPD with acute exacerbation and all-cause mortality. Poisson regression analysis was performed to evaluate the incidence rate ratios for the outcomes in the groups. Results: After propensity score matching, there were 2,856 patients in each group. After adjusting for confounding factors, we found that compared to BZD users, non-BZD and mix users had nonsignificant differences in outpatient management of acute exacerbations, hospitalization management of acute exacerbations, emergency department management of acute exacerbations and all-cause mortality. BZD and mix groups showed significantly increased admission for acute exacerbation of COPD compared with that of the nonuser group, with IRRs of 2.52 (95% CI, 1.52–4.18; p = 0.0004) and 2.63 (95% CI, 1.57–4.40; p = 0.0002), respectively. Conclusion: BZD, non-BZD, and mix users showed increased COPD-related respiratory events compared to nonusers in Asian subjects.

Dynamics of Leukocyte Subpopulations Reconstitution Predict Infection Propensity in a Multiethnic Real World Cohort Treated with Anti-CD19 CAR-T Cell Therapy (Axicabtagene-Ciloleucel)

Background: Adoptive immunotherapy using CD19-targeted Chimeric Antigen Receptor T-cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We have demonstrated the efficacy of FDA-approved axicabtagene ciloleucel (Yescarta) in a multiethnic New York City underserved population with 80% complete response (CR) rate in the first ten patients treated at our institution (Abbasi et al., 2020). There is limited data on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. Methods: We conducted a retrospective study of patients who received CAR-T therapy at our institution between 2018-2020. Variables collected include patient demographics, absolute neutrophil (ANC), lymphocyte (ALC) and monocyte counts (AMC) at Day 30, hematologic reconstitution (ANC≥ 1500/µL) at Day 90 (D90), presence or absence of infections after D30 by clinical and/or microbiological parameters. Associations between presence of infection and D30 ANC, ALC, AMC, ANC/ALC ratio, AMC/ALC ratio were assessed using Kruskal-Wallis test. Association between infection and hematologic reconstitution at D90 was done using Chi-square test. Kaplan-Meier curves with log-rank test were used to evaluate overall survival (OS) and progression-free survival (PFS). Results: Nineteen patients were evaluated in our study, consisting of 42% (8) Hispanic, 32% (6) Caucasian, 21% (4) African-American, and 5% (1) Asian subjects. Based on clinical and microbiologic data, 47% (9) developed an infection after D30 (infection group) while 53% (10) of subjects remained infection-free after D30 (non-infection group). The most common infection type observed was viral (11 patients) followed by bacterial (8 patients) and fungal (3 patients) (Table 1). Of 25 total infectious events, 44% (11) were grade 1 or 2 and 48% (12) were grade 3 with 10 being viral in etiology. Two deaths occurred due to an infectious process. Three patients tested SARS-CoV-2 positive and were hospitalized with COVID-19 pneumonia. Median OS and PFS has not been reached in either group. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median ALC (1000/µL vs 600/µL p=0.04), a lower median ANC/ALC ratio (1.4 vs 4.5 p&amp;lt;0.01) and a lower median AMC/ALC at D30 (0.36 vs 1.33, p=0.01) (Table 2). In addition, patients in the infection group had a lower rate of hematologic reconstitution (ANC &amp;gt;1500/µL) at D90. We observed that only 22% (2) of patients had recovered ANC &amp;gt; 1500/µLin the infection group as opposed to 80% (8) in the non-infection group at D90 (p= 0.038). Rates of cytokine release syndrome (CRS) were comparable between the two groups (55.6% vs 70% p=0.52). Surprisingly, rates of immune-effector cell associated neurotoxicity syndrome (ICANS) was lower (55.6%) in the infection group compared to (90%) non-infection group (p=0.09). Fourteen of 19 patients had follow-up over one year, of which 8 (57%) remained in complete remission (CR). Conclusions: We demonstrate an infection rate of 47% (9) beyond D30 in patients undergoing CD19 CAR-T. Increased ALC, lower ANC/ALC and AMC/ALC ratios at D30 may be predictive of infectious complications. Median OS has not been reached in our cohort. Given the potential clinical impact, our observations should be corroborated using larger datasets. Disclosures Steidl: Pieris Pharmaceuticals: Consultancy; Bayer Healthcare: Research Funding; Stelexis Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Aileron Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Janakiram:ADC Therapeutics, FATE therapeutics, TAKEDA pharmaceuticals: Research Funding. Verma:BMS: Consultancy, Research Funding; acceleron: Consultancy, Honoraria; Janssen: Research Funding; stelexis: Current equity holder in private company; Medpacto: Research Funding.

Identification of biomarkers for early diagnosis of diabetic nephropathy disease using direct flow through mass spectrometry

Background and aimsAlbuminuria is not an effective marker for early diagnosis of diabetic renal complication with several subjects progressing to chronic kidney disease without any albuminuria. A biomarker that can predict early changes of the diabetic kidney will be useful in effective management of type 2 diabetes. Mass spectrometry based metabolomics approach offers tremendous promise for the identification of novel metabolite biomarkers. MethodsA case-control approach was carried out to identify renal biomarkers among Asian Indian subjects in a hospital setting. A total of 29 subjects were included in the study that included groups of diabetic controls, diabetic subjects with eGFR >90 ml/min/1.72 m2 and diabetic subjects with eGFR between 60 and 89 ml/min/1.72 m2 and eGFR between 15 and 30 ml/min/1.72 m2. We employed an un-targeted mass spectrometry method for the identification of plasma metabolites. ResultsA total of 1414 and 975 metabolites were identified in the positive and negative ion mode respectively. 19 metabolites were up regulated and 18 metabolites were down regulated in CKD2 and CKD4 groups when compared to control. Correlation analysis of the differential metabolites revealed Pregnenolone sulfate, creatinine and ganglioside GA1 to be negatively correlated and hexyl glucoside, all-trans-carophyll yellow and PG to be positively correlated with eGFR. ConclusionWe have identified Pregnenolone sulfate, GA1, PG and all-trans-Carophyll yellow as biomarkers for early identification of diabetic nephropathy. These markers could aid in better management of diabetic nephropathy that may result delaying the progression of the disease.

Divide and Conquer: Gendered Division Within the Process of Internalised Racism

ABSTRACT Utilising a socio-psychological understanding of the concept of internalised racism (IR), this article examines the racialised romantic/sexual preferences for White Western men amongst Asian Australians subjects. By psychoanalytically analysing the notion of White nation-building and its inherent gendered dynamics, the article examines how the White patriarchal national will aims to secure its dominance over national space. In doing so, it necessarily engages in two simultaneous strategic plays of power. First, it must secure access to the racialised female element – a symbolic penetration of the motherland’s other. Second, as corollary and catalyst, the national will engenders an emasculation of the racialised male element – a symbolic castration of the phallic signifier of the counter-will. By examining how both these dynamics are internalised by racialised subjects, this article demonstrates how IR ultimately works to fracture a racialised community from within.

Vogt-Koyanagi-Harada disease: a retrospective and multicentric study of 41 patients

BackgroundEast and South East Asian subjects as well as Amerindians and Hispanic subjects are predominantly affected by Vogt-Koyanagi-Harada disease.In Europe, only few studies have described the clinical features and treatment of this disease, especially in France.MethodsThis retrospective case series was based on data collected from patients with a VKH disease diagnosed from January 2000 to March 2017, provided by three French Tertiary Centers.ResultsForty-one patients (16 men and 25 women) were diagnosed: average age at diagnosis was 38.7 years. Patients were mainly from Maghreb (58%), but ethnic origins were multiple. Pleiocytosis was observed in 19 cases (63%) and 17 out of 41 patients showed audio vestibular signs (41%), and 11 showed skin signs (27%). Thirty-four were treated with corticosteroids (83%), 11 with an immunosuppressant treatment (27%) and 5 with biological therapy drugs (13%). Relapse was observed in 41% patients, even though final average visual acuity had improved. We did not find any significant clinical difference in the population from Maghreb compared to other populations, but for age and sex trends, since there was a majority of younger women.ConclusionWe report here the second largest French cohort reported to date to our knowledge. The multiethnicity in our study suggests that VKH disease should be evoked whatever patients’ ethnicity.

Ethnic pharmacokinetic comparison of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) between Asian and Western healthy subjects

BackgroundThe Phase III KRONOS study (NCT02497001) found the fixed-dose combination triple therapy budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) to be efficacious and well tolerated versus corresponding dual therapies in patients with moderate-to-very severe COPD from North America, China and Japan. However, pharmacokinetic (PK) studies of other drugs have shown that ethnic factors (e.g. genetic factors affecting drug metabolism) can affect the bioavailability of drugs which may impact upon efficacy and safety outcomes. MethodsThis was a post-hoc analysis of data from four randomised, double-blind Phase I studies of BGF MDI 320/18/9.6 μg and 160/18/9.6 μg in Chinese (NCT03075267), Japanese (NCT02197975) and Western (NCT01980615, NCT02189304) healthy subjects. PK properties (area under the plasma concentration–time curve 0–12 h post-dose [AUC0–12] and maximum plasma concentration, [Cmax]) were recorded following single and repeated dosing of BGF MDI 320/18/9.6 μg or 160/18/9.6 μg. Potential ethnic differences in the PK properties of budesonide, glycopyrrolate and formoterol in Chinese, Japanese and Western healthy subjects were derived by non-compartmental analysis, and ethnic insensitivity factors evaluated based on criteria from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Guideline E5 Ethnic Factors in the Acceptability of Foreign Clinical Data. ResultsThe analyses included data from 64 Chinese, 31 Japanese and 169 Western subjects. Overall, PK properties following single or repeated dosing of BGF MDI were similar across Chinese, Japanese and Western subjects. After single dosing at either dose level, AUC0–12 and Cmax for budesonide, glycopyrrolate and formoterol appeared generally similar for Asian (Chinese and Japanese) versus Western subjects, with most geometric least squares mean ratios within the range of 0.92–1.22. The exception was that Cmax for glycopyrrolate was slightly lower in Asian versus Western subjects (0.6–0.7). Of the 10 ethnic insensitivity factors evaluated, six were met for budesonide, nine for glycopyrrolate and nine for formoterol, suggesting that BGF MDI can be classified as an ethnically insensitive drug. ConclusionsOverall, these analyses suggest no appreciable ethnic differences in the PK of BGF MDI across Chinese, Japanese and Western healthy subjects.

David Henry Hwang’s Post-Racial Aesthetics in Late Capitalism: A Transversal Butterfly with Prosthetic Agency in M. Butterfly

This paper examines how Butterfly functions as a prosthetic prop to ramp up the affective capacities of both Asian and white subjects to become creolized in the late-capitalist US culture in David H. Hwang’s M. Butterfly. Hwang’s interpretation of Butterfly is invested in casting off entrenched Orientalist discourses all too prevalent in the United States history. However, despite considerable scholarly attention directed to the play, less focus has been paid to the character trajectories concerning how the performative ontology of their race, gender, and sexuality are both effected and affected by the different settings of time and space in it. This new historicist approach helps situate the play within the larger question of Asian American representation in the Cold War context and its related political economy during the second half of the 20th century, a point that this paper investigates through Marc and Renee who reify the libidinal economy of capitalist biopower and an anti-authoritarian precursor of neoliberal capitalism, respectively. Thus, this study shows how Butterfly is teased out as something creolized at the intersections of the different shifting identities of race, gender, and sexuality&#8212;a prosthetic prop to enable the “misfit” subjects to claim agency beyond their ontological limits against the American regime of heteronormativity and white supremacy. The embodiment of Butterfly as transversal and creolized serves to materialize Hwang’s aspirations to create an affective model of the American identity, not hyphenated, but more representative of what the US is becoming in terms of post-racial aesthetics.

Higher Febuxostat Exposure Observed in Asian Compared with Caucasian Subjects Independent of Bodyweight.

Febuxostat is a xanthine oxidase inhibitor indicated for gout and hyperuricemia. This work investigates potential clinically relevant covariates for febuxostat pharmacokinetics with a special focus on Asian race and bodyweight. Febuxostat plasma concentrations from 141 male subjects were obtained from two phase II studies in patients with hyperuricemia/gout (NCT02246673, NCT02317861) and one study in healthy volunteers (NCT01883167). Subjects were administered febuxostat oral doses from 10 to 80mg. The pharmacokinetics of febuxostat was analyzed using non-linear mixed-effects modeling as implemented in NONMEM 7.3.0. The dataset consisted of racially diverse subjects, 40% being Japanese, 10% of unknown Asian origin, 39% Caucasian, and 10% Black. Most subjects (n = 92, 63%) had normal creatinine clearance (90mL/min), while 52 subjects (36%) had mild renal impairment (creatinine clearance > 60 to < 90) at baseline. The effect of disease state, body weight, and creatinine clearance on febuxostat pharmacokinetics was investigated using stepwise covariate modeling. Febuxostat pharmacokinetics was well described by a two-compartment disposition model. Asian race was the only covariate resulting in a potentially clinically important increase in febuxostat area under the curve (1.64-fold, 90% confidence interval 1.48-1.79) compared with Caucasian individuals. The difference in body weight between Asian and Caucasian subjects did not explain the difference in febuxostat exposure. Absorption was modeled as a sequential zero- to first-order process with lag-time. In this pooled analysis of three studies, we show that Asian individuals have a 1.64-fold higher febuxostat exposure than Caucasians, independent of bodyweight or other investigated covariates.These findings may be of importance when selecting starting febuxostat doses in Asian patients.

Development of a serum miRNA panel for detection of early stage non-small cell lung cancer.

Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects. Using RT-qPCR and a tightly controlled workflow, we quantified the absolute expression of 520 circulating microRNAs (miRNAs) in a Chinese cohort of 180 early stage NSCLC cases and 216 healthy controls (male smokers). Candidate biomarkers were verified in two case-control cohorts of 432 Chinese and 218 Caucasians, respectively (including females and nonsmokers). A multimiR panel for NSCLC detection was developed using a twofold cross-validation and validated in three additional Asian cohorts comprising 642 subjects. We discovered 35 candidate miRNA biomarkers, verified 22 of them, and developed a five-miR panel that detected NSCLC with area under curve (AUC) of 0.936-0.984 in the discovery and verification cohorts. The panel was validated in three independent cohorts with AUCs of 0.973, 0.916, and 0.917. The sensitivity of five-miR test was 81.3% for all stages, 82.9% for stages I and II, and 83.0% for stage I NSCLC, when the specificity is at 90.7%. We developed a minimally invasive five-miR serum test for detecting early stage NSCLC and validated its performance in multiple patient cohorts independent of smoking status, gender, and ethnicity.