Delivering integrated strategies from a mobile unit to address the intertwining epidemics of HIV and addiction in people who inject drugs: the HPTN 094 randomized controlled trial protocol (the INTEGRA Study).

BACKGROUND: Persons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, "whole-person" strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit ("mobile unit") with peer navigation compared to peer navigation alone to access these services at brick and mortar locations. METHODS: HPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of "one-stop" integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization. DISCUSSION: This trial responds to a need for evidence on using a "whole-person" strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04804072 . Registered on 18 March 2021.

Persistently Elevated Risk of Syphilis Among Human Immunodeficiency Virus-Positive Men Receiving Care in a Status-Neutral Setting: A Retrospective Analysis.

BACKGROUND: Over the past decade, the incidence of primary and secondary syphilis has increased dramatically in the United States and Western Europe. Men living with human immunodeficiency virus (HIV) and those at risk of HIV infection experience disproportionately high rates of early syphilis (ES). We compared the odds of ES among HIV-positive and HIV-negative men participating in a status-neutral comprehensive HIV prevention and treatment program (CHP). METHODS: We conducted a retrospective analysis of men aged 18 to 65 years with ≥ 1 CHP visit and ≥2 rapid plasma reagin (RPR) tests performed between January 1, 2018, and December 31, 2021. Early syphilis was defined as newly reactive RPR with a minimum titer of ≥1:4 or a ≥ 4-fold increase in the RPR titer. Multiple logistic regression analyses were performed to determine predictors of ES. RESULTS: A total of 2490 men met the inclusion criteria, of whom 1426 (57.3%) were HIV-positive and 1064 (42.7%) were HIV-negative. Of the 393 men with ES, 284 (72.3%) were HIV-positive and 109 (27.7%) were HIV-negative. Human immunodeficiency virus-positive men had higher adjusted odds of ES (adjusted odds ratio, 2.86; 95% confidence interval, 2.45-3.27) than HIV-negative men did. Chlamydia or gonorrhea infection did not differ according to HIV status (adjusted odds ratio, 0.93; 95% confidence interval, 0.82-1.04). CONCLUSIONS: In our status-neutral care setting, HIV-positive status was associated with significantly higher odds of ES, but not chlamydia or gonorrhea. Our findings emphasize the vulnerability of HIV-positive men to syphilis in an era of effective HIV biomedical prevention.

Low-Dose Metronomic Topotecan and Pazopanib (TOPAZ) in Children with Relapsed or Refractory Solid Tumors: A C17 Canadian Phase I Clinical Trial.

Oral metronomic topotecan represents a novel approach to chemotherapy delivery which, in preclinical models, may work synergistically with pazopanib in targeting angiogenesis. A phase I and pharmacokinetic (PK) study of this combination was performed in children with relapsed/refractory solid tumors. Oral topotecan and pazopanib were each administered daily without interruption in 28-day cycles at five dose levels (0.12 to 0.3 mg/m2 topotecan and 125 to 160 mg/m2 pazopanib powder for oral suspension (PfOS)), with dose escalation in accordance with the rolling-six design. PK studies were performed on day 1 and at steady state. Thirty patients were enrolled, with 26 evaluable for dose-limiting toxicity (DLT), with median age 12 years (3-20). Toxicities were generally mild; the most common grade 3/4 adverse events related to protocol therapy were neutropenia (18%), thrombocytopenia (11%), lymphopenia (11%), AST elevation (11%), and lipase elevation (11%). Only two cycle 1 DLTs were observed on study, both at the 0.3/160 mg/m2 dose level comprising persistent grade 3 thrombocytopenia and grade 3 ALT elevation. No AEs experienced beyond cycle 1 required treatment discontinuation. The best response was stable disease in 10/25 patients (40%) for a median duration of 6.4 (1.7-45.1) months. The combination of oral metronomic topotecan and pazopanib is safe and tolerable in pediatric patients with solid tumors, with a recommended phase 2 dose of 0.22 mg/m2 topotecan and 160 mg/m2 pazopanib. No objective responses were observed in this heavily pre-treated patient population, although 40% did achieve stable disease for a median of 6 months. While this combination is likely of limited benefit for relapsed disease, it may play a role in the maintenance setting.

An assessment of the psychometric properties of the Stoplight Pain Scale in a Canadian paediatric emergency department.

OBJECTIVE: This study aimed to validate a novel, three faced, colour-coded, action-oriented tool: The Stoplight Pain Scale (SPS). METHODS: A prospective observational cohort study was conducted at a Canadian paediatric emergency department from November 2014 to February 2017. Patients aged 3 to 12 years and their caregivers were asked to rate pain using the SPS and the Faces Pain Scale-Revised (FPS-R). Pain was measured just before analgesia administration, 30 minutes after analgesia administration, and immediately following a painful procedure. RESULTS: A total of 227 patients were included; 26.9% (61/227) were 3 to 5 years old while 73.1% (166/227) were 6 to 12 years old. Using Cohen's κ, agreement for SPS and FPS-R was 'fair' for children (0.28 [95% confidence interval {CI} 0.20 to 0.36]) and 'poor' for caregivers (0.14 [95% CI 0.07 to 0.21]), at initial measurement. The SPS had 'fair' agreement between child and caregiver scores, (0.37 [95% CI 0.27 to 0.47]), compared to FPS-R which showed 'poor' agreement (0.20 [95% CI 0.12 to 0.29]). Absolute agreement between child and caregiver SPS scores improved with repeat exposure; 30 minutes after analgesia administration, caregivers and children had fair agreement (κ=0.38, 95% CI 0.28 to 0.48); they had moderate agreement directly following painful procedures (κ=0.46, 95% CI 0.34 to 0.59). Overall, 72.4% (139/192) of children and 60.2% (118/196) of caregivers preferred SPS over FPS-R. CONCLUSION: The SPS demonstrates fair agreement with FPS-R for children and fair-moderate agreement between children and caregivers; agreement improved with repeat use. The SPS is simple and easy to use; it may have a role in empowering direct child and family involvement in pain management.

Should Needlestick Protocols Influence Documentation or Disclosure of a Patient's HIV Status?

Heightened privacy and confidentiality stakes around HIV have resulted in unique anonymity and nondisclosure policies and practices. This commentary on an occupational exposure case considers benchmarks in the evolution of HIV testing. Persistent stigma continues to exacerbate ethical complexities and ambiguities clinicians face in an "end the epidemic" era.

COVID-19 preparedness at health facilities and community service points serving people living with HIV in Sierra Leone.

After a decade of civil war and the 2014-2016 West African Ebola outbreak, Sierra Leone now faces the COVID-19 pandemic with a fragile health system. As was demonstrated during Ebola, preparedness is key to limiting a health crisis' spread and impact on health systems and ensuring continued care for vulnerable populations including people living with HIV (PLHIV). To assess COVID-19 preparedness and inform interventions to ensure continuity of HIV services at health facilities (HFs) and community service points (CSPs), we conducted site readiness assessments in Freetown, the epicenter of COVID-19 in Sierra Leone. Data were collected at nine high-volume HIV HFs and seven CSPs in April 2020, a month after COVID-19 was declared a pandemic. CSPs comprised three community drop-in centers providing HIV counseling and testing services as well as HIV prevention services (e.g., condoms and lubricants) for key and priority populations and four community-based support groups serving PLHIV. At the time of assessment, CSPs did not provide antiretroviral therapy (ART) but were considered potential sites for expansion of differentiated service delivery (DSD)-a client-centered approach to HIV care-in the context of COVID-19. Overall, 5/9 HFs had trained staff on use of personal protective equipment (PPE) and prevention of COVID-19 transmission. Most had access to masks (5/9) and gloves (7/9) for management of suspected/confirmed COVID-19 cases, and 4/9 HFs had triage procedures for isolation of suspected cases. Conversely, few CSPs had access to masks (2/7) or gloves (2/7) and no staff were trained on PPE use or COVID-19 transmission. 7/9 HFs had adequate ART stock for multi-month dispensing though few had procedures for (3/9) or had trained staff in providing DSD (2/9). Among CSPs where measures were applicable, 2/4 had procedures for DSD, 1/3 had staff trained on DSD and none had adequate ART stock. Identification of gaps in COVID-19 preparedness is a critical step in providing support for infection control and modified service delivery. Findings from this assessment highlight gaps in COVID-19 preparedness measures at sites supporting PLHIV in Sierra Leone and indicate CSPs may require intensive supervision and training to ensure HIV services are uninterrupted while minimizing COVID-19 risk, especially if used as sites to scale up DSD.

Para-spermatic cord proximal-type epithelioid sarcoma.

Proximal-type epithelioid sarcoma is an ultra-rare, high-grade soft tissue malignancy usually presenting as a deep-seated painless mass in the proximal extremities. Most patients are diagnosed as young adults, between 20 and 40 years of age. Perineal and genital masses do occur but are extremely rare and represent a challenging tumour to diagnose and treat. Early radical excision is recommended due to its aggressive behaviour and poor prognosis. Median overall survival from initial diagnosis is 30 months. We present the case of a 22-year-old man with a left groin proximal-type epithelioid sarcoma who is sadly deceased 12 months after initial presentation despite early surgical excision, completion of both first-line and palliative chemotherapy, and palliative radiotherapy.

Missed Opportunities for Engagement in the Prevention Continuum in a Predominantly Black and Latino Community in New York City.

Even though over the last 25 years, the Centers for Disease Control and Prevention recommendations for HIV screening have expanded to encompass population-wide screening in all healthcare settings, and despite the availability of pre-exposure prophylaxis (PrEP), a large proportion of individuals at risk of infection are not linked to prevention care. We evaluated missed opportunities for HIV screening and linkage to PrEP from 2006 through 2017 at an urban academic medical center serving a predominantly minority community. A missed opportunity for HIV screening was a provider visit that did not include HIV testing and occurred within the 12 months before the first positive HIV test. A missed opportunity for prevention was a visit after 2012 that included a negative HIV test, no evaluation for PrEP, and was followed by a positive HIV test. Univariate analysis was performed to assess characteristics of individuals with missed opportunities for screening and prevention services. Between 2006 and 2017, 721 patients were newly diagnosed with HIV. Two hundred forty-seven diagnoses were made in the early period (2006-2010), 236 in the middle period (2010-2013), and 238 in the late period (2014-2017). Overall 60% of patients had at least one missed opportunity, 36% for HIV screening, and 42% for PrEP. There was no improvement in the rates of individuals with a missed opportunity for HIV screening over time. Ending the HIV epidemic will require concerted efforts to bolster access to testing and ensure that all individuals are offered screening, counseling, and linkage to prevention and care services.

The Use of Routine Blood Cultures in Pediatric Appendicitis.

OBJECTIVES: To determine the proportion of true-positive blood culture results in children presenting to the ED with suspected appendicitis. To describe the current practice of obtaining blood cultures in children with suspected appendicitis. METHODS: We performed a 2-year retrospective health record review of all children aged 2 through 17 years investigated for suspected appendicitis at a tertiary Pediatric Emergency Department. Subjects were identified by searching (a) institutional records for ICD-10-CA coding, (b) diagnostic imaging records of ultrasounds for appendicitis, and (c) surgical database records for nonincidental appendectomies. Abstracted demographic and clinical data were matched to regional laboratory services data to describe the performance and result of blood cultures. RESULTS: Overall, 1315 children investigated for appendicitis were reviewed. Seven hundred fifty (57.0%) were girls, the average age was 11.7 years (SD, 4.0). Blood cultures were obtained in 288 (21.9%) of 1315 patients. Of the 11 (3.8%) cultures that were positive, only 1 (0.35%) was a true positive. Young age, high triage acuity, and presence of fever were associated with the acquisition of cultures (P < 0.001 for all). The proportion of children undergoing appendectomy and the negative appendectomy rate was similar between those with and without blood culture (P = 0.10 and P = 0.96, respectively). CONCLUSIONS: True-positive blood cultures are very rare in children presenting to the ED with suspected appendicitis. Given the potential for false-positive cultures and the social/economic implications of initial testing/retesting of false positives, the use of routine blood cultures for children with suspected appendicitis is not supported.

Ondansetron Oral Dissolve Tab vs. Oral Solution in Children Presenting to the Emergency Department with Gastroenteritis.

BACKGROUND: Ondansetron is often used in the emergency department (ED) to promote oral rehydration in children with acute gastroenteritis (AGE), yet medication solutions administered orally may be poorly tolerated in this population. OBJECTIVES: We compared the tolerability of ondansetron oral dissolve tab (ODT) to oral solution (OS) in children presenting to the ED with AGE. METHODS: Using alternate-day controlled clinical trial design, children aged 3 months to 10 years received either ondansetron ODT or OS. Our primary outcome was early vomiting (within 15 min of drug administration). The secondary outcome was intravenous (i.v.) fluid administration. RESULTS: There were 462/534 eligible children who met study criteria. Demographics, severity, and duration of illness were similar between groups. Using intention-to-treat analysis, early vomiting occurred in 8/209 ODT vs. 19/253 OS children (3.8% vs. 7.5%; odds ratio [OR] 0.49; 95% confidence interval [CI] 0.18-1.21). Using as-treated analysis, 6/222 (2.7%) children receiving ODT experienced early vomiting, compared with 21/221 (9.5%) of the OS group (OR 0.26; 95% CI 0.09-0.70). The proportion of children discharged without i.v. fluids was not different (intention-to-treat: ODT = 91.4% (191/209), OS = 94.1% (238/253), OR 1.49, 95% CI 0.69-3.28; as-treated: ODT = 92.3% (205/222), OS = 93.2% (206/221), OR 0.88, 95% CI 0.40-1.93). CONCLUSIONS: Using a conservative intention-to-treat analysis, we found that children presenting to an ED with AGE did not have statistically less early vomiting with ondansetron ODT as compared with OS. However, our as-treated analysis demonstrates that children receiving ondansetron ODT experienced early vomiting approximately one-third as often as those receiving OS. The rate of i.v. fluid administration was no different between groups regardless of the type of analysis used.

A forgotten population: older adults with newly diagnosed HIV.

Limited data are available regarding adults age ≥50 at initial HIV diagnosis. Improved understanding of this group is critical in designing interventions to facilitate earlier diagnosis and linkage to HIV care. We characterize individuals newly diagnosed with HIV, particularly those ≥50 years old, and examine the relationship between age and late diagnosis defined as concurrent HIV and AIDS diagnoses. This is a retrospective study of individuals newly diagnosed with HIV from 2006-2011 at an academic medical center in New York City. Multivariable logistic regression was performed to evaluate the effect of age, gender, race/ethnicity, risk factor, and prior medical visits on late diagnosis. Adults age ≥50 comprised 21.3% of all newly diagnosed individuals. Among these older adults, 70.0% were diagnosed as inpatients and 68.9% concurrent with AIDS, compared to 41.7% and 38.9% of younger adults, respectively. On adjusted analyses, age ≥50 (OR 3.13, 95% CI 1.63, 5.98) and injection drug use (OR 4.4, 95% CI 1.31, 14.75) were positively associated with late diagnosis, whereas female gender was negatively associated with late diagnosis (OR 0.52, 95% CI 0.28, 0.98). Our data suggest that HIV testing efforts targeting older adults are essential to address the unmet needs of this population, including implementation of HIV screening guidelines in primary care settings.

Outcomes of children with suspected appendicitis and incompletely visualized appendix on ultrasound.

OBJECTIVES: The objective was to review the clinical outcomes of children with suspected appendicitis after an ultrasound (US) examination fails to fully visualize the appendix, the diagnostic characteristics of US in children with suspected appendicitis, and the predictive value of secondary signs of appendicitis when the appendix is not fully visualized. METHODS: This was a retrospective health record review of children aged 3 to 17 years presenting to a tertiary pediatric emergency department (ED) with suspected appendicitis. Descriptive statistics and diagnostic test characteristics are reported. RESULTS: Overall, 968 children had US. The appendix was fully visualized in 442 cases (45.7%), and 526 (54.3%) children had incompletely visualized appendices. The disposition of those with incompletely visualized appendices were as follows: 59.1% were discharged home, 10.5% went directly to the operating room, and 30.4% were admitted to the hospital for further observation. Of those discharged home based on clinical findings after incompletely visualized appendices, fewer than 0.3% ended up having appendicitis. Ultimately 15.6% of children with incompletely visualized appendices had pathology-confirmed appendicitis. The sensitivity and specificity of US for children with fully visualized appendices were 99.5% (95% confidence interval [CI] = 96.7% to 100%) and 81.3% (95% CI = 75.2% to 86.2%), respectively. The sensitivity and specificity for the presence of any secondary sign in diagnosing appendicitis were 40.2% (95% CI = 29.6% to 51.7%) and 90.6% (95% CI = 87.5% to 93.2%), respectively. CONCLUSIONS: Children with incompletely visualized appendices on US can be safely discharged home based on clinical findings with an acceptable rate of missed appendicitis. Children with nonreassuring clinical examinations following incompletely visualized appendices on US may benefit from further imaging studies prior to appendectomy, to reduce the rate of negative appendectomy. While the presence of secondary signs of inflammation can be used to rule in appendicitis, statistical strength to rule out appendicitis in the absence of secondary signs is insufficient.

A conformationally mobile cysteine residue (Cys-561) modulates Na+ and H+ activation of human CNT3.

In humans, the SLC28 concentrative nucleoside transporter (CNT) protein family is represented by three Na+-coupled members; human CNT1 (hCNT1) and hCNT2 are pyrimidine and purine nucleoside-selective, respectively, whereas hCNT3 transports both purine and pyrimidine nucleosides and nucleoside drugs. Belonging to a phylogenetic CNT subfamily distinct from hCNT1/2, hCNT3 also mediates H+/nucleoside cotransport. Using heterologous expression in Xenopus oocytes, we have characterized a cysteineless version of hCNT3 (hCNT3C-). Processed normally to the cell surface, hCNT3C- exhibited hCNT3-like transport properties, but displayed a decrease in apparent affinity specific for Na+ and not H+. Site-directed mutagenesis experiments in wild-type and hCNT3C- backgrounds identified intramembranous Cys-561 as the residue responsible for this altered Na+-binding phenotype. Alanine at this position restored Na+ binding affinity, whereas substitution with larger neutral amino acids (threonine, valine, and isoleucine) abolished hCNT3 H+-dependent nucleoside transport activity. Independent of these findings, we have established that Cys-561 is located in a mobile region of the hCNT3 translocation pore adjacent to the nucleoside binding pocket and that access of p-chloromercuribenzene sulfonate to this residue reports a specific H+-induced conformational state of the protein ( Slugoski, M. D., Ng, A. M. L., Yao, S. Y. M., Smith, K. M., Lin, C. C., Zhang, J., Karpinski, E., Cass, C. E., Baldwin, S. A., and Young, J. D. (2008) J. Biol. Chem. 283, 8496-8507 ). The present investigation validates hCNT3C- as a template for substituted cysteine accessibility method studies of CNTs and reveals a pivotal functional role for Cys-561 in Na+- as well as H+-coupled modes of hCNT3 nucleoside transport.

Synthesis and bioactivity of the gibberellin, 18-hydroxy-GA1 (GA132).

As part of a study to confirm putative structural assignments to new gibberellins and to furnish sufficient quantities for biological investigations, a twenty step synthesis of 18-hydroxy GA1 from gibberellic acid (GA3) is described, allowing the confirmation of structure for a new gibberellin, GA132, that occurs in developing grains of barley (Hordeum vulgare). The early part of the sequence involved cleavage of the C(3)-C(4) bond in the A-ring of a 3-oxo intermediate. The ring was then reformed as part of a "domino" process involving the conjugate addition of alkoxide to an alpha-methylene lactone moiety followed by an intramolecular aldol reaction. The bioactivities of the new GA, and its 18-hydroxy-GA4 relative, have been confirmed in dwarf barley growth and alpha-amylase induction assays.

The effects of the Penicillium mycotoxins citrinin, cyclopiazonic acid, ochratoxin A, patulin, penicillic acid, and roquefortine C on in vitro proliferation of porcine lymphocytes.

The in vitro effect of each of the Penicillium mycotoxins citrinin (CIT), cyclopiazonic acid (CPA), ochratoxin A (OTA), patulin (PAT), penicillic acid (PIA) and roquefortine C (RQC) on mitogen induced lymphocyte proliferation was determined using purified lymphocytes from 6 piglets. Dose response curves for each mycotoxin were generated and the concentrations producing 50% inhibition of cell proliferation (IC(50)) were estimated. OTA and PAT were the most potent toxins with IC(50) of 1.3 and 1.2 micromol/l, respectively (0.52 and 0.18 mg/l, respectively). Based on molar concentrations, OTA was 15, 30, 40, and 65 times more potent as an inhibitor than PIA, CIT, CPA and RQC, respectively.

Combined effects of selected Penicillium mycotoxins on in vitro proliferation of porcine lymphocytes.

The in vitro effect of combinations of the Penicillium mycotoxins citrinin (CIT), cyclopiazonic acid (CPA), ochratoxin A (OTA), patulin (PAT), penicillic acid (PIA) and roquefortine C (RQC) on mitogen induced lymphocyte proliferation was determined using purified lymphocytes from six piglets. Dose-response curves for each mycotoxin and mycotoxin combinations were generated. The combined effects of toxin pairs based on IC20 were illustrated in isobole diagrams and statistically calculated. OTA and CIT elicited a synergistic effect. Four toxin pairs elicited additive effects, four pairs less-than-additive effects and six pairs independent effects. Thus, the majority of toxin pairs tested produced lower combined effects than an additive effect. The results indicate that the sum effect of all toxins is less than that from the summation of concentrations of the individual compounds, adjusted for differences in potencies.

Mycotoxin production by Fusarium avenaceum strains isolated from Norwegian grain and the cytotoxicity of rice culture extracts to porcine kidney epithelial cells.

The secondary metabolites of 24 isolates of Fusarium avenaceum from Norwegian cereals and grown on rice have been characterized. Moniliformin (MON), enniatins (ENNs), and beauvericin (BEA) were analyzed by high-performance liquid chromatography. Porcine kidney epithelial cells (PK15, American Type Culture Collection) were used to study the cytotoxicity of MON in the extracts. The following metabolites were produced by all isolates, ranked by concentration in rice cultures: ENN-B, MON, ENN-B1, and ENN-A. BEA was produced by eight isolates. The productions of BEA and ENN-A were significantly correlated, as was the case with ENN-B and ENN-B1. MON production was correlated neither to any of the other toxins nor to toxicity.

Cytotoxicity of trichothecenes and fusarochromanone produced by Fusarium equiseti strains isolated from Norwegian cereals.

The cytotoxicity and secondary metabolites of 28 Norwegian strains of Fusarium equiseti have been characterized. Trichothecenes and fusarochromanone (FUCH) in rice culture extracts of the strains were analysed by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC). The following metabolites were found in all isolates: FUCH, nivalenol (NIV), scirpentriol (SCIRP), 4-acetylnivalenol (4-ac-NIV, also called fusarenon-X), 15-acetyl-nivalenol (15-ac-NIV), and diacetoxyscirpenol (DAS). 4,15-diacetyl-nivalenol (diacetyl-NIV) was found in 5 isolates. Porcine kidney epithelial cells (PK15. American Type Culture Collection) were exposed to rice culture extracts to study cytotoxicity. Descriptive statistics and factor analysis of the identified secondary metabolites show that their main metabolites were FUCH, NIV, SCIRP, DAS and 15-ac-NIV, consecutively. The individual trichothecenes were highly intercorrelated, whereas the production of acetylated NIV and DAS was slightly less. Stepwise multiple regression analysis of cytotoxicity and metabolite profiles of rice culture extracts ascribed the toxicity mainly to a combination of FUCH and 15-ac-NIV, though SCIRP or DAS are agents in the combined toxicity as well.