Examining the Role of Self-Harm in the Relationship between Emergency Department Service Utilization and Trauma-Induced Homelessness among Homeless Individuals in Texas.

Homelessness is a complex public health problem in the United States. Current or ongoing history of trauma among individuals adds to the complexity and challenges of homelessness. Our study assessed the moderating role of self-harm in the association between emergency department (ED) service utilization and trauma-induced homelessness (TIH) among adults in Texas. Homeless adults (N = 282) who completed their baseline Vulnerability Index Service Prioritization Decision Assistance Prescreen Tool survey between February 2021 and February 2022 at a Local Mental Health Authority in Texas were selected. The outcome variable, TIH, was assessed by current period of homelessness due to experiencing trauma or abuse. The main independent variable was ED utilization, while self-harm in the past year was assessed as the moderating variable. A multivariate logistic regression with a moderation analysis was conducted while adjusting for the covariates. Individuals who utilized ED services and engaged in self-harm and risky behaviors had greater odds of experiencing current period of TIH. Male respondents were less likely to experience TIH. Finally, engaging in self-harm significantly moderated the association between ED service use and TIH. This study may help inform efforts to develop tailored interventions and promote resilience-based approaches to improve health outcomes among individuals experiencing homelessness due to TIH.

Pelvic mapping to explore patterns of chronic pelvic pain.

PURPOSE: Chronic pelvic pain syndromes (CPPS) are commonly encountered by urologists and urogynecologists and pose diagnostic and therapeutic challenges. Body maps have been helpful adjuncts to verbal descriptions of pain and may serve a role in phenotyping what is known to be a heterogeneous patient population. The aim of this study was to assess whether patterns of pain as marked on a body map of the pelvis exist among common CPPS diagnoses. The secondary aim was to investigate the association between the total number of pain locations marked on the map and clinical indices in patients with 1 to 3 CPPS diagnoses. MATERIALS AND METHODS: Data was collected on patients who visited the Northwell Health Pelvic Pain Treatment Center (PPTC) from January to May 2022 and were diagnosed with at least one of four major CPPS diagnoses: interstitial cystitis/bladder pain syndrome (IC/BPS), pelvic floor myalgia (PFM), chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and vulvodynia. Demographic data as well as survey data from pelvic pain maps, Genitourinary Pain Index (GUPI) forms, and the short form-6 of the Pain Catastrophizing Scale (PCS-6) were recorded. Descriptive statistics among CPPS groups and Pearson correlations among the number of CPPS diagnoses were computed. RESULTS: One hundred seventy females and 125 males with CPPS were included in the study. Significant cross-over in mapping patterns was notable between IC/BPS and PFM groups, both most commonly marking "abdomen" and "genital" regions. The most distinct pattern of pain was seen in patients with CP/CPPS and in patients with vulvodynia. Among the total sample, as the mean number of pain locations marked within the pelvis increased, GUPI and PCS scores increased (p < 0.05). As the number of CPPS diagnoses increased, the strength of the relationship independently increased. CONCLUSIONS: Pelvic body mapping demonstrated that different forms of CPPS displayed different distributions of pain, but mapping was not predictive of any diagnostic group. Nevertheless, the pelvic body map proved useful in identifying precise locations of pain and may help uncover regions of pain that cannot be easily communicated. The total number of pain sites marked appeared to correlate with worse clinical features.

The nutritional role of free sialic acid, a human milk monosaccharide, and its application as a functional food ingredient.

N-Acetyl-d-neuraminic acid (NANA), more commonly known by its trivial name sialic acid, is an endogenous human and ubiquitous nutritional monosaccharide. As a bound sugar at the terminal positions of glycans NANA is known to play important roles in many biological events. The data that exist on the occurrence of the free monosaccharide in breast milk and nutrition, however, are less commonly discussed. In most foods of animal origin, sialic acid occurs as a mixture of NANA and N-glycolyl-d-neuraminic acid (NGNA), a hydroxylated derivative of NANA that is not found in humans. The dietary intake of NGNA has been identified as a risk factor for long-term adverse health effects. Therefore, we present summaries on the biochemistry, metabolism, bioavailability, and the data on NANA and NGNA levels that occur in diverse foods. Finally, we discuss the emerging data demonstrating that free NANA is linked to positive nutritional effects including pronounced antioxidative properties. These data and the extremely high safety profile of NANA justify dietary enrichment at levels that correspond to the dietary intake of NANA in infants through breast milk.

Safety evaluation of the human-identical milk monosaccharide, l-fucose.

l-Fucose is a natural monosaccharide present in mammals where it is found predominantly as an O-glycosidically linked component of glycoproteins, glycolipids, and oligosaccharides. It is also present in its free form in human breast milk (human milk monosaccharide). l-Fucose plays important roles in the development of the immune and nervous systems and is involved in cognitive function and memory formation. The human-identical milk monosaccharide l-fucose is therefore proposed for use in infant formulas to better simulate the free saccharides present in human breast milk. As part of the safety evaluation of l-fucose, a subchronic dietary toxicity study preceded by an in utero phase was conducted in Sprague-Dawley rats. l-Fucose was without maternal toxicity or compound-related adverse effects on female reproduction and general growth and development of offspring at a maternal dietary level up to 1%, equivalent to a dose of 1655 mg/kg body weight (bw)/day. During the subchronic phase, no compound-related adverse effects were observed in first generation rats at dietary levels of up to 1% (highest level tested), corresponding to doses of 516 and 665 mg/kg bw/day in males and females, respectively. l-Fucose was non-genotoxic in a series of in vitro genotoxicity/mutagenicity tests. These results support the safe use of l-fucose in infant formula and as a food ingredient at levels equivalent to those present in human breast milk.

Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation.

Inorganic polyphosphate is widespread in biology and exhibits striking prohemostatic, prothrombotic, and proinflammatory effects in vivo. Long-chain polyphosphate (of the size present in infectious microorganisms) is a potent, natural pathophysiologic activator of the contact pathway of blood clotting. Medium-chain polyphosphate (of the size secreted from activated human platelets) accelerates factor V activation, completely abrogates the anticoagulant function of tissue factor pathway inhibitor, enhances fibrin clot structure, and greatly accelerates factor XI activation by thrombin. Polyphosphate may have utility as a hemostatic agent, whereas antagonists of polyphosphate may function as novel antithrombotic/anti-inflammatory agents. The detailed molecular mechanisms by which polyphosphate modulates blood clotting reactions remain to be elucidated.

Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation.

Inorganic polyphosphates are linear polymers of orthophosphate that modulate blood clotting and inflammation. Polyphosphate accumulates in infectious microorganisms and is secreted by activated platelets; long-chain polyphosphate in particular is an extremely potent initiator of the contact pathway, a limb of the clotting cascade important for thrombosis but dispensable for hemostasis. Polyphosphate inhibitors therefore might act as novel antithrombotic/anti-inflammatory agents with reduced bleeding side effects. Antipolyphosphate antibodies are unlikely because of polyphosphate's ubiquity and simple structure; and although phosphatases such as alkaline phosphatase can digest polyphosphate, they take time and may degrade other biologically active molecules. We now identify a panel of polyphosphate inhibitors, including cationic proteins, polymers, and small molecules, and report their effectiveness in vitro and in vivo. We also compare their effectiveness against the procoagulant activity of RNA. Polyphosphate inhibitors were antithrombotic in mouse models of venous and arterial thrombosis and blocked the inflammatory effect of polyphosphate injected intradermally in mice. This study provides proof of principle for polyphosphate inhibitors as antithrombotic/anti-inflammatory agents in vitro and in vivo, with a novel mode of action compared with conventional anticoagulants.

Controversies regarding the new oral anticoagulants for stroke prevention in patients with atrial fibrillation.

Increasing use of the new oral anticoagulants (NOACs) - dabigatran, rivaroxaban, and apixaban - has prompted considerable discussion in the medical community even as warfarin remains the mainstay of therapy. This article raises 10 controversial issues regarding the use of NOACs for stroke prevention in patients with atrial fibrillation, and offers a review of the latest available evidence. We provide a brief overview of the mechanism and dosing of these drugs, as well as a summary of the key clinical trials that have brought them into the spotlight. Comparative considerations relative to warfarin such as NOAC safety, efficacy, bleeding risk, reversibility, drug-transitioning and use in patients well controlled on warfarin are addressed. Use in select populations such as the elderly, those with coronary disease, renal impairment, or on multiple anti-platelet drugs is also discussed. Finally, we consider such specific issues as comparative efficacy, off-label use, cost, rebound and management during events. Ultimately, the rise of the NOACs to mainstream use will depend on further data and clinical experience amongst the medical community.

Safety evaluation of the human-identical milk monosaccharide sialic acid (N-acetyl-d-neuraminic acid) in Sprague-Dawley rats.

N-Acetyl-d-neuraminic acid (Neu5Ac) is the predominant form of sialic acid (Sia) in humans, while other mammals express Sia as a mixture with N-glycolyl-d-neuraminic acid (Neu5Gc). Neu5Ac occurs in highest levels in the brain and in breast milk, and is therefore, coined a human-specific milk monosaccharide, and is thought to play an important nutritional role in the developing infant. Synthesized human-identical milk monosaccharide (HiMM) Neu5Ac is proposed for use in infant formulas to better simulate the free saccharides present in human breast milk. As part of the safety evaluation of HiMM Neu5Ac, a subchronic dietary toxicity study preceded by an in utero phase was conducted in Sprague-Dawley rats. Neu5Ac was without maternal toxicity or compound-related adverse effects on female reproduction and on the general growth and development of offspring at a maternal dietary level of up to 2%, equivalent to a dose of 1895mg/kg body weight (bw)/day. During the subchronic phase, no compound-related adverse effects were observed in first generation rats at dietary levels of up to 2% (highest level tested), corresponding to doses of 974 and 1246mg/kgbw/day in males and females, respectively. Neu5Ac also was non-genotoxic in a series of in vitro genotoxicity/mutagenicity tests. These results support the safe use of Neu5Ac both in infant formula and as a food ingredient at levels equivalent to those found naturally in human breast milk.

Emerging Novel Functional Imaging and Immunotherapy in Renal Cell Carcinoma and Current Treatment Sequencing Strategies After Immunotherapy.

The management of renal cell carcinoma (RCC) has advanced significantly in the past two decades. Many promising functional imaging modalities such as radiolabeled tracer targeting carbonic anhydrase IX and prostate-specific membrane antigen are under development to detect primary kidney tumors, stage systemic disease, and assess treatment response in RCC. Immune checkpoint inhibitors targeting PD-1 and cytotoxic T-cell lymphocyte-4 have changed the treatment paradigm in advanced RCC. Trials investigating novel mechanisms such as LAG-3 immune checkpoint inhibition, chimeric antigen receptor T-cell therapies, and T-cell engagers targeting RCC-associated antigens are currently ongoing. With the rapidly changing treatment landscape of RCC, the treatment sequence strategies will continue to evolve. Familiarity with the toxicities associated with the therapeutic agents and how to manage them are essential to achieve optimal patient outcomes. This review summarizes the recent developments of functional imaging and immunotherapy strategies in RCC, and the evidence supports treatment sequencing.

Third-Line Overactive Bladder Therapies on TikTok: What Does the Public Learn?

IMPORTANCE: Millions of people rely on social media platforms, including TikTok, for health-related information. TikTok has not yet been evaluated as an information source for overactive bladder (OAB) third-line therapies. OBJECTIVES: Our aim was to assess TikTok videos on third-line therapies for OAB for misinformation and quality. STUDY DESIGN: In this cross-sectional analysis, we abstracted the top 50 TikTok videos for keywords: "Axonics," "sacral neuromodulation," "Interstim," "PTNS," "posterior tibial nerve stimulation," and "bladder Botox." Videos were scored for quality by 3 independent reviewers using the Medical Quality Video Evaluation Tool (MQ-VET). Two reviewers determined if videos contained misinformation. RESULTS: Of 300 videos screened, 119 videos were included. Twenty-four (21%) were created by medical professionals (MPs). Medical professional videos were more frequently shared (5 vs 1, P < 0.01) but had similar views, likes, comments, and length. Although MP videos had significantly higher MQ-VET scores (43 vs 27, P < 0.01), there was no difference in the rate of misinformation between MP and non-MP videos (21% vs 18%). Twenty-two videos (18.4%) contained misinformation, which were 3 times longer (50.5 vs 15 seconds, P < 0.01) and had higher MQ-VET scores (34.5 vs 27, P = 0.03) than those without misinformation. Common themes of misinformation pertained to therapy indication, mechanism of action, and patient limitations after undergoing therapy. CONCLUSIONS: Many TikTok videos on OAB third-line therapies contain misinformation. Most of these videos were not of high quality and created by the public. Medical professionals should be aware of misinformation permeating TikTok, given its large audience, and aim to promote or offer educational material of better accuracy and quality.

Characterization of Wnt Signaling Pathway Aberrations in Metastatic Prostate Cancer.

Wnt-signaling pathway (WSP) alterations have been identified in patients with prostate cancer (PCa) and are implicated in disease progression and hormonal resistance. We utilized a multi-institutional dataset to characterize molecular alterations in the canonical and non-canonical WSP in PCa. Patients with PCa who underwent tissue-based genomic sequencing were investigated. Tumors with somatic activating mutations in CTNNB1 or RSPO2, or inactivating mutations in either APC or RNF43 were characterized as having aberrant canonical Wnt signaling (WSP-activated). Overall survival (OS) analyses were restricted to microsatellite stable (MSS) tumors lacking RNF43 G659fs* mutations. We also investigated non-canonical WSP by evaluation of ROR1, ROR2, and WNT5 in WSP-activated versus WSP wild-type (WSP-WT) tumors. Of 4,138 PCa samples, 3,684 were MSS. Among MSS tumors, 42.4% were from metastatic sites, of which 19.1% were WSP-activated, and 57.6% from the prostate, of which 10.1% were WSP-activated. WSP-activated tumors were more prevalent in metastatic sites than in primary PCa. WSP-activated PCa exhibited more SPOP mutations and higher expression of canonical WSP activators than WSP-WT tumors. ROR1 gene expression was elevated in WSP-activated tumors from both primary and metastatic sites. M2 macrophages predominated the tumor microenvironment in WSP-activated tumors. There was no significant difference in OS between WSP-activated and WSP-WT PCa patients. WSP-activated PCa demonstrated a more immunosuppressed tumor microenvironment and a pronounced upregulation of ROR1 gene expression, underscoring its potential involvement in the crosstalk between canonical and non-canonical Wnt signaling pathways. Implications: Our findings may provide rationale for developing novel therapeutic strategies targeting Wnt-activated PCa.

Polyphosphate is a cofactor for the activation of factor XI by thrombin.

Factor XI deficiency is associated with a bleeding diathesis, but factor XII deficiency is not, indicating that, in normal hemostasis, factor XI must be activated in vivo by a protease other than factor XIIa. Several groups have identified thrombin as the most likely activator of factor XI, although this reaction is slow in solution. Although certain nonphysiologic anionic polymers and surfaces have been shown to enhance factor XI activation by thrombin, the physiologic cofactor for this reaction is uncertain. Activated platelets secrete the highly anionic polymer polyphosphate, and our previous studies have shown that polyphosphate has potent procoagulant activity. We now report that polyphosphate potently accelerates factor XI activation by α-thrombin, ß-thrombin, and factor XIa and that these reactions are supported by polyphosphate polymers of the size secreted by activated human platelets. We therefore propose that polyphosphate is a natural cofactor for factor XI activation in plasma that may help explain the role of factor XI in hemostasis and thrombosis.

Safety evaluation of glucose oxidase from Penicillium chrysogenum.

Glucose oxidase (ß-d-glucose:oxygen 1-oxidoreductase; EC 1.1.2.3.4) is used in the food and beverage industry as a preservative and stabilizer and is commonly derived from the fungus Aspergillus niger. Although the safety of glucose oxidase preparations from A. niger is well-established, the use of preparations derived from other fungal species is of interest; however, an assessment of their safety is warranted. Here, we report on the safety of a glucose oxidase preparation derived from the fungus Penicillium chrysogenum (designated as PGO) for commercial use in food processing, as well as an ingredient in food. In a repeated dose 90-day oral toxicity study conducted in rats, PGO was without compound-related adverse effects at doses of up to 15,600U/kg body weight/day, equivalent to 193mg total organic solids/kg body weight/day. In addition, PGO was non-genotoxic in a series of genotoxicity tests, including a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and a combined in vivo mammalian erythrocyte micronucleus test and comet assay. The results of these studies support the safe use of PGO in food for human consumption.

Polyphosphate exerts differential effects on blood clotting, depending on polymer size.

Polyphosphate, a linear polymer of inorganic phosphate, is secreted by activated platelets and accumulates in many infectious microorganisms. We recently showed that polyphosphate modulates the blood coagulation cascade at 3 steps: it triggers the contact pathway, it accelerates factor V activation, and it enhances fibrin polymerization. We now report that polyphosphate exerts differential effects on blood clotting, depending on polymer length. Very long polymers (≥ 500mers, such as those present in microorganisms) were required for optimal activation of the contact pathway, while shorter polymers (∼ 100mers, similar to the polymer lengths released by platelets) were sufficient to accelerate factor V activation and abrogate the anticoagulant function of the tissue factor pathway inhibitor. Optimal enhancement of fibrin clot turbidity by polyphosphate required ≥ 250mers. Pyrophosphate, which is also secreted by activated platelets, potently blocked polyphosphate-mediated enhancement of fibrin clot structure, suggesting that pyrophosphate is a novel regulator of fibrin function. In conclusion, polyphosphate of the size secreted by platelets is very efficient at accelerating blood clotting reactions but is less efficient at initiating them or at modulating clot structure. Microbial polyphosphate, which is highly procoagulant, may function in host responses to pathogens.

Impact of in-hospital major bleeding on outcomes in acute coronary syndromes.

PURPOSE OF REVIEW: To describe the hazard of in-hospital major bleeding after acute coronary syndromes. RECENT FINDINGS: Long-term complications of early bleeding can extend to over 3 years beyond the index event. Nonaccess-site bleeding accounts for much of the higher risk associated with major in-hospital bleeding. SUMMARY: Bleeding complications after percutaneous coronary intervention are a consistent and independent predictor of adverse clinical outcomes. The majority of complications associated with major bleeding are attributable to in-hospital early bleeds. Whether the link between bleeding and increased mortality is causal has not been established. Bleeding may simply be a marker of higher comorbidity. When possible, bleeding should be avoided, and strategies such as use of risk scores, bivalirudin, vascular closure devices and radial access may decrease major bleeding. In the highest-risk patients, however, bleeding avoidance strategies may not be effective.

Comprehensive treatment of extensively drug-resistant tuberculosis.

BACKGROUND: Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. METHODS: A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. RESULTS: Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [+/-SD] number of regimens, 4.2+/-1.9 vs. 3.2+/-1.6; P<0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4+/-1.1 vs. 5.3+/-1.5; P<0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3+/-1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). CONCLUSIONS: Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis.

Safety evaluation of Propionibacterium freudenreichii ET-3 culture.

Propionibacterium freudenreichii ET-3 culture, a cell-free product of whey fermentation using P. freudenreichii ET-3 (7025), has been shown to promote the growth of Bifidobacteria through the action of 1,4-dihydroxy-2-naphthoic acid (DHNA), and therefore, has potential use in the food and supplement industries. Although currently used as a food ingredient in Japan, the safety of this novel ingredient has not been previously evaluated through traditional toxicity testing. Therefore, here we report the results of standard toxicological testing performed on P. freudenreichii ET-3 culture. In a 4-week oral toxicity study, administration of 6000mg/kg body weight/day P. freudenreichii ET-3 culture was without compound-related adverse effects on clinical signs, body weights, food consumption, ophthalmology, hematology, clinical chemistry, urinalysis, organ weights, and gross and microscopic findings in male and female Sprague-Dawley rats. Furthermore, in vitro mutagenicity testing demonstrated that P. freudenreichii ET-3 culture was non-mutagenic in the bacterial reverse mutation assay using a standard battery of bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, and TA1537 and Escherichia coli WP2 uvrA) and non-clastogenic in Chinese hamster lung cells in the mammalian chromosome aberration test. Together, the results of these studies support the safety of P. freudenreichii ET-3 culture for use in foods for human consumption.

A functional genomics screen identifying blood cell development genes in Drosophila by undergraduates participating in a course-based research experience.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.

Phosphoramidate end labeling of inorganic polyphosphates: facile manipulation of polyphosphate for investigating and modulating its biological activities.

Polyphosphates, linear polymers of inorganic phosphates linked by phosphoanhydride bonds, are widely present among organisms and play diverse roles in biology, including functioning as potent natural modulators of the human blood clotting system. However, studies of protein-polyphosphate interactions are hampered by a dearth of methods for derivatizing polyphosphate or immobilizing it onto solid supports. We now report that EDAC (1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide) efficiently promotes the covalent attachment of a variety of primary amine-containing labels and probes to the terminal phosphates of polyphosphates via stable phosphoramidate linkages. Using (31)P NMR, we confirmed that EDAC-mediated reactions between primary amines and polyphosphate result in phosphoramidate linkages with the terminal phosphate groups. We show that polyphosphate can be biotinylated, labeled with fluorophores, and immobilized onto solid supports, that immobilized polyphosphate can be readily used to quantify protein binding affinities, that covalently derivatized or immobilized polyphosphate retains its ability to trigger blood clotting, and that derivatizing the ends of polyphosphate with spermidine protects it from exopolyphosphatase degradation. Our findings open up essentially the entire armamentarium of protein chemistry to modifying polyphosphate, which should greatly facilitate studies of its biological roles.

Safety evaluation of highly-branched cyclic dextrin and a 1,4-alpha-glucan branching enzyme from Bacillus stearothermophilus.

Highly-branched cyclic dextrin (HBCD), a dextrin food ingredient presently only used in Japan, was investigated for digestibility and potential toxicity. HBCD was readily hydrolyzed in vitro to maltose and maltotriose by human salivary and porcine pancreatic alpha-amylases. Incubation of HBCD with a rat intestinal homogenate, containing digestive enzymes, resulted in the formation of maltose, maltotriose, and maltotetraose, and with longer incubation times, resulted in the formation of glucose. In an acute toxicity study, Wistar rats orally administered a single-dose of 2000mg/kg body weight of HBCD did not display mortality or any signs or symptoms of toxicity or abnormalities upon necropsy. Transient loose stools were observed, but were resolved within 24h of HBCD administration, and therefore, were not considered as compound-specific adverse effects. In the Ames assay, HBCD was non-mutagenic with or without metabolic activation. Toxicity testing of the branching enzyme (BE) involved in the synthesis of HBCD showed that the BE also was not acutely toxic when orally administered to rats and was non-mutagenic in the mouse lymphoma assay. The results of this study demonstrate that HBCD is digested to normal and safe products of carbohydrate digestion, and therefore, support the safety of HBCD for human consumption.