Prevalence of HTLV-1 and Hepatitis B Surface Antigen (HBsAg) Positivity among MSM Attending a Large HIV Treatment Centre in Trinidad.

HIV-1, Hepatitis B and HTLV-1 have similar risk factors and shared routes of transmission and MSM are disproportionately affected by HIV. The aim of the study was to determine the prevalence of HTLV-1 and HBsAg positivity at initial enrolment among MSM attending a large HIV Clinic in Trinidad. Chart reviews were conducted between 2 and 15 January 2024, among self-identified MSM and a comparative group of randomly selected self-identified heterosexual males where sociodemographic, clinical and laboratory data were collected and analysed using SPSS Version 25. During the period April 2002-31 October 2023, in total there were 10,424 patients registered at the clinic, of whom 1255 (12.0%) were self-identified MSM, with an age range of 19-85 years and a median age of 40 years. There were 1822 randomly selected heterosexual males, with an age range of 18-94 years old and a median age of 52 years. Among the MSM, there were 21 (1.67%) patients who were HIV-1/HTLV-1-coinfected, 64 (5.10%) who were HIV-1/HBsAg-coinfected and two (0.16%) who were coinfected with all three viruses (HIV-1/HTLV-1/HBsAg) as compared to 47 ((2.58%) HIV-1/HTLV-1-coinfected (p = 0.12), 69 (3.79%) HIV-1/HBsAg-coinfected (p = 0.10) and three (0.16%) patients coinfected with all three viruses among the heterosexual males. There were no patients with HTLV-1-related diseases among the HIV-1/HTLV-1-coinfected patients and there were no deaths from chronic liver disease in patients coinfected with HIV-1/HBsAg. Despite the availability of an efficacious vaccine, there is a prevalence of hepatitis B of 5.1% among MSM attending the HIV Clinic in Trinidad; therefore, programmes to increase health literacy, screening and immunization are urgently needed.

Clinical Features and Follow-Up of the First Two Cases of Mpox From Trinidad and Tobago.

Mpox is a viral zoonotic disease that is endemic in Central and West Africa and belongs to the Orthopoxvirus genus. A global outbreak of mpox began in May 2022, mainly due to the transmission of the clade 11b virus through person-to-person contact with the lesions or scabs of a person infected with mpox. The data on mpox infection in the Caribbean is sparse. Here we report the clinical features and follow-up of the first two confirmed cases of mpox in Trinidad and Tobago (T&T). Both patients were men who have sex with men (MSM) who presented with genital lesions and expressed concern about increased stigma towards their already marginalized community.

The Burden of Pretreatment HIV Drug Resistance in Trinidad and Tobago.

Strategies to improve the scale-up of antiretroviral therapy (ART) for patients with HIV in Trinidad and Tobago, including the adoption of the "Test and Treat All" policy, have accompanied an increase in the number of patients with pretreatment HIV drug resistance (PDR) in the country. However, the scale of this public health problem is not well established. The objective of this study was to estimate the prevalence of PDR and evaluate its impact on viral suppression among patients with HIV receiving care at a large HIV treatment center in Trinidad and Tobago. We retrospectively analyzed data from the Medical Research Foundation of Trinidad and Tobago of patients newly diagnosed with HIV who had HIV genotyping performed. PDR was defined as having at least one drug-resistant mutation. We assessed the impact of PDR on achieving viral suppression within 12 months of ART initiation, using a Cox extended model. Among 99 patients, 31.3% had PDR to any drug, 29.3% to a non-nucleoside reverse transcriptase inhibitor (NNRTI), 3.0% to a nucleoside reverse transcriptase inhibitor, and 3.0% to a protease inhibitor. Overall, 67.1% of the patients who initiated ART (n = 82) and 66.7% (16/24) of patients with PDR achieved viral suppression within 12 months. We found no significant association between PDR status and achieving viral suppression within 12 months [adjusted hazard ratio: 1.08 (95% confidence interval: 0.57-2.04)]. There is a high prevalence of PDR in Trinidad and Tobago, specifically driven by NNRTI resistance. Although we found no difference in virologic suppression by PDR status, there is an urgent need for an effective HIV response to address the many drivers of virologic failure. Accelerating access to affordable, quality-assured generic dolutegravir and adopting it as the preferred first-line ART therapy are critical.

Understanding divergent substrate stereoselectivity in the isothiourea-catalysed conjugate addition of cyclic α-substituted ß-ketoesters to α,ß-unsaturated aryl esters.

The development of enantioselective synthetic methods capable of generating vicinal stereogenic centres, where one is tetrasubstituted (such as either an all-carbon quaternary centre or where one or more substituents are heteroatoms), is a recognised synthetic challenge. Herein, the enantioselective conjugate addition of a range of carbo- and heterocyclic α-substituted ß-ketoesters to α,ß-unsaturated aryl esters using the isothiourea HyperBTM as a Lewis base catalyst is demonstrated. Notably, divergent diastereoselectivity is observed through the use of either cyclopentanone-derived or indanone-derived substituted ß-ketoesters with both generating the desired stereodefined products with high selectivity (>95 : 5 dr, up to 99 : 1 er). The scope and limitations of these processes are demonstrated, alongside application on gram scale. The origin of the divergent substrate selectivity has been probed through the use of DFT-analysis, with preferential orientation driven by dual stabilising CH⋯O interactions. The importance of solvation with strongly polar transition-states is highlighted and the SMD solvation model is demonstrated to capture solvation effects reliably.

The incidence of histoplasmosis and cryptococcal antigenemia among patients attending a large HIV clinic in Trinidad.

Our aim was to determine the incidence disseminated histoplasmosis and cryptococcal antigenemia among 280 patients with a CD4<350 cells/mm3 attending a large HIV clinic in Trinidad over the period November 2021-June 2022. Sera were screened for cryptococcal antigen (CrAg) using the Immy CrAg Immunoassay (EIA) and the Immy CrAg lateral flow assay (LFA). Urine was screened for Histoplasma antigen using the Immy EIA and the Optimum Imaging Diagnostics (OIDx) LFA. For the purposes of analysis, it was assumed, that all patients with positive urine Histoplasma antigen tests by both EIA and LFA and those with a single positive urine Histoplasma antigen test and clinical features of disseminated histoplasmosis were true positives. The incidence of probable disseminated histoplasmosis and cryptococcal antigenemia were 6.4% (18/280) and 2.5% (7/280) respectively. The sensitivity and specificity of the Immy Histoplasma EIA were 100% (95% CI, 81.5%-100%) and 98.5% (95% CI, 96.1% - 99.6%) respectively as compared to the OIDx Histoplasma LFA of 88.9% (95% CI, 65.3% - 98.6%) and 93.9% (95% CI, 90.3% - 96.5%) respectively, with substantial agreement between the 2 test kits (Kappa value = 0.763; 95% CI 0.685, 0.841). Testing for disseminated histoplasmosis in HIV patients is important in endemic areas.

Correlates and Predictors of COVID-19 Vaccine Hesitancy Among Persons Living With HIV in Trinidad and Tobago.

BACKGROUND: Persons living with HIV may be at risk of more severe forms of COVID-19 infection and minimizing health risks largely depends on their acceptance of the COVID-19 vaccinations. OBJECTIVE: This study examined the correlates and predictors of COVID-19 vaccine hesitancy among persons living with HIV in Trinidad and Tobago. METHODS: A cross-sectional survey using a structured interview was conducted. Data were compiled on patient socio-demographics, diagnosed chronic diseases, psychological factors, and decisions to take the COVID-19 vaccine. Pearson χ2 tests examined the associations between study variables and COVID-19 vaccine hesitancy, and multivariable logistic regression analyses examined its predictors. RESULTS: In this study, 84% were virally suppressed, i.e., HIV viral load <1000 copies/ml. COVID-19 vaccine hesitancy was found to be 39%. Univariate analysis showed that higher vaccine hesitancy was significantly associated with females (OR 2.02, 95% CI 1.23-3.33) and patients of mixed ethnicity (OR 1.84, 95% CI 1.07-3.15). In our multivariable analysis, psychological factors namely, confidence in the COVID-19 vaccine (OR 0.16, 95% CI 0.05-0.47), the perceived benefits of the vaccine (OR 0.54, 95% CI 0.37-0.79), and cues to action (OR 0.68, 95% CI 0.47-0.97) were observed as predictors of COVID-19 vaccine hesitancy. CONCLUSION: Psychological factors such as confidence in the COVID-19 vaccine, perceived benefits of the vaccine, and cues to action were possible predictors of COVID-19 vaccine hesitancy. This study underscored the continued need for strategies to increase confidence and knowledge about the benefits of taking the COVID-19 vaccine among persons living with HIV.

Trichomoniasis refractory to 5-nitroimidazole therapy in Trinidad.

Trichomoniasis is the most common non-viral sexually transmitted infection (STI) occurring worldwide and the majority of infected persons (70-85%) have mild or no genital symptoms. Symptoms in women may include a vaginal discharge which may be associated with vulval irritation and most infections can be effectively treated with metronidazole 500mg bd for seven days. Trichomoniasis unresponsive to 5-nitroimidazole therapy is uncommon but results in substantial therapeutic challenges, especially in resource limited countries. We present such a case which was eventually treated with a low-cost intravaginal combination of boric acid and clotrimazole cream.

HTLV-1 Coinfection among Patients Attending a Large HIV Treatment Centre in Trinidad.

Studies have shown that HIV-1/HTLV-1 coinfected patients tend to have higher CD4+ counts than HIV singly infected patients. Two chart reviews were conducted at initial enrolment among patients attending a large HIV Clinic in Trinidad, one to determine the prevalence of HIV-1/HVLV-1 coinfection and another to compare the CD4+ counts and opportunistic infections among HIV-1/HTLV-1 coinfected patients compared to a randomly selected comparison group of HIV-1 singly infected patients. Sociodemographic, clinical and laboratory data were collected and analysed using SPSS Version 25. During the period April 2002−December 2018, 8916 HIV-1 patients were enrolled at the clinic; 159 were HIV-1/HTLV-1 coinfected; the age range was 18−81 years; the median age was 40 years; 87 (54.7%) were females; and the median CD4+ count and median HIV-1 viral load at enrolment were 300 cells/mm3 and 128,543 copies/mL, respectively, with an HTLV-1 seroprevalence of 1.78%. Among the 477 HIV-1 singly infected patients, the age range was 18−71 years; the median age was 33 years; 248 (52.0%) were males; and the median CD4+ count and the median HIV viral load were 295 cells/mm3 and 23,369 copies/mL, respectively. Opportunistic infections (OIs) were diagnosed in 59 (37.1%) of the coinfected patients versus 48 (10.1%) among those HIV singly infected (p < 0.001). HIV-1/HTLV-1 coinfected patients had higher HIV-1 viral loads (p < 0.001) and more OIs, suggesting a worse prognosis though there were no statistically significant differences in CD4+ counts (p = 0.96) as compared to the HIV-1 mono-infected patients.

Arylboronic Acid-Catalyzed Racemization of Secondary and Tertiary Alcohols.

The use of 2-carboxyphenylboronic acid (5 mol %) and oxalic acid (10 mol %) with 2-butanone as a solvent for the racemization of a range of enantiomerically pure secondary and tertiary alcohols is demonstrated. The process is postulated to proceed via reversible Brønsted acid-catalyzed C-O bond cleavage through an achiral carbocation intermediate.

Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,ß-Unsaturated Aryl Esters.

An enantioselective Michael addition of malonates to α,ß-unsaturated para-nitrophenyl esters was achieved using the Lewis basic isothiourea HyperBTM, giving excellent levels of product enantioselectivity (up to >99:1 enantiomeric ratio) in good yields and with complete regioselectivity (>20:1 regioselectivity ratio) in the presence of alternative (phenyl ketone and ethyl ester) Michael acceptors. Density functional theory calculations indicate that N-acylation is rate-limiting. This constitutes a rare example of a highly enantioselective addition of simple, readily available malonates to α,ß-unsaturated esters.

Correlates of prevalent syphilis infection among men who have sex with men (MSM) living with HIV attending the HIV clinic in Trinidad.

BACKGROUND: Syphilis among men who have sex with men (MSM) living with HIV is of public health concern, thus the objective of the study is to determine the correlates of prevalent syphilis infection in this population so that urgent interventions could be instituted. METHODS: A cross-sectional study was conducted during the period September 2020-June 2021 among MSM who attended a large HIV Clinic in Trinidad. A questionnaire was administered to obtain socio-demographic data and correlates of prevalent syphilis and patients were screened for syphilis using the traditional algorithm. Descriptive and bivariate analyses were conducted and multivariable logistic regression factors was used to assess factors significantly associated with a syphilis diagnosis. RESULTS: Two hundred and sixty four MSM were enrolled; age range 18-64 years, median age 33 years and 89 (34.4%) were actively bisexual. The prevalence of syphilis was 28% (74/264) and 89.2% (66/74) of these infections were asymptomatic. Multivariable logistic regression analysis showed that those patients who participated in sex with anonymous partners (OR 2.09; 95% CI, 1.03-4.26), those with a previous diagnosis of syphilis (OR 5.16; 95% CI, 1.03-25.83) and those who used marijuana in the last 12 months (OR 2.13; 95% CI, 1.14-3.96) were more likely to be diagnosed with syphilis. CONCLUSION: There is a high prevalence of asymptomatic syphilis among MSM living with HIV in Trinidad. Repeat episodes of syphilis and anonymous sex may play a role in the transmission dynamics of T pallidum infection in this population, thus urgent public health prevention interventions are warranted.

Psoriasis in Patients Attending a Large HIV Clinic in Trinidad.

The data on psoriasis in persons infected with HIV in the Caribbean is sparse. A cross-sectional study was conducted on patients attending the HIV Clinic diagnosed with psoriasis where sociodemographic data and data on the pattern of psoriasis were collected and analysed using SPSS version 25. Over the period April 2002-December 2018, 37 persons attending the HIV clinic were diagnosed with psoriasis, age range at psoriasis diagnosis 13-70 years, mean age at diagnosis 37.7 years and 32 (86.5%) were male. Over the study period, 8916 patients were registered at the HIV Clinic and the prevalence of psoriasis among these patients was 0.42% which is less than the reported prevalence of psoriasis among persons infected with HIV of 2-3% in other studies. Severe/generalised psoriasis was present in 7 (18.9%) patients while 30 (81.1%) patients had mild/moderate psoriasis. A family history of psoriasis was present in 1 (2.7%) patient, psoriatic arthritis was present in 2 (5.4%) patients and 31 (83.8%) patients reported that there was improvement in the psoriasis with the topical therapy provided. The study makes an original contribution in the determination of the prevalence and pattern of psoriasis among patients attending a HIV Clinic in Trinidad.

Clinical presentation of herpes simplex virus infection mimicking neoplasia on the face of persons living with HIV.

The clinical presentations of herpes simplex virus (HSV) infections are varied and range from asymptomatic to a prodrome of tingling and burning followed by painful vesicles, erosions and ulcers. Resolution leads to latent infection of the sensory ganglia. HSV-1 is associated with most of the nongenital HSV-induced infections and HSV-2 is generally associated with anogenital lesions; however, lesions at either site may be caused by both viruses. In persons living with HIV (PLHIV), the lesions have been described as verrucous/hypertrophic, exophytic or vegetative and may suggest a neoplastic rather than an infective process and this can be a diagnostic dilemma in resource-limited countries with no access to confirmatory diagnostic testing for HSV. We report on two PLHIV who developed rapidly growing lesions on the face that clinically mimicked neoplasia but were found to be HSV-associated squamous proliferative lesions which responded to high dose acyclovir.

A three-step enantioselective synthesis of (+)- and (-)-α-thujone.

The stereocontrolled three-step synthesis of either enantiomer of α-thujone from commercially available 3-methyl-1-butyne is described. The enantioselectivity originates from a Brown crotylation which is then conferred to the all-carbon quaternary center via chirality transfer in a gold-catalyzed cycloisomerization. The route is highly atom economical and requires no protecting groups or redox manipulations.

Syphilis among men who have sex with men attending a large HIV clinic in Trinidad.

A chart review study was conducted to determine the prevalence of syphilis and explore the associated risk factors among men who have sex with men (MSM) who attended a large HIV clinic in Trinidad during the period January-December 2019. Patients were routinely screened for syphilis annually, and demographic, clinical, and laboratory data were extracted from the medical records. Descriptive and bivariate analyses were performed, and factors significantly associated with a syphilis diagnosis were assessed using multivariate logistic regression. During the period, 218 MSM were seen, age range 19-67 years, and median age 34.0 years. The prevalence of syphilis was 41.3% (90/218), and 71.1% (64//90) of these infections were asymptomatic. Multivariate analysis using logistic regression showed that MSM living with HIV in the 30-34 years old-age group (OR, 4.32; 95% CI, 1.04-18.02), and those with a previous history of treated syphilis (OR, 10.18; 95% CI, 4.60-22.53) were more likely to be diagnosed with syphilis. The prevalence of syphilis is high among MSM attending the HIV clinic in Trinidad, and most of these infections were asymptomatic; hence, targeted and sustained interventions to reduce syphilis transmission are urgently required. Repeat episodes of syphilis may play a role in the transmission dynamics of syphilis in MSM.

Malignant Pleural Mesothelioma Interactome with 364 Novel Protein-Protein Interactions.

Malignant pleural mesothelioma (MPM) is an aggressive cancer affecting the outer lining of the lung, with a median survival of less than one year. We constructed an 'MPM interactome' with over 300 computationally predicted protein-protein interactions (PPIs) and over 2400 known PPIs of 62 literature-curated genes whose activity affects MPM. Known PPIs of the 62 MPM associated genes were derived from Biological General Repository for Interaction Datasets (BioGRID) and Human Protein Reference Database (HPRD). Novel PPIs were predicted by applying the HiPPIP algorithm, which computes features of protein pairs such as cellular localization, molecular function, biological process membership, genomic location of the gene, and gene expression in microarray experiments, and classifies the pairwise features as interacting or non-interacting based on a random forest model. We validated five novel predicted PPIs experimentally. The interactome is significantly enriched with genes differentially ex-pressed in MPM tumors compared with normal pleura and with other thoracic tumors, genes whose high expression has been correlated with unfavorable prognosis in lung cancer, genes differentially expressed on crocidolite exposure, and exosome-derived proteins identified from malignant mesothelioma cell lines. 28 of the interactors of MPM proteins are targets of 147 U.S. Food and Drug Administration (FDA)-approved drugs. By comparing disease-associated versus drug-induced differential expression profiles, we identified five potentially repurposable drugs, namely cabazitaxel, primaquine, pyrimethamine, trimethoprim and gliclazide. Preclinical studies may be con-ducted in vitro to validate these computational results. Interactome analysis of disease-associated genes is a powerful approach with high translational impact. It shows how MPM-associated genes identified by various high throughput studies are functionally linked, leading to clinically translatable results such as repurposed drugs. The PPIs are made available on a webserver with interactive user interface, visualization and advanced search capabilities.

The expansion of a patient tracer programme to identify and return patients loss to follow up at a large HIV clinic in Trinidad.

BACKGROUND: Patients who default from HIV care are usually poorly adherent to antiretroviral treatment which results in suboptimal viral suppression. The study assessed the outcomes of retention in care and viral suppression by expansion of an intervention using two patient tracers to track patients lost to follow up at a large HIV clinic in Trinidad. METHODS: Two Social Workers were trained as patient tracers and hired for 15 months (April 2017-June 2018) to call patients who were lost to follow up for 30 days or more during the period July 2016-May 2018 at the HIV clinic Medical Research Foundation of Trinidad and Tobago. RESULTS: Over the 15-month period, of the of 2473 patients who missed their scheduled visits for 1 month or more, 261 (10.6%) patients were no longer in active care-89 patients dead, 65 migrated, 55 hospitalized, 33 transferred to another treatment clinic and 19 incarcerated. Of the remaining 2212 patients eligible for tracing, 1869 (84.5%) patients were returned to care, 1278 (68.6%) were virally unsuppressed (viral load > 200 copies/ml) and 1727 (92.4%) were re-initiated on ART. Twelve months after their return, 1341 (71.7%) of 1869 patients were retained in care and 1154 (86.1%) of these were virally suppressed. Multivariate analysis using logistic regression showed that persons were more likely to be virally suppressed if they were employed (OR, 1.39; 95% CI 1.07-1.80), if they had baseline CD4 counts < 200 cells/mm3 (OR, 1.71; 95% CI 1.26-2.32) and if they were retained in care at 12 months (OR, 2.48; 95% CI 1.90-3.24). Persons initiated on ART for 4-6 years (OR, 3.09; 95% CI 1.13-8.48,), 7-9 years (OR, 3.97; 95% CI 1.39-11.31), > 10 years (OR, 5.99; 95% CI 1.74-20.64 were more likely to be retained in care. CONCLUSIONS: Patient Tracing is a feasible intervention to identify and resolve the status of patients who are loss to follow up and targeted interventions such as differentiated care models may be important to improve retention in care.

Updated estimated incidence and prevalence of serious fungal infections in Trinidad and Tobago.

Objective: : To estimate the incidence and prevalence of serious fungal infections in Trinidad and Tobago (T&T), with a population of 1 394 973 million. Methods: : The medical literature was searched to obtain published data on the incidence and prevalence of fungal infections in the Caribbean. If data were unavailable, estimations were performed using the frequencies of fungal infection in populations at risk. Asthma and pulmonary tuberculosis rates were used to derive the prevalence of allergic bronchopulmonary aspergillosis (ABPA), severe asthma with fungal sensitization (SAFS), and chronic pulmonary aspergillosis (CPA). Results: : The estimated annual burden of fungal infections was 46 156 persons (3.3% of the population), including 21 455 women with recurrent vulvovaginal candidiasis, 118 persons with invasive aspergillosis, 3637 adults with ABPA, 4800 with SAFS, and 178 with CPA. Annually, we estimated 70 cases of candidemia and 14 647 cases of tinea capitis in children. Of the 11 000 persons living with HIV/AIDS, it was estimated that there were 40 cases of cryptococcal meningitis, 88 cases of disseminated histoplasmosis, and 124 cases of Pneumocystis pneumonia. Conclusion: : There seems to be an extensive burden of fungal infections in T&T. Hence, targeted interventions are required to improve clinical and laboratory diagnosis and a national surveillance system should be implemented.

A possible relationship between telomere length and markers of neurodegeneration in rat brain after welding fume inhalation exposure.

Inhalation of welding fume (WF) can result in the deposition of toxic metals, such as manganese (Mn), in the brain and may cause neurological changes in exposed workers. Alterations in telomere length are indicative of cellular aging and, possibly, neurodegeneration. Here, we investigated the effect of WF inhalation on telomere length and markers of neurodegeneration in whole brain tissue in rats. Male Fischer-344 (F-344) rats were exposed by inhalation to stainless steel WF (20 mg/m3 x 3 h/d x 4 d/wk x 5 wk) or filtered air (control). Telomere length, DNA-methylation, gene expression of Trf1, Trf2, ATM, and APP, protein expression of p-Tau, α-synuclein, and presenilin 1 and 2 were assessed in whole brain tissue at 12 wk after WF exposure ended. Results suggest that WF inhalation increased telomere length without affecting telomerase in whole brain. Moreover, we observed that components of the shelterin complex, Trf1 and Trf2, play an important role in telomere end protection, and their regulation may be responsible for the increase in telomere length. In addition, expression of different neurodegeneration markers, such as p-Tau, presenilin 1-2 and α-synuclein proteins, were increased in brain tissue from the WF-exposed rats as compared to control. These findings suggest a possible correlation between epigenetic modifications, telomere length alteration, and neurodegeneration because of the presence of factors in serum after WF exposure that may cause extra-pulmonary effects as well as the translocation of potentially neurotoxic metals associated with WF to the central nervous system (CNS). Further studies are needed to investigate the brain region specificity and temporal response of these effects.

Effect of a High-Fat Diet and Occupational Exposure in Different Rat Strains on Lung and Systemic Responses: Examination of the Exposome in an Animal Model.

The exposome is the measure of all exposures of an individual in a lifetime and how those exposures relate to health. The goal was to examine an experimental model integrating multiple aspects of the exposome by collecting biological samples during critical life stages of an exposed animal that are applicable to worker populations. Genetic contributions were assessed using strains of male rats with different genetic backgrounds (Fischer-344, Sprague Dawley, and Brown-Norway) maintained on a regular or high-fat diet for 24 weeks. At week 7 during diet maintenance, groups of rats from each strain were exposed to stainless steel welding fume (WF; 20 mg/m3 × 3 h/d × 4 days/week × 5 weeks) or air until week 12, at which time some animals were euthanized. A separate set of rats from each strain were allowed to recover from WF exposure until the end of the 24-week period. Bronchoalveolar lavage fluid and serum were collected at 7, 12, and 24 weeks to assess general health indices. Depending on animal strain, WF exposure and high-fat diet together worsened kidney toxicity as well as altered different serum enzymes and proteins. Diet had minimal interaction with WF exposure for pulmonary toxicity endpoints. Experimental factors of diet, exposure, and strain were all important, depending on the health outcome measured. Exposure had the most significant influence related to pulmonary responses. Strain was the most significant contributor regarding the other health indices examined, indicating that genetic differences possibly drive the exposome effect in each strain.