Contributions of GeneXpert® to TB diagnosis in Myanmar.

BACKGROUND: Xpert® MTB/RIF, a rapid, molecular TB diagnostic assay, can detect Mycobacterium tuberculosis and rifampin resistance directly from clinical sputum samples in <2 h with high sensitivity and specificity. The added diagnostic value of Xpert over smear microscopy at a national level in Myanmar has not been previously reported.METHODS: We evaluated 339,358 Xpert and demographic records captured from January 2015 to December 2018 as part of the Myanmar National TB Program Data Utilization and Connectivity Project to examine the additional diagnostic yield of Xpert relative to smear for the detection of M. tuberculosis for TB diagnosis in Myanmar, with a focus on people living with HIV (PLHIV) and sample type.RESULTS: Use of Xpert increased TB case detection by 40% compared to smear microscopy results. Among PLHIV, use of Xpert increased TB case detection by almost 100% compared to smear microscopy results.CONCLUSION: Xpert testing identified more patients with TB than smear microscopy alone, particularly in cohorts with significant proportions of PLHIV. The use of Xpert as a screening tool in countries with a high burden of TB could lead to significantly increased diagnosis of TB at a regional and national level.

Treatment success among Myanmar migrants with TB in Thailand.

SETTING: Two facilities, one providing clinic-based care and another providing residential care to Myanmar migrants with TB, in a Thailand-Myanmar border area.OBJECTIVE: To determine the effects of health insurance, total delay and the model of care on treatment success of TB.METHODS: A prospective study was conducted among adult Myanmar migrants under treatment for newly diagnosed TB. Effects of health insurance, total delay and model of care on treatment success at completion of 6-month treatment were analysed using multiple logistic regression models.RESULTS: Of 191 Myanmar migrants with TB, 167 (87.4%) had treatment success. Median time delays from symptom onset to treatment initiation among migrants with health insurance receiving clinic-based care were significantly shorter than those without health insurance. Those who received residential care had higher odds of treatment success than those under clinic-based care (aOR 6.0, 95% CI 1.5-23.3); having health insurance (aOR 1.0, 95% CI 0.3-2.9) and total delay (aOR 1.7, 95% CI 0.7-4.2) were not significantly associated with treatment success.CONCLUSIONS: A high treatment success rate was associated with receiving residential care among Myanmar migrants with TB on the Thai-Myanmar border. The residential care model, implemented under a non-governmental organisation, was feasible and effective for the migrant population.

Influence of handler relationships and experience on health parameters, glucocorticoid responses and behaviour of semi-captive Asian elephants.

Declining wild populations combined with accumulating captive populations of e.g. livestock, pets, draught and zoo animals have resulted in some threatened species with substantial proportions of their populations in captivity. The interactions animals have with humans in captivity depend on handler familiarity and relationship quality and can affect animal health, growth and reproduction with consequences for the success of conservation programmes. However, assessments of how specific human-animal relationships affect a range of physiological and behavioural outcomes are rare. Here, we studied semi-captive Asian elephants with detailed records of elephant-handler (mahout) relationships and veterinary management, allowing assessment of multiple welfare indicators in relation to specific mahout-elephant relationship lengths and mahout experience. These included measures of physiological stress (faecal glucocorticoid metabolite [FGM], heterophil:lymphocyte ratio [H:L]), muscle damage (creatine kinase [CK]), immunological health (total white blood cell count [TWBC]) and behaviour (response to mahout verbal commands). We found no evidence that FGM or H:L related to aspects of the mahout-elephant relationship. Longer overall mahout experience (i.e. years of being a mahout) was linked to increased muscle damage and inflammation, but the lengths of specific mahout-elephant relationships were inversely associated with muscle damage in working-age elephants. Elephants responded more to familiar mahouts in behavioural tasks and faster to mahouts they had known for longer. In summary, our results found little evidence that the mahout-elephant relationship affects physiological stress in this population based on FGM and H:L, but mahout experience and relationships were linked to other physiological responses (CK, TWBC), and elephants require behavioural adjustment periods following mahout changes.

Chemical constituents and their biological activities from Taunggyi (Shan state) medicinal plants.

Medicinal plants are essential aspects of readily available primary healthcare remedies. Phytochemical constituents of medicinal plants cover a broad variety of chemical fields to explore medicines. This review highlights selected empirical data on traditional uses, phytochemistry, and pharmacological properties of Taunggyi medicinal plants, Andrographis paniculata, Physalis peruviana, and Cassia fistula. Historically, these plants have been used for many infections and diseases in Taunggyi. More than 361 chemical compounds have been isolated and identified from the selected plants. Some of the chemical constituents have substantial pharmacological properties. It is clear that these herbs have significant potential for useful natural supplements in many contemporary diseases. Thus, the aim of this review compiles an ethnobotanical survey and documentation of medicinal plants in Taunggyi (Myanmar). This review will also inspire Myanmar researcher's to further investigate the potential of these plants in their future work into new compound and new drugs.

The "timeless" use of influenza-like illness criteria for influenza detection in the tropics.

OBJECTIVE: We assessed the performance of influenza-like illness (ILI) case definitions by the Centers for Disease Control and Prevention (CDC), European Centers for Disease Control and Prevention and World Health Organization (WHO) in the tropics where seasonal patterns of respiratory viruses in acute upper respiratory tract infections (AURTIs) are ill-defined. METHODS: Clinical data and samples for respiratory multiplex polymerase chain reaction test were collected from 717 consecutive patients attending an emergency department in Singapore for uncomplicated AURTI in 2016-2018. RESULTS: Influenza (20.6%), rhinoviruses (14.4%), and coronaviruses (3.6%) were the most common viral pathogens identified. Biannual peaks with year-round activity were identified for influenza. Although higher rhinovirus activity was observed in inter-influenza seasonal periods, rhinoviruses and coronaviruses circulated year-round without distinct seasonal patterns. During high influenza activity months, the CDC and WHO ILI case definitions had moderate-to-high positive likelihood ratio (LR+) of 3.8-6.8 and 4.5-10.7, respectively, for ruling in influenza. They had moderately-high LR + of 3.3-3.8 and 3.9-4.6 for diagnosing influenza during other months. The ILI case definitions had high specificity (77.2%-85.4%) for rhinoviruses and coronaviruses. CONCLUSION: The CDC and WHO ILI case definitions can be applied to clinically diagnose influenza in the tropics, regardless of the time of the year.

Cognitive ageing is premature among a community sample of optimally treated people living with HIV.

OBJECTIVES: Evidence of premature cognitive ageing amongst people living with HIV (PLHIV) remains controversial due to previous research limitations including underpowered studies, samples with suboptimal antiretroviral access, varying rate of virological control, high rate of AIDS, over-representation of non-community samples, and inclusion of inappropriate controls. The current study addresses these limitations, while also considering mental health and non-HIV comorbidity burden to determine whether PLHIV showed premature cognitive ageing compared with closely comparable HIV-negative controls. METHODS: This study enrolled 254 PLHIV [92% on antiretroviral therapy; 84% with HIV RNA < 50 copies/mL; 15% with AIDS) and 72 HIV-negative gay and bisexual men [mean (SD) age = 49 (10.2) years] from a single primary care clinic in Sydney, Australia. Neurocognitive function was evaluated with the Cogstate Computerized Battery (CCB) at baseline and 6 months after. Linear mixed-effects (LME) models examined main and interaction effects of HIV status and chronological age on the CCB demographically uncorrected global neurocognitive z-score (GZS), adjusting for repeated testing, and then adjusting sequentially for HIV disease markers, mental health and comorbidities. RESULTS: HIV status and age interacted with a lower GZS (ß = -0.43, P < 0.05). Higher level of anxiety symptoms (ß = -0.11, P < 0.01), historical AIDS (ß = -0.12, P < 0.05) and historical HIV brain involvement (ß = -0.12, P < 0.05) were associated with lower GZS. CONCLUSIONS: We found a robust medium-sized premature ageing effect on cognition in a community sample with optimal HIV care. Our study supports routine screening of cognitive and mental health among PLHIV aged ≥ 50 years.

'TB or not TB': the conundrum of pre-European contact tuberculosis in the Pacific.

Tuberculosis (TB) is a major global health threat, infecting one-third of the world's population. Despite this prominence, the age, origin and spread of the disease have been topics of contentious debate. Molecular studies suggest that Mycobacterium tuberculosis 'sensu stricto', the most common strain of TB infecting humans today, originated in Africa and from there spread into Europe and Asia. The M. tuberculosis strains most commonly found across the Pacific and the Americas today are most closely related to European strains, supporting a hypothesis that the disease only reached these regions relatively recently via European sailors or settlers. However, this hypothesis is inconsistent with palaeopathological evidence of TB-like lesions in human remains from across the Pacific that predate European contact. Similarly, genetic evidence from pre-European South American mummies challenges the notion of a European introduction of the disease into the Pacific. Here, we review the complex evidence for the age and origin of TB in the Pacific, and discuss key gaps in our knowledge and how these may be addressed. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.

A single meal has the potential to alter brain oxylipin content.

Our objective was to determine whether consumption of a single meal has the potential to alter brain oxylipin content. We examined the cerebrum of mice fed a single high-fat/high-sucrose Western meal or a low-fat/low-sucrose control meal, as well as fasted mice. We found no changes in fatty acid composition of cerebrum across the groups. The cerebral oxylipin profile of mice fed a Western meal is distinct from the profile of mice fed a low-fat/low-sucrose meal. Cerebral gene expression of cyclooxygenase 1, cyclooxygenase 2, and epoxide hydrolase 1 were elevated in Western meal-fed mice compared to low-fat/low-sucrose meal-fed mice. Mice that consumed either meal had lower gene expression of cytochrome P450, family 2, subfamily j, polypeptide 12 than fasted mice. Our data in this hypothesis-generating study indicates that the composition of a single meal has the potential to alter brain oxylipins and the gene expression of the enzymes responsible for their production.

Strategy and Efficacy of Generic and Pan-genotypic Sofosbuvir/Velpatasvir in Chronic Hepatitis C Virus: A Myanmar Experience.

BACKGROUND: In resource-constrained areas, generic direct-acting antivirals (DAAs) have considerably reduced the cost of hepatitis C virus (HCV) therapy while there remain significant costs related to the baseline and follow-up virologic assays. AIM: The aim was to assess the efficacy and safety of HCV therapy in Myanmar with pan-genotypic generic DAA sofosbuvir/velpatasvir (SOF/VEL) and with and without the baseline genotype testing, while the duration of treatment and use of ribavirin (RBV) was dictated by cirrhosis and prior treatment failure. METHODS: Between September 2016 and June 2017, data from the 359 participants who completed treatment with SOF/VEL (± RBV) for 12-24 weeks were analyzed. Two hundred one patients did not have the baseline HCV genotype tested. RESULTS: Regimens included SOF/VEL for 12 weeks (n = 43), SOF/VEL/RBV for 12 weeks (n = 275), or SOF/VEL/RBV for 24 weeks (n = 41). The mean age was 52 years, 44% were men (n = 159), 41 (11.4%) had a history of previous DAA therapy, 7 (1.9%) had a history of hepatocellular carcinoma, and 55 (15.3%) had cirrhosis. Overall, the sustained viral response (SVR)12 rate was 98.6% (354/359) and with a good adverse event profile. SVR rates were similar to those with and without baseline genotype testing and also across all genotypes in those who had genotype tested. CONCLUSIONS: In Myanmar, generic and pan-genotypic SOF/VEL ± RBV is a highly effective and safe treatment for HCV, regardless of the HCV genotype, and therefore, the requirement for the baseline genotype can be eliminated. Future strategies should include elimination of treatment and end of treatment HCV RNA testing to enhance treatment uptake and further reduce cost.

Enhancement of Low pH Stress Tolerance in Anthocyanin-Enriched Transgenic Petunia Overexpressing RsMYB1 Gene.

We investigated whether the presence of anthocyanins in plants could contribute to low pH stress tolerance using anthocyanin-enriched transgenic petunia lines (PM2, PM6, and PM8) expressing RsMYB1 and wild-type (WT) plants. We examined several physiological and biochemical factors and the transcript levels of genes involved in abiotic stress tolerance. A reduction in plant growth, including plant height and fresh weight, was observed when plants (PM2, PM6, PM8, and WT) were exposed to low pH (pH 3.0) conditions compared to growth under normal (pH 5.8) conditions. A small reduction in the growth of PM6 was observed, followed by that in PM2, PM8, and WT, reflecting the anthocyanin levels in the plants (PM6 > PM2 and PM8 > WT). An analysis of physiological and biochemical factors also supports the degree of low pH tolerance in the plants (PM6 > PM2 and PM8 > WT). In addition, an enhanced expression of the genes [superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), osmotin, and vacuolar H+-ATPase (V-ATPase)] was observed in the transgenic lines (PM2, PM6, and PM8). The resultant of the enhanced transcript levels of the genes could promote antioxidant activities, proline content, and pH homeostasis involved in the mechanisms underlying abiotic stress tolerance in plants. These results suggest that anthocyanin-enriched plants overexpressing RsMYB1 enhances low pH stress tolerance by elevating the transcript levels of the relevant genes.

Overexpression of Rosea1 From Snapdragon Enhances Anthocyanin Accumulation and Abiotic Stress Tolerance in Transgenic Tobacco.

The co-expression of Rosea1 (Ros1) and Delila (Del) regulates anthocyanin levels in snapdragon flowers, as well as in tomato, petunia, and tobacco. However, there is little information on how Ros1 expression alone controls anthocyanin regulation and whether it is involved in the mechanism that leads to abiotic stress tolerance. In the present study, tobacco (Nicotiana tabacum 'Xanthi') transgenic plants overexpressing Ros1 (T2-Ros1-1, T2-Ros1-2, T2-Ros1-3, and T2-Ros1-4) promoted accumulation of anthocyanin in leaves and flowers by elevating the transcription of all key genes involved in the biosynthesis of this pigment. This promotion largely occurred through the upregulation of dihydroflavonol 4-reductase (DFR), and anthocyanidin synthase genes in leaves and upregulation of DFR in flowers. Under normal conditions, the transgenic lines and wild type (WT) plants showed well-developed broad leaves and regular roots, whereas a reduction in plant growth was observed under cold and drought stresses. However, the transgenic T2-Ros1 lines were able to tolerate the stresses better than the WT line by inducing reactive oxygen species scavenging activities, and the expression of antioxidant-related and stress-responsive genes. In addition, phylogenetic analysis clustered Ros1 with many transcription factors (TFs) that confer tolerance to different abiotic stresses. Overall, the results obtained here suggest that Ros1 overexpression upregulates anthocyanin biosynthetic, antioxidant-related, and stress-responsive genes thereby enhancing anthocyanin accumulation and abiotic stress tolerance.

Involvement of Sodium Nitroprusside (SNP) in the Mechanism That Delays Stem Bending of Different Gerbera Cultivars.

Longevity of cut flowers of many gerbera cultivars (Gerbera jamesonii) is typically short because of stem bending; hence, stem bending that occurs during the early vase life period is a major problem in gerbera. Here, we investigated the effects of sodium nitroprusside (SNP) on the delay of stem bending in the gerbera cultivars, Alliance, Rosalin, and Bintang, by examining relative fresh weight, bacterial density in the vase solution, transcriptional analysis of a lignin biosynthesis gene, antioxidant activity, and xylem blockage. All three gerbera cultivars responded to SNP by delaying stem bending, compared to the controls; however, the responses were dose- and cultivar-dependent. Among the treatments, SNP at 20 mg L-1 was the best to delay stem bending in Alliance, while dosages of 10 and 5 mg L-1 were the best for Rosalin and Bintang, respectively. However, stem bending in Alliance and Rosalin was faster than in Bintang, indicating a discrepancy influenced by genotype. According to our analysis of the role of SNP in the delay of stem bending, the results revealed that SNP treatment inhibited bacterial growth and xylem blockage, enhanced expression levels of a lignin biosynthesis gene, and maintained antioxidant activities. Therefore, it is suggested that the cause of stem bending is associated with the above-mentioned parameters and SNP is involved in the mechanism that delays stem bending in the different gerbera cultivars.

Synergistic Effect of Nano-Sliver with Sucrose on Extending Vase Life of the Carnation cv. Edun.

We investigated the effects of sucrose and nano-silver (NAg) on extending the vase life of cut carnation flowers "Edun". Sucrose (pulse treatment) suppressed ethylene production by downregulating the genes that code for its biosynthesis. Relative to the control, however, sucrose significantly promoted xylem blockage on cut stem surfaces and reduced relative fresh weight, antioxidant activity, and cysteine proteinase inhibitor gene (DcCPi) expression. Consequently, the sucrose-treated flowers had shorter vase lives than the control. In contrast, NAg suppressed ethylene production in the petal, prevented xylem blockage in the cut stem surface, and improved all the aforementioned parameters. Therefore, NAg increased flower longevity. The most effective treatment in terms of longevity extension and parameter improvement, however, was the combination of NAg and sucrose. These results suggest that sucrose can suppress ethylene production but does not necessarily extend the vase life of the flower cultivar. The role of NAg in increasing cut carnation longevity is mainly to inhibit xylem blockage rather than suppress ethylene production, and the combined effect of NAg and sucrose is most effective at prolonging cut carnation vase life, likely due to their synergetic effects on multiple modes of action.

Role of Nano-silver and the Bacterial Strain Enterobacter cloacae in Increasing Vase Life of Cut Carnation 'Omea'.

We investigated the role of nano-silver (NAg) and the bacterial strain Enterobacter cloacae in increasing the vase life of cut carnation flowers 'Omea.' NAg treatment extended vase life of the flowers by increasing relative fresh weight, antioxidant activities, and expression level of the cysteine proteinase inhibitor gene (DcCPi), and by suppressing bacterial blockage in stem segments, ethylene production and expression of ethylene biosynthesis genes and DcCP1 gene, compared with the control. Out of all the treatments, administration of 25 mg L-1 NAg gave the best results for all the analyzed parameters. Interestingly, application of E. cloacae also extended the vase life of cut flowers by 3 days in comparison with control flowers, and overall, showed better results than the control for all the analyzed parameters. Taken together, these results demonstrate the positive role of NAg and E. cloacae in increasing the longevity of cut carnation flowers, and indicate that this effect is brought about through multiple modes of action.

Is bigger better? The relationship between size and reproduction in female Asian elephants.

The limited availability of resources is predicted to impose trade-offs between growth, reproduction and self-maintenance in animals. However, although some studies have shown that early reproduction suppresses growth, reproduction positively correlates with size in others. We use detailed records from a large population of semi-captive elephants in Myanmar to assess the relationships between size (height and weight), reproduction and survival in female Asian elephants, a species characterized by slow, costly life history. Although female height gain during the growth period overlapped little with reproductive onset in the population, there was large variation in age at first reproduction and only 81% of final weight had been reached by peak age of reproduction at the population level (19 years). Those females beginning reproduction early tended to be taller and lighter later in life, although these trends were not significant. We found that taller females were more likely to have reproduced by a given age, but such effects diminished with age, suggesting there may be a size threshold to reproduction which is especially important in young females. Because size was not linked with female survival during reproductive ages, the diminishing effect of height on reproduction with age is unlikely to be due to biased survival of larger females. We conclude that although reproduction may not always impose significant costs on growth, height may be a limiting factor to reproduction in young female Asian elephants, which could have important implications considering their birth rates are low and peak reproduction is young - 19 years in this population.

Erratum to: Frailty has a stronger association with inflammation than age in older veterans.

[This corrects the article DOI: 10.1186/s12979-016-0082-z.].

Frailty has a stronger association with inflammation than age in older veterans.

BACKGROUND: Upregulation of pro-inflammatory cytokines has not only been associated with increased morbidity and mortality in older adults but also has been linked to frailty. In the current study we aimed to compare the relative relationship of age and frailty on inflammation and thrombosis in older veterans. RESULTS: We analyzed 117 subjects (age range 62-95 years; median 81) divided into 3 cohorts: non-frail, pre-frail and frail based on the Fried phenotype of frailty. Serum inflammatory markers were determined using commercially available ELISA kits. Frail and pre-frail (PF) subjects had higher levels than non-frail (NF) subjects of IL-6 (NF vs. PF: p = 0.002; NF vs. F: p < 0.001), TNFR1 (NF vs. F: p = 0.012), TNFRII (NF vs. F: 0.002; NF vs. PF: p = 0.005) and inflammatory index: = 0.333*log(IL-6) + 0.666*log(sTNFR1) (NF vs. F: p = 0.009; NF vs. PF: p < 0.001). Frailty status explained a greater percent of variability in markers of inflammation than age: IL-6 (12 % vs. 0.3 %), TNFR1 (5 % vs. 4 %), TNFR2 (11 % vs. 6 %), inflammatory index (16 % vs. 8 %). Aging was significantly associated with higher fibrinogen (p = 0.04) and D-dimer levels (p = 0.01) but only among NF subjects. CONCLUSION: In conclusion, these data suggest that among older veterans, frailty status has a stronger association with inflammation and the inflammatory index than age does. Larger studies, in more diverse populations are needed to confirm these findings.

CD4 T-cell cytokine correlates of diagnostic tests for latent tuberculous infection in HIV-1-infected subjects.

SETTING: Public human immunodeficiency virus (HIV) clinic and tuberculosis (TB) clinics in Kampala, Uganda. OBJECTIVE: To examine TB-specific CD4 T-cell single and polyfunctional cytokine correlates of clinical diagnostic tests for latent tuberculous infection (LTBI) in HIV-1-infected subjects. DESIGN: Thirty antiretroviral therapy-naïve HIV-1-infected adults without active TB disease underwent clinical tuberculin skin test (TST), interferon-gamma release assay (IGRA), and in vitro flow cytometry analysis on cells stimulated with purified protein derivative (PPD) and TB antigens early secreted antigenic target 6 + culture filtrate protein 10 (EC) for frequencies of interleukin (IL) 2, IL-17, interferon-gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) expressing cells. RESULTS: PPD-specific CD4 T-cell expression of TNF-α and IFN-γ was higher in the TST-positive than in the TST-negative group. EC-specific CD4 T-cell expression of TNF-α and IL-2 was higher in the TST+ group than in the TST- group. Expression of both PPD and EC-specific expression of IL-2, IFN-γ and TNF-α were greater in IGRA-positive than in IGRA-negative subjects. The TST+ group exhibited greater polyfunctionality than the TST- group. All cytokine combinations that contained TNF-α correlated strongly with TST size. CONCLUSION: While IL-2, IFN-γ and TNF-α correlate with clinical tests of LTBI, TNF-α is the dominant cytokine correlating with both TST size and magnitude of IGRA response.

Inhibition of Mycobacterium tuberculosis-induced signalling by transforming growth factor-ß in human mononuclear phagocytes.

Tuberculosis (TB) is associated with excessive production and bioactivation of transforming growth factor bets (TGF-ß) in situ. Here, modification of expression of components of plasminogen/plasmin pathway in human monocytes (MN) by inhibitors of TGF-ß signalling was examined. Smad3 siRNA effectively inhibited TGF-ß-induced urokinase plasminogen activator receptor (uPAR). Agents known to interfere with TGF-ß signalling, including the Smad inhibitors SIS3 and erythromycin derivatives, and ALK5 receptor inhibitor (SB 431542) in inhibition of uPAR expression in response to Mycobacterium tuberculosis (MTB) were examined. Inhibition by SIS3 only inhibited uPAR mRNA significantly. SIS3 may prove to be an effective adjunct to TB therapy.

Fine particulate matter from urban ambient and wildfire sources from California's San Joaquin Valley initiate differential inflammatory, oxidative stress, and xenobiotic responses in human bronchial epithelial cells.

Environmental particulate matter (PM) exposure has been correlated with pathogenesis of acute airway inflammatory disease such as asthma and COPD. PM size and concentration have been studied extensively, but the additional effects of particulate components such as biological material, transition metals, and polycyclic aromatic hydrocarbons could also impact initial disease pathogenesis. In this study, we compared urban ambient particulate matter (APM) collected from Fresno, California with wildfire (WF) particulate matter collected from Escalon, California on early transcriptional responses in human bronchial epithelial cells (HBE). Global gene expression profiling of APM treated HBE activated genes related to xenobiotic metabolism (CYP 1B1), endogenous ROS generation and response genes (DUOX1, SOD2, PTGS2) and pro-inflammatory responses associated with asthma or COPD such as IL-1α, IL-1ß, IL-8, and CCL20. WF PM treatments also induced a pro-inflammatory gene response, but elicited a more robust xenobiotic metabolism and oxidative stress response. Inhibitor studies targeting endotoxin, ROS, and trace metals, found endotoxin inhibition had modest selective inhibition of inflammation while inhibition of hydrogen peroxide and transition metals had broad effects suggesting additional interactions with xenobiotic metabolism pathways. APM induced a greater inflammatory response while WF PM had more marked metabolism and ROS related responses.