It also reaches into the personal lives of staff by forbidding them from having a personal supply of tobacco while at work, which may be viewed as an invasion of privacy by some staff. Methods Participants Participants are 261 substance selleck chem inhibitor abuse treatment counselors and 80 clinical supervisors working in a 50 freestanding substance abuse treatment centers, affiliated with 16 treatment organizations throughout NYS. Due to the large population census and corresponding high concentration of treatment centers in the greater New York City area, 26 of the treatment centers reside in the five boroughs of New York City. The remaining 24 centers are in other geographic regions of NYS (e.g., Buffalo, Niagara Falls, Mount Kisco).

Based on a survey completed by program administrators, the majority of the participating treatment organizations are nonprofit (81%) and accredited by entities such as JCAHO, CARF, or COA (entire organization, 60%; methadone-only, 13%). About three-quarters (73%) are freestanding entities that are not on a hospital campus. Treatment organizations offer a wide range of services (e.g., inpatient detoxification, residential, aftercare, adult inpatient psychiatric, outpatient detoxification, day treatment, outpatient nonmethadone, outpatient methadone). Both adult and adolescent service providers are included in the sample. The most frequently reported substances used among patients seeking treatment are alcohol (39%), marijuana (29%), cocaine (27%), and heroin (27%). In terms of characteristics of the specific treatment programs, 38% offer inpatient and 60% offer outpatient or day treatment services (three programs offer both).

Eighty-five percent offer treatment for adults and 45% offer treatment for adolescents (18 programs offer treatment for both adults and adolescents). Counselors report an average organizational tenure of 4.77 years (SD = 5.52 years). Sixty percent of counselors are licensed substance abuse professionals, 50% hold a master��s degree or higher, and 44% are personally in recovery. Counselors are 60% Caucasian, 61% female, and, on average, 44 years of age (SD = 13.15 years). They work an average of 39 hr per week (SD = 8.05 hr) at the clinical site being studied and earn an average of $37,415 a year (SD = $11,850). Clinical supervisors report an average organizational tenure of 8.82 years (SD = 7.50 years).

On average, clinical supervisors are 48 years old (SD = 11.71 years), supervise around six counselors (SD = 3.80 counselors), work 43 hr a week (SD = 7.91 hr) at the clinical site under study, and earn $58,524 (SD = $16,870) per year. Over 77% of clinical supervisors are licensed substance abuse professionals, and 52% are personally in recovery. Moreover, 58% of clinical supervisors are female, 70% are Caucasian, and 62.5% hold a Batimastat master��s degree or higher.

, 1980) and interfere with quit attempts in nonpregnant populations (Richter, Ahluwalia, Mosier, Nazir, & Ahluwalia, 2002; Stapleton, Keaney, & Sutherland, 2009), although marijuana use has Vorinostat solubility not been demonstrated to do so (Nemeth-Coslett, Henningfield, O��Keeffe, & Griffiths, 1986). However, we know of one study where marijuana use was correlated with failure to quit smoking during pregnancy (Haskins, Bertone-Johnson, Pekow, Carbone, & Chasan-Taber, 2010). While not examined in this study, a major concern about drug use during pregnancy is adverse fetal effects. While marijuana was the most common drug seen in this study effects of marijuana use on birth outcomes are not well established. Indeed, when potentially confounding influences of sociodemographic variables and cigarette smoking are controlled for, marijuana use may have no discernible adverse effects on birth outcomes (Bada et al.

, 2002; Bailey, McCook, Hodge, & McGrady, 2012). Cigarette smoking during pregnancy continues to be the strongest predictor of adverse fetal effects of drug use. In a large, multisite trial cigarette smoking was shown to have greater adverse effects on birth weight, intrauterine growth restriction, and premature birth than illicit drug use (Bada et al., 2005). Abolishing maternal smoking appears to be the most effective way to improve fetal health, especially when the higher prevalence of maternal smoking, compared with maternal drug use, is considered (Burstyn, Kapur, & Cherry, 2010). A few limitations of this study merit mention.

We were not able to test the samples for buprenorphine, which is abused in the study area; therefore, the number of opioid users may be an underestimation. Additionally, this sample consists of treatment-seeking pregnant smokers, which may be inherently different than the general population of pregnant smokers (e.g., perhaps less likely to use other drugs). As this study was retrospective, we could only examine a limited number of characteristics as potential predictors of drug use. Overall, considering the relatively high prevalence of illicit drug use in this pregnant smoker population, as well as possible adverse consequences of such use on smoking cessation, it may be prudent for those providing smoking-cessation therapy to be prepared to assist pregnant women with obtaining services for other drug use as well.

The American College of Obstetricians and Gynecologists (ACOG) provides guidelines regarding screening, assessment, and brief intervention in this population (ACOG, 2008). FUNDING This study was supported by research grant DA14028 and training grant DA007242 from the National Institutes of Brefeldin_A Health, National Institute on Drug Abuse.
Secondhand smoke (SHS), the tobacco smoke generated by active smokers, remains a widespread health hazard worldwide (U.S. Department of Health and Human Services, 2006).

, 2003). Respondents aged 30 years or younger, regardless of smoking status, and respondents indicating selleck chemicals that they had quit smoking in the past 2 years also were contacted again. Those who initiated (n=1) or resumed (n=34) smoking at wave 2 were included in the 2-year longitudinal analyses. Measures Smoking status. At each interview, all adults aged 18 years or older who reported that they had smoked at least 100 cigarettes in their lives were asked (a) if they currently smoked every day or some days and (b) how many CPD they smoked, on average, over the past 30 days. Each smoker’s level of smoking was categorized at each wave using these two dimensions. Cigarette consumption was categorized into three groups: ��5, 6�C10, and >10 CPD. Our focus on smokers consuming ��10 CPD follows Okuyemi et al.

(2002). The decision to further split smokers above and below 5 CPD is based on the ��chipper�� literature. Chippers are smokers who consume no more than 5 CPD over an extended period of time and who may have limited or no nicotine dependence (Shiffman, 1989). We use the term very light to refer to all smokers consuming no more than 5 CPD and light to refer to smokers consuming no more than 10 CPD. Smoking frequency was defined as smoking every day (daily smokers) or less than daily (nondaily smokers). Covariates. The survey assessed demographic factors, socioeconomic status, smoking and quitting behavior, social environment, and no-smoking policies at home and at work. Demographic factors included sex, age, race/ethnicity, and marital status.

Race/ethnicity categories (84% White, 4% Hispanic, 6% Black, 1% Asian, and 4% other) were collapsed into the two categories of White and non-White because the numbers of respondents in individual non-White categories were insufficient to provide statistically stable estimates. Socioeconomic status was measured by years of education and income. Measures of smoking behavior included the following: CPD, age at which the respondent began smoking, and the time to first cigarette after waking (a measure of nicotine dependence; Heatherton, Kozlowski, Frecker, Rickert, & Robinson, 1989).

A pattern of social smoking was assessed with the question ��Do you smoke mainly when you are with other people, mainly when you are alone, or as often by yourself as with others?�� Quitting behaviors included having made an intentional quit attempt lasting 1 day or longer in the past 12 months, having a plan to quit smoking in the next 30 days, and self-efficacy for quitting (��How sure are you that you could refrain from smoking for at least 1 month if you wanted to?��; ��very sure�� = 1, else = 0). Smoking Drug_discovery in the social environment was assessed by asking how many friends were also smokers and the smoking policy of the respondent’s home and workplace.

21, p < .001). Table 1. Participant Characteristics As depicted in Table 2, smoking in the past three months was associated with lower education, greater alcohol use, and higher LGBIS scores. Among smokers, smoking ��10 selleck chemical Paclitaxel CPD versus light smoking was related to lower LGBIS scores and marginally related to older age and greater alcohol use. Table 2. Logistic Regression Model Predicting Past Three Month Smoking Among Chinese MSM and Smoking ��10 CPD Among Chinese MSM Smokers Discussion This study provides important findings, as little is known about smoking among sexual minorities outside of North America. Higher smoking prevalence was found among Chinese MSM (66%) versus MSM in North America (34%�C55%; Greenwood et al., 2005; Lampinen et al., 2006) and versus the general urban male population in China (56%; S.

Lee et al., 2009). The 10% higher rate among Chinese MSM versus non-MSM may reflect a ceiling effect since smoking rates among Chinese men are quite high. Thus, this study highlights a particularly high-risk underserved population that has received little attention. This research identified important factors associated with smoking among Chinese MSM. First, as previously documented, lower education was associated with smoking (Zhu, Giovino, Mowery, & Eriksen, 1996) and older age was associated with heavier smoking (CDC, 1997; Thompson et al., 2007). Second, drinking was related to smoking and heavier drinking was associated with heavier smoking. Our findings support prior research on concurrent alcohol use and smoking (Bachman, Wadsworth, O��Malley, Johnston, & Schulenberg, 1997) and high prevalence of smoking and alcohol use among MSM in China (Ruan et al.

, 2009). Interestingly, less comfort with one��s sexuality was more highly correlated with smoking than depressive symptoms or social support. The Substance Abuse and Mental Health Services Administration (Kelly, 1995) listed five empirically based substance abuse-specific risk factors for the LGBT population, particularly lack of sense of self-worth, connectedness to social support, alternative ways to view being different, role models, and opportunities to socialize with other gays/lesbians outside of bars. Some of these risk factors are reflected by LGBIS. Further examination should focus on how specific aspects of gay identity contribute to health-risk behavior.

The reasons for the connection between higher LGBIS scores and light smoking are unclear. Perhaps, there are different triggers for smoking among those who were more uncomfortable with Carfilzomib their sexual identity, such as being in uncomfortable social situations or coping with situational stressors, rather than being addicted. Further examination of this phenomenon is warranted. This research has implications for research and practice. Greater attention regarding health behaviors, particularly smoking, among MSM in developing countries is warranted.

The American Society of Heating, Refrigeration, and Air Conditioning Engineers (ASHRAE, 2011), in its 2008 position on SHS, concluded that a smoking ban was the only means of effectively eliminating indoor exposure to SHS and ��no sellekchem other engineering approaches, including current and advanced dilution ventilation or air cleaning technologies, have been demonstrated or should be relied upon to control health risk from ETS exposure���� (ASHRAE, 2008). Separation of smokers from nonsmokers, ventilation systems, air cleaning, and filtration are all ineffective strategies to eliminate SHS exposure and its harmful effects. The tobacco industry has been supporting each of these ineffective strategies, especially the accommodation strategy, at different levels worldwide (Aguinaga Bialous, Pressman, Gigliotti, Muggli, & Hurt, 2010; Bialous & Glantz, 2002; Campbell & Balbach, 2011; Dearlove, Bialous, & Glantz, 2002; Drope, Bialous, & Glantz, 2004; Sebrie & Glantz, 2007).

Increasing evidence also indicates that SHS can infiltrate from separated smoking into nonsmoking areas in multifamily dwellings (Bohac, Hewett, Hammond, & Grimsrud, 2011; King, Travers, Cummings, Mahoney, & Hyland, 2010; Kraev, Adamkiewicz, Hammond, & Spengler, 2009). Furthermore, air monitoring results (using particulate matter [PM] and airborne nicotine levels as SHS markers) have consistently proven the industry��s ��accommodation program�� and partial smoking restrictions to be ineffective in bars, restaurants, and casinos (Agbenyikey et al., 2011; Akbar-Khanzadeh, Milz, Ames, Spino, & Tex, 2004; Barnoya, Mendoza-Montano, & Navas-Acien, 2007; Erazo et al.

, 2010; Jiang et al., 2011; Kim, Sohn, & Lee, 2010; Lambert, Samet, & Spengler, 1993; Milz et al., 2007; Repace, 2009; Repace et al., 2011). Since the main reason for smoke-free environments is the health consequences of SHS exposure, research was instrumental in documenting the ineffectiveness of ventilation systems. The ventilation rate required to reduce SHS to ��acceptable�� levels of cancer risk would have to be increased 22,500 times compared with current ventilation standards (Repace, 2005; Repace & Johnson, 2006). The Tobacco Industry and Smoke-Free Environments Previously secret industry documents became available for free as a result of litigation in the 1990s in the United States (http://legacy.library.ucsf.

edu/about/about_collections.jsp). These expose the industry��s strategies to prevent and obstruct the spread of smoke-free laws, investing in multimillion-dollar campaigns to confuse the public and slow down the Batimastat rate of decline in cigarette consumption and social acceptability of smoking (Glantz, Barnes, Bero, Hanauer, & Slade, 1995; Muggli, Hurt, & Blanke, 2003). Worldwide, the industry has secretly hired consultants, sponsored symposia, financed research, and engaged in lobbying in order to fuel the controversy on the relationship between SHS and disease (Barnoya & Glantz, 2002; Hammond & Assunta, 2003; Muggli et al.

For the cycloheximide experiment, cells were pretreated with 20 ��g/ml of cycloheximide for 20 min, and RA (1 ��M) was added and cells were incubated for another 4�C6 h at 37��C in 5% CO2. For Nutlin-3a buy the RAR pan-antagonist LE540 experiment, CaCo-2 cells were pretreated with 1 ��M of LE540 for 1 h; after which 1 ��M RA was added, and cells were incubated for an additional 4 h. Control cells were not treated or were treated with 1 ��M RA alone for 4 h. After harvesting, cells were then processed for total RNA. mRNA expression of relevant genes was determined by qRT-PCR with gene-specific probe sets (ABI). HepG2 cells were cultured in 100-cm2 dishes and transfected with 4�C6 ��g of purified plasmid DNA (pISX-WT) by using LipofectAMINE 2000 (L2000) and Opti-MEM according to manufacturer��s instructions (Invitrogen).

Cells were harvested 48�C72 h post-transfection, and total protein was extracted and processed as detailed below. Protein isolation and Western blot analyses Total protein from animal tissue or cultured cells was isolated at indicated time points by using the M-PER mammalian protein extraction reagent with protease inhibitors (Roche, Basel, Switzerland) according to manufacturer��s instructions (Pierce). Mice were sacrificed by cervical dislocation. Small intestines were collected, rinsed in ice-cold phosphate buffered saline (PBS; pH 7.4), and snap-frozen in liquid nitrogen. Mouse intestine (~100 mg) was then homogenized in liquid nitrogen using a mortar and pestle and transferred directly into M-PER buffer (500 ��l) containing protease inhibitors.

Proteins (30�C50 ��g) were fractionated on 4�C10% SDS-PAGE gels using the Bio-Rad Minigel system and transferred onto polyvinylidene fluoride (PVDF) membranes (Millipore). Equal protein loading was confirmed by routine immunoblotting of the membranes with Ponceau S staining and by Western blot analysis using anti-RAN as the loading control. PVDF membranes were blocked with 5% milk prepared in Tris-buffered saline (pH 7.4) containing 0.05% Tween (TBS-T) for 1 h and then probed with either anti-ISX, anti-SR-BI, or anti-BCMO1 (1:1000 dilution) antibody overnight at 4��C, followed by incubation with the appropriate HRP-conjugated secondary antibody, before being visualized with the enhanced ECL chemiluminescence detection system (Pierce or Pharmacia). For determination of liver retinol binding protein (RBP4) levels, Anacetrapib a commercially available polyclonal antiserum raised against human RBP4 (DakoCytomation, Hamburg, Germany) was used in a 1:1000 dilution. WT ISX plasmid construction Total RNA (1 ��g) from the human colonic CaCo-2 cell line was reverse transcribed by using the SuperScript One-Step RT-PCR for LongTemplates system (Invitrogen).

However in the bordering metaplastic tissues of six out of 10 patients with adenocarcinoma and in dysplastic tissue from two other patients, MT concentrations were on average two-fold higher than those in normal oesophagus. The levels of MT in adenocarcinoma were unremarkable and there was no obvious association between the these MT content and the histological grading. Table 1 Characteristics of patients, histological diagnosis and metallothionein levels in normal, transitional and cancerous oesophageal tissue Metallothionein concentrations were increased in Barrett’s epithelium in 17 out of 20 patients by an average of 108% (Table 2). The mean MT concentration in normal and Barrett’s epithelium was 204��22 (pmol Cd boundmg?1 protein; mean��s.d.) and 411��68, respectively.

The difference between MT concentrations in normal and Barrett’s epithelium was highly significant (P<0.004). There was no association between the MT levels in Barrett's epithelium and the histological diagnosis of inflammation, metaplasia or dysplasia. Table 2 Characteristics of patients, histological diagnosis and metallothionein levels in normal and Barett's epithelium DISCUSSION It has been argued that in Barrett's oesophagus there is a large intra- and interobserver variation in the reporting of various grade dysplasia with inflammatory atypia making the diagnosis problematic. Thus it can be difficult to monitor the progression of oesophagitis to dysplasia in order to detect cancer at a curable stage (Ortiz-Hidalgo et al, 1998).

This has led to the search for new objective indicators which may complement and help reduce the observer variability with histological diagnosis. MT is a potential marker of carcinogenesis and its expression in human cancers can be up- or down-regulated (Cherian et al, 1994). Few studies have focused on the expression of MT in human oesophageal tumours and this is the first to quantitatively measure the concentration of MT in human adenocarcinoma of the oesophagus and in Barrett’s epithelium, which is generally considered to be the premalignant lesion, although the primary cells leading to adenocarcinoma have not been identified. In one study, in situ hybridisation with MT DNA probes and immunochemistry was used to determine MT mRNA and MT protein expression in resected oesophageal tissue from patients with squamous cell carcinoma.

It was concluded that MT expression was a potential marker of the proliferative and metastatic behaviour of this cancer (Hishikawa et al, 1997, 1999). Here we demonstrate that MT expression was not increased above matched normal-appearing oesophagus in 10 patients we investigated with AV-951 adenocarcinoma. In each case, there was histological confirmation that the adenocarcinoma arose from columnar lined Barrett’s mucosa.

024). In longitudinal analyses of each abstinence outcome stratified by genotype Seliciclib Cdc2 (Supplementary Tables 6 and 7), we observed significant association of (a) treatment in individuals with a VNTR L+ genotype for both abstinence outcomes (point prevalence abstinence [OR = 2.74, 95% CI: 1.14�C6.59, p = .025] and continuous abstinence [OR = 3.15, 95% CI: 1.12�C8.88, p = .030] respectively); (b) time in individuals with a VNTR SS genotype at 6MO with point prevalence abstinence and at 6MO and 12MO with continuous abstinence; (c) gender in individuals with a VNTR SS genotype with continuous abstinence; and (d) age (age squared) in individuals with a VNTR L+ genotype with continuous abstinence. We also observed three principal components of population genetic variation significantly associated with continuous abstinence in individuals with a SS genotype (ps < .

033). The effect sizes of treatment in individuals with a VNTR SS genotype in multivariate (EOT, 6MO, and 12MO) and longitudinal analyses of point prevalence and continuous abstinence outcomes were nonsignificant: OR = 1.39, 95% CI: 0.78�C2.48, p = .262; OR = 1.29, 95% CI: 0.69�C2.41, p = .428; OR = .96, 95% CI: 0.48�C1.90, p = .896; OR = 1.48, 95% CI: 0.80�C2.77, p = .215; OR = 1.92, 95% CI: 0.91�C4.06, p = .087; OR = 1.42, 95% CI: 0.58�C3.47, p = .441; OR = 1.38, 95% CI: 0.78�C2.44, p = .27; and OR = 1.47, 95% CI: 0.78�C2.75, p = .23, respectively. The power to detect the gene by environment effect reported by Leventhal et al. (2012) with the abstinent (case) and nonabstinent (control) sample sizes, dominantly coded genotype prevalence, and treatment prevalence of the Lerman et al.

(2003) sample, and the average placebo abstinence rate of 13.8% from 80 placebo arms (Fiore et al., 2008), was 11.5%. Under the same assumptions, a sample size of 3,362 individuals would be required to detect the gene by treatment interaction effect reported by Leventhal et al. (2012) with 80% power. DISCUSSION In analyses of the relations between bupropion treatment and VNTR genotype in N = 416 self-identified White treatment-seeking smokers, we observed statistically significant effects of treatment in multivariate analyses of both abstinence outcomes at EOT and at 6MO, and in longitudinal analyses of both abstinence outcomes, but only in individuals with a VNTR L+ genotype.

We did not observe statistically significant associations of genotype or genotype by treatment interaction. Time was observed to be significantly associated with both abstinence outcomes, as expected. There Drug_discovery were a few covariate associations with both abstinence outcomes, including principal components of population genetic variation. The magnitude of the statistically significant association of active treatment with both abstinence outcomes was not significantly different from the magnitude of effects previously observed in samples not stratified by DRD4 VNTR genotype (Brown et al., 2007; Hurt et al.

m. and became detectable in the samples collected at 10a.m., but their concentration levels were below 10pg/100��g of proteins. Statistical comparisons of the IRSF that were detected at both time-points showed significantly higher concentrations of the pro-inflammatory cytokines IL-1��, IL-7 and IL-9 at 10a.m. compared with 4p.m. The http://www.selleckchem.com/products/Sorafenib-Tosylate.html largest increase was observed in IL-1��, which changed from 43.9pg/100��g at 4p.m. to 94.9pg/100��g of protein at 10a.m. (Table (Table22 and Figure Figure1).1). The chemokines and CSF eotaxin, MIG and VEGF also showed higher concentration values at 10a.m., while MCP-1 and MIP-1�� had lower values at this time-point as compared with the samples collected at 4p.m. The largest decline in chemokine concentration was observed in MIP-1��, which dropped from 300 to 154pg/100��g of protein (Table (Table2).

2). Therefore, a subset of IRSF expression appears to be regulated by circadian mechanisms. Figure 1 Analysis of immune response-associated soluble factors expression in fetal brain homogenates after maternal innate immune activation. Pregnant mice received a single i.p. injection of poly(I:C) or PBS on GD16 and were killed 6h and 24h … Activation of maternal innate immune response by poly(I:C) caused a rapid and significant increase in the pro-inflammatory cytokines IL-7 (205%) and IL-13 (356%) 6h after treatment compared with PBS-treated animals (Table (Table22 and Figure Figure1).1). The cytokines IL-1��, IL-9, IL-15, IL-17 and IL-10 were not substantially affected 6h after poly(I:C) injection.

The concentration levels of the pro-inflammatory cytokines IL-7 and IL-13 remained stable 24h after injection. By contrast, IL-1�� was significantly up-regulated (34%) at this later time-point, suggesting that the induction of this cytokine required a longer time to develop and is presumably more persistent. It should be noted that IL-1�� was the only cytokine significantly up-regulated at 24h post-poly(I:C) treatment and showed the highest level of expression in fetal brain homogenates (127pg/100��g of protein). IL-9 was also present at a high concentration in brain samples (128pg/100��g of protein) but its expression Batimastat levels were unaffected by poly(I:C). Poly(I:C) also induced a significant change in chemokine and CSF concentrations in the fetal brain, including IP-10, MIG, VEGF, MCP-1 and MIP-1��. Interestingly, poly(I:C) induced the up-regulation of the subset of IRSF detected in control fetal brain, indicating that poly(I:C) and/or maternal innate immune activation modulate expression levels of IRSF already present in the fetal brain.

Zonation was similarly observed for the mitochondrial fatty acid oxidation enzymes, acyl-CoA dehydrogenase and very long chain (ACADVL; S3D) and 2,4-dienoyl CoA reductase 1 (DECR1; S3E), the http://www.selleckchem.com/products/kpt-330.html cytoplasmic enzymes acetyl-CoA carboxylase (ACACB; Figure S3F) and diacylglycerol O-acyltransferase 2 (DGAT2; Figure S3G) as well as the lipid droplet associated protein perilipin 1(PLIN1; Figure S3H). In particular, several proteins facilitating phospholipid metabolism also displayed zonal expression. Preferential perivenular (zone 3) zonation was clearly evident for choline kinase �� (CHKA; Figure S3I), phosphocholine cytidylyltransferase 1 (PYCT1A; Figure S3J), phosphatidylethanolamine N-methyltransferase (PEMT; Figure S3K), glycerol-3-phosphate acyltransferase 2 (GPAT2; S3M) as well as the phospholipases A2 G15, A2 G4F and B1(PLA2G15, PLA2G4F and PLA2B1 Figure S3N-S3P, respectively).

Only phosphocholine cytidylyltransferase 2 (PCYT2; Figure S3L) displayed a perivenular dominant (zone 1 to zone 3) expression pattern. To gain insight into what, if any, changes may exist with regard to PC biosynthetic enzymes commensurate with NAFLD progression, we examined in situ the localization of PEMT, a primary PC biosynthetic enzyme. Figure 5A illustrates the strong perivenular localization of this enzyme in a histologically normal obese liver. This contrasts with panlobular distribution of the enzyme in SS (Figure 5B) and NASH, and with notable localization in necroinflammatory sites in NASH specimens (Figure 5C). Figure 5 Phosphatidylethanolamine methyltransferase (PEMT) localization differs with progression of NAFLD.

Discussion Aberrant hepatic lipid metabolism has long been proposed to be central in the pathogenesis of NASH, but the exact mechanism(s) underlying necroinflammatory changes on background steatosis remain to be fully understood. The differential abundance of phospholipids, particularly PCs and PEs, has been studied quantitatively but these studies have largely been either in mice [34], [35], [36], [37], in anthropomorphically-diverse cohorts [30], or with destructive analytical methods such as methylation or acid/alkaline digestion that provide information on fatty acid composition within a lipid class but do not identify a specific PC [31], [38], [39]. The current study identifies, quantifies and localizes specific choline-containing lipids in human liver and reveals a previously unappreciated zonation of specific molecular PCs that are either lost or preserved in association with NAFLD severity. Given these ostensibly protein-mediated changes, we further demonstrated the zonation pattern of one hallmark PC metabolic enzyme, AV-951 PEMT.