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BackgroundThe prevalence of HIV in Panama is estimated to be 1.0%; only 71% of individuals on antiretroviral treatment (ART) were virally suppressed in 2022. This study aimed to describe the prevalence of suboptimal adherence (≥1 missed doses in previous four weeks) and limited retention in HIV care (≥1 missed HIV care appointments in previous 12 months) among adults (aged ≥18 years) who attended the most populous urban ART Clinic in Panama City.MethodsIn this cross-sectional study, participants completed a self-administered questionnaire. Univariable and bivariable analyses were used to describe the prevalence of suboptimal adherence and limited retention in HIV care. Multivariable logistic regression identified factors associated with suboptimal adherence at pResultsWe included 375 participants (209 identified as men, 158 as women, 8 another gender). Of those who responded, 37.3% (n = 125/335) reported suboptimal adherence: 28.6% (n = 53/185) of men, 49.0% (n = 71/145) women, 20.0% (n = 1/5) another gender; pConclusionsThis study found high prevalence of suboptimal ART adherence and limited retention in care, especially among women; these factors were associated with severe depressive symptoms, as well as lifetime emotional and physical IPV. These results show the need for integrated mental health and IPV intervention for all individuals, including focused support for women.

Background: The prevalence of HIV in Panama is estimated to be 1.0%; only 71% of individuals on antiretroviral treatment (ART) were virally suppressed in 2022. This study aimed to describe the prevalence of suboptimal adherence (≥1 missed doses in previous four weeks) and limited retention in HIV care (≥1 missed HIV care appointments in previous 12 months) among adults (aged ≥18 years) who attended the most populous urban ART Clinic in Panama City. Methods: In this cross-sectional study, participants completed a self-administered questionnaire. Univariable and bivariable analyses were used to describe the prevalence of suboptimal adherence and limited retention in HIV care. Multivariable logistic regression identified factors associated with suboptimal adherence at p<0.05. Results: We included 375 participants (209 identified as men, 158 as women, 8 another gender). Of those who responded, 37.3% (n = 125/335) reported suboptimal adherence: 28.6% (n = 53/185) of men, 49.0% (n = 71/145) women, 20.0% (n = 1/5) another gender; p<0.01; 18.6% (n = 69/371) reported limited retention in care:13.6% (n = 28/206) men, 24.2% (n = 38/157) women, 37.5% (n = 3/8) another gender, p = 0.01. In multivariable analyses, suboptimal adherence was associated with gender (49.0%women vs. 28.6% men, AOR = 1.86, 95%CI:0.97–3.57), depressive symptoms:46.2% severe symptoms vs. 28.1% minimal-mild, AOR = 2.19,95%CI:0.96–5.04), and lifetime intimate partner emotional violence (IPV) 48.2% vs.no emotional IPV 32.2%, OR = 1.96,95%CI:1.15–2.90, and lifetime physical IPV 46.9% vs.no physical IPV 32.6%, OR = 1.82, 95%CI:1.15–2.90. In unadjusted analyses, limited retention in care was associated with gender (24.2%women vs.13.6% men OR = 2.03, 95%CI:1.18–3.49), difficulty paying rent/mortgage/utilities (22.6% vs.14.9% no difficulty paying, OR = 1.67,95%CI = 0.98–2.83); no variables were associated in the multivariable model. Conclusions: This study found high prevalence of suboptimal ART adherence and limited retention in care, especially among women; these factors were associated with severe depressive symptoms, as well as lifetime emotional and physical IPV. These results show the need for integrated mental health and IPV intervention for all individuals, including focused support for women. [ABSTRACT FROM AUTHOR]

PurposeResearch establishes the critical need to address the underrepresentation of women and racial/ethnic minorities in science, technology, engineering, and mathematics (STEM). While emergent research addresses similar challenges for sexual and gender minorities (SGM), this research remains scant and focuses on adult experiences. This analysis examines subgroup differences and the impact of bullying on STEM engagement outcomes among a national sample of SGM secondary students in the U.S.MethodThis report provides descriptive and multivariable regression analysis of national survey data (n = 539) on the experiences of pre-college students who identify as SGM, including the effects of within-school anti-SGM bullying on STEM identity, perceptions of STEM climate, and STEM intentions.ResultsRoughly 50% of the sample intended to enter a STEM field (compared to 25% in previous general samples). Bullying in school was negatively associated with STEM identity and perceptions of STEM climate. Sense of belonging is positively associated with perceptions of STEM climate and STEM intentions. Being non-binary and being a transgender man were associated with decreased sense of belonging and negative perception of STEM climate.ConclusionThis report is the first to identify factors influencing STEM engagement among SGM secondary students and suggests that issues of STEM engagement are already present in adolescence. Moreover, the findings also establish the relationship between anti-SGM bullying and STEM outcomes highlighting the importance of this marginalization experience. Future research should further examine sub-group differences and the persistence of these effects. These findings highlight the need for research and intervention addressing STEM outcomes in SGM populations.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03511131.

BackgroundFecal microbial transplantation (FMT) has been used with the therapeutic intent to change the functions of the gut microbial community in metabolism and host immunity. For most of these therapies, the recipients are not given antibiotics to eliminate the microbial community prior to transplant with donor fecal microbes resulting in the initial gut microbial community following FMT consisting of a consortium of donor and recipient microbes. The detailed analysis of the fecal samples from these FMT over time provides a unique opportunity to study the changes in the gut microbial strain community that occurs following the introduction of new microbial strains (donor) into an established community (recipient).MethodsIn this study, we have metagenomic data set consisting of 5 FMT that contained donor, recipient and recipient post FMT taken multiple times for periods up to 535 days after the FMT. We used two established strain tracking methods, Window-based Single Nucleotide Variant (SNV) Similarity (WSS) and StrainPhlAn, to determine the presence of donor and recipient microbial strains following FMT. To assess recombination between donor and recipient strains of Bacteroides vulgatus post FMT, we used BLAST+ to analyze the data sets for Bacteroidales-specific antimicrobial proteins (BSAP-3) that have known functions to restrict species specific replication.ResultsWe found that Alistipes onderdonkii, Alistipes shahii, Alistipes putredinis, and Parabacteroides merdae, all had patterns post FMT consisting of either dominant donor or recipient microbial strains in the feces. In contrast, the analysis of Bacteroides spp. in five FMT pairs revealed inter-individual oscillation over time with the appearance of either donor or recipient fecal strain dominance. In some instances, B. vulgatus and B. uniformis were also identified after FMT that were not related to either the donor or recipient. Finally, in one of the FMT, we identified a distinct B. vulgatus strain post-FMT that matched the pre-FMT strain but was BSAP-3 positive, suggesting a possible recombination event between the donor and recipient strains.ConclusionThe complex oscillating patterns of the appearance of fecal dominant donor, recipient or unrelated strains following extended times post FMT provide new insights into the dynamics of the microbial community interactions with the recipients following FMT. The result from our analysis has implications for the use of FMT to predictably change the biological functions of the gut community in metabolism and host immunity.

Background & aimNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy.DesignCholine Deficient L-Amino Acid (CDAA) and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens.ResultsWe observed statistically significant differences in the level of extracellular vesicles (EVs) in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p

ObjectiveTo identify recommendations for conducting public health research with trauma-exposed populations.MethodsResearchers searched Embase, PubMed, Scopus, Web of Science, Open Grey, and Google Scholar for recommendations. Trauma that causes psychological impact was our exposure of interest and we excluded clinical articles on treating physical trauma. We reviewed titles and abstracts of 8,070 articles and full text of 300 articles. We analyzed recommendations with thematic analysis, generated questions from the existing pool of recommendations, and then summarized select gaps.ResultsWe abstracted recommendations from 145 articles in five categories: community benefit, participant benefit, safety, researcher well-being, and recommendations for conduct of trauma research.ConclusionsGold standards to guide the conduct of trauma-informed public health research do not yet exist. The literature suggests participation in trauma research is not inherently harmful, and current recommendations concern using research to benefit communities and participants, protecting participants and researchers from harm, and improving professional practice. As public health researchers increasingly analyze trauma as a determinant of health, gold standards for the conduct of trauma-informed public health research would be appropriate and timely.

Kdm6a/Utx, a gene on the X chromosome, encodes a histone H3K27me3 demethylase that has an orthologue on the Y chromosome (Uty) (Zheng et al. 2018). We previously identified inactivating mutations of Kdm6a in approximately 50% of mouse acute promyelocytic leukemia samples; however, somatic mutations of KDM6A are more rare in human AML samples, ranging in frequency from 2–15% in different series of patients, where their role in pathogenesis is not yet clear. In this study, we show that female Kdm6aflox/flox mice (with allele inactivation initiated by Vav1-Cre in hematopoietic stem and progenitor cells (HSPCs) have a sex-specific phenotype that emerges with aging, with features resembling a myelodysplastic syndrome (MDS). Female Kdm6a-knockout (KO) mice have an age-dependent expansion of their HSPCs with aberrant self-renewal, but they did not differentiate normally into downstream progeny. These mice became mildly anemic and thrombocytopenic, but did not develop overt leukemia, or die from these cytopenias. ChIP-seq and ATAC-seq studies showed only minor changes in H3K27me3, H3K27ac, H3K4me, H3K4me3 and chromatin accessibility between Kdm6a-WT and Kdm6a-KO mice. Utilizing scRNA-seq, Kdm6a loss was linked to the transcriptional repression of genes that mediate hematopoietic cell fate determination. These data demonstrate that Kdm6a plays an important role in normal hematopoiesis, and that its inactivation may contribute to AML pathogenesis.

Use of dental services in childhood, especially preventive care, is associated with many important oral health outcomes throughout life. The Andersen behavioral model of healthcare utilization posits that predisposing characteristics, enabling resources, and need factors predict utilization in oral and other healthcare domains. Inequities that produce lower utilization of dental services in north-central Appalachia have been documented in comparison to the USA generally. Additionally, within Appalachia, there are disparities, such as those across different states related to varying public policies and resources supporting healthcare. Predictors of dental utilization in Appalachia have been a focus in adults, but less so in children. The aim of the current study was to understand predictors of dental utilization in children in north-central Appalachia in order to inform future research about how to intervene to address these disparities. In this study, there were 1,178 children, ages 1 through 10 years, from selected representative counties in West Virginia and Pennsylvania, along with a parent/caregiver, who were part of the Center for Oral Health Research in Appalachia (COHRA1) cohort. Use of dental services by their child was indicated by parents/caregivers, who also reported on sociodemographic, dental care-related anxiety and fear, and values and attitudes associated with oral healthcare. Results indicated that use of professional dental services by children was related to child age, dental anxiety and fear, and parental oral health values and attitudes. Older children in this age group, those who evidenced more dental care-related anxiety and fear, and whose parent/caregiver placed higher value on oral health and healthcare for themselves, were more likely to have had a dental visit in the past year.

Breast cancer is the second leading cause of cancer-related mortality in women. Various nutritional compounds possess anti-carcinogenic properties which may be mediated through their effects on the gut microbiota and its production of short-chain fatty acids (SCFAs) for the prevention of breast cancer. We evaluated the impact of broccoli sprouts (BSp), green tea polyphenols (GTPs) and their combination on the gut microbiota and SCFAs metabolism from the microbiota in Her2/neu transgenic mice that spontaneously develop estrogen receptor-negative [ER(-)] mammary tumors. The mice were grouped based on the dietary treatment: control, BSp, GTPs or their combination from beginning in early life (BE) or life-long from conception (LC). We found that the combination group showed the strongest inhibiting effect on tumor growth volume and a significant increase in tumor latency. BSp treatment was integrally more efficacious than the GTPs group when compared to the control group. There was similar clustering of microbiota of BSp-fed mice with combination-fed mice, and GTPs-fed mice with control-fed mice at pre-tumor in the BE group and at pre-tumor and post-tumor in the LC group. The mice on all dietary treatment groups incurred a significant increase of Adlercreutzia, Lactobacillus genus and Lachnospiraceae, S24-7 family in the both BE and LC groups. We found no change in SCFAs levels in the plasma of BSp-fed, GTPs-fed and combination-fed mice of the BE group. Marked changes were observed in the mice of the LC group consisting of significant increases in propionate and isobutyrate in GTPs-fed and combination-fed mice. These studies indicate that nutrients such as BSp and GTPs differentially affect the gut microbial composition in both the BE and LC groups and the key metabolites (SCFAs) levels in the LC group. The findings also suggest that temporal factors related to different time windows of consumption during the life-span can have a promising influence on the gut microbial composition, SCFAs profiles and ER(-) breast cancer prevention.

BackgroundOral drugs can have side effects such as diarrhea that indicate the perturbation of the gut microbial community. To further understand the dynamics of perturbation, we have assessed the strain relatedness of samples from previously published data sets from pre and post bowel evacuation, episodes of diarrhea, and administration of oral drugs to treat diabetes and rheumatoid arthritis.MethodsWe analyzed a total of published five data sets using our strain-tracking tool called Window-based Single Nucleotide Variant (SNV) Similarity (WSS) to identify related strains from the same individual.ResultsStrain-tracking analysis using the first data set from 8 individuals pre and 21-50 days post iso-osmotic bowel wash revealed almost all microbial strains were related in an individual between pre and post samples. Similarly, in a second study, strain-tracking analysis of 4 individuals pre and post sporadic diarrhea revealed the majority of strains were related over time (up to 44 weeks). In contrast, the analysis of a third data set from 22 individuals pre and post 3-day exposure of oral metformin revealed that no individuals had a related strain. In a fourth study, the data set taken at 2 and 4 months from 38 individuals on placebo or metformin revealed individual specific sharing of pre and post strains. Finally, the data set from 18 individuals with rheumatoid arthritis given disease-modifying antirheumatic drugs methotrexate or glycosides of the traditional Chinese medicinal component Tripterygium wilfordii showed individual specific sharing of pre and post strains up to 16 months.ConclusionOral drugs used to treat chronic disease can result in individual specific microbial strain change for the majority of species. Since the gut community provides essential functions for the host, our study supports personalized monitoring to assess the status of the dominant microbial strains after initiation of oral drugs to treat chronic disease.

BACKGROUND:Given the increasing realization of the important functions of the gut microbial community in human health, it is important to determine whether the increased age of the host coupled with inevitable environmental changes can alter the stability of individual microbial strains of the gut microbial community. Since early studies demonstrated that pairs of twins possess the related gut microbial communities, to gain insights into the temporal stability of the reservoir of gut microbial strains in humans, we have assessed the strain relatedness of samples from two previously published data sets that were obtained from twin children and adults (36-80 years old) who have been either living together or apart for different times. METHODS:We analyzed the two data sets; twin children (n = 24) and adults (n = 50) using our previously developed strain-tracking program called Window-based Single Nucleotide Variant (SNV) Similarity (WSS) that can distinguish a related strain pair from a non-related strain pair based on the overall genome-wide SNV similarity. To independently substantiate the identification of distinct microbial genomic variants (herein strains) observed from WSS analysis, we used analysis by StrainPhlAn. RESULTS:Analysis of the twin children data set revealed a significantly (P-value

Protection of the world's remaining forests and biodiversity is a matter of global concern. Yunnan, China is home to China's only mainland tropical rainforests, and 20% of China's total biodiversity. Despite restoration measures and establishment of new protected areas, this region is still experiencing biodiversity loss due to inadequate management and monitoring. We evaluate restoration success of China's tropical forests in Xishuangbanna National Nature Reserve (XSBN-NNR), Yunnan, China using dung beetles as an indicator taxon. We sampled across a land-use gradient of human alteration: protected forest, restored forest, community owned forest, and rubber plantation. We collected 3,748 dung beetles from 21 species over a 3 month period. Multivariate analyses revealed unique assemblages in each land-use category, but with restored forest most similar to protected areas, suggesting restoration success in this region. Community forests were more diverse than plantations, suggesting that community forests may be a valuable and practical conservation tool in this region. Most species were generalists, although some had dietary and habitat preferences. Furthermore, dietary niche breadths were, on average, higher in disturbed areas, suggesting that disturbance may result in dietary changes. We show that restoration of tropical forests appears to be successful for a key ecological and biological indicator group- dung beetles. Furthermore, community-owned forests appear to be valuable and practical method of maintaining ecosystem health and biodiversity in the region. Future management in this region would likely benefit from encouragement to maintain community-owned forests, economic incentives for restoring farmland to forest, and increased environmental monitoring across the land-use gradient.

Fusobacterium necrophorum (Fn), a gram-negative anaerobe, is increasingly implicated as an etiologic agent in older adolescents and young adults with sore throat. Inadequately treated Fn pharyngitis may result in suppurative complications such as peritonsillar abscess and Lemierre's syndrome. Data from the literature suggest that the incidence of life-threating complications in these age groups from Fn pharyngitis (Lemierre's syndrome) in the United States exceeds those associated with group A beta-hemolytic streptococcal (GAS) pharyngitis (acute rheumatic fever). Using real-time PCR, we previously reported about a 10% prevalence of Fn in asymptomatic medical students and about 20% in students complaining of sore throat at a university student health clinic (p = 0.009). In this study, a comprehensive microbiome analysis of the same study samples confirms that Fn pharyngitis was more common than GAS pharyngitis. Eighteen patients were found to have Fn OTU values exceeding an arbitrary cutoff value of 0.1, i.e. greater than 10% of total sequences, with five subjects reaching values above 0.7. By contrast only 9 patients had GAS OTU values greater than 0.1 and none exceeded 0.6. When the data were analyzed using five separate assessments of alpha diversity, in each case for Fn there were statistically significant differences between Fn positive_high (OTU abundance > 0.1) vs control, Fn positive_high vs Fn negative (OTU abundance = 0), Fn positive_high vs Fn positive_low (OTU abundance > 0 and < 0.1). When the data were analyzed using three beta diversity indexes (Bray-Curtis, weighted unifrac, and unweighted unifrac), there were statistically significant differences between Fn positive_high (OTU abundance ≥ 0.1) vs control for all three. Statistically significant differences remained if we chose somewhat different OTU abundance cutoffs of 0.05 or 0.15. We conclude that Fn appears to play a dominant role in bacterial pharyngitis in the older adolescent and young adult age groups and that the development of a productive mucosal infection with Fn is linked to a significant decrease in the diversity of the associated tonsillar microbiome.

Since dietary polyphenols can have beneficial effects in prevention and treatment of cancer, we tested the hypothesis that breast cancer patients' intestinal microbiota is modulated by genistein (GE), an isoflavone found in soy, and that microbial alterations may offset the side effects brought about by chemotherapy. We demonstrated successful humanization of germ-free mice by transplanting fecal samples from breast cancer patients before and after chemotherapy. Mice were then grouped based on chemotherapy status and GE or control diet. We did not find any significant differences between pre-chemotherapy and post-chemotherapy bacterial composition and abundances. Germ-free mice on a GE diet showed differences in microbial composition as compared to mice on control diet. Four weeks after introduction of the customized GE diet, there was distinct clustering of GE-fed mice as compared to the control-fed group. In the gut microbiome of GE-treated humanized mice, there was an increase in abundance of genera Lactococcus and Eubacterium. Phylum Verrucomicrobia showed statistically significant (p = 0.02) differences in abundances between the GE-fed and control-fed groups. There was an increase in bacteria belonging to family Lachnospiraceae and Ruminococcaceae in GE-fed mice. Marked changes were observed in GE catabolism in mice humanized with fecal material from two of three patients' post-chemotherapy with complete disappearance of 4-ethylphenol and 2-(4-hydroxyphenol) propionic acid conjugates. The post-tumor samples did not show any distinct clustering of the gut microbiota between the two diet groups. There was an increase in latency of about 25% for tumor growth of the humanized mice that were on a GE diet as compared to humanized mice on a control diet. The average tumor size for the GE group was significantly decreased compared to the non-GE group. Collectively, our results suggest that the intestinal microbiota becomes altered with a GE diet before induction of tumor. Our findings indicate that GE modulates the microbiome in humanized mice that may contribute to its effects on increasing the latency of breast tumor and reducing tumor growth.

Research on the spatial patterns of human-wildlife conflict is fundamental to understanding the mechanisms underlying it and to identifying opportunities for mitigation. In the state of Xishuangbanna, containing China's largest tropical forest, an imbalance between nature conservation and economic development has led to increasing conflicts between humans and Asian elephants (Elephas maximus), as both elephant numbers and conversion of habitable land to rubber plantations have increased over the last several decades. We analyzed government data on the compensation costs of elephant-caused damage in Xishuangbanna between 2008 and 2012 to understand the spatial and temporal patterns of conflict, in terms of their occurrence, frequency and distribution. More than 18,261 incidents were reported, including episodes involving damage to rubber trees (n = 10,999), damage to crops such as paddy, upland rice, corn, bananas and sugarcane (n = 11,020), property loss (n = 689) and attacks on humans (n = 19). The conflict data reconfirmed the presence of elephants in areas which have lacked records since the late 1990s. Zero Altered Negative Binomial models revealed that the risk of damage to crops and plantations increased with proximity to protected areas, increasing distance from roads, and lower settlement density. The patterns were constant across seasons and types of crop damaged. Damage to rubber trees was essentially incidental as elephants searched for crops to eat. A predictive map of risks revealed hotspots of conflict within and around protected areas, the last refuges for elephants in the region, and along habitat corridors connecting them. Additionally, we analyzed how mitigation efforts can best diminish the risk of conflict while minimizing financial costs and adverse biological impacts. Our analytical approach can be adopted, adjusted and expanded to other areas with historical records of human-wildlife conflict.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy.Choline Deficient L-Amino Acid (CDAA) and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens.We observed statistically significant differences in the level of extracellular vesicles (EVs) in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p

Using transgenic zebrafish (fli1:egfp) that stably express enhanced green fluorescent protein (eGFP) within vascular endothelial cells, we recently developed and optimized a 384-well high-content screening (HCS) assay that enables us to screen and identify chemicals affecting cardiovascular development and function at non-teratogenic concentrations. Within this assay, automated image acquisition procedures and custom image analysis protocols are used to quantify body length, heart rate, circulation, pericardial area, and intersegmental vessel area within individual live embryos exposed from 5 to 72 hours post-fertilization. After ranking developmental toxicity data generated from the U.S. Environmental Protection Agency's (EPA's) zebrafish teratogenesis assay, we screened 26 of the most acutely toxic chemicals within EPA's ToxCast Phase-I library in concentration-response format (0.05-50 µM) using this HCS assay. Based on this screen, we identified butafenacil as a potent inducer of anemia, as exposure from 0.39 to 3.125 µM butafenacil completely abolished arterial circulation in the absence of effects on all other endpoints evaluated. Butafenacil is an herbicide that inhibits protoporphyrinogen oxidase (PPO)--an enzyme necessary for heme production in vertebrates. Using o-dianisidine staining, we then revealed that severe butafenacil-induced anemia in zebrafish was due to a complete loss of hemoglobin following exposure during early development. Therefore, six additional PPO inhibitors within the ToxCast Phase-I library were screened to determine whether anemia represents a common adverse outcome for these herbicides. Embryonic exposure to only one of these PPO inhibitors--flumioxazin--resulted in a similar phenotype as butafenacil, albeit not as severe as butafenacil. Overall, this study highlights the potential utility of this assay for (1) screening chemicals for cardiovascular toxicity and (2) prioritizing chemicals for future hypothesis-driven and mechanism-focused investigations within zebrafish and mammalian models.

The retina is a light-sensitive tissue lining the inner surface of the eye and one of the few human organs whose cholesterol maintenance is still poorly understood. Challenges in studies of the retina include its complex multicellular and multilayered structure; unique cell types and functions; and specific physico-chemical environment.We isolated specimens of the neural retina (NR) and underlying retinal pigment epithelium (RPE)/choroid from six deceased human donors and evaluated them for expression of genes and proteins representing the major pathways of cholesterol input, output and regulation. Eighty-four genes were studied by PCR array, 16 genes were assessed by quantitative real time PCR, and 13 proteins were characterized by immunohistochemistry. Cholesterol distribution among different retinal layers was analyzed as well by histochemical staining with filipin. Our major findings pertain to two adjacent retinal layers: the photoreceptor outer segments of NR and the RPE. We demonstrate that in the photoreceptor outer segments, cholesterol biosynthesis, catabolism and regulation via LXR and SREBP are weak or absent and cholesterol content is the lowest of all retinal layers. Cholesterol maintenance in the RPE is different, yet the gene expression also does not appear to be regulated by the SREBPs and varies significantly among different individuals.This comprehensive investigation provides important insights into the relationship and spatial distribution of different pathways of cholesterol input, output and regulation in the NR-RPE region. The data obtained are important for deciphering the putative link between cholesterol and age-related macular degeneration, a major cause of irreversible vision loss in the elderly.