Unraveling brain palmitic acid: Origin, levels and metabolic fate.

In the human brain, palmitic acid (16:0; PAM) comprises nearly half of total brain saturates and has been identified as the third most abundant fatty acid overall. Brain PAM supports the structure of membrane phospholipids, provides energy, and regulates protein stability. Sources underlying the origin of brain PAM are both diet and endogenous synthesis via de novo lipogenesis (DNL), primarily from glucose. However, studies investigating the origin of brain PAM are limited to tracer studies utilizing labelled (14C/11C/3H/2H) PAM, and results vary based on the model and tracer used. Nevertheless, there is evidence PAM is synthesized locally in the brain, in addition to obtained directly from the diet. Herein, we provide an overview of brain PAM origin, entry to the brain, metabolic fate, and factors influencing brain PAM kinetics and levels, the latter in the context of age, as well as neurological diseases and psychiatric disorders. Additionally, we briefly summarize the role of PAM in signaling at the level of the brain. We add to the literature a rudimentary summary on brain PAM metabolism.

Patient experiences of buprenorphine dispensing from a mobile medical unit.

BACKGROUND: Overdose deaths continue to rise within the United States, despite effective treatments such as buprenorphine and methadone for opioid use disorder (OUD). Mobile medical units with the ability to dispense buprenorphine have been developed to engage patients and eliminate barriers to accessing OUD treatment. This study reports survey responses of patients of a mobile medical unit dispensing buprenorphine in areas of Chicago, IL with high overdose rates. METHODS: All patients who were dispensed buprenorphine via the mobile medical unit were invited to participate in a 7-item anonymous survey between May 24, 2023, and August 25, 2023. The survey included 5-point satisfaction scale, multiple-choice, and open-ended questions. Outcomes included satisfaction with buprenorphine dispensing from the mobile medical unit, satisfaction with filling buprenorphine at a pharmacy in the past, barriers experienced at pharmacies when filling buprenorphine, and whether the client would have started treatment that day if the mobile medical unit had not been present. Satisfaction scale and multiple-choice question responses were assessed using descriptive statistics. Wilcoxon signed-rank test was used to compare median satisfaction levels between receiving buprenorphine from the mobile medical unit versus filling a buprenorphine prescription at a community pharmacy. Open-ended questions were analyzed qualitatively using inductive thematic analysis. RESULTS: 106 unique patients were dispensed buprenorphine from the mobile unit during the study period. Of these patients, 54 (51%) completed the survey. Respondents reported high satisfaction with the buprenorphine dispensing process as a part of a mobile medical unit. Of those who had previously filled buprenorphine at a pharmacy, 83% reported at least one barrier, with delays in prescription dispensing from a community pharmacy, lack of transportation to/from the pharmacy, and opioid withdrawal symptoms being the most common barriers. 87% reported they would not have started buprenorphine that same day if the mobile medical unit had not been present. Nearly half of survey participants reported having taken buprenorphine that was not prescribed to them. Qualitative analysis of open-ended survey responses noted the importance of convenient accessibility, comprehensive care, and a non-judgmental environment. CONCLUSIONS: Mobile medical units that dispense buprenorphine are an innovative model to reach patients with OUD who have significant treatment access barriers. This study found that patients who experienced barriers to accessing buprenorphine from a pharmacy were highly satisfied with the mobile medical unit's buprenorphine dispensing process. Programs seeking to develop mobile buprenorphine dispensing programs should consider patient priorities of accessibility, comprehensive care, and welcoming, non-judgmental environments.

MRIO: the Magnetic Resonance Imaging Acquisition and Analysis Ontology.

Magnetic resonance imaging of the brain is a useful tool in both the clinic and research settings, aiding in the diagnosis and treatments of neurological disease and expanding our knowledge of the brain. However, there are many challenges inherent in managing and analyzing MRI data, due in large part to the heterogeneity of data acquisition. To address this, we have developed MRIO, the Magnetic Resonance Imaging Acquisition and Analysis Ontology. MRIO provides well-reasoned classes and logical axioms for the acquisition of several MRI acquisition types and well-known, peer-reviewed analysis software, facilitating the use of MRI data. These classes provide a common language for the neuroimaging research process and help standardize the organization and analysis of MRI data for reproducible datasets. We also provide queries for automated assignment of analyses for given MRI types. MRIO aids researchers in managing neuroimaging studies by helping organize and annotate MRI data and integrating with existing standards such as Digital Imaging and Communications in Medicine and the Brain Imaging Data Structure, enhancing reproducibility and interoperability. MRIO was constructed according to Open Biomedical Ontologies Foundry principles and has contributed several classes to the Ontology for Biomedical Investigations to help bridge neuroimaging data to other domains. MRIO addresses the need for a "common language" for MRI that can help manage the neuroimaging research, by enabling researchers to identify appropriate analyses for sets of scans and facilitating data organization and reporting.

Potentiation of the M 1 muscarinic acetylcholine receptor normalizes neuronal activation patterns and improves apnea severity in Mecp2+/- mice.

Rett syndrome (RTT) is a neurodevelopmental disorder that is caused by loss-of-function mutations in the methyl-CpG binding protein 2 ( MeCP2 ) gene. RTT patients experience a myriad of debilitating symptoms, which include respiratory phenotypes that are often associated with lethality. Our previous work established that expression of the M 1 muscarinic acetylcholine receptor (mAchR) is decreased in RTT autopsy samples, and that potentiation of the M 1 receptor improves apneas in a mouse model of RTT; however, the population of neurons driving this rescue is unclear. Loss of Mecp2 correlates with excessive neuronal activity in cardiorespiratory nuclei. Since M 1 is found on cholinergic interneurons, we hypothesized that M 1 -potentiating compounds decrease apnea frequency by tempering brainstem hyperactivity. To test this, Mecp2 +/- and Mecp2 +/+ mice were screened for apneas before and after administration of the M 1 positive allosteric modulator (PAM) VU0453595 (VU595). Brains from the same mice were then imaged for c-Fos, ChAT, and Syto16 using whole-brain light-sheet microscopy to establish genotype and drug-dependent activation patterns that could be correlated with VU595's efficacy on apneas. The vehicle-treated Mecp2 +/- brain exhibited broad hyperactivity when coupled with the phenotypic prescreen, which was significantly decreased by administration of VU595, particularly in regions known to modulate the activity of respiratory nuclei (i.e. hippocampus and striatum). Further, the extent of apnea rescue in each mouse showed a significant positive correlation with c-Fos expression in non-cholinergic neurons in the striatum, thalamus, dentate gyrus, and within the cholinergic neurons of the brainstem. These results indicate that Mecp2 +/- mice are prone to hyperactivity in brain regions that regulate respiration, which can be normalized through M 1 potentiation.

An Automated Tool to Classify and Transform Unstructured MRI Data into BIDS Datasets.

The increasing use of neuroimaging in clinical research has driven the creation of many large imaging datasets. However, these datasets often rely on inconsistent naming conventions in image file headers to describe acquisition, and time-consuming manual curation is necessary. Therefore, we sought to automate the process of classifying and organizing magnetic resonance imaging (MRI) data according to acquisition types common to the clinical routine, as well as automate the transformation of raw, unstructured images into Brain Imaging Data Structure (BIDS) datasets. To do this, we trained an XGBoost model to classify MRI acquisition types using relatively few acquisition parameters that are automatically stored by the MRI scanner in image file metadata, which are then mapped to the naming conventions prescribed by BIDS to transform the input images to the BIDS structure. The model recognizes MRI types with 99.475% accuracy, as well as a micro/macro-averaged precision of 0.9995/0.994, a micro/macro-averaged recall of 0.9995/0.989, and a micro/macro-averaged F1 of 0.9995/0.991. Our approach accurately and quickly classifies MRI types and transforms unstructured data into standardized structures with little-to-no user intervention, reducing the barrier of entry for clinical scientists and increasing the accessibility of existing neuroimaging data.

Quantifying methane emissions from United States landfills.

Methane emissions from solid waste may represent a substantial fraction of the global anthropogenic budget, but few comprehensive studies exist to assess inventory assumptions. We quantified emissions at hundreds of large landfills across 18 states in the United States between 2016 and 2022 using airborne imaging spectrometers. Spanning 20% of open United States landfills, this represents the most systematic measurement-based study of methane point sources of the waste sector. We detected significant point source emissions at a majority (52%) of these sites, many with emissions persisting over multiple revisits (weeks to years). We compared these against independent contemporaneous in situ airborne observations at 15 landfills and established good agreement. Our findings indicate a need for long-term, synoptic-scale monitoring of landfill emissions in the context of climate change mitigation policy.

Integrated Proteomics Characterization of NLRP3 Inflammasome Inhibitor MCC950 in Monocytic Cell Line Confirms Direct MCC950 Engagement with Endogenous NLRP3.

Inhibition of the NLRP3 inflammasome is a promising strategy for the development of new treatments for inflammatory diseases. MCC950 is a potent and selective small-molecule inhibitor of the NLRP3 pathway and has been validated in numerous species and disease models. Although the capacity of MCC950 to block NLRP3 signaling is well-established, it is still critical to identify the mechanism of action and molecular targets of MCC950 to inform and derisk drug development. Quantitative proteomics performed in disease-relevant systems provides a powerful method to study both direct and indirect pharmacological responses to small molecules to elucidate the mechanism of action and confirm target engagement. A comprehensive target deconvolution campaign requires the use of complementary chemical biology techniques. Here we applied two orthogonal chemical biology techniques: compressed Cellular Thermal Shift Assay (CETSA) and photoaffinity labeling chemoproteomics, performed under biologically relevant conditions with LPS-primed THP-1 cells, thereby deconvoluting, for the first time, the molecular targets of MCC950 using chemical biology techniques. In-cell chemoproteomics with inlysate CETSA confirmed the suspected mechanism as the disruption of inflammasome formation via NLRP3. Further cCETSA (c indicates compressed) in live cells mapped the stabilization of NLRP3 inflammasome pathway proteins, highlighting modulation of the targeted pathway. This is the first evidence of direct MCC950 engagement with endogenous NLRP3 in a human macrophage cellular system using discovery proteomics chemical biology techniques, providing critical information for inflammasome studies.

Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcription.

Tight regulation of macrophage immune gene expression is required to fight infection without risking harmful inflammation. The contribution of RNA-binding proteins (RBPs) to shaping the macrophage response to pathogens remains poorly understood. Transcriptomic analysis reveals that a member of the serine/arginine-rich (SR) family of mRNA processing factors, SRSF7, is required for optimal expression of a cohort of interferon-stimulated genes in macrophages. Using genetic and biochemical assays, we discover that in addition to its canonical role in regulating alternative splicing, SRSF7 drives transcription of interferon regulatory transcription factor 7 (IRF7) to promote antiviral immunity. At the Irf7 promoter, SRSF7 maximizes STAT1 transcription factor binding and RNA polymerase II elongation via cooperation with the H4K20me1 histone methyltransferase KMT5a (SET8). These studies define a role for an SR protein in activating transcription and reveal an RBP-chromatin network that orchestrates macrophage antiviral gene expression.

Increased iron uptake by splenic hematopoietic stem cells promotes TET2-dependent erythroid regeneration.

Hematopoietic stem cells (HSCs) are capable of regenerating the blood system, but the instructive cues that direct HSCs to regenerate particular lineages lost to the injury remain elusive. Here, we show that iron is increasingly taken up by HSCs during anemia and induces erythroid gene expression and regeneration in a Tet2-dependent manner. Lineage tracing of HSCs reveals that HSCs respond to hemolytic anemia by increasing erythroid output. The number of HSCs in the spleen, but not bone marrow, increases upon anemia and these HSCs exhibit enhanced proliferation, erythroid differentiation, iron uptake, and TET2 protein expression. Increased iron in HSCs promotes DNA demethylation and expression of erythroid genes. Suppressing iron uptake or TET2 expression impairs erythroid genes expression and erythroid differentiation of HSCs; iron supplementation, however, augments these processes. These results establish that the physiological level of iron taken up by HSCs has an instructive role in promoting erythroid-biased differentiation of HSCs.

Upregulated hepatic lipogenesis from dietary sugars in response to low palmitate feeding supplies brain palmitate.

Palmitic acid (PAM) can be provided in the diet or synthesized via de novo lipogenesis (DNL), primarily, from glucose. Preclinical work on the origin of brain PAM during development is scarce and contrasts results in adults. In this work, we use naturally occurring carbon isotope ratios (13C/12C; δ13C) to uncover the origin of brain PAM at postnatal days 0, 10, 21 and 35, and RNA sequencing to identify the pathways involved in maintaining brain PAM, at day 35, in mice fed diets with low, medium, and high PAM from birth. Here we show that DNL from dietary sugars maintains the majority of brain PAM during development and is augmented in mice fed low PAM. Importantly, the upregulation of hepatic DNL genes, in response to low PAM at day 35, demonstrates the presence of a compensatory mechanism to maintain total brain PAM pools compared to the liver; suggesting the importance of brain PAM regulation.

Protein concentrations and activities of fatty acid desaturase and elongase enzymes in liver, brain, testicle, and kidney from mice: Substrate dependency.

The synthesis rates of n-3 and n-6 polyunsaturated fatty acids (PUFAs) in rodents and humans are not agreed upon and depend on substrate availability independently of the capacity for synthesis. Therefore, we aimed to assess the activities of the enzymes for n-3 and n-6 PUFA synthesis pathways in liver, brain, testicle, kidney, heart, and lung, in relation to their protein concentration levels. Eight-week-old Balb/c mice (n = 8) were fed a standard chow diet (6.2% fat, 18.6% protein, and 44.2% carbohydrates) until 14 weeks of age, anesthetized with isoflurane and tissue samples were collected (previously perfused) and stored at -80°C. The protein concentration of the enzymes (Δ-6D, Δ-5D, Elovl2, and Elovl5) were assessed by ELISA kits; their activities were assayed using specific PUFA precursors and measuring the respective PUFA products as fatty acid methyl esters by gas chromatographic analysis. The liver had the highest capacity for PUFA biosynthesis, with limited activity in the brain, testicles, and kidney, while we failed to detect activity in the heart and lung. The protein concentration and activity of the enzymes were significantly correlated. Furthermore, Δ-6D, Δ-5D, and Elovl2 have a higher affinity for n-3 PUFA precursors compared to n-6 PUFA. The capacity for PUFA synthesis in mice mainly resides in the liver, with enzymes having preference for n-3 PUFAs.

Blood and tissue docosahexaenoic acid (DHA, 22:6n-3) turnover rates from Ahiflower® oil are not different than from DHA ethyl ester oil in a diet switch mouse model.

Ahiflower® oil is high in α-linolenic and stearidonic acids, however, tissue/blood docosahexaenoic acid (DHA, 22:6n-3) turnover from dietary Ahiflower oil has not been investigated. In this study, we use compound-specific isotope analysis to determine tissue DHA synthesis/turnover from Ahiflower, flaxseed and DHA oils. Pregnant BALB/c mice (13-17 days) were placed on a 2 % algal DHA oil diet of high carbon-13 content (δ13C) and pups (n = 132) were maintained on the diet until 9 weeks old. Mice were then randomly allocated to a low δ13C-n-3 PUFA diet of either: 1) 4 % Ahiflower oil, 2) 4.35 % flaxseed oil or 3) 1 % fish DHA ethyl ester oil for 1, 3, 7, 14, 30, 60 or 120 days (n = 6). Serum, liver, adipose and brains were collected and DHA levels and δ13C were determined. DHA concentrations were highest (p < 0.05) in the liver and adipose of DHA-fed animals with no diet differences in serum or brain (p > 0.05). Based on the presence or absence of overlapping 95 % C.I.'s, DHA half-lives and synthesis/turnover rates were not different between Ahiflower and DHA diets in the liver, adipose or brain. DHA half-lives and synthesis/turnover rates from flaxseed oil were significantly slower than from the DHA diet in all serum/tissues. These findings suggest that the distinct Ahiflower oil n-3 PUFA composition could support tissue DHA needs at a similar rate to dietary DHA, making it a unique plant-based dietary option for maintaining DHA turnover comparably to dietary DHA.

Direct measurements of methane emissions from key facilities in Alberta's oil and gas supply chain.

The Canadian government aims to achieve a 40-45 % reduction of oil and gas (O&G) methane (CH4) emissions by 2025, and 75 % by 2030, although recent studies consistently show that Canada's federal inventory underestimates emissions by a factor of 1.4 to 2.0. We conducted aerial mass balance measurements at sixteen upstream O&G facilities in Alberta between September 29 and November 6, 2021, and our measurements revealed that emissions were, on average, 1.7 (standard deviation (SD): 0.6) times higher than the reported emissions for the same year. On a subsequent campaign from August 12 to September 27, 2022, we focused on understudied O&G sectors covering 24 midstream and end-use facilities. These sites were found to be emitting, on average, 3.4 (SD: 1.1) times more CH4 than reported. By extrapolating our measurements to Alberta, we found that underground gas storage contributed to 1.6 % of provincial O&G emissions, followed by natural gas power stations/refineries less than 1.0 %. The widespread underreporting of CH4 emissions highlights the necessity for more empirical measurements of midstream and end-use facilities.

Dietary triacetin, but not medium chain triacylglycerides, blunts weight gain in diet-induced rat model of obesity.

Consumption of a Western diet (WD) is known to increase the risk of obesity. Short or medium chain fatty acids influence energy metabolism, and triacetin, a synthetic short chain triacylglyceride, has been shown to lower body fat under normal conditions. This study aimed to investigate if triacetin as part of a WD modifies rat weight and body fat. Male rats were fed a control diet or WD for 8 weeks. At week 8, rats in the WD group were maintained on a WD diet or switched to a WD diet containing 30% energy from medium-chain triacylglyceride (WD-MCT) or triacetin (WD-T) for another 8 weeks. At week 16, rats were euthanized and liver, adipose and blood were collected. Tissue fatty acids (FAs) were quantified by gas chromatography (GC) and hepatic FAs were measured by GC-combustion-isotope ratio mass spectrometry for δ13 C-palmitic acid (PAM)-a novel marker of de novo lipogenesis (DNL). Rats fed WD-T had a body weight not statistically different to the control group, and gained less body weight than rats fed WD alone. Furthermore, WD-T fed rats had a lower fat mass, and lower total liver and plasma FAs compared to the WD group. Rats fed WD-T did not differ from WD in blood ketone or glucose levels, however, had a significantly lower hepatic δ13 C-PAM value than WD fed rats; suggestive of lower DNL. In summary, we show that triacetin has the potential to blunt weight gain and adipose tissue accumulation in a rodent model of obesity, possibly due to a decrease in DNL.

MRIO: The Magnetic Resonance Imaging Acquisition and Analysis Ontology.

Objective: Magnetic resonance imaging of the brain is a useful tool in both the clinic and research settings, aiding in the diagnosis and treatments of neurological disease and expanding our knowledge of the brain. However, there are many challenges inherent in managing and analyzing MRI data, due in large part to the heterogeneity of data acquisition. Materials and Methods: To address this, we have developed MRIO, the Magnetic Resonance Imaging Acquisition and Analysis Ontology. Results: MRIO provides well-reasoned classes and logical axioms for the acquisition of several MRI acquisition types and well-known, peer-reviewed analysis software, facilitating the use of MRI data. These classes provide a common language for the neuroimaging research process and help standardize the organization and analysis of MRI data for reproducible datasets. We also provide queries for automated assignment of analyses for given MRI types. Discussion: MRIO aids researchers in managing neuroimaging studies by helping organize and annotate MRI data and integrating with existing standards such as Digital Imaging and Communications in Medicine and the Brain Imaging Data Structure, enhancing reproducibility and interoperability. MRIO was constructed according to Open Biomedical Ontologies Foundry principals and has contributed several terms to the Ontology for Biomedical Investigations to help bridge neuroimaging data to other domains. Conclusion: MRIO addresses the need for a "common language" for MRI that can help manage the neuroimaging research, by enabling researchers to identify appropriate analyses for sets of scans and facilitating data organization and reporting.

Serine arginine-rich splicing factor (SRSF7) cooperates with the histone methyltransferase KMT5a to promote the type I interferon response via transcriptional activation of IRF7.

Tight regulation of macrophage immune gene expression is required to fight infection without risking harmful inflammation. The contribution of RNA binding proteins (RBPs) to shaping the macrophage response to pathogens remains poorly understood. Transcriptomic analysis revealed that a member of the serine/arginine-rich (SR) family of mRNA processing factors, SRSF7, is required for optimal expression of a cohort of interferon stimulated genes (ISGs) in macrophages. Using genetic and biochemical assays, we discovered that in addition to its canonical role in regulating alternative splicing, SRSF7 drives transcription of interferon regulatory transcription factor 7 (IRF7) to promote antiviral immunity. At the Irf7 promoter, SRSF7 maximizes STAT1 transcription factor binding and RNA polymerase II elongation via cooperation with the H4K20me1 histone methyltransferase KMT5a (SET8). These studies define an unorthodox role for an SR protein in activating transcription and reveal an unappreciated RNA binding protein-chromatin network that orchestrates macrophage antiviral gene expression.

The use of virtual reality hypnosis for prostate cancer patients during transperineal biopsy/gold seed implantation: A needs assessment study.

BACKGROUND: Patients having radiation therapy treatment to the prostate may require invasive preparation procedures under local anesthesia (LA), such as the insertion of gold seeds into the prostate or targeted biopsies. These procedures can induce pain and anxiety for some patients. Virtual Reality Hypnosis (VRH) is the combination of a 360-degree video display with audio and mental guides for relaxation and distraction during medical procedures. The objective of this research was to assess the level of patient interest in the use of VRH during gold seed insertion and biopsy, and to identify a subset of patients that would be most likely to benefit from the use of VRH. METHODS: This single arm, prospective pilot study included patients who were receiving biopsy and/or gold seed insertion using a 2-step LA procedure. Participants were asked to complete a questionnaire about their level of knowledge and interest in VRH before and after their procedure. At the same time, pain and anxiety levels were collected before and after the procedure, as well as during each LA step and at the mid-seed drop/biopsy core extraction. A visual analogue scale for pain and the National Comprehensive Cancer Network's Distress Thermometer were used to verbally rate pain and distress respectively. Descriptive statistics and Pearson's correlation coefficient were calculated for all variables of interest. RESULTS: 24 patients were recruited and 1 had their procedure cancelled, so a total of 23 patients completed this study. 74% of patients (n=23) agreed to try VRH before their procedures, whereas 65% of patients (n=23) were willing to try VRH after the procedure. Pain scores were highest at deep LA injection (mean= 5.48, SD= 2.56) and distress scores were also highest at deep LA injection (mean= 4.28, SD= 2.92). After the procedure, 83% of participants with pain scores above the mean at deep LA injection and 80% with anxiety scores above the mean at deep LA injection agreed that they would be willing to try VRH. CONCLUSIONS: Patients with higher pain and distress scores had more interest in trying VRH with the standard LA for gold seed insertion/biopsy procedures. Patients with a history of lower pain tolerance or who express having experienced high levels of pain during previous biopsies will be the target population for using VRH in future trials to determine feasibility and effectiveness.

Excess methane emissions from shallow water platforms elevate the carbon intensity of US Gulf of Mexico oil and gas production.

The Gulf of Mexico is the largest offshore fossil fuel production basin in the United States. Decisions on expanding production in the region legally depend on assessments of the climate impact of new growth. Here, we collect airborne observations and combine them with previous surveys and inventories to estimate the climate impact of current field operations. We evaluate all major on-site greenhouse gas emissions, carbon dioxide (CO2) from combustion, and methane from losses and venting. Using these findings, we estimate the climate impact per unit of energy of produced oil and gas (the carbon intensity). We find high methane emissions (0.60 Tg/y [0.41 to 0.81, 95% confidence interval]) exceeding inventories. This elevates the average CI of the basin to 5.3 g CO2e/MJ [4.1 to 6.7] (100-y horizon) over twice the inventories. The CI across the Gulf varies, with deep water production exhibiting a low CI dominated by combustion emissions (1.1 g CO2e/MJ), while shallow federal and state waters exhibit an extraordinarily high CI (16 and 43 g CO2e/MJ) primarily driven by methane emissions from central hub facilities (intermediaries for gathering and processing). This shows that production in shallow waters, as currently operated, has outsized climate impact. To mitigate these climate impacts, methane emissions in shallow waters must be addressed through efficient flaring instead of venting and repair, refurbishment, or abandonment of poorly maintained infrastructure. We demonstrate an approach to evaluate the CI of fossil fuel production using observations, considering all direct production emissions while allocating to all fossil products.

Epidemiological correlates of overweight and obesity in the Northern Cape Province, South Africa.

Background: In the past several decades, obesity has become a major public health issue worldwide, associated with increased rates of chronic disease and death. Like many developing nations, South Africa is experiencing rapid increases in BMI, and as a result, evidence-based preventive strategies are needed to reduce the increasing burden of overweight and obesity. This study aimed to determine the prevalence and predictors of overweight and obesity among a multi-ethnic cohort from the rural Northern Cape of South Africa. Methods: These data were collected as part of a tuberculosis (TB) case-control study, with 395 healthy control participants included in the final analysis. Overweight and obesity were defined according to WHO classification. Multivariate linear models of BMI were generated using sex, age, education level, smoking, alcohol consumption, and diabetes as predictor variables. We also used multivariable logistic regression analysis to assess the relationship of these factors with overweight and obesity. Results: The average BMI in our study cohort was 25.2. The prevalence of overweight was 18.0% and the prevalence of obesity was 25.0%. We find that female sex, being older, having more years of formal education, having diabetes, and being in a rural area are all positively associated with BMI in our dataset. Women (OR = 5.6, 95% CI [3.3-9.8]), rural individuals (OR = 3.3, 95% CI [1.9-6.0]), older individuals (OR = 1.02, 95% CI [1-1.04]), and those with more years of education (OR = 1.2, 95% CI [1.09-1.32]) were all more likely to be overweight or obese. Alternatively, being a smoker is negatively associated with BMI and decreases one's odds of being overweight or obese (OR = 0.28, 95% CI [0.16-0.46]). Conclusions: We observed a high prevalence of overweight and obesity in this study. The odds of being overweight and obese were higher in women, those living in rural areas, and those with more education, and increases with age. Community-based interventions to control obesity in this region should pay special attention to these groups.

Quantitative and carbon isotope ratio analysis of fatty acids isolated from human brain hemispheres.

Our knowledge surrounding the overall fatty acid profile of the adult human brain has been largely limited to extrapolations from brain regions in which the distribution of fatty acids varies. This is especially problematic when modeling brain fatty acid metabolism, therefore, an updated estimate of whole-brain fatty acid concentration is necessitated. Here, we sought to conduct a comprehensive quantitative analysis of fatty acids from entire well-characterized human brain hemispheres (n = 6) provided by the Douglas-Bell Canada Brain Bank. Additionally, exploratory natural abundance carbon isotope ratio (CIR; δ13 C, 13 C/12 C) analysis was performed to assess the origin of brain fatty acids. Brain fatty acid methyl esters (FAMEs) were quantified by gas chromatography (GC)-flame ionization detection and minor n-6 and n-3 polyunsaturated fatty acid pentafluorobenzyl esters by GC-mass spectrometry. Carbon isotope ratio values of identifiable FAMEs were measured by GC-combustion-isotope ratio mass spectrometry. Overall, the most abundant fatty acid in the human brain was oleic acid, followed by stearic acid (STA), palmitic acid (PAM), docosahexaenoic acid (DHA), and arachidonic acid (ARA). Interestingly, cholesterol as well as saturates including PAM and STA were most enriched in 13 C, while PUFAs including DHA and ARA were most depleted in 13 C. These findings suggest a contribution of endogenous synthesis utilizing dietary sugar substrates rich in 13 C, and a combination of marine, animal, and terrestrial PUFA sources more depleted in 13 C, respectively. These results provide novel insights on cerebral fatty acid origin and concentration, the latter serving as a valuable resource for future modeling of fatty acid metabolism in the human brain.