Gene expression patterns following unilateral traumatic brain injury reveals a local pro-inflammatory and remote anti-inflammatory response.

BackgroundTraumatic brain injury (TBI) results in irreversible damage at the site of impact and initiates cellular and molecular processes that lead to secondary neural injury in the surrounding tissue. We used microarray analysis to determine which genes, pathways and networks were significantly altered using a rat model of TBI. Adult rats received a unilateral controlled cortical impact (CCI) and were sacrificed 24 h post-injury. The ipsilateral hemi-brain tissue at the site of the injury, the corresponding contralateral hemi-brain tissue, and naïve (control) brain tissue were used for microarray analysis. Ingenuity Pathway Analysis (IPA) software was used to identify molecular pathways and networks that were associated with the altered gene expression in brain tissues following TBI.ResultsInspection of the top fifteen biological functions in IPA associated with TBI in the ipsilateral tissues revealed that all had an inflammatory component. IPA analysis also indicated that inflammatory genes were altered on the contralateral side, but many of the genes were inversely expressed compared to the ipsilateral side. The contralateral gene expression pattern suggests a remote anti-inflammatory molecular response. We created a network of the inversely expressed common (i.e., same gene changed on both sides of the brain) inflammatory response (IR) genes and those IR genes included in pathways and networks identified by IPA that changed on only one side. We ranked the genes by the number of direct connections each had in the network, creating a gene interaction hierarchy (GIH). Two well characterized signaling pathways, toll-like receptor/NF-kappaB signaling and JAK/STAT signaling, were prominent in our GIH.ConclusionsBioinformatic analysis of microarray data following TBI identified key molecular pathways and networks associated with neural injury following TBI. The GIH created here provides a starting point for investigating therapeutic targets in a ranked order that is somewhat different than what has been presented previously. In addition to being a vehicle for identifying potential targets for post-TBI therapeutic strategies, our findings can also provide a context for evaluating the potential of therapeutic agents currently in development

The development and usability of a web-based mobile application as a dairy intake screener for South African adults

Paper-based dietary assessment tools such as food frequency questionnaires (FFQ) and especially dietary screeners are making way for versions that use technology. Amidst low intakes of dairy and dairy-related nutrients in South Africa, and to increase public awareness thereof, we aimed to develop and evaluate the usability of an application (app) to screen for dairy intake in higher income South African adults. In a consultative process, a dairy intake screener (‘Dairy Diary’) was developed as an eight-item quantitative FFQ with four types of commonly consumed local dairy products: milk, maas (fermented milk), yoghurt, and cheese. For each dairy product, usual frequency of consumption and portion size per eating occasion were scored resulting in three risk classes: <1 serving daily; 1≤2 servings daily; ≥2 servings daily. Digitalisation included product- and portion-specific graphics with linkage to risk class-relevant preliminary dairy-related guidance as part of a web-based mobile app. For the evaluation of the usability, the 26-item end-user version of the Mobile Application Rating Scale (uMARS) was used in an online cross-sectional survey (Qualtrics; April 2020). Items were scored on a 5-point Likert-type scale, resulting in three final app scores. From a conveniently recruited sample of 1102, 703 (64%; 81% female; mean age 29.8 ± 11.0 years) were retained for analysis. uMARS-informed descriptive statistics summarise the findings. The uMARS app mean objective quality score (3.9 ± 0.85), app subjective quality score (3.5 ± 0.77), app-specific score (3.6 ± 0.94), and additional question on e-portion (4.3 ± 0.78) met the minimum acceptability score of ≥3.0. For the subscales, the mean score for aesthetics was the highest (4.4 ± 0.82), followed by information (4.3 ± 0.90) and functionality (4.0 ± 1.33). Engagement scored lowest (3.0 ± 1.55). The ‘Dairy Diary’ is a user-friendly screener for dairy intake.The development of the “Dairy Diary” was supported by the CEP of Milk SA and study is partially funded by Nestle Nutrition Institute of Africa (NNIA).https://www.cambridge.org/core/journals/journal-of-dairy-researchhj2023Human Nutritio

Mutant U2AF1-induced alternative splicing of H2afy (macroH2A1) regulates B-lymphopoiesis in mice

Somatic mutations in spliceosome genes are found in ∼50% of patients with myelodysplastic syndromes (MDS), a myeloid malignancy associated with low blood counts. Expression of the mutant splicing factor U2AF1(S34F) alters hematopoiesis and mRNA splicing in mice. Our understanding of the functionally relevant alternatively spliced target genes that cause hematopoietic phenotypes in vivo remains incomplete. Here, we demonstrate that reduced expression of H2afy1.1, an alternatively spliced isoform of the histone H2A variant gene H2afy, is responsible for reduced B cells in U2AF1(S34F) mice. Deletion of H2afy or expression of U2AF1(S34F) reduces expression of Ebf1 (early B cell factor 1), a key transcription factor for B cell development, and mechanistically, H2AFY is enriched at the EBF1 promoter. Induced expression of H2AFY1.1 in U2AF1(S34F) cells rescues reduced EBF1 expression and B cells numbers in vivo. Collectively, our data implicate alternative splicing of H2AFY as a contributor to lymphopenia induced by U2AF1(S34F) in mice and MDS

Prematurity, Opioid Exposure and Neonatal Pain: Do They Affect the Developing Brain?

Background: Traditionally, 10 years ago, children born preterm often routinely received morphine, especially during mechanical ventilation. Studies in neonatal rats, whose stage of brain development roughly corresponds to that of children born preterm, found negative long-term effects after pain and opioid exposure. Objectives: We studied possible effects of prematurity, procedural pain and opioids in humans 10 years later. We hypothesized that these factors would negatively influence neurobiological, neuropsychological and sensory development later in life. Methods: We included 19 children born preterm who as neonates participated in an RCT on the short-term effects of morphine administration and who previously participated in our follow-up studies at ages 5 and 8/9 years. We assessed associations between brain morphology (n = 11), neuropsychological functioning (n = 19) and thermal sensitivity (n = 17) and prematurity, opioid exposure and neonatal pain. Results: Significant correlations (coefficients 0.60-0.85) of gestational age, number of painful procedures and morphine exposure with brain volumes were observed. Significant correlations between these factors and thermal sensitivity were not established. Neuropsychological outcome was significantly moderately correlated with morphine exposure in only two subtests, and children performed in general 'average' by Dutch norms. Conclusions: Although prematurity, opioid exposure and neonatal pain were significantly associated with brain volume, no major associations with neuropsychological functioning or thermal sensitivity were detected. Our findings suggest that morphine administration during neonatal life does not affect neurocognitive performance or thermal sensitivity during childhood in children born preterm without brain damage during early life. Future studies with larger sample sizes are needed to confirm these findings

Association of the Joint Effect of Menopause and Hormone Replacement Therapy and Cancer in African American Women: The Jackson Heart Study

Cancer is the second leading cause of death in the US and in Mississippi. Breast cancer (BC) is the most common cancer among women, and the underlying pathophysiology remains unknown, especially among African American (AA) women. The study purpose was to examine the joint effect of menopause status (MS) and hormone replacement therapy (HRT) on the association with cancers, particularly BC using data from the Jackson Heart Study. The analytic sample consisted of 3202 women between 35 and 84 years of which 73.7% and 22.6% were postmenopausal and on HRT, respectively. There were a total of 190 prevalent cancer cases (5.9%) in the sample with 22.6% breast cancer cases. Menopause (p < 0.0001), but not HRT (p = 0.6402), was independently associated with cancer. Similar results were obtained for BC. BC, cancer, hypertension, type 2 diabetes, prevalent cardiovascular disease, physical activity and certain dietary practices were all significantly associated with the joint effect of menopause and HRT in the unadjusted analyses. The family history of cancer was the only covariate that was significantly associated with cancer in the age-adjusted models. In examining the association of cancer and the joint effect of menopause and HRT, AA women who were menopausal and were not on HRT had a 1.97 (95% CI: 1.15, 3.38) times odds of having cancer compared to pre-menopausal women after adjusting for age; which was attenuated after further adjusting for family history of cancer. Given that the cancer and BC cases were small and key significant associations were attenuated after adjusting for the above mentioned covariates, these findings warrant further investigation in studies with larger sample sizes of cancer (and BC) cases

Relationship between Medication Use and Cardiovascular Disease Health Outcomes in the Jackson Heart Study

Even though some medications have the potential to slow the progress of atherosclerosis and development of CVD, there are many at-risk individuals who continue to resist the benefits that are available by not following the advice of medical professionals. Non-adherence to prescribed drug regimens is a pervasive medical problem that negatively affects treatment outcomes. Information from standardized interviews of 5301 African Americans participating in the Jackson Heart Study was examined to determine the association between demographic parameters, behavior including adherence to prescribed medical regimens, and health outcomes. Data were also collected at Annual Follow-Up and Surveillance visits. During the two weeks prior to the examination visit, almost 52% of the participants reported taking blood pressure medication, 14% took cholesterol medication, 16% took medication for diabetes, and 19% took blood thinning medication. Of those who did not take the prescribed medications, the reasons given were the following: 47% were in a hurry, too busy, or forgot to take medications; 23% were trying to do without medications; 18% had no money to purchase medications; 19% indicated that the medications made them feel bad; 17% felt that they could not carry out daily functions when taking medications. The African American population can benefit from heightened awareness of the risk factors that are associated with CVD and the benefits of following a prescribed treatment regimen. Unacceptable secondary effects of prescribed medication comprised an important cause of non-compliance. Encouragement of this population to communicate with their healthcare providers to ensure that medication regimens are better tolerated could increase compliance and improve health outcomes

Racism, the media … and alternative (sonic) culture

This essay develops Titley’s discussion of racism and the media through a concerted engagement with popular culture, and specifically with sound and YouTube video culture. Expanding Titley’s notion of “debatability”, it asks what alternatives to racism are held in popular culture, and in a time of nationalist, racist and authoritarian assertion, why the identification of such alternatives might matter for a leftist anti-racist project

A multi-country comparison of jurisdictions with and without mandatory nutrition labelling policies in restaurants: analysis of behaviours associated with menu labelling in the 2019 International Food Policy Study

Abstract Objective: To examine differences in noticing and use of nutrition information comparing jurisdictions with and without mandatory menu labelling policies and examine differences among sociodemographic groups. Design: Cross-sectional data from the International Food Policy Study (IFPS) online survey. Setting: IFPS participants from Australia, Canada, Mexico, United Kingdom and USA in 2019. Participants: Adults aged 18–99; n 19 393. Results: Participants in jurisdictions with mandatory policies were significantly more likely to notice and use nutrition information, order something different, eat less of their order and change restaurants compared to jurisdictions without policies. For noticed nutrition information, the differences between policy groups were greatest comparing older to younger age groups and comparing high education (difference of 10·7 %, 95 % CI 8·9, 12·6) to low education (difference of 4·1 %, 95 % CI 1·8, 6·3). For used nutrition information, differences were greatest comparing high education (difference of 4·9 %, 95 % CI 3·5, 6·4) to low education (difference of 1·8 %, 95 % CI 0·2, 3·5). Mandatory labelling was associated with an increase in ordering something different among the majority ethnicity group and a decrease among the minority ethnicity group. For changed restaurant visited, differences were greater for medium and high education compared to low education, and differences were greater for higher compared to lower income adequacy. Conclusions: Participants living in jurisdictions with mandatory nutrition information in restaurants were more likely to report noticing and using nutrition information, as well as greater efforts to modify their consumption. However, the magnitudes of these differences were relatively small