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Fruits of Schinus terebinthifolia Raddi were investigated. A fast and efficient method for the simultaneous determination of 11 polyphenolic substances by high performance liquid chromatography-diode array detector (HPLC-DAD) was applied. Limits of quantification ranged between 0.78 and 3.14 mg L-1. High concentrations of kaempferol were found. An exploratory evaluation was performed using principal component analysis (PCA) for fruit origin differentiation. Total phenolic content (TPC) ranged from 274 to 517 mg GAE 100 g-1; total flavonoid content (TFC) ranged from 101 to 283 mg QE 100 g-1. In vitro analyses showed that antioxidant capacity with 2,2-diphenyl-1-picrylhydrazyl (DPPH) ranged from 1.7 to 7 µM DPPH 100 g-1. The bacteriostatic and bactericidal effect were also evaluated against: Bacillus subtilis, B. cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella choleraesuis, Candida albicans and C. glabrata, using broth microdilution assay. It can be inferred that S. terebinthifolia Raddi fruit has the potential to act as an ally in the search for new alternatives in the action against pathogens, and it can be used as a potential natural antioxidant and antimicrobial agent. Metals (Cu, Fe, Mg, Mn and Zn) were also determined by flame atomic absorption spectrometry (FAAS), with emphasis on high concentrations of Mg, Zn and Fe.

Staphylococcus aureus is a bacterium responsible for resistance to multiple drugs and the efflux system is widely studied among the resistance mechanisms developed by this species. The present study evaluates the inhibition of the MepA efflux pump by thiadiazine-derived compounds. For this purpose, thiadiazine-derived compounds (IJ-14 to IJ-20) were tested against S. aureus K2068 strains. Microdilution tests were initially conducted to assess the Minimum Inhibitory Concentration (MIC) of the compounds and their efflux pump inhibition activity. In addition, fluorimetry tests were performed using BrEt emission and tests were conducted to inhibit the expression of the mepA gene. This involved comparing the bacterial gene expression with the antibiotic alone to the gene expression after combining compounds (IJ-17 and IJ-20) with the antibiotic. Furthermore, membrane permeability assessment tests and in silico molecular docking tests were performed. It was observed that the IJ17 and IJ20 compounds exhibited direct activity against the tested strain. The IJ17 compound produced significant results in the gene inhibition tests, which was also evidenced through the membrane permeability alteration test. These findings suggest that thiadiazine-derived compounds have promising effects against one of the main resistance mechanisms, with the IJ17 compound presenting observable mechanisms of action.

Insect meals have the potential to be used as a source of nutrients in aquafeeds due to their high nutritional profile and cost effectiveness. The objective of this study was to elucidate the impact of black soldier fly larvae meal (BSFLM) as a replacement for fish meal (FM) on Nile tilapia (Oreochromis niloticus, L) growth performance, survival rate, somatic indexes and economic benefits. Four experimental diets were prepared; three with BSFLM as a substitute for FM at 25 % (T25 %), 50 % (T50 %) and 75 % (T75 %) and a control diet without BSFLM (T0 %, 100 % FM). A total of 360 fingerlings weighing about 20 - 30 gs each were assigned to twelve cages built in a 720m2 earthen pond, with 30 fingerlings in each cage in a completely randomized design with three replications in each treatment group. The fingerlings were fed the experimental diets for 26 weeks. The results showed that the treatment diets did not significantly affect body weight gain and daily feed intake (p > 0.05). However, treatment T50 % (52.16 g) had the highest body weight gain while treatment T75 % (46.00 g) had the lowest body weight gain even though not statistically different (p > 0.05). The body length also followed the same trend being higher in T50 % (16.50 cm) and lowest in T75 % (15.91 cm). The survival rate was significantly influenced (p < 0.05) by the diet treatment groups, while blood parameters, visceral somatic and hepatosomatic indexes did not vary significantly (p > 0.05) across the treatment diets. Return on investment and the cost-benefit ratio were significantly (p < 0.05) affected by the partial replacement of FM with BSFLM. Diets T25 %, T50 % and T75 % had higher (p < 0.05) profit margins when compared with diet T0 % (control). The study found that BSFLM can replace FM in diets for Nile tilapia without compromising on the growth performance of the fish while also increasing the profitability.

The prevailing global market demands locally produced, sustainable oils for biomedical applications. This study focused on evaluating the quality of cricket-derived oils and meals from Scapsipedus icipe Hugel, Tanga, and Gryllus bimaculatus De Geer common delicacy in Africa, following standard methods for physicochemical properties, fatty acid composition, and phytochemicals (oxalates, phytates, tannins, and polyphenols). The cricket oils physicochemical properties aligned with Codex Alimentarius standards for edible oils, including low solidification temperature (< 2 °C), a high refractive index (1.46), and a specific gravity of 0.88. Notably, peroxide values (1.9 to 2.5 mg mEq O2/kg), acid values (1.1 to 2.2 mg KOH/g), and saponification values (234–246 mg KOH/g) all are indicative of lightness and unsaturated fatty acids. Nutritionally, cricket powder was rich in protein (56.8–56.9% -) and fat (31.7–33.5% -of dry matter), with significant amounts of essential omega-3 and omega-6 fatty acids. Predominant saturated and monounsaturated fatty acids were palmitic (23.9–31.2 mg/100 g-) and oleic acids (10.9–11.4 mg/100 g- of oil), respectively. Antioxidant values (48.0 to 65.0 mg/100 g), inferred from total polyphenols, suggests a stable oil with long shelf-life. These results highlight the promising and sustainable potential of cricket-derived oils for applications in the food and pharmaceutical industries.

Through analysis of semi-structured interviews of 30 Latinx college students, we examined how Latinx students experience belonging, acceptance, and affirmations at a Hispanic-Serving Research Institution (HSRI) in California. Drawing from the theoretical perspectives of racial micro-affirmations, we uncovered two major themes: the importance of close friendships and the impact that ethnic studies courses have on ethnoracial identity development. This study contributes to the ongoing discussion of the on-campus experiences of underrepresented students as well as how to best serve and affirm them at HSRIs.

Prunus africana, a widely utilized medicinal plant in various African ethnic communities, continues to hold significant importance in traditional healing practices. Research has identified phytochemical compounds in this plant, exhibiting diverse pharmacological activities that offer potential for pharmaceutical development. Notably, P. africana is employed in treating various ailments such as wounds, diabetes mellitus, malaria, benign prostatic hyperplasia, chest pain, and prostate cancer. Its pharmacological properties are attributed to a spectrum of bioactive compounds, including tannins, saponins, alkaloids, flavonoids, terpenoids, phytosterols, and fatty acids. Multiple studies have documented the anti-inflammatory, antimicrobial, antiandrogenic, antiangiogenic, antioxidant, antidipeptidyl peptidase-4 activity, analgesic, and astringent properties of P. africana extracts. This review offers a comprehensive compilation of ethnomedicinal applications, phytochemical composition, pharmacological effects, and toxicity assessments of P. africana, serving as a foundation for future preclinical and clinical investigations. By understanding its traditional uses and chemical constituents, researchers can target specific medical conditions with greater precision, potentially expediting the development of safe and effective pharmaceuticals. Moreover, toxicity assessments provide crucial insights into the safety profile of P. africana extracts, ensuring the development of safe pharmaceuticals to treat various diseases.

Prior research has shown that a belief in personal justice (i.e., justice for self) is associated with better health and well-being, whereas a belief in justice more generally (i.e., justice for others) is unrelated. However, an emerging perspective is that racial differences may overlay the relationships between multidimensional beliefs about justice and indices of well-being. This includes that well-being among African Americans may be additionally supported by rejecting rather than endorsing some forms of believing in justice. In the present study, we consider racial similarities and differences in the links between beliefs about justice for self and others and emotional well-being. African Americans (N = 117) and White Americans (N = 188) completed measures of beliefs about justice for self and others, and also measures of dispositional tendencies towards experiencing positive and negative emotion (i.e., positive and negative affectivity). In both groups, beliefs about justice for the self were associated with greater positive affect and reduced negative affect. However, beliefs about justice for others were additionally associated with greater negative affect only among African Americans. The link between justice for others and negative affect among African Americans was not attributable to measurement or mean differences in justice beliefs across racial groups, or to socioeconomic differences. Results align with an emerging perspective that simultaneously endorsing and rejecting justice beliefs may be vital to preserving well-being for some racial minorities.

Summary: An efficient neutrophil response is critical for fighting bacterial infections, which remain a significant global health concern; therefore, modulating neutrophil function could be an effective therapeutic approach. While we have a general understanding of how neutrophils respond to bacteria, how neutrophil function differs in response to diverse bacterial infections remains unclear. Here, we use a microfluidic infection-on-a-chip device to investigate the neutrophil response to four bacterial species: Pseudomonas aeruginosa, Salmonella enterica, Listeria monocytogenes, and Staphylococcus aureus. We find enhanced neutrophil extravasation to L. monocytogenes, a limited overall response to S. aureus, and identify IL-6 as universally important for neutrophil extravasation. Furthermore, we demonstrate a higher percentage of neutrophils generate reactive oxygen species (ROS) when combating gram-negative bacteria versus gram-positive bacteria. For all bacterial species, we found the percentage of neutrophils producing ROS increased following extravasation through an endothelium, underscoring the importance of studying neutrophil function in physiologically relevant models.

Abstract Background Recent advances in MRI acquisitions and image analysis have increased the utility of neuroimaging in understanding disease-related changes. In this work, we aim to demonstrate increased sensitivity to disease progression as well as improved diagnostic accuracy in Amyotrophic lateral sclerosis (ALS) with multimodal MRI of the brain and cervical spinal cord. Methods We acquired diffusion MRI data from the brain and cervical cord, and T1 data from the brain, of 20 participants with ALS and 20 healthy control participants. Ten ALS and 14 control participants, and 11 ALS and 13 control participants were re-scanned at 6-month and 12-month follow-ups respectively. We estimated cross-sectional differences and longitudinal changes in diffusion metrics, cortical thickness, and fixel-based microstructure measures, i.e. fiber density and fiber cross-section. Results We demonstrate improved disease diagnostic accuracy and sensitivity through multimodal analysis of brain and spinal cord metrics. The brain metrics also distinguished lower motor neuron-predominant ALS participants from control participants. Fiber density and cross-section provided the greatest sensitivity to longitudinal change. We demonstrate evidence of progression in a cohort of 11 participants with slowly progressive ALS, including in participants with very slow change in ALSFRS-R. More importantly, we demonstrate that longitudinal change is detectable at a six-month follow-up visit. We also report correlations between ALSFRS-R and the fiber density and cross-section metrics. Conclusions Our findings suggest that multimodal MRI is useful in improving disease diagnosis, and fixel-based measures may serve as potential biomarkers of disease progression in ALS clinical trials.

Abstract Lattice reconstruction and corresponding strain accumulation plays a key role in defining the electronic structure of two-dimensional moiré superlattices, including those of transition metal dichalcogenides (TMDs). Imaging of TMD moirés has so far provided a qualitative understanding of this relaxation process in terms of interlayer stacking energy, while models of the underlying deformation mechanisms have relied on simulations. Here, we use interferometric four-dimensional scanning transmission electron microscopy to quantitatively map the mechanical deformations through which reconstruction occurs in small-angle twisted bilayer MoS2 and WSe2/MoS2 heterobilayers. We provide direct evidence that local rotations govern relaxation for twisted homobilayers, while local dilations are prominent in heterobilayers possessing a sufficiently large lattice mismatch. Encapsulation of the moiré layers in hBN further localizes and enhances these in-plane reconstruction pathways by suppressing out-of-plane corrugation. We also find that extrinsic uniaxial heterostrain, which introduces a lattice constant difference in twisted homobilayers, leads to accumulation and redistribution of reconstruction strain, demonstrating another route to modify the moiré potential.

In this work, we report the synthesis of Na-TiNTs sodium titanate nanotubes prepared by the hydrothermal method in a highly alkaline subsequently modified by the substitution of Na+ ions present in the walls of the nanotubes by ions of Sr2+ and Ga3+ revealing the presence of phases such as SrOH2 and α-GaOOH through the analysis by X-ray diffraction. Raman spectroscopy showed the characteristic peaks of the vibrational modes of the titanate nanotube structure. UV–Vis analysis revealed a blueshift of absorption edge that leads to an increase in the bandgap with the insertion of Sr and Ga ions. The ion exchange causes a decrease in the Urbach energy, which suggests a certain attenuation in the concentration of structural defects.Through the SEM images it is observed the cluster of interwoven nanotubes it self is characteristic of titanate nanotubes and, the elemental mapping shows the complete efficiency of the reaction process of sodium ion exchange by strontium and gallium in the Sr-TiNT and Ga-TiNT samples respectively, showing the environment of the chemical composition of the surface with the presence of chemical elements such as Sr, Ga. The Na-TiNT, Sr-TiNT, and Ga-TiNT nanotubes did not show direct antibacterial activity against the tested strains. The Na, Ga, and Sr TiNTs of the ampicillin antibiotic exhibited significant values against the microorganism S. aureus 10 compared to the control antibiotic, thereby reducing its inhibitory concentration. The same was observed for gentamicin. The Na-TiNT, in combination with gentamicin, displayed a reduction in inhibitory concentration compared to the control for P. aeruginosa 24. In E. coli 06, the Na, Sr, and Ga TiNTs showed a reduction in concentration when combined with gentamicin, indicating a potential synergistic effect.

Abstract An idealized aquaplanet moist global atmospheric model with realistic radiative transfer but no clouds and no convective parameterization is found to possess multiple climate equilibria. When forced symmetrically about the equator, in some cases the Inter Tropical Convergence Zone (ITCZ) migrates to an off‐equatorial equilibrium position. Mechanism denial experiments prescribing relative humidity imply that radiation‐circulation coupling is essential to this instability. The cross‐equatorial asymmetry occurs only when the underlying slab ocean is sufficiently deep and the atmosphere's spectral dynamical core is sufficiently coarse (∼T170 or less with our control parameters). At higher resolutions, initializing with an asymmetric state indicates metastability with very slow (thousands of days) return to hemispheric symmetry. There is some sensitivity to the model timestep, which affects the time required to transition to the asymmetric state, with little effect on the equilibrium climate. The instability is enhanced when the planetary boundary layer scheme favors deeper layers or by a prescribed meridional heat transport away from the equator within the slab. The instability is not present when the model is run with a convective parameterization scheme commonly utilized in idealized moist models. We argue that the instability occurs when the asymmetric heating associated with a spontaneous ITCZ shift drives a circulation that rises poleward of the perturbed ITCZ. These results serve as a warning of the potential for instability and non‐uniqueness of climate that may complicate studies with idealized models of the tropical response to perturbations in forcing.

False codling moth (FCM) Thaumatotibia leucotreta Meyrick (Lepidoptera: Tortricidae) is currently the main pest of phytosanitary concern in international trade, causing rejection and decline of horticultural produce from Kenya exported to the European Union (EU). Overreliance on synthetic insecticides to control this pest is ineffective and unsustainable in the long run, whereas continuous use of pesticides results in high levels of residues in the produce. To gather farmers’ knowledge, attitudes, and practices used by smallholder farmers to manage this pest, a field survey was carried out in 10 Capsicum sp. (Solanales: Solanaceae)-producing counties in Kenya. Data were collected using semi-structured questionnaires administered through face-to-face interviews and focus group discussions involving 108 individual farmers, 20 key informants, and 10 focus group discussions. The majority of the respondents (83.33%) were aware of the FCM infesting Capsicum sp. About three quarters of the farmers (76.85%) reported yield losses and unmarketable quality of FCM-infested Capsicum sp. Most farmers interviewed (99.07%) used insecticides as a management tool. In contrast, only 39.81% of the farmers applied integrated pest management strategies including use of biological control agents and intercropping with repellent plants to control this pest. The results show that FCM is perceived as a significant threat to the horticultural industry of Kenya. Training needs for smallholder farmers and key informants to avoid overreliance on synthetic chemical pesticides and to maintain export goals to the EU where identified.

DNA methylation is an epigenetic mechanism that regulates gene expression without altering gene sequences in health and disease. DNA methyltransferases (DNMTs) are enzymes responsible for DNA methylation, and their dysregulation is both a pathogenic mechanism of disease and a therapeutic target. DNMTs change gene expression by methylating CpG islands within exonic and intergenic DNA regions, which typically reduces gene transcription. Initially, mutations in the DNMT genes and pathologic DNMT protein expression were found to cause hematologic diseases, like myeloproliferative disease and acute myeloid leukemia, but recently they have been shown to promote cardiovascular diseases, including coronary artery disease and pulmonary hypertension. We reviewed the regulation and functions of DNMTs, with an emphasis on somatic mutations in DNMT3A, a common cause of clonal hematopoiesis of indeterminant potential (CHIP) that may also be involved in the development of pulmonary arterial hypertension (PAH). Accumulation of somatic mutations in DNMT3A and other CHIP genes in hematopoietic cells and cardiovascular tissues creates an inflammatory environment that promotes cardiopulmonary diseases, even in the absence of hematologic disease. This review summarized the current understanding of the roles of DNMTs in maintenance and de novo methylation that contribute to the pathogenesis of cardiovascular diseases, including PAH.

Molecular predissociation, the spontaneous nonradiative bond-breaking process, can limit the ability to scatter a large number of photons required to reach the ultracold regime in laser cooling. Unlike rovibrational branching, predissociation is irreversible since the fragments fly apart with high kinetic energy. Of particular interest is the simple diatomic molecule CaH, for which the two lowest electronically excited states used in laser cooling, A^{2}Π_{1/2} and B^{2}Σ^{+}, lie above the dissociation threshold of the ground potential. In this work, we present measurements and calculations that quantify the predissociation probabilities P_{pd} affecting the cooling cycle. For the lowest vibrational levels, we find P_{pd} of ∼10^{−6} for A(v^{′}=0) and ∼10^{−3} for B(v^{′}=0). The results allow us to design a laser-cooling scheme that will enable the creation of an ultracold and optically trapped cloud of CaH molecules. In addition, we use the results to propose a two-photon pathway to controlled dissociation of the molecules in order to gain access to their ultracold fragments, including hydrogen.

Abstract Recurrent droughts and long-term changes to climate, social structures, and the economy in the world’s arid and semi-arid lands have impacted pastoralists’ livelihood activities over time, resulting in different livelihood pathways. Some pastoralists continue to follow more traditional strategies of herd accumulation, while others frequently engage in livestock markets and value addition activities, and others still are dropping out of pastoralism. Using data collected over 6 years from 924 households in northern Kenya and applying a generalized structural dynamic multinomial logit model, this study quantitatively determined the dynamic transitions between livelihood categories conditional on drought incidences. From the results, there were considerable and frequent transitions between livelihood pathways within the panel period (2009–2015). Notably, many households that started in the low-cash income, larger herd size category denoted as hanging in, were transitioning to lower cash income with small herds (dropping out). At the same time, there was a great deal of back and forth between the category with low-cash income and small herd size (dropping out) and the category with higher cash income and small herd size (moving out), indicating that moving out was the only way out of poverty. Also, an increase in vegetation index from a drought season where the index was at a 10% level to a good season where the level was 90% decreased the likelihood of households dropping out from a predicted probability of 37.9 to 28.7% and increased the likelihood of moving up and moving out from 22.2 to 25.0% and 22.6 to 34.3%, respectively, unconditionally. The study findings imply that any livelihood interventions aimed at reducing the impact of drought and alleviating poverty among pastoral households should support the transition to market-oriented, relatively successful pathways and also protect households from falling back into the ranks of poverty by dropping out.

Summary: While gaining interest as treatment for cancer and infectious disease, the clinical efficacy of Vγ9Vδ2 T cell-based immunotherapeutics has to date been limited. An improved understanding of γδ T cell heterogeneity across lymphoid and non-lymphoid tissues, before and after pharmacological expansion, is required. Here, we describe the phenotype and tissue distribution of Vγ9Vδ2 T cells at steady state and following in vivo pharmacological expansion in pigtail macaques. Intravenous phosphoantigen administration with subcutaneous rhIL-2 drove robust expansion of Vγ9Vδ2 T cells in blood and pulmonary mucosa, while expansion was confined to the pulmonary mucosa following intratracheal antigen administration. Peripheral blood Vγ9Vδ2 T cell expansion was polyclonal, and associated with a significant loss of CCR6 expression due to IL-2-mediated receptor downregulation. Overall, we show the tissue distribution and phenotype of in vivo pharmacologically expanded Vγ9Vδ2 T cells can be altered based on the antigen administration route, with implications for tissue trafficking and the clinical efficacy of Vγ9Vδ2 T cell immunotherapeutics.

The liver is a highly regenerative organ, yet the presence of a dedicated stem cell population remains controversial. Here, we interrogate a severe hepatocyte injury model in adult zebrafish to define that regeneration involves a stem cell population. After near-total hepatocyte ablation, single-cell transcriptomic and high-resolution imaging analyses throughout the entire regenerative timeline reveal that biliary epithelial cells undergo transcriptional and morphological changes to become hepatocytes. As a population, biliary epithelial cells give rise to both hepatocytes and biliary epithelial cells. Biliary epithelial cells proliferate and dedifferentiate to express hepatoblast transcription factors prior to hepatocyte differentiation. This process is characterized by increased MAPK, PI3K, and mTOR signaling, and chemical inhibition of these pathways impairs biliary epithelial cell proliferation and fate conversion. We conclude that, upon severe hepatocyte ablation in the adult liver, biliary epithelial cells act as facultative liver stem cells in an EGFR-PI3K-mTOR–dependent manner.

Abstract Background Many of the world’s population, across all age groups and abilities, are not meeting or even aware of internationally recommended physical activity (PA) and sedentary behaviour (SB) guidelines. In order to enhance awareness and uptake, guidelines should be perceived positively by targeted users. The purpose of this study was to review the literature on end-user and stakeholder perceptions of PA and SB guidelines. Methods The electronic databases APA PsycInfo, CINAHL, MEDLINE, and SPORTDiscus, using EBSCOhost Research Platform, and Web of Science were searched from inception to June, 2021 with keyword synonyms for “perceptions”, “PA guidelines”, and “SB guidelines”. Studies of any design that collected stakeholder and/or end-user responses to a PA and/or SB guideline were included and assessed for risk of bias. The PA and/or SB guideline could be any type of official form (e.g., national documents, organizational guidelines, expert consensus statements, etc.) from any country, that targets individuals at the regional, provincial/statewide, national, or international level, and includes all types of guidelines (e.g., strength, aerobic, clinical, nonclinical, screen-time, sitting, etc.). Data were extracted and analyzed using thematic synthesis. Results After screening 1399 abstracts and applying citation screening, 304 full-texts were retrieved. A total of 31 articles met the inclusion criteria. End-users and stakeholders for PA guidelines across all age groups expressed the need for simplified language with more definitions, relatable examples and imagery, and quantification of PA behaviours. There was concern for the early years and child PA guidelines leading to guilt amongst parents and the SB guidelines, particularly the recommendations to limit screen-time, being unrealistic. General age group PA guidelines were not perceived as usable to populations with differing abilities, clinical conditions, and socioeconomic status. Guidelines that targeted clinical populations, such as persons with multiple sclerosis and persons with spinal cord injury, were well received. Conclusions There is a clear need to balance the evidence base with the pragmatic needs of translation and uptake so that the guidelines are not ignored or act as a barrier to actual engagement.

Abstract Background Staphylococcus aureus cause diseases both in humans and animals. These diseases range from mild to fatal infections thus necessitating development of a specific molecular method for detection of pathogenic S. aureus. Objectives To identify and analyze genetic profile of pathogenic S. aureus using bacteriophage based genetic biomarkers. Methods Using culture and biochemical methods, 148 S. aureus (87 %) were isolated from 170 raw milk samples taken from 10 dairy farms in Marsabit and Isiolo counties in Northern Kenya between June 2016 and February 2017. The samples were collected directly from dairy lactating cows previously diagnosed with S. aureus in a follow‐up study. The isolates were analyzed by PCR and sequencing of beta hemolysin (hlb) gene. The genetic relationship between five Kenyan S. aureus isolates and five isolates previously identified was inferred. Results From the 96 isolates screened for hlb gene, 75 (78.1%) tested positive. Some of the positive isolates yielded a band size of 975 bp, while others 1100 bp. Through Basic Local Alignment Search Tool (BLAST) search analysis, the two different band sizes (975 bp and 1100 bp) were both confirmed to be hlb gene from S. aureus isolates indicating that the difference in band size may have been due to deletions that were detected in the 975 bp hlb gene. Some S. aureus isolates from Kenya appeared to be closely related to isolates from other parts of the world, while some showed a distant relationship. Conclusions Phage‐derived hlb gene is a suitable molecular marker for detection of pathogenic S. aureus.

Food crops (bush mango (n=12), roasted cashew nut (n=12), dried okra (n=12), sesame (n=35) and sorghum (n=36)) sold in markets in Nasarawa state, Nigeria, were analyzed using a LC-MS/MS mycotoxin method. The hepatocarcinogenic aflatoxin B1 was detected in 42%, 25% and 19% of bush mango, dried okra and sorghum samples at mean concentrations of 19.2, 8.27 and 4.75 µg/kg, respectively, while fumonisin B1 contaminated 9% of the sesame (mean: 12.5 µg/kg) and 47% of the sorghum (mean: 461 µg/kg) samples. At least 19% of the sorghum samples were co-contaminated with aflatoxin B1 andfumonisin B1. The nephrotoxic ochratoxin A was detected in bush mango, sorghum and, for the first time to the best of our knowledge, in dried okra. These vended food crops in the local markets are therefore prone to mycotoxin contamination,which may pose a health threat to consumers, and require intentional mitigation efforts.

Ethanol (EtOH) is a commonly encountered teratogen that can disrupt organ development and lead to fetal alcohol spectrum disorders (FASDs); many mechanisms of developmental toxicity are unknown. Here, we used transcriptomic analysis in an established zebrafish model of embryonic alcohol exposure (EAE) to identify the ubiquitin-proteasome system (UPS) as a critical target of EtOH during development. Surprisingly, EAE alters 20S, 19S, and 11S proteasome gene expression and increases ubiquitylated protein load. EtOH and its metabolite acetaldehyde decrease proteasomal peptidase activity in a cell type–specific manner. Proteasome 20S subunit β 1 (psmb1hi2939Tg) and proteasome 26S subunit, ATPase 6 (psmc6hi3593Tg), genetic KOs define the developmental impact of decreased proteasome function. Importantly, loss of psmb1 or psmc6 results in widespread developmental abnormalities resembling EAE phenotypes, including growth restriction, abnormal craniofacial structure, neurodevelopmental defects, and failed hepatopancreas maturation. Furthermore, pharmacologic inhibition of chymotrypsin-like proteasome activity potentiates the teratogenic effects of EAE on craniofacial structure, the nervous system, and the endoderm. Our studies identify the proteasome as a target of EtOH exposure and signify that UPS disruptions contribute to craniofacial, neurological, and endodermal phenotypes in FASDs.

Abstract Huntington’s disease (HD) is a monogenic, fully penetrant neurodegenerative disorder. Widespread white matter damage affects the brain of patients with HD at very early stages of the disease. Fixel-based analysis (FBA) is a novel method to investigate the contribution of individual crossing fibers to the white matter damage and to detect possible alterations in both fiber density and fiber-bundle morphology. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS), on the other hand, quantifies the motion of brain metabolites in vivo, thus enabling the investigation of microstructural alteration of specific cell populations. The aim of this study was to identify novel specific microstructural imaging markers of white matter degeneration in HD, by combining FBA and DW-MRS. Twenty patients at an early stage of HD and 20 healthy controls were recruited in a monocentric study. Using diffusion imaging we observed alterations to the brain microstructure and their morphology in patients with HD. Furthermore, FBA revealed specific fiber populations that were affected by the disease. Moreover, the mean diffusivity of the intra-axonal metabolite N-acetylaspartate, co-measured with N-acetylaspartylglutamate (tNAA), was significantly reduced in the corpus callosum of patients compared to controls. FBA and DW-MRS of tNAA provided more specific information about the biological mechanisms underlying HD and showed promise for early investigation of white matter degeneration in HD.

Renal angiomyolipomas (AMLs) are a subset of perivascular epithelioid cell neoplasms (PEComas) that are associated with tuberous sclerosis complex (TSC). Epithelioid angiomyolipomas (EAMLs) are a rare variant of AML with more aggressive propensities. EAMLs with malignant potential can be difficult to distinguish from relatively benign AMLs and other renal tumors. Although there are no established criteria for predicting EAML malignancy, there are proposed histologic parameters that are associated with higher tumor risk. EAML can be treated with surgical resection as well as mTOR inhibitors. Here, we present a unique case of a patient with a 36-cm renal EAML metastatic to the lungs that was treated with complete surgical resection of the primary lesion and mTOR inhibition.

Systemic racism is pervasive in US society and disproportionately limits opportunities for education, work, and health for historically marginalized and minoritized racial and ethnic groups, making it an urgent issue of social justice. Because systemic racism is a social determinant of health prevalent across multiple social and institutional structures, it requires multilevel intervention approaches using effective designs and analytic methods to measure and evaluate outcomes. Racism is a fundamental cause of poor health outcomes, including mental health outcomes; thus, mental health services and programs that address racism and discrimination are key to promoting positive mental health of racial and ethnic minority youth. While multilevel interventions are well-suited for improving outcomes like youth mental health disparities, their evaluation poses unique methodological challenges, requiring specialized design and analytic approaches. There has been limited methodological guidance provided to researchers on how to test multilevel interventions using approaches that balance methodological rigor, practicality, and acceptability across stakeholder groups, especially within communities most affected by systemic racism. This paper addresses this gap by providing an example of how to rigorously evaluate a hypothetical, theoretically based, multilevel intervention promoting mental health equity in three US school systems using an anti-racist approach intervening at the macro- (i.e., school system), meso- (i.e., school), and micro- (i.e., family and student) levels to improve mental health in adolescents. We describe the design, sample size considerations, and analytic methods to comprehensively evaluate its effectiveness while exploring the extent to which the components interact synergistically to improve outcomes. The methodological approach proposed can be adapted to other multilevel interventions that include strategies addressing macro-, meso-, and micro-levels of influence.

Abstract Background In the US, EU and elsewhere, basic clinical research studies with positron emission tomography (PET) radiotracers that are generally recognized as safe and effective (GRASE) can often be conducted under institutional approval. For example, in the United States, such research is conducted under the oversight of a Radioactive Drug Research Committee (RDRC) as long as certain requirements are met. Firstly, the research must be for basic science and cannot be intended for immediate therapeutic or diagnostic purposes, or to determine the safety and effectiveness of the PET radiotracer. Secondly, the PET radiotracer must be generally recognized as safe and effective. Specifically, the mass dose to be administered must not cause any clinically detectable pharmacological effect in humans, and the radiation dose to be administered must be the smallest dose practical to perform the study and not exceed regulatory dose limits within a 1-year period. In our experience, the main barrier to using a PET radiotracer under RDRC approval is accessing the required information about mass and radioactive dosing. Results The University of Michigan (UM) has a long history of using PET radiotracers in clinical research studies. Herein we provide dosing information for 55 radiotracers that will enable other PET Centers to use them under the approval of their own RDRC committees. Conclusions The data provided herein will streamline future RDRC approval, and facilitate further basic science investigation of 55 PET radiotracers that target functionally relevant biomarkers in high impact disease states.

The Phytexponent is used to treat pain and inflammation in complementary and alternative medicine practices; however, empirical data supporting its pharmacological efficacy and safety is scanty, hence the present study. We used the carrageenan-induced paw oedema and the acetic acid-induced writhing techniques to determine the anti-inflammatory and analgesic efficacies, respectively, of the Phytexponent in Swiss albino mice models. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay technique was used to investigate the in vitro cytotoxic effects of the Phytexponent in the Vero E6 cell line. The Phytexponent exerted significant ( P 1000 µg/ml) compared to cyclophosphamide (CC 50 = 2.48 µg/ml). Thus, the Phytexponent has significant in vivo anti-inflammatory and analgesic efficacy in mice models and is not cytotoxic to Vero E6 cell line, depicting its therapeutic potential upon further empirical investigation.

Mapping the characteristics of Africa’s smallholder-dominated croplands, including the sizes and numbers of fields, can provide critical insights into food security and a range of other socioeconomic and environmental concerns. However, accurately mapping these systems is difficult because there is 1) a spatial and temporal mismatch between satellite sensors and smallholder fields, and 2) a lack of high-quality labels needed to train and assess machine learning classifiers. We developed an approach designed to address these two problems, and used it to map Ghana’s croplands. To overcome the spatio-temporal mismatch, we converted daily, high resolution imagery into two cloud-free composites (the primary growing season and subsequent dry season) covering the 2018 agricultural year, providing a seasonal contrast that helps to improve classification accuracy. To address the problem of label availability, we created a platform that rigorously assesses and minimizes label error, and used it to iteratively train a Random Forests classifier with active learning, which identifies the most informative training sample based on prediction uncertainty. Minimizing label errors improved model F1 scores by up to 25%. Active learning increased F1 scores by an average of 9.1% between first and last training iterations, and 2.3% more than models trained with randomly selected labels. We used the resulting 3.7 m map of cropland probabilities within a segmentation algorithm to delineate crop field boundaries. Using an independent map reference sample (n = 1,207), we found that the cropland probability and field boundary maps had respective overall accuracies of 88 and 86.7%, user’s accuracies for the cropland class of 61.2 and 78.9%, and producer’s accuracies of 67.3 and 58.2%. An unbiased area estimate calculated from the map reference sample indicates that cropland covers 17.1% (15.4–18.9%) of Ghana. Using the most accurate validation labels to correct for biases in the segmented field boundaries map, we estimated that the average size and total number of field in Ghana are 1.73 ha and 1,662,281, respectively. Our results demonstrate an adaptable and transferable approach for developing annual, country-scale maps of crop field boundaries, with several features that effectively mitigate the errors inherent in remote sensing of smallholder-dominated agriculture.

IntroductionDrug development for neurodegenerative diseases such as Friedreich's ataxia (FRDA) is limited by a lack of validated, sensitive biomarkers of pharmacodynamic response in affected tissue and disease progression. Studies employing neuroimaging measures to track FRDA have thus far been limited by their small sample sizes and limited follow up. TRACK-FA, a longitudinal, multi-site, and multi-modal neuroimaging natural history study, aims to address these shortcomings by enabling better understanding of underlying pathology and identifying sensitive, clinical trial ready, neuroimaging biomarkers for FRDA.Methods200 individuals with FRDA and 104 control participants will be recruited across seven international study sites. Inclusion criteria for participants with genetically confirmed FRDA involves, age of disease onset ≤ 25 years, Friedreich's Ataxia Rating Scale (FARS) functional staging score of ≤ 5, and a total modified FARS (mFARS) score of ≤ 65 upon enrolment. The control cohort is matched to the FRDA cohort for age, sex, handedness, and years of education. Participants will be evaluated at three study visits over two years. Each visit comprises of a harmonized multimodal Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) scan of the brain and spinal cord; clinical, cognitive, mood and speech assessments and collection of a blood sample. Primary outcome measures, informed by previous neuroimaging studies, include measures of: spinal cord and brain morphometry, spinal cord and brain microstructure (measured using diffusion MRI), brain iron accumulation (using Quantitative Susceptibility Mapping) and spinal cord biochemistry (using MRS). Secondary and exploratory outcome measures include clinical, cognitive assessments and blood biomarkers.DiscussionPrioritising immediate areas of need, TRACK-FA aims to deliver a set of sensitive, clinical trial-ready neuroimaging biomarkers to accelerate drug discovery efforts and better understand disease trajectory. Once validated, these potential pharmacodynamic biomarkers can be used to measure the efficacy of new therapeutics in forestalling disease progression.Clinical trial registrationClinicalTrails.gov Identifier: NCT04349514.

Abstract Background B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE). Methods Female C57BL/6 J mice were induced with EAE through immunization with myelin oligodendrocyte glycoprotein (MOG1–125). PET imaging of naïve and EAE mice was performed 19 h after administration of [64Cu]CD19-mAb. Thereafter, radioactivity in organs of interest was determined by gamma counting, followed by ex vivo autoradiography of central nervous system (CNS) tissues. Anti-CD45R (B220) immunostaining of brain tissue from EAE and naïve mice was also conducted. Results Radiolabelling of DOTA-conjugated CD19-mAb with 64Cu was achieved with a radiochemical purity of 99% and molar activity of 2 GBq/μmol. Quantitation of CD19 PET images revealed significantly higher tracer binding in whole brain of EAE compared to naïve mice (2.02 ± 0.092 vs. 1.68 ± 0.06 percentage of injected dose per gram, % ID/g, p = 0.0173). PET findings were confirmed by ex vivo gamma counting of perfused brain tissue (0.22 ± 0.020 vs. 0.12 ± 0.003 % ID/g, p = 0.0010). Moreover, ex vivo autoradiography of brain sections corresponded with PET imaging results and the spatial distribution of B cells observed in B220 immunohistochemistry—providing further evidence that [64Cu]CD19-mAb enables visualization of B cell infiltration into the CNS of EAE mice. Conclusion CD19-PET imaging can be used to detect elevated levels of B cells in the CNS of EAE mice, and has the potential to impact the way we study, monitor, and treat clinical MS.

Abstract We document the configuration and emergent simulation features from the Geophysical Fluid Dynamics Laboratory (GFDL) OM4.0 ocean/sea ice model. OM4 serves as the ocean/sea ice component for the GFDL climate and Earth system models. It is also used for climate science research and is contributing to the Coupled Model Intercomparison Project version 6 Ocean Model Intercomparison Project. The ocean component of OM4 uses version 6 of the Modular Ocean Model and the sea ice component uses version 2 of the Sea Ice Simulator, which have identical horizontal grid layouts (Arakawa C‐grid). We follow the Coordinated Ocean‐sea ice Reference Experiments protocol to assess simulation quality across a broad suite of climate‐relevant features. We present results from two versions differing by horizontal grid spacing and physical parameterizations: OM4p5 has nominal 0.5° spacing and includes mesoscale eddy parameterizations and OM4p25 has nominal 0.25° spacing with no mesoscale eddy parameterization. Modular Ocean Model version 6 makes use of a vertical Lagrangian‐remap algorithm that enables general vertical coordinates. We show that use of a hybrid depth‐isopycnal coordinate reduces the middepth ocean warming drift commonly found in pure z* vertical coordinate ocean models. To test the need for the mesoscale eddy parameterization used in OM4p5, we examine the results from a simulation that removes the eddy parameterization. The water mass structure and model drift are physically degraded relative to OM4p5, thus supporting the key role for a mesoscale closure at this resolution.

Parastomal hernias (PH) are a well-known complication following ileal conduit urinary diversion. We present a case report of a woman in her mid-nineties with a symptomatic parastomal hernia at the site of her ileal conduit which was repaired laparoscopically by an inverted top-hat technique. The “top hat” is constructed by assembling a transected ring of synthetic mesh with a secondary mesh cylinder and laparoscopically securing this mesh construct in an underlay fashion. At eighteen months follow-up, the patient remains pain free and without evidence of hernia recurrence.

Bacterial products are able to act on nociceptive neurons during pathogenic infection. Neurogenic inflammation is an active part of pain signaling and has recently been shown to impact host-pathogen defense. Bacillus anthracis Edema Toxin (ET) produces striking edema in peripheral tissues, but the cellular mechanisms involved in tissue swelling are not completely understood. Here, we find that nociceptive neurons play a role in ET-induced edema and inflammation in mice. Subcutaneous footpad infection of B. anthracis Sterne caused ET-dependent local mechanical allodynia, paw swelling and body weight gain. Subcutaneous administration of ET induced paw swelling and vascular leakage, the early phases of which were attenuated in the absence of Trpv1+ or Nav1.8+ nociceptive neurons. Nociceptive neurons express the anthrax toxin receptor ANTXR2, but this did not mediate ET-induced edema. ET induced local cytokine expression and neutrophil recruitment, which were dependent in part on Trpv1+ nociceptive neurons. Ablation of Trpv1+ or Nav1.8+ nociceptive neurons also attenuated early increases in paw swelling and body weight gain during live B. anthracis infection. Our findings indicate that nociceptive neurons play an active role in inflammation caused by B. anthracis and Edema Toxin to potentially influence bacterial pathogenesis.

Globally, there is growing interest to integrate cricket-based ingredients (flour) into food products to combat food and nutrition insecurity. However, there is lack of information on in-depth nutrient profile of the two cricket species (Scapsipedus icipe and Gryllus bimaculatus), which are the most widely consumed in Africa. Here we determined the nutrient composition of two cricket species and compared them with published records of key animal and plant sources. Our results revealed that the crude protein contents of S. icipe and G. bimaculatus were similar (56.8 and 56.9%, respectively) and comparable to those of animal protein sources. Both cricket species had balanced amino acid profiles that are superior to that of animal and plant sources, except for histidine and cysteine. The protein digestibility of S. icipe and G. bimaculatus ranged between 80 and 88%, which is comparable to that of common plant foods but slightly lower than that of animal proteins. The iron, Zinc, and potassium contents were considerably higher in both cricket species compared to that of plant and animal sources. The calcium contents of both crickets (S. icipe and G. bimaculatus) was superior to that of plant and animal origin except for kidney beans and eggs, respectively. Riboflavin, thiamine, and folic acid concentrations of S. icipe and G. bimaculatus were superior to that of the conventional sources. Vitamin A levels were significantly higher in S. icipe compared to G. bimaculatus. This implies that S. icipe and G. bimaculatus can adequately contribute to our daily required nutrient intake. Thus, integrating cricket flours into ready-to-eat food products would address some of the most pressing nutritional deficiency challenges that many developing countries have to grapple with, particularly high risk to serious health problems such as anemia, poor pregnancy outcomes, hypertension, increased risk of morbidity and mortality, stunted growth and impaired physical and cognitive development. We conclude that edible crickets present unique opportunities for improving food and nutritional insecurity status of both resource-poor and Western populations.

Periodontitis is induced by periodontal dysbiosis characterized by the predominance of anaerobic species. TLRs constitute the classical pathway for cell activation by infection. Interestingly, the Toll/IL-1 receptor homology domain adapters initiate signaling events, leading to the activation of the expression of the genes involved in the host immune response. The aim of this study was to evaluate the effects of Porphyromonas gingivalis on the expression and protein-protein interactions among five TIR adapters (MAL, MyD88, TRIF, TRAM and SARM) in gingival epithelial cells and endothelial cells. It was observed that P. gingivalis is able to modulate the signaling cascades activated through its recognition by TLR4/2 in gingival epithelial cells and endothelial cells. Indeed, MAL-MyD88 protein-protein interactions associated with TLR4 was the main pathway activated by P. gingivalis infection. When transient siRNA inhibition was performed, cell viability, inflammation, and cell death induced by infection decreased and such deleterious effects were almost absent when MAL or TRAM were targeted. This study emphasizes the role of such TIR adapter proteins in P. gingivalis elicited inflammation and the precise evaluation of TIR adapter protein interactions may pave the way for future therapeutics in both periodontitis and systemic disease with a P. gingivalis involvement, such as atherothrombosis.

Neutrophils are the primary responders to infection, rapidly migrating to sites of inflammation and clearing pathogens through a variety of antimicrobial functions. This response is controlled by a complex network of signals produced by vascular cells, tissue resident cells, other immune cells, and the pathogen itself. Despite significant efforts to understand how these signals are integrated into the neutrophil response, we still do not have a complete picture of the mechanisms regulating this process. This is in part due to the inherent disadvantages of the most-used experimental systems: in vitro systems lack the complexity of the tissue microenvironment and animal models do not accurately capture the human immune response. Advanced microfluidic devices incorporating relevant tissue architectures, cell-cell interactions, and live pathogen sources have been developed to overcome these challenges. In this review, we will discuss the in vitro models currently being used to study the neutrophil response to infection, specifically in the context of cell-cell interactions, and provide an overview of their findings. We will also provide recommendations for the future direction of the field and what important aspects of the infectious microenvironment are missing from the current models.

The incidence of hepatocellular carcinoma (HCC) and the mortality resulting from HCC are both increasing. Most patients with HCC are diagnosed at advanced stages when curative treatments are impossible. Current drug therapy extends mean overall survival by only a short period of time. Genetic mutations associated with HCC vary widely. Therefore, transgenic and mutant animal models are needed to investigate the molecular effects of specific mutations, classify them as drivers or passengers, and develop targeted treatments. Cirrhosis, however, is the premalignant state common to 90% of HCC patients. Currently, no specific therapies are available to halt or reverse the progression of cirrhosis to HCC. Understanding the genetic drivers of HCC as well as the biochemical, mechanical, hormonal, and metabolic changes associated with cirrhosis could lead to novel treatments and cancer prevention strategies. Although additional therapies recently received Food and Drug Administration approval, significant clinical breakthroughs have not emerged since the introduction of the multikinase inhibitor sorafenib, necessitating alternate research strategies. Zebrafish (Danio rerio) are effective for disease modeling because of their high degree of gene and organ architecture conservation with human beings, ease of transgenesis and mutagenesis, high fecundity, and low housing cost. Here, we review zebrafish models of HCC and identify areas on which to focus future research efforts to maximize the advantages of the zebrafish model system. Keywords: Cirrhosis, Tumor Microenvironment, Model Organisms, Inflammation, Drug-Induced Liver Injury, Autophagy

Abstract Background We recently upgraded our [18F]fludeoxyglucose (FDG) production capabilities with the goal of futureproofing our FDG clinical supply, expanding the number of batches of FDG we can manufacture each day, and improving patient throughput in our nuclear medicine clinic. In this paper we report upgrade of the synthesis modules to the GE FASTLab 2 platform (Phase 1) and cyclotron updates (Phase 2) from both practical and regulatory perspectives. We summarize our experience manufacturing FDG on the FASTLab 2 module with a high-yielding self-shielded niobium (Nb) fluorine-18 target. Results Following installation of Nb targets for production of fluorine-18, a 55 μA beam for 22 min generated 1330 ± 153 mCi of [18F]fluoride. Using these cyclotron beam parameters in combination with the FASTLab 2, activity yields (AY) of FDG were 957 ± 102 mCi at EOS, corresponding to 72% non-corrected AY (n = 235). Our workflow, inventory management and regulatory compliance have been greatly simplified following the synthesis module and cyclotron upgrades, and patient wait times for FDG PET have been cut in half at our nuclear medicine clinic. Conclusions The combination of FASTlab 2 and self-shielded Nb fluorine-18 targets have improved our yield of FDG, and enabled reliable and repeatable manufacture of the radiotracer for clinical use.

Summary: Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory skin disease. However, the global scope and organization of this complex cellular program remain undefined. Here we report single-cell RNA sequencing profiles of 92,889 human epidermal cells from 9 normal and 3 inflamed skin samples. Transcriptomics-derived keratinocyte subpopulations reflect classic epidermal strata but also sharply compartmentalize epithelial functions such as cell-cell communication, inflammation, and WNT pathway modulation. In keratinocytes, ∼12% of assessed transcript expression varies in coordinate patterns, revealing undescribed gene expression programs governing epidermal homeostasis. We also identify molecular fingerprints of inflammatory skin states, including S100 activation in the interfollicular epidermis of normal scalp, enrichment of a CD1C+CD301A+ myeloid dendritic cell population in psoriatic epidermis, and IL1βhiCCL3hiCD14+ monocyte-derived macrophages enriched in foreskin. This compendium of RNA profiles provides a critical step toward elucidating epidermal diseases of development, differentiation, and inflammation. : Cheng et al. report single-cell RNA sequencing of normal and inflamed human epidermis, revealing a discrete set of specialized keratinocytes that exhibit a distinct composition at different anatomic sites. Myeloid dendritic cells and macrophages also vary sharply with epidermal anatomic site and inflammation, indicating dynamic programming of antigen-presenting cells. Keywords: epidermis, single-cell RNA-seq, keratinocyte, skin