Childhood cardiometabolic risk factors associated with the perinatal environment of the maternal-paternal-child triad.

INTRODUCTION: Clustering of cardiometabolic risk factors in childhood significantly increases the risk of atherosclerotic cardiovascular disease later in life. Identification of modifiable parental factors that contribute to offspring cardiometabolic health is critical for the prevention of disease. The objective was to identify factors associated with child cardiometabolic risk factors at age 5 years. METHODS: Triads from a longitudinal cohort were recalled at 5 years (n = 68). Dietary intake, anthropometrics, physical activity and serum-based risk factors were collected. Best subset selection, linear and logistic regressions were used to identify triad variables associated with increased risk of cardiometabolic risk factor clustering at age 5 years. RESULTS: In this cohort, best subset modelling revealed that increased paternal fat mass, serum low-density lipoproteins and triglycerides, maternal dietary added sugar and being female were associated with increased odds of offspring having two or more cardiometabolic risk factors at age 5 years. CONCLUSIONS: Dietary and exercise interventions prior to conception targeting paternal adiposity and dyslipidaemia as well as maternal dietary habits could decrease children's cardiometabolic risk in later life.

Synthesis and Biochemical Evaluation of Ethanoanthracenes and Related Compounds: Antiproliferative and Pro-Apoptotic Effects in Chronic Lymphocytic Leukemia (CLL).

Chronic lymphocytic leukemia (CLL) is a malignancy of mature B cells, and it is the most frequent form of leukemia diagnosed in Western countries. It is characterized by the proliferation and accumulation of neoplastic B lymphocytes in the blood, lymph nodes, bone marrow and spleen. We report the synthesis and antiproliferative effects of a series of novel ethanoanthracene compounds in CLL cell lines. Structural modifications were achieved via the Diels-Alder reaction of 9-(2-nitrovinyl)anthracene and 3-(anthracen-9-yl)-1-arylprop-2-en-1-ones (anthracene chalcones) with dienophiles, including maleic anhydride and N-substituted maleimides, to afford a series of 9-(E)-(2-nitrovinyl)-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-diones, 9-(E)-3-oxo-3-phenylprop-1-en-1-yl)-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-diones and related compounds. Single-crystal X-ray analysis confirmed the structures of the novel ethanoanthracenes 23f, 23h, 24a, 24g, 25f and 27. The products were evaluated in HG-3 and PGA-1 CLL cell lines (representative of poor and good patient prognosis, respectively). The most potent compounds were identified as 20a, 20f, 23a and 25n with IC50 values in the ranges of 0.17-2.69 µM (HG-3) and 0.35-1.97 µM (PGA-1). The pro-apoptotic effects of the potent compounds 20a, 20f, 23a and 25n were demonstrated in CLL cell lines HG-3 (82-95%) and PGA-1 (87-97%) at 10 µM, with low toxicity (12-16%) observed in healthy-donor peripheral blood mononuclear cells (PBMCs) at concentrations representative of the compounds IC50 values for both the HG-3 and PGA-1 CLL cell lines. The antiproliferative effect of the selected compounds, 20a, 20f, 23a and 25n, was mediated through ROS flux with a marked increase in cell viability upon pretreatment with the antioxidant NAC. 25n also demonstrated sub-micromolar activity in the NCI 60 cancer cell line panel, with a mean GI50 value of 0.245 µM. This ethanoanthracene series of compounds offers potential for the further development of lead structures as novel chemotherapeutics to target CLL.

Human quad liver-on-chip system as a tool toward bridging the gap between animals and humans regarding toxicology and pharmacology of a cannabidiol-rich cannabis extract.

Cannabidiol (CBD) is a major phytocannabinoid from Cannabis sativa. It is currently widely available and widely used in the USA, but despite its rapid progress to market, the pharmacology and toxicology of both CBD and cannabidiol-rich cannabis extracts (CRCE) remain largely unknown. The goals of this study were to investigate the potential of a novel human microphysiological system to emulate CRCE-induced hepatotoxicity and pharmacological properties demonstrated in animal models. For this purpose, C57BL6/J male mice were subjected to dosing with either 0, 61.5, 184.5, or 615 mg/kg of CRCE for 10 days. The liver-on-chip system, incorporating human primary hepatocytes, sinusoidal endothelial cells, as well as Kupffer and stellate cells was subjected to 0, 300, 1,200, or 4,400 ng/mL of CRCE (8 h exposure followed by 16 h washout) for 5 days. Administration of CRCE in mice resulted in nearly 4-fold elevations of plasma ALT at 615 mg/kg (p < 0.01) and a dose-dependent decrease in intrahepatic miR-122. Elevated levels of ALT, paralleled by decreased intrahepatic and increased effluent levels of miR-122, were also observed in the liver-on-chip, although these results were not statistically significant. Exposure to CRCE resulted in a robust and dose-dependent induction of key cytochrome P450 enzymes, namely Cyp1a2, Cyp2b6 (CYP2B10), Cyp2e1, and Cyp2c9 (CYP2C19) in both mouse livers and liver-on-chip. The results of this study demonstrate the congruence between the responses observed in mouse and human liver-on-chip experimental systems and provide evidence of the potential microphysiological systems hold for translating animal data into clinical practice.

Inter-strain variability in responses to a single administration of the cannabidiol-rich cannabis extract in mice.

Cannabidiol (CBD) has gained widespread popularity; however, its pharmacological and toxicological profiles in the context of human genetic diversity remain largely unexplored. Here, we investigated the variability in metabolism and toxicity of CBD-rich cannabis extract (CRCE) in genetically diverse mouse models: C57BL/6J, B6C3F1/J, and NZO/HlLtJ strains. Mice received a single dose of CRCE containing 57.9% CBD at dosages of 0, 246, 738, and 2460 mg/kg of CBD. At 24 h after treatment, no appreciable histomorphological changes were detected in the liver. Plasma bilirubin levels increased markedly in all strains at the highest CBD dose. Mice in all treatment groups displayed significant but distinct increases in ALT and AST levels. While B6C3F1/J and NZO/HlLtJ mice had negligible plasma CBD levels at 738 mg/kg, C57BL/6J mice exhibited levels exceeding 7000 ng/mL. At 2460 mg/kg, high CBD concentrations were found in B6C3F1/J and C57BL/6J mice, but markedly lower levels were seen in NZO/HlLtJ mice. Gene expression profiling showed significant increases in Cyp2b10 across all strains but varying responses in Cyp1a1 expression, indicating strain-specific CYP dysregulation. Genetically diverse mice exhibited differential pharmacological and toxicological responses to CRCE, suggesting a high potential for inter-individual variability in the pharmacology and toxicology of CBD in humans.

Impact of prescribed fire on soil microbial communities in a Southern Appalachian Forest clear-cut.

Escalating wildfire frequency and severity, exacerbated by shifting climate patterns, pose significant ecological and economic challenges. Prescribed burns, a common forest management tool, aim to mitigate wildfire risks and protect biodiversity. Nevertheless, understanding the impact of prescribed burns on soil and microbial communities in temperate mixed forests, considering temporal dynamics and slash fuel types, remains crucial. Our study, conducted at the University of Tennessee Forest Resources AgResearch and Education Center in Oak Ridge, TN, employed controlled burns across various treatments, and the findings indicate that low-intensity prescribed burns have none or minimal short-term effects on soil parameters but may alter soil nutrient concentrations, as evidenced by significant changes in porewater acetate, formate, and nitrate concentrations. These burns also induce shifts in microbial community structure and diversity, with Proteobacteria and Acidobacteria increasing significantly post-fire, possibly aiding soil recovery. In contrast, Verrucomicrobia showed a notable decrease over time, and other specific microbial taxa correlated with soil pH, porewater nitrate, ammonium, and phosphate concentrations. Our research contributes to understanding the intricate relationships between prescribed fire, soil dynamics, and microbial responses in temperate mixed forests in the Southern Appalachian Region, which is valuable for informed land management practices in the face of evolving environmental challenges.

Apolipoprotein E controls Dectin-1-dependent development of monocyte-derived alveolar macrophages upon pulmonary ß-glucan-induced inflammatory adaptation.

The lung is constantly exposed to the outside world and optimal adaptation of immune responses is crucial for efficient pathogen clearance. However, mechanisms that lead to lung-associated macrophages' functional and developmental adaptation remain elusive. To reveal such mechanisms, we developed a reductionist model of environmental intranasal ß-glucan exposure, allowing for the detailed interrogation of molecular mechanisms of pulmonary macrophage adaptation. Employing single-cell transcriptomics, high-dimensional imaging and flow cytometric characterization paired with in vivo and ex vivo challenge models, we reveal that pulmonary low-grade inflammation results in the development of apolipoprotein E (ApoE)-dependent monocyte-derived alveolar macrophages (ApoE+CD11b+ AMs). ApoE+CD11b+ AMs expressed high levels of CD11b, ApoE, Gpnmb and Ccl6, were glycolytic, highly phagocytic and produced large amounts of interleukin-6 upon restimulation. Functional differences were cell intrinsic, and myeloid cell-specific ApoE ablation inhibited Ly6c+ monocyte to ApoE+CD11b+ AM differentiation dependent on macrophage colony-stimulating factor secretion, promoting ApoE+CD11b+ AM cell death and thus impeding ApoE+CD11b+ AM maintenance. In vivo, ß-glucan-elicited ApoE+CD11b+ AMs limited the bacterial burden of Legionella pneumophilia after infection and improved the disease outcome in vivo and ex vivo in a murine lung fibrosis model. Collectively these data identify ApoE+CD11b+ AMs generated upon environmental cues, under the control of ApoE signaling, as an essential determinant for lung adaptation enhancing tissue resilience.

Tracking the cellular uptake and phototoxicity of Ru(ii)-polypyridyl-1,8-naphthalimide Tröger's base conjugates.

Ruthenium(ii) complexes are attracting significant research attention as a promising class of photosensitizers (PSs) in photodynamic therapy (PDT). Having previously reported the synthesis of two novel Ru(ii)-polypyridyl-1,8-naphthalimide Tröger's base compounds 1 and 2 with interesting photophysical properties, where the emission from either the Ru(ii) polypyridyl centres or the naphthalimide moieties could be used to monitor binding to nucleic acids, we sought to use these compounds to investigate further and in more detail their biological profiling, which included unravelling their mechanism of cellular uptake, cellular trafficking and cellular responses to photoexcitation. Here we demonstrate that these compounds undergo rapid time dependent uptake in HeLa cells that involved energy dependent, caveolae and lipid raft-dependent mediated endocytosis, as demonstrated by confocal imaging, and transmission and scanning electron microscopy. Following endocytosis, both compounds were shown to localise to mostly lysosomal and Golgi apparatus compartments with some accumulation in mitochondria but no localisation was found to the nucleus. Upon photoactivation, the compounds increased ROS production and induced ROS-dependent apoptotic cell death. The photo-activated compounds subsequently induced DNA damage and altered tubulin, but not actin structures, which was likely to be an indirect effect of ROS production and induced apoptosis. Furthermore, by changing the concentration of the compounds or the laser used to illuminate the cells, the mechanism of cell death could be changed from apoptosis to necrosis. This is the first detailed biological study of Ru(ii)-polypyridyl Tröger's bases and clearly suggests caveolae-dependent endocytosis is responsible for cell uptake - this may also explain the lack of nuclear uptake for these compounds and similar results observed for other Ru(ii)-polypyridyl complexes. These conjugates are potential candidates for further development as PDT agents and may also be useful in mechanistic studies on cell uptake and trafficking.

Molecular autopsy for fetal structural anomaly: diagnostic and clinical utility of multidisciplinary team approach.

OBJECTIVE: In the West Midlands regional genetics service, cases of perinatal death with a possible genetic diagnosis are evaluated by the perinatal pathology genetic multidisciplinary team (MDT). The MDT assesses autopsy findings and suggests appropriate genomic assessment. The objective of this retrospective service evaluation was to determine the clinical utility of the MDT in assessing perinatal deaths associated with structural anomaly. This is the first evaluation since the introduction of whole-genome and whole-exome sequencing in routine clinical care. METHODS: This was a retrospective service evaluation including all cases of perinatal death with an associated structural anomaly and suspected genetic etiology that underwent perinatal MDT assessment between January and December 2021. All cases received a full or partial postmortem examination and at least a chromosomal microarray analysis. Demographic characteristics, phenotype, genotype, MDT recommendations, diagnoses, outcomes and impact of postmortem analysis and genetic testing data were collected from patient case notes. RESULTS: Overall, 123 cases were discussed at the MDT meetings in 2021. Genetic evaluation was recommended in 84 cases and accepted in 64 cases. A range of genetic tests were requested according to indication and availability. Thirty diagnoses were made in 29 cases from 26 unrelated families. The diagnostic yield was 24% (29/123) in all cases or 45% (29/64) in cases with a suspected genetic diagnosis who underwent genetic testing. Postmortem examination provided clinically actionable phenotypic data in 79% of cases. A genetic diagnosis enabled accurate recurrence risk counseling and provision of appropriate follow-up, including prenatal testing and preimplantation diagnosis for patients with inherited conditions. CONCLUSIONS: Genomic testing was a clinically useful addition to (but not a substitute for) postmortem examination in cases of perinatal death associated with structural anomaly. The MDT approach helped assess cases and plan appropriate follow-up. Expedited whole-genome sequencing or panel-agnostic analysis were most appropriate for heterogeneous presentations. This broad approach can also expand knowledge of prenatal phenotypes and detect novel disease genes, and should be a priority in future research. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Sex- and operation-dependent effects on 5-year weight loss results of bariatric surgery.

BACKGROUND: Weight loss response after bariatric surgery is highly variable, and several demographic factors are associated with differential responses to surgery. Preclinical studies demonstrate numerous sex-specific responses to bariatric surgery, but whether these responses are also operation dependent is unknown. OBJECTIVE: To examine sex-specific weight loss outcomes up to 5 years after laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). SETTING: Single center, university, United States. METHODS: Retrospective, observational cohort study including RYGB (n = 5057) and vertical SG (n = 2041) patients from a single, academic health center. Percentage total weight loss (TWL) over time was examined with generalized linear mixed models to determine the main and interaction effects of surgery type on weight loss by sex. RESULTS: TWL demonstrated a strong sex-by-procedure interaction, with women having a significant advantage with RYGB compared with SG (adjusted difference at 5 yr: 8.0% [95% CI: 7.5-8.5]; P < .001). Men also experienced greater TWL over time with RYGB or SG, but the difference was less and clinically insignificant (adjusted difference at 5 yr: 2.9% [2.0-3.8]; P < .001; P interaction between sex and procedure type = .0001). Overall, women had greater TWL than men, and RYGB patients had greater TWL than SG patients (adjusted difference at 5 yr: 3.1% [2.4-3.2] and 6.9% [6.5-7.3], respectively; both P < .0001). Patients with diabetes lost less weight compared with those without (adjusted difference at 5 yr: 3.0% [2.7-3.2]; P < .0001). CONCLUSIONS: Weight loss after bariatric surgery is sex- and procedure-dependent. There is an association suggesting a clinically insignificant difference in weight loss between RYGB and SG among male patients at both the 2- and 5-year postsurgery time points.

Roadmap for the expression of canonical and extended endocannabinoid system receptors and metabolic enzymes in peripheral organs of preclinical animal models.

The endocannabinoid system is widely expressed throughout the body and is comprised of receptors, ligands, and enzymes that maintain metabolic, immune, and reproductive homeostasis. Increasing interest in the endocannabinoid system has arisen due to these physiologic roles, policy changes leading to more widespread recreational use, and the therapeutic potential of Cannabis and phytocannabinoids. Rodents have been the primary preclinical model of focus due to their relative low cost, short gestational period, genetic manipulation strategies, and gold-standard behavioral tests. However, the potential for lack of clinical translation to non-human primates and humans is high as cross-species comparisons of the endocannabinoid system have not been evaluated. To bridge this gap in knowledge, we evaluate the relative gene expression of 14 canonical and extended endocannabinoid receptors in seven peripheral organs of C57/BL6 mice, Sprague-Dawley rats, and non-human primate rhesus macaques. Notably, we identify species- and organ-specific heterogeneity in endocannabinoid receptor distribution where there is surprisingly limited overlap among the preclinical models. Importantly, we determined there were no receptors with identical expression patterns among mice (three males and two females), rats (six females), and rhesus macaques (four males). Our findings demonstrate a critical, yet previously unappreciated, contributor to challenges of rigor and reproducibility in the cannabinoid field, which has implications in hampering progress in understanding the complexity of the endocannabinoid system and development of cannabinoid-based therapies.

Synthesis and Pro-Apoptotic Effects of Nitrovinylanthracenes and Related Compounds in Chronic Lymphocytic Leukaemia (CLL) and Burkitt's Lymphoma (BL).

Chronic lymphocytic leukaemia (CLL) is a malignancy of the immune B lymphocyte cells and is the most common leukaemia diagnosed in developed countries. In this paper, we report the synthesis and antiproliferative effects of a series of (E)-9-(2-nitrovinyl)anthracenes and related nitrostyrene compounds in CLL cell lines and also in Burkitt's lymphoma (BL) cell lines, a rare form of non-Hodgkin's immune B-cell lymphoma. The nitrostyrene scaffold was identified as a lead structure for the development of effective compounds targeting BL and CLL. The series of structurally diverse nitrostyrenes was synthesised via Henry-Knoevenagel condensation reactions. Single-crystal X-ray analysis confirmed the structure of (E)-9-chloro-10-(2-nitrobut-1-en-1-yl)anthracene (19f) and the related 4-(anthracen-9-yl)-1H-1,2,3-triazole (30a). The (E)-9-(2-nitrovinyl)anthracenes 19a, 19g and 19i-19m were found to elicit potent antiproliferative effects in both BL cell lines EBV-MUTU-1 (chemosensitive) and EBV+ DG-75 (chemoresistant) with >90% inhibition at 10 µM. Selected (E)-9-(2-nitrovinyl)anthracenes demonstrated potent antiproliferative activity in CLL cell lines, with IC50 values of 0.17 µM (HG-3) and 1.3 µM (PGA-1) for compound 19g. The pro-apoptotic effects of the most potent compounds 19a, 19g, 19i, 19l and 19m were demonstrated in both CLL cell lines HG-3 and PGA-1. The (E)-nitrostyrene and (E)-9-(2-nitrovinyl)anthracene series of compounds offer potential for further development as novel chemotherapeutics for CLL.

Concentrated ionic liquids for proteomics: Caveat emptor!

The use of concentrated ionic liquids (ILs) in the bioanalytical chemistry of proteins is sparse; typically, dilute aqueous IL solutions are used. Concentrated ILs have unique properties that may allow researchers to dissolve previously insoluble protein analytes, to increase the depth and robustness of sample preparation and the analysis of proteins. Previous research using concentrated ILs for this purpose is sparse and there is a need to systematically investigate the structure-activity relationship between the IL structure and its capacity to solubilise proteins. Here, bovine serum albumin was dissolved in various ionic liquids and monitored over time by light microscopy and SDS-PAGE. While qualitative, these measures provide a good estimate of, respectively, the dissolving power of an IL towards the given protein and the retained integrity of the protein. Hydrophilic ILs show the best solubilisation capacity and higher temperatures (in a restricted sense) improve the solubility of the protein. Higher temperatures and longer reaction times reduce the molecular weight of the protein, which could inhibit their applicability in proteomics, unless the conditions are judiciously controlled. Researchers should exercise caution when using concentrated ILs for protein analysis until the full scope and limitations are known, an aspect we are presently investigating.

Antimicrobial effects of XF drugs against Candida albicans and its biofilms.

Compared with antibiotics for treating bacterial infections, there are a limited number of antifungal agents. This is due to several factors, including the difficulties of identifying suitable antifungals that target the fungal cell without damaging host cells, and the reduced rates of diagnosis of fungal infections compared with those caused by bacteria. The problem of treating fungal infections is exacerbated by an increasing incidence of antifungal resistance among human fungal pathogens. Three XF drugs (XF-73, XF-70, and DPD-207) have previously displayed innate bactericidal effects and a low propensity for microbial resistance, with XF-73 and XF-70 having a second, light-activated mechanism of action [known as photodynamic therapy (PDT)]. In an effort to expand the repertoire of antifungal agents, this research assessed the in vitro activity of XF drugs via both mechanisms of action against six strains of the fungal pathogen Candida albicans in both planktonic and biofilm cultures. In addition, this research examined the effects of XF drug treatment on biofilms of C. albicans in a reconstituted human oral epithelium model. All C. albicans strains tested were susceptible to XF-73 and XF-70, with minimum inhibitory concentrations (MICs) between 0.25 µg/mL and 2 µg/mL; DPD-207 was less potent, with MICs between 4 µg/mL and 16 µg/mL, and light activation did not enhance these MICs. Complete biofilm eradication was not reported at the tested XF drug concentrations. However, live and dead staining of C. albicans cells in biofilms after XF drug treatment demonstrated that XF-73 and XF-70 were active against most Candida biofilms tested from 64 µg/mL; again, light activation did not enhance anti-biofilm activity. Candida biofilms were more resistant to DPD-207, with fungicidal effects occurring from 256 µg/mL. XF-73 and XF-70 reduced penetration of C. albicans biofilm into reconstituted human oral epithelium (RHOE) and resulted in less damage (as determined by reduced lactate dehydrogenase release) than untreated biofilms. Overall, the results highlight the potential of XF drugs as new drugs for the management of topical infections caused by C. albicans. Further studies are warranted on the development of XF drugs as antifungals, particularly for XF-73 and XF-70.

Correction: Time-resolved infra-red studies of photo-excited porphyrins in the presence of nucleic acids and in HeLa tumour cells: insights into binding site and electron transfer dynamics.

Correction for 'Time-resolved infra-red studies of photo-excited porphyrins in the presence of nucleic acids and in HeLa tumour cells: insights into binding site and electron transfer dynamics' by Páraic M. Keane et al., Phys. Chem. Chem. Phys., 2022, 24, 27524-27531, https://doi.org/10.1039/D2CP04604K.

Canine models of Charcot-Marie-Tooth: MTMR2, MPZ, and SH3TC2 variants in golden retrievers with congenital hypomyelinating polyneuropathy.

Congenital hypomyelinating polyneuropathy (HPN) restricted to the peripheral nervous system was reported in 1989 in two Golden Retriever (GR) littermates. Recently, four additional cases of congenital HPN in young, unrelated GRs were diagnosed via neurological examination, electrodiagnostic evaluation, and peripheral nerve pathology. Whole-genome sequencing was performed on all four GRs, and variants from each dog were compared to variants found across >1,000 other dogs, all presumably unaffected with HPN. Likely causative variants were identified for each HPN-affected GR. Two cases shared a homozygous splice donor site variant in MTMR2, with a stop codon introduced within six codons following the inclusion of the intron. One case had a heterozygous MPZ isoleucine to threonine substitution. The last case had a homozygous SH3TC2 nonsense variant predicted to truncate approximately one-half of the protein. Haplotype analysis using 524 GR established the novelty of the identified variants. Each variant occurs within genes that are associated with the human Charcot-Marie-Tooth (CMT) group of heterogeneous diseases, affecting the peripheral nervous system. Testing a large GR population (n = >200) did not identify any dogs with these variants. Although these variants are rare within the general GR population, breeders should be cautious to avoid propagating these alleles.

Roadmap For The Expression Of Canonical and Extended Endocannabinoid System Receptors and Proteins in Peripheral Organs of Preclinical Animal Models.

The endocannabinoid system is widely expressed throughout the body and is comprised of receptors, ligands, and enzymes that maintain metabolic, immune, and reproductive homeostasis. Increasing interest in the endocannabinoid system has arisen due to these physiologic roles, policy changes leading to more widespread recreational use, and the therapeutic potential of Cannabis and phytocannabinoids. Rodents have been the primary preclinical model of focus due to their relative low cost, short gestational period, genetic manipulation strategies, and gold-standard behavioral tests. However, the potential for lack of clinical translation to non-human primates and humans is high as cross-species comparisons of the endocannabinoid system has not been evaluated. To bridge this gap in knowledge, we evaluate the relative gene expression of 14 canonical and extended endocannabinoid receptors in seven peripheral organs of C57/BL6 mice, Sprague-Dawley rats, and non-human primate rhesus macaques. Notably, we identify species- and organ-specific heterogeneity in endocannabinoid receptor distribution where there is surprisingly limited overlap among the preclinical models. Importantly, we determined there were only five receptors (CB2, GPR18, GPR55, TRPV2, and FAAH) that had identical expression patterns in mice, rats, and rhesus macaques. Our findings demonstrate a critical, yet previously unappreciated, contributor to challenges of rigor and reproducibility in the cannabinoid field, which has profound implications in hampering progress in understanding the complexity of the endocannabinoid system and development of cannabinoid-based therapies.

An Outbreak Investigation of Vibrio parahaemolyticus Infections in the United States Linked to Crabmeat Imported from Venezuela: 2018.

Vibrio parahaemolyticus is the leading cause of seafood-related foodborne illness globally. In 2018, the U.S. federal, state, and local public health and regulatory partners investigated a multistate outbreak of V. parahaemolyticus infections linked to crabmeat that resulted in 26 ill people and nine hospitalizations. State and U.S. Food and Drug Administration (FDA) laboratories recovered V. parahaemolyticus, Salmonella spp., and Listeria monocytogenes isolates from crabmeat samples collected from various points of distribution and conducted phylogenetic analyses of whole-genome sequencing data. Federal, state, and local partners conducted traceback investigations to determine the source of crabmeat. Multiple Venezuelan processors that supplied various brands of crabmeat were identified, but a sole firm was not confirmed as the source of the outbreak. Travel restrictions between the United States and Venezuela prevented FDA officials from conducting on-site inspections of cooked crabmeat processors. Based on investigation findings, partners developed public communications advising consumers not to eat crabmeat imported from Venezuela and placed potentially implicated firms on import alerts. While some challenges limited the scope of the investigation, epidemiologic, traceback, and laboratory evidence identified the contaminated food and country of origin, and contributed to public health and regulatory actions, preventing additional illnesses. This multistate outbreak illustrates the importance of adhering to appropriate food safety practices and regulations for imported seafood.

Visible to Near-Infrared Reflectance Spectroscopy of Asteroid (16) Psyche: Implications for the Psyche Mission's Science Investigations.

The NASA Psyche mission will explore the structure, composition, and other properties of asteroid (16) Psyche to test hypotheses about its formation. Variations in radar reflectivity, density, thermal inertia, and visible to near-infrared (VNIR) reflectance spectra of Psyche suggest a highly metallic composition with mafic silicate minerals (e.g., pyroxene) heterogeneously distributed on the surface in low abundance (<10 vol.%). The Psyche spacecraft's Multispectral Imager is designed to map ≥80% of the surface at high spatial resolution (≤20 m/pixel) through a panchromatic filter and provide compositional information for about ≥80% of the surface using seven narrowband filters at VNIR wavelengths (∼400-1,100 nm) and at spatial scales of ≤500 m/pixel. We analyzed 359 reflectance spectra from samples consistent with current uncertainties in Psyche's composition and compared them to published reflectance spectra of the asteroid using a chi-square test for goodness of fit. The best matches for Psyche include iron meteorite powder, powders from the sulfide minerals troilite and pentlandite, and powder from the CH/CBb chondrite Isheyevo. Comparison of absorption features support the interpretation that Psyche's surface is a metal-silicate mixture, although the exact abundance and chemistry of the silicate component remains poorly constrained. We convolve our spectra to the Imager's spectral throughput to demonstrate preliminary strategies for mapping the surface composition of the asteroid using filter ratios and reconstructed band parameters. Our results provide predictions of the kinds of surface compositional information that the Psyche mission could reveal on the solar system's largest M-type asteroid.

Pinniped electroencephalography: Methodology and findings in California sea lions (Zalophus californianus).

This study was designed to identify abnormalities in the electroencephalograms (EEGs) recorded from stranded California sea lions (Zalophus californianus) with suspected domoic acid (DA) toxicosis. Recordings from animals presenting for non-neurological issues were also obtained to better understand the normal EEG (background activity and transient events) in this species, as, to date, studies have focused on examining natural sleep in pinnipeds. Most animals were sedated for electrode placement and EEG acquisition with some receiving antiepileptic medications or isoflurane during the procedure. A total of 103 recordings were read and scored from 0 (normal) to 3 (severely abnormal). Epileptiform discharges, consisting of spikes, sharp waves, slow waves, and/or spike waves, were present in all EEGs with scores of 1, 2, or 3. The distribution of these events over the scalp varied. While often generalized, others were lateralized over one hemisphere, bifrontal, bioccipital, and/or bitemporal, while some discharges were multifocal. Findings were different between sea lions and occasionally changed within the EEG on a given sea lion. No clinical seizures were observed during the recording but a few sea lions had findings consistent with electroencephalographic seizures. When available, supporting diagnostic results obtained from magnetic resonance imaging (MRI) and/or necropsy/histopathology were described, as well as the status of those sea lions that recovered and were released with satellite tags.

A longitudinal observational study of skeletal development between ages 3 mo and 6 y in children fed human milk, milk formula, or soy formula.

BACKGROUND: Early infant feeding can affect skeletal development. Most children are fed with breast milk, dairy-based infant formula, or soy-based infant formula during the first year of life. The National Health and Nutrition Examination Survey 2003-2010 reports that 12% of the US infants consume soy-based infant formula. Despite potential effects of soy-associated isoflavones on skeletal development, studies investigating bone metabolism and structural and functional bone indices in children are lacking. OBJECTIVE: The aim of this observational study was to investigate early effects of soy-based infant formula (SF group) intake on bone metabolism and structure during the first 6 y of life comparing with those of infants fed with breast milk (BF group) and dairy-based infant formula (MF group). METHODS: A total of 433 healthy infants were followed up from 3 mo to 6 y of age. Children's skeletal development was assessed using dual-energy X-ray absorptiometry (DXA; N = 433) and peripheral quantitative computed tomography (pQCT; n = 78). The urinary biomarkers of bone metabolism (N-terminal telopeptide of type I collagen [NTx] and osteocalcin) were evaluated using immunoassays at 6, 24, 60, and 72 mo. RESULTS: No statistically significant group differences were observed in bone mineral density (BMD) between the BF, MF, and SF groups, assessed using DXA or pQCT. At 6 y of age, children in the SF group showed significantly greater whole-body bone mineral content measured using DXA than those in the MF group. Six-month-old boys in the SF group demonstrated significantly greater levels of NTx than those in the MF group and significantly greater osteocalcin levels than those in the BF group. CONCLUSIONS: Together, these data suggest that although infants at age 6 mo in the SF group showed some enhanced bone metabolism compared with those in the BF and MF groups, as indicated by the urinary biomarkers, no differences in bone metabolism or BMD were noted between ages 2 and 6 y. This trial was registered at clinicaltrials.gov as NCT00616395.