Agenesis of the left hepatic lobe: a cadaveric case report.

Agenesis of the left hepatic lobe is a rare anomaly described as the absence of liver tissue on the left side of the gallbladder fossa or falciform ligament. Here we report a case of agenesis of the left hepatic lobe identified during educational dissection of an 84-year-old male formalin-fixed cadaver. The gross anatomical characteristics, embryological origin, and clinical relevance of this rare variation are described in this report.

Polycyclic aromatic hydrocarbons in silicone wristbands of Uruguayan children: measurement and exposure source exploration.

Polycyclic aromatic hydrocarbons (PAHs) pose health risks to children, potentially resulting in stunted growth, obesity, and cognitive deficits, but lack of reliable and noninvasive means to measure PAHs results in poor understanding of exposure patterns and sources in this vulnerable population. In this study, 24 children aged ∼7 years (9 boys and 15 girls) from Montevideo, Uruguay wore silicone wristbands for 8 days to monitor the exposure of 27 PAHs. Wristbands were extracted using a modified ethyl acetate tandem solid phase extraction clean up and then analyzed via gas chromatography with tandem mass spectrometry. This analysis has reported LODs for 27 PAHs between 0.05 and 3.91 µg L-1. Eighteen PAHs were detected in >50% of the samples with concentration medians ranging 1.2-16.3 ng g-1 of wristband. Low molecular weight PAHs (2-3 rings) such as naphthalene and its alkyl derivatives were highly correlated (0.7-0.9) in the wristbands, suggesting exposure from related sources. Exposure source exploration focused on secondhand tobacco smoke, potentially through caregivers who reported on smoking habits in an associated survey. A principal components analysis (PCA) was conducted to examine patterns in PAH compounds detected in the wristbands; subsequently, the resulting components were compared according to current smoking among caregivers. The PCA analysis revealed a grouping of participants based on higher exposure of 1-methyl naphthalene, pyrene, fluoranthene, 1-methylphenanthrene, dibenzothiophene and 2-phenyl naphthalene. The derived components did relate with parental smoking, suggesting that some participants experienced exposure to a common source of certain PAHs outside of parental smoking. This is the first study to assess PAH exposure in young children from South America. Using wristbands, our study indicates exposure to multiple, potentially harmful chemicals. Wristbands could provide a comprehensive picture of PAH exposure in children, complementing other non-invasive biomonitoring approaches.

Development of EBV Related Diffuse Large B-cell Lymphoma in Deficiency of Adenosine Deaminase 2 with Uncontrolled EBV Infection.

Deficiency of Adenosine Deaminase 2 (DADA2) patients presenting with primary immunodeficiency are at risk of uncontrolled EBV infection and secondary malignancies including EBV-related lymphoproliferative disorders (LPD). This paper describes the first case of EBV related diffuse large B-cell lymphoma in a patient with DADA2 and uncontrolled EBV infection. Consideration should be given to monitoring for EBV viraemia and to preventative EBV specific therapy in DADA2 and patients with at risk primary immunodeficiencies. A type I interferon (IFN) gene signature is associated with DADA2 though its association with immune dysregulation is unclear.

Elucidation of the role of metals in the adsorption and photodegradation of herbicides by metal-organic frameworks.

Here, four MOFs, namely Sc-TBAPy, Al-TBAPy, Y-TBAPy, and Fe-TBAPy (TBAPy: 1,3,6,8-tetrakis(p-benzoic acid)pyrene), were characterized and evaluated for their ability to remediate glyphosate (GP) from water. Among these materials, Sc-TBAPy demonstrates superior performance in both the adsorption and degradation of GP. Upon light irradiation for 5 min, Sc-TBAPy completely degrades 100% of GP in a 1.5 mM aqueous solution. Femtosecond transient absorption spectroscopy reveals that Sc-TBAPy exhibits enhanced charge transfer character compared to the other MOFs, as well as suppressed formation of emissive excimers that could impede photocatalysis. This finding was further supported by hydrogen evolution half-reaction (HER) experiments, which demonstrated Sc-TBAPy's superior catalytic activity for water splitting. In addition to its faster adsorption and more efficient photodegradation of GP, Sc-TBAPy also followed a selective pathway towards the oxidation of GP, avoiding the formation of toxic aminomethylphosphonic acid observed with the other M3+-TBAPy MOFs. To investigate the selectivity observed with Sc-TBAPy, electron spin resonance, depleted oxygen conditions, and solvent exchange with D2O were employed to elucidate the role of different reactive oxygen species on GP photodegradation. The findings indicate that singlet oxygen (1O2) plays a critical role in the selective photodegradation pathway achieved by Sc-TBAPy.

Inclusion of People With Disabilities in Community Health Needs Assessments in Florida, United States.

Community health needs assessments (CHNAs) play a crucial role in identifying health needs of communities. Yet, unique health needs of people with disabilities (PWDs) are often underrecognized in public health practice. In 2010, the Patient Protection and Affordable Care Act (ACA) required the implementation of standardized data collection guidelines, including disability status, among federal agencies. The extent to which guidance from ACA and the U.S. Centers for Disease Control and Prevention has impacted disability inclusion in CHNAs is unknown. This study used a content analysis approach to review CHNAs conducted by local health councils and the top 11 nonprofit hospitals in Florida (n = 77). We coded CHNAs based on mentioning disability in CHNA reports, involving disability-related stakeholders, and incorporating data on disability indicators. Findings indicate that PWDs are widely not included in CHNAs in Florida, emphasizing the need for equitable representation and comprehensive understanding of PWDs in community health planning.

Transcriptional and functional consequences of Oncostatin M signaling on young Dnmt3a-mutant hematopoietic stem cells.

Age-associated clonal hematopoiesis (CH) occurs due to somatic mutations accrued in hematopoietic stem cells (HSCs) that confer a selective growth advantage in the context of aging. The mechanisms by which CH-mutant HSCs gain this advantage with aging are not comprehensively understood. Using unbiased transcriptomic approaches, we identified Oncostatin M (OSM) signaling as a candidate contributor to age-related Dnmt3a-mutant CH. We found that Dnmt3a-mutant HSCs from young adult mice (3-6 months old) subjected to acute OSM stimulation do not demonstrate altered proliferation, apoptosis, hematopoietic engraftment, or myeloid differentiation. Dnmt3a-mutant HSCs from young mice do transcriptionally upregulate an inflammatory cytokine network in response to acute in vitro OSM stimulation as evidenced by significant upregulation of the genes encoding IL-6, IL-1ß, and TNFα. OSM-stimulated Dnmt3a-mutant HSCs also demonstrate upregulation of the anti-inflammatory genes Socs3, Atf3, and Nr4a1. In the context of an aged bone marrow (BM) microenvironment, Dnmt3a-mutant HSCs upregulate proinflammatory genes but not the anti-inflammatory genes Socs3, Atf3, and Nr4a1. The results from our studies suggest that aging may exhaust the regulatory mechanisms that HSCs employ to resolve inflammatory states in response to factors such as OSM.

Arthralgia in midlife Singaporean women: the Integrated Women's Health Program (IWHP).

OBJECTIVE: Arthralgia is a common menopausal complaint in midlife women, and its causes remain unclear. We examined the prevalence of menopausal arthralgia with various factors including sleep quality, depression/anxiety, muscle strength and physical performance among midlife Singaporean women. METHODS: The Integrated Women's Health Program (IWHP) comprised 1120 healthy, community-dwelling women of Chinese, Malay or Indian ethnicities (aged 45-69 years) attending well-women clinics at the National University Hospital, Singapore. Sociodemographic, menopausal, reproductive and health data were obtained with validated questionnaires. Muscle strength, physical performance and dual-energy X-ray absorptiometry were measured. Women with moderate to very severe symptoms using the Menopause Rating Scale were classified as having arthralgia. Multivariable logistic regression analyses examined risk factors for arthralgia. RESULTS: One-third of the participants reported arthralgia, and 12.7%, 16.2% and 71.2% were in the premenopausal, perimenopausal and postmenopausal period, respectively. Menopausal symptoms, such as vaginal dryness (adjusted odds ratio [aOR]: 2.64, 95% confidence interval [CI]: 1.64, 4.24) and physical/mental exhaustion (aOR: 2.83, 95% CI: 1.79, 4.47), were independent risk factors for arthralgia. Poor muscle strength (aOR: 2.20, 95% CI: 1.29, 3.76), obesity (aOR: 1.94, 95% CI: 1.13, 3.32) and rheumatoid arthritis (aOR: 7.73, 95% CI: 4.47, 13.36) were also independently associated with arthralgia after adjustment for confounders. CONCLUSIONS: Arthralgia in midlife Singaporean women was associated with menopausal symptoms of vaginal dryness and physical and mental exhaustion. Women with poor muscle strength were more likely to experience menopausal arthralgia.

Characterization of an Osmr Conditional Knockout Mouse Model.

Oncostatin M (OSM) is a member of the interleukin-6 (IL-6) family of cytokines and has been found to have distinct anti-inflammatory and pro-inflammatory properties in various cellular and disease contexts. OSM signals through two receptor complexes, one of which includes OSMRß. To investigate OSM-OSMRß signaling in adult hematopoiesis, we utilized the readily available conditional Osmrfl/fl mouse model B6;129-Osmrtm1.1Nat/J, which is poorly characterized in the literature. This model contains loxP sites flanking exon 2 of the Osmr gene. We crossed Osmrfl/fl mice to interferon-inducible Mx1-Cre, which is robustly induced in adult hematopoietic cells. We observed complete recombination of the Osmrfl allele and loss of exon 2 in hematopoietic (bone marrow) as well as non-hematopoietic (liver, lung, kidney) tissues. Using a TaqMan assay with probes downstream of exon 2, Osmr transcript was lower in the kidney but equivalent in bone marrow, lung, and liver from Osmrfl/fl Mx1-Cre versus Mx1-Cre control mice, suggesting that transcript is being produced despite loss of this exon. Western blots show that liver cells from Osmrfl/fl Mx1-Cre mice had complete loss of OSMR protein, while bone marrow, kidney, and lung cells had reduced OSMR protein at varying levels. RNA-seq analysis of a subpopulation of bone marrow cells (hematopoietic stem cells) finds that some OSM-stimulated genes, but not all, are suppressed in Osmrfl/fl Mx1-Cre cells. Together, our data suggest that the B6;129-Osmrtm1.1Nat/J model should be utilized with caution as loss of Osmr exon 2 has variable and tissue-dependent impact on mRNA and protein expression.

Boron Chalcogen Mixture Method-Assisted Alkali Halide Flux Crystal Growth of an Extensive Family of Quaternary Rare Earth Transition-Metal Thiosilicates: Investigation of Their Structures and Magnetic Properties.

A series of transition-metal-containing rare earth thiosilicates, RE3TM0.5SiS7 (RE = Gd-Yb; TM = Fe, Co, Ni), was obtained via flux crystal growth utilizing the boron chalcogen mixture (BCM) method. The series includes the first reported ytterbium-containing thiosilicates crystallizing in this structure type. The thiosilicates crystallize in the hexagonal crystal system in space group P63. The use of the BCM method to synthesize phase-pure samples of the title compounds for magnetic measurements is discussed, highlighting how the approach avoids some of the difficulties that plague typical chalcogenide syntheses. Magnetic measurements demonstrate that some of the compounds order antiferromagnetically and exhibit transition temperatures below 15 K.

PhyloMatcher: a tool for resolving conflicts in taxonomic nomenclature.

Summary: Large-scale comparative studies rely on the application of both phylogenetic trees and phenotypic data, both of which come from a variety of sources, but due to the changing nature of phylogenetic classification over time, many taxon names in comparative datasets do not match the nomenclature in phylogenetic trees. Manual curation of taxonomic synonyms in large comparative datasets can be daunting. To address this issue, we introduce PhyloMatcher, a tool which allows for programmatic querying of the National Center for Biotechnology Information Taxonomy and Global Biodiversity Information Facility databases to find associated synonyms with given target species names. Availability and implementation: PhyloMatcher is easily installed as a Python package with pip, or as a standalone GUI application. PhyloMatcher source code and documentation are freely available at https://github.com/Lswhiteh/PhyloMatcher, the GUI application can be downloaded from the Releases page.

Synthesis, Characterization, and Magnetic Properties of Uranium-Containing 2H-Perovskite-Related Sulfides: Ba3MUS6 (M = Mn, Fe, Co, Ni) and Ba3Co0.858(5)Mg0.142(5)US6.

The uranium-containing 2H-perovskite-related chalcogenide family of compounds was revisited using the recently developed boron-chalcogen mixture (BCM) method for actinides to aid in their syntheses and to obtain magnetic measurements. Two known 2H-perovskite-related structures, Ba3MnUS6 and Ba3FeUS6, were synthesized using the BCM method and were found to exhibit antiferromagnetic transitions at TN = ∼7.6 and 10.8 K, respectively. Combining the BCM method with the molten flux crystal growth technique resulted in single crystals of three new compositions, Ba3NiUS6, Ba3CoUS6, and Ba3Co0.858(5)Mg0.142(5)US6, the synthesis and characterization of which is reported. Magnetic measurements of Ba3NiUS6 revealed a complex magnetic susceptibility consisting of a weak, glassy, antiferromagnetic transition near 65 K followed by an antiferromagnetic transition at TN = ∼18 K. A reduced radius ratio plot for the existing chalcogenide compositions and new additions to this structure type reported herein is presented to aid in the search for additional 2H-perovskite-related sulfides.

Cryo-EM structure of a human LECT2 amyloid fibril reveals a network of polar ladders at its core.

ALECT2 systemic amyloidosis is associated with deposition of the leukocyte cell-derived chemotaxin-2 (LECT2) protein in the form of fibrils. In ALECT2 amyloidosis, ALECT2 fibrils deposit in the glomerulus, resulting in renal failure. Patients lack effective treatment options outside of renal transplant or dialysis. The structure of globular LECT2 has been determined but structures of ALECT2 amyloid fibrils remain unknown. Using single-particle cryo-EM, we find that recombinant human LECT2 forms robust twisting fibrils with canonical amyloid features. ALECT2 fibrils contain two mating protofilaments spanning residues 55-75 of the LECT2 sequence. The geometry of the ALECT2 fibril displays features in line with other pathogenic amyloids. Its core is tightly packed and stabilized by both hydrophobic contacts and hydrogen-bonded uncharged polar residues. The robustness of ALECT2 fibril cores is illustrated by their resistance to denaturants and proteases. This ALECT2 fibril structure presents a potential new target for treatments against ALECT2 systemic amyloidosis.

Mental health problems associated with idiopathic anaphylaxis.

BACKGROUND: Idiopathic Anaphylaxis (IA) is the most common anaphylactic syndrome in adults. Mental health problems associated with IA are not well recognised. We aimed to assess if patients diagnosed with IA were more likely to experience mental health problems compared to a normative Australian population. We additionally hypothesised that the number of anaphylactic episodes would correlate with symptoms of anxiety. METHODS: A total of 34 patients with at least one episode of IA were recruited from an adult immunology clinic. Patients were recruited as part of a separate study evaluating alternative aetiologies in IA. Mental health problems were measured using the Depression, Anxiety and Stress Scale (DASS-21). An extension of the survey included questions specifically focused on the psychological impact of IA. RESULTS: Compared to population norms, those with IA had significantly higher levels of mental health problems. Statistically significant DASS-21 scores were identified for depression 4.24 vs. 2.57 (p < 0.001), anxiety 4.76 vs. 1.74 (p < 0.012), stress 7.35 vs. 3.95 (p < 0.001) and total score 16.35 vs. 8.00 (p < 0.001). There was no association between two or more episodes of anaphylaxis and increased anxiety levels (ß = 0.52, CI -2.59-3.62, p = 0.74). CONCLUSIONS: This is the first paper to demonstrate that patients living with idiopathic anaphylaxis are more symptomatic for mental illness than those in the community. Screening for mental illness and referral for psychological support should be undertaken in people with IA.

PhyloMatcher: a tool for resolving conflicts in taxonomic nomenclature.

Summary: Large-scale comparative studies rely on the application of both phylogenetic trees and phenotypic data, both of which come from a variety of sources, but due to the changing nature of phylogenetic classification over time, many taxon names in comparative datasets do not match the nomenclature in phylogenetic trees. Manual curation of taxonomic synonyms in large comparative datasets can be daunting. To address this issue, we introduce PhyloMatcher, a tool which allows for programmatic querying of two commonly used taxonomic databases to find associated synonyms with given target species names. Availability and implementation: PhyloMatcher is easily installed as a Python package with pip, or as a standalone GUI application. PhyloMatcher source code and documentation are freely available at https://github.com/Lswhiteh/PhyloMatcher, the GUI application can be downloaded from the Releases page. Contact: Lswhiteh@unc.edu. Supplemental Information: We provide documentation for PhyloMatcher, including walkthrough instructions for the GUI application on the Releases page of https://github.com/Lswhiteh/PhyloMatcher.

Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV.

While the protective role of neutrophil extracellular traps (NETs) in limiting human immunodeficiency virus (HIV) spread to susceptible cells has been documented, there is comparatively little insight into whether NET formation is harmful in people living with HIV (PLWH). To gain insight into neutrophil dysregulation and the pathological role of NETs in HIV, we examined expressions of NET-associated markers [cell-free DNA (cfDNA) and citrullinated histone H3 (CitH3)] in the plasmas from a cohort of the Hawaii Aging with HIV-cardiovascular and HIV-seronegative (HIV-) individuals. In a subset of participants, circulating low-density granulocyte (LDG) levels and their maturation and activation status were analyzed via flow cytometry. We demonstrated higher plasma levels of CitH3 in PLWH compared to HIV- individuals. LDGs from PLWH had heightened CD66b, but reduced CD16 expression. The percentages and counts of CD10+ LDGs were significantly decreased in PLWH. In addition, the CD16Lo LDG subsets were enriched in PLWH, compared to HIV- group, indicating that immature LDGs are increased in PLWH. Moreover, LDGs from PLWH exhibited significantly higher NET forming capacity. In summary, our study presents evidence that LDGs from PLWH on ART display an immature and altered phenotype with increased NET formation. Among PLWH, plasma NET levels as well as LDG parameters correlated with blood markers for inflammation and coagulation, suggesting that neutrophil activation and NETs may exert proinflammatory and coagulation effects. Our data provide insights into the pathologic role of LDGs at least in part mediated through NET formation in PLWH.

Single-cell RNA sequencing reveals characteristics of myeloid cells in pulmonary post-acute sequelae of SARS-CoV-2.

Background: Although our understanding of the immunopathology and subsequent risk and severity of COVID-19 disease is evolving, a detailed account of immune responses that contribute to the long-term consequences of pulmonary complication in COVID-19 infection remain unclear. Few studies have detailed the immune and cytokine profiles associated with post-acute sequalae of SARS-CoV-2 infection with persistent pulmonary symptoms (PPASC). However, the dysregulation of the immune system that drives pulmonary sequelae in COVID-19 survivors and PASC sufferers remains largely unknown. Results: To characterize the immunological features of pulmonary PASC (PPASC), we performed droplet-based single-cell RNA sequencing to study the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from participants naïve to SARS-CoV-2 (Control) and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC). We analyzed more than 34,139 PBMCs by integrating our dataset with previously reported control datasets (GSM4509024) cell distribution. In total, 11 distinct cell populations were identified based on the expression of canonical markers. The proportion of myeloid-lineage cells ([MLCs]; CD14 + /CD16 + monocytes and dendritic cells) was increased in PPASC compared to controls. MLCs from PPASC displayed up-regulation of genes associated with pulmonary symptoms/fibrosis, while glycolysis metabolism-related genes were downregulated. Similarly, pathway analysis showed that fibrosis- related ( VEGF , WNT , and SMAD ) and cell death pathways were up-regulated, but immune pathways were down-regulated in PPASC. In PPASC, we observed interactive VEGF ligand- receptor pairs among MLCs, and network modules in CD14 + (cluster 4) and CD16 + (Cluster 5) monocytes displayed a significant enrichment for biological pathways linked to adverse COVID- 19 outcomes, fibrosis, and angiogenesis. Further analysis revealed a distinct metabolic alteration in MLCs with a down-regulation of glycolysis/gluconeogenesis in PPASC compared to SARS- CoV-2 naïve samples. Conclusion: This study offers valuable insights into the immune response and cellular landscape in PPASC. The presence of elevated MLC levels and their corresponding gene signatures associated with fibrosis, immune response suppression, and altered metabolic states suggests their potential role as a driver of PPASC.

Oncostatin M is a Master Regulator of an Inflammatory Network in Dnmt3a -Mutant Hematopoietic Stem Cells.

Age-associated clonal hematopoiesis (CH) occurs due to somatic mutations accrued in hematopoietic stem cells (HSCs) that confer a selective advantage in the context of aging. The mechanisms by which CH-mutant HSCs gain this advantage with aging are not comprehensively understood. Using unbiased transcriptomic approaches, we identify Oncostatin M (OSM) signaling as a candidate contributor to aging-driven Dnmt3a -mutant CH. We find that Dnmt3a -mutant HSCs from young mice do not functionally respond to acute OSM stimulation with respect to proliferation, apoptosis, hematopoietic engraftment, or myeloid differentiation. However, young Dnmt3a -mutant HSCs transcriptionally upregulate an inflammatory cytokine network in response to acute OSM stimulation including genes encoding IL-6, IL-1ß and TNFα. In addition, OSM-stimulated Dnmt3a -mutant HSCs upregulate the anti-inflammatory genes Socs3, Atf3 and Nr4a1 , creating a negative feedback loop limiting sustained activation of the inflammatory network. In the context of an aged bone marrow (BM) microenvironment with chronically elevated levels of OSM, Dnmt3a -mutant HSCs upregulate pro-inflammatory genes but do not upregulate Socs3, Atf3 and Nr4a1 . Together, our work suggests that chronic inflammation with aging exhausts the regulatory mechanisms in young CH-mutant HSCs that resolve inflammatory states, and that OSM is a master regulator of an inflammatory network that contributes to age-associated CH.

Population-level variation in insecticide tolerance across three life stages of the trematode Echinostoma trivolvis.

Ecotoxicological studies using single test populations may miss the inherent variation of natural systems and limit our understanding of how contaminants affect focal species. Though population-level variation in pesticide tolerance is commonly observed in host taxa, few studies have assessed population-level differences in the tolerance of parasites to different contaminants. We investigated population-level variation in insecticide tolerance of three Echinostoma trivolvis life stages (egg, miracidium, and cercaria) to three insecticides (carbaryl, chlorpyrifos, and diazinon). We tested two relevant metrics of insecticide tolerance-baseline and induced-across up to eight different parasite populations per life stage. Across all life stages, the insecticide treatments tended to reduce survival, but the magnitude of their effects often varied significantly among populations. Surprisingly, we found that exposure to chlorpyrifos increased the hatching success of echinostome eggs relative to the control treatment in three of six tested populations. We also found that cercariae shed from snails previously exposed to a sublethal concentration of chlorpyrifos had a significantly lower mortality rate when subsequently exposed to a lethal concentration of chlorpyrifos relative to individuals from snails that were not previously exposed; this suggests inducible tolerance in cercariae. We found no evidence that insecticide tolerance is correlated across parasite life stages within a population. Together the findings of our study demonstrate that single-population toxicity assays may greatly over- or underestimate the effects of pesticides on the survival of free-living parasite stages, insecticide tolerance levels may not be predictable from one parasite life stage to the next, and insecticides can have both expected and counterintuitive effects on non-target taxa.