Intergenerational toxicity of 17α-ethinylestradiol (EE2): Effects of parental exposure on early larval development and transcriptomic profiles in the Sydney rock oyster, Saccostrea glomerata.

This study exposed adult Sydney rock oysters, of either sex or both, to the synthetic estrogen 17α-ethinylestradiol (EE2) at 50 ng/L for 21 days, followed by an examination of developmental endpoints and transcriptomic responses in unexposed larvae. Reduced survival was observed at 1 day post-fertilisation (dpf) in larvae from bi-parental exposure (FTMT). Motile larvae at 2 dpf were fewer from maternal (FTMC), paternal (FCMT), and FTMT exposures. Additionally, shell length at 7 dpf decreased in larvae from FTMC and FTMT parents. RNA sequencing (RNA-seq) revealed 1064 differentially expressed genes (DEGs) in 1-dpf larvae from FTMT parents, while fewer DEGs were detected in larvae from FTMC and FCMT parents, with 258 and 7, respectively. GO and KEGG analyses showed significant enrichment of DEGs in diverse terms and pathways, with limited overlap among treatment groups. IPA results indicated potential inhibition of pathways regulating energy production, larval development, transcription, and detoxification of reactive oxygen species in FTMT larvae. qRT-PCR validation confirmed significant downregulation of selected DEGs involved in these pathways and relevant biological processes, as identified in the RNA-seq dataset. Overall, our results suggest that the intergenerational toxicity of EE2 is primarily maternally transmitted, with bi-parental exposure amplifying these effects.

Peri-surgical imaging of intersex and gender diverse youths.

This publication provides an overview of current imaging indications and practices for patients undergoing gender-affirming surgery, with an emphasis on the importance of tailored, patient-specific care. Gender-affirming surgeries are performed with personalized approaches at various stages of life for those with intersex traits or differences in sex development (I/DSD) and transgender and gender diverse (TGD) individuals. For I/DSD patients, ultrasound, genitography, or MRI occurs during infancy and puberty to evaluate genital and gonadal anatomy. Facial harmonization involves bony and soft tissue modifications, guided by maxillofacial computerized tomography (CT) with three-dimensional reconstruction. Ultrasound is the main modality in assessing hormone-related and post-surgical changes in the chest. Imaging for genital reconstruction uses cross-sectional images and fluoroscopy to assess neoanatomy and complications.

Fertility preservation in transfeminine adolescents using TESE at the time of Histrelin Acetate subcutaneous implant placement: A Case Series.

BACKGROUND: Fertility preservation (FP) is an important aspect of the care of transgender patients in whom Gender Affirming Medical Treatment (GAT) may begin before puberty is completed. While there are overall few studies that can be used to guide conversations about long-term effects of GAT, there are concerns that GAT could negatively impact fertility. Prior studies have shown low utilization of FP in this population, with avoidance of delay in starting GAT cited as one of the most common reasons for foregoing FP. It is possible that strategies to mitigate delay in commencement of GAT can facilitate higher FP utilization, maintaining options for future family building. OBJECTIVE: To describe our institution's experience with Testicular Sperm Extraction (TESE) for FP and Histrelin Acetate (Supprelin) Subcutaneous Implantation for GAT commencement. STUDY DESIGN: A retrospective review of transfeminine adolescents at our institution from 2010 to 2022 who underwent TESE for FP at the time of Supprelin placement for GAT (FP/SP). Outcomes of interest included successful sperm retrieval, age at first visit to our institution's Transgender Multispecialty Service Health clinic (GeMS), age at time of FP/SP, testicular volume, and Tanner stage at time of FP/SP, and age when GnRH agonist (GnRHa) therapy was prescribed. Testosterone, LH, FSH, and Inhibin B values prior to combination FP/SP were also obtained. RESULTS: Ten patients from 2017 to 2022 underwent FP/SP after prescription of GnRHa based on Endocrine Society Guidelines. Successful sperm retrieval and storage was achieved in all patients. Median age at FP/SP was fourteen years 5.5 months (range 12y5m-16y8m). Median time from GnRHa prescription to FP/SP was two months (range 2-5 m). Mean testicular volume at time of FP/SP was 13.2 cc (SD 3.38 cc, range 8-17 cc), and median Tanner Stage was IV (range III-V). Average testosterone level was 301.60 (SD 173.04), LH 3.00 (SD 1.25), FSH 3.33 (SD 1.71), Inhibin B 208.50 (SD 87.44). CONCLUSIONS: Performing TESE for FP is feasible for transgender youth undergoing Histrelin implant placement, leading to short delays in starting GAT. Testicular volume and endocrine markers can provide preoperative insight into likelihood of successful sperm retrieval during TESE, are needed to identify which patients will have successful sperm retrieval to ensure optimal counseling and informed decision making for providers, patients and families.

Applying Shear Wave and Magnetic Resonance Elastography to Grade Brain Tumors: Systematic Review and Meta-Analysis.

BACKGROUND: Reports find that magnetic resonance elastography (MRE) and shear wave elastography (SWE) can classify intracranial tumors according to stiffness. However, systematic syntheses of these articles are lacking. In this report, a systematic review and meta-analysis was performed to evaluate whether SWE and MRE can predict meningioma and glioma grades. METHODS: PubMed and Scopus were searched between February 10, 2022. and March 2, 2022. using manual search criteria. Eight out of 106 non-duplicate records were included, encompassing 84 patients with low-grade tumors (age 42 ± 13 years, 71% female) and 92 patients with high-grade tumors (age 50 ± 13 years, 42% female). Standardized mean difference in stiffness between high-grade and low-grade tumors were measured using a forest plot. The I2, χ2, and t tests were performed, and bubble plots were constructed to measure heterogeneity. An adapted QUADAS-2 scale evaluated study quality. Additionally, a funnel plot was constructed, and an Egger's intercept test determined study bias. RESULTS: Low-grade tumors were stiffer than high-grade tumors (Cohen's D = -1.25; 95% CI -1.88, -0.62). Moderate heterogeneity was observed (I2 = 67%; P = 0.006) but controlling for publication year (I2 = 0.2%) and age (I2 = 0.0%-17%) reduced heterogeneity. Included studies revealed unclear or high bias for the reference standard and flow and timing (>50%). CONCLUSIONS: Elastography techniques have potential to grade tumors intraoperatively and postoperatively. More studies are needed to evaluate the clinical utility of these technologies.

Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC/BPS. One family has a previously reported SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier-White disease. Two private heterozygous variants are identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (likely pathogenic)), indicative of Hailey-Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare ATP2C1 variants in the IC/BPS cases versus a control cohort (p = 0.03, OR = 6.76), though does not survive Bonferroni correction. The data suggest that some individuals with IC/BPS may have unrecognized Mendelian syndromes. Comprehensive phenotyping and genotyping aid in understanding the range of diagnoses in the population-based IC/BPS cohort. Conversely, ATP2C1, ATP2A2, and SIX5 may be candidate genes for IC/BPS. Further evaluation with larger numbers is needed. Genetically screening individuals with IC/BPS may help diagnose and treat this painful disorder due to its heterogeneous nature.

Offspring of metal contaminated saltmarsh (Juncus acutus) exhibit tolerance to the essential metal Zn but not the nonessential metal Pb.

Halophytes residing in metal-contaminated saltmarsh habitats may employ strategies to enhance fitness of the next generation. We aimed to test the hypothesis that Juncus acutus individuals inhabiting metal-contaminated locations would experience elevated tolerance of offspring to metals compared to plants residing in locations with no metal contamination history. J. acutus seeds (F1 generation) were collected from F0 parent plants residing at eight locations of a contemporary sediment metal gradient (contaminated to uncontaminated) across the coast of NSW, Australia (Hunter river, Lake Macquarie and Georges River). Seeds were exposed in the laboratory to incremental Zn (0.0-1.6 mM) and Pb (0.0-0.50 mM) for nine (9) days, and % germination, germination rate, root elongation and vigour index were assessed for the determination of tolerance. Greater root accumulation (BCF = 1.01) of Zn and subsequent translocation to aerial parts (culm BCF = 0.58 and capsule BCF = 0.85) were exhibited in parents plants, whereas Pb was excluded from roots (BCF = 0.60) and very little translocation to aerial portions of the plant was observed (culm BCF = 0.02 and capsule BCF = 0.05). F1 offspring exhibited tolerance to Zn with EC50 (% germination) significantly correlated with their parents' culm (R2 = 0.93, p = 0.00) and capsule (R2 = 0.57; p = 0.03) Zn. No correlations were observed between offspring Pb tolerance and Pb in parents' plant tissues. Enhanced tolerance to the essential metal Zn may be because Zn is very mobile in the parent plant and seeds experience greater Zn load as a significant portion of sediment Zn reaches capsules (85%). Thus, Zn tolerance in J. acutus seeds is likely attributable to acclimation via maternal transfer of Zn; however, further manipulative experiments are required to disentangle potential acclimation, adaptation or epigenetic effects in explaining the tolerance observed.

Serum Cholesterol Efflux Capacity in Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

Purpose: To investigate serum cholesterol efflux capacity (the ability of the serum to accept cholesterol) and factors that regulate it using nuclear magnetic resonance-quantified measures of lipoprotein particle composition and size and apolipoproteins metrics in patients with age-related macular degeneration (AMD). Design: Case-control study. Participants: Four hundred two serum samples from 80 patients with early AMD (eAMD), and 212 patients with neovascular AMD (nAMD), including 80 with typical nAMD (tAMD) and 132 with polypoidal choroidal vasculopathy (PCV), and 110 age- and gender matched control participants. Methods: Serum from participants showed cholesterol efflux capacity measured using in vitro cell assays and lipoprotein subfractions measured using nuclear magnetic resonance (Nightingale, Ltd). Associations between cholesterol efflux capacity (measured in percentage) and lipid subfractions were investigated in the patients and control participants. Main Outcome Measures: Cholesterol efflux capacity and lipid subfractions in control, eAMD, and nAMD. Associations between HDL subfractions and cholesterol efflux capacity. Results: Cholesterol efflux capacity was higher in patients with eAMD (68.0 ± 11.3% [mean ± standard deviation]) and nAMD (75.9 ± 27.7%) than in the control participants (56.9 ± 16.7%) after adjusting for age, gender, and use of lipid-lowering drug (P < 0.0001). Nuclear magnetic resonance lipidomics demonstrated that the mean diameter of HDL was larger both in eAMD (9.96 ± 0.27 mm [mean ± standard deviation]) and PCV (9.97 ± 0.23 mm) compared with that of the control participants (9.84 ± 0.24 mm; P = 0.0001 for both). Among the 28 HDL subfractions, most of the small, medium, and large HDLs, but none of the 7 extra large HDLs fractions, were associated moderately with cholesterol efflux capacity in eAMD and PCV (R = 0.149-0.277). Conclusions: Serum cholesterol efflux capacity was increased in eAMD and PCV, but not tAMD, possibly reflecting differential underlying pathophysiologic features of lipid dysregulation in tAMD and PCV. Further studies should be directed toward investigating the diverse biological activities of HDL in AMD, including macular pigment transport, regulation of inflammation, and local cholesterol transport system.

HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid.

High-temperature requirement A1 (HtrA1) has been identified as a disease-susceptibility gene for age-related macular degeneration (AMD) including polypoidal choroidal neovasculopathy (PCV). We characterized the underlying phenotypic changes of transgenic (Tg) mice expressing ubiquitous CAG promoter (CAG-HtrA1 Tg). In vivo imaging modalities and histopathology were performed to investigate the possible neovascularization, drusen formation, and infiltration of macrophages. Subretinal white material deposition and scattered white-yellowish retinal foci were detected on CFP [(Tg­33% (20/60) and wild-type (WT)­7% (1/15), p < 0.05]. In 40% (4/10) of the CAG-HtrA1 Tg retina, ICGA showed punctate hyperfluorescent spots. There was no leakage on FFA and OCTA failed to confirm vascular flow signals from the subretinal materials. Increased macrophages and RPE cell migrations were noted from histopathological sections. Monocyte subpopulations were increased in peripheral blood in the CAG-HtrA1 Tg mice (p < 0.05). Laser induced CNV in the CAG-HtrA1 Tg mice and showed increased leakage from CNV compared to WT mice (p < 0.05). Finally, choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p < 0.05). Signs of subclinical inflammation was observed in CAG-HtrA1 Tg mice. Such subclinical inflammation may have resulted in increased RPE cell activation and angiogenic potential.

In Vitro Growth Inhibition, Caspase-Dependent Apoptosis, and S and G2/M Phase Arrest in Breast Cancer Cells Induced by Fluorine-Incorporated Gold I Compound, Ph3PAu[SC(OMe)=NC6H4F-3].

Gold-based anticancer compounds have been attracting increasing research interest due to their ability to kill cancer cells resistant to platinum-based compounds. Gold I- and gold III-based complexes have shown satisfactory anticancer activities. In this study, two new fluorine-incorporated gold (I) compounds such as Ph3PAu[SC(OMe)=NC6H4F-3] and DPPFeAu2[(SC(OMe)=NC6H4F-3)]2 were evaluated for their in vitro activities against human breast cancer cell lines, primary breast cancer cells, and breast cancer stem cells (parental breast cancer stem cells, BCSC-P, and breast cancer stem cells, BCSC). Assays for growth inhibition and cytotoxicity, including real-time cell analysis, were carried out to screen effective antibreast cancer compounds. In addition, further in vitro assays such as apoptosis, caspase 3/7 activity, and cell cycle analysis were performed to observe the action and mechanism of killing breast cancer cells by the selected gold I compound, Ph3PAu[SC(OMe)=NC6H4F-3]. The gold (I) compound, Ph3PAu[SC(OMe)=NC6H4F-3], showed low toxicity to H9c2 normal cells and significant growth inhibition in MDA-MB-231 and MCF-7 cells, primary breast cancer cells, and breast cancer stem cells (BCSC-P and BCSC). The IC50 doses of the gold (I) compound Ph3PAu[SC(OMe)=NC6H4F-3] against the breast cancer cell lines MDA-MB-231 and MCF-7 were approximately 6-fold lower than that of cisplatin (cis-diamineplatinum (II) dichloride, CDDP). Moreover, the compound Ph3PAu[SC(OMe)=NC6H4F-3] induced caspase 3/7-dependent apoptosis and cell cycle arrest at S and G2/M phases. Ph3PAu[SC(OMe)=NC6H4F-3], a gold (I) compound incorporated with fluorine, is a potential candidate for the treatment of breast cancer.

Cell-to-cell transmission of HIV-1 from provirus-activated cells to resting naïve and memory human primary CD4 T cells is highly efficient and requires CD4 and F-actin but not chemokine receptors.

Latently infected cells harboring replication-competent proviruses represent a major barrier to HIV-1 cure. One major effort to purge these cells has focused on developing the "shock and kill" approach for forcing provirus reactivation to induce cell killing by viral cytopathic effects, host immune responses, or both. We conducted kinetic and mechanistic studies of HIV-1 protein expression, virion production, and cell-to-cell virus transmission during provirus reactivation. Provirus-activated ACH-2 cells stimulated with romidepsin (RMD) or PMA produced Nef early, and then Env and Gag in parallel with the appearance of virions. Env on the surface of provirus-activated cells and cellular F-actin were critical in the formation of virological synapses to mediate cell-to-cell transmission of HIV-1 from provirus-activated cells to uninfected cells. This HIV-1 cell-to-cell transmission was substantially more efficient than transmission seen via cell-free virus spread and required F-actin remodeling and CD4, but not chemokine receptors. Resting human primary CD4+ T cells including naïve and memory subpopulations and, especially the memory CD4+ T cells, were highly susceptible to HIV-1 infection via cell-to-cell transmission. Cell-to-cell transmission of HIV-1 from provirus-activated cells was profoundly decreased by protease inhibitors (PIs) and neutralizing antibodies (nAbs) that recognize the CD4-binding site (CD4bs) such as VRC01, but not by reverse transcriptase (RT) inhibitor Emtricitabine (FTC). Therefore, our results suggest that PIs with potent blocking abilities should be used in clinical application of the "shock and kill" approach, most likely in combination with CD4bs nAbs, to prevent new HIV-1 infections.

Clinical outcomes in pediatric hydrocephalus patients treated with endoscopic third ventriculostomy and choroid plexus cauterization: a systematic review and meta-analysis.

OBJECTIVE: Endoscopic third ventriculostomy and choroid plexus cauterization (ETV+CPC) is a novel procedure for infant hydrocephalus that was developed in sub-Saharan Africa to mitigate the risks associated with permanent implanted shunt hardware. This study summarizes the hydrocephalus literature surrounding the ETV+CPC intraoperative abandonment rate, perioperative mortality rate, cerebrospinal fluid infection rate, and failure rate. METHODS: This systematic review and meta-analysis followed a prespecified protocol and abides by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy using MEDLINE, EMBASE, PsychInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science was conducted from database inception to October 2019. Studies included controlled trials, cohort studies, and case-control studies of patients with hydrocephalus younger than 18 years of age treated with ETV+CPC. Pooled estimates were calculated using DerSimonian and Laird random-effects modeling, and the significance of subgroup analyses was tested using meta-regression. The quality of the pooled outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: After screening and reviewing 12,321 citations, the authors found 16 articles that met the inclusion criteria. The pooled estimate for the ETV+CPC failure rate was 0.44 (95% CI 0.37-0.51). Subgroup analysis by geographic income level showed statistical significance (p < 0.01), with lower-middle-income countries having a lower failure rate (0.32, 95% CI 0.28-0.36) than high-income countries (0.53, 95% CI 0.47-0.60). No difference in failure rate was found between hydrocephalus etiology (p = 0.09) or definition of failure (p = 0.24). The pooled estimate for perioperative mortality rate (n = 7 studies) was 0.001 (95% CI 0.00-0.004), the intraoperative abandonment rate (n = 5 studies) was 0.04 (95% CI 0.01-0.08), and the postoperative CSF infection rate (n = 5 studies) was 0.0004 (95% CI 0.00-0.003). All pooled outcomes were found to be low-quality evidence. CONCLUSIONS: This systematic review and meta-analysis provides the most comprehensive pooled estimate for the ETV+CPC failure rate to date and demonstrates, for the first time, a statistically significant difference in failure rate by geographic income level. It also provides the first reported pooled estimates for the risk of ETV+CPC perioperative mortality, intraoperative abandonment, and CSF infection. The low quality of this evidence highlights the need for further research to improve the understanding of these critical clinical outcomes and their relevant explanatory variables and thus to appreciate which patients may benefit most from an ETV+CPC. Systematic review registration no.: CRD42020160149 (https://www.crd.york.ac.uk/prospero/).

Microplastics act as a carrier for wastewater-borne pathogenic bacteria in sewage.

Microplastic pollution, a pressing global environmental problem, has a severe impact on both aquatic ecosystems and public health worldwide. Due to the small size of microplastics, they are able to pass through the filtration systems of municipal wastewater treatment works (WWTWs). In recent years, studies have focused on the environmental abundance and ecotoxicological effects of microplastics, but there are limited studies investigating the colonization of microplastics by bacteria, especially those pathogenic ones. In this study, we examined the colonization and composition of the bacterial communities on polyethylene microbeads after incubation in raw sewage collected from three municipal WWTWs in Hong Kong (Sha Tin Sewage Treatment Works, Stonecutters Island Sewage Treatment Works, and Shek Wu Hui Sewage Treatment Works). Scanning electron microscopy (SEM) results indicate that bacterial cells were colonized on the surfaces of the microbeads and formed biofilms after sewage incubation. Metagenomic sequencing data demonstrated an increase in bacterial diversity after 21 days of sewage incubation when compared to shorter incubation periods of 6, 11 and 16 days. Importantly, human and fish pathogens such as Arcobacter cryaerophilus, Aeromonas salmonicida, Vibrio areninigrae and Vibrio navarrensis were found in the resident bacterial communities. Taken together, our results demonstrate that microplastics could act as a carrier for wastewater-borne pathogenic bacteria in municipal sewage.

Vaginectomy in Transmasculine Patients: A Review of Techniques in an Emerging Field.

PURPOSE: This report reviews the various techniques for vaginal obliterative surgery in the transmasculine patient population, including advantages and drawbacks with differing methods and reflects on the focus of future research and surgical efforts. FINDINGS: Existing techniques for vaginal obliterative surgery by vaginectomy or colpocleisis vary without strong evidence to identify a superior approach. SUMMARY: The increasing number of transmasculine patients seeking vaginectomy as a part of gender-affirming surgery must be matched by evidence-based techniques that provide a safe, long-term outcome.

Soluble Immune Checkpoints Are Dysregulated in COVID-19 and Heavy Alcohol Users With HIV Infection.

Immune checkpoints (ICPs) consist of paired receptor-ligand molecules that exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance. ICPs exist in both membrane and soluble forms in vivo and in vitro. Imbalances between inhibitory and stimulatory membrane-bound ICPs (mICPs) in malignant cells and immune cells in the tumor immune microenvironment (TIME) have been well documented. Blockades of inhibitory mICPs have emerged as an immense breakthrough in cancer therapeutics. However, the origin, structure, production regulation, and biological significance of soluble ICPs (sICPs) in health and disease largely remains elusive. Soluble ICPs can be generated through either alternative mRNA splicing and secretion or protease-mediated shedding from mICPs. Since sICPs are found in the bloodstream, they likely form a circulating immune regulatory system. In fact, there is increasing evidence that sICPs exhibit biological functions including (1) regulation of antibacterial immunity, (2) interaction with their mICP compartments to positively or negatively regulate immune responses, and (3) competition with their mICP compartments for binding to the ICP blocking antibodies, thereby reducing the efficacy of ICP blockade therapies. Here, we summarize current data of sICPs in cancer and infectious diseases. We particularly focus on sICPs in COVID-19 and HIV infection as they are the two ongoing global pandemics and have created the world's most serious public health challenges. A "storm" of sICPs occurs in the peripheral circulation of COVID-19 patients and is associated with the severity of COVID-19. Similarly, sICPs are highly dysregulated in people living with HIV (PLHIV) and some sICPs remain dysregulated in PLHIV on antiretroviral therapy (ART), indicating these sICPs may serve as biomarkers of incomplete immune reconstitution in PLHIV on ART. We reveal that HIV infection in the setting of alcohol misuse exacerbates sICP dysregulation as PLHIV with heavy alcohol consumption have significantly elevated plasma levels of many sICPs. Thus, both stimulatory and inhibitory sICPs are present in the bloodstream of healthy people and their balance can be disrupted under pathophysiological conditions such as cancer, COVID-19, HIV infection, and alcohol misuse. There is an urgent need to study the role of sICPs in immune regulation in health and disease.

Presence of Autoantibodies in Males and Females With Rheumatoid Arthritis: A Systematic Review and Metaanalysis.

OBJECTIVE: Rheumatoid arthritis (RA) is more common in females, and although the cause of RA is unknown, it is characterized by the production of autoantibodies. The aims of this study were to determine whether RA-associated autoantibodies are more often found in females than males and to identify factors that influence the relationship between sex and seropositivity. METHODS: Databases were searched and studies of RA (N ≥ 100) were included if they reported proportion of seropositive patients with RA by sex. Metaanalyses and metaregression were conducted using the random-effects model. Covariates regressed were smoking, age, BMI, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Disease Activity Score in 28 joints (DAS28). RESULTS: Eighty-four studies with a total of 141,381 subjects with rheumatoid factor (RF) seropositivity and 95,749 subjects with anticitrullinated protein antibody (ACPA) seropositivity met inclusion criteria. The mean age of participants ranged from 37 to 68 years and the proportion of female subjects ranged from 9% to 92%. Results indicated that females were less likely than males to be seropositive: odds ratio (OR) 0.84 [95% CI 0.77-0.91] for RF and OR 0.88 [95% CI 0.81-0.95] for ACPA. BMI, smoking, mean age, DAS28, and HAQ-DI did not affect the relationship between sex and seropositivity. CONCLUSION: Although studies report that females have higher RA disease activity than males and that seropositivity predicts worse outcomes, females were less likely to be seropositive than males.

Prostatic metaplasia of the vagina in transmasculine individuals.

PURPOSE: To determine the prevalence of prostatic metaplasia in an expanded cohort of transmasculine individuals undergoing gender-affirming resection of vaginal tissue. METHODS: Institutional Review Board approval was obtained. Clinical records were reviewed for all transmasculine individuals undergoing vaginal tissue resection at our institution between January 2018 and July 2021. Corresponding pathology specimens were examined grossly and microscopically, including immunohistochemical stains for NKX3.1, prostate-specific antigen (PSA), and androgen receptor (AR). Vaginal specimens from three patients without androgen supplementation were used as controls. RESULTS: Twenty-one patients met inclusion criteria. The median age at surgery was 26.4 years (range 20.6-34.5 years). All patients had been assigned female gender at birth and lacked endocrine or genetic abnormalities. All were on testosterone therapy; median duration of therapy at surgery was 4.4 years (range 1.4-12.1 years). In the transmasculine group, no gross lesions were identified. Microscopically, all specimens demonstrated patchy intraepithelial glandular proliferation along the basement membrane and/or nodular proliferation of prostate-type tissue within the subepithelial stroma. On immunohistochemical staining, performed for a subset of cases, the glandular proliferation was positive for NKX3.1 (16/16 cases; 100%), PSA (12/14 cases; 85.7%), and AR (8/8 cases; 100%). Controls showed no evidence of prostatic metaplasia. CONCLUSION: One hundred percent of vaginal specimens obtained from transmasculine individuals on testosterone therapy (21/21 cases) demonstrated prostatic metaplasia. Further investigation is warranted to characterize the natural history and clinical significance of these changes. Patients seeking hormone therapy and/or gender-affirming surgery should be counseled on the findings and their yet-undetermined significance.

The accumulation and distribution of arsenic species and selected metals in the saltmarsh halophyte, spiny rush (Juncus acutus).

This study examined the accumulation of As species, Se, Cu, Zn, Cd and Pb in the halophyte Juncus acutus, collected from three anthropogenically impacted estuaries in NSW, Australia. As concentration ranged from 4 to 22 µg/g at Georges River, 2-16 µg/g at Lake Macquarie and 6 µg/g at Hunter Estuary. Inorganic As was accumulated mainly in roots with low translocation to culm with a greater abundance of AsV. However, AsIII (TF = 0.32) showed greater mobility from the roots to shoots than AsV (TF = 0.04), indicating a higher quantity of AsIII specific transporter assemblages in the plasmalemma of the endodermis or cytoplasmic reduction of AsV to AsIII in culms. Metal(loid)s, including As (90%), were predominantly in root tissues and very limited translocation to culm, indicating the species is a useful phytostabiliser. As and all other metal(loid)s in roots were correlated with sediment loads (p < 0.05, R2 = 0.10-0.52), indicating the species would be an accumulative bioindicator.

The radiologist's role in assessing differences of sex development.

When infants are identified with a difference of sex development (DSD), a thoughtful approach to imaging is essential to appropriate clinical management. This review provides a comprehensive guide for radiologists who are tasked with performing this critical assignment. We review the embryologic basis of DSDs, with attention to the imaging findings that can indicate specific diagnoses. We also discuss techniques for optimal imaging, including strategies for identifying the gonads by US, tactics for performing genitograms with fluoroscopy and contrast-enhanced US, and the appropriate utilization of MRI. Finally, we review the clinical data and imaging findings that characterize some of the most common DSDs, including congenital adrenal hyperplasia, complete androgen insensitivity syndrome and gonadal dysgenesis.