Presentation and outcomes of thoracic and thoracoabdominal aortic aneurysms in females, existing gaps, and future directions: A descriptive review.

Thoracic and thoracoabdominal aortic aneurysms are more common in men. Yet, females often have worse outcomes, fewer interventions, and lower treatment rates. Females have also benefited less from the research and treatment of those diseases than men. Understanding sex- and sex-specific differences in thoracic and thoracoabdominal aortic aneurysms can improve care delivery, reduce disparities, and optimize outcomes for females with thoracic aortic aneurysms and thoracoabdominal aortic aneurysms. The authors reviewed the literature on the presentation and outcomes of thoracic and thoracoabdominal aortic aneurysms in females, discussing the existing gaps and future directions to address them.

Pubertal progression in relation to peripubertal exposure to organochlorine chemicals in a cohort of Russian boys.

Background: Peripubertal concentrations of serum dioxins and polychlorinated biphenyls (PCBs) have demonstrated associations with altered age of pubertal onset and sexual maturity in boys, but associations with pubertal progression have received less attention. Methods: The Russian Children's Study is a prospective cohort of 516 boys enrolled in 2003-2005 at age 8 or 9 and followed annually up to 19 years of age. Serum concentrations of dioxin-like toxic equivalents (TEQs), polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and non-dioxin-like PCBs (NDL-PCBs) and whole blood lead levels (BLLs) were quantified from blood samples collected at study entry (age 8-9). Testicular volume (TV) was assessed annually using a Prader orchidometer. Pubertal trajectories were identified by applying Group-Based Trajectory Models (GBTMs) to TV measured from ages 8-19. Associations of peripubertal serum TEQs, PCDDs, PCDFs, and NDL-PCBs with specific progression trajectories were modeled using multinomial logistic regression, adjusting for each boy's birthweight, and for BLL, body mass index and nutritional factors at study entry. Results: Among 489 eligible boys with available exposure measures, we identified three pubertal trajectories using GBTMs: slower (34% of boys), moderate (48%) and faster (18%). Boys with higher peripubertal serum TEQs had higher adjusted odds of being in the moderate versus faster trajectory (adjusted odds ratio (aOR) 1.79, 95% CI 1.01, 3.13) and the slower versus faster trajectory (aOR 1.52, 95% CI 0.82, 2.78) per 1 log unit increase in serum TEQs. Boys with higher peripubertal serum PCDFs had higher adjusted odds of being in the moderate compared to the faster trajectory (aOR 1.92, 95% CI 1.20, 3.03) and of being in the slower versus the faster trajectory (aOR 1.42, 95% CI 0.91, 2.33) per 1 log unit increase. Boys with higher NDL-PCBs had higher adjusted odds of being in the faster trajectory versus the moderate (aOR 2.56, 95% CI 0.91-7.20) or slower (aOR 3.31, 95% CI 1.07, 10.25) trajectory. Boys with higher blood lead levels also had higher adjusted odds of being in the slower trajectory of pubertal progression, compared to either the faster (aOR 1.47, 95% CI 0.89, 2.44) or moderate (aOR 1.20, 95% CI 0.83, 1.75) trajectories, per 1 log unit increase in BLL, although these associations did not attain statistical significance. Conclusion: Boys' peripubertal exposure to dioxins and certain PCBs may alter pubertal progression.

Artificial intelligence for the vascular surgeon.

In recent years, artificial intelligence (AI) has permeated different aspects of vascular surgery to solve challenges in clinical practice. Although AI in vascular surgery is still in its early stages, there have been promising developments in its applications to vascular diagnosis, risk stratification, and outcome prediction. By establishing a baseline knowledge of AI, vascular surgeons are better equipped to use and interpret the data from these types of projects. This review aims to provide an overview of the fundamentals of AI and highlight its role in helping vascular surgeons overcome the challenges of clinical practice. In addition, we discuss the limitations of AI and how they affect AI applications.

Clinical and molecular heterogeneity of syndromic hypothalamic hamartoma.

Two children are presented who have a distinct syndrome of multiple buccolingual frenula, a stiff and short fifth finger with small nails, a hypothalamic hamartoma, mild to moderate neurological impairment, and mild endocrinological symptoms. No variant assessed to be pathogenic or likely pathogenic was detected in the GLI3 gene in either child. This syndrome appears to be distinct from the inherited Pallister-Hall syndrome associated with GLI3 variants, which is characterized by hypothalamic hamartoma, mesoaxial polydactyly, and other anomalies. In the individuals described here, manifestations outside of the central nervous system were milder and the mesoaxial polydactyly, which is common in individuals with Pallister-Hall syndrome, was absent. Instead, these children had multiple buccolingual frenula together with the unusual appearance of the fifth digit. It remains unclear whether these two individuals represent a separate nosologic entity or if they represent a milder manifestation of one of the more severe syndromes associated with a hypothalamic hamartoma.

Prospective study of thyroid function in the first year of life in infants with Down syndrome.

Current American Academy of Pediatrics (AAP) Guidelines recommend monitoring thyroid function in infants with Down syndrome (DS) at birth, 6 and 12 months, and annually thereafter. This study aimed to determine whether these guidelines are optimal for early diagnosis and treatment of (subclinical) hypothyroidism. Enrolled infants with DS less than age 7 months, born at ≥ 30 weeks gestation to monitor thyroid function test (TFT). A filter paper (FP) blood sample was analyzed for TSH and total T4 at ages 2 and 4 weeks and monthly thereafter until 12 months. Subjects with abnormal FP sample and confirmatory serum TFT for hypothyroidism promptly started treatment. Subjects with thyroid dysfunction identified had thyroid antibodies measured at diagnosis and 12 months. Descriptive statistics determined average time to diagnosis of abnormal TFT. Sixteen (30%) of 54 subjects were diagnosed with a thyroid disorder, the majority with subclinical hypothyroidism (SH) and 1 with hyperthyroidism. Diagnosis occurred in 6 (11%), 9 (17%), and 12 (22.2%) infants in the first 30, 60, and 90 days of life (DOL), respectively. Eight infants had an abnormal NBS and half were diagnosed with a thyroid disorder by DOL 8 and the remainder prior to 4 months. Among subjects with a normal NBS, four were diagnosed at a mean of 104 days and three at a mean of 101 days prior to the 6-month and 12-month routine screens, respectively.  Conclusion: Based on current AAP guidelines, thyroid disorder diagnosis would have been delayed in nearly 20% of the subjects. An additional TFT screen at 1 and 3 months can lead to earlier diagnosis and treatment. What is Known: • Current American Academy of Pediatrics (AAP) Guidelines recommend thyroid function tests (TFT) in infants with Down syndrome (DS) at birth and 6 and 12 months. • Peer- reviewed retrospective studies report an increased incidence of hypothyroidism in infants with DS undetected by the newborn screen (NBS) and prior to 6 months. What is New: • This prospective study monitored TFT in infants with DS at age 2 weeks and monthly throughout the first year of life. • The findings in this study support additional TFT screens at 1 and 3 months in infants with DS.

Stents in the Management of Stenotic and Occlusive Lesions in the Venous System.

Occlusive disease of the iliac veins or major intrathoracic veins have traditionally been managed by conservative management or by major vascular reconstructive procedures. Over the past 15-20 years, these lesions have become amenable to management with venous stents. Lesions in the iliac venous system are typically due to thrombus secondary to deep vein thrombosis, and lesions in the superior vena cava are due to either malignant intrathoracic lesions, indwelling central venous catheters, pacemaker leads, or enlarged nodes due to granulomatous disease. The success rate for implantation is between 92% and 95% and associated implantation complications vary between 2% and 5%. Primary patency of iliac stents is 70-90% at three years. Venous stents have higher patency in the treatment of stenotic lesions compared to totally occlusive lesions. Primary patency of stents placed in the superior vena cava is also about 70-90% and generally lower in lesions due to malignancy likely related to life expectancy. Stents in the venous system are associated with few complications at the time of insertion and have excellent long-term patency.

PRMT5 activates AKT via methylation to promote tumor metastasis.

Protein arginine methyltransferase 5 (PRMT5) is the primary methyltransferase generating symmetric-dimethyl-arginine marks on histone and non-histone proteins. PRMT5 dysregulation is implicated in multiple oncogenic processes. Here, we report that PRMT5-mediated methylation of protein kinase B (AKT) is required for its subsequent phosphorylation at Thr308 and Ser473. Moreover, pharmacologic or genetic inhibition of PRMT5 abolishes AKT1 arginine 15 methylation, thereby preventing AKT1 translocation to the plasma membrane and subsequent recruitment of its upstream activating kinases PDK1 and mTOR2. We show that PRMT5/AKT signaling controls the expression of the epithelial-mesenchymal-transition transcription factors ZEB1, SNAIL, and TWIST1. PRMT5 inhibition significantly attenuates primary tumor growth and broadly blocks metastasis in multiple organs in xenograft tumor models of high-risk neuroblastoma. Collectively, our results suggest that PRMT5 inhibition augments anti-AKT or other downstream targeted therapeutics in high-risk metastatic cancers.

Urinary phthalate metabolite concentrations during four windows spanning puberty (prepuberty through sexual maturity) and association with semen quality among young Russian men.

AIM: To prospectively investigate the associations of urinary phthalate metabolite concentrations measured at four time points spanning pubertal development with semen parameters in Russian men. DESIGN: 516 boys were enrolled at ages 8-9 years (2003-2005) and followed annually. METHODS: Urine samples were collected annually and pooled into four exposure windows [prepuberty, early puberty, late puberty and sexual maturity] based on physician assessed Tanner genitalia stages and testicular volume. Fifteen phthalate metabolites were quantified using isotope dilution HPLC-MS/MS at Moscow State University. We calculated molar sums (∑) of di-2-ethylhexyl phthalate (DEHP), di-isononyl phthalate (DiNP), di-isodecyl phthalate (DiDP) and anti-androgenic phthalate (AAP) metabolites. At sexual maturity (ages 18-19 years), the men provided 1-2 semen samples for analysis. We estimated the associations of quintiles of urinary ∑phthalate metabolites as well as mono-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and mono-benzyl phthalate (MBzP) at each pubertal window, with semen parameters by fitting generalized linear mixed models with random intercepts and adjusting for confounders. RESULTS: A total of 223 men who provided semen samples had phthalates measured at one or more pubertal windows. Higher urinary concentrations of ∑DiNP metabolites during late puberty were related to poorer semen quality (men with the highest quintile of urinary ∑DiNP had 30% lower sperm concentration, 32% lower count and 30% lower progressive motile count, compared to men in the lowest quintile). Also, young men with higher urinary concentrations of MiBP metabolites in early puberty tended to have poorer semen quality. No associations were observed for ∑DEHP metabolites, ∑DiDP metabolites, ∑AAP, MBzP or MnBP metabolites with semen quality parameters. CONCLUSIONS: ∑DiNP metabolites measured during late puberty and MiBP metabolites at early puberty were related to poorer semen quality, highlighting the importance of considering specific windows of exposure when investigating chemical exposures in relation to measures of reproductive health in men.

Associations of prepubertal urinary phthalate metabolite concentrations with pubertal onset among a longitudinal cohort of boys.

BACKGROUND: Although phthalate exposures have been associated with adverse effects on male reproductive health, few studies have explored longitudinal associations with male pubertal development. OBJECTIVES: We examined the association of prepubertal urinary concentrations of phthalate metabolites with age at pubertal onset in a prospective cohort of Russian boys. METHODS: At enrollment at ages 8-9 years, medical history, dietary, and demographic information was collected. At entry and annually, physical examinations and pubertal staging [Genitalia (G), Pubarche (P), and testicular volume (TV, in ml)] were conducted and spot urines were collected. Prepubertal urine samples (defined as either TV = 1, 2 and G = 1, 2 or TV = 3 and G = 1) were pooled for each boy and phthalate metabolite concentrations were quantified using isotope dilution LC-MS/MS at Moscow State University. We measured 15 metabolites including those from anti-androgenic parent phthalates (AAPs) such as di (2-ethylhexyl) (DEHP) and di-isononyl (DiNP) phthalates as well as monobenzyl (MBzP), mono-n-butyl (MnBP), and mono-isobutyl (MiBP) metabolites. We calculated the molar sums of DEHP (∑DEHP), DiNP (∑DiNP), and AAP (∑AAP) metabolites. Separate interval-censored models were used to assess associations of quartiles of prepubertal phthalate metabolites with each pubertal onset indicator, G2+, P2+ and TV > 3 mL, adjusted for covariates and urine specific gravity. RESULTS: 304 boys had 752 prepubertal urine samples (median 2, range: 1-6) for pooling. In adjusted models, higher urinary AAPs were consistently associated with later pubertal onset (P2) with mean shifts ranging from 8.4 to 14.2 months for the highest versus lowest quartiles. Significantly later onset for G2 and TV > 3 mL was observed for higher versus lower quartiles of MiBP, MBzP, ∑DEHP and ∑DiNP. CONCLUSIONS: On average, boys with higher concentrations of prepubertal urinary AAPs had later pubertal onset by six months to over a year. The impact of AAPs on timing of male puberty may be attributable to disruption of androgen-dependent biological pathways.

Genomic surveillance of SARS-CoV-2 in the state of Delaware reveals tremendous genomic diversity.

The use of next generation sequencing is critical for the surveillance of severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, transmission, as single base mutations have been identified with differences in infectivity. A total of 1,459 high quality samples were collected, sequenced, and analyzed in the state of Delaware, a location that offers a unique perspective on transmission given its proximity to large international airports on the east coast. Pangolin and Nextclade were used to classify these sequences into 16 unique clades and 88 lineages. A total of 411 samples belonging to the Alpha 20I/501Y.V1 (B.1.1.7) strain of concern were identified, as well as one sample belonging to Beta 20H/501.V2 (B.1.351), thirteen belonging to Epsilon 20C/S:452R (B.1.427/B.1.429), two belonging to Delta 20A/S:478K (B.1.617.2), and 15 belonging to Gamma 20J/501Y.V3 (p.1). A total of 2217 unique coding mutations were observed with an average of 17.7 coding mutations per genome. These data paired with continued sample collection and sequencing will give a deeper understanding of the spread of SARS-CoV-2 strains within Delaware and its surrounding areas.

Association of peripubertal blood lead levels with reproductive hormones and semen parameters in a longitudinal cohort of Russian men.

STUDY QUESTION: Are peripubertal blood lead levels (BLLs) associated with semen parameters and serum reproductive hormones among young Russian men? SUMMARY ANSWER: We observed a suggestion of lower ejaculate volume with higher peripubertal BLL but no associations of BLLs with reproductive hormones measured throughout adolescence or with other sperm parameters measured at adulthood. WHAT IS KNOWN ALREADY: Lead is a known reproductive toxicant and endocrine disruptor. Previous literature has shown associations between high lead exposure and poorer semen quality both in occupationally and environmentally exposed men. However, to our knowledge, no longitudinal studies have explored the association of childhood lead exposure with semen parameters and reproductive hormones in young men. STUDY DESIGN, SIZE, DURATION: The Russian Children's Study is a prospective cohort study that enrolled 516 boys at age 8-9 years in 2003-2005 and followed them annually for 10 years. BLLs were measured at entry and lifestyle and health questionnaires were completed. Reproductive hormones were measured in blood samples collected every 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 516 boys enrolled, 481 had BLLs measured at entry. Of these, 453 had at least one measurement of serum testosterone, follicle stimulating hormone (FSH) or luteinizing hormone (LH) (median = 5 samples per boy) and 223 had semen samples collected ∼10 years after enrolment. Semen assessment included ejaculated volume, sperm concentration, progressive motility and total sperm count, and parameters were categorized using published andrology standards for low semen quality based on sperm count and motility. Linear mixed models were used to examine the associations of log-transformed BLLs (and BLL categories) with reproductive hormones and semen parameters, adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 223 young men with peripubertal BLLs and at least one semen sample (total samples = 438), the median (interquartile range) BLL was 3 (2, 5) µg/dl and 27% had BLL ≥5 µg/dl. Overall, 49% of the semen samples fell below reference levels for sperm count and/or motility. Men with peripubertal BLL ≥5 µg/dl had significantly lower ejaculated volume than those with BLL <5 µg/dl (mean = 2.42 vs 2.89 ml, P = 0.02), but this difference was attenuated in adjusted models (mean = 2.60 vs 2.83 ml, P = 0.25). No associations were observed between BLL measured at age 8-9 years and reproductive hormone levels or sperm parameters, including sperm concentration, total count, progressive motility and total progressive motile sperm count, or with the probability of having low semen quality based on sperm count/motility. LIMITATIONS, REASONS FOR CAUTION: Only a subset of the original cohort participated in the semen quality portion of the study, although inverse probability weighting was used to account for possible selection bias. BLLs were only measured at a single time in peripuberty, and other exposure time periods, including later or longer-term childhood exposure, may be more predictive of semen quality. The young men were also exposed to other chemical contaminants before and during pubertal development. WIDER IMPLICATIONS OF THE FINDINGS: While semen volume often receives less attention than other sperm parameters, it is an important component of male fertility. Additional prospective studies covering different exposure windows and including other seminal plasma biomarkers are warranted to explore our finding of potentially lower ejaculated volume with higher BLLs and to confirm the lack of associations for other semen parameters among youth exposed to environmental BLLs. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided through grants R01ES0014370 and P30ES000002 from the National Institute of Environmental Health Sciences, grant R82943701 from the U.S. Environmental Protection Agency, and grant 18-15-00202 from the Russian Science Foundation (O.S and Y.D.). All authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Peripubertal serum levels of dioxins, furans and PCBs in a cohort of Russian boys: can empirical grouping methods yield meaningful exposure variables?

BACKGROUND: Dioxins, furans and polychlorinated biphenyls (PCBs) are endocrine disruptors with half-lives of months to years in humans. Peripubertal exposure to these chemicals may disrupt pubertal timing. Biomarker exposure metrics like the sum of non-dioxin-like PCBs in serum (∑NDL-PCBs) involve chemicals with different hypothetical effects. Empirical exposure metrics represent an alternative that requires no knowledge of biological mechanisms. METHODS: From 2003 to 2005, 516 Russian boys aged 8-9 residing near a plant that historically produced organochlorine pesticides were enrolled in the Russian Children's Study. At enrollment, blood was collected for measurement of organochlorine chemicals by the Centers for Disease Control and Prevention (CDC). Variable cluster analysis was used to empirically group serum levels of 45 dioxins, furans and PCBs into eight cluster scores. These scores were compared to the sum of dioxin-like toxic equivalents (∑TEQs) and ∑NDL-PCBs using Spearman correlation coefficients. RESULTS: Clustering appeared to reflect number and position of chlorine atoms. Clusters 4, 7 and 1 contained, respectively, tri/tetra-, tetra/penta-, and hexa/hepta-chlorinated PCBs with chlorines at the 4,4' positions. Clusters 2, 8 and 5 contained, respectively, tetra-to hexa-, hexa/hepta-, and hepta/octa-chlorinated PCBs with chlorines at the 2,2' positions. ∑NDL-PCBs were highly correlated with 4,4'-chlorinated clusters 1 and 7 (Spearman's ρ = 0.8) and less so with all other clusters (Spearman's ρ = 0.4-0.5). CONCLUSIONS: In this cohort of Russian boys, baseline serum dioxins, furans and PCBs seemed to cluster by chlorination pattern, possibly reflecting shared persistence, metabolism or source of exposure. The widely used measure ∑NDL-PCB seemed most representative of 4,4'-chlorinated PCBs.

Peripubertal serum concentrations of organochlorine pesticides and semen parameters in Russian young men.

BACKGROUND: Epidemiologic literature on the relation of organochlorine pesticides (OCPs) with semen quality among adult men has been inconclusive, and no studies have prospectively explored the association between peripubertal serum OCPs and semen parameters in young men. OBJECTIVE: To evaluate prospective associations of peripubertal serum concentrations of hexachlorobenzene (HCB), ß-hexachlorocylohexane (ß-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) with semen parameters among young Russian men. METHODS: This prospective cohort study included 152 young men who enrolled in the Russian Children's Study (2003-2005) at age 8-9 years and were followed annually until young adulthood. HCB, ß-HCH, and p,p'-DDE concentrations were measured at the CDC by mass spectrometry in serum collected at enrollment. Between 18 and 23 years, semen samples (n = 298) were provided for analysis of volume, concentration, and progressive motility; we also calculated total sperm count and total progressive motile count. Linear mixed models were used to examine the longitudinal associations of quartiles of serum HCB, ß-HCH and p,p'-DDE with semen parameters, adjusting for total serum lipids, body mass index, smoking, abstinence time and baseline dietary macronutrient intake. RESULTS: Lipid-adjusted medians (IQR) for serum HCB, ßHCH and p,p-DDE, respectively, were 150 ng/g lipid (102-243), 172 ng/g lipid (120-257) and 275 ng/g lipid (190-465). In adjusted models, we observed lower ejaculated volume with higher serum concentrations of HCB and ßHCH, along with reduced progressive motility with higher concentrations of ßHCH andp,p-DDE. Men in the highest quartile of serum HCB had a mean (95% Confidence Interval, CI) ejaculated volume of 2.25 mL (1.89, 2.60), as compared to those in the lowest quartile with a mean (95% CI) of 2.97 mL (2.46, 3.49) (p = 0.03). Also, men in the highest quartile of serum p,p-DDE had a mean (95% CI) progressive motility of 51.1% (48.6, 53.7), as compared to those in the lowest quartile with a mean (95% CI) of 55.1% (51.7, 58.5) (p = 0.07). CONCLUSION: In this longitudinal Russian cohort study, peripubertal serum concentrations of selected OCPs were associated with lower ejaculated volume and progressive motility highlighting the importance of the peripubertal window when evaluating chemical exposures in relation to semen quality.

Ureteral stenosis following iliac artery stenting.

Ureteral complications after open aortoiliac reconstruction for aneurysmal and occlusive disease have been reported previously. However, ureteral complications from endovascular interventions for iliac artery disease are relatively rare. We describe a case of left ureteral stenosis resulting in hydroureteronephrosis after multiple endovascular interventions involving the left common and external iliac arteries. The intraoperative findings during robotic ureterolysis revealed significant peri-iliac fibrosis and scarring in the area of the iliac stents. This case illustrates that, although uncommon, ureteral stenosis may occur after iliac stenting owing to peristent fibrosis.

Comparison of bioimpedance body composition in young adults in the Russian Children's Study.

BACKGROUND & AIMS: Body mass index is a simple anthropometric measure (kg/m2) used as an indirect estimate of body fat in individuals, and in assessments of population health and comparisons between populations. Bioelectrical impedance analysis (BIA) is often used to provide additional information on body fat and fat-free mass, and has been used to generate body composition reference data in national health surveys. However, BIA measurements are known to be device-specific and there are few published studies comparing results from different BIA instruments. Therefore, we compared the performance of two BIA instruments in the Russian Children's Study (RCS) of male growth, pubertal development and maturation. METHODS: Paired BIA measurements were obtained using the Tanita BC-418MA (Tanita Corp., Tokyo, Japan) and ABC-01 'Medas' (Medas Ltd, Moscow, Russia) BIA instruments. Cross-sectional data on 236 RCS subjects aged 18-22 years were used for the BIA comparison and the development of a conversion formula between measured resistances; follow-up data (n = 96) were used for validation of the conversion formula. RESULTS: Whole-body resistances were highly correlated (Spearman rho = 0.95), but fat mass (FM) estimates were significantly higher with the Medas than the Tanita device (median difference 3.3 kg, 95% CI: 2.9, 3.6 kg) with large limits of agreement (LoA) for the FM difference (-2.0, 8.6 kg). A conversion formula between the resistances (Res) was obtained: Medas Res = 0.882 × Tanita Res+26.2 (r2 = 0.91, SEE = 17.6 Ohm). After applying the conversion formula to Tanita data and application of the Medas assessment algorithm, the 'converted' Tanita FM estimates closely matched the Medas original estimates (median difference -0.1 kg, 95% CI: -0.3, 0.2 kg), with relatively small LoA for the FM difference (-2.3 to 2.1 kg), suggesting potential interchangeability of the ABC-01 'Medas' and Tanita BC-418MA data at the group level. CONCLUSIONS: Our results support the importance of cross-calibration of BIA instruments for population comparisons and proper data interpretation in clinical and epidemiological studies.

Perspectives on Molecular Diagnostic Testing for the COVID-19 Pandemic in Delaware.

The United States has quickly transitioned into one of the epicenters for the coronavirus pandemic. Limitations for rapid testing for the virus responsible for the pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the single most important barrier for early detection and prevention of future outbreaks. Combining innovative molecular biology techniques, such as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas nuclease systems and next generation sequencing (NGS) may prove to be an effective solution to establish a high-throughput diagnostic and genomic surveillance workflow for COVID-19 in the State of Delaware. Integrating key expertise across the medical institutions in Delaware, including ChristianaCare and Nemours/Alfred I. duPont Hospital for Children, is one potential solution for overcoming current barriers and driving a successful implementation of these techniques.

Associations of peri-pubertal serum dioxins and polychlorinated biphenyls with growth and body composition among Russian boys in a longitudinal cohort.

BACKGROUND: Childhood exposure to organochlorines has been associated with alterations in somatic growth. We evaluated the associations of peri-pubertal serum levels of dioxin-like compounds (DLCs) and nondioxin-like polychlorinated biphenyls (NDL-PCBs), with adolescent growth, body composition, and near adult height (NAH) in a longitudinal cohort study of Russian boys. METHODS: 473 8-9 year-old boys had serum DLCs and associated toxic equivalents (TEQs) and NDL-PCBs concentrations measured. Physical examinations were performed at enrollment between 2003 and 2005, and annually over 11 years to 2016; annual bio-electric impedance analysis (BIA) of body composition began in 2006. We used mixed effects models to evaluate associations of quartiles of serum chemical concentrations with longitudinal measurements through age 19 of body mass index (BMI-Z) and height (HT-Z) z-scores, annual height velocity (HV), and BIA-derived height-adjusted fat (FMi) and fat-free mass (FFMi) indexes. Potential modification by age of the associations of chemical exposures with growth was evaluated. NAH (defined as HV < 1 cm/year) and age at NAH attainment were estimated using parametric survival models accounting for right censoring. RESULTS: The medians of serum ∑TEQs, ∑DLCs, and ∑NDL-PCBs were 21.1 pg TEQ/g lipid, 362 pg/g lipid, and 250 ng/g lipid, respectively. In multivariable models, higher serum concentrations of peri-pubertal ∑TEQs, ∑DLCs, and ∑NDL-PCBs were associated with significantly lower BMI-Z, FMi, and FFMi over 11 years of follow-up. The differences in FFMi for boys with higher versus lower ΣTEQs and ΣNDL-PCBs increased with age. In multivariable models, higher ∑NDL-PCBs were associated with lower HT-Z, with attenuation of the association with age (interaction p < 0.001). The highest versus the lowest quartiles of ∑NDL-PCBs were not associated with differences in NAH, but were associated with an average of 6 months later attainment of NAH. CONCLUSIONS: Our findings suggest that dioxin and NDL-PCB exposures during childhood are associated with alterations in body composition and subsequent somatic growth.

Blood lead levels and timing of male sexual maturity: A longitudinal study of Russian boys.

BACKGROUND: Higher blood lead levels (BLLs) have been linked to neurologic deficits and impaired growth, but few studies have evaluated their association with timing of sexual maturity or pubertal progression in boys. METHODS: In a longitudinal cohort of Russian boys enrolled at age 8-9 and followed to adulthood, BLLs were measured at study entry, and pubertal staging (genitalia and pubic hair) and testicular volume (TV) measurements were obtained annually. We used interval-censored regression models to estimate differences between boys with higher BLL (≥5 µg/dL) and lower BLL in mean ages at sexual maturity (genitalia stage 5, pubic hair stage 5, or TV ≥ 20 mL) and duration of pubertal progression (onset to maturity), adjusting for potential confounders. Mediation analyses were conducted to quantify the percent of lead's effect attributable to its association with reduced somatic growth. RESULTS: Among 481 evaluable boys, 28% had BLL ≥ 5 µg/dL. Adjusted mean ages at sexual maturity were 14.7 years for genitalia, 16.1 for pubic hair, and 13.9 for TV. In adjusted models, boys with BLLs ≥5 µg/dL had later maturity than those with lower levels by 4-5 months depending on pubertal indicator. In mediation analyses, height and body mass index at age 11 accounted for 40-71% of the shift in age at maturity for boys with higher compared to lower BLLs. Higher BLLs were not associated with pace of pubertal progression. CONCLUSIONS: Higher lead levels were associated with later attainment of sexual maturity in males, but not with the duration of pubertal progression. A high proportion of the delay in sexual maturity for boys with higher as compared to lower BLL was shown to be attributable to mediating effects of BLL on reduced growth.

Prioritizing Racial Equity: How Efforts to Advance Racial Equity Helped Shape the W.K. Kellogg Food & Fitness Initiative.

Racial equity is closely linked to principles of fairness and justice. It is distinct from the concept of racial equality. Community engaged strategies aimed at creating racial equity have generated effective ways to dismantle structural racism-the racialized policies and practices that have shaped economic and social institutions in the United States throughout its history. In crafting the Food & Fitness Initiative, the W.K. Kellogg Foundation made advancing racial equity a top priority. By doing so, it encouraged the community partnerships funded under the initiative to apply theories of expanding equity to real-world situations in order to reduce racial disparities in their neighborhoods. This article reviews the methods that were employed over the course of the initiative to support the partnerships with their efforts. It highlights three key components: (1) being intentional about maintaining a focus on racial equity, (2) concentrating on changing policies and systems, and (3) consistently incorporating meaningful and authentic community engagement into the work. The importance of making the concept of equity concrete and measurable is explored. Furthermore, the article discusses strategies that strengthened the capacity of the partnerships to navigate the policy-making process and to build leadership and shift power to community residents. The article concludes by detailing measures that could guide future efforts to make racial equity a priority and emphasizes that doing so is crucial given the rapid demographic shifts underway across the country.