Novel insights into the phenotypic spectrum and pathogenesis of Hardikar syndrome.

PURPOSE: Hardikar syndrome (HS, MIM #301068) is a female-specific multiple congenital anomaly syndrome characterized by retinopathy, orofacial clefting, aortic coarctation, biliary dysgenesis, genitourinary malformations, and intestinal malrotation. We previously showed that heterozygous nonsense and frameshift variants in MED12 cause HS. The phenotypic spectrum of disease and the mechanism by which MED12 variants cause disease is unknown. We aim to expand the phenotypic and molecular landscape of HS and elucidate the mechanism by which MED12 variants cause disease. METHODS: We assembled and clinically and molecularly characterized a cohort of 11 previously-unreported individuals with HS. We additionally studied the effect of MED12 deficiency on ciliary biology and hedgehog and YAP signaling, pathways implicated in diseases with phenotypic overlap with HS. RESULTS: We report novel phenotypes associated with HS, including cardiomyopathy, arrhythmia, and vascular anomalies and expand the molecular landscape of HS to include splice site variants. We additionally demonstrate that MED12 deficiency causes decreased cell ciliation and impairs hedgehog and YAP signaling. CONCLUSION: Our data support updating HS standard-of-care to include regular cardiac imaging, arrhythmia screening, and vascular imaging. We further propose that dysregulation of ciliogenesis and YAP and hedgehog signaling contributes to the pathogenesis of HS.

Optimal cardiovascular health is associated with slower cognitive decline.

BACKGROUND: Life's Simple 7, a lifestyle and cardiovascular index associated with cognition, has been updated to Life's Essential 8 (LE8) to include sleep. LE8 has been related to cardiovascular outcomes but its association with cognition is unclear. METHODS: In this longitudinal analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), LE8 score was based on health behaviors (diet, physical activity, nicotine exposure, and sleep health) as well as health-related factors (body mass index, blood lipids, blood glucose, and blood pressure). Cognition was assessed in three waves, 4 years apart, using the Consortium to Establish a Registry for Alzheimer's Disease - Word List, semantic and phonemic verbal fluency, the Trail-Making Test B (TMT-B), and a global composite score. We used linear mixed-model analysis, inverse probability weighting, and interaction analysis. RESULTS: At baseline, the mean age of the study cohort was 51.4 ± 8.9 years, 56% were women, and 53% were White. Higher baseline LE8 scores were associated with slower decline in global cognition (ß = 0.001, 95% confidence interval [CI] 0.001, 0.002; p < 0.001), memory (ß = 0.001, 95% CI 0.000, 0.002; p = 0.013), verbal fluency (ß = 0.001, 95% CI 0.000, 0.002; p = 0.003), and TMT-B (ß = 0.004, 95% CI 0.003, 0.005; p < 0.001). This association was mainly driven by LE8 health factors, particularly blood glucose and blood pressure. Age, sex, and race were modifiers of the association between LE8 and global cognitive decline (p < 0.001), suggesting it was more pronounced in older, male, and Black participants. CONCLUSIONS: Higher baseline LE8 scores were associated with slower global and domain-specific cognitive decline during 8 years of follow-up, mainly due to health factors such as blood glucose and blood pressure. Sociodemographic factors were modifiers of this association.

Rates of pulmonary vein reconnection at repeat ablation for recurrent atrial fibrillation and its impact on outcomes among females and males.

BACKGROUND: Several studies have demonstrated that females have a higher risk of arrhythmia recurrence after pulmonary vein (PV) isolation for atrial fibrillation (AF). There are limited data on sex-based differences in PV reconnection rates at repeat ablation. We aimed to investigate sex-based differences in electrophysiological findings and atrial arrhythmia recurrence after repeat AF ablation METHODS: We conducted a retrospective study of 161 consecutive patients (32% female, age 65 ± 10 years) who underwent repeat AF ablation after index PV isolation between 2010 and 2022. Demographics, procedural characteristics and follow-up data were collected. Recurrent atrial tachycardia (AT)/AF was defined as any atrial arrhythmia ≥30 s in duration. RESULTS: Compared to males, females tended to be older and had a significantly higher prevalence of prior valve surgery (10 vs. 2%; P = .03). At repeat ablation, PV reconnection was found in 119 (74%) patients. Males were more likely to have PV reconnection at repeat ablation compared to females (81 vs. 59%; P = .004). Excluding repeat PV isolation, there were no significant differences in adjunctive ablation strategies performed at repeat ablation between females and males. During follow-up, there were no significant differences in freedom from AT/AF recurrence between females and males after repeat ablation (63 vs. 59% at 2 years, respectively; P = .48). CONCLUSIONS: After initial PV isolation, significantly fewer females have evidence of PV reconnection at the time of repeat ablation for recurrent AF. Despite this difference, long-term freedom from AT/AF was similar between females and males after repeat ablation.

Horizontal and vertical distribution of Clarireedia spp., in asymptomatic and symptomatic creeping bentgrass cultivars.

Dollar spot is an important disease of both cool- and warm-season turfgrasses caused by six fungal species in the genus Clarireedia, yet the ecology and epidemiology of these pathogens remains poorly understood. The goal of this study was to determine the distribution of Clarireedia in asymptomatic and symptomatic creeping bentgrass (Agrostis stolonifera) in the field using a previously developed qPCR assay. To determine the horizontal distribution of the pathogen, the abundance of Clarireedia spp. was measured in leaf and crown tissue from 90, 1-cm diameter cores spaced 10-cm apart in May 2019 and 2020 (asymptomatic tissue) and August 2019 and July 2020 (symptomatic tissue). Thirty-seven to 69% of cores sampled from asymptomatic turfgrass and 77 to 95% of cores taken from symptomatic turfgrass yielded positive detections for Clarireedia. Spatial analysis indicated that Clarireedia was randomly distributed in the field in both asymptomatic and symptomatic turfgrass. To assess the vertical distribution of the pathogen, the abundance of Clarireedia was measured in the foliar, crown, and thatch layers of 39, 1-cm dia. x 2.5-cm deep cores of creeping bentgrass maintained at fairway height (9.5 mm) during 2019 and 2020. Clarireedia was most abundant in foliar tissue, followed by crown tissue, and thatch (lowest abundance) throughout the two-year study. Both studies provide evidence that Clarireedia is widely distributed in turfgrass swards prior to symptom development and that it can persist within turfgrass as an endophyte. These findings will improve our understanding of Clarireedia epidemiology and may lead to more sustainable dollar spot management.

First Report of Phialocephala bamuru Causing Root Rot on Hard Fescue (Festuca brevipila) in the United States.

Turfgrasses are susceptible to a wide variety of ectotrophic root-infecting (ERI) fungi that cause root rot (Tredway et al., 2023). Among the root rot diseases, fairway patch, caused by Phialocephala bamuru P.T.W. Wong & C. Dong sp. nov., was recently identified and characterized in Australia infecting bermudagrass (Cynodon dactylon) and kikuyu (Pennisetum clandestinum) grass (Wong et al., 2015). Symptoms begin as small, 5-10 cm diameter patches of yellowed turf that may coalesce into larger areas of diseased grass. A characteristic sign of fairway patch is roots colonized by dark brown to black, ectotrophic mycelium. In June 2020, many tan colored, irregular-shaped patches ranging from 10-30 cm in diameter developed on a hard fescue (Festuca brevipila) cultivar 'Beacon' turfgrass field in North Brunswick, New Jersey, USA. The centers of these patches later died and became sunken or filled in partially by recovering hard fescue. The patches grew into tan irregular-shaped rings with diameters up to 3 m by Aug 2023. Symptoms were indicative of a root disease. Five 'Beacon' hard fescue soil cores at the interface of the symptomatic and non-symptomatic area were sampled in Aug 2023. Root and crown samples were observed under a dissecting microscope and dark ectotrophic hyphae were observed on both. Roots with visible ectotrophic mycelium were removed, rinsed in sterile water three times, cut into 5 mm pieces, and plated onto 10% potato dextrose agar amended with streptomycin and gentamicin at 100 mg/L (PDA+). The plates were incubated at 25°C in the dark for 5 days. The most abundant colonies being characteristic long, septate hyphae that were hyaline at the edge and dark brown to black in the center and resembled the fungus described in Wong et al., 2015. These colonies were subcultured onto PDA+ medium and selected for molecular identification. Other less abundant colonies could be identified using morphology after subcultured and had no record being pathogenic to turfgrass. To confirm the isolate's identity, its internal transcribed spacer (ITS) region was amplified in PCR using the ITS1F/ITS4 primers (Bellemain et al., 2010). The amplicon was then sequenced with both ITS1 and ITS4 primers by Sanger sequencing. Sequences were assembled (GenBank #PP000819). The consensus sequence was then BLASTn analyzed with default settings, and the result showed 99.64% sequence identity with P. bamuru (GenBank #MG195534.1). Koch's postulate was conducted in an environmentally controlled growth chamber. Six healthy 'Beacon' hard fescue plugs were sampled from the field. Three of the six plugs (treatment) were each inoculated with P. bamuru by placing 20 g of P. bamuru colonized millets beneath and around the plug before filling the pots with sand. The other three plugs (control) received the same treatment except the P. bamuru colonized millets were autoclaved. The pots were incubated in the growth chamber with a 16 h light period and 25/20°C day/night temperatures. Symptoms resembling those observed in the field appeared on the treatment pots after 21 days of incubation while the control pots remained healthy. The roots from the treatment pots were examined under the dissecting microscope to confirm the colonization of P. bamuru on the roots, and P. bamuru was reisolated and confirmed using the aforementioned morphological traits and molecular assays (GenBank #PP000820). This is the first report of a turfgrass root rot disease caused by P. bamuru in the United States. Further epidemiological, disease ecological, and pathogen biological studies are required to clarify the importance of this disease in the United States and establish proper disease containment or control measures.

Fgf, Hh, and pax2a differentially regulate expression of pax5 and pou3f3b in vestibular and auditory maculae in the zebrafish otic vesicle.

BACKGROUND: The vertebrate inner ear contains distinct sensory epithelia specialized for auditory or vestibular function. In zebrafish, the first sensory epithelia form at opposite ends of the otic vesicle and are functionally distinct: the anterior utricular macula is essential for vestibular function whereas the posterior saccular macula is critical for hearing. Mechanisms distinguishing these maculae are not clear. Here, we examined the effects of manipulating Fgf or Hh on expression of pax5 and pou3f3b, unique markers of utricular and saccular identity. We also examined the roles of pax2a and atoh1a/b, early regulators of sensory specification. RESULTS: fgf3 and fgf8a were uniquely required for pax5 and pou3f3b, respectively. Elevating Fgf or blocking Hh expanded expression of pax5 but repressed pou3f3b, while blocking Fgf had the opposite effect. Blocking sensory specification did not affect pax5 or pou3f3b, but both markers were lost in pax2a-/- mutants. Maintenance of pax2a expression requires Fgf, Hh and Pax2a itself. CONCLUSION: Specification of utricular identity requires high Fgf and is repressed by Hh, whereas saccular identity requires Hh plus low Fgf. pax2a acts downstream of Fgf and Hh to maintain both fates. Comparison with mouse suggests this may reflect a broadly conserved developmental mechanism.

Pax2a, Sp5a and Sp5l act downstream of Fgf and Wnt to coordinate sensory-neural patterning in the inner ear.

In zebrafish, sensory epithelia and neuroblasts of the inner ear form simultaneously in abutting medial and lateral domains, respectively, in the floor of the otic vesicle. Previous studies support regulatory roles for Fgf and Wnt, but how signaling is coordinated is poorly understood. We investigated this problem using pharmacological and transgenic methods to alter Fgf or Wnt signaling from early placodal stages to evaluate later changes in growth and patterning. Blocking Fgf at any stage reduces proliferation of otic tissue and terminates both sensory and neural specification. Wnt promotes proliferation in the otic vesicle but is not required for sensory or neural development. However, sustained overactivation of Wnt laterally expands sensory epithelia and blocks neurogenesis. pax2a, sp5a and sp5l are coregulated by Fgf and Wnt and show overlapping expression in the otic placode and vesicle. Gain- and loss-of-function studies show that these genes are together required for Wnt's suppression of neurogenesis, as well as some aspects of sensory development. Thus, pax2a, sp5a and sp5l are critical for mediating Fgf and Wnt signaling to promote spatially localized sensory and neural development.

Early Stroke and Mortality After Percutaneous Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation.

BACKGROUND: Percutaneous endocardial left atrial appendage occlusion (LAAO) is an alternative therapy for stroke prevention in patients with atrial fibrillation who are poor candidates for oral anticoagulants. Oral anticoagulation is generally discontinued 45 days following successful LAAO. Real-world data on early stroke and mortality following LAAO are lacking. METHODS: Using International Classification of Diseases, Tenth Revision, Clinical-Modification codes, we performed a retrospective observational registry analysis to examine the rates and predictors of stroke, mortality, and procedural complications during index hospitalization and 90-day readmission among 42 114 admissions in the Nationwide Readmissions Database for LAAO between 2016 and 2019. Early stroke and mortality were defined as events occurring during index admission or 90-day readmission. Data on timing of early strokes post-LAAO were collected. Multivariable logistic regression modeling was used to ascertain predictors of early stroke and major adverse events. RESULTS: LAAO was associated with low rates of early stroke (0.63%), early mortality (0.53%), and procedural complications (2.59%). Among patients who had readmissions with strokes after LAAO, the median time from implant to readmission was 35 days (interquartile range, 9-57 days); 67% of readmissions with strokes occurred <45 days postimplant. Between 2016 and 2019, the rates of early stroke after LAAO significantly decreased (0.64% versus 0.46% P-for-trend <0.001), while early mortality and major adverse event rates were unchanged. Peripheral vascular disease and a history of prior stroke were independently associated with early stroke after LAAO. Early post-LAAO stroke rates were similar between low, medium, and high LAAO volume tertile centers. CONCLUSIONS: In this contemporary real-world analysis, the early stroke rate after LAAO was low, with the majority occurring within 45 days of device implantation. Despite an increase in LAAO procedures between 2016 and 2019, there with a significant decline in early strokes after LAAO during that period.

T1Gd is reduced in bone marrow lesions overlying cartilage in the hip.

OBJECTIVE: Bone Marrow Lesions (BMLs) are areas in bone with high fluid signal on MRI associated with painful and progressive OA. While cartilage near BMLs in the knee has been shown to be degenerated, this relationship has not been investigated in the hip. RESEARCH QUESTION: is T1Gd lower in areas of cartilage overlying BMLs in the hip? DESIGN: 128 participants were recruited from a population-based study of hip pain in 20-49-year-olds. Proton-density weighted fat-suppressed and delayed Gadolinium Enhanced MR Imaging of Cartilage (dGEMRIC) images were acquired to locate BMLs and quantify hip cartilage health. BML and cartilage images were registered and cartilage was separated into BML overlying and surrounding regions. Mean T1Gd was measured in 32 participants with BMLs in both cartilage regions and in matched regions in 32 age- and sex-matched controls. Mean T1Gd in the overlying cartilage was compared using linear mixed-effects models between BML and control groups for acetabular and femoral BMLs, and between cystic and non-cystic BML groups. RESULTS: Mean T1Gd of overlying cartilage was lower in the BML group compared to the control group (acetabular: -105 ms; 95% CI: -175, -35; femoral: -8 ms; 95% CI: -141, 124). Mean T1Gd in overlying cartilage was lower in cystic compared to non-cystic BML subjects, but the confidence interval is too large to provide certainty in this difference (-3 [95% CI: -126, 121]). CONCLUSIONS: T1Gd is reduced in overlying cartilage in hips from a population-based sample of adults aged 20-49, which suggests BMLs are associated with local cartilage degeneration in hips.

Initial experience with stylet-driven versus lumenless lead delivery systems for left bundle branch area pacing.

INTRODUCTION: Left bundle branch area pacing (LBBP) has emerged as an alternative method for conduction system pacing. While initial experience with delivery systems for stylet-driven and lumenless lead implantation for LBBP has been described, data comparing outcomes of stylet-driven versus lumenless lead implantation for LBBP are limited. In this study, we compare success rates and outcomes of LBBP with stylet-driven versus lumenless lead delivery systems. METHODS: Eighty-three consecutive patients (mean age 74.1 ± 11.2 years; 56 [68%] male) undergoing attempted LBBP at a single institution were identified. Cases were grouped by lead delivery systems used: stylet-driven (n = 53) or lumenless (n = 30). Baseline characteristics and procedural findings were recorded and compared between the cohorts. Intermediate term follow-up data on ventricular lead parameters were also compared. RESULTS: Baseline characteristics were similar between groups. Successful LBBP was achieved in 77% of patients, with similar success rates between groups (76% in stylet-driven, 80% in lumenless, p = 0.79), and rates of adjudicated LBB capture and other paced QRS parameters were also similar. Compared with the lumenless group, the stylet-driven group had significantly shorter procedure times (90 ± 4 vs. 112 ± 31 min, p = 0.004) and fluoroscopy times (10 ± 5 vs. 15 ± 6 min, p = 0.003). Ventricular lead parameters at follow-up were similar, and rates of procedural complications and need for lead revision were low in both groups. CONCLUSION: Delivery systems for stylet-driven and for lumenless leads for LBBP have comparable acute success rates. Long-term follow-up of lead performance following use of the various delivery systems is warranted.

Percentiles of predicted 10-year cardiovascular disease risk by sex and age in Brazil and their association with estimated risk of long-term atherosclerotic events.

OBJECTIVE: Expressing the cardiovascular disease (CVD) risk in relation to peers may complement the estimation of absolute CVD risk. We aimed to determine 10-year CVD risk percentiles by sex and age in the Brazilian population and evaluate their association with estimated long-term atherosclerotic CVD (ASCVD) risk. METHODS: A cross-sectional analysis of baseline data from the ELSA-Brasil study was conducted in individuals aged 40-74 years without prior ASCVD. Ten-year CVD risk and long-term ASCVD risk were estimated by the WHO risk score and the Multinational Cardiovascular Risk Consortium tool, respectively. Ten-year risk percentiles were determined by ranking the calculated risks within each sex and age group. RESULTS: Ten-year CVD risk versus percentile plots were constructed for each sex and age group using data from 13,364 participants (55% females; median age, 52 [IQR, 46-59] years). Long-term ASCVD risk was calculated in 12,973 (97.1%) participants. Compared to individuals at the <25th risk percentile, those at the ≥75th percentile had a greater risk of being in the highest quartile of long-term risk (ORs [95% CIs] 6.57 [5.18-8.30] in females and 11.59 [8.42-15.96] in males) in regression models adjusted for age, race, education, and 10-year CVD risk. In both sexes, the association between risk percentile and long-term risk weakened after age 50. A tool for calculating 10-year CVD risk and the corresponding percentile is available at https://bit.ly/3CzPUi6. CONCLUSIONS: We established percentiles of predicted 10-year CVD risk by sex and age in the Brazilian population, which independently reflect the estimated long-term ASCVD risk in younger individuals.

Reduction of left ventricular global longitudinal strain in patients with permanent pacemakers as a predictor of heart failure and mortality outcomes.

INTRODUCTION: Frequent right ventricular (RV) pacing is associated with cardiomyopathy. The impact of RV pacing on left ventricular (LV) global longitudinal strain (GLS) and clinical outcomes is unclear. METHODS: We analyzed GLS via two-dimensional speckle tracking and LV ejection fraction (EF) on pre- and post-implantation transthoracic echocardiograms of patients undergoing dual chamber pacemaker implantation. We collected long-term data on strain, LVEF, and clinical outcomes. RESULTS: One hundred and ten patients (mean age 76 ± 12 years; 59 [54%] female) were followed for mean 23 ± 17 months. Mean baseline LVEF was 58 ± 11% and mean GLS was -17 ± 4%. Twenty-four (22%) patients had an absolute decrease in LVEF > 10% and 43 (39%) patients had a relative reduction of GLS > 15%. Among patients with a reduction of GLS, a larger proportion of patients had RV pacing burden ≥20% (67% vs. 46%; p = .048). Compared to patients without GLS reduction, more patients with a reduction in GLS reached a composite endpoint of HF hospitalization, CRT upgrade or death (47% vs. 16%; p = .001). CONCLUSION: Reduction in LV GLS was seen in nearly four in 10 patients undergoing pacemaker implantation and was significantly associated with increased RV pacing burden. LV GLS reduction was associated with increased risk of adverse outcomes. LV GLS may have utility in predicting outcomes among patients with RV pacing.

Quantitative Assessment of Computed Tomography Energy Use and Cost Savings Through Overnight and Weekend Power Down in a Radiology Department.

Purpose: To assess energy and cost savings when a CT scanner is powered down during overnight non-operational times compared with the CT scanner left on full power or partial shutdown mode. Materials and Methods: Temporary portable power data loggers were placed on the power supply to the CT scanner to measure the energy consumption of the CT scanner in 3 power modes over 9 weeks: system ON (computer on, gantry on), computer ON (computer on/gantry off), and system shutdown (computer off/gantry off). Energy was separated into daily average consumption during normal operating hours and consumption after hours for three different day types: weekdays, Saturdays, and Sundays/Holidays. To estimate savings, the average after hours energy use per day during the system ON was compared to each of the two power saving modes. 95% confidence intervals were calculated for each mode and savings result. Results: Overnight and Sunday system shutdown compared to system ON mode is shown to save approximately 14 000 kWh over one year with a 95% confidence interval of (13 899 kWh, 14 464 kWh) as calculated by the electricity provider. Conclusion: Energy consumed by a CT scanner can be significantly reduced through system shutdown when the unit is non-operational, saving emissions and cost. In addition to cost and energy savings, this study emphasizes the importance of clinician leadership in convening interdisciplinary teams outside of usual healthcare silos to rethink how we purposefully use energy and reduce waste.

Utilization of Imaging for Severe Injuries at the Beijing 2022 Winter Olympic Games.

Purpose: In order to better understand the imaging of severe trauma in sport, this study describes the imaging modalities utilized to image athletes who experienced severe traumatic injuries at the Beijing Winter Olympic Games 2022, the distribution of these modalities in relation to the sporting facilities, and the types of injuries imaged in each sport. Methods: This is a retrospective analysis with descriptive tables and figures, performed on a single population (athletes of the Beijing Winter Olympic Games 2022). Results: Of the 2871 athletes in the Beijing Winter Olympic Games, there were 40 athletes with severe injuries who underwent medical imaging. MRI was used more often than Radiography or CT. Athletes at venues without MRI on site had to be transferred to adjacent hospitals for care. Alpine and Freestyle skiing athletes experienced the majority of severe traumatic injuries at this Olympic Games, and the majority of injuries were to the lower limb. Conclusions: Access to medical imaging for severely injured athletes is a critical consideration in the organization of any sporting event. MRI in particular is highly utilized in this population.

Knowledge and Perceptions of Competency-Based Medical Education in Diagnostic Radiology Post-Graduate Medical Education: Identifying Priorities and Developing a Framework for Professional Development Activities.

Introduction: We evaluated knowledge and perceptions of an established Competency-Based Medical Education (CBME) model developed by the Royal College of Physicians and Surgeons of Canada, Competence by Design (CBD), and identified evidence-informed priorities for professional development activities (PDAs). Materials and Methods: Teaching faculty and residents at a single, large diagnostic radiology post-graduate medical education (PGME) program were eligible to participate in this cross-sectional, survey-based study. Knowledge of CBD was evaluated through multiple choice questions (MCQs), which assessed participants' understanding of major principles and terms associated with CBD. Participants' perceptions of the anticipated impact of CBD on resident education and patient care were evaluated and priorities for PDAs were identified, which informed a framework for CBD PDAs. Results: Fifty faculty and residents participated. The faculty and resident response rates were 11.6% (n = 29/249) and 55.3% (n = 21/38), respectively. The mean ± standard deviation overall score on MCQs was 39.0% ± 20.4%. The majority of participants perceived the impact of CBD on resident education to be equivocal and to not impact patient care. Knowledge of CBD was not statistically significantly associated with participants' perceptions of the impact of CBD on either resident education or patient care (P > .05). Delivery of high-quality feedback was the greatest priority identified for PDAs. Discussion: Our results and proposed CBD PDAs framework may help to guide diagnostic radiology PGME programs in designing evidence-informed PDAs, which may meaningfully contribute to the successful implementation of CBD in diagnostic radiology PGME. As diagnostic radiology PGME programs throughout the world increasingly implement CBME models, evidence-informed PDAs will become of increasing importance.

Complement activation and regulation in preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome.

The complement system is critical to human health owing to its central role in host defense and innate immunity. During pregnancy, the complement system must be appropriately regulated to allow for immunologic tolerance to the developing fetus and placenta. Although some degree of complement activation can be seen in normal pregnancy, the fetus seems to be protected in part through the placental expression of complement regulatory proteins, which inhibit complement activation at different steps along the complement activation cascade. In women who develop preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, there is a shift toward increased complement activation and decreased complement regulation. There is an increase in placental deposition of C5b-9, which is the terminal effector of classical, lectin, and alternative complement pathways. C5b-9 deposition stimulates trophoblasts to secrete soluble fms-like tyrosine kinase-1, which sequesters vascular endothelial growth factor and placental growth factor. Pathogenic mutations or deletions in complement regulatory genes, which predispose to increased complement activation, have been detected in women with preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Before the disease, biomarkers of alternative complement pathway activation are increased; during active disease, biomarkers of terminal complement pathway activation are increased. Urinary excretion of C5b-9 is associated with preeclampsia with severe features and distinguishes it from other hypertensive disorders of pregnancy. Taken together, existing data link preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome with increased activation of the terminal complement pathway that, in some cases, may be influenced by genetic alterations in complement regulators. These findings suggest that the inhibition of the terminal complement pathway, possibly through C5 blockade, may be an effective strategy to treat preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, but this strategy warrants further evaluation in clinical trials.

Sex differences in the association between alcohol intake and cognitive decline over 4 years in a middle-aged cohort: The Brazilian Longitudinal Study of Adult Health.

BACKGROUND AND PURPOSE: The association between alcohol intake and cognitive decline has been widely studied. Sex differences and cognitive domains affected by alcohol intake patterns make this topic complex. The objective of this study was to investigate the effect of alcohol intake on cognition in middle-aged participants in the Brazilian Longitudinal Study of Adult Health by sex during 4 years of follow-up. METHODS: A total of 7595 participants (55% women) aged between 50 and 75 years at baseline were assessed. Semantic and phonemic fluency, memory, and executive functions were assessed at baseline (2008-2010) and repeated during Visit 2. Linear mixed models were used to investigate the association between cognition and current abstainers, never drinkers, light drinkers, moderate drinkers, and heavy drinkers. RESULTS: Heavy alcohol intake accentuated the decline in executive functions for men (ß = -0.01, p < 0.05), and in semantic fluency (ß = -0.02, p < 0.05) and memory (ß = -0.02, p < 0.05) for women. Never drinker men also showed an accentuated decline in semantic fluency (ß = -0.02, p < 0.01). Moderate alcohol intake slowed cognitive decline in phonemic fluency for men (ß = 0.02, p < 0.01) and women (ß = 0.01, p < 0.01), and in executive functions (ß = 0.01, p < 0.05) for women. CONCLUSIONS: Having more than 14 drinks per week can impact executive functions in men and memory in women. In addition, alcohol consumption of seven to 14 drinks per week may have a protective effect on gender-specific cognitive functions. These findings should be considered in public health policies and guidelines on alcohol and cognitive aging.

The inflammatory food index and its association with weight gain and incidence of diabetes: Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND AND AIMS: Diet plays a central role in regulating inflammation and is closely related to the development of chronic diseases. We aimed to develop an inflammatory food index (IFI) based on the relationship of food items with biomarkers of inflammation and to evaluate its association with weight gain and type 2 diabetes. METHODS AND RESULTS: A sample of 9909 participants of the ELSA-Brasil study was analyzed. Standardized measurements including interviews, anthropometry, and laboratory exams were performed at baseline and follow-up. A baseline food frequency questionnaire was used to derive IFI scores using reduced rank regression (RRR). The inflammatory pattern derived included 11 pro-inflammatory food groups: processed meat, red meat, pork, sugary soda, and hot dogs. The anti-inflammatory pattern included seven food groups: fruits, nuts, and wine. The IFI score, adjusted through logistic regression for multiple sociodemographic, behavioral, and clinical covariates, including body mass index, predicted the development of a large weight gain (tertile 3 vs. 1: OR = 1.30; 95%CI 1.08-1.55). The score, adjusted for sociodemographic factors through proportional hazard models, predicted incident diabetes (tertile 3 vs. 1: HR = 1.26; 95%CI 1.04-1.52). CONCLUSION: These findings support the hypothesis that subclinical inflammation caused by a pro-inflammatory food pattern, characterized mainly by greater ultra-processed food consumption, underlies weight gain and the development of type 2 diabetes. This study was registered at clinicaltrials.com as NCT02320461.

Incidence of excess body weight and annual weight gain in women and men: Results from the ELSA-Brasil cohort.

OBJECTIVE: To estimate annual weight gain and the incidence of overweight and obesity, stratified according to gender and socioeconomic factors. METHODS: From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we included 13 625 women and men aged 35-74 (2008-2010) who attended a follow-up visit after a mean 3.8-years. Standardized questionnaires were used to record sociodemographic data, and height and weight were measured on all participants during in-person visits at research centers. The incidence rate to overweight was calculated among those not having excess weight at baseline, and incident obesity among those not having this condition at baseline. We evaluated the incidence of overweight and obesity in men and women, adjusted by age, through Poisson regression with robust variance. Large annual weight gain by gender was being defined as ≥90th percentile in the cohort. RESULTS: A global incidence of 7.7% for overweight and 10.6% for obesity was observed, with higher levels seen among black woman (28.5%), young men (21.1%) and woman with low educational level (35.0%). The proportions of overweight and obesity increased with age at both time points, more commonly among those with the lowest levels of per capita income and fewer years of schooling. Large annual weight gain was greater among participants with an intermediate level of education and those who self-identified as black. CONCLUSIONS: A high overall risk of becoming overweight/obese was found, especially among women. The roles of race and education level are fundamental to understanding the effects produced by social inequalities in rates of excess weight.

Imaging-detected bone stress injuries at the Tokyo 2020 summer Olympics: epidemiology, injury onset, and competition withdrawal rate.

BACKGROUND: Prevention and early detection of injuries are essential in optimising sport participation and performance. The aim of this study is to investigate the epidemiology, athlete injury history, and competition withdrawal rate of imaging-detected bone stress injuries during the Tokyo 2020 Olympic Games. METHODS: We collected and analysed imaging and clinical information in athletes with bone stress injuries diagnosed in the Olympic Village polyclinic during the Games. Two physicians independently and retrospectively reviewed all imaging examinations of bone stress injuries. RESULTS: A total of 11,315 individual athletes from 206 National Olympic Committees competed at the Games, during which 567 MRIs and 352 X-rays were performed at the Olympic Village polyclinic. Radiology examinations revealed four stress fractures and 38 stress reactions in 29 athletes (median age 24 years, range 18-35 years). Of these, 72% of athletes (n = 21) had symptoms before entering the Olympic Village. Bone stress injuries were most common in women (55%), the lower extremities (66%), and track and field athletes (45%). Six athletes (21%) did not start or did not finish their competitions. CONCLUSIONS: This study revealed 42 imaging-detected bone stress injuries in the polyclinic of the Tokyo 2020 Olympic Village. The high proportion of athletes with symptoms before entering the village and the high proportion of competition withdrawals suggests the usefulness of an early MRI examination.