IFN-γ stimulates Paneth cell secretion through necroptosis mTORC1 dependent.

Immune mediators affect multiple biological functions of intestinal epithelial cells (IECs) and, like Paneth and Paneth-like cells, play an important role in intestinal epithelial homeostasis. IFN-γ a prototypical proinflammatory cytokine disrupts intestinal epithelial homeostasis. However, the mechanism underlying the process remains unknown. In this study, using in vivo and in vitro models we demonstrate that IFN-γ is spontaneously secreted in the small intestine. Furthermore, we observed that this cytokine stimulates mitochondrial activity, ROS production, and Paneth and Paneth-like cell secretion. Paneth and Paneth-like secretion downstream of IFN-γ, as identified here, is mTORC1 and necroptosis-dependent. Thus, our findings revealed that the pleiotropic function of IFN-γ also includes the regulation of Paneth cell function in the homeostatic gut.

Ultrasound-Derived Fat Fraction for Hepatic Steatosis Assessment: Prospective Study of Agreement With MRI PDFF and Sources of Variability in a Heterogeneous Population.

BACKGROUND. Metabolic dysfunction-associated steatotic liver disease is a growing global public health concern. Quantitative ultrasound measurements, such as ultrasound-derived fat fraction (UDFF), could provide noninvasive, cost-effective, and portable steatosis evaluation. OBJECTIVE. The purpose of this article was to evaluate utility of UDFF for steatosis assessment using proton density fat fraction (PDFF) as reference in patients undergoing liver MRI for heterogeneous indications and to assess UDFF variability. METHODS. This prospective study included a primary analysis of 187 patients (mean age, 53.8 years; 112 men, 75 women) who underwent 3-T liver MRI for any clinical indication from December 2020 to July 2021. Patients underwent investigational PDFF measurement, including determination of PDFFwhole-liver (mean PDFF of entire liver), and PDFFvoxel (PDFF in single voxel within right lobe, measured by MR spectroscopy), as well as investigational ultrasound with UDFF calculation (mean of five inter-costal measurements) within 1 hour after MRI. In a subanalysis, 21 of these patients underwent additional UDFF measurements 1, 3, and 5 hours after meal consumption. The study also included repeatability and reproducibility analysis of 30 patients (mean age, 26.3 years; 10 men, 20 women) who underwent clinical abdominal ultrasound between November 2022 and January 2023; in these patients, three operators sequentially performed UDFF measurements. RESULTS. In primary analysis, UDFF and PDFFwhole-liver measurements showed intra-class correlation coefficient (ICC) of 0.79. In Bland-Altman analysis, UDFF and PDFFvoxel measurements showed mean difference of 1.5% (95% CI, 0.6-2.4%), with 95% limits of agreement from -11.0% to 14.0%. UDFF measurements exhibited AUC for detecting PDFFvoxel at historic thresholds of 6.5% and greater, 17.4% and greater, and 22.1% and greater of 0.90, 0.95, and 0.95, respectively. In subanalysis, mean UDFF was not significantly different across time points with respect to meal consumption (p = .21). In repeatability and reproducibility analysis, ICC for intraoperator repeatability ranged from 0.98 to 0.99 and for interoperator reproducibility from 0.90 to 0.96. Visual assessment of patient-level data plots indicated increasing variability of mean UDFF measurements across operators and of intercostal measurements within individual patients with increasing steatosis. CONCLUSION. UDFF showed robust agreement with PDFF, diagnostic performance for steatosis grades, and intraoperator repeatability and interoperator reproducibility. Nonetheless, UDFF exhibited bias toward slightly larger values versus PDFF; intraoperator and interoperator variation increased with increasing steatosis. CLINICAL IMPACT. UDFF shows promise for steatosis assessment across diverse populations, although continued optimization remains warranted.

Identification of ABCC3 and its isoforms as potential biomarker in hepatocellular carcinoma.

Liver diseases preceding the occurrence of hepatocellular carcinoma (HCC) play a crucial role in the progression and establishment of HCC, a malignancy ranked as the third deadliest cancer worldwide. Late diagnosis, alongside ineffective treatment, leads patients to a poor survival rate. This scenario argues for seeking novel alternatives for detecting liver alterations preceding the early occurrence of HCC. Experimental studies have reported that ABCC3 protein increases within HCC tumors but not in adjacent tissue. Therefore, we analyzed ABCC3 expression in public databases and investigated the presence of ABCC3 and its isoforms in plasma, urine and its release in extracellular vesicles (EVs) cargo from patients bearing cirrhosis and HCC. The UALCAN and GEPIA databases were used to analyze the expression of ABCC3 in HCC. The results were validated in a case-control study including 41 individuals bearing cirrhosis and HCC, and the levels of ABCC3 in plasma and urine samples, as well as EVs, were analyzed by ELISA and western blot. Our data showed that ABCC3 expression was higher in HCC tissues than in normal tissues and correlated with HCC grade and stage. ABCC3 protein levels were highly increased in both plasma and urine and correlated with liver disease progression and severity. The isoforms MRP3A and MRP3B of ABCC3 were significantly increased in both EVs and plasma/urine of patients bearing HCC. ABCC3 expression gradually increases in HCC tissues, and its protein levels are increased in both plasma and urine of patients with cirrhosis and HCC. MRP3A and MRP3B isoforms have the potential to be prognostic biomarkers of HCC.

The effects of xeno-free cryopreservation on the contractile properties of human iPSC derived cardiomyocytes.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have advanced our ability to study the basic function of the heart and model cardiac diseases. Due to the complexities in stem cell culture and differentiation protocols, many researchers source their hiPSC-CMs from collaborators or commercial biobanks. Generally, the field has assumed the health of frozen cardiomyocytes is unchanged if the cells adhere to the substrate and commence beating. However, very few have investigated the effects of cryopreservation on hiPSC-CM's functional and transcriptional health at the cellular and molecular level. Here we review methods and challenges associated with cryopreservation, and examine the effects of cryopreservation on the functionality (contractility and calcium handling) and transcriptome of hiPSC-CMs from six healthy stem cell lines. Utilizing protein patterning methods to template physiological cell aspect ratios (7:1, length:width) in conjunction with polyacrylamide (PA) hydrogels, we measured changes in force generation and calcium handling of single hiPSC-CMs. We observed that cryopreservation altered the functionality and transcriptome of hiPSC-CMs towards larger sizes and contractile force as assessed by increased spread area and volume, single cell traction force microscopy and delayed calcium dynamics. hiPSC-CMs are broadly used for basic science research, regenerative medicine, and testing biological therapeutics. This study informs the design of experiments utilizing hiPSC-CMs to avoid confounding functional changes due to cryopreservation with other treatments.

A common temperature dependence of nutritional demands in ectotherms.

In light of ongoing climate change, it is increasingly important to know how nutritional requirements of ectotherms are affected by changing temperatures. Here, we analyse the wide thermal response of phosphorus (P) requirements via elemental gross growth efficiencies of Carbon (C) and P, and the Threshold Elemental Ratios in different aquatic invertebrate ectotherms: the freshwater model species Daphnia magna, the marine copepod Acartia tonsa, the marine heterotrophic dinoflagellate Oxyrrhis marina, and larvae of two populations of the marine crab Carcinus maenas. We show that they all share a non-linear cubic thermal response of nutrient requirements. Phosphorus requirements decrease from low to intermediate temperatures, increase at higher temperatures and decrease again when temperature is excessive. This common thermal response of nutrient requirements is of great importance if we aim to understand or even predict how ectotherm communities will react to global warming and nutrient-driven eutrophication.

Leptin receptor and prolactin in pubertal disorders and chronic kidney disease.

BACKGROUND: Knowledge of chronic kidney disease (CKD) with pubertal disorders (PD) in adolescent boys is limited as few studies have explored this disorder. This study aimed to identify the usefulness of assessing hormonal parameters in male adolescents with CKD and their correlation with PD in a 12-month follow-up period. METHODS: A prospective cohort study was conducted among male adolescents with CKD (stages IV and V). Data regarding the age at puberty onset were collected from the patients' clinical records and through interview. The patients were followed up for 12 months during their pubertal development. At the beginning, routine hormonal profile tests were performed to examine the patients' thyroid profile, prolactin levels, luteinizing hormone, follicle-stimulating hormone, testosterone, leptin, and receptor leptin. The hormonal profiles of patients with and without PD were compared. Comparisons between the groups were performed using the Student t-test and Fisher's exact tests. Logistic regression analysis was also performed. RESULTS: Data of 64 patients (26/64 with PD) were analyzed. The median age was 15 years and the median time for CKD evolution was 11 months. No differences between groups were noted in the general or biochemical characteristics of the patients. The hormonal parameters, prolactin levels were higher and the free leptin and free thyroxine levels were lower in patients with PD. Leptin receptor levels of >0.90 ng/mL (risk ratio [RR], 8.6; P = 0.004) and hyperprolactinemia (RR, 21.3; P = 0.049) were the risk factors for PD. CONCLUSIONS: Leptin receptor levels of >0.90 ng/mL and hyperprolactinemia are associated with the development of PD in male adolescents with CKD.

3'5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by parenchymal scarring, leading progressively to alveolar architecture distortion, respiratory failure, and eventually death. Currently, there is no effective treatment for IPF. Previously, 3'5-dimaleamylbenzoic acid (3'5-DMBA), a maleimide, demonstrated pro-apoptotic, anti-inflammatory, and anti-cancer properties; however, its potential therapeutic effects on IPF have not been addressed. Bleomycin (BLM) 100 U/kg was administered to CD1 mice through an osmotic minipump. After fourteen days of BLM administration, 3'5-DMBA (6 mg/kg or 10 mg/kg) and its vehicle carboxymethylcellulose (CMC) were administered intragastrically every two days until day 26. On day 28, all mice were euthanized. The 3'5-DMBA effect was assessed by histological and immunohistochemical staining, as well as by RT-qPCR. The redox status on lung tissue was evaluated by determining the glutathione content and the GSH/GSSG ratio. 3'5-DMBA treatment re-established typical lung histological features and decreased the expression of BLM-induced fibrotic markers: collagen, α-SMA, and TGF-ß1. Furthermore, 3'5-DMBA significantly reduced the expression of genes involved in fibrogenesis. In addition, it decreased reduced glutathione and increased oxidized glutathione content without promoting oxidative damage to lipids, as evidenced by the decrease in the lipid peroxidation marker 4-HNE. Therefore, 3'5-DMBA may be a promising candidate for IPF treatment.

Maternal and cohort effects modulate offspring responses to multiple stressors.

Current concerns about climate change have led to intensive research attempting to understand how climate-driven stressors affect the performance of organisms, in particular the offspring of many invertebrates and fishes. Although stressors are likely to act on several stages of the life cycle, little is known about their action across life phases, for instance how multiple stressors experienced simultaneously in the maternal environment can modulate the responses to the same stressors operating in the offspring environment. Here, we study how performance of offspring of a marine invertebrate (shore crab Carcinus maenas) changes in response to two stressors (temperature and salinity) experienced during embryogenesis in brooding mothers from different seasons. On average, offspring responses were antagonistic: high temperature mitigated the negative effects of low salinity on survival. However, the magnitude of the response was modulated by the temperature and salinity conditions experienced by egg-carrying mothers. Performance also varied among cohorts, perhaps reflecting genetic variation, and/or maternal conditions prior to embryogenesis. This study contributes towards the understanding of how anthropogenic modification of the maternal environment drives offspring performance in brooders.

An atlas of larval organogenesis in the European shore crab Carcinus maenas L. (Decapoda, Brachyura, Portunidae).

BACKGROUND: The life history stages of brachyuran crustaceans include pelagic larvae of the Zoea type which grow by a series of moults from one instar to the next. Zoeae actively feed and possess a wide range of organ systems necessary for autonomously developing in the plankton. They also display a rich behavioural repertoire that allows for responses to variations in environmental key factors such as light, hydrostatic pressure, tidal currents, and temperature. Brachyuran larvae have served as distinguished models in the field of Ecological Developmental Biology fostering our understanding of diverse ecophysiological aspects such as phenotypic plasticity, carry-over effects on life-history traits, and adaptive mechanisms that enhance tolerance to fluctuations in environmental abiotic factors. In order to link such studies to the level of tissues and organs, this report analyses the internal anatomy of laboratory-reared larvae of the European shore crab Carcinus maenas. This species has a native distribution extending across most European waters and has attracted attention because it has invaded five temperate geographic regions outside of its native range and therefore can serve as a model to analyse thermal tolerance of species affected by rising sea temperatures as an effect of climate change. RESULTS: Here, we used X-ray micro-computed tomography combined with 3D reconstruction to describe organogenesis in brachyuran larvae. We provide a detailed atlas of the larval internal organization to complement existing descriptions of its external morphology. In a multimethodological approach, we also used cuticular autofluorescence and classical histology to analyse the anatomy of selected organ systems. CONCLUSIONS: Much of our fascination for the anatomy of brachyuran larvae stems from the opportunity to observe a complex organism on a single microscopic slide and the realization that the entire decapod crustacean bauplan unfolds from organ anlagen compressed into a miniature organism in the sub-millimetre range. The combination of imaging techniques used in the present study provides novel insights into the bewildering diversity of organ systems that brachyuran larvae possess. Our analysis may serve as a basis for future studies bridging the fields of evolutionary developmental biology and ecological developmental biology.

Evaluation of Breast Cancer Patients with Genetic Risk in a University Hospital: Before and After the Implementation of a Heredofamilial Cancer Unit.

The identification of patients at risk for breast cancer by genetic testing has proven to reduce breast cancer mortality. In 2010, due to a lack of systematization in hereditary cancer assistance in our center, we implemented a multidisciplinary Heredofamilial Cancer Unit (HFCU). We analyze if the HFCU improved the rates of referrals and preventive management of breast cancer patients with genetic risk. We retrospectively compared family history records, referrals of high-risk patients to genetic counseling, and detection and management of patients with BRCA1/2 mutations in two cohorts of breast cancer patients diagnosed before (first period: 2007-2010) and after the creation of the HFCU (second period: 2010-2013). In the first period, 893 patients were included, and 902 were included in the second. Due to the inability to establish their genetic risk, 142 patients (15.9%) vs. 70 (7.8%) were excluded from analysis (p < 0.001). Among the evaluable patients, 194 (25.8%) vs. 223 (26.8%) fulfilled one or more risk criteria (p = 0.65). Family history documentation in patient's medical records (92.4 vs. 97.8%, p < 0.001) and referral rate (26.3 vs. 52%, p < 0.0001) significantly increased in the second period. Eight BRCA1/2 mutations were detected among patients referred in the first period and 17 among those referred to the HFCU. The rate of preventive surgeries in patients with BRCA mutations significantly increased in the second period (25 vs. 76.5%, p = 0.03). In conclusion, there was a clear improvement in family history records, referrals, and preventive surgeries in breast cancer patients with genetic risk after the implementation of the HFCU.

Multicenter analysis of neoadjuvant docetaxel, carboplatin, and trastuzumab in HER2-positive breast cancer.

PURPOSE: In an era where neoadjuvant dual blockade is emerging as the standard of care for early and locally advanced HER2-positive breast cancer, we aimed to identify predictors of response to single-blockade chemotherapy. METHODS: This retrospective analysis reviewed all the incident stage I-III HER2-positive breast cancer patients who received neoadjuvant docetaxel, carboplatin, and trastuzumab (TCH) in three institutions. pCR was defined as the absence of invasive tumor in breast and axillary nodes (ypT0/isypN0). RESULTS: From 2008 to 2015, 84 patients receiving neoadjuvant TCH were identified within our institutions. The mean age at diagnosis was 51.8 years. 59.5% of the patients were hormone receptor (HR) positive, lymph node involvement occurred in 67.9%, and clinical distribution was 2.4, 65.5, and 32.1% for stage I, II, and III, respectively. pCR rate was 47.6%; there was a significantly lower response in HR-positive patients compared to HR-negative ones (34 vs 67.6%, p = 0.005). pCR rate was associated with tumor size, whereas differences did not reach significance either for stage or for nodal status. Multivariate analysis found that only HR status was associated with response (p = 0.003). At a median follow-up of 31.7 months, disease-free survival, distant disease-free survival, and overall survival were 78.6, 85.7, and 94%, respectively. Breast-conserving surgery was performed in 44% of the patients. Overall, TCH was well tolerated, with low rates of grade 3-4 adverse events, and neither late toxicities nor cardiac dysfunctions were reported. CONCLUSIONS: Neoadjuvant TCH, an anthracycline-free single-blockade regimen, achieved a pCR of 47.6%. Further molecular analyses are required in order to identify stronger predictive markers of pCR and thus for an accurate selection of patients who do not benefit from dual blockade.

Bone mineral density and mammographic density in Mexican women.

BACKGROUND: Bone mineral density (BMD) is a putative marker for lifetime exposure to estrogen. Studies that have explored whether BMD is a determinant of mammographic density (MD) have observed inconsistent results. Therefore,we examined this potential association in a sample of women (n = 1,516) from the clinical sub-cohort in the Mexican teachers' cohort (n = 115,315). METHODS: We used multivariable linear regression to assess the association between quartiles of BMD and percent MD, as well as total dense and non-dense area of the breast, stratified by menopausal status. We also examined the associations by body mass index (BMI) (< 30 kg/m(2), ≥ 30 kg/m(2)). RESULTS: Overall, there was no association between BMD and MD among premenopausal women. However, when we stratified by BMI, there was a modest inverse association between BMD and percent MD (difference between extreme quartiles = -2.8, 95 % CI -5.9, 0.27, p trend = 0.04) among women with BMI < 30 kg/m(2), but a positive association among obese women (comparable difference = 5.1, 95 % CI 0.02, 10.1, p trend = 0.03;p interaction < 0.01). Among postmenopausal women, BMD and percent MD were positively associated after adjustment for BMI (p trend < 0.01). Postmenopausal women in the highest two quartiles of BMD had 4­5 % point higher percent MD compared to women in the lowest quartile. The association did not differ by BMI in postmenopausal women (p interaction = 0.76). CONCLUSION: Among obese premenopausal women as well as postmenopausal women, BMD was positively associated with percent MD. Among leaner premenopausal women, BMD and percent MD were modestly inversely associated. These findings support the hypothesis that cumulative exposure to estrogen (as measured by BMD) may influence MD.

The transmembrane transporter ABCC3 participates in liver cancer progression and is a potential biomarker.

The poor prognosis, few available treatment options, and multidrug resistance present in hepatocellular carcinoma are major problems, and new early biomarkers are needed to reduce the liver cancer death rate. ATP-binding cassette sub-family C member 3 (Abcc3) is overexpressed in different cancers and is associated with multidrug resistance and a carcinogenic stem cell phenotype. We present evidence for the first time that ABCC3 is a potential sanguine biomarker and anticancer target in hepatocellular carcinoma. Abcc3 mRNA expression was elevated in liver nodules and tumors in rat hepatocarcinogenesis model. Accordingly, the ABCC3 protein was preferentially overexpressed within the nodules and tumors during hepatocellular carcinoma progression and was secreted into the bloodstream of rat hepatocarcinogenesis model. The ABCC3 protein was expressed in human hepatoma cells and, importantly, was also present in HepG2- and Huh7-conditioned media. Furthermore, ABCC3 was overexpressed in human hepatocellular carcinoma. This report is the first to describe liver overexpression of Abcc3 during the cancer initiation, promotion, and progression periods in rat hepatocarcinogenesis model and in human hepatocellular carcinoma.

Temporal artifact minimization in sonoelastography through optimal selection of imaging parameters.

Sonoelastography is an ultrasonic technique that uses Kasai's autocorrelation algorithms to generate qualitative images of tissue elasticity using external mechanical vibrations. In the absence of synchronization between the mechanical vibration device and the ultrasound system, the random initial phase and finite ensemble length of the data packets result in temporal artifacts in the sonoelastography frames and, consequently, in degraded image quality. In this work, the analytic derivation of an optimal selection of acquisition parameters (i.e., pulse repetition frequency, vibration frequency, and ensemble length) is developed in order to minimize these artifacts, thereby eliminating the need for complex device synchronization. The proposed rule was verified through experiments with heterogeneous phantoms, where the use of optimally selected parameters increased the average contrast-to-noise ratio (CNR) by more than 200% and reduced the CNR standard deviation by 400% when compared to the use of arbitrarily selected imaging parameters. Therefore, the results suggest that the rule for specific selection of acquisition parameters becomes an important tool for producing high quality sonoelastography images.

Ultrasound backscatter coefficient for fat quantification is affected by the measurement depth.

PURPOSE: It has been reported that the estimate of ultrasound attenuation coefficient (AC) is affected by depth of measurement, with linear decrease of values with depth. It is unknown whether backscatter coefficient (BSC) has similar behavior. METHODS: This retrospective study was performed with Sequoia US system equipped with ultrasound derived fat fraction (UDFF) algorithm (Siemens Healthineers, Issaquah, WA, USA) that combines BSC with AC. UDFF was obtained positioning upper edge of the region of interest at 1.5,2,3,4,5 cm below liver capsule. BSC data were extracted from UDFF offline. A fractional polynomial regression, which selects the best model considering the polynomial development of the variables of interest, was used. Covariates included were age, sex, skin-to-liver-capsule distance, stiffness. Distance was included as linear factor or with a power ranging from - 2 to 3, and the best fitting model was chosen according to partial F test. Body mass index (BMI) was not included because of collinearity with skin-to-liver capsule distance. RESULTS: 104 individuals (56 females; age: 57.9 ± 13.0 years; BMI: 29.0 ± 6.5 kg/m2; skin-to-liver-capsule distance: 2.3 ± 0.7 cm; liver stiffness: 7.5 ± 5.5 kiloPascal) were studied. Best fitting model for BSC included a combination of depth as linear factor and square root. BSC showed a decrease of - 13.98 dB/cm-steradian for each logarithmic increase of 1 cm depth (coefficient: - 13.98; 95% CI: - 21.016; - 5.379; p = .001). Skin-to-liver-capsule distance and stiffness also were independent predictors of BSC. CONCLUSIONS: The estimation of the BSC in the liver exhibits a depth dependence that significantly affects results. A standardized acquisition protocol is needed to compare results and reliably assess changes over time.

Earthquakes, Hurricanes, Pandemics: Pharmacy Students Impacting Pharmacy Practice in Puerto Rico Through Medication Therapy Management Services During Disasters.

BACKGROUND: Community-based medication therapy management advanced pharmacy practice experiences (MTM APPE) can engage pharmacy students in public health initiatives, including emergency response preparedness, to successfully impact patient care. This study aimed to evaluate pharmacy students' perceptions of their experience on an MTM APPE during disasters in Puerto Rico. METHODS: After completing the MTM APPE during times of hurricanes, earthquake or pandemic, pharmacy students were asked to voluntarily participate in a questionnaire about their perception of assisting during a disaster. The survey consisted of 5 questions. Four questions were based on a Likert scale with answers choices ranging from Agree, Not Sure, Disagree, or Not Applicable. One question requested free text comments from participants. RESULTS: Sixteen students completed the survey. Pharmacy students agreed that the MTM APPE taught them the clinical skills needed to assist and educate individual patients and the community that suffered from a disaster, and that the role of the pharmacist is vital when a disaster disrupts a community's health-care system. CONCLUSIONS: Training in emergency response to disasters should be a considered component of MTM APPE.

Cardiometabolic factors and vitamin D deficiency in pediatric patients with chronic kidney disease.

Background: Patients with chronic kidney disease (CKD) are at increased risk for cardiovascular disease. Up to 80% of patients with CKD may exhibit inadequate vitamin D (VD) levels, which have been linked to the presence of cardiometabolic factors (CFs) in the adult population. However, research on this association in the pediatric population is limited. Objective: To analyze the effects of 25-hydroxyvitamin D3 (25-[OH]D) levels and status on the presence of CFs in children receiving kidney replacement therapy (KRT). Materials and methods: This cross-sectional study included pediatric patients receiving KRT, aged 8-17 years, who were receiving hemodialysis or peritoneal dialysis from January 2021 to March 2024. We conducted anthropometric measurements, blood pressure assessments, and glucose, 25-(OH)D, and lipid profiling for all participants. The daily dose of cholecalciferol supplementation, as well as other medications affecting bone and lipid metabolism and antihypertensive drugs, were documented. Statistical analyses were performed using Student's t-tests and chi-square tests to compare the CFs between groups with and without VD deficiency. Results: The study involved 156 patients with an average age of 12.9 years and a mean serum VD level of 22.5 ng/dL. Patients with VD deficiency presented higher levels of total cholesterol and diastolic blood pressure (p < 0.05). No statistically significant differences were found in other biochemical profile variables or in the frequency of cardiometabolic factors. Conclusion: Vitamin D deficiency seems to increase the risk of dyslipidemia and uncontrolled hypertension in children and adolescents with end-stage CKD.

Comparing Focused-Tracked and Plane Wave-Tracked ARFI Log(VoA) In Silico and in Application to Human Carotid Atherosclerotic Plaque, Ex Vivo.

A significant risk factor for ischemic stroke is carotid atherosclerotic plaque that is susceptible to rupture, with rupture potential conveyed by plaque morphology. Human carotid plaque composition and structure have been delineated noninvasively and in vivo by evaluating log(VoA), a parameter derived as the decadic log of the second time derivative of displacement induced by an acoustic radiation force impulse (ARFI). In prior work, ARFI-induced displacement was measured using conventional focused tracking; however, this requires a long data acquisition period, thereby reducing framerate. We herein evaluate if ARFI log(VoA) framerate can be increased without a reduction in plaque imaging performance using plane wave tracking instead. In silico, both focused- and plane wave-tracked log(VoA) decreased with increasing echobrightness, quantified as signal-to-noise ratio (SNR), but did not vary with material elasticity for SNRs below 40 dB. For SNRs of 40-60 dB, both focused- and plane wave-tracked log(VoA) varied with SNR and material elasticity. Above 60 dB SNR, both focused- and plane wave-tracked log(VoA) varied with material elasticity alone. This suggests that log(VoA) discriminates features according to a combination of their echobrightness and mechanical property. Further, while both focused- and plane-wave tracked log(VoA) values were artifactually inflated by mechanical reflections at inclusion boundaries, plane wave-tracked log(VoA) was more strongly impacted by off-axis scattering. Applied to three excised human cadaveric carotid plaques with spatially aligned histological validation, both log(VoA) methods detected regions of lipid, collagen, and calcium (CAL) deposits. These findings support that plane wave tracking performs comparably to focused tracking for log(VoA) imaging and that plane wave-tracked log(VoA) is a viable approach to discriminating clinically relevant atherosclerotic plaque features at a 30-fold higher framerate than by focused tracking.

Thermal acclimation and habitat-dependent differences in temperature robustness of a crustacean motor circuit.

Introduction: At the cellular level, acute temperature changes alter ionic conductances, ion channel kinetics, and the activity of entire neuronal circuits. This can result in severe consequences for neural function, animal behavior and survival. In poikilothermic animals, and particularly in aquatic species whose core temperature equals the surrounding water temperature, neurons experience rather rapid and wide-ranging temperature fluctuations. Recent work on pattern generating neural circuits in the crustacean stomatogastric nervous system have demonstrated that neuronal circuits can exhibit an intrinsic robustness to temperature fluctuations. However, considering the increased warming of the oceans and recurring heatwaves due to climate change, the question arises whether this intrinsic robustness can acclimate to changing environmental conditions, and whether it differs between species and ocean habitats. Methods: We address these questions using the pyloric pattern generating circuits in the stomatogastric nervous system of two crab species, Hemigrapsus sanguineus and Carcinus maenas that have seen a worldwide expansion in recent decades. Results and discussion: Consistent with their history as invasive species, we find that pyloric activity showed a broad temperature robustness (>30°C). Moreover, the temperature-robust range was dependent on habitat temperature in both species. Warm-acclimating animals shifted the critical temperature at which circuit activity breaks down to higher temperatures. This came at the cost of robustness against cold stimuli in H. sanguineus, but not in C. maenas. Comparing the temperature responses of C. maenas from a cold latitude (the North Sea) to those from a warm latitude (Spain) demonstrated that similar shifts in robustness occurred in natural environments. Our results thus demonstrate that neuronal temperature robustness correlates with, and responds to, environmental temperature conditions, potentially preparing animals for changing ecological conditions and shifting habitats.