Association of biomarkers of endothelial function, coagulation activation and kidney injury with persistent albuminuria in sickle cell anaemia.

Persistent albuminuria (PA) is common in sickle cell anaemia (SCA). With the association of chronic kidney disease (CKD) with increased mortality, biomarkers that predict its development or progression are needed. We evaluated the association of select biomarkers with PA in adults with SCA using Kruskal-Wallis rank-sum test and logistic regression models, with adjustment for multiple testing. Of 280 subjects, 100 (35.7%) had PA. Median plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) (1176.3 vs. 953.4 ng/mL, false discovery rate [FDR] q-value <0.003), thrombin-antithrombin complex (5.5 vs. 4.7 ng/mL, FDR q-value = 0.04), and urinary angiotensinogen (AGT) (12.2 vs. 5.3 ng/mg, FDR q-value <0.003), urinary nephrin (30.6 vs. 27.2 ng/mg, FDR q-value = 0.04), and urinary kidney injury molecule-1 (KIM-1) (0.8 vs. 0.5 ng/mg, FDR q-value <0.003), normalized to urine creatinine, were significantly higher in subjects with PA. In multivariable analysis, only urinary AGT (odds ratio = 1.058, FDR q-value <0.0001) remained a significant predictor of PA. In addition, soluble VCAM-1 (FDR q-value <0.0001), D-dimer (FDR q-value <0.0001), urinary AGT (FDR q-value <0.0001), KIM-1 (FDR q-value <0.0001), and nephrin (FDR q-value <0.0001) were significantly associated with urine albumin-creatinine ratio in multivariable analyses. Longitudinal studies to evaluate the predictive capacity of biomarkers for the development and progression of CKD in SCA are warranted.

Barriers and facilitators to home blood pressure monitoring in women with pregnancies complicated by hypertensive disorders: a qualitative study.

BACKGROUND/OBJECTIVE: Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality in the US. Improved diagnosis and treatment of HDP may be achieved through home blood pressure monitoring (HBPM). However, there are challenges to effective HBPM during pregnancy. This qualitative study was conducted to explore patients' perspectives and experiences with HBPM. METHODS: Pregnant or recently postpartum women with HDP (≥18 years) were recruited from an academic medical center to virtual focus groups from March to September 2023. The discussions centered on experiences with HDP and barriers and facilitators to HBPM. Qualitative thematic analysis was performed. RESULTS: Among 20 participants, the mean age was 33.8 (SD 5.9) years, with 35% Hispanic and 35% Black/African-American. Facilitators to HBPM included understanding the parameters/purpose of HBPM, prior experience with healthcare/duration of hypertension, free access to HBPM equipment and decision support, creating a routine, external support/counseling (e.g., partner/healthcare/family), and technology support. Barriers to HBPM included uncertainty/lack of training about the HBPM process, accessing/using HBPM equipment, the belief that clinic monitoring was sufficient/achieving good control, and activation barriers to making HBPM a priority (e.g., fear of affirming the diagnosis, higher priorities/life stressors). CONCLUSION: Many of the barriers to HBPM in pregnancy can be overcome through patient education/counseling, technology support, clinician/family reinforcement, and better access to validated blood pressure monitors. Given the importance of HBPM in improving outcomes for HDP, it is important for healthcare providers and policy makers to work to reduce barriers and amplify facilitators to HBPM for better adoption.

Alterations in cortical and subcortical neuroanatomy and associations with behavior in females with fragile X syndrome.

AIM: To address substantial gaps in the literature on neuroanatomical variations in females with fragile X syndrome (FXS). METHOD: Surface-based modeling techniques were applied to the magnetic resonance imaging of 45 females with FXS (mean age = 10 years 9 months, range 6 years-16 years 4 months, SD = 2 years 9 months) and 33 age-matched and developmentally matched females without FXS to elucidate differences in cortical gray matter volume, surface area, and thickness. Gray matter volumes in subcortical regions were examined to ascertain differences in subcortical volume. RESULTS: In females with FXS, cortical volume was greater bilaterally in the occipital pole and smaller in the right postcentral gyrus. Seven regions demonstrated lower surface area in participants with FXS, while cortical thickness was significantly greater over the posterior and medial surfaces in the group with FXS. Subcortical region of interest analyses demonstrated greater volume in the caudate nucleus, globus pallidus, and nucleus accumbens in the group with FXS. Global gray matter volume, pial thickness, and surface area were associated with behavioral outcomes in the group with FXS but not in the comparison group. INTERPRETATION: Females with FXS demonstrated unique cortical and subcortical gray matter anatomy relative to a matched comparison group. These findings may be relevant to the pathogenesis of the FXS behavioral phenotype and provide insights into behavioral interventions targeted to this population.

Exploring antiviral and antiparasitic activity of gold N-heterocyclic carbenes with thiolate ligands.

Gold(I) N-heterocyclic carbenes have been explored for their therapeutic potential against several diseases. Neglected tropical diseases, including leishmaniasis, Chagas disease, and viral infections, such as zika, mayaro, and chikungunya, urgently require new treatment options. The emergent SARS-CoV-2 also demands significant attention. Gold complexes have shown promise as alternative treatments for these conditions. Previously, gold(I)(1,3-bis(mesityl)imidazole-2-ylidene)Cl (AuIMesCl) demonstrated significant leishmanicidal and anti-Chikungunya virus activities. In this study, we synthesized and fully characterized a series of gold(I)(1,3-bis(mesityl)imidazole-2-ylidene)(SR) complexes, where SR includes thiolate donor species such as 1,3-thiazolidine-2-thione, 1,3-benzothiazole-2-thione, 2-mercaptopyrimidine, and 2-thiouracil. These compounds were stable in solution, and ligand exchange reactions with N-acetyl-L-cysteine indicated that complexes with SR ligands are more labile than those with chloride. Although the reactions are rapid, they reach equilibrium at varying molar ratios depending on the SR ligand. The increased lability of these compounds results in higher cytotoxicity to host cells, such as Vero E6 and bone marrow-differentiated macrophages, compared to AuIMesCl. Despite this, the compounds effectively inhibited viral replication, achieving 95.5% inhibition of Zika virus replication at 2 µM with 96% host cell viability. Although active at low concentrations (∼2 µM) against Leishmania (L.) amazonensis and Trypanosoma cruzi, their high cytotoxicity for macrophages confirmed AuIMesCl as a better candidate with a higher selectivity index. This work correlates the coordination chemistry of pyrimidines and thiazolidines with their in vitro biological activities against significant diseases.

Alterations in Neural Activation During Facial Emotion Processing in Adolescent Male Participants With Klinefelter Syndrome.

OBJECTIVE: Klinefelter syndrome (KS) is the most common sex-chromosome aneuploidy (47,XXY), affecting 1 in 500 male participants. The phenotype of male participants with KS includes both physical features, such as tall stature and testicular insufficiency, and behavioral alterations, including difficulties in social functioning, anxiety, and depression. Studies examining underlying neural alterations associated with the behavioral phenotype, however, are sparse. We aimed to address this gap in knowledge using functional magnetic resonance imaging in conjunction with an emotion processing paradigm. METHOD: Functional magnetic resonance imaging was conducted on 38 children and adolescents with KS ( Mage = 12.85, SD = 2.45) and 47 typical developing (control) boys ( Mage = 12.04, SD = 1.82) as they completed a facial emotion processing task. Group differences in activation occurring during the processing of angry versus neutral faces were examined while controlling for age. RESULTS: The results indicated that relative to typically developing boys, boys with KS exhibited anomalous increases in activation of frontal, temporal, and occipital cortices. Within the KS group, secondary analyses indicated that greater activation in these regions was associated with more internalizing symptoms (e.g., anxiety, depression, withdrawn behaviors) and greater social impairments (e.g., social cognition, social communication, social motivation, social communication and interaction, functional communication). CONCLUSION: The findings from this study indicate a possible neural correlation for difficulties in social and emotional function in KS and add to a growing body of research aimed at increasing our understanding of neural biomarkers in this condition. Future studies that examine the influence of testosterone-replacement therapy on these differences are warranted.

[Translated article] Total hip arthroplasty with second generation dual mobility system as a treatment for primary coxarthrosis, medium-term results.

INTRODUCTION: Osteoarthritis is a disabling pathology characterised by joint pain and stiffness. A prevalence of coxarthrosis of 7.4% is reported in our country. Total hip joint replacement is indicated in advanced stages, a procedure that is not free of complications, the most frequent being prosthetic dislocation, which can be prevented with dual mobility systems. The following study aims to determine the rate of complications and clinical outcomes in dual mobility systems in primary coxarthrosis. MATERIALS AND METHODS: A retrospective study included 120 cases in 114 patients diagnosed with grade III coxarthrosis, mean age was 62.43 years, with a mean follow-up of 4.5 years. Joint replacement was performed by Hardinge approach. All cases were assessed clinically using the Harris Hip Score (HHS) and radiologically to demonstrate mid-term results. RESULTS: The preoperative value on the HHS scale had a mean of 56.45, postoperative at one month 74.23; 6 months 85.40; 1 year 94.01 and at 5 years 94.84 points, representing a functional improvement of 17.78 postoperative month; 28.95 at 6 months postoperative; 37.56 at one year postoperative and 38.39 points at 5 years postoperative. A complication rate of 3.44%; 0.86% of complications were associated with the prosthetic components. CONCLUSION: The dual mobility system should be considered as a therapeutic option in primary hip joint replacement due to excellent functional results and low complication rates. EVIDENCE LEVEL: IV. Retrospective observational case series study.

Associations between brain network, puberty, and behaviors in boys with Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS), also referred to as XXY syndrome, is a significant but inadequately studied risk factor for neuropsychiatric disability. Whether alterations in functional brain connectivity or pubertal delays are associated with aberrant cognitive-behavioral outcomes in individuals with KS is largely unknown. In this observational study, we investigated KS-related alterations in the resting-state brain network, testosterone level, and cognitive-behavioral impairment in adolescents with Klinefelter syndrome. METHODS: We recruited 46 boys with KS, ages 8 to 17 years, and 51 age-matched typically developing (TD) boys. All participants underwent resting-state functional magnetic resonance imaging scans, pubertal, and cognitive-behavioral assessments. Resting-state functional connectivity and regional brain activity of the participants were assessed. RESULTS: We found widespread alterations in global functional connectivity among the inferior frontal gyrus, temporal-parietal area, and hippocampus in boys with KS. Aberrant regional activities, including enhanced fALFF in the motor area and reduced ReHo in the caudate, were also found in the KS group compared to the TD children. Further, using machine learning methods, brain network alterations in these regions accurately differentiated boys with KS from TD controls. Finally, we showed that the alterations of brain network properties not only effectively predict cognitive-behavioral impairment in boys with KS, but also appear to mediate the association between total testosterone level and language ability, a cognitive domain at particular risk for dysfunction in this condition. CONCLUSION: Our results offer an informatic neurobiological foundation for understanding cognitive-behavioral impairments in individuals with KS and contribute to our understanding of the interplay between pubertal status, brain function, and cognitive-behavioral outcome in this population.

A novel protocol for three-dimensional mapping of sand tiger shark (Carcharias taurus) enclosure use in aquaria: Implications for management.

This study investigated sand tiger shark (STS; Carcharias taurus) spatial use and exclusion in public aquarium enclosures using a novel protocol for three-dimensional mapping. Fifty-one STS were observed in 14 enclosures, and swimming pattern, depth, and location were recorded in ZooMonitor. Data were converted into quantitative, three-dimensional representations using ArcGIS® Pro v. 2.9. All observed STS except one swam in circular patterns, and 80% (n = 41) showed a directional swimming bias. Most STS (80%; n = 41) predominantly utilized the top two-thirds of the enclosures, though 83% (n = 34) of those had swimming obstructions in the bottom of the enclosure. Avoidance of obstructed areas, sections <7 m wide, as well as behavioral spatial separation, resulted in utilization of between 27% and 66% of available enclosure space. STS underutilized corners, pinch-points, and obstructed areas requiring abrupt directional changes and instead exhibited continual, unimpeded swimming patterns. In addition, this study found no relationship between directional swimming bias or use of smaller enclosure volumes and spinal deformity, a health issue affecting 26% of STS 10 years ago but now with an incidence of 6%. Using novel protocols for three-dimensional mapping and volume estimation, this study demonstrated that enclosures facilitating unimpeded, continuous swimming are most usable for STS and provides important information that will be useful for future enclosure design.

Hypothalamic AgRP neurons regulate the hyperphagia of lactation.

OBJECTIVE: The lactational period is associated with profound hyperphagia to accommodate the energy demands of nursing. These changes are important for the long-term metabolic health of the mother and children as altered feeding during lactation increases the risk of mothers and offspring developing metabolic disorders later in life. However, the specific behavioral mechanisms and neural circuitry mediating the hyperphagia of lactation are incompletely understood. METHODS: Here, we utilized home cage feeding devices to characterize the dynamics of feeding behavior in lactating mice. A combination of pharmacological and behavioral assays were utilized to determine how lactation alters meal structure, circadian aspects of feeding, hedonic feeding, and sensitivity to hunger and satiety signals in lactating mice. Finally, we utilized chemogenetic, immunohistochemical, and in vivo imaging approaches to characterize the role of hypothalamic agouti-related peptide (AgRP) neurons in lactational-hyperphagia. RESULTS: The lactational period is associated with increased meal size, altered circadian patterns of feeding, reduced sensitivity to gut-brain satiety signals, and enhanced sensitivity to negative energy balance. Hypothalamic AgRP neurons display increased sensitivity to negative energy balance and altered in vivo activity during the lactational state. Further, using in vivo imaging approaches we demonstrate that AgRP neurons are directly activated by lactation. Chemogenetic inhibition of AgRP neurons acutely reduces feeding in lactating mice, demonstrating an important role for these neurons in lactational-hyperphagia. CONCLUSIONS: Together, these results show that lactation collectively alters multiple components of feeding behavior and position AgRP neurons as an important cellular substrate mediating the hyperphagia of lactation.

Transorbital ultrasound in the diagnosis of giant cell arteritis.

OBJECTIVES: The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms. METHODS: Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries. RESULTS: We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: ß = -1.91; P = 0.029; EDV: ß = -0.57; P = 0.032) and significantly elevated OND (ß = 0.79; P = 0.003) compared with controls. RI did not significantly differ from controls (ß = -0.06, P = 0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (P = 0.048) and EDV (P = 0.040). No association was found with RI (P = 0.249), while a positive significant association was noted with OND (P < 0.001). CONCLUSIONS: This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA.

Pediatric Pulmonary Milestones 2.0: Development, Lessons Learned, and Future Directions.

Pediatric pulmonology fellowship training programs are required by the Accreditation Council for Graduate Medical Education to report Pediatric Subspecialty Milestones biannually to track fellow progress. However, several issues, such as lack of subspecialty-specific context and ambiguous language, have raised concerns about their validity and applicability to use for fellow assessment and curriculum development. In this Perspective, we briefly share the process of the Pediatric Pulmonology Milestones 2.0 Work Group in creating new specialty-specific Milestones and tailoring information on the Harmonized Milestones to pediatric pulmonologists, with the goal of improving the Milestones' utility for stakeholders, including pulmonology fellows, faculty, program directors, and accrediting bodies. In addition, we created a supplemental guide to better link the Milestones to pulmonary-specific scenarios to create a shared mental model between stakeholders and remove a potential detriment to validity. Through the process, a number of guiding principles were clarified, including: 1) every Milestone should be able to be assessed independently, without overlap with other Milestones; 2) there should be clear developmental progression from one Milestone to the next; 3) Milestones should be based on the unique skills expected of pediatric pulmonologists; and 4) health equity should be a core component to highlight as a top priority to all stakeholders. In this Perspective, we describe these principles that guided formulation of the Pediatric Pulmonary Milestones to help familiarize the pediatric pulmonary community with the new Milestones. In addition, we share lessons learned and challenges in our process to inform other specialties that may soon participate in this process.

Workforce strategies during the first wave of the COVID-19 pandemic: a retrospective online survey at intensive care units in Germany.

BACKGROUND: As the COVID-19 pandemic swept across the globe at the beginning of 2020, healthcare systems were forced to rapidly adapt and expand to meet the sudden surge in demand for intensive care services. This study is the first systematic analysis of the strategies employed by German hospitals to recruit personnel and expand bed capacities during the first wave of the pandemic, and to evaluate the effectiveness of those recruitment measures. METHODS: 152 German hospitals with intensive care capacities were selected and invited to participate in an online-based retrospective survey. Factors like the geographic distribution, individual COVID burden and level of care were considered for inclusion in the sample. The data were analyzed descriptively. RESULTS: A total of 41 hospitals participated in the survey. The additional demand for intensive care beds was met primarily by activating intensive care beds that were previously considered as non-operational in existing intensive care units (81% of respondents) and by upgrading recovery rooms (73%). The physician staffing requirements were met at approximately 75%, while the nursing staffing requirements were only met by about 45%. Staffing needs were met through reallocations/transfers (85%), staff recruitment from parental leave or retirement (49%), increased hours worked by internal staff (49%), new staff hiring (44%) and increased use of temporary staff (32%). Staff reallocations/transfers to critical care within a hospital were rated as the most effective measure. In this context, specialized personnel mostly from anesthesiology departments were appointed to intensive care medicine. CONCLUSIONS: Despite multiple recruitment efforts, the pandemic has exacerbated the nursing staff shortage. The reallocation of existing staff within hospitals was a key element in covering the staffing needs. However, additional measures and efforts are required in order to ensure that critically ill patients can be cared for without compromise. The results of this study may have important implications for healthcare providers and policymakers, offering an evidence-based foundation for responding to future public health emergencies with agility, efficiency, and success.