Age-appropriate Controls Research Articles

Current Recommended Estrogen Dosing for Pubertal Induction in Turner Syndrome Results in Normal Uterine Growth.

Most individuals with Turner syndrome (TS) require estrogen for pubertal induction. Current estrogen dosing guidelines are based on expert consensus opinion. Evaluate whether current international guidelines for estrogen dosing during pubertal induction of individuals with TS result in normal uterine growth. We hypothesized that uterine size in individuals with TS who reached adult estrogen dosing is smaller than in mature females without TS. Cross-sectional study of patients with TS at the Cincinnati Center for Pediatric and Adult Turner Syndrome Care. Twenty-nine individuals (age 15-26 years) with primary ovarian insufficiency who reached adult estrogen dosing (100 µg of transdermal or 2 mg of oral 17β-estradiol) were included. Comparison of uterine measurements with a published sample of 292 age-appropriate (age 15-20 years) controls without TS. Uterine length, volume, and fundal-cervical ratio (FCR) were measured. Clinical information (karyotype, Tanner staging for breast development, laboratory data) was extracted from an existing institutional patient registry. There was no evidence of compromise of the uterine size/configuration in the TS cohort compared with the controls; in fact, uterine length, mean 7.7 cm (±1.3) vs 7.2 cm (±1.0) (P = .03), and volume, mean 60.6 cm3 (±26.6) vs 50.5 cm3 (±20.5) (P = .02), were both larger in individuals with TS. Current international guidelines for hormone replacement using 17β-estradiol in individuals with TS appear adequate to allow for normal uterine growth by the end of pubertal induction.

A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia

Biliary atresia (BA) is an obstructive cholangiopathy that initially affects the extrahepatic bile ducts (EHBDs) of neonates. The etiology is uncertain, but evidence points to a prenatal cause. Fetal tissues have increased levels of hyaluronic acid (HA), which plays an integral role in fetal wound healing. The objective of this study was to determine whether a program of fetal wound healing is part of the response to fetal EHBD injury. Mouse, rat, sheep, and human EHBD samples were studied at different developmental time points. Models included a fetal sheep model of prenatal hypoxia, human BA EHBD remnants and liver samples taken at the time of the Kasai procedure, EHBDs isolated from neonatal rats and mice, and spheroids and other models generated from primary neonatal mouse cholangiocytes. A wide layer of high molecular weight HA encircling the lumen was characteristic of the normal perinatal but not adult EHBD. This layer, which was surrounded by collagen, expanded in injured ducts in parallel with extensive peribiliary gland hyperplasia, increased mucus production and elevated serum bilirubin levels. BA EHBD remnants similarly showed increased HA centered around ductular structures compared with age-appropriate controls. High molecular weight HA typical of the fetal/neonatal ducts caused increased cholangiocyte spheroid growth, whereas low molecular weight HA induced abnormal epithelial morphology; low molecular weight HA caused matrix swelling in a bile duct-on-a-chip device. The fetal/neonatal EHBD, including in human EHBD remnants from Kasai surgeries, demonstrated an injury response with prolonged high levels of HA typical of fetal wound healing. The expanded peri-luminal HA layer may swell and lead to elevated bilirubin levels and obstruction of the EHBD. Biliary atresia is a pediatric cholangiopathy associated with high morbidity and mortality rates; although multiple etiologies have been proposed, the fetal response to bile duct damage is largely unknown. This study explores the fetal pathogenesis after extrahepatic bile duct damage, thereby opening a completely new avenue to study therapeutic targets in the context of biliary atresia.

Cognitive impairment after a stroke in young adults: A systematic review and meta-analysis.

Information about cognitive functioning is vital in the management of stroke, but the literature is mostly based on data from individuals older than 50 years of age who make up the majority of the stroke population. As cognitive functioning is subject to change due to aging, it is unclear whether such cognitive impairment patterns from the general stroke literature apply to the growing population of younger people with a stroke. The aim of the study was to conduct a systematic review and meta-analysis of the proportion and severity of cognitive impairment in young-stroke patients. MEDLINE, Embase, PsycINFO, and Web of Science were systematically searched up to 11 October 2022. Studies were included if they reported on a population of young-stroke patients, evaluated cognitive functioning as an outcome measure, and reported original data. We estimated the pooled prevalence rates for cognitive impairment and for aphasia. In addition, we calculated the pooled estimates for the severity of impairment per cognitive domain in the chronic phase (defined as >6 months post-stroke). Six hundred thirty-five articles were identified, of which 29 were eligible for inclusion. The pooled prevalence of cognitive impairment was 44% (k = 10; 95% confidence interval (CI): 34-54%) and of aphasia 22% (k = 13; 95% CI: 12-39%). Young-stroke patients in the chronic phase performed worse than stroke-free healthy age-appropriate controls across all cognitive domains examined, with Hedges' g effect sizes ranging from -0.49 to -1.64. Around half of all young-stroke patients present with cognitive impairment and around a quarter with aphasia. Our data suggest that patterns of impairment in young-stroke patients follow those in the general stroke literature.

Proteomic characterization of atopic dermatitis blood from infancy to adulthood

Patients with atopic dermatitis (AD) have systemic biomarker dysregulation that differs by age group; however, the proteomic characteristics of these age-based changes are unknown. To profile blood proteins of patients with AD across different age groups versus age-appropriate controls. Using the Olinkhigh-throughput proteomic platform, we profiled 375 serum proteins of 20 infants (age, 0-5years), 39 children (age, 6-11years), 21 adolescents (age, 12-17years), and 20 adults (age, ≥18years) with moderate-to-severe AD and 83 age-appropriate controls. Each group presented a distinct systemic proteomic signature. Th2-related proteins were increased in infant AD and further intensified with age through adolescence and adulthood (interleukin 4/CCL13/CCL17). In contrast, Th1 axis down-regulation was detected in infants with AD and gradually reversed to increased Th1 products (interferon γ/CXCL9/CXCL10/CCL2) in patients with AD from childhood to adulthood. Despite their short disease duration, infants already had evidence of systemic inflammation, with significant upregulation of innate immunity (interleukin 17C/ interleukin-1RN), T-cell activation/migration (CCL19), Th2 (CCL13/CCL17), and Th17 (PI3) proteins. Adults with AD present unique upregulation of cardiovascular proteins related to coagulation and diabetes. Cross-sectional observational study with a single time point. Systemic immune signatures of AD are age-specific beyond the shared Th2 immune activation. These data advocate for precision medicine approaches based on age-specific AD profiles.

LEFT ATRIAL VOLUME INDEX (LAVI) AS A PREDICTOR OF PAROXYSMAL ATRIAL FIBRILLATION IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION

Objective: Heart damage in hypertension occurs at three stages, a compensatory, reversible subclinical and irreversible clinical phase. Atrial fibrillation appears in the third phase, but we can find echocardiographic signs pointing to it in the subclinical phase. Although cardioembolic stroke is a feared cardiovascular complication with a possible life-long impact on a patient’s health, silent atrial fibrillation is not routinely screened in patients with advanced hypertension. The aim of the work was to assess the relationship of left atrial dilation and silent atrial fibrillation in patients with resistant arterial hypertension. Design and method: Data were collected in 211 patients with arterial hypertension treated with at least three combinations of antihypertensives with no prior history of atrial fibrillation. The first 109 patients with paroxysmal atrial fibrillation detected at 24-hour monitoring were assigned 102 age-appropriate controls with normal ECG Holter. Transthoracic echocardiography was performed on all patients, comparing baseline parameters of systolic and diastolic function - ejection fraction (EF), E/A velocity ratio, E/e motion velocity ratio, LAVI and peak tricuspid regurgitation gradient (PPG TR). Results: Patients with arterial hypertension and newly captured paroxysmal atrial fibrillation had a significantly higher E wave height (p = 0.005), a higher E/A ratio (p = 0.0004), a comparable E/e’ (p = 0.21), a higher PPG TR (p = 0.045) and a significantly greater left atrial indexed volume-LAVI (36.1 ± 10.3 vs 31.0 ± 9.6, p = 0.0002). Conclusions: Patients with resistant arterial hypertension and paroxysmal atrial fibrilation have significantly higher indexed left atrial volume. Patients with increased LAVI may benefit from performing extended cardiac rhythm monitoring in the prevention of cardioembolic events.

Comparison of Cervical Cancer Screen Results on Female-to-Male Transgender Patients With Female Patients.

There are limited data on cervical screen results from female-to-male (FTM) transgender patients. Herein, we compiled demographic information and cervical screen testing on FTM transgender patients and compared with age-appropriate controls. A search of our previous and current databases was performed for Papanicolaou (Pap) tests from patients taking testosterone and/or with a diagnosis of gender dysphoria, transsexualism, or transvestism. Patient data were reviewed. Relative risks of abnormal Pap smear and human papillomavirus (HPV) infection were calculated against age-matched controls. Eighty-nine Pap tests from FTM transgender individuals were identified, with a mean age of 31.3 years (range, 21-60 years). The Pap test diagnoses were distributed as follows: negative for intraepithelial lesion (n = 84, 94.4%), atypical squamous cells of undetermined significance (n = 0), low-grade intraepithelial lesion (n = 4, 4.5%), and high-grade squamous intraepithelial lesion (n = 1, 1.1%). Fifty (56.2%) patients had concurrent high-risk HPV testing with four (8%) positive results. Relative risk was 0.625 (95% confidence interval [CI], 0.25-1.59; P = .32) for an abnormal Pap test and 0.55 (95% CI, 0.19-1.52; P = .24) for HPV compared with 267 age-matched controls. Of note, 13.5% of patients older than 21 years had documentation of never having a prior Pap test in our medical record. In our study, FTM transgender individuals were not at a higher or lower risk of HPV infection or abnormal Pap test result compared with women. However, larger studies are needed to support our findings.

Osteocalcin: the relationship between bone metabolism and glucose homeostasis in diabetes mellitus

Recent studies have demonstrated the importance of bone as an endocrine organ that produces biologically active substances, which regulate both local bone metabolism and metabolic functions throughout the body. In the process of bone remodeling (formation/destruction), the active cells secrete specific biomarkers that help detect osteometabolic dysfunction. Among bone hormones, osteocalcin plays an important role as a coordinator of bone modeling processes, energy homeostasis, metabolism of glucose, lipids and minerals. Osteocalcin is a structural protein of the bone matrix, which is synthesized by osteoblasts and enters the bloodstream in the process of bone resorption. The level of osteocalcin in the serum is used as a specific marker of bone formation. Osteocalcin promotes pancreatic β-cell proliferation and insulin secretion, and also affects the insulin sensitivity of peripheral tissues. The inverse association of glycemia with the level of osteocalcin was revealed. Patients with type 2 diabetes mellitus usually have normal or even slightly elevated bone mineral density compared to age-appropriate controls. Decreased bone quality and increased risk of fractures are associated with changes in bone microarchitecture and local humoral environment. An imbalance in osteoblast/osteoclast activity may be due to oxidative stress and the accumulation of glycosylation end products, which contributes to chronic inflammation and bone resorbtion in patients with diabetes. It is shown that the level of osteocalcin in the blood serum is significantly reduced compared to healthy controls, both in patients with type 1 diabetes mellitus and, especially, in type 2 diabetes mellitus. Given the importance of developing new approaches to the diagnosis and correction of metabolic disorders in diabetic patients, the study of the influence of bone hormones on hormonal and metabolic parameters and bone status, including the risk of fractures, remains relevant in modern diabetology.

Octogenarians Undergoing Medial Unicompartmental Knee Arthroplasty Have Similar Patient-Reported Outcomes as Their Younger Counterparts

BackgroundAs a procedure with lower surgical morbidity, unicompartmental knee arthroplasty (UKA) may present a practical solution for elderly patients with unicompartmental arthritis. However, few studies have analyzed the results of UKA in the extreme elderly. This study compared the functional and perioperative outcomes between octogenarians and age-appropriate controls undergoing UKA. MethodsProspectively collected data of 44 patients aged ≥80 years who underwent unilateral UKA were analyzed. Each octogenarian was matched 1:3 with 132 patients aged 65-74 years using propensity scores adjusting for gender, body mass index, Charlson comorbidity index, and preoperative scores. Knee Injury and Osteoarthritis Outcome Score for Joint Replacement and Short Form-12 were collected preoperatively and 2 years postoperatively. Complications, reoperations, readmissions, and unplanned visits were recorded up to 1 year postoperatively. ResultsThe mean age was 70.0 ± 2.7 years in the control group and 83.0 ± 3.0 years in the octogenarian group (P < .001). The percentage of outpatient procedures was comparable (control 50.0%; octogenarian 45.5%; P = .601). With the exception of poorer Short Form-12 physical scores in octogenarians at 2 years (39.4 ± 14.1 vs 44.9 ± 9.2, P = .028), there was no difference in final postoperative scores or improvement in scores between the groups. The rate of complications, reoperations, readmissions, and emergency room visits was also similar. The five-year survivorship was 97% in the control group and 93% in the octogenarian group (P = .148). ConclusionOctogenarians undergoing UKA can experience clinical outcomes that are similar to those of their younger counterparts. The clinical trajectory outlined may help clinicians provide valuable prognostic information to elderly patients and guide preoperative counseling.

The molecular features of normal and atopic dermatitis skin in infants, children, adolescents, and adults

Although atopic dermatitis (AD) often presents in infancy and persists into adulthood, comparative characterization of AD skin among different pediatric age groups is lacking. We sought to define skin biopsy profiles of lesional and nonlesional AD across different age groups (0-5-year-old infants with disease duration <6 months, 6-11-year-old children, 12-17-year-old adolescents, ≥18-year-old adults) versus age-appropriate controls. We performed gene expression analyses by RNA-sequencing and real-time PCR (RT-PCR) and protein expression analysis using immunohistochemistry. TH2/TH22 skewing, including IL-13, CCL17/thymus and activation-regulated chemokine, IL-22, and S100As, characterized the common AD signature, with a global pathway-level enrichment across all ages. Nevertheless, specific cytokines varied widely. For example, IL-33, IL-1RL1/IL-33R, and IL-9, often associated with early atopic sensitization, showed greatest upregulations in infants. TH17 inflammation presented a 2-peak curve, with highest increases in infants (including IL-17A and IL-17F), followed by adults. TH1 polarization was uniquely detected in adults, even when compared with adolescents, with significant upregulation in adults of IFN-γ and CXCL9/CXCL10/CXCL11. Although all AD age groups had barrier abnormalities, only adults had significant decreases in filaggrin expression. Despite the short duration of the disease, infant AD presented robust downregulations of multiple barrier-related genes in both lesional and nonlesional skin. Clinical severity scores significantly correlated with TH2/TH22-related markers in all pediatric age groups. The shared signature of AD across ages is TH2/TH22-skewed, yet differential expression of specific TH2/TH22-related genes, other TH pathways, and barrier-related genes portray heterogenetic, age-specific molecular fingerprints.

Maturation of the Human Immunoglobulin Heavy Chain Repertoire With Age.

B cells play a central role in adaptive immune processes, mainly through the production of antibodies. The maturation of the B cell system with age is poorly studied. We extensively investigated age-related alterations of naïve and antigen-experienced immunoglobulin heavy chain (IgH) repertoires. The most significant changes were observed in the first 10 years of life, and were characterized by altered immunoglobulin gene usage and an increased frequency of mutated antibodies structurally diverging from their germline precursors. Older age was associated with an increased usage of downstream IgH constant region genes and fewer antibodies with self-reactive properties. As mutations accumulated with age, the frequency of germline-encoded self-reactive antibodies decreased, indicating a possible beneficial role of self-reactive B cells in the developing immune system. Our results suggest a continuous process of change through childhood across a broad range of parameters characterizing IgH repertoires and stress the importance of using well-selected, age-appropriate controls in IgH studies.

Can Octogenarians Undergoing Total Knee Arthroplasty Experience Similar Functional Outcomes, Quality of Life, and Satisfaction Rates as Their Younger Counterparts? A Propensity Score Matched Analysis of 1188 Patients

BackgroundCurrent literature lacks consensus regarding the impact of advanced age on the clinical outcomes of total knee arthroplasty (TKA). Moreover, there is paucity of literature on the subjective benefit reported by elderly patients. We compared the functional outcomes, quality of life, and satisfaction rates between octogenarians and age-appropriate controls undergoing primary TKA with a minimum follow-up of 2 years. MethodsProspectively collected registry data of 594 patients aged ≥80 years (n = 594) and a propensity score matched cohort of 594 patients aged 65-74 years who underwent primary TKA at a single institution were reviewed. The range of motion, clinical outcome scores, and satisfaction rates were assessed at 6 months and 2 years. Revision rates were also recorded. ResultsOctogenarians had a significantly lower Knee Society Function Score, Oxford Knee Score, and SF-36 Physical Component Summary at 6 months and 2 years (P < .05 for each). Furthermore, a lower proportion of octogenarians achieved the minimal clinically important difference for each score (P < .05 for each). Although the rates were similar at 6 months (P = .853), octogenarians were less satisfied at 2 years compared to age-appropriate controls (89.3% vs 93.3%, P = .042), and there was a trend toward poorer expectation fulfillment (88.4% vs 92.1%, P = .062). ConclusionOctogenarians undergoing TKA had a relatively lower rate of satisfaction and clinically meaningful improvement compared to younger controls. Nevertheless, elderly patients still experienced a successful outcome after surgery. The clinical trajectory outlined may help clinicians provide valuable prognostic information to elderly patients and guide preoperative counseling.

Identification of Potential Core Genes in Immunoglobulin-Resistant Kawasaki Disease Using Bioinformatics Analysis.

Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) is a complex disease, leading to the damage of multiple systems. The pathogen that triggers this sophisticated disease is still unknown. The aim of this study was to identify gene signatures during IVIG-resistant KD and uncover their potential mechanisms. The gene expression profiles of GSE18606 were downloaded from the GEO database. The GSE18606 dataset contained eight IVIG-resistant KD samples and nine healthy age-appropriate controls. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed, and protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software. In total, 73 DEGs were identified in IVIG-resistant KD, including 58 upregulated genes and 15 downregulated genes. GO analysis results showed that DEGs were significantly enriched in biological processes of neutrophil degranulation, neutrophil mediated immunity, and neutrophil activation involved in immune response. Among them, 10 hub genes (S100A8, S100A9, S100A12, HGF, LCN2, LY96, CTGF, MMP8, IRAK3, and SLPI) with a high degree of connectivity were selected. The present study indicated that the identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of IVIG-resistant KD, and might be used as molecular targets and diagnostic biomarkers for the treatment of IVIG-resistant KD.

Exposure to the Chinese famine of 1959–61 in early life and long-term health conditions: a systematic review and meta-analysis

Most Chinese people over 55 years old today have experienced the Great Leap Forward Famine of 1959-61. Many reports suggested that the famine could have profound long-term health effects for exposed birth cohorts. A systematic review and meta-analysis was carried out to summarize reported famine effects on long-term health. Relevant reports were identified by searching PubMed, Embase, Chinese Wanfang Data and Chinese National Knowledge Infrastructure databases. Long-term health conditions were compared in exposed birth cohorts and unexposed controls. Fixed-effects models and random-effects models were used to combine results on adult overweight, obesity, type 2 diabetes, hyperglycaemia, hypertension, the metabolic syndrome and schizophrenia. The heterogeneity across reports was assessed. Subgroup analyses were carried out using reported famine severity, provincial mortality during famine, sex and other report characteristics. In all, 36 reports were eligible for systematic review and 21 could be used for meta-analysis. The number of events we analysed ranged from 1029 for hyperglycaemia to 8973 for hypertension. As reported by others, overweight, type 2 diabetes, hyperglycaemia, the metabolic syndrome, and schizophrenia were more common among adults born during the famine compared with controls born after the famine. By contrast, there were no increases in overweight [odds ratio (OR) 0.68; 95% confidence interval (CI): 0.27-1.72], type 2 diabetes (OR 0.96; 95% CI: 0.73-1.28), hyperglycaemia (OR 0.99; 95% CI: 0.72-1.36) or the metabolic syndrome (OR 1.11; 95% CI: 1.00-1.22) comparing adults born during the famine with controls born either after or before the famine. For schizophrenia, the effect estimates (OR 1.60; 95% CI: 1.50-1.70, combining control groups) were similar in the two scenarios. Our findings suggest that uncontrolled age differences between famine and post-famine births could explain most effects commonly attributed to the famine. For more reliable estimates of long-term famine effects in China, other analyses will be needed with age-appropriate controls and better information on the severity and timing of the famine in the populations included.

Left Atrial 4-Dimensional Flow Magnetic Resonance Imaging: Stasis and Velocity Mapping in Patients With Atrial Fibrillation.

Left atrial (LA) 4-dimensional flow magnetic resonance imaging (MRI) was used to derive anatomic maps of LA stasis, peak velocity, and time-to-peak (TTP) velocity in patients with atrial fibrillation (AF) and to identify relationships between LA flow with LA volume and patient characteristics. Four-dimensional flow MRI for the in vivo assessment of time-resolved 3-dimensional LA blood flow velocities was performed in 111 subjects: 42 patients with a history of AF and in sinus rhythm (AF-sinus), 39 patients with persistent AF (AF-afib), 10 young healthy volunteers (HVs), and 20 age-appropriate controls (CTRL). Data analysis included the 3-dimensional segmentation of the LA and the calculation of LA stasis, peak velocity, and TTP maps. Regional LA flow dynamics were quantified by calculating mean stasis, peak velocity, and TTP in the LA center region and the region adjacent to the LA wall. A sensitivity analysis identified thresholds for global LA stasis (<0.1 m/s) and peak velocity (top 5% LA velocities), which detected significant differences between AF patients and controls for global LA stasis (HV, 25% ± 5%; CTRL, 29% ± 10%; AF-sinus, 41% ± 13%; AF-afib, 52% ± 17%) and peak velocity (HV, 0.43 ± 0.02 m/s; CTRL, 0.37 ± 0.04 m/s; AF-sinus, 0.33 ± 0.05 m/s; AF-afib, 0.30 ± 0.05 m/s). Regional analysis revealed significantly increased stasis at both LA center and wall for AF patients compared with age-appropriate controls (29%-84% difference, P < 0.006) and for AF-afib versus AF-sinus patients (22%-30% difference, P < 0.004). In addition, stasis close to the LA wall was significantly elevated (P < 0.001) compared with the LA center for all subject groups. Multiple regressions revealed significant (RAdj = 0.45-0.50, P < 0.001) relationships between impaired global LA flow (reduced velocity and increased stasis) with age (|β| = 0.27-0.50, P < 0.002) and LA volume (|β| = 0.26-0.50, P < 0.003). Atrial 4-dimensional flow MRI detected changes in global and regional LA flow dynamics associated with AF, age, and LA volume. Longitudinal studies are needed to test the diagnostic value of LA flow metrics as potential risk factors for thromboembolic events.

Three-dimensional left atrial blood flow characteristics in patients with atrial fibrillation assessed by 4D flow CMR.

To apply 4D flow cardiac magnetic resonance (CMR) for the volumetric measurement of 3D left atrial (LA) blood flow to evaluate its potential to detect altered LA flow in patients with atrial fibrillation (AF) and to investigate associations of changes in systolic and diastolic LA flow with the current clinical risk score (CHA2DS2-VASc) used for the assessment of thromboembolic risk in AF. 4D flow CMR was performed in 40 patients with a history of AF (in sinus rhythm during CMR scan, age = 61 ± 11 years), 20 age-appropriate controls (59 ± 7 years), and 10 young healthy volunteers (24 ± 2 years) to measure in vivo time-resolved 3D LA blood flow. LA velocities were characterized with respect to atrial function and timing by calculating normalized LA flow velocity histograms during ventricular systole, early diastole, mid-late diastole, and the entire cardiac cycle. Mean, median, and peak LA velocity steadily decreased when comparing young volunteers, age-appropriate controls, and AF patients by 10-44% and 8-26% for early diastole and the entire cardiac cycle, respectively (P < 0.01 for all comparisons except median velocity for young vs. older volunteers and peak velocity for older volunteers and AF patients). There were moderate but significant inverse relationships between increased CHA2DS2-VASc score and reduced mean LA velocity (early diastole: r = -0.37, P < 0.001; entire RR-interval: r = -0.33, P = 0.005), median LA velocity (r = -0.33, P = 0.003; r = -0.25, P = 0.017), and peak velocity (r = -0.36, P = 0.001; r = -0.45, P < 0.001). LA flow indices also correlated significantly with age and LA volume (R2 = 0.44-0.62, P < 0.001), but not with left ventricular ejection fraction. Left atrial 4D flow CMR demonstrated significantly reduced LA blood flow velocities in patients with AF. Further study is needed to determine whether these measures can improve upon the CHA2DS2-VASc score for stroke risk prediction and enhance individual decisions on anticoagulation in patients with AF.

High-Fat Diet–Induced Retinal Dysfunction

The purpose of this study was to investigate the impact of obesity-induced prediabetes/early diabetes on the retina to provide new evidence on the pathogenesis of type 2 diabetes-associated diabetic retinopathy (DR). A high-fat diet (HFD)-induced obesity mouse model (male C57BL/6J) was used in this study. At the end of the 12-week HFD feeding regimen, mice were evaluated for glucose and insulin tolerance, and retinal light responses were recorded by electroretinogram (ERG). Western immunoblot and immunohistochemical staining were used to determine changes in elements regulating calcium homeostasis between HFD and control retinas, as well as unstained human retinal sections from DR patients and age-appropriate controls. Compared to the control, the scotopic and photopic ERGs from HFD mice were decreased. There were significant decreases in molecules related to cell signaling, calcium homeostasis, and glucose metabolism from HFD retinas, including phosphorylated protein kinase B (pAKT), glucose transporter 4, L-type voltage-gated calcium channel (L-VGCC), and plasma membrane calcium ATPase (PMCA). Similar changes for pAKT, PMCA, and L-VGCC were also observed in human retinal sections from DR patients. Obesity-induced hyperglycemic and prediabetic/early diabetic conditions caused detrimental impacts on retinal light sensitivities and health. The decrease of the ERG components in early diabetes reflects the decreased neuronal activity of retinal light responses, which may be caused by a decrease in neuronal calcium signaling. Since PI3K-AKT is important in regulating calcium homeostasis and neural survival, maintaining proper PI3K-AKT signaling in early diabetes or at the prediabetic stage might be a new strategy for DR prevention.

Circulation: Clinical Summaries.

Circulation: Clinical Summaries.

Serum zinc levels in hospitalized children with acute lower respiratory infections in the north-central region of Nigeria

Macronutrient deficiency has continued to attract significant research interest, where as the import of micronutrients like zinc has only recently become the focus of interest. Thus against the background of a dearth of data on zinc levels in Nigerian children with Acute Lower Respiratory Infection (ALRI), this study was carried out in Ilorin, Nigeria to determine the serum zinc levels in hospitalized children with ALRI. A comparative cross-sectional hospital based study involving 120 children aged two months to five years with ALRI recruited as subjects, and 120 age-appropriate controls without ALRI was carried out. Socio-demographic, clinical and laboratory data were obtained. The serum zinc was analyzed with a Jenway™ spectrophotometer after an initial preparation with the QuantiChrom™ zinc assay kit. The male/ female ratio was 1.6:1. The mean (SD) serum zinc level in subjects with ALRI of 18.7(11.8)µg/dl was significantly lower than the corresponding value of 53.1(18.5)µg/dl recorded in the controls, p=0.001. The prevalence of 98.3% for low serum zinc levels recorded in children with ALRI was significantly higher than that recorded in controls of 64.2%, p=0.001. Low serum zinc levels are significantly associated with ALRI. There is a need to determine whether hospitalized children managed for ALRI might benefit from post discharge zinc supplementation.

Elevated serum lactate dehydrogenase isoenzymes and aspartate transaminase distinguish Albers-Schönberg disease (Chloride Channel 7 Deficiency Osteopetrosis) among the sclerosing bone disorders

Osteopetrosis (OPT) refers to the consequences of generalized failure of skeletal resorption during growth. Most cases are explained by loss-of-function mutation within the genes that encode either chloride channel 7 (CLCN7) or a vacuolar proton pump subunit (TCIRG1), each compromising acid secretion by osteoclasts. Patients suffer fractures and sometimes cranial nerve entrapment and insufficient medullary space for hematopoiesis. In 1996, we reported that a high serum level of the brain isoenzyme of creatine kinase (BB-CK), the CK of osteoclasts, characterizes OPT dueamong the sclerosing bone disorders (J Clin Endocrinol Metab. 1996;11:1438). Now, we show that elevation in serum of multiple lactate dehydrogenase (LDH) isoenzymes with aspartate transaminase (AST) distinguishes autosomal dominant OPT due to loss-of-function mutation in CLCN7 [Albers-Schönberg disease (A-SD)] among these conditions. Serum total LDH and AST levels as high as 3× and 2×, respectively, the upper limits of normal for age-appropriate controls, were persistent and essentially concordant in A-SD. Serum LDH was elevated in 7 of 9 children and in the 2 adults studied with A-SD. LDH isoenzyme quantitation showed excesses of LDH-2, -3, and -4. Neither total LDH nor AST increases were found in other forms of OPT, including bisphosphonate-induced OPT, or in 41 children and 6 adults representing 20 additional sclerosing bone disorders. Serum TRACP-5b and BB-CK also were markedly elevated in A-SD. Hence, high serum levels of several enzymes characterize A-SD. Elevated serum LDH isoenzymes and AST indicate a disturbance (of uncertain clinical significance) within multiple extraosseous tissues when there is CLCN7 deficiency.

Age-dependent changes in peripheral blood dendritic cell subsets in normal children and children with specific polysaccharide antibody deficiency (SPAD)

Myeloid and plasmacytoid dendritic cells (MDC/PDC) play crucial roles in bridging adaptive and innate immunity by affecting development of both cellular and humoral immunity. The immune system evolves after birth as reflected in dynamic changes in numbers and functions of various immune cells with age. However, age-associated changes in DC subsets in children have not been elucidated despite the fact that such normative data are crucial for evaluating alternations of DC subsets in various pediatric diseases. This study addressed age-associated changes in DC subsets and CD40/86 expression on PDC (markers of maturation/activation) in 50 healthy children in comparison with 25 children with specific polysaccharide antibody deficiency (SPAD). Our results revealed age-dependent decrease of PDC numbers (p < 0.0001), although there was no age-associated changes in CD40/CD86 expression. MDC1/MDC2 numbers did not reveal such linear age-dependent changes and MDC1/PDC ratio reached around 2 as typically seen in young adults after 10 years of age. In contrast, SPAD patients did not reveal such age-associated changes and showed decreased fluorescence intensity of CD86 in PDC cells. These results indicate lineage specific, age-dependent changes in DC subsets in normal children and possible altered development of these cells in SPAD children, emphasizing the importance of age-appropriate controls.