Age-dependent Structural Changes Research Articles

Developing an interactive online curriculum directed at pediatric trainees for instruction on pediatric electrocardiogram interpretation

BackgroundInterpretation of pediatric ECG is a specific skill set that requires familiarity with normal electrographic changes in the developing heart, common pediatric dysrhythmias, and conduction alterations secondary to structural lesions. Previous studies showed that pediatric trainees are neither comfortable nor proficient in ECG reading. ObjectivesWe aimed to develop an interactive self-learning curriculum for teaching pediatric ECG interpretation. MethodsIn a collaboration between pediatric residents and cardiologists, we identified high-yield topics, ‘red flags,’ and age-related normal variances that are important to recognize. We built a 5–10-minute teaching module for each topic using Adobe Captivate. The modules were available online on a shared server. Participants were asked to take pre- and post-participation surveys and interpretation skill tests to define knowledge gaps and to focus our curricular development. ResultsThe workgroup defined 14 topics for the teaching modules. The pre-participation survey and test were completed by 74 learners (53 % pediatric residents, 29% pediatric advanced care provider fellows, and others). Only 22 % and 26 % reported comfort with distinguishing normal from abnormal ECG or identifying common arrhythmias, respectively; only one learner reported feeling comfortable identifying signs of structural abnormalities. Of this group, 16 participants completed all 14 modules and took the post-test. They reported improved confidence and scored higher on performance test (p = 0.02). ConclusionWe present a newly developed educational program for ECG interpretation that centers on visual learning and pattern recognition of high-yield findings in pediatrics. Initial surveys confirm the need for an accessible teaching tool that is asynchronous and can answer the specific topics of interest of each learner. We intend to share our education material for broader use outside of our institution.

Infiltration of subcutaneous adipose layer into the dermal layer with aging.

The elasticity of the dermal layer decreases with aging, leading to ulcer formation and wrinkling, but the mechanism of this change is not fully understood, because it is difficult to access the complex three-dimensional (3D) internal structure of the dermis. To clarify age-dependent changes in the overall 3D structure of the dermal layer by means of 3D analysis technology. We observed sun-protected human skin by means of X-ray micro CT, identified the layers of the skin, and reconstructed the 3D structure on computer. Age-dependent structural changes of the dermal layer were evaluated by statistical comparison of young and aged skin. Histological observations suggested the presence of two types of ectopic fat deposits, namely infiltrated subcutaneous fat and isolated fat, in the lower region of the reticular dermal layer in aged skin. To elucidate their nature, we observed skin specimens by X-ray microCT. The epidermis, dermal layer, and subcutaneous adipose layer were well differentiated on CT images, and 3D skin was digitally reconstructed on computer. This method clearly showed that the isolated fat observed histologically was in fact connected to the subcutaneous fat, namely all ectopic fat is connected to the subcutaneous adipose layer. Statistical analysis showed that the severity of fat infiltration into dermal layer is significantly increased in aged skin compared with young skin. Our findings indicate that subcutaneous fat infiltrates into the dermal layer of aged skin. Our 3D analysis approach is advantageous to understand changes of complex internal skin structures with aging.

Why is delirium more frequent in the elderly?

An aging-related reduction in the brain’s functional reserve may explain why delirium is more frequent in the elderly than in younger people insofar as the reserve becomes inadequate to cover the metabolic requirements that are critically increased by stressors. The aim of this paper is to review the normal aging-related changes that theoretically compromise complex mental activities, neuronal and synaptic densities, and the neurocomputational flexibility of the functional reserve. A pivotal factor is diminished connectivity, which is substantially due to the loss of synapses and should specifically affect association systems and cholinergic fibres in delirious patients. However, micro-angiopathy with impaired blood flow autoregulation, increased blood/brain barrier permeability, changes in cerebrospinal fluid dynamics, weakened mitochondrial performance, and a pro-inflammatory involution of the immune system may also jointly affect neurons and their synaptic assets, and even cause the progression of delirium to dementia regardless of the presence of co-existing plaques, tangles, or other pathological markers. On the other hand, the developmental growth in functional reserve during childhood and adolescence makes the brain increasingly resistant to delirium, and residual reserve can allow the elderly to recover. These data support the view that functional reserve is the variable that confronts stressors and governs the risk and intensity of and recovery from delirium. Although people of any age are at risk of delirium, the elderly are at greater risk because aging and age-dependent structural changes inevitably affect the brain’s functional reserve.

Astrocyte dystrophy in ageing brain parallels impaired synaptic plasticity.

Little is known about age‐dependent changes in structure and function of astrocytes and of the impact of these on the cognitive decline in the senescent brain. The prevalent view on the age‐dependent increase in reactive astrogliosis and astrocytic hypertrophy requires scrutiny and detailed analysis. Using two‐photon microscopy in conjunction with 3D reconstruction, Sholl and volume fraction analysis, we demonstrate a significant reduction in the number and the length of astrocytic processes, in astrocytic territorial domains and in astrocyte‐to‐astrocyte coupling in the aged brain. Probing physiology of astrocytes with patch clamp, and Ca2+ imaging revealed deficits in K+ and glutamate clearance and spatiotemporal reorganisation of Ca2+ events in old astrocytes. These changes paralleled impaired synaptic long‐term potentiation (LTP) in hippocampal CA1 in old mice. Our findings may explain the astroglial mechanisms of age‐dependent decline in learning and memory.

Conditional Deletion of HIF-2α in Mouse Nucleus Pulposus Reduces Fibrosis and Provides Mild and Transient Protection From Age-Dependent Structural Changes in Intervertebral Disc.

Hypoxia-inducible factors (HIFs) are critical to the development and homeostasis of hypoxic tissues. Although HIF-2α, one of the main HIF-α isoforms, is expressed in nucleus pulposus (NP) cells, its functions remain unknown. We deleted HIF-2α in the NP tissue using a notochord-specific FoxA2Cre allele to study HIF-2α function in the adult intervertebral disc. Unlike observations in HIF-1αcKO mice, fate mapping studies using Rosa26-mTmG reporter showed that HIF-2α loss in NP did not negatively impact cell survival or affect compartment development. Rather, loss of HIF-2α resulted in slightly better attributes of NP morphology in 14-month-old HIF-2αcKO mice as evident from lower scores of degeneration. These 14-month-old HIF-2αcKO mice also exhibited significant reduction in NP tissue fibrosis and lower collagen turnover in the annulus fibrosis (AF) compartment. Imaging-Fourier transform-infrared (FTIR) analyses showed decreased collagen and protein content in the NP and maintained chondroitin sulfate levels in 14-month-old HIF-2αcKO . Mechanistically, global transcriptomic analysis showed enrichment of differentially expressed genes with Gene Ontology (GO) terms related to metabolic processes and cell development, molecular functions concerned with histone and protein binding, and associated pathways, including oxidative stress. Noteworthy, these morphological differences were not apparent in 24-month-old HIF-2αcKO , indicating that aging is the dominant factor in governing disc health. Together these data suggest that loss of HIF-2α in the NP compartment is not detrimental to the intervertebral disc development but rather mitigates NP tissue fibrosis and offers mild but transient protection from age-dependent early degenerative changes. © 2022 American Society for Bone and Mineral Research (ASBMR).

Influence of the structural development of bursa on the susceptibility of chickens to infectious bursal disease virus

Infectious bursal disease (IBD), caused by IBD virus (IBDV), is an acute, highly contagious immunosuppressive avian disease. Although age-dependent changes in susceptibility of chickens to IBDV have been established, the relationship between age-dependent structural changes in bursa of Fabricius and susceptibility of chickens to IBDV is still unclear. In the present study, we examined the bursa anatomical structure and pathological changes in specific-pathogen-free (SPF) white leghorn chickens 0 to 8 weeks post hatch (w.p.h.) and IBDV BC6/85-infected SPF chickens 2 to 6 w.p.h. respectively, by histology, histopathology, immunohistochemistry, and transmission electron microscopy. Almost all IBDV-exposed chickens (2 to 6 w.p.h.) were infected, with the severest bursal inflammation and complication in chickens at 3 w.p.h. Furthermore, the bursae of healthy chickens at 3 to 6 w.p.h. had decreased laminin immunoreactivities, lots of splits, and irregular shapes in basement membrane (BM) of cortico-medullary epithelium (CME), irregularly arranged CME, and large numbers of immunoglobulin M-bearing (IgM+) B lymphocytes in the medulla. The decreased barrier function of corticomedullary border and large amount of IgM+ B lymphocytes provide a chance for IBDV to easily contact and infect target cells at 3 to 6 w.p.h. By contrast, regular BM, neatly arranged CME, and few IgM+ B lymphocytes in healthy chickens younger than 2 w.p.h., as well as reduced IgM+ B lymphocytes and high immunoglobulin A (IgA) content in healthy chickens older than 8 w.p.h., were observed, suggesting that the integrity of corticomedullary border barrier, a small amount of target cells and high IgA content of the bursa could be the reasons for these chickens being less susceptible to IBDV. Although studies have shown how IBDV affects bursa, we focus first on the age-dependent changes of CME, BM of CME and IgA content, and our findings are the first to elucidate the structural development of bursa in relation to IBDV susceptibility from a morphological perspective.

Normal Developmental Globe Morphology on Fetal MR Imaging.

Age-dependent structural changes of the globes occur during gestation. The posterolateral globe margins bulge outward, and the eyes are conical in early gestation. Later, the globes are ellipsoid. The purpose of this study was to establish normal developmental fetal globe morphology. The fetal MR imaging data base at an academic children's hospital was queried for all brain MRIs performed during 8 years. Motion artifacts, brain/craniofacial/globe malformations, and chromosomal defects were exclusion criteria. Two board-certified neuroradiologists evaluated each examination for globe shape (elliptic/nonelliptic) and hyaloid visibility. Logistic regression was used to evaluate correlations among variables. Age-specific cut-points for globe shape and hyaloid visibility were chosen to optimize specificity. We identified 1243 examinations from 1177 patients. Six hundred eighty-two examinations met the inclusion criteria (17-39 weeks). Receiver operating characteristic analysis showed that age was highly predictive of globe shape (area under the curve = 0.99) and fetal vasculature visibility (area under the curve = 0.94). Nonelliptic globes were universal up to 22 weeks. Thereafter, globes gradually assumed an elliptic shape, present in nearly all patients 29 weeks and older (sensitivity, 81%; 95% CI, 76%-85%; specificity, 99%; 95% CI, 98%-100%). The hyaloid vasculature was visible in most patients up to 19 weeks and occasionally in those at 20-24 weeks, but never in those 25 weeks and older (sensitivity, 69%; 95% CI, 65%-72%; specificity, 100%; 95% CI, 95%-100%). Physiologic nonspheric globe shapes are normal up to 29 weeks' gestation and should not be misinterpreted as pathologic. Thereafter, globes are generally elliptic. The timing of this process coincides with the resolution of the primary vitreous and may be related.

Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.

Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.

Abstract 15308: SPARC Deletion Suppresses Age-related Cardiac Inflammation

Secreted protein acidic and rich in cysteine (SPARC) is a collagen-binding matricellular protein that facilitates the formation and assembly of mature cross-linked collagen fibrils. We previously reported that aged mice exhibit increased SPARC levels in the heart, and SPARC deletion inhibits age-related collagen deposition. The present study investigated whether SPARC deletion could suppress age-related cardiac inflammation. Six groups of mice were studied: young (3-5 month old), middle-aged (10-12 m.o.) and old (18-29 m.o.) C57BL/6J wild type (WT) and SPARC-null (Null) mice (n=5-10 per group). Echocardiography and histology revealed that LV wall thickness and myocyte size were 15% and 43% increased with age in WT, respectively (both p<0.05 old versus young). These age-dependent structural changes were blunted in the Null. The pro-inflammatory chemokines Ccl5 and Ccr2 were increased in middle-aged and old WT, and Cxcl1 was increased in old WT, compared to young WT (all p<0.05). Interestingly, the age-dependent increases in Ccl5, Ccr2, and Cxcl1 were delayed in Null. Migration inhibitory factor (Mif) and Cx3cl1 showed an age-dependent increase in both WT and Null. Cxcl5 expression levels increased age-dependently only in Null, suggesting a compensatory increase for the decline of other chemokines. In summary, these results suggest that SPARC deletion slowed age-related cardiac inflammation.

Choline Alphoscerate (Alpha-Glyceryl-Phosphoryl-Choline) An Old Choline- containing Phospholipid with a Still Interesting Profile As Cognition Enhancing Agent

Cholinergic precursors have represented the first approach to counter cognitive impairment occurring in adultonset dementia disorders. These compounds were early leaved because their clinical efficacy was not clearly demonstrated. This is probably not true for some choline-containing phospholipids including choline alphoscerate. Choline alphoscerate increases the release of acetylcholine in rat hippocampus, facilitates learning and memory in experimental animals, improves brain transduction mechanisms and decreases age-dependent structural changes occurring in rat brain areas involved in learning and memory. The compound exerts neuroprotective effects in models of altered cholinergic neurotransmission and of brain vascular injury. In clinical studies choline alphoscerate improved memory and attention impairment, as well as affective and somatic symptoms in dementia disorders. An ongoing trial indicates that association between the acetylcholinesterase inhibitor donepezil and choline alphoscerate is accompanied by an improvement in several cognitive tests superior to that induced by donepezil alone. It is suggested that this association may represent a therapeutic option to prolong beneficial effects of cholinergic therapies in Alzheimer's disease patients with concomitant ischemic cerebrovascular disorders. In summary, choline alphoscerate has significant effects on cognitive function with a good safety profile and tolerability. Although limited both in terms of size of the samples investigated and of the length of treatment, preclinical and clinical results presented suggest that cognitive enhancing capabilities of choline alphoscerate merit of being further investigated in appropriate trials.

Diffusion tensor imaging: the normal evolution of ADC, RA, FA, and eigenvalues studied in multiple anatomical regions of the brain

The aim of our work was to investigate the process of myelination in healthy patients using the diffusion parameters apparent diffusion coefficient (ADC), relative anisotropy (RA), fractional anisotropy (FA), and eigenvalues. Age-dependent changes were assessed using the slope m of the fit functions that best described the data. Seventy-two patients (3 weeks-19 years) without pathological magnetic resonance imaging findings were selected from all pediatric patients scanned with diffusion tensor imaging over a 5-year period at our institution. ADC, RA, FA, and eigenvalue maps were calculated and regions of interest were selected in anterior/posterior pons, genu/splenium of corpus callosum (CC), anterior/posterior limb of internal capsule (IC), and white matter (WM) regions (frontal, temporal, parietal, occipital WM). Statistical analysis was performed using Spearman correlation coefficient and regression analysis. Mean values ranged 71.6 x 10(-5) to 90.3 x 10(-5) mm(2)/s (pons/parietal WM) for ADC, 0.32-0.94 (frontal WM/CC) for RA, and 0.36-0.81 (frontal WM/splenium) for FA. Logarithmic fit functions best described the data. Strong age influences were observed for CC, pons, and parietal/frontal WM and changes were significant for all three eigenvalues, most pronounced for perpendicular eigenvalues. Changes in RA and FA differed depending on the structure anisotropy. Changes observed for ADC, RA, FA, and eigenvalues with age were consistent with previous findings. Changes detected for RA and FA varied due to the different scaling of both parameters. We found that the use of the largely linear scaled RA adds more valuable information for the assessment of age-dependent structural changes as compared to FA. Additionally, we report normative values for the diffusion parameters studied.

Age-dependent changes in structure and function of the male labial gland in Bombus terrestris

The cephalic region of the labial gland in the buff-tailed bumblebee, Bombus terrestris, consists of numerous acini (formed by associated secretory cells and a central lumen) and connecting ducts. Age-dependent changes in secretion production (both qualitative and quantitative) are associated with changes in the amount of rough endoplasmic reticulum (RER), Golgi apparatus, and smooth endoplasmic reticulum (SER). The main secretory organelle is RER in the youngest individuals (pharate, and less-than-a-day old males), Golgi apparatus in 1-day-old males, and SER in males older than 2 days. Secretory cell death starts at 5 days of age, with maximal longevity to 10 days. Pheromone production starts immediately after eclosion, with pheromone quantities increasing until day 7. 2,3-Dihydrofarnesol, the main component of the male-marking pheromone, appears in 1-day-old male glands, and reaches a maximum at 7 days of age, when its presence in the gland starts to decrease gradually. Older glands contain compounds not present in young ones. Variation in pheromone quantity and composition are reflected sensitively in the response of the queen antennae. Though queen antennae responded to gland extracts of all ages examined, maximum sensitivity was observed in response to extracts of glands 2–10 days old, while extracts of older glands gradually lose their effectiveness. Both major and minor components of the labial gland secretion extract elicited queen antennal responses suggesting that the pheromone is a multicomponent blend. Age-dependent changes in pheromone production, accumulation and tuning of pheromone activity are all synchronized approximately with male flight from the hive.

Speed of sound measurements in mandibular and phalangeal bone during growth

The micromechanical and elastic properties of bone, its structural maturity and, indirectly, mineral density are important factors for the planning and assessment of orthodontic and/or jaw orthopaedic treatment. This clinical study was undertaken to evaluate age-related changes in the anterior mandibular body. The speed of sound (SOS) has demonstrated age dependency in various peripheral bones and has been proposed as an alternative method for investigating bone parameters without the use of radiation. The ultrasound transmission velocity was measured in 184 healthy subjects (93 females, 91 males; mean age 17.6 +/- 13.7 years). According to the statistical analysis, the data did not reveal any gender-related differences, but were significantly age-dependent. Different kinetics were established between the maturity of the phalanx and the anterior mandible. Further clinical investigations of age-dependent structural changes in bone maturation parameters may provide information that should be taken into account for early functional jaw orthopaedic treatment.

Effect of long-term treatment with EGb 761 on age-dependent structural changes in the hippocampi of three inbred mouse strains

Female mice of the inbred strains C57BL/6J, BALB/cJ and DBA/2J were used to determine the possible existence of a genetically-based differential susceptibility to the effects of treatment with an extract of Ginkgo biloba (EGb 761). Timm's silver-sulphide staining method was used to visualize and determine changes in the areas of the hippocampal structures of aged subjects, and more specifically on the projection fields of the mossy fibers which appear to decrease as a function of ageing. Experiments were begum when the animals were 15 months old. Treated animals received EGb 761 (50 mg/kg/day, p.o.) for 7 months in their drinking water. Inter-strain differences existed for the areas of the whole regio inferior, stratum pyramidale, stratum lacunosum moleculare and hilus (CA4) and for the projection field of intra- and infrapyramidal mossy fibers (iipMF) in the CA3 region of the hippocampus. Chronic treatment with EGb 761 significantly increased the projection field of iipMF and significantly reduced the area of the stratum radiatum, as compared with control mice. No differential sensitivity to EGb 761 existed among the mouse strains tested. Antioxydant properties of EGb 761 may explain its neuroprotective and neurotrophic actions on the hippocampus, and might explain certain improvements in memory and other cognitive functions in both humans and experimental animals.

Age-dependent structural changes in intact human lenses detected by synchrotron radiation X-ray scattering. Correlation with Maillard reaction protein fluorescence.

To understand alterations in the spatial organization of the crystallins, the major determinant of lens transparency, the x-ray scattering by intact normal human lenses from individuals 6-82 years of age was measured using synchrotron radiation. The angular dependence of the integrated scattering intensity is consistent with short-range order within the crystallin assemblies. A significant change in the scattering patterns of the lenses occurs after 55 years of age, in parallel with an increase of the fluorescence of the urea-insoluble crystallin fraction. This correlation suggests a gradual derangement of the short-range order as a result of cross-linking of the crystallin subunits by advanced Maillard reaction products that are generated by the continuous reaction of sugars, such as glucose or fructose, with proteins.

Long-term choline alfoscerate treatment counteracts age-dependent structural changes in the rat hippocampus

Long-term choline alfoscerate (αGFC) treatment counteracts age-dependent structural changes in the hippocampus of Sprague-Dawley rats. Animals treated with a daily dose of 100 mg/kg αGFC from 18 to 24 months of age had more cells in the CA-1 to CA-3 fields and in the dentate gyrus compared to age-matched cohorts. The density of silver-gold stained fibers within the stratum oriens of the CA-1 to CA-2 fields was greater in rats treated with αGFC than in age-matched controls. The ramifications of these findings are discussed. © 1992 Wiley-Liss, Inc.

Age-dependent structural changes in the myocardium of rats. A quantitative light- and electron-microscopic study on the right and left chamber wall

Myocardial fine structure of 6-week-old and 2-year-old female Wistar rats was examined after fixation by perfusion. Qualitatively, lipid droplets, lipofuscin granules and myelin figures were found more often in the older animals. Quantitatively, the volume density of the interstitium of the right ventricular myocardium had significant increased (52%) in the 2-year-old rats. In these animals a reduction (9%) in the volume fraction of mitochondria in the left ventricular myocytes was seen, while the volume fraction of myofibrils had increased by 10%. The numerical density of mitochondria had significantly increased in the left ventricular myocardium of the older rats by 42%. A decrease in the average size of a mitochondrion by 36% could be shown in the left and by 11% in the right ventricular myocytes of the 2-year-old rats. In these animals the myofibrillar transverse diameter diminished by 15% in the left and by 6% in the right ventricular wall, while the number of myofibrils had increased by 36% and 12%, respectively; these findings signify a close relationship in the number of mitochondria and myofibrils in myocytes. Quantitative alterations in the myocytes of aged rats are more obvious in the left than in the right chamber wall. A reduced mitochondria/myofibril ratio may contribute to the diminished functional adaptability of the aging heart.

Morphologische Veränderungen im Ganglion ciliare bei Gesunden und Glaukomkranken

The authors studied morphological changes in eleven ciliary ganglions. Seven ganglions were obtained from four corpses of patients with primary glaucoma in different stages, and four control ganglions were obtained from corpses of healthy people. The ciliary ganglion neurons of healthy subjects demonstrated age-related changes revealing nucleus shift toward the periphery, atypical hairy Kahal neurons, nerve fiber irritation phenomena, and other effects. The stage-dependent changes observed included: devastation areas, reactive proliteration around prolapsed neurons, nerve fiber degeneration, and hemorrhages. Maturing glaucomatous nerve cells and fiber degeneration also grew in proportion. In absolute glaucoma, ganglion cells were not present in ganglions. The authors believe that the existence of age-dependent structural changes in ciliary ganglia shows that ciliary ganglia are responsible for neurotropic innervation of eye membranes and participate in the glaucomatous process.

Age dependent structural changes in the diol esters of uropygial glands of chicken.

AbstractThe chain lengths and diastereoisomer composition of alkane‐2, 3‐diol diesters of the uropygial glands of chicken changed significantly as the birds became physiologically mature. The C24 diol decreased, and C22 and C23 diols increased. Threo isomer content of the diols decreased. In the acyl portion, the shorter (C12−C15) acids decreased, and the longer (C17−C20) acids increased.