Age-dependent Patterns Research Articles

Two-Age-Structured COVID-19 Epidemic Model: Estimation of Virulence Parameters to Interpret Effects of National and Regional Feedback Interventions and Vaccination

The COVID-19 epidemic has recently led in Italy to the implementation of different external strategies in order to limit the spread of the disease in response to its transmission rate: strict national lockdown rules, followed first by a weakening of the social distancing and contact reduction feedback interventions and finally the implementation of coordinated intermittent regional actions, up to the application, in this last context, of an age-stratified vaccine prioritization strategy. This paper originally aims at identifying, starting from the available age-structured real data at the national level during the specific aforementioned scenarios, external-scenario-dependent sets of virulence parameters for a two-age-structured COVID-19 epidemic compartmental model, in order to provide an interpretation of how each external scenario modifies the age-dependent patterns of social contacts and the spread of COVID-19.

Dynamic Changes of Brain Cilia Transcriptomes across the Human Lifespan.

Almost all brain cells contain primary cilia, antennae-like microtubule sensory organelles, on their surface, which play critical roles in brain functions. During neurodevelopmental stages, cilia are essential for brain formation and maturation. In the adult brain, cilia play vital roles as signaling hubs that receive and transduce various signals and regulate cell-to-cell communications. These distinct roles suggest that cilia functions, and probably structures, change throughout the human lifespan. To further understand the age-dependent changes in cilia roles, we identified and analyzed age-dependent patterns of expression of cilia’s structural and functional components across the human lifespan. We acquired cilia transcriptomic data for 16 brain regions from the BrainSpan Atlas and analyzed the age-dependent expression patterns using a linear regression model by calculating the regression coefficient. We found that 67% of cilia transcripts were differentially expressed genes with age (DEGAs) in at least one brain region. The age-dependent expression was region-specific, with the highest and lowest numbers of DEGAs expressed in the ventrolateral prefrontal cortex and hippocampus, respectively. The majority of cilia DEGAs displayed upregulation with age in most of the brain regions. The transcripts encoding cilia basal body components formed the majority of cilia DEGAs, and adjacent cerebral cortices exhibited large overlapping pairs of cilia DEGAs. Most remarkably, specific α/β-tubulin subunits (TUBA1A, TUBB2A, and TUBB2B) and SNAP-25 exhibited the highest rates of downregulation and upregulation, respectively, across age in almost all brain regions. α/β-tubulins and SNAP-25 expressions are known to be dysregulated in age-related neurodevelopmental and neurodegenerative disorders. Our results support a role for the high dynamics of cilia structural and functional components across the lifespan in the normal physiology of brain circuits. Furthermore, they suggest a crucial role for cilia signaling in the pathophysiological mechanisms of age-related psychiatric/neurological disorders.

Age-dependent patterns of spatial autocorrelation in fish populations.

The degree of spatial autocorrelation in population fluctuations increases with dispersal and geographical covariation in the environment, and decreases with strength of density dependence. Because the effects of these processes can vary throughout an individual's lifespan, we studied how spatial autocorrelation in abundance changed with age in three marine fish species in the Barents Sea. We found large interspecific differences in age-dependent patterns of spatial autocorrelation in density. Spatial autocorrelation increased with age in cod, the reverse trend was found in beaked redfish, while it remained constant among age classes in haddock. We also accounted for the average effect of local cohort dynamics, i.e. the expected local density of an age class given last year's local density of the cohort, with the goal of disentangling spatial autocorrelation patterns acting on an age class from those formed during younger age classes and being carried over. We found that the spatial autocorrelation pattern of older age classes became increasingly determined by the distribution of the cohort during the previous year. Lastly, we found high degrees of autocorrelation over long distances for the three species, suggesting the presence of far-reaching autocorrelating processes on these populations. We discuss how differences in the species' life history strategies could cause the observed differences in age-specific variation in spatial autocorrelation. As spatial autocorrelation can differ among age classes, our study indicates that fluctuations in age structure can influence the spatio-temporal variation in abundance of marine fish populations.

'Keeping the kids at home' can limit the persistence of contagious pathogens in social animals.

Social networks are considered to be 'highly modular' when individuals within one module are more connected to each other than they are to individuals in other modules. It is currently unclear how highly modular social networks influence the persistence of contagious pathogens that generate lifelong immunity in their hosts when between-group interactions are age dependent. This trait occurs in social species with communal nurseries, where juveniles are reared together for a substantial period in burrows or similar forms of containment and are thus in isolation from contact with individuals in other social groups. Our main objective was to determine whether, and to what extent, such age-dependent patterns of between-group interactions consistently increased the fade-out probability of contagious pathogens that generate lifelong immunity in their hosts. We hypothesised that in populations of species where juveniles are raised in communal nurseries, a high proportion of recovered adults in a group would form a 'protective barrier' around susceptible juveniles against pathogen transmission, thereby increasing the probability of epidemic fade-out in the population. To test this idea, we implemented a spatially implicit individual-based susceptible-infected-recovered (SIR) model for a large range of generic host and pathogen traits. Our results indicated that (a) the probability of epidemic fade-out was consistently higher in populations with communal nurseries, especially for highly contagious pathogens (high basic reproduction number, R0 ) and (b) communal nurseries can counteract the cost of group living in terms of infection risk to a greater extent than variation in other traits. We discuss our findings in relation to herd immunity and outline the importance of considering the network structure of a given host population before implementing management measures such as vaccinations, since interventions focused on individuals with high between-group contact should be particularly effective for controlling pathogen spread in hosts with communal nurseries.

Examining age-dependent DNA methylation patterns and gene expression in the male and female mouse hippocampus

DNA methylation is a well-characterized epigenetic modification involved in numerous molecular and cellular functions. Methylation patterns have also been associated with aging mechanisms. However, how DNA methylation patterns change within key brain regions involved in memory formation in an age- and sex-specific manner remains unclear. Here, we performed reduced representation bisulfite sequencing (RRBS) from mouse dorsal hippocampus – which is necessary for the formation and consolidation of specific types of memories – in young and aging mice of both sexes. Overall, our findings demonstrate that methylation levels within the dorsal hippocampus are divergent between sexes during aging in genomic features correlating to mRNA functionality, transcription factor binding sites, and gene regulatory elements. These results define age-related changes in the methylome across genomic features and build a foundation for investigating potential target genes regulated by DNA methylation in an age- and sex-specific manner.

Neonatal FeNO, risk factors, and respiratory morbidity in infants: A cohort study.

Respiratory symptoms in infancy are more common in premature infants. Nitric oxide (NO) is involved in prenatal and neonatal lung development. Measurement of exhaled NO is easy and well-tolerated by neonates. We investigated whether neonatal exhaled NO can be used to predict subsequent respiratory symptoms. Furthermore, we sought to determine prenatal and postnatal factors associated with increased respiratory symptom risk during the first year of life in premature and mature infants. Tidal fractional exhaled NO (FeNO) was measured in a birth cohort (n = 135) of premature and mature infants, up to six times during the first month of life. Primary outcomes were troublesome respiratory symptoms (TRS) and doctor-diagnosed asthmatic bronchitis (AB) at 1 year of age. The correlation between FeNO and TRS changed significantly in an age-dependent pattern in moderately premature infants (p = .02). Moderately premature infants with a low FeNO of 2 ppb on postnatal Day 3 had a 48% (95% confidence interval [CI]: 17%-80%) probability of TRS, compared with a probability of 12% (95% CI: 1%-64%) for otherwise similar infants with a FeNO of 11 ppb. Respiratory syncytial virus infection and parental smoking significantly increased the TRS risk in premature infants. Parental asthma and maternal antibiotic use during pregnancy significantly increased the TRS risk in mature infants. An age-specific association between neonatal FeNO and respiratory symptoms was seen in moderately premature infants. TRS risk was associated with postnatal factors in premature and prenatal factors in mature infants.

Projecting the timescale of initial increase in fishery yield after implementation of marine protected areas

Abstract Adaptive management of marine protected areas (MPAs) to determine whether they are meeting their intended goals requires predicting how soon those goals will be realized. Such predictions have been made for increases in fish abundance and biomass inside MPAs. However, projecting increases in fishery yield (“fishery spillover”) is more complex because it involves both how the fishery is managed and uncertainty in larval connectivity. We developed a two-patch, age-structured population model, based on a renewal equation approach, to project the initial timing of increase in fishery yield from larvae exported from a no-take MPA. Our results link our understanding of the predicted timing of increases in biomass (and thus reproduction) in MPAs with the time-lags associated with new recruits entering the fishery. We show that the time-lag between biomass peaking within the MPA and the increased fishery yield outside the MPA reaching its maximum depends, in a predictable way, on the age-dependent patterns of growth, natural mortality, and fishing mortality. We apply this analysis to 16 fishery species from the US Pacific coast; this difference ranged from 7 to 18 years. This model provides broadly applicable guidance for this important emerging aspect of fisheries management.

Organ-, sex-and age-dependent patterns of endogenous L1 mRNA expression at a single locus resolution.

Expression of L1 mRNA, the first step in the L1 copy-and-paste amplification cycle, is a prerequisite for L1-associated genomic instability. We used a reported stringent bioinformatics method to parse L1 mRNA transcripts and measure the level of L1 mRNA expressed in mouse and rat organs at a locus-specific resolution. This analysis determined that mRNA expression of L1 loci in rodents exhibits striking organ specificity with less than 0.8% of loci shared between organs of the same organism. This organ specificity in L1 mRNA expression is preserved in male and female mice and across age groups. We discovered notable differences in L1 mRNA expression between sexes with only 5% of expressed L1 loci shared between male and female mice. Moreover, we report that the levels of total L1 mRNA expression and the number and spectrum of expressed L1 loci fluctuate with age as independent variables, demonstrating different patterns in different organs and sexes. Overall, our comparisons between organs and sexes and across ages ranging from 2 to 22 months establish previously unforeseen dynamic changes in L1 mRNA expression in vivo. These findings establish the beginning of an atlas of endogenous L1 mRNA expression across a broad range of biological variables that will guide future studies.

General Cognition Shows Age-Dependent Patterns of Genetic Overlap With Schizophrenia Liability

Cognition shares substantial genetic overlap with schizophrenia, yet it remains unclear whether such genetic effects increase during developmental periods of elevated risk for schizophrenia, such as the peak age of onset. Should these genetic effects increase around this period, the genetic correlation between cognition and schizophrenia would be expected to differ for individuals who have not yet reached the peak age of onset for schizophrenia compared to those who have reached this age.

Predictors and age-dependent pattern of psychologic problems in childhood atopic dermatitis.

Little is known about the predictors and trends of psychological comorbidities in childhood atopic dermatitis (AD), or whether they occur in an age-dependent pattern. We hypothesized racial/ethnic and socioeconomic disparities lead to increased psychological problems among children with AD and psychological comorbidities occur in an age-dependent manner. We analyzed cross-sectional data on 228898 children aged 2-17years from the 1997-2018 National Health Interview Survey. Children with AD had higher proportions of depression/sadness (17.2% vs 12.6%; odds ratio [95% confidence interval]: 1.44 [1.37-1.51]), attention deficit (hyperactivity) disorder (ADD/ADHD) (10.0% vs 7.1%; 1.46 [1.38-1.55]), emotional/behavioral difficulties (29.9% vs 23.5%; 1.77 [1.69-1.84]), feelings of frequent worry (38.8% vs 23.5%; 1.66 [1.58-1.74]), and autism (1.9% vs 0.9%; 2.00 [1.75-2.29]). Among children with AD, psychologic comorbidity was associated with atopic comorbidities and multimorbidity and white race, households with lower income and education, and no insurance coverage. In children with or without AD, the prevalence of autism peaked during pre-adolescence; ADD/ADHD and emotional/behavioral difficulties peaked in adolescence; and depression/sadness and feelings of frequent worry increased steadily throughout childhood without plateau. Atopic dermatitis was associated with multiple psychologic disorders, particularly among those with atopic comorbidities, white race, and low household income. Psychologic comorbidities increased in an age-dependent pattern, though similar to children without AD.

Age-dependent patterns of the baseline cytokine levels in unstimulated peripheral blood samples

The cytokine levels in unstimulated peripheral blood samples differ in relation to age, living conditions (environmental situation, state of medical care, quality of life, etc). Thus, the essential task is to determine normal levels of peripheral blood cytokines for different age groups with respect to regional characteristics. This study aimed to investigate age-associated patterns of the baseline levels for some cytokines in unstimulated peripheral blood samples in healthy children and adults. The studies were carried out at the Laboratory of Clinical Immunology (Clinical and Diagnostic Centre, Yekaterinburg). Peripheral blood samples were taken in 149 healthy children aged from 7 months to 18 years. Group 1 was 7 to 12 months old (29 infants); group 2 was 1 to 3 years old (33 children); group 3 was 4 to 7 years old (29 children); 4th group was 8 to 14 years old (26 children); 5th group, 15 to 18 years old (32 children); and 6th group included 42 adults (19 to 45 years old). The concentrations of TNFα, IFNγ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, and IL-18 in blood serum were determined by common ELISA technique using Vector-Best kits (Novosibirsk, Russia). Analysis of the data made it possible to identify various patterns of age-dependent changes of baseline levels for the determined cytokines: IL-2 showed an increase in concentration by the age of 1-3 years, stable contents up to 18 years, and decreased concentrations in adulthood. IFNγ was at zero levels in children and adolescents, followed by increased levels in adults. IL-4 and IL-6 showed consistently low levels in children and adolescents, with a decrease to zero levels in adult subjects. IL-18, TNFα were at maximal levels at the age of below 7 years followed by a decrease in concentration; IL-1β, IL-17 exhibited bimodal changes, with maximal contents at the age of 1-3 years, and repeated increase in adult age. Nearly stable baseline concentration was noted for IL-10, with a slight increase at 1-3 years, like as for IL-8, with a moderate increase at 15-18 years. For majority of analyzed cytokines, the maximal baseline contents in unstimulated peripheral blood samples were found in children aged 1-3 years.

Infantile leukemia-What factors determine its distinct biological nature? Clinicopathological study of 78 cases.

Infantile leukemia encompasses a heterogeneous group which needs stratifying for treatment selection. We collected 78 cases of infantile leukemia and retrospectively analyzed their clinicopathological data. Infantile leukemia featured a ratio of acute myeloid leukemia (AML) to B-lymphoblastic leukemia (B-ALL) of 1:2, with a better survival for AML than B-ALL (median survival 36 vs 24 months). When stratified by age, "early" infantile B-ALL (2-6 months) showed a high rate of KMT2A rearrangement (100%), similar to the rate seen in congenital B-ALL (1 month) (100%) and higher than seen in "late" infantile B-ALL (≥7 months) (68%). The three categories of infantile B-ALL exhibited an age-dependent increase in survival (median survival 8.5, 24, and >24 months, respectively). The age-dependent survival benefit remained after excluding the cases negative for KMT2A rearrangement. Conversely, infantile AML lacked an age-dependent pattern of survival. The clinical outcome of infantile leukemia depends on the type of leukemia. Given the age-dependent survival, infantile B-ALL can be divided into three subcategories.

A Focus on the Cerebellum: From Embryogenesis to an Age-Related Clinical Perspective.

The cerebellum and its functional multiplicity and heterogeneity have been objects of curiosity and interest since ancient times, giving rise to the urge to reveal its complexity. Since the first hypothesis of cerebellar mere role in motor tuning and coordination, much more has been continuously discovered about the cerebellum’s circuitry and functioning throughout centuries, leading to the currently accepted knowledge of its prominent involvement in cognitive, social, and behavioral areas. Particularly in childhood, the cerebellum may subserve several age-dependent functions, which might be compromised in several Central Nervous System pathologies. Overall, cerebellar damage may produce numerous signs and symptoms and determine a wide variety of neuropsychiatric impairments already during the evolutive age. Therefore, an early assessment in children would be desirable to address a prompt diagnosis and a proper intervention since the first months of life. Here we provide an overview of the cerebellum, retracing its morphology, histogenesis, and physiological functions, and finally outlining its involvement in typical and atypical development and the age-dependent patterns of cerebellar dysfunctions.

Age-Dependent Trends in the Celiac Disease: A Tertiary Center Experience.

Celiac disease (CD) is a common intestinal autoimmune disorder with diverse presenting features. We aimed to determine age-dependent patterns in CD presentation, diagnosis and management at a large tertiary referral center. A retrospective review of electronic medical records of pediatric patients diagnosed with CD between January 1999 and December 2018 at Schneider Children's Medical Center of Israel. We compared demographics, clinical and laboratory parameters between four age groups at CD presentation. A cohort of 932 children was divided into four groups by age (in years) at diagnosis: 0-3 (17.9%), 3-6 (31.8%), 6-12 (34.5%), 12-18 (15.8%). The youngest age group presented more frequently with diarrhea, weight loss, abdominal distention, vomiting and lower weight z scores, P < 0.01. Hypoalbuminemia and zinc deficiency were also more frequent in this age group, compared to older patients (P < 0.05, each). Rates of anemia were higher in younger age groups (0-3 and 3-6 years), compared to older age groups, P < 0.05. Patients in the younger age groups (0-3 and 3-6 years) presented more frequently with tissue transglutaminase (TTG) levels above 10 times the upper limit of normal (ULN; P < 0.05), and more often normalized their CD serologies by 24 months of gluten-free diets (GFD) compared to older age groups (P < 0.05). There is an age-dependent variation in CD presentation during childhood. Younger patients present more often with malabsorptive features, and higher TTG levels, yet normalize TTG while on GFD more rapidly than older patients. Clinicians should be aware of the diversity in CD presentation and course at the various presentation age.

Social-pragmatic contextual comprehension in Italian preschool and school-aged children: a study using the Pragma test

Abstract Efficient communication requires the interplay of linguistic, cognitive and social skills, including the ability to make contextual inferences and to understand others’ intentions and emotions. The capacity to effectively use language in specific contexts (i.e., pragmatic ability) develops with age, and an assessment of this ability is important for understanding both typical and atypical development. The Pragma test was originally developed and validated on Finnish children to assess social-pragmatic comprehension. The present study utilizes a slightly adapted version of the Pragma test, translated into Italian, and presents the results of the test given to 110 typically developing Italian children (4–8 years of age). The Italian version of the Pragma test shows content and concurrent validity, interrater reliability, and internal consistency, and it proves to be sensitive in detecting an age-dependent pattern of performance, across pre-school and school age children, in the pragmatic parameters investigated. The present study has ramifications for clinical contexts, as data for typical pragmatic development enables identification of strengths and weaknesses in the pragmatic performance in clinical populations. Finally, the results indicate that the Pragma test is relevant to both Finnish and Italian cultural contexts, thus providing the opportunity to make cross-cultural comparisons.

Melody complexity of infants\u2019 cry and non-cry vocalisations increases across the first six months

In early infancy, melody provides the most salient prosodic element for language acquisition and there is huge evidence for infants’ precocious aptitudes for musical and speech melody perception. Yet, a lack of knowledge remains with respect to melody patterns of infants’ vocalisations. In a search for developmental regularities of cry and non-cry vocalisations and for building blocks of prosody (intonation) over the first 6 months of life, more than 67,500 melodies (fundamental frequency contours) of 277 healthy infants from monolingual German families were quantitatively analysed. Based on objective criteria, vocalisations with well-identifiable melodies were grouped into those exhibiting a simple (single-arc) or complex (multiple-arc) melody pattern. Longitudinal analysis using fractional polynomial multi-level mixed effects logistic regression models were applied to these patterns. A significant age (but not sex) dependent developmental pattern towards more complexity was demonstrated in both vocalisation types over the observation period. The theoretical concept of melody development (MD-Model) contends that melody complexification is an important building block on the path towards language. Recognition of this developmental process will considerably improve not only our understanding of early preparatory processes for language acquisition, but most importantly also allow for the creation of clinically robust risk markers for developmental language disorders.

Temporal and age-related variations in calling and mating patterns of the Indian population of spotted pod borer, Maruca vitrata Fabricius (Lepidoptera: Crambidae)

Maruca vitrata is an important pantropical and polyphagous insect pest of grain legumes. The adult emergence pattern and temporal variations in the calling and mating behaviour of M. vitrata across ages were studied. Observations revealed that adult emergence was not influenced significantly by sex, but by the time of the day. Calling activity is a strong determinant of male mating success in insects. An age-dependent female calling pattern was observed. Females seldom called on their day of emergence, calling percentage was low to nil in the first four hours of scotophase but reached a peak in the fifth hour. The calling patterns of females of different ages were similar except that there were two peaks of calling for 3 and 4 days old females. Like calling, the mating pattern was also age-dependent, i.e. M. vitrata mating frequency was maximum at 3-days of age and thereafter decreased gradually with age. The highest mating frequency (30.83%) was observed at 2200 h for 3-day-old moths. The current study revealed that age dependant and distinct patterns in female calling, synchronous male responsiveness leading to mating in M. vitrata. The output of the study could be utilized in various aspects of M. vitrata semiochemical based research.

Age-dependent changes of gender disparities in nasopharyngeal carcinoma survival

BackgroundThe mortality of nasopharyngeal carcinoma (NPC) is usually lower in females than in males, but the underlying mechanism remains largely unknown. We sought to describe the age-dependent patterns of gender disparities in NPC survival and explore the extent to which the confounder or mediation effects could explain these differences.MethodsA total of 11,980 patients with NPC were reviewed. The effect of gender on cancer-specific survival (CSS) was assessed using Cox regression analyses. Two propensity score methods were conducted to control the confounding bias between genders. Restricted cubic spline regression was used to model the association of gender and age with mortality flexibly. Multiple mediation analysis was applied to estimate the direct or indirect effect of gender on CSS.ResultsOverall, 7026 males and 2320 females were analyzed. The crude CSS was significantly higher for females than males (10-year CSS 78.4% vs 70.3%; P < 0.001). Similar results were observed after adjusting for confounding bias. Gender disparities in NPC-specific mortality were age-dependent, where they would increase with age until peaking at age 55–60 years and decline rapidly afterward. Subgroup analyses revealed that females’ survival advantage was observed in the 18–45 age group and was more prominent in the 46–55 age group, but vanished in the > 55 age group. Either confounder or mediation effects only accounted for approximately 20% of the gender differences.ConclusionsGender disparities in cancer-specific mortality for patients with NPC were age-dependent. The differences mostly cannot be explained by confounder or mediation effects.

Gender Disparities in the Prevalence, Awareness, Treatment, and Control of High Blood Pressure.

The gender effects in arterial hypertension (HT) epidemiology remain poorly clarified to date. We present an up-to-date review of the data regarding gender disparities in HT's prevalence, awareness, treatment, and control. Based on the data from three consecutive national-representative SEPHAR (Study for the Evaluation of Prevalence of Hypertension and Cardiovascular Risk in Romania) surveys conducted between 2005 and 2016, we provide insights into gender differences in HT's epidemiology and their 11- years the evolutionary trend in a high-CV risk European country. Our data displays gender effects in different age-dependent epidemiological patterns in terms of hypertension prevalence, awareness, treatment, and control, mainly due to hormonal status. Hypertension's prevalence is higher in younger men and older women. Although women are more often aware of their hypertensive condition and receive more often antihypertensive treatment, BP control is lower in older women compared to men of the same age, mainly due to a higher treatment side-effect rate. There is no solid evidence that different antihypertensive drugs exhibit different effects in lowering BP values between genders. In high CV risk European countries like Romania, if all the influencing conditions remain similar to those in the past 11 years, gender discrepancies in terms of HT's prevalence will diminish over time, awareness and treatment of hypertension will continue to be higher in females than in men, with an upward trend of BP control predicted only for women, while in men HT treatment control rate is expected to stagnate.

Electroclinical features and outcome of ANKRD11-related KBG syndrome: A novel report and literature review

Electroclinical features and outcome of ANKRD11-related KBG syndrome: A novel report and literature review