The factor structure of the functional state of boys aged 13–14 years

We determined the independent factors that reflect the fundamental characteristics of the functional state (FS) in adolescents aged 13–14 years (n = 162): the sympathetic regulation and parasympathetic regulation of FS, physical working capability; the efficiency of cognitive performance; the hemodynamic basis of cognitive activity; nonspecific resistance to upper respiratory tract infections. Using the systematic approach, we investigated the physiological basis of these factors and determined the indices suitable for estimating the FS of adolescents at different stages of puberty. We observed progressive dynamics of FS parameters related to factors listed above in boys of the same chronological age at different puberty stages. Beginning from stage II to stage IV, we observed a heterochronic and nonlinear decrease in the tension of system of autonomic FS regulation, an increase in the efficiency of cognitive activity and its hemodynamic supply, as well as an improvement of anaerobic working capability.     

β-Adrenergic receptor activity of cerebral microvessels is reduced in aged rats

The effect of age on beta-() adrenergic receptor number (B_max) and adenylate cyclase (AC) activity was determined in microvessels isolated from male F-344 rats at 3, 18, and 24 months of age. Scatchard analysis of [¹²⁵I]iodocyanopindolol (ICYP) binding indicated reduced Bmax (fmol/mg) of microvessels isolated from 24 month old rats (27.2±4.9) compared with 3 month old (50.4±5.2) and 18 month old rats (p<0.01) (61.4±7.6). The basal AC activity (pmol cAMP/mg) in 24 month old rats (32.0 ±6.7) and in 18 month old rats (30.4±2.1) were significantly reduced compared to the basal activity in the young (50.1±4.2). The net isoproterenol or NaF stimulated AC activity in 24 month old rats (zero and 15.6±8.5 respectively) was also reduced compared to young rats (10.1±3.9 and 166.0±21.2 respectively). It is concluded that aging is associated with reduced isoproterenol stimulated AC activity of cerebral microvessels. This reduction is the product of reduced -adrenergic receptor number and reduced activity of AC in aged rat cerebral microvessels.     

Comparison of baltic amber and an ‘aged’ Pinus halepensis resin by means of infrared spectroscopy

The infrared spectrum of ‘aged’ Pinus halepensis resin indicates the presence of a methylene group in a terminal position, which is characteristic of Baltic amber.     

Effects of daily iron supplementation in primary-school–aged children: systematic review and meta-analysis of randomized controlled trials

Background:

Anemia is an important public health and clinical problem. Observational studies have linked iron deficiency and anemia in children with many poor outcomes, including impaired cognitive development; however, iron supplementation, a widely used preventive and therapeutic strategy, is associated with adverse effects. Primary-school–aged children are at a critical stage in intellectual development, and optimization of their cognitive performance could have long-lasting individual and population benefits. In this study, we summarize the evidence for the benefits and safety of daily iron supplementation in primary-school–aged children.

Methods:

We searched electronic databases (including MEDLINE and Embase) and other sources (July 2013) for randomized and quasi-randomized controlled trials involving daily iron supplementation in children aged 5–12 years. We combined the data using random effects meta-analysis.

Results:

We identified 16 501 studies; of these, we evaluated 76 full-text papers and included 32 studies including 7089 children. Of the included studies, 31 were conducted in low- or middle-income settings. Iron supplementation improved global cognitive scores (standardized mean difference 0.50, 95% confidence interval [CI] 0.11 to 0.90, p = 0.01), intelligence quotient among anemic children (mean difference 4.55, 95% CI 0.16 to 8.94, p = 0.04) and measures of attention and concentration. Iron supplementation also improved age-adjusted height among all children and age-adjusted weight among anemic children. Iron supplementation reduced the risk of anemia by 50% and the risk of iron deficiency by 79%. Adherence in the trial settings was generally high. Safety data were limited.

Interpretation:

Our analysis suggests that iron supplementation safely improves hematologic and nonhematologic outcomes among primary-school–aged children in low- or middle-income settings and is well-tolerated.An estimated 25% of school-aged children worldwide are anemic.¹ Iron deficiency is thought to account for about half of the global cases of anemia² and is associated with inadequate dietary iron and, in developing settings, hookworm and schistosomiasis.³ In developed settings, anemia is prevalent among disadvantaged populations, including newly arrived refugees, indigenous people⁴ and some ethnic groups (e.g., Hispanic people in the United States).^5,6 About 3% of primary-school–aged children in Canada are anemic.⁷ Programs to address anemia are constrained by concerns that iron supplements cause adverse effects, including an increased risk of infections such as malaria in endemic areas.⁸In observational studies, iron deficiency has been associated with impaired cognitive and physical development. It has been estimated that each 10 g/L decrement in hemoglobin reduces future intelligence quotient (IQ) by 1.73 points.⁹ However, observational data are susceptible to confounding,¹⁰ and a causal relation between iron deficiency and cognitive impairment has not been confirmed.¹¹ Randomized controlled trials should overcome confounding, but results of trials examining this question have not agreed.Optimizing cognitive and physical development in primary-school–aged children could have life-long benefits.¹² However, anemia-control recommendations must balance safety and efficacy. We performed a systematic review of the effects of daily iron supplementation, a commonly used strategy to combat anemia,² in primary-school–aged children. We examined cognitive, growth and hematologic outcomes and adverse effects across all settings.     

Prion infection promotes extensive accumulation of α-synuclein in aged human α-synuclein transgenic mice

In neurodegenerative disorders of the aging population, misfolded proteins, such as PrP^Sc, α-synuclein, amyloid β protein and tau, can interact resulting in enhanced aggregation, cross seeding and accelerated disease progression. Previous reports have shown that in Creutzfeldt-Jakob disease and scrapie, α-synuclein accumulates near PrP^Sc deposits. However, it is unclear if pre-existing human α-synuclein aggregates modified prion disease pathogenesis, or if PrP^Sc exacerbates the α-synuclein pathology. Here, we inoculated infectious prions into aged α-synuclein transgenic (tg) and non-transgenic littermate control mice by the intracerebral route. Remarkably, inoculation of RML and mNS prions into α-synuclein tg mice resulted in more extensive and abundant intraneuronal and synaptic α-synuclein accumulation. In addition, infectious prions led to the formation of perineuronal α-synuclein deposits with a neuritic plaque-like appearance. Prion pathology was unmodified by the presence of α-synuclein. However, with the mNS prion strain there was a modest but significant acceleration in the time to terminal prion disease in mice having α-synuclein aggregates as compared with non-tg mice. Taken together, these studies support the notion that PrP^Sc directly or indirectly promotes α-synuclein pathology.     

Prion infection promotes extensive accumulation of α-synuclein in aged human α-synuclein transgenic mice

In neurodegenerative disorders of the aging population, misfolded proteins, such as PrP^Sc, α-synuclein, amyloid β protein and tau, can interact resulting in enhanced aggregation, cross seeding and accelerated disease progression. Previous reports have shown that in Creutzfeldt-Jakob disease and scrapie, α-synuclein accumulates near PrP^Sc deposits. However, it is unclear if pre-existing human α-synuclein aggregates modified prion disease pathogenesis, or if PrP^Sc exacerbates the α-synuclein pathology. Here, we inoculated infectious prions into aged α-synuclein transgenic (tg) and non-transgenic littermate control mice by the intracerebral route. Remarkably, inoculation of RML and mNS prions into α-synuclein tg mice resulted in more extensive and abundant intraneuronal and synaptic α-synuclein accumulation. In addition, infectious prions led to the formation of perineuronal α-synuclein deposits with a neuritic plaque-like appearance. Prion pathology was unmodified by the presence of α-synuclein. However, with the mNS prion strain there was a modest but significant acceleration in the time to terminal prion disease in mice having α-synuclein aggregates as compared with non-tg mice. Taken together, these studies support the notion that PrP^Sc directly or indirectly promotes α-synuclein pathology.     

Identification of potential ‘lifestyle-responsive’ epigenomic biomarkers in healthy women aged 18–40

Context: Human health is complex and multifaceted; there is a need for biomarkers that reflect the multidimensional nature of health.

Objective: To identify potential epigenomic biomarkers of health in women aged 18–40 participating in a six-month lifestyle intervention, next level health.

Materials and methods: Methylation data were obtained by reduced representation bisulphite sequencing of 21 female intervention participants as well as three non-participants. The Differential Methylation Analysis Package (DMAP) was used to investigate inter- and intra-individual variability and to identify potential targets of transient epigenetic control in the population studied.

Results: Eleven genes were identified as significantly differentially methylated post- intervention in all 21 participants. 1884 genomic locations were found to be differentially methylated amongst the total female population studied representing potential epigenomic biomarkers.

Conclusions: The ability to demonstrate epigenetic changes arising from a lifestyle intervention can provide key information on the relationship between gene regulation, human behaviour and health.     

Protective effect of 17β-estradiol on oxidative stress and liver dysfunction in aged male rats

In aging liver oxidative stress increases due to the decrease in antioxidant bio-molecules such as estrogens which can be modified by hormonal replacement therapy (HRT). With this in mind, we hypothesized that age-related decline in steroidogenesis may be associated with the impairment of the antioxidant defense cells in liver, the increase in lipid peroxidation, hepatic dysfunction and histological changes; estrogens prevent all these changes induced by aging. 17beta-estradiol treatment was initiated in 12 month-old Wistar rats, and continued until 18 months of age. Our results showed that 17beta-estradiol (E2) level in the serum of the aged untreated rats was reduced by -32% in 18 month-old rats compared to the young animals (4-month-old). The superoxide dismutase (SOD), catalase (CAT), and gluthatione peroxidase (GPX) activities were reduced by -47, -46, and -29% respectively in old rat liver. In addition, the TBARs in liver and hepatic dysfunction parameters in plasma such as gamma-glutamyl transferase (GGT), phosphatase alkalin (PAL) as well as bilirubin level increased significantly in old rats, and histological changes were investigated. In E2-treated rats, protective effects were observed. Indeed, 17beta-estradiol attenuates all changes induced by aging. The 17beta-estradiol level was higher in old E2-treated rats compared to the control rats. Moreover, the SOD, CAT and GPX activities were higher by +28, +15, and +11% respectively. This anti-aging effect of estrogens was clarified by a lower level of lipid peroxidation and liver dysfunction parameters as well as by histological observation.     

Reaction of the gastric glands in wrestlers aged 7–32 years to threshold-power bicycle ergometer exercise

Problems of quick adaptation of the gastric glands of wrestlers to threshold-power bicycle ergometer exercise during sports and postsports ontogeny are discussed. It has been established that threshold-power bicycle ergometer exercise may suppress, stimulate, or not affect the secretion of H₂O, HCl, and pepsinogen. The pattern of these shifts is aimed at optimizing the actual level of protein hydrolysis; it depends on the age, sports experience, and qualification and is correlated with the body weight.     

Self-perception of self-regulatory skills in children with attention-deficit/hyperactivity disorder aged 8–10 years

Several studies have reported a characteristic "positive illusory bias" in the self-evaluation of children with ADHD. However, results are controversial. The aim of the present study was to investigate whether children with ADHD aged 8 to 10 years can rate their self-regulatory skills accurately when assessed with an age appropriate instrument. Twenty-seven children with ADHD and 27 matched normal control children completed the Self-rating Scale of Self-regulatory Function (SelfReg), a new rating scale that has been specifically designed for this age group. As expected, children with ADHD rated themselves significantly more dysfunctional than control children. In most domains, self-ratings of children with ADHD did not diverge from parent and teacher ratings to a greater extent than self-ratings of control children, although overall results indicated a moderate tendency toward a positive bias. When a cluster analysis based on discrepancies between children's and adults' evaluations was carried out, three groups with different self-rating patterns emerged: A "positive bias" group containing exclusively children with ADHD, a "negative bias" group containing both children with ADHD and control children, and the largest group of accurate self-raters which also included children from both diagnostic groups. It is concluded that overly positive self-judgments are not a ubiquitous finding in ADHD, but may be confined to a specific subgroup of children whose specific characteristics remain to be determined.     

Local delivery of a PKCε-activating peptide limits ischemia reperfusion injury in the aged female rat heart

Reduced efficacy of cardioprotective interventions in the aged female heart, including estrogen replacement, highlights the need for alternative therapeutics to reduce myocardial ischemia-reperfusion (I/R) injury in postmenopausal women. Here, we sought to determine the efficacy of protein kinase-Cε (PKCε)-mediated cardioprotection in the aged, estradiol-deficient rat heart. Infarct size and functional recovery were assessed in Langendorff-perfused hearts from adult (5 mo) or aged (23 mo) female Fisher 344 ovary-intact or ovariectomized (OVX) rats administered a PKCε-activator, receptor for activated C kinase (ψεRACK) prior to 47-min ischemia and 60-min reperfusion. Proteomic analysis was conducted on left ventricular mitochondrial fractions treated with ψεRACK prior to I/R, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) 8plex labeling and tandem mass spectrometry. Real-time PCR was utilized to assess connexin 43 (Cx43) and RACK2 mRNA post-I/R. Greater infarct size in aged OVX (78%) vs. adult (37%) was reduced by ψεRACK (35%, P < 0.0001) and associated with greater mitochondrial PKCε localization (P < 0.0003). Proteomic analysis revealed three novel mitochondrial targets of PKCε-mediated cardioprotection with aging (P < 0.05): the antioxidant enzymes glutathione peroxidase (GPX) and MnSOD2, and heat shock protein 10. Finally, decreased levels of Cx43 and RACK2 mRNA seen with age were partially abrogated by administration of ψεRACK (P < 0.05). The mechanisms described here may represent important therapeutic candidates for the treatment of acute myocardial infarction in postmenopausal women and age-associated estradiol deficiency.     

Stimulation by transforming growth factor-β of epidermal growth factor-dependent growth of aged human fibroblasts: Recovery of high affinity EGF receptors and growth stimulation by EGF

Summary The stimulatory effects of transforming growth factor β (TGF-β) on epidermal growth factor (EGF)-dependent growth of adult and newborn human fibroblasts were investigated. EGF-stimulated growth in low serum of dermal fibroblasts from a 41 year-old adult (HSF-41) was less than half that of newborn foreskin fibroblasts (HFF). The EGF-stimulated growth of HFF after 55 population doublings (HFF-55) was similarly reduced. The decreased growth response to EGF of fibroblasts, agedin vivo andin vitro appeared to result principally from a decreased sensitivity to EGF due to a decreased number and affinity of high affinity EGF receptors (H-EGFR). Pre-incubation of HSF-41 and HFF-55 with 25 pM TGF-β enhanced the growth responses of these cells to EGF and increased the levels of high affinity EGF-binding by these cells Thus, the stimulation by TGF-β of EGF-dependent growth of human fibroblasts agedin vivo orin vitro is mediated by increased levels of high affinity EGF binding. This research was supported in part by a grant-in-aid for scientific research (61480388) and a special project research grant to Okayama University from the Japanese Ministry of Education, Science and Culture. Editor's statement TGF beta interaction with its receptor is known to affect EGF receptors. In this paper a functional biological association is established.     

Dietary calcium utilization among a group of spanish boys aged 11–14 years on their usual diets

Adolescence constitutes a period of nutritional vulnerability due to increased dietary requirements for growth and development and special dietary habits. A pilot trial was performed to evaluate the dietary calcium utilization among a sample of Spanish boys on their usual diets, in which the calcium intake and consumption of dairy products were as well examined. Nutrient and food intake was recorded using a 24-h dietary recall and a 2-d food consumption record for 21 subjects aged 11-14 years. Dietary calcium utilization was assessed by means of calcium intake in food and calcium output in faeces and urine as measured by flame atomic absorption spectrophotometry. Overall intake of dairy products was 399.3 +/- 22.1 g/d, and the single most consumed item was milk (72% of the total). An inverse relationship was found between dairy product consumption at breakfast (55% of the total) and BMI (p = 0.016, r = -0.5168). Dairy products contributed the majority of dietary calcium (66.9%). Mean calcium intake was 881.7 +/- 39.9 mg/d, 88% of the recommended value for Spanish adolescents. Net calcium absorption (271.7 +/- 51.7 mg/d) and retention (170.6 +/- 50.9 mg/d) seemed not to be sufficient to meet growth demands during puberty. The results shown that adolescents of the study absorbed 31% of dietary calcium and retained nearly 20% of the total intake, but dietary calcium intake and consumption of dairy products failed to meet recommended values. Optimizing calcium intake is of crucial importance among adolescents, to maximize calcium retention and to help prevent osteoporosis in later life.     

Wnt/β-catenin signaling is critical for dedifferentiation of aged epidermal cells in vivo and in vitro

Aged epidermal cells have the capacity to dedifferentiate into stem cell-like cells. However, the signals that regulate the dedifferentiation of aged epidermal cells remain unclear. Here, we provide evidence that Wnt/β-catenin is critical for aged epidermal cell dedifferentiation in vivo and in vitro. Some aged epidermal cells in human ultrathin epidermal sheets lacking basal stem cells transplanted onto wounds dedifferentiated into stem cell-like cells that were positive for CK19 and β1 integrin but negative for CK10. In addition, Wnt/β-catenin pathway was activated during this process. There was increased expression of Wnt-1, Wnt-4, Wnt-7a, β-catenin, cyclin D1, and c-myc. Secreted frizzled-related protein 1, a Wnt/β-catenin pathway inhibitor, blocked dedifferentiation in vivo. Then, the activator, a highly specific glycogen synthase kinase (GSK)-3β inhibitor, of Wnt/β-catenin pathway was added to the culture medium of aged epidermal cells. Surprisingly, we found that the activator induced higher expression of CK19, β1 integrin, Oct4, and Nanog proteins. The induced aged epidermal cells exhibited high colony-forming efficiency, long-term proliferative potential and could regenerate a skin equivalent (as do epidermal stem cells). These results suggested that activation of Wnt/β-catenin pathway induced the dedifferentiation of aged epidermal cells, which suggest a new approach to generate epidermal stem cell-like cells.     

N′-isopropylnornicotine: Its formation from nicotine in aged leaves of Nicotiana tabacum

An aqueous solution of nicotine-[2′-¹⁴C] was painted on the leaves of 4-month-old tobacco plants (Nicotiana tabacum) which were harvested 3 weeks later. This tracer was similarly applied to excised tobacco leaves which were allowed to dry in air for 4 weeks. The alkaloids, were extracted with the addition of N′-isopropylnornicotine, a compound which has been previously isolated from air-cured tobacco. Radioactive nicotine and nornicotine were isolated from the intact plants with only minute activity in the N′-isopropylnornicotine. All three of these alkaloids were radioactive from the air-cured leaves, and degradation of the labelled N'-isopropylnornicotine indicated that all the activity was located at the C-2′ position. A higher level of activity was found in N′-isopropylnornicotine which was obtained from excised leaves which were fed the nicotine- [2′- ¹⁴C] in aqueous acetone, and were treated on subsequent days with aqueous acetone. These results are consistent with the hypothesis that N′-isopropylnornicotine is produced in the curing of tobacco leaves by reaction of nornicotine (formed by the demethylation of nicotine) with acetoacetate, followed by decarboxylation and reduction. The ¹³C NMR chemical shifts of the methyl groups of N′-isopropylnornicotine and related 1-isopropylpyrrolidines which have chirality at the α-position of the pyrrolidine ring, are significantly different (up to 7.5 ppm).     

Under-use of adjuvant chemotherapy in women aged ≥70 years diagnosed with breast cancer in a university hospital

Introduction

Patient age often limits the therapeutic efforts of the oncologist. The aim of this study was to determine whether chemotherapy is used less frequently in elderly women aged 65-69 years diagnosed with breast cancer, compared to younger women.

Methods

A retrospective study was performed including women greater than 65 years old who had localised breast cancer and were treated at a University Hospital. Patients were classified into two groups, 65-69 years old and ≥ 70 years old. The differences in patient characteristics, tumour characteristics, chemotherapy treatment and chemotherapy-associated toxicity were analysed in both groups.

Results

A total of 164 women, with an average age of 73.7 years, were included in this study. There were no significant differences in the characteristics of the patients or their tumours. However, 75% of women <70 years old were treated with chemotherapy compared to just 34% of the older women (P<.001). The resulting levels of toxicity were similar between age groups.

Conclusions

Women ≥ 70 years old were treated with chemotherapy less frequently, even though the features and tumour characteristics of the women, as well as the toxicity of the treatment, were similar to that in younger women.     

Lasting effects of an impairment of Th1-like immune response in γ-irradiated mice: A resemblance between irradiated mice and aged mice

Although one of the several chronic effects of ionizing radiation is aging, there are no experimental data on radiation-induced immunological aging. The most interesting change in aging was a helper T (Th) 1/Th2 imbalance. We investigated chronic effect on immune responses after ionizing radiation and its effects in irradiated mice were compared with those of aged mice. The 2-month-old mice received a whole-body irradiation of 5 Gy. At 6 months after irradiation, we compared the immune functions of the irradiated mice with those of normal mice of the same age and with those of older. Interferon (IFN)-γ and antigen-specific immunoglobulin (Ig)G2a level were lower in the irradiated mice than in normal mice of same age, showing similar levels to those of old normal mice. In contrast, interleukin (IL)-4 and IL-5 and antigen-specific IgG1 level were increased in irradiated mice when compared with the same aged-normal mice. Next, we investigated the low expression of IL-12p70, IL-12 receptors and IL-18 receptors in irradiated and old mice. Also, the decrease of natural killer cell activity was intensified in the irradiated mice, showing lower than values to those of old mice. Interestingly, in irradiated mice, the absolute numbers and the percentages of natural killer (NK) cells was extremely decreased. But the absolute numbers of Th cells and cytotoxic T (Tc) cells in old mice were significantly decreased. In conclusion, an immunological imbalance by the whole-body irradiation of 5 Gy induces to persist in the long term, resulting in the similar results with aging. Our results suggest that the downregulation of the Th1-like immune response shown in old mice rapidly occurred through exposure of ionizing radiation.