Stage-related Changes Research Articles

Managing perimenopausal CNS symptoms

Complaints of cognitive difficulties are more common, and performance on objective cognitive tests declines, in the perimenopause compared to the premenopause. In longitudinal studies, the cognitive ability affected most reliably during the transition is verbal learning and memory, with some studies also showing effects on processing speed. These stage-related changes in cognition are not fully accounted for by age, mood or menopause symptoms, suggesting that changes in ovarian hormones likely play an important role. Studies of surgical menopause support that hypothesis. In addition, vasomotor symptoms (VMS), sleep disturbance and mood difficulties contribute to these changes. Increased frequency of VMS during the day and particularly at night, have been linked to changes in memory, as well as brain function, connectivity and structure. Initial evidence suggests that treating VMS may improve cognition, and large clinical trials are underway to determine if VMS may play a causal role in such changes. Importantly, the link between VMS and brain health is observed only when VMS are measured objectively using ambulatory skin conductance monitors. If these associations are found to be causal in future studies, then the treatment of VMS may be indicated to maintain cognitive performance. Nighttime VMS are associated with awakenings, and disturbed sleep is a key determinant of cognitive performance. Behavioral interventions for sleep disturbance, including sleep hygiene and insomnia cognitive behavioral therapy (iCBT) are evidence based to improve sleep. Depression and anxiety symptoms increase in the perimenopause and are associated with cognitive difficulties. Treating mood and anxiety with CBT and lifestyle interventions (i.e., exercise, yoga is therefore also important to optimizing cognition. Head-to-head clinical trial data suggests that conjugated equine estrogen but not oral estradiol improves mood in euthymic midlife women. Most women with a history of major depression depressive disorder (MDD) will experience a recurrence of MDD during the perimenopause. Although treating MDD is likely to improve cognition, research indicates that those with MDD continue to experience cognitive problems even when not experiencing a major depressive episode. There are no large randomized trials of hormone therapy on cognition in the perimenopause, though treating VMS with hormone therapy theoretically may confer benefits, particularly if those VMS are disrupting sleep.

Age-Related Changes in the Yeast Component of the Drosophila melanogaster Microbiome

Drosophila melanogaster fruit flies are an important model for studying the multifaceted interactions between a multicellular organism and its microbiome. The nature of these interactions is largely determined by the regular changes in abundance and composition of the microbiome that occur during the host’s life. The currently available data on age- and life cycle stage-related changes in the Drosophila microbiome relate mainly to its bacterial component, while little is known about such changes in the equally important yeast component. The present work describes the quantitative and qualitative composition of the yeast component of the D. melanogaster microbiome in three laboratory lines, reared under different conditions, at four developmental stages: late larvae and adults aged 1, 7, and 14 days after eclosion. In all three lines, the total yeast abundance changed similarly with the age of insects, with the highest and lowest yeast counts in 7- and 1-day adults, respectively. In the fly lines reared on moderately unfavorable substrates supplemented with 2 and 4% NaCl, the abundance and species diversity of yeasts at all four developmental stages was higher than in the flies reared on a standard (favorable) food substrate. Our results indicate the inconstancy of the yeast component of the D. melanogaster microbiome and its regular changes with the insect’s age, which must be taken into account when studying the relationships between symbiotic yeasts and their hosts.

Life stage-related changes in dietary habits and ecological niche of the Sakhalin taimen Parahucho perryi in the Shumarinai Lake system, Hokkaido, Japan

Life stage-related changes in dietary habits and ecological niche of the Sakhalin taimen <i>Parahucho perryi</i> in the Shumarinai Lake system, Hokkaido, Japan

Stage-associated differences in the serum N- and O-glycan profiles of patients with non-small cell lung cancer

BackgroundLung cancer is the leading cause of cancer death in China and around the world. Early detection is key to improving the survival rate of non-small cell lung cancer (NSCLC). Alteration in glycosylation has been observed in cancers, and glycans can be a source for the development of new biomarkers for NSCLC.MethodsIn this glycan biomarker discovery study, we measured serum N- and O-glycan profiles in NSCLC patients with different stages and healthy controls by performing lectin microarray analysis. The alterations of serum glycopatterns were compared between NSCLC patients and controls, and the stage-related changes in serum glycosylation were evaluated.ResultsThere were 18 lectins (e.g., AAL, Jacalin, GSL-I and DBA) to give significantly alterations of serum glycopatterns in lung adenocarcinoma compared with control group. Meanwhile, 16 lectins (e.g., Jacalin, HHL, and PHA-E+L) exhibited significantly alterations of serum glycopatterns in squamous cell carcinoma (SCC) compared with control group. Importantly, most of the lectins showing altered signals exhibited significantly increased or decreased NFIs in patients with early stage adenocarcinoma and SCC.ConclusionsThe serum glycan profiles were significantly different between NSCLC and healthy control, and most of the glycosylation changes had occurred at early stage. Further evaluation is needed to examine the diagnostic value of the glycan markers identified in this study.

Quantitative analysis of age and life-history stage related changes in DCX expression in the male Japanese quail (Cortunix japonica) telencephalon

Most avian neurogenesis studies focused on the song control system and little attention has been given to non-song birds such as the Japanese quail. However, the only few neurogenesis studies in quails mainly focused on the sex steroid sensitive areas of the brain such as the medial preoptic and lateral septal nuclei. Despite the important role the quail telencephalon plays in filial imprinting and passive avoidance learning, neurogenesis in this structure has been completely overlooked. The aim of this study was therefore to quantitatively determine how DCX expression in the Japanese quail telencephalon changes with post hatching age (3–12 weeks) and life history stage. In this study, DCX was used as a proxy for neuronal incorporation. Bipolar and multipolar DCX immunoreactive cells were observed in the entire telencephalon except for the entopallium and arcopallium. In addition, DCX expression in all the eight telencephalic areas quantified was strongly negatively correlated with post-hatching age. Furthermore, numbers of bipolar and multipolar DCX immunoreactive cells were higher in the juvenile compared to subadult and adult quails. In conclusion, neuronal incorporation in the quail telencephalon is widespread but it declines with post hatching age. In addition, the most dramatic decline in neuronal incorporation in the telencephalic areas quantified takes place just after the birds have attained sexual maturity.

Clinical disease stage related changes of serological factors in amyotrophic lateral sclerosis

Objective: Little is known whether disease clinical stage would influence the serological values in Amyotrophic lateral sclerosis (ALS). We aimed to explore the association between the levels of serological factors with clinical progression determined by the King’s College staging system. Methods: ALS Patients were registered from May 2008 to December 2016. The differences of serological values between patients and healthy controls, and the correlation of these serological values with disease stage were examined. Results: A total of 571 patients and 571 age-/gender-/BMI-matched healthy controls were included. The levels of creatinine, uric acid (UA), albumin, total protein, total cholesterol, and high-density lipoprotein (HDL) were significantly lower, and the low-density lipoprotein/HDL ratio was higher in ALS patients than those in healthy controls. The levels of UA, albumin, and total protein were significantly reversely correlated with diseases stages. The longitudinal observation of 81 ALS patients also showed that the levels of UA, creatinine, albumin, total protein, and HDL were significantly decreased in the second hematological examinations. Conclusions: In the present study, ALS patients and control subjects were evenly matched with regard to sex, age, and BMI value, this finding could be considered as a metabolite signature in ALS. The changes of metabolite-based serological factors with progression of disease stage might be related to the pathophysiology of disease, and might have clinical utility in clinical practice.

Brain organization of the preparation to visual recognition in preadolescent children

The brain organization of the process of preparation for the perception of incomplete images fragmented to different extents. The functional connections of ventrolateral and dorsoventral cortical zones with other zones in 10-11-year-old and 11-12-year-old children were studied at three successive stages of the preparation for the perception of incomplete images. These data were compared with those obtained for adults. In order to reveal the effect of preparatory processes on the image recognition, we also analyzed the regional event-related potentials. In adults, the functional interaction between dorsolateral and ventrolateral prefrontal cortex and other cortical zones of the right hemisphere was found to be enhanced at the stage of waiting for not-yet-recognizable image, while in the left hemisphere the links became stronger shortly before the successful recognition of a stimulus. In children the stage-related changes in functional interactions are similar in both hemispheres, with peak of interaction activity.at the stage preceding the successful recognition. It was found that in 11-12-year-old children the ventrolateral cortex is involved in both preparatory stage and recognition processes to a smaller extent as compared with adults and 10-11-year-old children. At the same time, the group of 11-12-year-old children had more mature pattern of the dorsolateral cortex involvement, which provided more effective recognition of incomplete images in this group as compared with 10-11-year-old children. It is suggested that the features of the brain organization of visual recognition and preceding preparatory processes in 11-12-year-old children are caused by multidirectional effects of sex hormones on the functioning of different zones of the prefrontal cortex at early stages of sexual maturation.

Quantitative high-throughput gene expression profiling of human striatal development to screen stem cell–derived medium spiny neurons

A systematic characterization of the spatio-temporal gene expression during human neurodevelopment is essential to understand brain function in both physiological and pathological conditions. In recent years, stem cell technology has provided an in vitro tool to recapitulate human development, permitting also the generation of human models for many diseases. The correct differentiation of human pluripotent stem cell (hPSC) into specific cell types should be evaluated by comparison with specific cells/tissue profiles from the equivalent adult in vivo organ. Here, we define by a quantitative high-throughput gene expression analysis the subset of specific genes of the whole ganglionic eminence (WGE) and adult human striatum. Our results demonstrate that not only the number of specific genes is crucial but also their relative expression levels between brain areas. We next used these gene profiles to characterize the differentiation of hPSCs. Our findings demonstrate a temporal progression of gene expression during striatal differentiation of hPSCs from a WGE toward an adult striatum identity. Present results establish a gene expression profile to qualitatively and quantitatively evaluate the telencephalic hPSC-derived progenitors eventually used for transplantation and mature striatal neurons for disease modeling and drug-screening.

Hydrodynamics and energetics of jumping copepod nauplii and copepodids.

Within its life cycle, a copepod goes through drastic changes in size, shape and swimming mode. In particular, there is a stark difference between the early (nauplius) and later (copepodid) stages. Copepods inhabit an intermediate Reynolds number regime (between ~1 and 100) where both viscosity and inertia are potentially important, and the Reynolds number changes by an order of magnitude during growth. Thus we expect the life stage related changes experienced by a copepod to result in hydrodynamic and energetic differences, ultimately affecting the fitness. To quantify these differences, we measured the swimming kinematics and fluid flow around jumping Acartia tonsa at different stages of its life cycle, using particle image velocimetry and particle tracking velocimetry. We found that the flow structures around nauplii and copepodids are topologically different, with one and two vortex rings, respectively. Our measurements suggest that copepodids cover a larger distance compared to their body size in each jump and are also hydrodynamically quieter, as the flow disturbance they create attenuates faster with distance. Also, copepodids are energetically more efficient than nauplii, presumably due to the change in hydrodynamic regime accompanied with a well-adapted body form and swimming stroke.

Rai stage-related changes within T/NK cell populations from B-CLL patients

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The influence of rice plant age on susceptibility to the rice water weevil, Lissorhoptrus oryzophilus

AbstractPlant age‐ and plant stage‐related changes in the resistance of rice, Oryza sativa, to its most important insect pest in the US, the rice water weevil (Lissorhoptrus oryzophilus), were investigated in a series of field and greenhouse choice and no‐choice studies. Rice plants were susceptible to infestation by rice water weevils over a broad range of plant ontogenetic stages, from at least the early vegetative stage to well into the reproductive stage. There was, however, a clear preference expressed by rice water weevils in both choice and no‐choice experiments for plants in (or nearly in) the tillering stage of development, with pre‐tillering and reproductive stage plants less preferred. The relationship between rice plant age and susceptibility to weevils is thus nonlinear. This study constitutes one of the most thorough studies to date of the relationship in a grass species between plant age and susceptibility to herbivores. The results provide a biological explanation for observed patterns of weevil infestations and a rationale for the cultural practice of delayed flooding.

Stage-related changes of peritoneal soluble TNFα and TNFR1 and TNFR2 in cells recovered from peritoneal fluid of women with endometriosis

B. Gharesi-Fard1,2,∗, F. Ghaderi-shabankareh1, L. Jafarzadeh1, J. Zolghadri3,2, E. Kamali-Sarvestani1,4 1 Shiraz University of Medical Sciences, Immunology Department, Shiraz, Iran, Islamic Republic of 2 Infertility Research Center, Shiraz, Iran, Islamic Republic of 3 Shiraz University ofMedical Sciences, Department of Obstetrics and Gynecology, Shiraz, Iran, Islamic Republic of 4 Autoimmune Diseases Research Center, Shiraz, Iran, Islamic Republic of

X-Ray Microanalysis Investigation of the Changes in Na, K, and Hemoglobin Concentration in Plasmodium falciparum-Infected Red Blood Cells

Plasmodium falciparum is responsible for severe malaria. During the ∼48 h duration of its asexual reproduction cycle in human red blood cells, the parasite causes profound alterations in the homeostasis of the host red cell, with reversal of the normal Na and K gradients across the host cell membrane, and a drastic fall in hemoglobin content. A question critical to our understanding of how the host cell retains its integrity for the duration of the cycle had been previously addressed by modeling the homeostasis of infected cells. The model predicted a critical contribution of excess hemoglobin consumption to cell integrity (the colloidosmotic hypothesis). Here we tested this prediction with the use of electron-probe x-ray microanalysis to measure the stage-related changes in Na, K, and Fe contents in single infected red cells and in uninfected controls. The results document a decrease in Fe signal with increased Na/K ratio. Interpreted in terms of concentrations, the results point to a sustained fall in host cell hemoglobin concentration with parasite maturation, supporting a colloidosmotic role of excess hemoglobin digestion. The results also provide, for the first time to our knowledge, comprehensive maps of the elemental distributions of Na, K, and Fe in falciparum-infected red blood cells.

Disease stage-related changes in T cell receptor-VB profile in cutaneous T cell lymphoma (88.10)

Abstract The objective of this study was to evaluate the T cell receptor-Vβ (TCR-Vβ; Vβ) repertoire in patients with Mycosis Fungoides (MF) and Sezary Syndrome (SS) variants of cutaneous T cell lymphoma (CTCL) across all stages, in order to identify relationships between Vβ expression levels and disease stage. Blood was drawn from MF/SS patients (n=31) and the percentage of CD4+ T cells expressing each Vβ was determined by multiparameter flow cytometery and the change in expression levels with progressive disease stage was calculated with Spearman's rank correlation coefficients. We found that individual TCR-Vβ families were expanded in some patients with advanced MF/SS. Further, we detected significant decreases in the proportion of five TCR-Vβs with progressive stages of disease, while the proportion of all other tested TCR-Vβ families did not change with disease stage. These data show disease stage-related changes in the expression of certain TCR-Vβs known to be activated by viral superantigens. In particular, there was a highly significant decrease in expression of TCR-Vβ13, which has been found to be activated by an EBV-associated superantigen, in advanced CTCL. Based on these findings, we theorize that in early stages of CTCL, viral infection may play a role in the expansion of specific superantigen-associated T-cells; while in later stages, these same T-cells become eliminated by a yet unknown mechanism. Funding Sources: National Institutes of Health, Dermatology Foundation, University of Pittsburgh Clinical &amp; Translational Research Center

Stage-related changes in functional capacity in Hodgkin’s disease: assessment by cardiopulmonary exercise testing before initiation of treatment

Our aim was to examine indices of cardiorespiratory capacity at rest and during exercise before initiation of therapy for Hodgkin's disease. We prospectively studied 24 patients divided into two groups according to the disease stage. Group 1 included eight patients in stage IA and four in stage IIA; group 2 included four patients in stage IIB, six in stage III, and two in stage IV. All patients underwent detailed cardiopulmonary evaluations at rest using electrocardiogram, echocardiogram, spirometry, and measurement of pulmonary diffusing capacity (DLCO), and during exercise using a cardiopulmonary exercise test. Groups 1 and 2 were similar with respect to sex distribution (eight women and four men in each), mean age (35+/-36 vs37+/-4.6 years), body mass index, and hemoglobin concentration (12.7+/-0.2 vs 12.1+/-0.3 g l-1). All patients had a normal cardiovascular status. All patients in group 1 had normal cardiorespiratory measurements at rest and during exercise. Forced vital capacity was significantly lower in group 2 (84.8+/-2.7% predicted) than in group 1 (105+/-3%, P<0.0001), without abnormalities in DLCO or in resting and exercise oxygen diffusion. Likewise, percentage predicted VO2max (65+/-4 vs 97+/-6, P<0.0002), oxygen pulse at peak exercise (0.12+/-0.01 vs 0.17+/-0.01, P<0.001), and DeltaVO2/DeltaW slope (8.4+/-0.3 vs 10.2+/-0.4, P<0.003) were significantly lower in group 2 than in group 1. Functional capacity during exercise was markedly reduced in patients suffering from Hodgkin's disease in advanced stages. This loss of exercise capacity appeared mainly related to a peripheral disorder.

Sex- and Developmental Stage-Related Changes in Energy Reserves in Fourth-instar Larvae of the MidgeChironomus ripariusMeigen (Diptera: Chironomidae): Implications for Ecotoxicity Testing

The aim of this study was to examine sex- and age-dependent changes in carbohydrate and lipid reserves throughout the fourth larval instar of Chironomus riparius Meigen. Individuals were sexed using genital discs and aged using phases of development defined through the observation of genital and thoracic imaginal discs. Glycogen concentration was measured in the eviscerated body (fat body, muscles, and cuticle), and the levels of glucose and trehalose were followed in the hemolymph, whereas the amounts of free glycerol and triglycerides were measured in both tissues. Compared with males, females had higher levels of body reserves, whereas the levels of sugars in the hemolymph were similar for both sexes, except for free glucose, which was slightly higher in males. The levels of energy-yielding substrates in both the eviscerated body and hemolymph varied significantly with the phase of development for both sexes, except for the concentration in free glycerol in the hemolymph. Analysis of variability indicated that selection of larvae for both the sex and phase of development significantly reduces uncertainty of biochemical measures. The results are discussed with respect to potential use of the levels of energy-yielding substrates as endpoints in toxicity tests with fourth-instar C. riparius larvae.

Amyotrophic lateral sclerosis: disease stage related changes of biochemical markers (tau protein, creatine kinase, sCD14) in CSF and serum

Amyotrophic lateral sclerosis: disease stage related changes of biochemical markers (tau protein, creatine kinase, sCD14) in CSF and serum

Increase of brain-stem high-frequency SEP subcomponents during light sleep in seizure-free epileptic patients

Objective Three hertz spike-and-wave (SW) occurrence is caused by the abnormal functioning of the same thalamo-cortical loop generating sleep spindles. In fact, SW preferably occurs during light sleep and transitional phases of the vigilance status. Since high-frequency somatosensory evoked potentials (HF-SEPs) are powerfully modulated by sleep and arousal, we verified whether they can reveal abnormalities of arousal-related structures in two patients having showed sporadic SW discharges during light sleep. Methods We recorded right median nerve SEPs in two adult patients who suffered since the infancy from childhood absence epilepsy (CAE). Sleep stage-related changes of HF-SEPs were compared to those observed in five healthy volunteers. Results HF-SEPs decreased during sleep in controls. By contrast, the amplitude of the subcortical component dramatically increased in CAE patients during phase II NREM sleep. Simultaneous EEG showed normally represented sleep spindles, but not SW discharges. Conclusions HF-SEP increase probably reflects the hyperactivation of brain-stem arousal-related structures. During such a hyperactivation no EEG abnormalities were observed. Significance We hypothesize that HF-SEP increase might reflect a protective mechanism against seizure occurrence during light sleep.

Apoptosis and differential expression of apoptosis-related proteins in endometriotic glandular and stromal cells.

Apoptosis is an important regulator of eutopic endometrial function. Endometriosis, the growth of endometrial tissue outside the uterus, could result from increased cellular proliferation or decreased apoptosis in response to appropriate stimuli. The objective of this study was to evaluate the rate of apoptosis and the expression of apoptosis-related Bcl-2 and Bax proteins in endometriotic tissues within the glandular and stromal compartments, according to the phase of the menstrual cycle and the stage of disease. Ovarian endometriosis samples were evaluated in 75 women who had surgery at a university hospital. Apoptotic cells were detected with the use of the dUTP nick-end labeling (TUNEL) assay. Bcl-2 and Bax expression were assessed by immunohistochemical techniques. The percentage of apoptotic cells was significantly higher in endometriotic stromal cells (73.3%) compared with glandular cells (48%; P =.002). In contrast, the expression of the apoptosis-related proteins Bcl-2 and Bax was significantly lower in the endometriotic stroma (17.3% for both) than in the glandular epithelium (38.6% and 41.3%, respectively; P <.004). No significant menstrual cycle phase-dependent changes or endometriosis stage-related changes were observed in TUNEL, Bcl-2, or Bax positivity within ovarian endometriotic tissues. Apoptosis occurs in ovarian endometriotic lesions at significantly higher levels in the stroma than the glandular epithelium. However, Bcl-2 and Bax proteins are distributed preferentially in glandular epithelial cells. The apoptotic rate as well as Bcl-2 and Bax expression in ovarian endometriotic cells were not affected by the stage of endometriosis or the phase of the menstrual cycle.

Axonal damage in patients with early multiple sclerosis: disease stage related changes of Tau protein level in cerebrospinal fluid

Background: Axonal damage has been proposed as the major morphological substrate of permanent clinical disability in multiple sclerosis (MS). Tau protein (tau), a phosphorylated microtubule-associated protein localised in neuronal axons, may serve as a biochemical surrogate to evaluate axonal loss in vivo. We intended to determine the extent of axonal degeneration in different stages and clinical subtypes of MS by investigating cerebrospinal fluid (CSF) tau concentrations.