Premature Decline Research Articles

Influence of Spirituality on Depression-Induced Inflammation and Executive Functioning in a Community Sample of African Americans.

African Americans (AAs) are disproportionately affected by cerebrovascular pathology and more likely to suffer from premature cognitive decline. Depression is a risk factor for poorer cognitive functioning, and research is needed to identify factors that serve to mitigate its negative effects. Studies have demonstrated positive influences of spirituality within the AA community. Determining whether spirituality attenuates the effects of depressive symptoms on cognitive functioning and the pathophysiological mechanisms that explain these relationships in AAs is paramount. This study examines the influence of daily spiritual experiences on the relationship between depressive symptoms and cognitive functioning, and how inflammatory markers may partially explain these associations. A sample of 212 (mean age= 45.6) participants completed the Daily Spiritual Experience Scale (DSES), Beck Depression Inventory-II (BDI-II), Trail Making Test A and B (TMT) and Stroop Color and Word Test (Stroop). Blood samples were collected to measure inflammatory mediators (IL-6, IL-1a, TNF-a). Linear regression analyses were used to evaluate associations. Higher BDI-II scores were associated with poorer psychomotor speed and visual scanning, measured by TMT A (B=1.49, P=.01). IL-6 explained a significant amount of variance in this relationship (B=.24, CI 95% [.00, .64]). IL-6 also significantly mediated the relationship between depressive symptoms and psychomotor speed and mental flexibility, measured by TMT B performance (B=.03, CI 95% [.003, .095]). Frequent spiritual experiences among AAs may ameliorate the negative influence of depressive symptoms on cognitive functioning.

OR18-3 Gonadal Function in Human Immunodeficiency Virus (HIV)-Infected Men Assessed by Isotopic Dilution-Liquid Chromatography-Tandem Mass Spectrometry (ID-LC-MS/MS) and Chemiluminescent Immunoassay

BACKGROUND: HIV-infection is associated to premature decline of serum T1,2. However, prevalence and biochemical characterization of hypogonadism in HIV-infected men are still to be well defined1,2. AIM: To evaluate the gonadal status in HIV-infected men by assessing circulating total T (TT) with either ID-LC-MS/MS or chemiluminescent immunoassay. METHODS: Prospective, cross-sectional, observational study on HIV-infected men with ongoing Highly Active Antiretroviral Therapy (HAART). Serum TT, gonadotropins and sex hormone-binding globulin (SHBG) were measured by chemiluminescent immunoassay. TT was also assessed by the gold standard ID-LC-MS/MS. Free T (FT) was calculated by Vermeulen equation. Hypogonadism was defined as serum TT levels below 320 ng/dL and/or free T levels below 64 pg/ml. Statistical analysis: Categorical variables were compared using Chi-Square test, while correlations were performed using linear regression models. RESULTS: 315 consecutive HIV-infected men were enrolled (mean age 45.56±5.61 years; average duration of HIV-infection 16.57±10.45 years). Considering serum TT levels assessed by LC-MS/MS and immunoassay, 11 patients out of 233 (4.8%) and 10 patients out of 315 (3.2%) had T deficiency, respectively. TT combined with luteinizing hormone (LH) levels was used to classify hypogonadism. No difference was found comparing the two methodologies used for TT measurement (p=0.914). 56 patients (17.8%) showed SHBG above the normal range (>71.4 nmol/L). Considering calculated FT, the incidence of hypogonadism raised to 6.9% using either immunoassay or LC-MS/MS, with no difference between methodologies (p=0.895). Including compensated form of hypogonadism, the prevalence raised to 13% for TT and to 15% for FT. FT showed an inverse relation with age (-0.340,p<0.0001,R2=0.116), years of infection (-0.339,p<0.0001,R2=0.120) and years of HAART (-0.346,p<0.0001,R2=0.117), but not with BMI of patients. CONCLUSIONS: To the best of our knowledge, this is the first properly-designed prospective study aiming to investigate the gonadal status of HIV-infected men with both LC-MS/MS and chemiluminescent assay, together with gonadotropins. In HIV-infected patients a) the two methodologies have equivalent reliability in TT measurement; b) SHBG for calculated FT is essential for the detection of T deficiency, revealing the real prevalence of hypogonadism in this context; c) duration of HIV-infection and HAART seem to be potent predictive factors for serum FT levels, suggesting a concomitant negative effect of virus per se and antiretroviral drugs on gonadal function. REFERENCES1Rochira V et al. Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS One. 2011;6(12):e28512. 2Rochira V & Guaraldi G. Hypogonadism in the HIV-infected man. Endocrinol Metab Clin North Am. 2014 Sep;43(3):709-30.

Sarcopenia among Adults with Cerebral Palsy in South Korea.

Most adults with cerebral palsy encounter newly developing physical health problems and premature functional decline with aging. These physical and functional losses along with the characteristic symptoms of cerebral palsy may heighten the risk of sarcopenia. To determine the prevalence of sarcopenia among a selected group of adults with cerebral palsy and to identify the factors associated with their sarcopenia among them. Cross-sectional study. University hospitals and communities for persons with disabilities. A total of 80 adults with cerebral palsy (46 men and 34 women with mean age of 42.8 ± 8.86 years) were included. Muscle mass, strength, and physical performance were measured to diagnose sarcopenia. Participants also completed a structured questionnaire for physical, psychological, or socioeconomic attributes and health-related quality of life. Prevalence of sarcopenia in adults with cerebral palsy. The prevalence of sarcopenia was 47.9%. Sarcopenia was significantly associated with sex, the Gross Motor Function Classification System (GMFCS), the Manual Ability Classification System (MACS), body mass index (BMI), and trunk fat. Male, higher GMFCS and lower BMI were significant risk factors of sarcopenia. Sarcopenic adults with cerebral palsy showed significantly lower health-related quality of life. The prevalence of sarcopenia in adults with cerebral palsy was higher than that of general population despite the young age of the selected group. Modifiable risk factor was a low BMI. III.

An empirical examination of the influencers of premature decline of African clusters: Evidence from textile clusters in Ghana

Background: Comparatively, industry clusters in Africa have retrogressed over the years while their counterparts in Asia, Europe and America serve as engines for innovation and economic development. The textile industry cluster in most African economies has been threatened and is negatively affecting productivity, employment and revenue generation. Their survival, growth and sustainability are critical because of the sector’s contribution to national development Objective: In this ariticle we investigate the role fators such as stakeholder relation among actors in the textile ecosystem, influence of supply chain networks, third-party pressures and technological changes affected the development of textile clusters in Ghana and how the country can rebuild the clusters. Method: Using partial least-square structural equation modelling techninque, we tested theoritical hypotheses using survey data from firms in the industrial enclave of Ghana. Result: The findings from the study acknowledges a sharp decline in the productivity and performance of firms in various industrial sectors especially the textile cluster. The influx of copycat products coupled with the firm’s inability to adapt to changing production technology have been a key influencer in the deteriorating state of the textile industries. Again, gaps in stakeholder interactions and underutilised supply chain networks create bottlenecks that hinder the competitiveness and performance of these enterprises. Conclusion: On the contrary, findings from our study suggest external pressure from donors, multinationals and political influencers do not affect the performance and competitiveness of the textile sector as suggested by previous studies. Resuscitating the industry sector requires deliberate effort to improve coordination, information and technology sharing between key actors.

Complement factor H regulates retinal development and its absence may establish a footprint for age related macular degeneration

Age related macular degeneration (AMD) is the most common blinding disease in those over 60 years. In 50% of cases it is associated with polymorphisms of complement factor H (FH), implicating immune vulnerability. But such individuals may exhibit abnormal outer retinal blood flow decades before disease initiation, suggesting an early disease footprint. FH is expressed in the retinal pigmented epithelium (RPE). During development the RPE is adjacent to the site of retinal mitosis and complex regulatory interactions occur between the relatively mature RPE and retinal neuronal precursors that control the cell cycle. Here we ask if the absence of FH from the RPE influences retinal development using a mouse CFH knockout (Cfh−/−) with an aged retinal degenerative phenotype. We reveal that from birth, these mice have significantly disrupted and delayed retinal development. However, once development is complete, their retinae appear relatively normal, although many photoreceptor and RPE mitochondria are abnormally large, suggesting dysfunction consistent with premature ATP decline in Cfh−/−. Total retinal mtDNA is also reduced and these deficits are associated shortly after with reduced retinal function. Cfh−/+ mice also show significant abnormal patterns of cell production but not as great as in Cfh−/−. These results reveal that not only is FH an important player in sculpting retinal development but also that the developmental abnormality in Cfh−/− likely establishes critical vulnerability for later aged retinal degeneration.

Chronic circadian misalignment results in reduced longevity and large-scale changes in gene expression in Drosophila

BackgroundCircadian clocks are found in nearly all organisms, from bacteria to mammals, and ensure that behavioral and physiological processes occur at optimal times of day and in the correct temporal order. It is becoming increasingly clear that chronic circadian misalignment (CCM), such as occurs in shift workers or as a result of aberrant sleeping and eating schedules common to modern society, has profound metabolic and cognitive consequences, but the proximate mechanisms connecting CCM with reduced organismal health are unknown. Furthermore, it has been difficult to disentangle whether the health effects are directly induced by misalignment or are secondary to the alterations in sleep and activity levels that commonly occur with CCM. Here, we investigated the consequences of CCM in the powerful model system of the fruit fly, Drosophila melanogaster. We subjected flies to daily 4-h phase delays in the light-dark schedule and used the Drosophila Activity Monitoring (DAM) system to continuously track locomotor activity and sleep while simultaneously monitoring fly lifespan.ResultsConsistent with previous results, we find that exposing flies to CCM leads to a ~ 15% reduction in median lifespan in both male and female flies. Importantly, we demonstrate that the reduced longevity occurs independent of changes in overall sleep or activity. To uncover potential molecular mechanisms of CCM-induced reduction in lifespan, we conducted whole body RNA-sequencing to assess differences in gene transcription between control and misaligned flies. CCM caused progressive, large-scale changes in gene expression characterized by upregulation of genes involved in response to toxic substances, aging and oxidative stress, and downregulation of genes involved in regulation of development and differentiation, gene expression and biosynthesis.ConclusionsMany of these gene expression changes mimic those that occur during natural aging, consistent with the idea that CCM results in premature organismal decline, however, we found that genes involved in lipid metabolism are overrepresented among those that are differentially regulated by CCM and aging. This category of genes is also among the earliest to exhibit CCM-induced changes in expression, thus highlighting altered lipid metabolism as a potentially important mediator of the negative health consequences of CCM.

Resolving intractable soil constraints in urban forestry through research–practice synergy

In compact urban areas, grey infrastructure tends to prevail over green infrastructure. The tight urban fabric challenges tree growth and restricts development of greener and healthier cities. The admirable forest-city goal demands innovative methods and solutions tailor-made to tackle inherent constraints. Research findings could be more proactively transformed and transferred into practices. The aerial tree growth space, relatively less difficult to ameliorate, attracts more attention. The more intractable subterranean constraints of confined soil volume acutely restrict root growth, root spread and tree health and contribute extensively to premature decline and tree hazard. Soil surface sealing by impermeable paving is associated with compaction, organic matter deficit, low nutrient and water holding capacity and meagre nutrient stock. Scanty application of research findings has kept practice quality at a low level, rendering the persistent soil problems in the bane of urban forestry. A systematic survey of state of play provides hints on novel solutions derived from existing knowledge and proposes new research practice. A package of measures with generic connotations has been distilled from the survey of chronic, critical yet widely neglected urban soil management issues. Urban forest managers and researchers can jointly adopt out-of-the-box thinking and generate actionable translational research. Policy makers and practitioners can more promptly be informed by new harvests of research–practice synergy. Intimate and reciprocal interactions between science and practice can be proactively nurtured to raise the quality of urban landscape.

Mitochondrial absorption of short wavelength light drives primate blue retinal cones into glycolysis which may increase their pace of aging.

Photoreceptors have high energy demands and densely packed mitochondria through which light passes before phototransduction. Old world primates including humans have three cone photoreceptor types mediating color vision with short (S blue), medium (M green), and long (L red) wavelength sensitivities. However, S-cones are enigmatic. They comprise &lt;10% of the total cone population, their responses saturate early, and they are susceptible in aging and disease. Here, we show that primate S-cones actually have few mitochondria and are fueled by glycolysis, not by mitochondrial respiration. Glycolysis has a limited ability to sustain activity, potentially explaining early S-cone saturation. Mitochondria act as optical filters showing reduced light transmission at 400-450 nm where S-cones are most sensitive (420 nm). This absorbance is likely to arise in a mitochondrial porphyrin that absorbs strongly in the Soret band. Hence, reducing mitochondria will improve S-cone sensitivity but result in increased glycolysis as an alternative energy source, potentially increasing diabetic vulnerability due to restricted glucose access. Further, glycolysis carries a price resulting in premature functional decline as seen in aged S-cones. Soret band absorption may also impact on mitochondrial rich M and L cones by reducing sensitivity at the lower end of their spectral sensitivity range resulting in increased differentiation from S-cone responses. These data add to the list of unique characteristic of S-cones and may also explain aspects of their vulnerability.

ORAL HEALTH DISPARITIES AMONG OLDER ADULTS: RACE/ETHNICITY, LIFESTYLE, AND STRUCTURAL ACCESS TO CARE

Poor oral health is associated with lower quality of life in older adulthood. Although everyone experiences age-related declines in oral health, those with social and economic disadvantages experience more rapid decline and at younger ages. Yet gerontologists have given little systematic attention to documenting these disparities. Using data from the NHANES III (1988–1994) for White, Black, and Mexican-origin adults ages 50 to 70 (N= 2,320/ 1,243/1,171), we examine predictors of three indicators of oral health: no natural teeth; fair/poor self-rated oral health; irregular dentist visits. Multivariate logistic regression models indicate that White older adults have a higher likelihood of no natural teeth but Black and Mexican American older adults have greater rates of fair/poor oral health and irregular dentist visits. Those with less education and income have worse oral health. Those who ever smoked, or currently consume high levels of sugar drinks are more likely to have fair/poor oral health. Foreign-born Mexican Americans are least likely to have regular dentist visits. Black men who served in the military are significantly more likely to have regular dental visits and more natural teeth, but not White or Mexican Americans. Our findings demonstrate substantial social and economic influences on oral health among older adults and important disparities between race and ethnic groups in the United States. Premature decline in oral health is yet another consequence of a lifetime of low socioeconomic status and limited access to health care.

Global re-analysis datasets to improve hydrological assessment and snow water equivalent estimation in a sub-Arctic watershed

Abstract. Hydrological modelling in the Canadian sub-Arctic is hindered by sparse meteorological and snowpack data. The snow water equivalent (SWE) of the winter snowpack is a key predictor and driver of spring flow, but the use of SWE data in hydrological applications is limited due to high uncertainty. Global re-analysis datasets that provide gridded meteorological and SWE data may be well suited to improve hydrological assessment and snowpack simulation. To investigate representation of hydrological processes and SWE for application in hydropower operations, global re-analysis datasets covering 1979–2014 from the European Union FP7 eartH2Observe project are applied to global and local conceptual hydrological models. The recently developed Multi-Source Weighted-Ensemble Precipitation (MSWEP) and the WATCH Forcing Data applied to ERA-Interim data (WFDEI) are used to simulate snowpack accumulation, spring snowmelt volume and annual streamflow. The GlobSnow-2 SWE product funded by the European Space Agency with daily coverage from 1979 to 2014 is evaluated against in situ SWE measurement over the local watershed. Results demonstrate the successful application of global datasets for streamflow prediction, snowpack accumulation and snowmelt timing in a snowmelt-driven sub-Arctic watershed. The study was unable to demonstrate statistically significant correlations (p &lt; 0.05) among the measured snowpack, global hydrological model and GlobSnow-2 SWE compared to snowmelt runoff volume or peak discharge. The GlobSnow-2 product is found to under-predict late-season snowpacks over the study area and shows a premature decline of SWE prior to the true onset of the snowmelt. Of the datasets tested, the MSWEP precipitation results in annual SWE estimates that are better predictors of snowmelt volume and peak discharge than the WFDEI or GlobSnow-2. This study demonstrates the operational and scientific utility of the global re-analysis datasets in the sub-Arctic, although knowledge gaps remain in global satellite-based datasets for snowpack representation, for example the relationship between passive-microwave-measured SWE to snowmelt runoff volume.

Impact of soil chemistry, nutrient supplements, and fungicides on the health and yield of field-grown processing tomatoes

We report the results of a 3-year study in which we collected and analyzed soil and yield data from experimental plots in six commercial processing tomato fields in Yolo and Solano counties in California. Our objective was to assess the effect of soil chemistry and soil-delivered nutrients and fungicides on tomato plant health and fruit yield at harvest. Marketable yield, leaf necrosis, and fruit loss due to sunburn differed significantly between individual fields, with averages ranging from 81.2–138.5 Mg ha−1, 32–72% leaf necrosis and 1.9 to 8.8% sunburnt fruit, respectively. Higher-yielding fields showed significantly lower levels of leaf necrosis and sunburn damage and a positive correlation with pre-plant soil parameters such as potassium concentration and cation exchange capacity (CEC). Interestingly, soil amendments of composted poultry manure or other nutrient supplements in low-CEC fields, but not high-CEC fields, resulted in higher fruit yield and less leaf necrosis. While all fields showed symptoms typical of Verticillium wilt and some fields showed symptoms of Fusarium wilt, Fusarium crown and root rot, corky root, and root knot nematode, none of our soil amendments, including chemical and biological fungicides, significantly or consistently reduced incidence or severity of these diseases. We discuss our findings in the context of premature vine decline of tomato, an emerging phenomenon in production fields in the Sacramento Valley, which is characterized by the loss of plant vigor and canopy cover at the onset of fruit ripening and for which causative agent(s) and management options in California remain elusive. (247 words).

Rapid and reversible impairment of episodic memory by a high-fat diet in mice

Alzheimer’s disease is a leading cause of morbidity and mortality with no cure and only limited treatment available. Obesity and type 2 diabetes are positively associated with the development of premature cognitive decline and Alzheimer’s disease, linking diet with these conditions. Here we demonstrate that in mice episodic memory, together with spatial and contextual associative memory, is compromised after only one day of high-fat diet. However, object memory remains intact. This shows not only a more rapid effect than previously reported but also that more complex memories are at higher risk of being compromised by a high-fat diet. In addition, we show that these memory deficits are rapidly reversed by switching mice from a high-fat diet back to a low-fat diet. These findings have important implications for the contribution of nutrition to the development of cognitive decline and Alzheimer’s disease.

Diminished ovarian reserve and poor response to stimulation in patients

Do infertile women aged <38 years with quantitative evidence of diminished ovarian reserve and/or poor response to stimulation also exhibit poor oocyte quality as measured by blastulation rates, aneuploidy rates, and live birth rates? Young women with evidence of accelerated follicular depletion, either by precycle ovarian reserve testing or postcycle evidence of low oocyte yield, exhibit equivalent blastulation rates, aneuploidy rates and live birth rates per euploid embryo transfer as age-matched controls with normal precycle and postcycle parameters. Previous studies are conflicted as to whether women with evidence of diminished ovarian reserve and/or poor ovarian response are also at increased risk of exhibiting evidence of poor oocyte quality. Most prior studies have failed to adequately control for the confounding effect of female age on typical markers of oocyte quality in poor responders. The rate of follicular depletion occurs at around 38 years on average; thus, evidence of quantitative depletion before this would indicate a premature diminution of ovarian reserve and allow evaluation of whether markers of oocyte quality are tied to quantitative markers. This was a retrospective cohort study at a single center between 2012 and 2016. This time frame was specifically chosen as all embryos were cultured to the blastocyst stage at this center during the study period (no cleavage stage transfers were performed). Two comparisons were made: precycle assessment of ovarian reserve (based on anti-mullerian hormone (AMH) level) and postcycle oocyte yield results. For each comparison, patients in <10th percentile were compared to patients in the interquartile range (IQR) with respect to blastulation rate, aneuploidy rate and live birth rate. A mixed effects model was created to control for female age (in the <38 year old range) and correlation among oocytes from a given cohort. For the precycle blastulation analysis, only patients with AMH data available were included (345 patients with AMH in the <10th percentile versus 1758 patients with AMH in the 25th to 75th percentile (IQR)). To compare aneuploidy rates, the subset of these patients who pursued preimplantation genetic testing for aneuploidy (PGT-A) was then analyzed (124 patients in the <10th percentile versus 782 patients in the IQR). For the postcycle blastulation analysis, all patients who proceeded to retrieval (whether or not they also had AMH data available) were included (535 patients with oocyte yield in the <10th percentile versus 2675 patients in the IQR). To compare aneuploidy rates, the subset of these patients who pursued PGT-A was then analyzed (156 patients in the <10th percentile versus 1100 patients in the IQR). The adjusted odds of a given fertilized oocyte developing to a blastocyst, being aneuploid or leading to a live birth after euploid transfer were no different if the oocyte was retrieved from a cycle with ovarian reserve parameters or oocyte yield in the <10th percentile compared to an oocyte retrieved in a cycle with those parameters in the 25-75th percentile. An AMH level in the <10th percentile did more commonly result in cycle cancellation prior to retrieval and after retrieval prior to transfer due to global arrest of embryos. The timing of retrieval in patients with fewer oocytes may be more optimal given the greater ability to discern the overall maturity of the cohort, thus enhancing performance per retrieved oocyte. Analyses included only first cycles. Subsequent adjustment of protocol due to prior performance may mean that some patients in the <10th percentile for oocyte yield are actually better prognosis patients than their first cycle indicates. Data on whether or not patients were on oral contraceptives at time that AMH level drawn was not available. Other unknown biases are also likely to be present given retrospective nature of the study. While young women with evidence of quantitative depletion of ovarian reserve have lower live birth rates per stimulation cycle, this not attributable to poor oocyte quality because the blastulation rate per fertilized oocyte and live birth rate per embryo transfer are equivalent to that in women with normal quantitative markers of ovarian reserve. Thus, the pathophysiology mediating a premature quantitative decline in ovarian reserve appears different than that which mediates markers of oocyte quality, such as aneuploidy. Young poor responders may use this information to help guide embryo accumulation strategies when considering their family building plans. None. N/A.

Effects of Ovarian Pathologies and Uterine Inflammations on Adenomyosis in Bitches

Background: Adenomyosis is a non-neoplastic condition, characterized by the presence of endometrial glands or cells in the myometrium. Adenomyosis is defined by post-operative microscopic examination of uterine tissue and a rarely seen infertility problem in bitches. The process of transformation of healthy uterus into adenomiotic uterus is still a mystery. We aimed to determine role of ovarian pathologies and uterine inflammations on pathogenesis of uterine adenomyosis in bitches.Cases: After ovariohysterectomy, the uteri were fixed and processed by routine methods. Sections were stained with HematoxylinEosin, Masson’s trichrome and Periodic-Acid-Schiff and immunohistochemically; with p53 protein, Ki-67, α-smooth-muscle actin, cytokeratin-CK 8, 14, 19 antibodies, estrogen and progesterone receptors by Avidin-Biotin-Complex-Peroxidase method. Histopathologically, 7 of the collected tissue samples (n = 38) were diagnosed as adenomyosis. There were unilateral (n = 6) or bilateral (n = 1) adenomyosis in which endometrial glands had broken through the myometrium, and in some cases there were fibromyoma, inflammation, papillary hyperplasia and cysts in glands. Vaginal fibroma, fibromyoma and benign mix tumor (n = 1), simple carcinoma (n = 3), carcinosarcoma (n = 3) in mammary gland were determinated histopathologically. In addition to these findings, follicular cysts (n = 4), parovarian cyst (n = 1), adenocarcinoma and Rete ovarii adenoma were diagnosed in some ovaries. The CK 19 was scored at endometrial glands (n = 2) positively and also, muscle fibers were stained positively with α-smooth-muscle actin antibody (n = 7).Discussion: Adenomyosis is an infertility problem in adult dogs and is hard to detect with routine gynecological examinations. Adenomyosis can be seen unaccompanied by other gynecological problems such as endometritis or leiomyomas, while mammary tumors with adenomyosis have been previously reported in women and in only one case of a bitch. Little is known of the interrelationships between gross pathological and endocrine features of ovarian cysts in bitches. Due to the local hormonal imbalance, most of these ovarian tumors and cystic structures might be accompanied with uterine-vaginal and mammary gland pathologies, cystic endometrial hyperplasia-pyometra, adenomyosis, vaginal fibroma and mammary tumors. The hyperestrogenic metabolic state may promote both the invagination process and the overall spreading of adenomyosis into the myometrium. Adenomyosis is often associated with polyps, anovulation, hyperplasia without cytological atypia, and uterine leiomyoma which are produced by hyperestrogenic states. Prolactin appears to induce adenomyosis in mice and hyperprolactinemia may cause myometrial degeneration/weakness and subsequent endometrial invasion in the presence of ovarian steroids in women. Premature decline in progesterone, a problem ensues with prolactin release which can promote hyperprolactinemia or endogenous prolactin release. In addition to hormonal problems, uterine infections, immune factors and their products like cytokines and inflammatory mediators, oxidative stress and free radical metabolism also might have roles in the occurrence of adenomyosis. In the present study, four of seven adenomyotic uterine tissues had inflammation and 3 of 7 cases had pre-inflammatory changes. Changes in uterine tissues may increase cell infiltration and proliferation as well as the activity of immune cells which may promote development of adenomyosis in bitches. It is therefore possible that a defect in the p53 tumor suppressor gene may play an important role in the de novo neoplastic transformation of adenomyosis. In conclusion, adenomyosis can be observed bilaterally or unilaterally in dogs. Tissue damage under the influence of inflammation or hormonal disturbances might have a role in the occurrence of uterine adenomyosis.

Dysregulation of DAF-16/FOXO3A-mediated stress responses accelerates oxidative DNA damage induced aging

DNA damage is presumed to be one type of stochastic macromolecular damage that contributes to aging, yet little is known about the precise mechanism by which DNA damage drives aging. Here, we attempt to address this gap in knowledge using DNA repair-deficient C. elegans and mice. ERCC1-XPF is a nuclear endonuclease required for genomic stability and loss of ERCC1 in humans and mice accelerates the incidence of age-related pathologies. Like mice, ercc-1 worms are UV sensitive, shorter lived, display premature functional decline and they accumulate spontaneous oxidative DNA lesions (cyclopurines) more rapidly than wild-type worms. We found that ercc-1 worms displayed early activation of DAF-16 relative to wild-type worms, which conferred resistance to multiple stressors and was important for maximal longevity of the mutant worms. However, DAF-16 activity was not maintained over the lifespan of ercc-1 animals and this decline in DAF-16 activation corresponded with a loss of stress resistance, a rise in oxidant levels and increased morbidity, all of which were cep-1/ p53 dependent. A similar early activation of FOXO3A (the mammalian homolog of DAF-16), with increased resistance to oxidative stress, followed by a decline in FOXO3A activity and an increase in oxidant abundance was observed in Ercc1-/- primary mouse embryonic fibroblasts. Likewise, in vivo, ERCC1-deficient mice had transient activation of FOXO3A in early adulthood as did middle-aged wild-type mice, followed by a late life decline. The healthspan and mean lifespan of ERCC1 deficient mice was rescued by inactivation of p53. These data indicate that activation of DAF-16/FOXO3A is a highly conserved response to genotoxic stress that is important for suppressing consequent oxidative stress. Correspondingly, dysregulation of DAF-16/FOXO3A appears to underpin shortened healthspan and lifespan, rather than the increased DNA damage burden itself.

Tree Vitality Assessment in Urban Landscapes

The recent prolonged drought in Melbourne, Australia has had a deleterious effect on the urban forest, resulting in the premature decline of many mature trees and a consequent decline in the environmental services that trees are able to provide to urban residents. Measuring the severity of tree stress and defoliation due to various climatic factors is essential to the ongoing delivery of environmental services such as shade and carbon sequestration. This study evaluates two methods to assess the vitality of drought stressed Elm trees within an inner-city environment—bark chlorophyll fluorescence measured on large branches and an urban visual vitality index. Study species were Ulmus procera Salisb. (English Elm) and Ulmus × hollandica (Dutch Elm), which are important character and shade tree species for Melbourne. Relationships were identified between leaf water potential and the urban visual vitality index and between leaf water potential and bark chlorophyll fluorescence measured on large branches, indicating that these methods could be used to assess the effect of long-term drought and other stressors on urban trees.

Municipal asset management in China’s small cities and towns: Findings and strategies ahead

Chinese municipalities have developed a large stock of capital assets during a period of rapid growth and urbanization, but have yet to modernize asset management practices. Cities face challenges such as premature decline of fixed assets and spiking liabilities related to operating and maintaining assets. This paper evaluates the asset management practices in three selected small cities and towns in China, using a benchmarking assessment tool followed by an in-depth field assessment. The paper finds that overall performance is below half the international benchmark for good practice in all three cities. Management practices are considerably more advanced for land than for buildings and infrastructure. Key deficiencies in data availability and reporting, governance, capacity, and financial management indicate increased risks for local government finance and the delivery of public services. For small cities and towns where public revenues are often uncertain and limited, urban public services will be at risk of deterioration unless good asset management practices are put in place. The paper recommends strategic actions for upper and lower levels of government, to advance local asset management practices and facilitate the reform agenda.

Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression

Aging and major depressive disorder are risk factors for dementia, including Alzheimer’s Disease (AD), but the mechanism(s) linking depression and dementia are not known. Both AD and depression show greater prevalence in women. We began to investigate this connection using females of the genetic model of depression, the inbred Wistar Kyoto More Immobile (WMI) rat. These rats consistently display depression-like behavior compared to the genetically close control, the Wistar Kyoto Less Immobile (WLI) strain. Hippocampus-dependent contextual fear memory did not differ between young WLI and WMI females, but, by middle-age, female WMIs showed memory deficits compared to same age WLIs. This deficit, measured as duration of freezing in the fear provoking-context was not related to activity differences between the strains prior to fear conditioning. Hippocampal expression of AD-related genes, such as amyloid precursor protein, amyloid beta 42, beta secretase, synucleins, total and dephosphorylated tau, and synaptophysin, did not differ between WLIs and WMIs in either age group. However, hippocampal transcript levels of catalase (Cat) and hippocampal and frontal cortex expression of insulin-like growth factor 2 (Igf2) and Igf2 receptor (Igf2r) paralleled fear memory differences between middle-aged WLIs and WMIs. This data suggests that chronic depression-like behavior that is present in this genetic model is a risk factor for early spatial memory decline in females. The molecular mechanisms of this early memory decline likely involve the interaction of aging processes with the genetic components responsible for the depression-like behavior in this model.

Genes, Proteins, and Biological Pathways Preventing Chromothripsis.

The highly complex structural genome variations chromothripsis, chromoanasynthesis, and chromoplexy are subsumed under the term chromoanagenesis, which means chromosome rebirth. Precipitated by numerous DNA double-strand breaks, they differ in number of and distances between breakpoints, associated copy number variations, order and orientation of segments, and flanking sequences at joining points. Results from patients with the autosomal dominant cancer susceptibility disorder Li-Fraumeni syndrome implicated somatic TP53 mutations in chromothripsis. TP53 participates in the G2/M phase checkpoint, halting cell cycling after premature chromosome compaction during the second half of the S phase, thus preventing chromosome shattering. By experimental TP53 ablation and micronucleus induction, one or a few isolated chromosomes underwent desynchronized replication and chromothripsis. Secondly, chromothripsis occurred after experimental induction of telomere crisis after which dicentric chromosomes sustained TREX1-mediated resolution of chromosome bridges and kataegis. Third, DNA polymerase Polθ-dependent chromothripsis has been documented. Finally, a family with chromothripsis after L1 element-dependent retrotransposition and Alu/Alu homologous recombination has been reported. Human chromosomal instability syndromes share defects in responses to DNA double-strand breaks, characteristic cell cycle perturbations, elevated rates of micronucleus formation, premature chromosome compaction, and apoptosis. They are also associated with elevated susceptibility to malignant disease, such as medulloblastomas and gliomas in ataxia-telangiectasia, leukemia and lymphoma in Bloom syndrome, and osteosarcoma and soft tissue sarcoma in Werner syndrome. The latter syndrome is characterized by a premature aging-like progressive decline of mesenchymal tissues. In all thus far studied cases, constitutional chromothripsis occurred in the male germline and male patients with defects in the double-strand break response genes ATM, MRE11, BLM, LIG4, WRN, and Ku70 show impaired fertility. Conceivably, chromothripsis may, in a stochastic rather than deterministic way, be implicated in germline structural variation, malignant disease, premature aging, genome mosaicism in somatic tissues, and male infertility.

Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years.

Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain blood flow responses to cognitive challenges among prehypertensive individuals would predict subsequent progression of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP underwent neuropsychological testing and assessment of regional cerebral blood flow (rCBF) response to cognitive challenges. Neuropsychological performance measures were derived for verbal and logical memory (memory), executive function, working memory, mental efficiency, and attention. A pseudo-continuous arterial spin labeling magnetic resonance imaging sequence compared rCBF responses with control and active phases of cognitive challenges. Brain areas previously associated with BP were grouped into composites for frontoparietal, frontostriatal, and insular-subcortical rCBF areas. Multiple regression models tested whether BP after 2 years was predicted by initial BP, initial neuropsychological scores, and initial rCBF responses to cognitive challenge. The neuropsychological composite of working memory (standardized beta, -0.276; se=0.116; P=0.02) and the frontostriatal rCBF response to cognitive challenge (standardized beta, 0.234; se=0.108; P=0.03) significantly predicted follow-up BP. Initial BP failed to significantly predict subsequent cognitive performance or rCBF. Changes in brain function may precede or co-occur with progression of BP toward hypertensive levels in midlife.