The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p < 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent condition such as cIVDD

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH

Health-seeking behaviours of older black women living with non-communicable diseases in an urban township in South Africa

BACKGROUND: Various studies have shown that non-communicable diseases (NCDs) especially diabetes and hypertension are prevalent among older women living in South African urban areas, placing a heavy burden on the healthcare system. This study aimed to understand the health-seeking behaviour, healthcare practices and prevalence of traditional herbal medicine (THM) use among older women self-reporting NCDs from the Prospective Urban Rural Epidemiology study (PURE). METHOD: A homogenous purposive sampling of PURE participants was used to recruit women who were 50 years or older (n = 250). Descriptive statistics were used to examine the number of NCDs reported by the study sample, health seeking behaviour and practices as well as THM use. Logistic regression was also employed to investigate possible associations between reported conditions and THM use or medical pluralism. RESULTS: Within the study sample, 72 % self-reported an NCD. Of those with self-reported NCDs, 46 % had one, and 54 % had two or more NCDs. Those with NCDs usually visited public clinics (80 %), relied on doctors (90 %) and nurses (85 %) for health information, and mostly used conventional medicine (CM) to manage high blood pressure (81 %). About 30 % of those with NCDs indicated using THM, of whom 29 (53 %) reported practicing medical pluralism. Participants with dental problems (OR: 3.24, 95 % CI: 1.30–8.20), headaches (OR: 2.42, 95 % CI: 1.24–4.94), heart burn (OR: 2.30, 95 % CI: 1.18–4.48) and severe tiredness (OR: 2.05, 95 % CI: 1.08–3.99) were more likely to use THM. Anxiety and allergies increased the likelihood to practise medical pluralism by five and 20 times, respectively. CONCLUSION: Self-reported NCD with co-morbidities was prevalent among the participants in the study. Most of the study participants utilized state-owned clinics and hospitals for the management of their chronic conditions. THM use was not very common. However, among those who used THM, medical pluralism was prevalent. Family history was the most common reason for THM use, with many THM patrons utilizing these for treatment of a health condition. Older black women with anxiety and allergies were more likely to practise medical pluralism

Understanding the decomposition reaction mechanism of chrysanthemic acid: a computational study

<p>Abstract</p> <p>Background</p> <p>Chrysanthemic acid (<b>CHA</b>) is a major product from the photodecomposition of pyrethrin which is an important class of pesticide compounds.</p> <p>In the following paper, Hybrid density functional theory (DFT) calculations of the potential energy surface (PES) for three possible channels decomposition of chrysanthemic acid <b>(</b>cis-trans isomerization, rearrangement and fragmentation) have been carried at the B3LYP/6-311+G** level of theory. DFT was employed to optimize the geometry parameters of the reactants, transition states, intermediates and products based on detailed potential energy surfaces (PES).</p> <p>Results</p> <p>Our results suggest that all three pathways of <b>CHA </b>are endothermic. DFT calculations revealed that the activation barriers for cis-trans isomerization are low, leading to a thermodynamically favorable process than other two pathways. We also investigated the solvent effect on the PES using the polarizable continuum model (PCM). In addition, time-dependent density functional theory (TDDFT) calculations showed that these reactions occur in the ground state rather than in an excited state.</p> <p>Conclusion</p> <p>The rearrangement process seems to be more favorable than the decomposition of <b>CHA </b>to carbene formation. The solvent effect calculations indicated no changes in the shape of the PES with three continua (water, ethanol and cyclohexane), although the solvents tend to stabilize all of the species.</p

On the relevance of animal behavior to the management and conservation of fishes and fisheries

There are many syntheses on the role of animal behavior in understanding and mitigating conservation threats for wildlife. That body of work has inspired the development of a new discipline called conservation behavior. Yet, the majority of those synthetic papers focus on non-fish taxa such as birds and mammals. Many fish populations are subject to intensive exploitation and management and for decades researchers have used concepts and knowledge from animal behavior to support management and conservation actions. Dr. David L. G. Noakes is an influential ethologist who did much foundational work related to illustrating how behavior was relevant to the management and conservation of wild fish. We pay tribute to the late Dr. Noakes by summarizing the relevance of animal behavior to fisheries management and conservation. To do so, we first consider what behavior has revealed about how fish respond to key threats such as habitat alteration and loss, invasive species, climate change, pollution, and exploitation. We then consider how behavior has informed the application of common management interventions such as protected areas and spatial planning, stock enhancement, and restoration of habitat and connectivity. Our synthesis focuses on the totality of the field but includes reflections on the specific contributions of Dr. Noakes. Themes emerging from his approach include the value of fundamental research, management-scale experiments, and bridging behavior, physiology, and ecology. Animal behavior plays a key role in understanding and mitigating threats to wild fish populations and will become more important with the increasing pressures facing aquatic ecosystems. Fortunately, the toolbox for studying behavior is expanding, with technological and analytical advances revolutionizing our understanding of wild fish and generating new knowledge for fisheries managers and conservation practitioners

Haploinsufficiency of the E3 Ubiquitin Ligase C-Terminus of Heat Shock Cognate 70 Interacting Protein (CHIP) Produces Specific Behavioral Impairments

The multifunctional E3 ubiquitin ligase CHIP is an essential interacting partner of HSP70, which together promote the proteasomal degradation of client proteins. Acute CHIP overexpression provides neuroprotection against neurotoxic mitochondrial stress, glucocorticoids, and accumulation of toxic amyloid fragments, as well as genetic mutations in other E3 ligases, which have been shown to result in familial Parkinson's disease. These studies have created a great deal of interest in understanding CHIP activity, expression and modulation. While CHIP knockout mice have the potential to provide essential insights into the molecular control of cell fate and survival, the animals have been difficult to characterize in vivo due to severe phenotypic and behavioral dysfunction, which have thus far been poorly characterized. Therefore, in the present study we conducted a battery of neurobehavioral and physiological assays of adult CHIP heterozygotic (HET) mutant mice to provide a better understanding of the functional consequence of CHIP deficiency. We found that CHIP HET mice had normal body and brain weight, body temperature, muscle tone and breathing patterns, but do have a significant elevation in baseline heart rate. Meanwhile basic behavioral screens of sensory, motor, emotional and cognitive functions were normative. We observed no alterations in performance in the elevated plus maze, light-dark preference and tail suspension assays, or two simple cognitive tasks: novel object recognition and spontaneous alternation in a Y maze. Significant deficits were found, however, when CHIP HET mice performed wire hang, inverted screen, wire maneuver, and open field tasks. Taken together, our data indicate a clear subset of behaviors that are altered at baseline in CHIP deficient animals, which will further guide whole animal studies of the effects of CHIP dysregulation on cardiac function, brain circuitry and function, and responsiveness to environmental and cellular stress

Weight and metabolic effects of cpap in obstructive sleep apnea patients with obesity

<p>Abstract</p> <p>Background</p> <p>Obstructive sleep apnea (OSA) is associated with obesity, insulin resistance (IR) and diabetes. Continuous positive airway pressure (CPAP) rapidly mitigates OSA in obese subjects but its metabolic effects are not well-characterized. We postulated that CPAP will decrease IR, ghrelin and resistin and increase adiponectin levels in this setting.</p> <p>Methods</p> <p>In a pre- and post-treatment, within-subject design, insulin and appetite-regulating hormones were assayed in 20 obese subjects with OSA before and after 6 months of CPAP use. Primary outcome measures included glucose, insulin, and IR levels. Other measures included ghrelin, leptin, adiponectin and resistin levels. Body weight change were recorded and used to examine the relationship between glucose regulation and appetite-regulating hormones.</p> <p>Results</p> <p>CPAP effectively improved hypoxia. However, subjects had increased insulin and IR. Fasting ghrelin decreased significantly while leptin, adiponectin and resistin remained unchanged. Forty percent of patients gained weight significantly. Changes in body weight directly correlated with changes in insulin and IR. Ghrelin changes inversely correlated with changes in IR but did not change as a function of weight.</p> <p>Conclusions</p> <p>Weight change rather than elimination of hypoxia modulated alterations in IR in obese patients with OSA during the first six months of CPAP therapy.</p

Tobacco and the risk of acute leukaemia in adults

Self-reported smoking histories were collected during face-to-face interviews with 807 patients with acute leukaemia and 1593 age- and sex-matched controls. Individuals who had smoked regularly at some time during their lives were more likely to develop acute leukaemia than those who had never smoked (odds ratio (OR) = 1.2, 95% confidence interval (CI) 1.0–1.4). The association was strongest for current smokers, defined here as smoking 2 years before diagnosis (OR = 1.4, 95% CI 1.1–1.7). With respect to the numbers of years smoked, risk estimates were raised in all groups except those who had smoked for fewer than 10 years. Similarly, the odds ratio decreased as the number of years ‘stopped smoking’ increased, falling to one amongst those who had given up smoking for more than 10 years. No significant linear trends were found, however, with either the numbers of years smoked or the numbers of years stopped smoking, and no significant differences were found between AML and ALL. © 1999 Cancer Research Campaig

Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis

BACKGROUND: Observational studies have consistently shown that aspirin and non-steroidal anti-inflammatory drug (NSAID) use is associated with a close to 50% reduced risk of colorectal cancer. Studies assessing the effects of NSAIDs on other cancers have shown conflicting results. Therefore, we conducted a meta-analysis to evaluate the relationship between NSAID use and cancer other than colorectal. METHODS: We performed a search in Medline (from 1966 to 2002) and identified a total of 47 articles (13 cohort and 34 case-control studies). Overall estimates of the relative risk (RR) were calculated for each cancer site using random effects models. RESULTS: Aspirin use was associated with a reduced risk of cancer of the esophagus and the stomach (RR, 0.51; 95%CI (0.38–0.69), and 0.73; 95%CI (0.63–0.84)). Use of NSAIDs was similarly associated with a lower risk of esophageal and gastric cancers (RR,0.65; 95% CI(0.46–0.92) and RR,0.54; 95%CI (0.39–0.75)). Among other cancers, only the results obtained for breast cancer were fairly consistent in showing a slight reduced risk among NSAID and aspirin users (RR, 0.77; 95%CI (0.66–0.88), and RR, 0.77; 95%CI (0.69–0.86) respectively)). CONCLUSIONS: The results of this meta-analysis show that the potential chemopreventive role of NSAIDs in colorectal cancer might be extended to other gastrointestinal cancers such as esophagus and stomach. Further research is required to evaluate the role of NSAIDs at other cancers sites