Miracle-dz/UniFAR-FTUs huggingface dataset:
Partner Loss in Monogamous Rodents: Modulation of Pain and Emotional Behavior in Male Prairie Voles

Objective Pain is modulated by psychosocial factors, and social stress–induced hyperalgesia is a common clinical symptom in pain disorders. To provide a new animal model for studying social modulation of pain, we examined pain behaviors in monogamous prairie voles experiencing partner loss. Methods After cohabitation with novel females, males (n = 79) were divided into two groups on the basis of preference test scores. Half of the males of each group were separated from their partner (loss group), whereas the other half remained paired (paired group). Thus, males from both groups experienced social isolation. Open field tests, plantar tests, and formalin tests were then conducted on males to assess anxiety and pain-related behaviors. Results Loss males showing partner preferences (n = 20) displayed a significant increase in anxiety-related behavior in the open-field test (central area/total distance: 13.65% [1.58%] for paired versus 6.45% [0.87%] for loss; p < .001), a low threshold of thermal stimulus in the plantar test (withdrawal latencies: 9.69 [0.98] seconds for paired versus 6.15 [0.75] seconds for loss; p = .037), and exacerbated pain behaviors in the formalin test (total number of lifts: 40.33 [4.46] for paired versus 54.42 [1.91] for loss; p = .042) as compared with paired males (n = 20). Thermal thresholds in the plantar test significantly correlated with anxiety-related behavior in the open-field test (r = 0.64). No such differences were observed in the males that did not display partner preferences (r = 0.15). Conclusions Results indicate that social bonds and their disruption, but not social housing without bonding followed by isolation, modulate pain and emotion in male prairie voles. The prairie vole is a useful model for exploring the neural mechanisms by which social relationships contribute to pain and nociceptive processing in humans.
Non‐clinical safety and biodistribution of AS03‐adjuvanted inactivated pandemic influenza vaccines

Pandemic‐influenza vaccines containing split‐inactivated‐virus antigen have been formulated with the immunostimulatory Adjuvant System AS03 to enhance the antigen immunogenicity and reduce antigen content per dose. AS03 is an oil‐in‐water emulsion containing α‐tocopherol, squalene and polysorbate 80. To support the clinical development of AS03‐adjuvanted pandemic‐influenza vaccines, the local and systemic toxicity of test articles containing split‐influenza A(H5N1) and/or AS03 were evaluated after 3–4 intramuscular (i.m.) injections in rabbits. Treatment‐related effects were restricted to mild inflammatory responses and were induced primarily by the test articles containing AS03. The injection‐site inflammation was mild at 3 days, and minimal at 4 weeks after the last injection; and was reflected by signs of activation in the draining lymph nodes and by systemic effects in the blood including a transient increase of neutrophils. In addition, a study in mice explored the biodistribution of A(H5N1) vaccines or AS03 through radiolabelling the antigen or constituents of AS03 prior to injection. In this evaluation, 57–73% of AS03's principal constituents had cleared from the injection site 3 days after injection, and their different clearance kinetics were suggestive of AS03's dissociation. All these AS03 constituents entered into the draining lymph nodes within 30 min after injection. In conclusion, the administration of repeated doses of the H5N1/AS03 vaccine was well tolerated in the rabbit, and was primarily associated with transient mild inflammation at the injection site and draining lymph nodes. The biodistribution kinetics of AS03 constituents in the mouse were consistent with AS03 inducing this pattern of inflammation. Copyright © 2015 John Wiley & Sons, Ltd.
Cardiovascular Stress Reactivity and Carotid Intima-Media Thickness: The Buffering Role of Slow-Wave Sleep

Objective Exaggerated cardiovascular reactivity to acute psychological stress has been associated with increased carotid intima-media thickness (IMT). However, interstudy variability in this relationship suggests the presence of moderating factors. The current study aimed to test the hypothesis that poor nocturnal sleep, defined as short total sleep time or low slow-wave sleep, would moderate the relationship between cardiovascular reactivity and IMT. Methods Participants (N = 99, 65.7% female, age = 59.3 ± 9.3 years) completed a two-night laboratory sleep study and cardiovascular examination where sleep and IMT were measured. The multisource interference task was used to induce acute psychological stress, while systolic and diastolic blood pressure and heart rate were monitored. Moderation was tested using the PROCESS framework in SPSS. Results Slow-wave sleep significantly moderated the relationship between all cardiovascular stress reactivity variables and IMT (all pinteraction ⩽ .048, all &Dgr;R2interaction ≥ .027). Greater stress reactivity was associated with higher IMT values in the low slow-wave sleep group and lower IMT values in the high slow-wave sleep group. No moderating effects of total sleep time were observed. Conclusions The results provide evidence that nocturnal slow-wave sleep moderates the relationship between cardiovascular stress reactivity and IMT and may buffer the effect of daytime stress-related disease processes.
A Prospective Study of PTSD and Early-Age Heart Disease Mortality Among Vietnam Veterans: Implications for Surveillance and Prevention

Objective: To examine prospectively early-age heart disease (HD) among a national random sample of 4328 male Vietnam veterans, who did not have HD at baseline in 1985. Studies have suggested that posttraumatic stress disorder (PTSD) may result in cardiovascular disease. However, many past studies had important methodological limitations to their designs. Method: Using Cox regressions, we assessed PTSD, age, race, intelligence, family history, obesity, smoking, alcohol abuse, antisocial personality, and depression in predicting HD mortality at follow-up in December 31, 2000. The men were <65 years old at follow-up. Results: Using two PTSD measures, a Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition (DSM-III) measure (D-PTSD) and one developed by Keane (K-PTSD), we found that among Vietnam theater and era veterans combined (era veterans had no Vietnam service), having PTSD was associated with HD mortality for D-PTSD (hazard ratio (HR) = 2.25, p = . 045) and approached significance for K-PTSD (HR = 2.16, p = .066). However, having higher PTSD symptoms on either scale was associated with mortality, with a 5-point increase associated with ∼20% increase in mortality risk (all p < .05). Controlling for lifetime depression only slightly altered the results. The effects for theater veterans alone were stronger (D-PTSD: HR = 2.58, p = .025; K-PTSD: HR = 2.73, p = .022). Among theater veterans, controlling for lifetime depression or combat exposure made little difference. Conclusion: PTSD was prospectively associated with HD mortality among veterans free of HD at baseline. This study suggests that early-age HD may be an outcome after military service among PTSD-positive veterans. TV = theater veteran; EV = era veteran; POW = prisoner of war; PTSD = posttraumatic stress disorder; DIS = Diagnostic Interview Schedule; DSM-III = Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition; HD = heart disease; ECG = electrocardiogram; BP = blood pressure; HPA = hypothalamic-pituitary-adrenocortical; SAM = sympathetic-adrenal-medullary; NDI = National Death Index; HR = hazard ratio; CI = Confidence Interval.
FIBER DISSOCIATION IN PERIPHERAL NEUROPATHY

The various functions of the peripheral nerve are not uniformly affected in the peripheral neuropathy accompanying alcoholism and other conditions leading to disturbed nutrition. With regard to sensation, it has been observed that modalities which are eventually to be carried in the posterior columns, and which are newer in the developmental (phylogenetic) scale, are likely to be impaired earlier and more severely. Neurologic textbooks1note that light touch, position and vibration senses are relatively severely affected, while pain sense may be either fairly well preserved or, more commonly, preserved in a "paradoxic" form. In this paper we have attempted to correlate these observations with certain experimental, clinical and metabolic data. FIBER TYPES The most extensive attempt to group fibers in the peripheral nerves on a functional basis was that of Head,2who divided sensation into the following types: Epicritic sensation: This includes light touch sensation over hairless
Major Depression, C-Reactive Protein, and Incident Ischemic Heart Disease in Healthy Men and Women

Objective: To investigate how C-reactive protein (CRP) and major depressive disorder (MDD) relate to each other and to incident ischemic heart disease (IHD). Studies have shown that both depression and raised CRP concentration predict IHD and that elevated CRP is linked with increased risk of depression. Methods: A prospective case-control study of healthy men and women, aged 45 to 79 years, was undertaken within the United Kingdom European Prospective Investigation into Cancer (EPIC)-Norfolk study. CRP concentration was measured for 726 (fatal or nonfatal) IHD cases and 1688 matched controls who completed a baseline MDD self-assessment, defined by restricted Diagnostic and Statistical Manual of Mental Disorders, 4th Edition diagnostic criteria. Results: Past-year MDD was associated with increased CRP concentration levels (4.31 mg/L for participants who reported episodes of MDD in the past year versus 3.65 mg/L for those who did not; p = .003), and the odds ratio for incident IHD associated with higher CRP concentration was 2.02 (comparing the top versus bottom quartile of CRP; 95% Confidence Interval (CI) = 1.52–2.68), adjusted for cigarette smoking, diabetes, systolic blood pressure, body mass index, and cholesterol. The association between past-year MDD and IHD was independent of CRP (odds ratio = 1.55; 95% CI = 1.01–2.37, with adjustments as above, and additionally for CRP). Conclusions: Evidence from this study is supportive of an association between MDD and CRP although it suggests that CRP does not account for the association between MDD and future IHD. BMI = body mass index; CRP = C-reactive protein; CVD = cardiovascular disease; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; EPIC-Norfolk = European Prospective Investigation into Cancer-Norfolk study; HLEQ = Health and Life Experiences Questionnaire; IHD = ischemic heart disease; MDD = major depressive disorder; MI = myocardial infarction; PRIME = Prospective Epidemiological Study of Myocardial Infarction; SBP = systolic blood pressure.
Arsenic inhibits mast cell degranulation via suppression of early tyrosine phosphorylation events

Exposure to arsenic is a global health concern. We previously documented an inhibitory effect of inorganic Arsenite on IgE‐mediated degranulation of RBL‐2H3 mast cells (Hutchinson et al., 2011; J. Appl. Toxicol. 31: 231–241). Mast cells are tissue‐resident cells that are positioned at the host–environment interface, thereby serving vital roles in many physiological processes and disease states, in addition to their well‐known roles in allergy and asthma. Upon activation, mast cells secrete several mediators from cytoplasmic granules, in degranulation. The present study is an investigation of Arsenite's molecular target(s) in the degranulation pathway. Here, we report that arsenic does not affect degranulation stimulated by either the Ca2+ ionophore A23187 or thapsigargin, which both bypass early signaling events. Arsenic also does not alter degranulation initiated by another non‐IgE‐mediated mast cell stimulant, the G‐protein activator compound 48/80. However, arsenic inhibits Ca2+ influx into antigen‐activated mast cells. These results indicate that the target of arsenic in the degranulation pathway is upstream of the Ca2+ influx. Phospho‐Syk and phospho‐p85 phosphoinositide 3‐kinase enzyme‐linked immunosorbent assays data show that arsenic inhibits early phosphorylation events. Taken together, this evidence indicates that the mechanism underlying arsenic inhibition of mast cell degranulation occurs at the early tyrosine phosphorylation steps in the degranulation pathway. Copyright © 2016 John Wiley & Sons, Ltd.
Trimetazidine reduces endogenous free fatty acid oxidation and improves myocardial efficiency in obese humans.

INTRODUCTION The metabolic modulator trimetazidine (TMZ) has been suggested to induce a metabolic shift from myocardial fatty acid oxidation (FAO) to glucose utilization, but this mechanism remains unproven in humans. The oxidation of plasma derived FA is commonly measured in humans, whereas the contribution of FA from triglycerides stored in the myocardium has been poorly characterized. AIMS To verify the hypothesis that TMZ induces a metabolic shift, we combined positron emission tomography (PET) and magnetic resonance spectroscopy ((1)H-MRS) to measure myocardial FAO from plasma and intracellular lipids, and myocardial glucose metabolism. Nine obese subjects were studied before and after 1 month of TMZ treatment. Myocardial glucose and FA metabolism were assessed by PET with (18)F-fluorodeoxyglucose and (11)C-palmitate. (1)H-MRS was used to measure myocardial lipids, the latter being integrated into the PET data analysis to quantify myocardial triglyceride turnover. RESULTS Myocardial FAO derived from intracellular lipids was at least equal to that of plasma FAs (P = NS). BMI and cardiac work were positively associated with the oxidation of plasma derived FA (P ≤ 0.01). TMZ halved total and triglyceride-derived myocardial FAO (32.7 ± 8.0 to 19.6 ± 4.0 μmol/min and 23.7 ± 7.5 to 10.3 ± 2.7 μmol/min, respectively; P ≤ 0.05). These changes were accompanied by increased cardiac efficiency since unchanged LV work (1.6 ± 0.2 to 1.6 ± 0.1 Watt/g × 10(2), NS) was associated with decreased work energy from the intramyocardial triglyceride oxidation (1.6 ± 0.5 to 0.4 ± 0.1 Watt/g × 10(2), P = 0.036). CONCLUSIONS In obese subjects, we demonstrate that myocardial intracellular triglyceride oxidation significantly provides FA-derived energy for mechanical work. TMZ reduced the oxidation of triglyceride-derived myocardial FAs improving myocardial efficiency.
Cutaneous lymphomas: An update

Cutaneous lymphomas are heterogeneous and distinct entities which have been in controversy since the time of conception. WHO EORTC defined them as distinct pathological entity compared to the nodal counterpart. They are defined as lymphomas having primary cutaneous presentation without any systemic involvement. As such the diagnosis of cutaneous lymphomas is a diagnosis of exclusion. These lymphomas are distinct from the nodal lymphomas in their presentation, behaviour and prognosis. These lymphomas have been divided into B cell and T cell type based on the presence of predominance of atypical lymphocytes of B or T lineage. The most common cutaneous lymphomas are T cell immunophenotype, and Mycosis fungoides constitutes the majority of cutaneous lymphomas. Cutaneous lymphomas needs to be differentiated from pseudolymphomas which are benign proliferation of lymphoid cells mimicking lymphomas and mostly have a benign course
Differences in the mechanisms of action of BDE‐47 and its metabolites on OVCAR‐3 and MCF‐7 cell apoptosis

Data concerning possible carcinogenic action of polybrominated diphenyl ethers (PBDEs) in hormone‐dependent tissues are limited. Our earlier studies showed that 2,2′,4,4′‐tetrabromodiphenyl ether (BDE‐47) stimulated OVCAR‐3 and MCF‐7 cell proliferation, while its hydroxylated metabolites (5‐OH‐BDE‐47 and 6‐OH‐BDE‐47) increased estrogen receptors protein expression and extracellular signal‐regulated kinase 1/2 and protein kinase Cα phosphorylation in these cell lines. In addition to cell proliferative disorder, a failure in the regulation of apoptosis can also lead to the formation and development of tumors. Therefore, in the present study, we investigated the effect of BDE‐47 and its metabolites (2.5–50 ng ml–1) on the expression of apoptosis regulatory genes and proteins, caspase‐8 and ‐9 activity and DNA fragmentation induced by extracellular signal‐regulated kinase inhibitor (PD098059) and protein kinase Cα inhibitor (Gӧ 6976) in ovarian (OVCAR‐3) and breast (MCF‐7) cancer cells. In OVCAR‐3 cells, BDE‐47 upregulated expression of most of the investigated genes and increased protein expression of tumor necrosis factor (TNF)‐α, TNF receptor 1, caspase‐6, Bcl‐xl and caspase‐8 activity. Whereas in MCF‐7 cells, BDE‐47 resulted in the downregulation of most of the investigated genes, and decreased caspase‐8 and ‐9 activity. In both OVCAR‐3 and MCF‐7 cells, the expression of most of the investigated genes were downregulated by metabolites. Exposure of OVCAR‐3 cells to 5‐OH‐BDE‐47 corresponded with a decrease in the protein expression of caspase‐6, caspase‐9 and Bcl‐xl and treatment with 6‐OH‐BDE‐47 decreased Bcl‐xl and TNF receptor 1 expression in OVCAR‐3 cells and caspase‐9 expression in MCF‐7 cells. Hydroxylated metabolites of BDE‐47 have strong inhibitory effects on apoptosis in ovarian and breast tumor cells and thus should be considered potential carcinogens in hormone‐dependent cancers. Copyright © 2016 John Wiley & Sons, Ltd.
Quantifying Stroke Risk Factors and Potentials for Risk Reduction

Identification of precursors of stroke is the first step in instituting a program for disease prevention. These precursors include risk factors: hypertension, diabetes, cigarette smoking, left ventricular hypertrophy by ECG, as well as predisposing diseases: coronary heart disease, cardiac failure and atrial fibrillation. Two preventive approaches may be taken: one is a public health approach whereby the entire population is informed of the dangers of certain highly prevalent risk factors for disease: antismoking and hypertension awareness campaigns and the current United States National Cholesterol Education Program are examples of this approach; the other is more focused and requires treatment by physicians of individuals found to be at increased risk of stroke. For the public health approach to be feasible, the risk factor under attack needs to be prevalent in the population and potent as a disease promotor. For precursors occurring infrequently in the population but with a high relative risk, or where the multiple borderline levels of risk factors are present, treatment of high risk individuals is in order. Use of the stroke risk function enables the treating physician to determine the conditional probability of stroke in the individual patient. The individual''s risk of stroke can be compared to that of an average person of the same age and sex and has been shown to be useful in predicting stroke recurrence and death.
Ang II and Ang IV: Unraveling the Mechanism of Action on Synaptic Plasticity, Memory, and Epilepsy

The central angiotensin system plays a crucial role in cardiovascular regulation. More recently, angiotensin peptides have been implicated in stress, anxiety, depression, cognition, and epilepsy. Angiotensin II (Ang II) exerts its actions through AT1 and AT2 receptors, while most actions of its metabolite Ang IV were believed to be independent of AT1 or AT2 receptor activation. A specific binding site with high affinity for Ang IV was discovered and denominated “AT4 receptor”. The beneficiary effects of AT4 ligands in animal models for cognitive impairment and epileptic seizures initiated the search for their mechanism of action. This proved to be a challenging task, and after 20 years of research, the nature of the “AT4 receptor” remains controversial. Insulin‐regulated aminopeptidase (IRAP) was first identified as the high‐affinity binding site for AT4 ligands. Recently, the hepatocyte growth factor receptor c‐MET was also proposed as a receptor for AT4 ligands. The present review focuses on the effects of Ang II and Ang IV on synaptic transmission and plasticity, learning, memory, and epileptic seizure activity. Possible interactions of Ang IV with the classical AT1 and AT2 receptor subtypes are evaluated, and other potential mechanisms by which AT4 ligands may exert their effects are discussed. Identification of these mechanisms may provide a valuable target in the development in novel drugs for the treatment of cognitive disorders and epilepsy.
Overload: Impact of Incident Stressful Events on Antiretroviral Medication Adherence and Virologic Failure in a Longitudinal, Multisite Human Immunodeficiency Virus Cohort Study

Objective: To examine the influence of incident stressful experiences on antiretroviral medication adherence and treatment outcomes. Past trauma history predicts poorer medication adherence and health outcomes. Human immunodeficiency virus (HIV)-infected individuals experience frequently traumatic and stressful events, such as sexual and physical assault, housing instability, and major financial, employment, and legal difficulties. Methods: We measured prospectively incident stressful and traumatic events, medication adherence, and viral load over 27 months in an eight-site, five-state study. Using multivariable logistic and generalized estimating equation modeling, we assessed the impact of incident stressful events on 27-month changes in self-reported medication adherence and virologic failure (viral load = ≥400 c/mL). Results: Of 474 participants on antiretroviral therapy at baseline, 289 persons were interviewed and still received treatment at 27 months. Participants experiencing the median number of incident stressful events (n = 9) had over twice the predicted odds (odds ratio = 2.32) of antiretroviral medication nonadherence at follow-up compared with those with no events. Stressful events also predicted increased odds of virologic failure during follow-up (odds ratio = 1.09 per event). Conclusions: Incident stressful events are exceedingly common in the lives of HIV-infected individuals and negatively affect antiretroviral medication adherence and treatment outcomes. Interventions to address stress and trauma are needed to improve HIV outcomes. ARV = antiretroviral therapy; ASI = Addiction Severity Index; BSI = Brief Symptoms Inventory; CHASE = coping with HIV/AIDS in the Southeast; CI = Confidence Interval; OR = odds ratio; PLWHA = people living with HIV/AIDS; VL = viral load.
Assessment of genotoxicity and biodistribution of nano‐ and micron‐sized yttrium oxide in rats after acute oral treatment

The increasing use of yttrium oxide (Y2O3) nanoparticles (NPs) entails an improved understanding of their potential impact on the environmental and human health. In the present study, the acute oral toxicity of Y2O3 NPs and their microparticles (MPs) was carried out in female albino Wistar rats with 250, 500 and 1000 mg kg−1 body weight doses. Before the genotoxicity evaluation, characterization of the particles by transmission electron microscopy, dynamic light scattering and laser Doppler velocimetry was performed. The genotoxicity studies were conducted using micronucleus and comet assays. Results showed that Y2O3 NP‐induced significant DNA damage at higher dose (1000 mg kg−1 body weight) in peripheral blood leukocytes and liver cells, micronucleus formation in bone marrow and peripheral blood cells. The findings from biochemical assays depicted significant alterations in aspartate transaminase, alanine transaminase, alkaline phosphatase, malondialdehyde, superoxide dismutase, reduced glutathione, catalase and lactate dehydrogenase levels in serum, liver and kidneys at the higher dose only. Furthermore, tissue biodistribution of both particles was analyzed by inductively coupled plasma optical emission spectrometry. Bioaccumulation of yttrium (Y) in all tissues was significant and dose‐, time‐ and organ‐dependent. Moreover, Y2O3 NP‐treated rats exhibited higher tissue distribution along with greater clearance through urine whereas Y2O3 MP‐dosed animals depicted the maximum amount of Y in the feces. Hence, the results indicated that bioaccumulation of Y2O3 NPs via its Y ions may induce genotoxic effects.