The role of microstructural evolution during spark plasma sintering on the soft magnetic and electronic properties of a CoFe–Al2O3 soft magnetic composite

Journal of Materials Science - For transformers and inductors to meet the world’s growing demand for electrical power, more efficient soft magnetic materials with high saturation magnetic...     

Congenic rats reveal three independent Copenhagen alleles within the Mcs1 quantitative trait locus that confer resistance to mammary cancer

It has previously been shown that the Copenhagen (COP) rat contains several genetic loci that contribute to its mammary tumor-resistant phenotype after 7,12-dimethylbenz(a)anthracene (DMBA) administration. One of these loci, mammary carcinoma susceptibility 1 (Mcs1), is located on the centromeric end of chromosome 2 and appears to act in a semidominant fashion. To confirm the existence and independent action of this locus and also aid in the identification of the physical location of the Mcs1 gene, congenic lines were generated by transferring the Mcs1 COP allele onto a Wistar Furth (WF) genetic background. Male carriers were genotyped using microsatellite markers spanning 20-30 cM of the Mcs1 locus. One of the congenic lines minimally retained the COP allele at D2Mit29 on the centromeric end of chromosome 2 and extended distally to D2Rat201. Heterozygous Mcs1 carrier rats were interbred, and the female offspring were treated with DMBA. The female rats from the Mcs1 congenic line that carried one or two COP alleles of the Mcs1 region had a significantly reduced (65 and 85%, respectively) tumor development (P < 0.001) compared with rats carrying zero COP alleles at this locus. A WF.COP-D2Mit29/D2Rat201 homozygous congenic strain derived at the N10 generation was treated with DMBA, and the COP homozygous rats developed 1.5 +/- 0.3 carcinomas/rat versus 6.3 +/- 0.5 in WF control rats (P < 0.0001). Fine mapping of this congenic interval using several recombinant lines identified three genetic loci within the Mcs1 congenic region that independently supported a tumor resistance phenotype. These genetic loci have been termed Mcs1a, Mcs1b, and Mcs1c. In rats for which each locus was homozygous for the COP allele, tumor development was reduced by approximately 60% compared with littermate controls. The identification of these independent loci within the Mcs1 COP allele provide a model of the genetic complexity of cancer.     

The effect of growth hormone replacement on cortisol metabolism and glucocorticoid sensitivity in hypopituitary adults

OBJECTIVE: Growth hormone (GH) replacement therapy in hypopituitary adults is associated with sodium and water retention. The underlying mechanisms are incompletely understood and a possible contribution of altered cortisol metabolism or action has not been evaluated. We have investigated the effect of GH replacement therapy on cortisol metabolism, cortisol binding globulin and in-vitro glucocorticoid sensitivity in a group of adult hypopituitary patients. DESIGN AND PATIENTS: We studied 19 adult hypopituitary patients (18 adult onset, M:F, 6:13), who were receiving conventional hydrocortisone (16 patients), thyroxine (14 patients), triiodothyronine (1 patient), sex steroid (9 patients), human chorionic gonadotrophin (1 patient) or desmopressin (6 patients) replacement during a 6-month, double blind controlled trial of GH therapy (active:placebo, 8:11) followed by a 6-month open phase of GH (mean dose: 0.2 IU/kg/week, range 0.051-0.27) and after a 6-week washout phase following discontinuation of GH therapy. MEASUREMENTS: Twenty-four-hour urine free cortisol, cortisol metabolites (CoM), ratio 11-hydroxy/11-oxo CoM (F/E) and ratio 5 alpha/beta tetrahydrocortisol were measured at 6 months, 12 months and after the 6 week washout phase. Serum cortisol binding globulin was measured basally, at 6 months, 12 months and after washout. Glucocorticoid sensitivity was determined in lymphocyte preparations from 8 patients, during GH therapy and after washout, using an in-vitro technique dependent on dexamethasone suppression of phytohaemagglutinin-stimulated thymidine incorporation into DNA. Plasma renin activity and aldosterone were measured after 6-12 months GH therapy and after washout. RESULTS: After 6 months of GH, in patients on hydrocortisone (n = 9), there were significant decreases in CoM (mean decrement 21%, P < 0.01), F/E (mean decreased from 1.27 to 1.0, P = 0.04; reference range 0.33-1.29) and 5 alpha/5 beta tetrahydrocortisol (mean decreased from 0.67 to 0.48, P = 0.01) and a subsequent increase after washout. Patients not on hydrocortisone (n = 2) demonstrated a normal basal F/E falling by 25% on GH therapy but no change in CoM. During 12 months of GH therapy, patients on hydrocortisone (n = 7) demonstrated a further trend to decrement in CoM (P = 0.09) which reversed after washout (P = 0.04). Urine free cortisol tended to fall during GH therapy and increased significantly following washout after 12 months treatment (P < 0.02). Serum cortisol binding globulin decreased by 20% (P < 0.05) during 12 months GH treatment but remained within the reference range. In-vitro studies demonstrated a trend to reduced glucocorticoid sensitivity on GH therapy; the maximum inhibition of phytohaemagglutinin by dexamethasone tended to be less on GH therapy (P = 0.052) and was also lower than in 29 normal volunteers (P < 0.05). There were no significant changes in plasma renin but there was a small increment in aldosterone in recumbent patients (P = 0.04) during the open phase of GH therapy in the placebo arm. CONCLUSIONS: GH therapy in hypopituitary adults is associated with an apparent reduction in availability of administered hydrocortisone as measured by urine cortisol metabolites and urine free cortisol. This effect is unlikely to be clinically significant except possibly in ACTH deficient subjects on suboptimal hydrocortisone replacement. The changes in F/E suggest that GH may directly or indirectly modulate the activity of 11 beta-hydroxysteroid dehydrogenase. The apparent decrease in glucocorticoid sensitivity during GH therapy, demonstrated in vitro, merits further investigation.     

Impaired interleukin-12 production is associated with a defective anti-tumor response in colorectal cancer

OBJECTIVE: Spontaneous spinal epidural hematoma (SSEH) is an idiopathic accumulation of blood in the vertebral epidural space without identifiable predisposing factors. First reported in 1869, the clinical outcome in children younger than 18 years old has not been clearly delineated. DESIGN: A comprehensive review of the English language literature revealed 26 patients younger than 18 years old with reported clinical outcomes. The 27th case is presented. RESULTS: Complete neurologic recovery occurred in 14 of 27 (52%) patients, partial recovery in 12 of 27 (44%) patients, and death in 1 of 27 (4%) patients. CONCLUSION: There is an overall good prognosis for neurologic recovery in children who experience SSEH.     

The role of cytotoxic chemotherapy in the management of aggressive and malignant pituitary tumors

Pituitary tumors are mostly benign lesions, although 5-35% are locally invasive. A small number exhibit a more aggressive course, infiltrating dura, bone and sinuses, and are designated highly aggressive. However, the presence of metastases separate from the pituitary in the central nervous system or at a distance is necessary to designate pituitary tumors as carcinomas, i.e. truly malignant. When conventional therapeutic modalities fail, systemic chemotherapy remains the last option. We report seven such patients, three with highly aggressive and four with malignant pituitary tumors (n=4) four women; median age, 32 yr; range, 23-48 yr), who received one or more courses of chemotherapy with lomustine and 5-fluorouracil (median, two courses; range, one to six courses). Three patients with systemic metastatic disease had a shorter survival (median, 5 months; range, 1-14 months) than the one patient with central nervous system metastases alone (10 yr). A patient with an aggressive nonmetastatic prolactinoma who initially responded to chemotherapy died from another nondisease-associated cause. Two patients, one with an aggressive and one with a metastatic tumor, achieved symptomatic improvement with a median duration of 6 months. A hormonal reduction greater than 50% was observed in two of seven patients; only one patient who had an aggressive tumor obtained an objective tumor response. The median survival from the time of initiation of chemotherapy in patients with malignant tumors ranged from 3-65 months. Two patients with malignant tumors developed disease progression while receiving chemotherapy; no patient with extracranial metastases showed a response. Treatment was well tolerated, with minimal individual side-effects. Three patients with no response to initial treatment received different chemotherapeutic regimens with no additional response. All patients with metastatic malignant tumors eventually died. Treatment with cytotoxic chemotherapy is noncurative, and current experience is limited. Until another more specific form of treatment is available, chemotherapy may still be of some value in patients with highly aggressive and malignant pituitary tumors, at least in achieving a temporary remission or delay in progression. The combination of lomustine/5-fluorouracil proved easy to administer with minimal toxicity, although the response rate was only 14%. Until a more specific treatment is found, an optimal chemotherapeutic regimen needs to be established.     

Lipid Droplet Motility Increases Following Viral Immune Stimulation

Lipid droplets (LDs) have traditionally been thought of as solely lipid storage compartments for cells; however, in the last decade, they have emerged as critical organelles in health and disease. LDs are highly dynamic within cells, and their movement is critical in organelle–organelle interactions. Their dynamics are known to change during cellular stress or nutrient deprivation; however, their movement during pathogen infections, especially at very early timepoints, is under-researched. This study aimed to track LD dynamics in vitro, in an astrocytic model of infection. Cells were either stimulated with a dsRNA viral mimic, poly I:C, or infected with the RNA virus, Zika virus. Individual LDs within infected cells were analysed to determine displacement and speed, and average LD characteristics for multiple individual cells calculated. Both LD displacement and mean speed were significantly enhanced in stimulated cells over a time course of infection with an increase seen as early as 2 h post-infection. With the emerging role for LDs during innate host responses, understanding their dynamics is critical to elucidate how these organelles influence the outcome of viral infection.     

Examining the correlates of psychological aggression among a community sample of couples.

In this study, the authors examined the correlates of psychological aggression victimization and perpetration among a community sample of 145 heterosexual couples. For both women and men, psychological aggression victimization was associated with greater psychological distress, anxiety, and physical health symptoms beyond the effects of physical aggression. Psychological aggression victimization was also uniquely associated with higher levels of depression for women. Trait anger and poor relationship adjustment were the strongest correlates of psychological aggression perpetration across genders. Childhood father-to-child and father-to-mother aggressions were associated with psychological aggression perpetration for men only, suggesting possible distinct etiologies across genders. These data highlight the importance of the further development of models for psychological aggression in both women and men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Arsenic in drinking water and incidence of urinary cancers

To investigate the effects of a new nonNMDA antagonist on the trisynaptic pathways in the hippocampus, the author examined kainate(KA)-induced generalized seizures in rats. A novel nonNMDA antagonist, YM90K, showed the blockade of the Schaffer collaterals in 2-deoxyglucose study (2-DG) and that the CA1-2 pyramidal cells of the hippocampus were preserved seven days after the KA injections. On the other hand, the control and MK-801 (NMDA-antagonist) treated rats did not depress the Schaffer collaterals and showed persistent hypermetabolism of glucose in the CA1 pyramidal cell layer, where neurons were not preserved seven days later. 2-DG was useful to reveal the effects of nonNMDA antagonist on the KA-induced generalized seizures. This suggests that YM90K is a potent nonNMDA antagonist and that it has a neuroprotective effect in rats.     

Posttraumatic stress disorder and intimate relationship problems: A meta-analysis.

Objective: The authors conducted a meta-analysis of empirical studies investigating associations between indices of posttraumatic stress disorder (PTSD) and intimate relationship problems to empirically synthesize this literature. Method: A literature search using PsycINFO, Medline, Published International Literature on Traumatic Stress (PILOTS), and Dissertation Abstracts was performed. The authors identified 31 studies meeting inclusion criteria. Results: True score correlations (ρ) revealed medium-sized associations between PTSD and intimate relationship discord (ρ = .38, N = 7,973, K = 21), intimate relationship physical aggression perpetration (ρ = .42, N = 4,630, K = 19), and intimate relationship psychological aggression perpetration (ρ = .36, N = 1,501, K = 10). The strength of the association between PTSD and relationship discord was higher in military (vs. civilian) samples, and when the study was conducted in the United States (vs. other country), and the study represented a doctoral dissertation (vs. published article). The strength of the association between PTSD and physical aggression was higher in military (vs. civilian) samples, males (vs. females), community (vs. clinical) samples, studies examining PTSD symptom severity (vs. diagnosis), when the physical aggression measure focused exclusively on severe violence (vs. a more inclusive measure), and the study was published (vs. dissertation). For the PTSD–psychological aggression association, 98% of the variance was accounted for by methodological artifacts such as sampling and measurement error; consequently, no moderators were examined in this relationship. Conclusions: Findings highlight a need for the examination of models explaining the relationship difficulties associated with PTSD symptomatology and interventions designed to treat problems in both areas. (PsycINFO Database Record (c) 2010 APA, all rights reserved)