Sociality and the telencephalic distribution of corticotrophin‐releasing factor,urocortin 3, and binding sites for CRF type 1 and type 2 receptors: A comparative study of eusocial naked mole‐rats and solitary Cape mole‐rats

Various aspects of social behavior are influenced by the highly conserved corticotrophin‐releasing factor (CRF) family of peptides and receptors in the mammalian telencephalon. This study has mapped and compared the telencephalic distribution of the CRF receptors, CRF₁ and CRF₂, and two of their ligands, CRF and urocortin 3, respectively, in African mole‐rat species with diametrically opposed social behavior. Naked mole‐rats live in large eusocial colonies that are characterized by exceptional levels of social cohesion, tolerance, and cooperation in burrowing, foraging, defense, and alloparental care for the offspring of the single reproductive female. Cape mole‐rats are solitary; they tolerate conspecifics only fleetingly during the breeding season. The telencephalic sites at which the level of CRF₁ binding in naked mole‐rats exceeds that in Cape mole‐rats include the basolateral amygdaloid nucleus, hippocampal CA3 subfield, and dentate gyrus; in contrast, the level is greater in Cape mole‐rats in the shell of the nucleus accumbens and medial habenular nucleus. For CRF₂ binding, the sites with a greater level in naked mole‐rats include the basolateral amygdaloid nucleus and dentate gyrus, but the septohippocampal nucleus, lateral septal nuclei, amygdalostriatal transition area, bed nucleus of the stria terminalis, and medial habenular nucleus display a greater level in Cape mole‐rats. The results are discussed with reference to neuroanatomical and behavioral studies of various species, including monogamous and promiscuous voles. By analogy with findings in those species, we speculate that the abundance of CRF₁ binding in the nucleus accumbens of Cape mole‐rats reflects their lack of affiliative behavior. J. Comp. Neurol. 523:2344–2371, 2015. © 2015 Wiley Periodicals, Inc.     

Changes of hemostatic variables during hormone replacement therapy

Hormone replacement therapy (HRT) is accompanied by many changes in the hemostatic system. Because several individual hemostatic variables have been suspected to be reasonable indicators of the hemostatic balance and because this balance is thought to play an important role in the pathogenesis of several diseases, careful examination of the changes in this system induced by HRT could be helpful, first to improve HRT and second to improve our understanding of mechanisms of cardiovascular disease. The effects of (several forms of) HRT on individual hemostatic variables are discussed in this article. The pattern that emerges is that HRT stimulates coagulation, inhibits anticoagulation, and stimulates fibrinolysis (partly by inhibition of fibrinolysis). There are, however, few data that give clear insight into the effects of HRT on hemostatic variables. Controlled randomized clinical studies are needed to evaluate further the effects of HRT on the hemostatic system, to understand the interplay between inflammation and coagulation (both pathways being affected by HRT), and to understand how HRT-associated changes are affected by differences in genetic background.     

Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death

In 328 type 2 diabetic patients followed for 9.0 years (mean), we investigated whether endothelial dysfunction and chronic inflammation (estimated from plasma markers) can explain the association between (micro)albuminuria and mortality. Of the patients, 113 died. Mortality was increased in patients with baseline microalbuminuria or macroalbuminuria (odds ratios as compared with normoalbuminuria, 1.78 [P < 0.05] and 2.86 [P < 0.01]) and in patients with soluble vascular cell adhesion molecule 1 in the third tertile and C-reactive protein in the second and third tertiles (odds ratios as compared with the first tertile, 2.05 [ P < 0.01], and 1.80 [P < 0.05] and 2.92 [ P < 0.01]). These associations were mutually independent. The mean yearly change in urinary albumin excretion was 9.4%; in von Willebrand factor, 8.1%; in tissue-type plasminogen activator, 2.8%; in soluble vascular cell adhesion molecule 1, 5.2%; in soluble E-selectin, -2.3%; in C-reactive protein, 3.8%; and in fibrinogen, 2.3%. The longitudinal development of urinary albumin excretion was significantly and independently determined by baseline levels of and the longitudinal development of BMI, systolic blood pressure, serum creatinine, glycated hemoglobin and plasma von Willebrand factor (baseline only), soluble E-selectin (baseline only), tissue-type plasminogen activator, C-reactive protein, and fibrinogen. The longitudinal developments of markers of endothelial function and inflammation were interrelated. In type 2 diabetes, increased urinary albumin excretion, endothelial dysfunction, and chronic inflammation are interrelated processes that develop in parallel, progress with time, and are strongly and independently associated with risk of death.     

Individual quality of life factors distinguishing low-burden and high-burden caregivers of dementia patients

Dementia patient (n = 72) and caregiver characteristics and individual quality of life (IQoL) factors distinguishing low- and high-burden caregivers were evaluated. Measures included patient cognitive, functional and behavioural status, and caregiver burden, well-being, social support appraisal and IQoL. The caregivers were divided by median split into low- and high-burden groups. In the high-burden group daughters were over-represented, psychological morbidity was higher, QoL was lower, the patients were more behaviourally disturbed, and there was a trend towards more negative appraisal of informal social support. Of the many QoL factors elicited from caregivers, only 'time for self' and 'finances' differed significantly between the groups. A need for more time away from the patient is a major QoL concern for highly burdened caregivers, and a perceived lack of adequate informal support and/or financial constraints are contributory factors.     

Comparative epidemiology of scrapie outbreaks in individual sheep flocks

Data recording the course of scrapie outbreaks in 4 sheep flocks (2 in Cheviot sheep and 2 in Suffolks) are compared. For each outbreak the data on scrapie incidence and sheep demography and pedigrees cover periods of years or decades. A key finding is that the incidence of clinical cases peaks in sheep 2-3 years old, despite very different forces-of-infection. This is consistent with age-specific susceptibility of sheep to scrapie, as has been reported for cattle to bovine spongiform encephalopathy and for humans to variant Creutzfeldt-Jakob disease. Scrapie incidence was higher in ewes than rams and at certain times of years, though these effects were not consistent between flocks. There was no evidence for high levels of vertical transmission.     

"Pumped-up propulsion" during front crawl swimming

PURPOSE: It is currently held that propulsion in human front crawl swimming is achieved by lift and drag forces predominantly generated by the hands. Calculation of these propulsive forces relies on the quasi-steady assumption that the fluid dynamic behavior of a hand model in a flow channel (constant velocity and orientation) is similar to that of a hand of a real swimmer. However, both experimental and theoretical analyses suggest that this assumption is questionable and that unsteady and rotational propulsion mechanisms play a significant role. Theoretical considerations suggest that arm rotation could lead to a proximodistal pressure gradient, which would induce significant axial flow along the arm toward the hand. METHODS: To gain insight into such mechanisms, we used tufts to study the flow directions around the arm and hand during the front crawl, which consists of a glide, an insweep, and an outsweep phase. In a second experiment, we measured pressure during the stroke at various points along the arm and hand. RESULTS: It was observed that 1) the flow during insweep and part of the outsweep was highly unsteady; 2) the arm movements were largely rotational; 3) a clear axial flow component, not in the direction of the arm movement, was observed during insweep and outsweep; and 4) both the V-shaped "contracting" arrangement of the tufts during the outsweep and pressure recordings point to a pressure gradient along the direction of the arm during the outsweep, as predicted on theoretical grounds. CONCLUSION: Our results demonstrate the reality of the predicted rotational and unsteady effects during front crawl swimming. We hypothesize that the axial flow observed during the outsweep has a propulsion-enhancing effect by increasing the pressure difference over the hand. Further investigation is required to establish more accurately the role of axial flow on propulsion.     

Radical radiation for localized prostate cancer: local persistence of disease results in a late wave of metastases.

PURPOSE: To assess whether failure to maintain local control (LC) of prostate cancer after radiation therapy results in a higher incidence of distant metastasis (DM). PATIENTS AND METHODS: From 1972 to 1999, 1,469 patients with clinically localized prostate cancer were treated with radical radiation therapy. Disease outcome was retrospectively reviewed for all patients with more than 2 years of follow-up. RESULTS: The actuarial 10-year LC rate was 79%. Gleason score > or = 7, prostate-specific antigen (PSA) more than 15, and T3 to T4 tumors predicted a higher incidence of local failure (LF) (palpable recurrence or positive rebiopsy). The 10-year distant metastasis-free survival (DMFS) was 74%. Gleason score > or = 7, PSA more than 15, and T3 to T4 tumors predicted a higher incidence of distant failure. LF was the strongest predictor for DM in a multivariate model. The 10-year DMFS for LC and LF patients was 77% and 61%, respectively. Median time to distant failure was prolonged in patients with LF compared with patients with locally controlled disease (54 v 34 months). Hazard rate analysis of the time to DM revealed that patients who maintain LC have a lower rate of DM, which remains constant over time. Patients who ultimately develop LF have a higher initial rate of DM, which increases with time. CONCLUSION: Patients with locally persistent prostate cancer are at greater risk of DM. The higher initial hazard of DM is consistent either with an increased likelihood of subclinical micrometastases before treatment or with posttreatment tumor embolization. The prolonged time to appearance of DM in locally failing patients and the increasing hazard of DM over time is most consistent with a late wave of metastases from a locally persistent tumor.     

Parathyroidectomy in chronic renal failure: short- and long-term results on parathyroid function, blood pressure and anemia

To evaluate the long-term results of parathyroidectomy (PTX) on parathyroid function, blood pressure and anemia, data of 45 patients with secondary Hyperparathyroidism in dialysis who had undergone PTX were collected retrospectively from 8 different dialysis units. The patients, 25 M and 20 F, mean age 56 +/- 11 years, who were followed up for an average period of 3.3 +/- 2.3 years, were divided into four groups according to the surgical procedure: 19 patients had had a subtotal PTX; 10 patients had undergone total PTX with autotransplantation (AT); 10 patients had had total PTX without AT, and 6 patients had undergone partial PTX. Taking a reduction in intact PTH > 50% as sign of successful PTX, only 5 patients did not attain this result. Considering values of PTH between 20 and 200 pg/ml at the mid-term observation (1-2 years) as the optimal result, values under 20 pg/ml as an expression of permanent hypoparathyroidism, and those above 200 pg/ml as indicating persistent/recurrent hyperparathyroidism, 65.5% of patients operated with subtotal PTX and total PTX + AT had a therapeutic success, versus 31.2% of patients in the other two groups, due to excess permanent hypoparathyroidism and persistent/recurrent hyperparathyroidism; 20 of 45 patients with preoperative hypertension experienced a statistically and clinically significant decrease in blood pressure levels. An increase in serum hemoglobin was also observed, despite a reduction of administered erythropoietin. In conclusion, the results of PTX obtained from this multicenter study are comparable to those reported by single leading centers. Recommended surgical procedures are subtotal PTX and total PTX with AT. The fall in blood pressure in hypertensive patients is clinically significant, and improvement in anemia is also observed with a reduction in erythropoietin dosage.     

Nasal inflammation and chronic ear disease in Australian Aboriginal children

Objective : Chronic middle ear disease is common in Aboriginal children, and may be linked to nasal inflammation and Eustachian tube dysfunction. The pattern of nasal inflammation is unknown. The study reported here was performed to define the role of allergy and infection in causing nasal inflammation in Aboriginal children with chronic middle ear disease.
Methodology : Thirty-one Aboriginal children aged between 3 and 7 years underwent clinical assessment, audiometry and allergy skin tests. Nasal swabs for bacterial culture and cytology were performed during the winter and again in spring to identify any seasonal variation. A randomized trial of nasal beclomethasone for 8 weeks was conducted in children with abnormal tympanometry to identify the effect of therapy upon nasal cytology.
Results : Twenty-six of the 31 children had abnormal tympanograms. Average hearing levels were reduced in nine children. Pathogenic organisms were isolated from most children: Streptococcus pneumoniae (82%), Haemophilus influenzae (79%), Moraxella catarrhalis (39%) and Staphylococcus aureus (29%). Eight of the 31 children (26%) were atopic. Nasal cytology disclosed a marked neutrophil infiltrate (80% of cells) during the winter, which fell significantly in spring to 52% of cells. Only two subjects had nasal eosinophilia of >10%. There was no effect of beclomethasone on nasal cytology.
Conclusions : Chronic ear disease in Aboriginal children is associated with nasal inflammation, neutrophil infiltration and the presence of bacteria. These features suggest respiratory infection as the main cause of chronic nasal inflammation in Aboriginal children with middle ear disease. There is a seasonal variation in the severity of the nasal infiltrate, consistent with increased infections during winter. Despite a high prevalence of atopy, allergic nasal disease was uncommon.