A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.     

Clinical factors predicting risk for aspiration and respiratory aspiration among patients with Stroke

Objective:

to investigate the association of risk factors with the Risk for aspiration nursing diagnosis and respiratory aspiration.

Method:

cross-sectional study assessing 105 patients with stroke. The instrument used to collect data addressing sociodemographic information, clinical variables and risk factors for Risk for aspiration. The clinical judgments of three expert RNs were used to establish the diagnosis. The relationship between variables and strength of association using Odds Ratio (OR) was verified both in regard to Risk for aspiration and respiratory aspiration.

Results:

risk for aspiration was present in 34.3% of the patients and aspiration in 30.5%. The following stood out among the risk factors: Dysphagia, Impaired or absent gag reflex, Neurological disorders, and Impaired physical mobility, all of which were statistically associated with Risk for aspiration. Note that patients who develop such a diagnosis were seven times more likely to develop respiratory aspiration.

Conclusion:

dysphagia, Impaired or absent gag reflex were the best predictors both for Risk for aspiration and respiratory aspiration.     

CaMKIIδ and cardiomyocyte Ca2+ signalling new perspectives on splice variant targeting

Control of cardiomyocyte cytosolic Ca²⁺ levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca²⁺, Ca²⁺/calmodulin‐dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca²⁺ channels/transporters. CaMKII is primarily expressed either in the δ_B or δ_C splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca²⁺ levels promote the binding of a Ca²⁺/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post‐translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post‐translational modification status of CaMKIIδ_B/δ_C variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type of CaMKII post‐translational modification has a role in determining target selectivity of downstream Ca²⁺ transporters. The study was also able to demonstrate that the phosphorylated form of CaMKII closely co‐localizes with CaMKIIδ_B in the nuclear/myofilament fraction, contrasting with a co‐enrichment of oxidized CaMKII in the membrane fraction with CaMKIIδ_C. It has also been possible to conclude that a hyper‐phosphorylation of CaMKII (Thr287) in reperfused hearts represents a hyper‐activation of the CaMKIIδ_B, which exerts anti‐arrhythmic actions through an enhanced capacity to selectively increase sarcoplasmic reticulum Ca²⁺ uptake and maintain cytosolic Ca²⁺ levels. This suggests that suppression of global CaMKIIδ may not be an efficacious approach to developing optimal pharmacological interventions for the vulnerable heart.     

Autonomic modulation analysis in active and sedentary kidney transplanted recipients

Modulation of the autonomic nervous system on heart rate can be compromised in chronic kidney disease and may result in changes in the frequency and duration of the cardiac cycle. The aim of this study was to evaluate autonomic modulation in active and sedentary renal transplant recipients. Twenty renal‐transplanted individuals were analyzed at the Centro de Prevenção de Doenças Renais (Kidney Disease Education Centre), in the academic hospital of Universidade Federal do Maranhão, and were divided into the active group (AG) and the sedentary group (SG). The AG comprised of six men and four women (age 43.10 ± 13.02) and was in regular concurrent training intervention for 8 weeks, while the SG was composed of three men and seven women (age 36.8 ± 9.26). Analysis of heart rate (HR) variability in time and frequency domain demonstrated that HR mean values in the SG and AG were 787.32 ± 79.60 and 870 ± 106.66 ms, respectively. Differences were observed in the time domain and frequency domain. The total index of low frequency and high frequency showed no differences between the SG and AG. Biochemical variables presented significantly lower levels after 8 weeks of training. Higher heart rate variability in the time domain and greater vagal modulation was observed in the AG. The AG ad greater vagal modulation when compared to the SG, with removal of the sympathetic and increased parasympathetic in the behaviour was confirmed by sympatho‐vagal balance. The AG also presented significant improvements in the frequency domain.     

Increased brain l‐arginine availability facilitates cutaneous heat loss induced by running exercise

The effects of increased brain availability of l ‐arginine (l ‐arg), a precursor for nitric oxide synthesis, on core body temperature (T_core) and cutaneous heat loss were evaluated in running rats. One week prior to the experiments, adult male Wistar rats received the following implants: a chronic guide cannula in the lateral cerebral ventricle and a temperature sensor in the abdominal cavity. On the day of the experiments, the rats were assigned to receive a 2‐μL intracerebroventricular injection of either NaCl (0.15 mol/L) or l ‐arg solution (0.825, 1.65 or 3.30 mol/L); T_core and tail skin temperature were measured while the rats ran at a speed of 18 m/min until they were fatigued. l ‐arginine induced a dose‐dependent reduction in the threshold T_core required for cutaneous heat loss (38.09 ± 0.20°C for 3.30‐mol/L l ‐arg vs 38.61 ± 0.10°C for saline; P < 0.05), which attenuated the exercise‐induced hyperthermia. Although the rats treated with l ‐arg presented a lower T_core at the end of exercise (~0.7°C lower after treatment with the highest dose), no changes in the time to fatigue were observed relative to the control trial. These results suggest that brain l ‐arg controls heat loss during exercise, most likely by modulating the sympathetic vasoconstrictor tonus to skin vessels. Furthermore, despite facilitating cutaneous heat loss mechanisms, increased brain l ‐arg availability did not enhance physical performance.     

A multivariate analysis of socio-demographic factors, water contact patterns and Schistosoma mansoni infection in an endemic area in Brazil.

Associations between socio-demographic factors, water contact patterns and Schistosoma mansoni infection were investigated in 506 individuals (87% of inhabitants over 1 year of age) in an endemic area in Brazil (Divino), aiming at determining priorities for public health measures to prevent the infection. Those who eliminated S. mansoni eggs (n = 198) were compared to those without eggs in the stools (n = 308). The following explanatory variables were considered: age, sex, color, previous treatment with schistosomicide, place of birth, quality of the houses, water supply for the household, distance from houses to stream, and frequency and reasons for water contact. Factors found to be independently associated with the infection were age (10-19 and > or = 20 yrs old), and water contact for agricultural activities, fishing, and swimming or bathing (Adjusted relative odds = 5.0, 2.4, 3.2, 2.1 and 2.0, respectively). This suggests the need for public health measures to prevent the infection, emphasizing water contact for leisure and agricultural activities in this endemic area.