What went wrong? The flawed concept of cerebrospinal venous insufficiency

In 2006, Zamboni reintroduced the concept that chronic impaired venous outflow of the central nervous system is associated with multiple sclerosis (MS), coining the term of chronic cerebrospinal venous insufficiency ('CCSVI'). The diagnosis of 'CCSVI' is based on sonographic criteria, which he found exclusively fulfilled in MS. The concept proposes that chronic venous outflow failure is associated with venous reflux and congestion and leads to iron deposition, thereby inducing neuroinflammation and degeneration. The revival of this concept has generated major interest in media and patient groups, mainly driven by the hope that endovascular treatment of 'CCSVI' could alleviate MS. Many investigators tried to replicate Zamboni's results with duplex sonography, magnetic resonance imaging, and catheter angiography. The data obtained here do generally not support the 'CCSVI' concept. Moreover, there are no methodologically adequate studies to prove or disprove beneficial effects of endovascular treatment in MS. This review not only gives a comprehensive overview of the methodological flaws and pathophysiologic implausibility of the 'CCSVI' concept, but also summarizes the multimodality diagnostic validation studies and open-label trials of endovascular treatment. In our view, there is currently no basis to diagnose or treat 'CCSVI' in the care of MS patients, outside of the setting of scientific research

3D printed Artificial Cornea for Corneal Stromal Transplantation

The aim of this study is to understand the optical, biocompatible, and mechanical properties of chitosan (CS) and polyvinyl-alcohol (PVA) based corneal stroma constructs using 3D printing process. Corneal stroma is tested for biocompatibility with human adipose tissue-derived mesenchymal stem cells (hASCs). Physico-chemical and chemical characterization of the construct was performed using scanning electron microscopy (SEM), fourier transforms infrared spectroscopy (FTIR). Optical transmittance was analyzed using UV-Spectrophotometer. Results showed fabricated constructs have required shape and size. SEM images showed construct has thickness of 400 µm. The FTIR spectra demonstrated the presence of various predicted peaks. The swelling and degradation studies of 13%(wt)PVA and 13%(wt)PVA/(1, 3, 5)%(wt)CS showed to have high swelling ratios of 7 days and degradation times of 30 days, respectively. The light transmittance values of the fabricated cornea constructs decreased with CS addition slightly. Tensile strength values decreased with increasing CS ratio, but we found to support intraocular pressure (IOP) which ranges from 12 to 22 mm-Hg. Preliminary biostability studies showed that composite constructs were compatible with hASCs even after 30 days’ of degradation, showing potential for these cells to be differentiated to stroma layer in future. This study has implications for the rapid and custom fabrication of various cornea constructs for clinical applications

The efficiency of US elastography in the differential diagnosis of thyroid nodules

Aim: To evaluate the efficiency of ultrasound elastography (USE) in the differential diagnosis of thyroid nodules. Methods: One hundred thyroid nodules in 100 patients (79 females, 21 males, age range 18-78; mean age = 45.6 years) were evaluated with real-time freehand USE, using Hitachi EUB 7500 equipment and elasticity scores were obtained. The elasticity was scored as follows: Score 1, elasticity in the entire nodule; Score 2, mainly elastic nodule with the presence of inelastic areas not constant during real time examination; Score 3, constant inelastic areas prevalently arranged at the periphery of the nodule; Score 4, constant inelastic areas prevalently arranged at the center of the nodule; Score 5, no elasticity in the nodule. Also mean strain ratio values were calculated for all nodules. Results: Eighty-four (86%) of cases were benign and sixteen (16%) were malignant. Elasticity score 3 and higher and strain ratio higher than 2.485 had statistically significant relation with malignancy (p < 0.05). Conclusions: USE including strain ratio calculations besides subjective evaluation of elasticity scores is an efficient imaging method which may contribute to the differential diagnosis of thyroid nodules

Calcium phosphate formation from sea urchin - (brissus latecarinatus) via modified mechano-chemical (ultrasonic) conversion method

This study aims to produce apatite structures, such as hydroxyapatite (HA) and fluorapatite (FA), from precursor calcium phosphates of biological origin, namely from sea urchin, with mechano-chemical stirring and hot-plating conversion method. The produced materials were heat treated at 800 °C for 4 hours. X-ray diffraction and scanning electron microscopy (SEM) studies were conducted. Calcium phosphate phases were developed. The SEM images showed the formation of micro to nano-powders. The experimental results suggest that sea urchin, Brissus latecarinatus skeleton could be an alternative source for the production of various mono or biphasic calcium phosphates with simple and economic mechano-chemical (ultrasonic) conversion method

Attachment and Proliferation of Osteoblasts on Lithium-Hydroxyapatite Composites

The biocompatibility and bioactivity properties of hydroxyapatites (HAs) modified through lithium addition were investigated. Hydroxyapatites obtained from bovine bone were mixed with lithium carbonate (Li), in the proportions of 0.25, 0.50, 1.00, and 2.00% wt, and sintered at 900°, 1000°, 1100°, 1200°, and 1300°C, creating LiHA samples. The osteoblast culture behavior was assessed in the presence of these LiHA compositions. The cellular interactions were analyzed by evaluating the viability and cellular proliferation, ALP production and collagen secretion. The cytotoxic potential was investigated through measurement of apoptosis and necrosis induction. The process of cellular attachment in the presence of the product of dissolution of LiHA, was evaluated trough fluorescence analysis. The physical characteristics of these materials and their cellular interactions were examined with SEM and EDS. The results of this study indicate that the LiHA ceramics are biocompatible and have variable bioactivities, which can be tailored by different combinations of the concentration of lithium carbonate and the sintering temperature. Our findings suggest that LiHA 0.25% wt, sintered at 1300°C, combines the necessary physical and structural qualities with favorable biocompatibility characteristics, achieving a bioactivity that seems to be adequate for use as a bone implant material

The Prometastatic Microenvironment of the Liver

The liver is a major metastasis-susceptible site and majority of patients with hepatic metastasis die from the disease in the absence of efficient treatments. The intrahepatic circulation and microvascular arrest of cancer cells trigger a local inflammatory reaction leading to cancer cell apoptosis and cytotoxicity via oxidative stress mediators (mainly nitric oxide and hydrogen peroxide) and hepatic natural killer cells. However, certain cancer cells that resist or even deactivate these anti-tumoral defense mechanisms still can adhere to endothelial cells of the hepatic microvasculature through proinflammatory cytokine-mediated mechanisms. During their temporary residence, some of these cancer cells ignore growth-inhibitory factors while respond to proliferation-stimulating factors released from tumor-activated hepatocytes and sinusoidal cells. This leads to avascular micrometastasis generation in periportal areas of hepatic lobules. Hepatocytes and myofibroblasts derived from portal tracts and activated hepatic stellate cells are next recruited into some of these avascular micrometastases. These create a private microenvironment that supports their development through the specific release of both proangiogenic factors and cancer cell invasion- and proliferation-stimulating factors. Moreover, both soluble factors from tumor-activated hepatocytes and myofibroblasts also contribute to the regulation of metastatic cancer cell genes. Therefore, the liver offers a prometastatic microenvironment to circulating cancer cells that supports metastasis development. The ability to resist anti-tumor hepatic defense and to take advantage of hepatic cell-derived factors are key phenotypic properties of liver-metastasizing cancer cells. Knowledge on hepatic metastasis regulation by microenvironment opens multiple opportunities for metastasis inhibition at both subclinical and advanced stages. In addition, together with metastasis-related gene profiles revealing the existence of liver metastasis potential in primary tumors, new biomarkers on the prometastatic microenvironment of the liver may be helpful for the individual assessment of hepatic metastasis risk in cancer patients

Measuring resting cerebral haemodynamics using MRI arterial spin labelling and transcranial Doppler ultrasound: comparison in younger and older adults

Introduction: Resting cerebral blood flow (CBF) and perfusion measures have been used to determine brain health. Studies showing variation in resting CBF with age and fitness level using different imaging approaches have produced mixed findings. We assess the degree to which resting CBF measures through transcranial Doppler (TCD) and arterial spin labelling (ASL) MRI provide complementary information in older and younger, fit and unfit cohorts. Methods: Thirty-five healthy volunteers (20 younger: 24±7y; 15 older: 66±7y) completed two experimental sessions (TCD/MRI). Aging and fitness effects within and between imaging modalities were assessed. Results: Middle cerebral artery blood velocity (MCAv, TCD) was lower and transit time (MRI) slower in older compared with younger participants (p < 0.05). The younger group had higher grey matter cerebral perfusion (MRI) than the older group, albeit not significantly (p=0.13). Surprisingly, fitness effects in the younger group (decrease/increase in MCAv/transit time with fitness, respectively) opposed the older group (increase/decrease in MCAv/transit time). Whole cohort transit times correlated with MCAv (r=-0.63; p < 0.05), whereas tissue perfusion did not correlate with TCD measures. Conclusion: TCD and MRI modalities provide complementary resting CBF measures, with similar effects across the whole cohort and between subgroups (age/fitness) if metrics are comparable (e.g., velocity [TCD] vs transit time [MRI])