Induction of neural-like differentiation in human mesenchymal stem cells derived from bone marrow, fat, spleen and thymus

Mesenchymal stem cells (MSCs) from bone marrow (BM) and sub-cutaneous fat are known to differentiate into neural cells under appropriate stimuli. We describe here the neural-like differentiation of human MSCs obtained from spleen and thymus, induced either with chemical factors or with co-culture with human Schwann cells (Sc). Under the effect of neural differentiation medium, most MSCs from BM, fat, spleen and thymus acquired morphological changes suggestive of cells of astrocytic/neuronal and oligodendroglial lineages with general up-regulation of neural molecules not correlated with morphological changes. The process was transient and reversible, as MSCs recovered basal morphology and phenotype, as well as their multilineage differentiation potential. Thus, we hypothesized that chemical factors may prime MSCs for neural differentiation, by inducing initial and poorly specific changes. By contrast, co-cultures of MSCs of different origin with Sc induced long-lasting and Sc differentiation, i.e., the expression of Sc myelin proteins for up to 12 days. Our results show that a MSC reservoir is present in tissues other than BM and fat, and that MSCs of different origin have similar neural differentiation potential. This evidence provides new insights into BM-like tissue plasticity and may have important implications for future therapeutic interventions in chronic neuropathies.     

Influence of VEGF-A gene variation and protein levels in breast cancer susceptibility and severity

Vascular endothelial growth factor-A (VEGF-A) plays an important role in tumour angiogenesis and cancer progression. VEGF gene variation may influence VEGF levels and therefore cancer susceptibility and progression. We studied the role of VEGF single nucleotide polymorphisms and haplotypes in breast cancer susceptibility and severity. We also studied the relationships of VEGF SNPs with circulating VEGF levels in healthy volunteers and protein expression in breast cancers. Single nucleotide polymorphisms (SNPs) in the regulatory regions of the VEGF gene were genotyped by high throughput methods in approximately 500 breast cancer cases and 500 appropriate controls. Haplotype frequencies were inferred using methods based on the Expectation Maximisation algorithm. The effect of VEGF genotypes on serum and plasma VEGF levels were studied in another cohort of healthy individuals. A semi-quantitative assessment of VEGF protein expression on tissue micro arrays (TMA) constructed from approximately 300 breast cancer samples was performed and compared with VEGF genotypes and with histopathological parameters and survival in breast cancer. The -460T/+405C/-7C/936C haplotype in the VEGF gene was found to be associated with decreased breast cancer risk (p = 0.029). The -7C>T polymorphism may influence overall breast cancer survival (p = 0.027). Individual polymorphisms however did not affect breast cancer susceptibility. There was no association between the individual polymorphisms and circulating VEGF levels in healthy volunteers and VEGF expression on the breast cancer micro array. VEGF expression in breast cancers was however associated with high grade (p = 0.002) and ER negative tumours (p = 0.03).     

Epidemiology of hip fractures in northwestern Italy: a multicentric regional study on incidence of hip fractures and their outcome at 3-year follow-up

Piedmont is a region in northwestern Italy counting 4.2 million inhabitants. The purpose of our study was to update data on incidence and outcomes of hip fractures (HF) in our region to present days. The data of all patients affected by HF in 2003 in Piedmont (total: 5,386 patients) were analyzed, determining the incidence of HF, mean age, sex, fracture pattern and treatment adopted. Additionally, 564 patients underwent a questionnaire on comorbidities, complications, functional outcome and survivorship. Overall incidence of HF was 126.13/100,000 inhabitants-year. Mean hospitalization was 13.67 days. Mean time to surgery was 2.67 days. Survivorship was 94% at 3-month, 71.32% at 1-year and 60.21% at 3-year follow-up. These up-to-date data on HF in our region are in accordance with the international literature and could prove useful for Orthopaedic and Trauma surgeons for giving information to patients and their relatives.     

Hip artroplasty: A transient reason not to be pregnant

Metal implants corrode and release metal ions, cobalt and chromium, which, in turn, may cause systemic toxicity, mostly in the first few months from implantation of metal-on-metal hip arthroplasty. At the time of delivery, the placenta reduces the passage of cobalt and chromium ions released from metal-on-metal prosthesis. From a biomechanical view point, hip replacement should not be considered a contraindication for pregnancy or for spontaneous delivery, and does not seem to have any negative effects in terms of risk of dislocation, loosening, fracture, or revision surgery, neither negative effects on clinical and functional outcomes. The long-term biological consequences of exposure to Co–Cr particles and ions remain largely unknown.     

A Survey of Persons Who Use Integrated Control Devices

Integrated devices allow users to operate multiple pieces of assistive technology items from a single input device. Through this single input device, users with severe physical limitations are able to operate several other devices such as a wheelchair, telephone, computer, and communication aid. Twenty-four integrated control users completed a telephone survey to ascertain consumer satisfaction with integrated controls. Eighteen were either satisfied or very satisfied with the evaluation for an integrated control, one was neither satisfied nor dissatisfied, two were very dissatisfied, and three did not respond to the question. Twenty were very satisfied or satisfied and four were either dissatisfied or very dissatisfied with the training they received. Twenty-two respondents indicated they were either very satisfied or satisfied with their integrated control device, one was neither satisfied nor dissatisfied, and one was very dissatisfied. In general, respondents were satisfied with their integrated control devices. Specifically, respondents were satisfied with the increase in independence and the ability to control other equipment such as television sets and computers. Simplicity, touch sensitivity, and visual/auditory feedback appeared to play important roles in satisfaction.     

Symptoms of anxiety and mood disturbance alter cardiac and peripheral autonomic control in patients with metabolic syndrome

Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.     

Liver transplantation from active COVID-19 donors: A lifesaving opportunity worth grasping?

COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors’ liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool.