Contamination of mesenchymal stem-cells with fibroblasts accelerates neurodegeneration in an experimental model of Parkinson's disease

Pre-clinical studies have supported the use of mesenchymal stem cells (MSC) to treat highly prevalent neurodegenerative diseases such as Parkinson’s disease (PD) but preliminary trials have reported controversial results. In a rat model of PD induced by MPTP neurotoxin, we first observed a significant bilateral preservation of dopaminergic neurons in the substantia nigra and prevention of motor deficits typically observed in PD such as hypokinesia, catalepsy, and bradykinesia, following intracerebral administration of human umbilical cord-derived MSC (UC-MSC) early after MPTP injury. However, surprisingly, administration of fibroblasts, mesenchymal cells without stem cell properties, as a xenotransplantation control was highly detrimental, causing significant neurodegeneration and motor dysfunction independently of MPTP. This observation prompted us to further investigate the consequences of transplanting a MSC preparation contaminated with fibroblasts, a plausible circumstance in cell therapy since both cell types display similar immunophenotype and can be manipulated in vitro under the same conditions. Here we show for the first time, using the same experimental model and protocol, that transplantation of UC-MSC induced potent neuroprotection in the brain resulting in clinical benefit. However, co-transplantation of UC-MSC with fibroblasts reverted therapeutic efficacy and caused opposite damaging effects, significantly exacerbating neurodegeneration and motor deficits in MPTP-exposed rats. Besides providing a rationale for testing UC-MSC transplantation in early phases of PD aiming at delaying disease progression, our pre-clinical study suggests that fibroblasts may be common cell contaminants affecting purity of MSC preparations and clinical outcome in stem cell therapy protocols, which might also explain discrepant clinical results.     

Cyclopia: an epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research

Cyclopia is characterized by the presence of a single eye, with varying degrees of doubling of the intrinsic ocular structures, located in the middle of the face. It is the severest facial expression of the holoprosencephaly (HPE) spectrum. This study describes the prevalence, associated malformations, and maternal characteristics among cases with cyclopia. Data originated in 20 Clearinghouse (ICBDSR) affiliated birth defect surveillance systems, reported according to a single pre-established protocol. A total of 257 infants with cyclopia were identified. Overall prevalence was 1 in 100,000 births (95%CI: 0.89-1.14), with only one program being out of range. Across sites, there was no correlation between cyclopia prevalence and number of births (r = 0.08; P = 0.75) or proportion of elective termination of pregnancy (r = -0.01; P = 0.97). The higher prevalence of cyclopia among older mothers (older than 34) was not statistically significant. The majority of cases were liveborn (122/200; 61%) and females predominated (male/total: 42%). A substantial proportion of cyclopias (31%) were caused by chromosomal anomalies, mainly trisomy 13. Another 31% of the cases of cyclopias were associated with defects not typically related to HPE, with more hydrocephalus, heterotaxia defects, neural tube defects, and preaxial reduction defects than the chromosomal group, suggesting the presence of ciliopathies or other unrecognized syndromes. Cyclopia is a very rare defect without much variability in prevalence by geographic location. The heterogeneous etiology with a high prevalence of chromosomal abnormalities, and female predominance in HPE, were confirmed, but no effect of increased maternal age or association with twinning was observed.     

Bladder exstrophy: an epidemiologic study from the International Clearinghouse for Birth Defects Surveillance and Research, and an overview of the literature

Bladder exstrophy (BE) is a complex congenital anomaly characterized by a defect in the closure of the lower abdominal wall and bladder. We aimed to provide an overview of the literature and conduct an epidemiologic study to describe the prevalence, and maternal and case characteristics of BE. We used data from 22 participating member programs of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). All cases were reviewed and classified as isolated, syndrome, and multiple congenital anomalies. We estimated the total prevalence of BE and calculated the frequency and odds ratios for various maternal and case characteristics. A total of 546 cases with BE were identified among 26,355,094 births. The total prevalence of BE was 2.07 per 100,000 births (95% CI: 1.90-2.25) and varied between 0.52 and 4.63 among surveillance programs participating in the study. BE was nearly twice as common among male as among female cases. The proportion of isolated cases was 71%. Prevalence appeared to increase with increasing categories of maternal age, particularly among isolated cases. The total prevalence of BE showed some variations by geographical region, which is most likely attributable to differences in registration of cases. The higher total prevalence among male cases and older mothers, especially among isolated cases, warrants further attention.     

Nurse practitioner management of chronic musculoskeletal pain: a chart review

This study explored NPs' management of chronic musculoskeletal pain via a record review of 50 uninsured patients. The findings include a summary of the utilization of services and treatments along with demographic data. Recommendations for education, practice, and further research are discussed.     

Self-reported cardiovascular risk factors in immigrants and Swiss nationals

ABSTRACT Objective: The purpose of this study was to investigate whether the prevalence of self‐reported cardiovascular risk factors differs between immigrants and Swiss nationals. Design and Sample: This study is a secondary data analysis of the Swiss Health Survey 2002, a cross‐sectional survey. In total, 19,249 individuals living in Switzerland were included. Measures: The prevalence of hypertension, high cholesterol level, smoking, diabetes, overweight, low fruit and vegetable intake, and physical inactivity were calculated for major immigrant groups and Swiss nationals. Demographic data were used to control for age and socioeconomic status. Results: Major immigrant groups were people from Italy, Germany, former Yugoslavia, Spain, Portugal, France, and Turkey. Compared with Swiss women, women from former Yugoslavia were more likely to have hypertension, and women from Germany were more likely to have high cholesterol levels. Women from Italy, former Yugoslavia, Spain, Portugal, and Turkey were more likely to show physical inactivity and (except Turkish women) to be overweight. Men from these countries (except Spanish men) were more likely to be overweight than Swiss men. Conclusions: Differences exist in the prevalence of modifiable cardiovascular risk factors between Swiss nationals and many of the immigrant groups. Age and socioeconomic status could only partly explain the differences.     

Intracranial depth electrodes implantation in the era of image-guided surgery

The advent of modern image-guided surgery has revolutionized depth electrode implantation techniques. Stereoelectroencephalography (SEEG), introduced by Talairach in the 1950s, is an invasive method for three-dimensional analysis on the epileptogenic zone based on the technique of intracranial implantation of depth electrodes. The aim of this article is to discuss the principles of SEEG and their evolution from the Talairach era to the image-guided surgery of today, along with future prospects. Although the general principles of SEEG have remained intact over the years, the implantation of depth electrodes, i.e. the surgical technique that enables this method, has undergone tremendous evolution over the last three decades, due the advent of modern imaging techniques, computer systems and new stereotactic techniques. The use of robotic systems, the constant evolution of imaging and computing techniques and the use of depth electrodes together with microdialysis probes will open up enormous prospects for applying depth electrodes and SEEG both for investigative use and for therapeutic use. Brain stimulation of deep targets and the construction of "smart" electrodes may, in the near future, increase the need to use this method.     

Relationship between fluid-attenuated inversion-recovery (FLAIR) signal intensity and inflammatory mediator's levels in the hippocampus of patients with temporal lobe epilepsy and mesial temporal sclerosis

We investigated a relationship between the FLAIR signal found in mesial temporal sclerosis (MTS) and inflammation. Twenty nine patients were selected through clinical and MRI analysis and submitted to cortico-amygdalo-hippocampectomy to seizure control. Glutamate, TNFα, IL1, nitric oxide (NO) levels and immunostaining against IL1β and CD45 was performed. Control tissues (n=10) were obtained after autopsy of patients without neurological disorders. The glutamate was decreased in the temporal lobe epilepsy (TLE) -MTS group (p<0.001), suggesting increased release of this neurotransmitter. The IL1β and TNFα were increased in the hippocampus (p<0.05) demonstrating an active inflammatory process. A positive linear correlation between FLAIR signal and NO and IL1β levels and a negative linear correlation between FLAIR signal and glutamate concentration was found. Lymphocytes infiltrates were present in hippocampi of TLE patients. These data showed an association between hippocampal signal alteration and increased inflammatory markers in TLE-MTS.