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.     

Laparoscopic Resection of a Small Bowel Lipoma with Incidental Intussusception

Background:

Small bowel tumors are rare entities that often present with nonspecific symptoms. The diagnosis is more likely in patients with occult gastrointestinal bleeding of unknown origin or in adults with small bowel intussusception. Even with exhaustive diagnostic testing, small bowel tumors are often not diagnosed preoperatively. Because 60% to 70% of small bowel tumors are malignant, surgical excision is always recommended.

Methods:

We report the case of a 73-year-old man with occult gastrointestinal bleeding. A small bowel tumor was discovered only after video capsule endoscopy, computed tomography, and multiple endoscopies were performed.

Results:

The patient underwent laparoscopic exploration. An incidental intussusception made the tumor simple to identify. By extending the umbilical port, the tumor was easily removed. The final pathology demonstrated a submucosal lipoma.

Conclusions:

Small bowel lipomas can cause intussusception and gastrointestinal bleeding. When diagnosed preoperatively, laparoscopic resection is feasible.     

Development of New Quality Measures for Hospital-Based Care of Suicidal Youth

Objectives

To develop, validate, and test the feasibility of implementation of 4 new quality measures assessing emergency department (ED) and inpatient care for suicidal youth.

Parental psychological distress during pregnancy and childhood cardiovascular development. The Generation R Study

Background

Maternal psychological distress during pregnancy might lead to higher fetal cortisol exposure, which subsequently leads to fetal cardiovascular developmental adaptations and cardiovascular dysfunction in later life.

Aims

We examined whether maternal and paternal psychological distress was associated with the cardiovascular outcome measurements in school age children.

Study design and subjects

In a population-based prospective cohort study among 4831 children, we assessed maternal and paternal psychological distress during pregnancy by questionnaire, using the Brief Symptom Inventory (see Fig. 1).

Outcome measures

At the child age of six years, we performed blood pressure and carotid–femoral pulse wave velocity measurements, and M-mode measurements of left cardiac structures and fractional shortening.

Results

We did not observe associations of high maternal and paternal psychological symptom scores with childhood blood pressure and carotid–femoral pulse wave velocity after adjustment for potential confounders. Maternal overall psychological symptoms were associated with a lower childhood left ventricular mass (difference − 1.10 g (95% confidence interval − 2.13 to − 0.07) between mothers with high scores and normal scores), but not with other cardiac structures and fractional shortening. Paternal overall psychological symptoms showed a similar association with childhood left ventricular mass (difference − 1.34 grams (95% confidence interval − 3.69 to 1.02) between fathers with high scores and normal scores).

Conclusions

Our results do not support the hypothesis that maternal psychological distress affects cardiovascular development in early life. Similar associations of maternal and paternal psychological distress with left ventricular mass suggest that these associations could be due to unmeasured social and environmental factors, rather than direct intra-uterine effects.     

Acute septic arthritis in children

Background:  Acute septic arthritis is a health-care problem in growing children. The aim of the present study was to determine the demographic features, clinical presentation, diagnostic evaluation, treatment and outcome of children suffering from acute septic arthritis.
Methods:  Retrospective review of consecutive admissions of children ≤14 years of age with a bacteriologically and/or radiologically confirmed diagnosis of septic arthritis during the 10 year period, January 1997–December 2006 at King Fahad Hospital, King Abdulaziz Medical City was undertaken.
Results:  Sixty-five patients (male : female, 2.4:1), 10 days–14 years of age (mean ± SD: 3.3 ± 3.2 years), met the inclusion criteria. More than half of the patients were under 2 years. The most frequent clinical features were pain (92%), fever (77%), limitation of joint movement (77%) and joint swelling (72%). Joint involvement was monoarticular in 97% of knees, and hips were affected in 75% of patients. Bacteria were isolated from joint aspirate or blood in 28 patients (43%), and Staphylococcus aureus was the most common organism, comprising 39% of the total bacterial isolates. Radiological diagnostic findings were observed in 19 (32%) of 60 patients with plain radiographs, nine (69%) of 16 patients with sonograms of the hip, 36 (80%) of 45 patients with Tc-labeled bone scan and nine (100%) of nine patients with magnetic resonance imaging. The joint infection resolved with no sequelae in 46 patients who were followed up for 6–36 months, but two had bone deformity and 17 were lost to follow up.
Conclusion:  According to the present series, septic arthritis is most common in young infants, mainly monoarticular, and is frequently localized in the knee and hip joints. Early diagnosis and appropriate treatment are associated with excellent outcome.     

Investigation into the controversial association of Streptococcus gallolyticus with colorectal cancer and adenoma

Background  

The seroprevalence of IgG antibodies of Streptococcus gallolyticus subspecies gallolyticus, CIP 105428, was evaluated to investigate the controversial association of S. gallolyticus with colorectal carcinoma and adenoma in attempt to investigate the nature of such association if any, by exploring the mRNA expression of NF-κB and IL-8. Moreover, the serological behavior of S. gallolyticus IgG antibodies was compared to that of an indicator bacterium of bowel, Bacteroides fragilis.     

Review of source-monitoring processes in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a severe mental illness characterized by persistent, intrusive and distressing obsessions and/or compulsions. Such symptoms have been conceptualized as resulting from a failure in source-monitoring processes, suggesting that patients with OCD fail to distinguish actions they perform from those they just imagine doing. In this study, we aimed to provide an updated and exhaustive review of the literature examining the relationship between source-monitoring and OCD. A systematic search in the literature through January 2019 allowed us to identify 13 relevant publications investigating source-monitoring abilities in patients with OCD or participants with subclinical compulsive symptoms. Most of the retrieved studies did not report any source-monitoring deficits in clinical and subclinical subjects compared with healthy volunteers. However, most of the studies reported that patients with OCD and subclinical subjects displayed reduced confidence in source-monitoring judgments or global cognitive confidence compared to controls. The present review highlighted some methodological and statistical limitations. Consequently, further studies are needed to explore source monitoring with regard to the subcategories of OCD symptoms (i.e., symmetry-ordering, contamination-washing, hoarding, aggressive obsession-checking, sexual-religious thoughts) and to clarify the relationship between source-monitoring subtypes (i.e., reality or internal source-monitoring) and confidence in these populations.     

Effect of Sex Differences on Computed Tomography Findings in Adults With Cystic Fibrosis: A Multicenter Study

BackgroundThe survival of women with cystic fibrosis (CF) is lower than that of men by approximately 5 years. While various factors have been put forward to account for this discrepancy, no specific reasons have been established. Our hypothesis was that anatomical-structural involvement is more pronounced in women with CF than in men and that this is reflected in thoracic HRCT findings.Material and methodsWe performed a prospective multicentre study, in which adult patients were consecutively included over 18 months. Chest HRCT was performed, and findings were scored by 2 thoracic radiologists using the modified Bhalla system. We also studied respiratory function, applied the CFQR 14+ questionnaire, and collected clinical variables.ResultsOf the 360 patients followed up in the participating units, 160 were eventually included. Mean age was 28 years, and 47.5% were women. The mean ± SD global score on the modified Bhalla score was 13.7 ± 3.8 in women and 15.2 ± 3.8 in men (p = 0.024). The highest scores were observed for sacculations, bronchial generations, and air trapping in women. Women had lower BMI, %FEV₁, %FVC, and %DLCO. Similarly, the results for the respiratory domain in CFQR 14+ were worse in women, who also had more annual exacerbations.ConclusionsThis is the first study to provide evidence of the implication of sex differences in HRCT findings in patients with CF. Women with CF present a more severe form of the disease that results in more frequent exacerbations, poorer functional and nutritional outcomes, deterioration of quality of life, and greater structural damage.