Maternal origin of transferrin receptor positive cells in venous blood of pregnant women

We studied the origin of transferrin receptor (CD71) positive cells in blood from seven women pregnant with a male fetus in order to explore if fetal cells could be detected among them. We used a technique that allows direct chromosomal analysis by in situ hybridization on immunologically and morphologically classified cells. Enrichment was performed by magnetic activated cell sorting (miniMACS)® using an anti-CD71 monoclonal antibody. The cells were immunophenotyped by alkaline phosphatase anti-alkaline phosphatase immunostaining with the same antibody. The origin of the immunophenotyped cells was studied by in situ hybridization using an X cosmid Y repeat chromosome specific probe cocktail. CD71 positive cells were found in six of the seven women at the range of 4 to 43 in respective samples. Over 90% of the CD71 positive cells were nucleated erythrocytes. None of the detected positive cells were shown to be fetal. Thus, the use of transferrin receptor antigen alone in combination with the miniMACS® may not be sufficient for enrichment of fetal cells.     

The effects of cognitive loading on balance control in patients with multiple sclerosis

The aim of this study was to compare the effects of concurrent cognitive task (silent backward counting) on balance performance between two groups of multiple sclerosis (MS) (n = 23) and healthy (n = 23) participates. Three levels of postural difficulty were studied on a force platform, i.e. rigid surface with eyes open, rigid surface with eyes closed, and foam surface with eyes closed. A mixed model analysis of variance showed that under difficult sensory condition of foam surface with eyes closed, execution of concurrent cognitive task caused a significant decrement in variability of sway velocity in anteroposterior direction for the patient group (P < 0.01) while this was not the case for healthy participants (P = 0.22). Also, the variability of sway velocity in mediolateral direction was significantly decreased during concurrent execution of cognitive task in patient group (P < 0.01) and not in healthy participants (P = 0.39). Furthermore, in contrast to single tasking, dual tasking had the ability to discriminate between the 2 groups in all conditions of postural difficulty. In conclusion, findings of variability in sway velocity seem to confirm the different response to cognitive loading between two groups of MS and healthy participants.     

Recurrent and Chronic Complete Ruptures of the Proximal Origin of the Hamstring Muscles Repaired With Fascia Lata Autograft Augmentation

Hamstring injuries are common, especially among athletes. A complete rupture of the proximal hamstring muscles requires surgical intervention. In this report we describe a reconstruction method for a complete proximal hamstring rupture using fascia lata autograft augmentation in addition to suture anchors. This method can be advocated in cases in which the primary repair has failed or in chronic injuries where a large defect between the distally retracted tendons and the ischial tuberosity prevents anatomic reinsertion. In our technique, a muscle-tendon flap is first created from the retracted tendon stump, turned proximally, and fixed to the ischial tuberosity by suture anchors. The fascia lata graft is then fixed from the midpart to the ischial tuberosity via the same sutures. The other sleeve of the graft is folded on the ventral side of the ruptured tendon stump and fixed by use of absorbable sutures. Then the other sleeve is folded on the dorsal side and fixed in the same manner. Finally, the fixation can still be reinforced with additional absorbable sutures passing through both sleeves of the graft, as well as the muscle-tendon bridge and the tendon stump.     

MicroRNA Profiling Identifies MicroRNA-155 as an Adverse Mediator of Cardiac Injury and Dysfunction During Acute Viral Myocarditis

Rationale: Viral myocarditis results from an adverse immune response to cardiotropic viruses, which causes irreversible myocyte destruction and heart failure in previously healthy people. The involvement of microRNAs and their usefulness as therapeutic targets in this process are unknown. Objective: To identify microRNAs involved in viral myocarditis pathogenesis and susceptibility. Methods and Results: Cardiac microRNAs were profiled in both human myocarditis and in Coxsackievirus B3-injected mice, comparing myocarditis-susceptible with nonsusceptible mouse strains longitudinally. MicroRNA responses diverged depending on the susceptibility to myocarditis after viral infection in mice. MicroRNA-155, -146b, and -21 were consistently and strongly upregulated during acute myocarditis in both humans and susceptible mice. We found that microRNA-155 expression during myocarditis was localized primarily in infiltrating macrophages and T lymphocytes. Inhibition of microRNA-155 by a systemically delivered LNA-anti-miR attenuated cardiac infiltration by monocyte-macrophages, decreased T lymphocyte activation, and reduced myocardial damage during acute myocarditis in mice. These changes were accompanied by the derepression of the direct microRNA-155 target PU.1 in cardiac inflammatory cells. Beyond the acute phase, microRNA-155 inhibition reduced mortality and improved cardiac function during 7 weeks of follow-up. Conclusions: Our data show that cardiac microRNA dysregulation is a characteristic of both human and mouse viral myocarditis. The inflammatory microRNA-155 is upregulated during acute myocarditis, contributes to the adverse inflammatory response to viral infection of the heart, and is a potential therapeutic target for viral myocarditis.     

Background factors of molar-incisor hypomineralization in a group of Finnish children

Objective. Molar-Incisor Hypomineralization (MIH) is a common developmental enamel defect characterized by demarcated opacities in permanent molars and incisors. Its etiology still remains unclear. The aim of this retrospective cohort study was to assess if the socioeconomic environment of the child is associated with MIH. Materials and methods. The study was located in two rural towns and three urban cities in Finland. A total of 818 children, between 7–13 years old, were examined for MIH using the evaluation criteria in line with those of the European Academy of Paediatric Dentistry, but excluding opacities smaller than 2 mm in diameter. The mothers filled in a questionnaire which included questions related to the family’s way of living (e.g. area of residency, farming, day care attendance) and socioeconomic status (family income, number of mother’s school years, level of maternal education). Results. The prevalence of MIH in the study population was 17.1%. Family income, urban residency and day care attendance were associated with MIH in the univariate analysis. In the multivariate analysis using binary logistic regression, only urban residency during a child’s first 2 years of life remained associated with MIH. The prevalence of MIH in urban areas was 21.3% and in rural areas 11.5% (OR = 2.18, CI = 1.35–3.53, p = 0.001). Conclusions. The prevalence of MIH was related to urban residency and could not be explained by any other factor included in the study.     

The impact of a state children's health insurance program on access to dental care

BACKGROUND: Access to dental care for low-income children is limited. The authors examined the impact of a new state children's health insurance program, or SCHIP, in North Carolina on children's access to dental care. METHODS: Parents of 639 school-aged children responded to two surveys that asked about their child's access to dental services before enrollment and one year after enrollment in the new program. The authors used two-tailed McNemar tests to detect statistically significant changes within subjects. RESULTS: The percentage of school-aged children with a visit to a dentist in the previous year increased from 48 percent at baseline to 65 percent after one year in the program. Reported unmet dental need decreased from 43 percent at baseline to 18 percent after one year of enrollment. The proportion of children reported to have a usual source of dental care improved after enrollment in the program. CONCLUSION: The SCHIP model in North Carolina is an innovative program that has made a significant impact on access to dental care for school-aged children. PRACTICE IMPLICATIONS: SCHIP dental programs that resemble private insurance models and reimburse dentists at rates close to market rates hold the potential to address problems associated with dental access for low-income children.     

Life satisfaction and pain interference in spine surgery patients before and after surgery: comparison between on-opioid and opioid-naïve patients

Quality of Life Research - Pain has a negative impact on life satisfaction (LS). Our primary aims were to compare LS in on-opioid and opioid-naïve spine surgery patients and to evaluate...     

Biallelic inactivation of fumarate hydratase (FH) occurs in nonsyndromic uterine leiomyomas but is rare in other tumors

Germline mutations in the fumarate hydratase (FH) gene at 1q43 predispose to dominantly inherited cutaneous and uterine leiomyomas, uterine leiomyosarcoma, and papillary renal cell cancer (HLRCC syndrome). To evaluate the role of FH inactivation in sporadic tumorigenesis, we analyzed a series of 299 malignant tumors representing 10 different malignant tumor types for FH mutations. Additionally, 153 uterine leiomyomas from 46 unselected individuals were subjected to and informative in loss of heterozygosity analysis at the FH locus, and the five (3.3%) tumors displaying loss of heterozygosity were subjected to FH mutation analysis. Although mutation search in the 299 malignant tumors was negative, somatic FH mutations were found in two nonsyndromic leiomyomas; a splice site change IVS4 + 3A>G, leading to deletion of exon four, and a missense mutation Ala196Thr. The occurrence of somatic mutations strongly suggests that FH is a true target of the 1q43 deletions. Although uterine leiomyomas are the most common tumors of women, specific inactivating somatic mutations contributing to the formation of nonsyndromic leiomyomas have not been reported previously. Taking into account the apparent risk of uterine leiomyosarcoma associated with FH germline mutations, the finding raises the possibility that also some nonsyndromic leiomyomas may have a genetic profile that is more prone to malignant degeneration. Our data also indicate that somatic FH mutations appear to be limited to tumor types observed in hereditary leiomyomatosis and renal cell cancer.     

CDK4 is a probable target gene in a novel amplicon at 12q13.3-q14.1 in lung cancer

Several chromosomal regions are recurrently amplified or deleted in lung tumors, but little is known about the underlying genes, which could be important mediators in tumor formation or progression. In lung cancer, the RB1-CCND1-CDKN2A pathway, involved in the G1-S transition, is damaged in nearly all tumors. In the present study, we localized a novel amplicon in lung tumors to a fragment of less than 0.5 Mb at 12q13.3-q14.1 by using comparative genomic hybridization (CGH) on cDNA microarrays. This approach enabled us to identify 10-15 genes with the most consistent amplifications. Semiquantitative RT-PCR analyses of 13 genes in this region showed that four of them (CDK4, CYP27B1, METTL1, and TSFM) were also highly up-regulated. Immunohistochemical (IHC) analysis of 141 tumor samples on a tissue microarray showed that CDK4 was expressed at a high level in 23% of lung tumors. Six (21.4%) of the tumors with high CDK4 expression (n = 28) were shown by fluorescence in situ hybridization (FISH) to contain the 12q13.3-q14.1 amplification. For CDK4, a positive correlation was found between gene copy number (FISH and CGH array), mRNA expression (RT-PCR), and level of protein expression (IHC). CDK4 expression did not correlate with CDKN2A methylation status. Amplification of CDK4 has been described in other tumor types, but its role in lung cancer remains to be elucidated. Although CDK4 amplification seems to be a relatively rare event (4.3%) in lung tumors, it indicates the significance of the RB1-CCND1 pathway in lung tumorigenesis.