Distribution of injected technetium99m‐labeled mesenchymal stem cells in horses with naturally occurring tendinopathy

This study aimed to investigate immediate cell survival and distribution following different administration routes of mesenchymal stem cells (MSCs) into naturally occurring tendon injuries. Ten million MSCs, labeled with technetium‐99m hexamethylpropyleneamine oxime, were implanted into 13 horses with naturally occurring tendon or ligament injuries intra‐lesionally, intravenously and by regional perfusion, and traced for up to 48 h using planar gamma scintigraphy. Labeling efficiencies varied between 1.8% and 18.5% (mean 9.3%). Cells were retained in the damaged area after intra‐lesional administration but only 24% of cells were still present within the tendon after 24 h. After intravenous injection, cells largely distributed to the lung fields, with no detectable cells in the tendon lesions. Significant labeling of the tendon lesions was observed in 11/12 horses following regional perfusion but at a lower level to intra‐lesional injection. The highest cell numbers were retained after intra‐lesional injection, although with considerable cell loss, while regional perfusion may be a viable alternative for MSC delivery. Cells did not “home” to damaged tendon in large numbers after intravenous administration. Cells were detected in the lungs most frequently after intravascular administration, although with no adverse effects. Low cell retention has important implications for designing effective clinical therapies for human clinical use. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1096–1102, 2013     

CD44 enhances tumor formation and lung metastasis in experimental osteosarcoma and is an additional predictor for poor patient outcome

Formation of metastases in the lungs is the major cause of death in patients suffering from osteosarcoma (OS). Metastases at presentation and poor response to preoperative chemotherapy are strong predictors for poor patient outcome. The elucidation of molecular markers that promote metastasis formation and/or chemoresistance is therefore of importance. CD44 is a plasma membrane glycoprotein that binds to the extracellular matrix component hyaluronan (HA) and has been shown to be involved in metastasis formation in a variety of other tumors. Here we investigated the role of CD44 expression on OS tumor formation and metastasis. High CD44 expression, evaluated with a tissue microarray including samples from 53 OS patients and stained with a pan‐CD44 antibody (Hermes3), showed a tendency (p < 0.08) to shortened overall survival. However, nonresponders and patients with lung metastases and high CD44 expression had significantly poorer prognosis than patients with low CD44 expression. Overexpression of the standard CD44 isoform (CD44s) and its HA‐binding defective mutant R41A in osteoblastic SaOS‐2 cells resulted in HA‐independent higher migration rates and increased chemoresistance, partially dependent on HA. In an orthotopic mouse model of OS, overexpression of CD44s in SaOS‐2 cells resulted in an HA‐dependent increased primary tumor formation and increased numbers of micrometastases and macrometastases in the lungs. In conclusion, although CD44 failed to be an independent predictor for patient outcome in this limited cohort of OS patients, increased CD44 expression was associated with even worse survival in patients with chemoresistance and with lung metastases. CD44‐associated chemoresistance was also observed in vitro, and increased formation of lung metastases was found in vivo in SCID mice. © 2013 American Society for Bone and Mineral Research.     

Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone,the murine model of X‐linked hypophosphatemia

X‐linked hypophosphatemia (XLH/HYP)—with renal phosphate wasting, hypophosphatemia, osteomalacia, and tooth abscesses—is caused by mutations in the zinc‐metallopeptidase PHEX gene (phosphate‐regulating gene with homologies to endopeptidase on the X chromosome). PHEX is highly expressed by mineralized tissue cells. Inactivating mutations in PHEX lead to distal renal effects (implying accumulation of a secreted, circulating phosphaturic factor) and accumulation in bone and teeth of mineralization‐inhibiting, acidic serine‐ and aspartate‐rich motif (ASARM)‐containing peptides, which are proteolytically derived from the mineral‐binding matrix proteins of the SIBLING family (small, integrin‐binding ligand N‐linked glycoproteins). Although the latter observation suggests a local, direct matrix effect for PHEX, its physiologically relevant substrate protein(s) have not been identified. Here, we investigated two SIBLING proteins containing the ASARM motif—osteopontin (OPN) and bone sialoprotein (BSP)—as potential substrates for PHEX. Using cleavage assays, gel electrophoresis, and mass spectrometry, we report that OPN is a full‐length protein substrate for PHEX. Degradation of OPN was essentially complete, including hydrolysis of the ASARM motif, resulting in only very small residual fragments. Western blotting of Hyp (the murine homolog of human XLH) mouse bone extracts having no PHEX activity clearly showed accumulation of an ～35 kDa OPN fragment that was not present in wild‐type mouse bone. Immunohistochemistry and immunogold labeling (electron microscopy) for OPN in Hyp bone likewise showed an accumulation of OPN and/or its fragments compared with normal wild‐type bone. Incubation of Hyp mouse bone extracts with PHEX resulted in the complete degradation of these fragments. In conclusion, these results identify full‐length OPN and its fragments as novel, physiologically relevant substrates for PHEX, suggesting that accumulation of mineralization‐inhibiting OPN fragments may contribute to the mineralization defect seen in the osteomalacic bone characteristic of XLH/HYP. © 2013 American Society for Bone and Mineral Research.     

Significant sleep disturbances in euthymic bipolar patients

Objective

A growing amount of data suggests that sleep dysfunction is frequently observed in bipolar disorder (BD) patients even when they do not fulfill the criteria for major mood episodes. Thus, we performed a case–control study assessing sleep status in a group of euthymic BD patients and a group of health controls.

Methods

A total of 209 subjects (104 health controls and 105 BD patients) were enrolled in the study. The Pittsburgh Sleep Quality Index (PSQI) was used for sleep assessment. Inclusion criteria for the BD group were a diagnosis of BD, following DSM-IV-TR criteria, according to the MINI-plus structured clinical interview. Euthymia was established as a score lower than 7 both in the Hamilton Depression Rating Scale (HDRS) and in the Young Mania Rating Scale (YMRS). Health controls were also interviewed using the MINI-plus and included in this study if they were free of any current or past DSM-IV-TR axis I psychiatric disorder as well the actual use of psychopharmacological medications.

Results

While 21.2 % of the control group displayed poor sleep quality according to the global PSQI-BR score, 82.9 % of the euthymic BD patients had poor sleep quality (p = 0.000). PSQI sleep duration subcomponent showed comparable results in the two groups (p = 0.535), even though BD patients had significant disruptions in sleep latency (p = 0.000) and sleep efficiency (p = 0.000) subcomponents.

Conclusion

We were able to show that BD patients, even in euthymic phase, exhibit a significantly worse sleep quality as compared with health controls as assessed by PSQI total score and five of its seven subcomponents.     

Negative association between quantities of body fat and physical fitness of university football players

Sport Sciences for Health - The aim of the present study was to assess, analyze and correlate tests of physical abilities (acceleration and maximum speed in 30&nbsp;m, Balsom agility test and...     

12 weeks of Brazilian jiu-jitsu training improves functional fitness in elderly men

Worldwide, there are up to 900 million people over 60 years old, of which more than half are physically inactive. Low physical fitness seems to be the major risk factor for cardiovascular diseases and mortality in this population. Alternative methods of exercise, such as martial arts, may be an option to improve physical fitness in the elderly. This study aimed to verify the effects of Brazilian jiu-jitsu (BJJ) training on the functional fitness of elderly men. Sixty-two elderly men were divided in two groups (experimental and control). The experimental group was submitted to a 12-week intervention of BJJ (2 times week^?1; 90-min session^?1). Physical fitness tests and anthropometric measurements were performed before and after intervention in both groups. No statistical differences were found between groups before and after the intervention. The experimental group improved in all performed physical fitness tests. Effect size showed that intervention had a small effect on upper body flexibility; a moderate effect for upper body strength, lower body flexibility, and motor agility/dynamic balance; and a large effect on lower body strength and aerobic endurance. BJJ seems to improve functional fitness in elderly men and may be an alternative method to enhance this population’s health and quality of life.     

Local adjunct effect of antimicrobial photodynamic therapy for the treatment of chronic periodontitis in type 2 diabetics: split-mouth double-blind randomized controlled clinical trial

Diabetes has become a global epidemic. Its complications can have a significant impact on quality of life, longevity, and public health costs. The presence of diabetes might impair the prognosis of periodontal treatments due to its negative influence on wound healing. Antimicrobial photodynamic therapy (aPDT) is a local approach that can promote bacterial decontamination in periodontal pockets. The aim of this study was to investigate the local effect of adjunct aPDT to ultrasonic periodontal debridement (UPD) and compare it to UD only for the treatment of chronic periodontitis in type 2 diabetic patients. Twenty type 2 diabetic patients with moderate to severe generalized chronic periodontitis were selected. Two periodontal pockets with probing depth (PD) and clinical attachment level (CAL) ≥5 mm received UPD only (UPD group) or UPD plus adjunct aPDT (UPD?+?aPDT group). Periodontal clinical measures were collected and compared at baseline and 30, 90, and 180 days. After 180 days of follow-up, there were statistically significant reductions in PD from 5.75?±?0.91 to 3.47?±?0.97 mm in the UPD group and from 6.15?±?1.27 to 3.71?±?1.63 mm in the UPD?+?aPDT group. However, intergroup analysis did not reveal statistically significant differences in any of the evaluated clinical parameters (p?>?0.05). The adjunct application of aPDT to UPD did not present additional benefits for the treatment of chronic periodontitis in type 2 diabetic patients. The ClinicalTrials.gov identifier of the present study is NCT02627534.     

Paediatric cervical spine injures. Nineteen years experience of a single centre

Purpose

This observational study aims to describe pediatric C-spine injuries from a level 1 trauma centre through a period of 19 years.

Methods

Clinical records of pediatric trauma patients admitted to a level 1 trauma centre between 1991 and 2009 were analyzed. Patients were stratified by age into groups A (8 or less) and B (9 to 16), and in lower (C0-C2) and upper (C3-C7) spine injuries. Several variables were studied.

Results

Seventy-five cases of C-spine injuries (nine SCIWORA) were identified. Group A included 23 patients and group B 52. In group A, skeletal injuries at the upper C-spine were more common than injuries at the lower C-spine, whereas in group B, injuries of the lower C-spine were more frequent (p?=?0.035). Motor vehicle accidents were the main cause of injury (44 %); 25.3 % of patients were surgically treated. Thirty-nine patients presented neurologic deficits, 16 of which improved. The overall mortality rate was 18.7 % and significantly higher in patients with neurological damages (p?<?0.001)

Conclusions

This study revealed a low incidence of cervical spine injuries in the paediatric population. As in previous reports younger children mainly sustained injuries at the upper C-spine, higher incidence of spinal injuries, and higher risk of death than older children.

     

Luteinizing hormone beta mutation and hypogonadism in men and women

Selective luteinizing hormone deficiency due to mutations in the luteinizing hormone beta-subunit gene (LHB) is a rare cause of hypogonadism. We describe the clinical features of a consanguineous family in which three siblings, two men and one woman, had hypogonadism related to isolated luteinizing hormone deficiency. These subjects have a newly discovered homozygous mutation of a 5' splice site in LHB: IVS2+1G-->C. This mutation disrupts the splicing of messenger RNA (mRNA), generating a gross abnormality in the processing of the luteinizing hormone beta-subunit mRNA, which abrogates the secretion of luteinizing hormone. We also determined that the female phenotype of this LHB mutation is characterized by normal pubertal development, secondary amenorrhea, and infertility.