Osteoporotic Animal Models of Bone Healing: Advantages and Pitfalls

The aim of this review was to summarize the advantages and pitfalls of the available osteoporotic animal models of bone healing. A thorough literature search was performed in MEDLINE via OVID and EMBASE to identify animal studies investigating the effect of experimental osteoporosis on bone healing and bone regeneration. The osteotomy model in the proximal tibia is the most popular osseous defect model to study the bone healing process in osteoporotic-like conditions, although other well-characterized models, such as the post-extraction model, might be taken into consideration by future studies. The regenerative potential of osteoporotic bone and its response to biomaterials/regenerative techniques has not been clarified yet, and the critical size defect model might be an appropriate tool to serve this purpose. Since an ideal animal model for simulating osteoporosis does not exist, the type of bone remodeling, the animal lifespan, the age of peak bone mass, and the economic and ethical implications should be considered in our selection process. Furthermore, the influence of animal species, sex, age, and strain on the outcome measurement should be taken into account. In order to make future studies meaningful, standardized international guidelines for osteoporotic animal models of bone healing need to be set up.     

Translation and validation of the Depression Outcomes Module (DOM) in Greece

In Greece, as in other countries, major depressive disorder is underdiagnosed. Its severity, implications and outcomes are often not adequately evaluated. The Depression Outcomes Module (DOM) was developed in order to meet the need for a global assessment of this disorder. The objective of the current study was to estimate the psychometric properties of DOM in a Greek population presenting depressive symptoms. The DOM was translated into Greek. Patients were examined twice (baseline and follow-up assessment). The psychometric properties of DOM were calculated. Subjects were 83 psychiatric inpatients and outpatients presenting depressive symptoms. The measures used were DOM, Structured Clinical Interview for DSM III-R (SCID) and Hamilton Rating Scale for Depression (Ham-D). The results were: (a) baseline assessment: test-retest reliability k = 0.90, internal consistency 0.93, sensitivity 97%, specificity 90%; (b) follow up assessment: test-retest reliability k = 0.89, sensitivity 81% and specificity 67%. Recovery from depression detected by DOM at the follow-up was significantly correlated both with pharmacotherapy and with a combination of pharmacotherapy and supportive psychotherapy. It was concluded that the Greek version of DOM is a comprehensive, useful instrument for diagnosing, assessing depression and evaluating its outcomes.     

Bone tissue engineering in oral peri‐implant defects in preclinical in vivo research: A systematic review and meta‐analysis

The regeneration and establishment of osseointegration within oral peri‐implant bone defects remains a clinical challenge. Bone tissue engineering (BTE) is emerging as a promising alternative to autogenous and/or biomaterial‐based bone grafting. The objective of this systematic review was to answer the focused question: in animal models, do cell‐based BTE strategies enhance bone regeneration and/or implant osseointegration in experimental peri‐implant defects, compared with grafting with autogenous bone or only biomaterial scaffolds? Electronic databases were searched for controlled animal studies reporting on peri‐implant defects and implantation of mesenchymal stem cells (MSC) or other cells seeded on biomaterial scaffolds, following Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines. Random effects meta‐analyses were performed for the outcomes histomorphometric bone area fraction (BA) and bone‐to‐implant contact (BIC). Nineteen studies reporting on large animal models (dogs and sheep) were included. Experimental defects were created surgically (16 studies) or via ligature‐induced peri‐implantitis (LIPI, three studies). In general, studies presented with an unclear to high risk of bias. In most studies, MSC were used in combination with alloplastic mineral phase or polymer scaffolds; no study directly compared cell‐loaded scaffolds vs. autogenous bone. In three studies, cells were also modified by ex vivo gene transfer of osteoinductive factors. The meta‐analyses indicated statistically significant benefits in favour of: (a) cell‐loaded vs. cell‐free scaffolds [weighted mean differences (WMD) of 10.73–12.30% BA and 11.77–15.15% BIC] in canine surgical defect and LIPI models; and (b) gene‐modified vs. unmodified cells (WMD of 29.44% BA and 16.50% BIC) in canine LIPI models. Overall, heterogeneity in the meta‐analyses was high (I² 70–88%); considerable variation was observed among studies regarding the nature of cells and scaffolds used. In summary, bone regeneration and osseointegration in peri‐implant defects are enhanced by the addition of osteogenic cells to biomaterial scaffolds. Although the direction of treatment outcome is clearly in favour of BTE strategies, due to the limited magnitude of treatment effect observed, no conclusive statements regarding the clinical benefit of such procedures for oral indications can yet be made. Copyright © 2017 John Wiley & Sons, Ltd.     

A comparative study of postendoscopic sphincterotomy complications with various types of electrosurgical current in patients with choledocholithiasis

BACKGROUND: Whether the type of electrosurgical current used for endoscopic sphincterotomy influences the frequency of postsphincterotomy complications is unknown. METHODS: One hundred eighty-six patients with choledocholithiasis were prospectively randomized to undergo endoscopic sphincterotomy with pure cutting current (n = 62, Group A), blended current (n = 62, Group B), or pure cutting initially followed by blended current (n = 62, Group C). Serum concentrations of amylase and lipase were evaluated in all patients 12 and 24 hours after sphincterotomy. Clinical pancreatitis was classified as mild, moderate, or severe. Postsphincterotomy bleeding was defined as a decrease in hematocrit of greater than 5%. RESULTS: Serum concentrations of amylase and lipase were greater in Groups B and C at 12 and 24 hours after the procedure, as compared with Group A. Clinical mild pancreatitis occurred in 2 patients in Group A (3.2%), 8 in Group B (12.9%), and in 8 in Group C (12.9%). The differences were statistically significant for Group A compared with either Group B or Group C (p = 0.048). Postsphincterotomy bleeding occurred in 3 patients (1.6%), one in each group. CONCLUSION: The use of pure cutting electrosurgical current during endoscopic sphincterotomy in patients with choledocholithiasis is associated with a lesser degree of pancreatic enzyme elevation and lower frequency of pancreatitis, whereas bleeding is not increased compared with blended current. Changing from pure cutting to blended current after the first 3 to 5 mm of the incision is associated with an increased rate of complications compared to the use of pure cutting current for the entire sphincterotomy.     

Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies

Adiponectin is an adipocyte-secreted protein that circulates in high concentrations in the serum and acts to increase insulin sensitivity. Previous studies have shown that serum adiponectin is inversely associated with fat mass and insulin resistance in humans and that acute fasting decreases adipose tissue adiponectin mRNA expression in rodents. Whether acute energy deprivation, body fat distribution, or serum hormone levels are associated with circulating adiponectin in humans remains largely unknown. To identify predictors of serum adiponectin levels, we evaluated the association of adiponectin with several anthropometric, metabolic, and hormonal variables in a cross-sectional study of 121 women without a known history of diabetes. We also performed interventional studies to assess whether fasting for 48 h and/or leptin administration regulates serum adiponectin in healthy men and women. Our cross-sectional study shows that, in addition to overall obesity, central fat distribution is an independent negative predictor of serum adiponectin and suggests that adiponectin may represent a link between central obesity and insulin resistance. In addition, estradiol is negatively and independently associated with adiponectin, whereas there is no association between serum adiponectin and leptin, cortisol, or free testosterone levels. Our interventional studies demonstrate that neither fasting for 48 h, resulting in a low leptin state, nor leptin administration at physiological or pharmacological doses alters serum adiponectin levels. Further studies are needed to fully elucidate the physiology of adiponectin in humans and its role in the pathogenesis of insulin-resistant states.     

Cryptic speciation in a model invertebrate chordate

We applied independent species concepts to clarify the phylogeographic structure of the ascidian Ciona intestinalis, a powerful model system in chordate biology and for comparative genomic studies. Intensive research with this marine invertebrate is based on the assumption that natural populations globally belong to a single species. Therefore, understanding the true taxonomic classification may have implications for experimental design and data management. Phylogenies inferred from mitochondrial and nuclear DNA markers accredit the existence of two cryptic species: C. intestinalis sp. A, genetically homogeneous, distributed in the Mediterranean, northeast Atlantic, and Pacific, and C. intestinalis sp. B, geographically structured and encountered in the North Atlantic. Species-level divergence is further entailed by cross-breeding estimates. C. intestinalis A and B from allopatric populations cross-fertilize, but hybrids remain infertile because of defective gametogenesis. Although anatomy illustrates an overall interspecific similarity lacking in diagnostic features, we provide consistent tools for in-field and in-laboratory species discrimination. Finding of two cryptic taxa in C. intestinalis raises interest in a new tunicate genome as a gateway to studies in speciation and ecological adaptation of chordates.     

Effects of age on volumes of cortex, white matter and subcortical structures

The effect of age was investigated in and compared across 16 automatically segmented brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, the accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, the lateral ventricle, the inferior lateral ventricle, and the 3rd and 4th ventricle. Significant age effects were found for all volumes except pallidum and the 4th ventricle. Heterogeneous age responses were seen in that age relationships for cortex, amygdala, thalamus, the accumbens area, and caudate were linear, while cerebral white matter, hippocampus, brainstem, cerebellar white, and gray matter, as well as volume of the lateral, inferior lateral, and 3rd ventricles showed curvilinear relationships with age. In general, the findings point to global and large effects of age across brain volumes.