Biomechanical consideration regarding bone substitutes use in surgical treatment of chronic osteomyelitis

The main aim of this study is to present the use of bone substitutes in chronic ostheomielitis surgical treatment and its biomechanical influence. MATERIAL AND METHODS: First step is three-dimensional reconstruction to one femur using CT sections; the second is the reconstruction of infected bone volume, synthesis of material properties, synthesis of loading forces, synthesis of boundary condition and, finally, finite element analysis. RESULTS: The calculated Von Mises stress as a result of finite element analysis indicates that bone substitute implantation lead to a stress distribution in bone similar with a health femur.     

Cetuximab-based or bevacizumab-based first-line treatment in patients with KRAS p.G13D-mutated metastatic colorectal cancer: a pooled analysis

KRAS p.G13D mutant metastatic colorectal cancer (mCRC) has been identified as representing a cetuximab-sensitive subtype of KRAS mutant mCRC. This analysis aims to answer the question of whether first-line treatment of p.G13D mCRCs should include cetuximab or bevacizumab. Fifty-four patients with p.G13D mutant mCRC were pooled in this analysis. All patients underwent systemic first-line treatment with a fluoropyrimidine and oxaliplatin/irinotecan that was combined with either cetuximab or bevacizumab. The analysis of cetuximab-based and bevacizumab-based regimens in mCRC patients with p.G13D-mutated tumours indicated comparable data for the overall response rate (58 vs. 57%) and progression-free survival (8.0 vs. 8.7 months; hazard ratio: 0.96, P=0.9). Overall survival (OS) was 20.1 months in patients treated with cetuximab-based first-line therapy compared with 14.9 months in patients receiving bevacizumab-containing regimens (hazard ratio: 0.70, P=0.29). Logistic regressions modelling OS revealed oxaliplatin-based first-line treatment to correlate with a poor outcome (P=0.03). Moreover, a strong trend in favour of capecitabine compared with infusional 5-FU (P=0.06) was observed. Response to treatment correlated with OS in patients receiving cetuximab-based, but not bevacizumab-based regimens. This retrospective pooled analysis suggests comparable efficacy of cetuximab-based and bevacizumab-based first-line therapy in patients with p.G13D mutant mCRC. The combination with capecitabine and irinotecan was associated with a more favourable outcome compared with infusional 5-FU and oxaliplatin.     

The potential value of early screening for neurological deficits in participants in certain sports

Physicians occasionally encounter the punch-drunk syndrome among boxers after longlasting careers characterized by blows to the head. The list of sports leading to punch-drunk syndrome is rapidly increasing, making it a notable public health problem. A lack of specific findings leads to defects in reporting the condition, and consequently to delay in treatment. Although the rigorous enforcement of sport rules and constant improvements of sporting equipment have decreased the occurrence of the syndrome, early detection of punch-drunk syndrome is crucial and would have comprehensive benefits. Two groups of signs and symptoms can be identified: dementia and Parkinsonism. A prompt diagnosis with a correct classification of the suspected cases is crucial. Therefore, we offer an overview of the symptomatology as well as proposing the introduction of a screening method among risk groups based on generic and minute neurological examination and dementia testing.     

Comparison of Pulmonary Inflammatory and Antioxidant Responses to Intranasal Live and Heat-Killed Streptococcus pneumoniae in Mice

Inflammatory and antioxidant responses, in male C57Bl6J mice, to single intranasal inoculations with live or heat-killed Streptococcus pneumoniae were studied in order to tease out differences in responses. Heat-killed bacteria elicited weak lung neutrophil infiltration and raised concentrations (peak 6–8 h), in serum or lung tissue, of CXCL1 and 2, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and granulocyte-macrophage-colony stimulating factor, with later increases in CCL2 and IL-1β. Live bacteria induced profound pulmonary neutrophil infiltration and acute chemokine/cytokine elevations. After 72–96 h, live S. pneumoniae induced a delayed rise in chemokines CXCL2 and CCL2, preceded by increases in TNFα, IL-1β, and IL-6 and mononuclear infiltration of lungs. With both live and heat-killed bacteria, alveolar epithelial type II cells and alveolar macrophages were the main sources of TNFα and IL-1β. Only live bacteria caused an acute decrease in lung glutathione peroxidase, an increase in superoxide dismutase, and a sustained increase in serum amyloid protein A. Acute innate immune responses to live and heat-killed S. pneumoniae are similar. In response to live bacteria, inflammation is greater, accompanied by changes in antioxidant enzymes and has an additional, later mononuclear component.     

Forensic DNA databases in Western Balkan region: retrospectives, perspectives, and initiatives

The European Network of Forensic Science Institutes (ENFSI) recommended the establishment of forensic DNA databases and specific implementation and management legislations for all EU/ENFSI members. Therefore, forensic institutions from Bosnia and Herzegovina, Serbia, Montenegro, and Macedonia launched a wide set of activities to support these recommendations. To assess the current state, a regional expert team completed detailed screening and investigation of the existing forensic DNA data repositories and associated legislation in these countries. The scope also included relevant concurrent projects and a wide spectrum of different activities in relation to forensics DNA use. The state of forensic DNA analysis was also determined in the neighboring Slovenia and Croatia, which already have functional national DNA databases. There is a need for a 'regional supplement' to the current documentation and standards pertaining to forensic application of DNA databases, which should include regional-specific preliminary aims and recommendations.     

Development of a humanized in vitro blood-brain barrier model to screen for brain penetration of antiepileptic drugs

PURPOSE: A biotechnologic breakthrough for the study of drug permeability across the blood-brain barrier (BBB) would be the use of a reproducible in vitro model that recapitulates the functional, structural, and pathologic properties of the BBB in situ. We developed a humanized dynamic in vitro BBB model (DIV-BBB) based on cocultures of human microvascular endothelial cells (HBMECs) from "normal" and drug-resistant epileptic brain tissue with human brain astrocytes (HAs) from epilepsy patients or controls. METHODS: HBMECs and HAs were cocultured for 28 days in polypropylene capillaries. HBMECs were exposed to physiologic levels of shear stress generated by intraluminal flow. Permeability to [3H]sucrose, [14C]phenytoin, and [14C]diazepam was measured in control and drug-resistant DIV-BBB with and without pretreatment with the MDR1 inhibitor XR9576. BBB integrity was monitored by transendothelial electrical resistance measurements (TEERs). Cell growth and viability were assessed by measurement of glucose consumption and lactate production. RESULTS: PSucrose and TEER values did not depend on the origin of the endothelium used (epileptic or normal). PPhenytoin was 10-fold less (1.54 x 10(-6) cm/s) in drug-resistant BBB models than in controls (1.74 x 10(-5) cm/s). MDR1 blockade with XR9576 was effective (3.5-fold increase) only in drug-resistant cultures. PDiazepam in control and drug-resistant DIV-BBB was not affected by XR9576 and did not depend on the epileptic or control origin of endothelia. The overall contribution of epileptic glia to pharmacoresistance was negligible. CONCLUSIONS: These results show that, for the substances used, the humanized DIV-BBB recapitulates the physiologic permeability properties of the BBB in vivo and is also capable of mimicking a drug-resistant BBB phenotype.     

Antagonism of peripheral inflammation reduces the severity of status epilepticus

Status epilepticus (SE) is one of the most serious manifestations of epilepsy. Systemic inflammation and damage of blood-brain barrier (BBB) are etiologic cofactors in the pathogenesis of pilocarpine SE while acute osmotic disruption of the BBB is sufficient to elicit seizures. Whether an inflammatory-vascular-BBB mechanism could apply to the lithium–pilocarpine model is unknown. LiCl facilitated seizures induced by low-dose pilocarpine by activation of circulating T-lymphocytes and mononuclear cells. Serum IL-1β levels increased and BBB damage occurred concurrently to increased theta EEG activity. These events occurred prior to SE induced by cholinergic exposure. SE was elicited by lithium and pilocarpine irrespective of their sequence of administration supporting a common pathogenetic mechanism. Since IL-1β is an etiologic trigger for BBB breakdown and its serum elevation occurs before onset of SE early after LiCl and pilocarpine injections, we tested the hypothesis that intravenous administration of IL-1 receptor antagonists (IL-1ra) may prevent pilocarpine-induced seizures. Animals pre-treated with IL-1ra exhibited significant reduction of SE onset and of BBB damage. Our data support the concept of targeting systemic inflammation and BBB for the prevention of status epilepticus.