Efficacy of radiofrequency in lumbar facet joint pain: a systematic review and meta-analysis of placebo-controlled randomized controlled trials.

BACKGROUND: Lumbar facet joint pain (LFJP) is one of the main causes of chronic low back pain (LBP) and can be treated using radiofrequency (RF) sensory denervation. The aim of this work is to analyze the efficacy of RF in LFJP through a systematic review and meta-analysis of randomized controlled trials (RCTs) with placebo control. MATERIALS AND METHODS: A systematic search was conducted in the Medline (PubMed), Scopus, Web of Science databases, and the Cochrane Central Register of Controlled Trials (CENTRAL). The variables of interest were pain, functional status, quality of life (QoL), and global perceived effect (GPE) measured at different time intervals: short (< 3 months), medium (> 3 and < 12 months), and long term (> 12 months). RESULTS: Eight RCTs with placebo control were included. RF showed significant benefits over placebo in pain relief in the short (MD - 1.01; 95% CI - 1.98 to -0.04; p = 0.04), medium (MD - 1.42; 95% CI - 2.41 to - 0.43; p = 0.005), and long term (MD - 1.12; 95% CI - 1.57 to - 0.68; p < 0.001), as well as improvement in functional disability in the short (SMD - 0.94; 95% CI - 1.73 to - 0.14; p = 0.02) and long term (SMD - 0.74; 95% CI - 1.09 to - 0.39; p < 0.001). No statistically significant differences were observed in QoL or quantitative GPE, but benefits for RF were observed in dichotomous GPE in the medium (OR 0.19; 95% CI 0.07-0.52; p = 0.001) and long term (OR 0.22; 95% CI 0.06-0.78; p = 0.02). Subgroup analyses showed more benefits for RF in LBP < 1 year in the short term and in RCTs that did not require performing an MRI for patient selection. CONCLUSIONS: RF demonstrated significant improvement in pain and functionality, but the benefits in terms of QoL and GPE are inconclusive. Future clinical trials should investigate the long-term effects of RF, its impact on quality of life, and define appropriate criteria for patient selection.

SIRT6 stabilization and cytoplasmic localization in macrophages regulates acute and chronic inflammation in mice.

Acute and chronic inflammations are key homeostatic events in health and disease. Sirtuins (SIRTs), a family of NAD-dependent protein deacylases, play a pivotal role in the regulation of these inflammatory responses. Indeed, SIRTs have anti-inflammatory effects through a myriad of signaling cascades, including histone deacetylation and gene silencing, p65/RelA deacetylation and inactivation, and nucleotide­binding oligomerization domain, leucine rich repeat, and pyrin domain­containing protein 3 inflammasome inhibition. Nevertheless, recent findings show that SIRTs, specifically SIRT6, are also necessary for mounting an active inflammatory response in macrophages. SIRT6 has been shown to positively regulate tumor necrosis factor alpha (TNFα) secretion by demyristoylating pro-TNFα in the cytoplasm. However, how SIRT6, a nuclear chromatin-binding protein, fulfills this function in the cytoplasm is currently unknown. Herein, we show by Western blot and immunofluorescence that in macrophages and fibroblasts there is a subpopulation of SIRT6 that is highly unstable and quickly degraded via the proteasome. Upon lipopolysaccharide stimulation in Raw 264.7, bone marrow, and peritoneal macrophages, this population of SIRT6 is rapidly stabilized and localizes in the cytoplasm, specifically in the vicinity of the endoplasmic reticulum, promoting TNFα secretion. Furthermore, we also found that acute SIRT6 inhibition dampens TNFα secretion both in vitro and in vivo, decreasing lipopolysaccharide-induced septic shock. Finally, we tested SIRT6 relevance in systemic inflammation using an obesity-induced chronic inflammatory in vivo model, where TNFα plays a key role, and we show that short-term genetic deletion of SIRT6 in macrophages of obese mice ameliorated systemic inflammation and hyperglycemia, suggesting that SIRT6 plays an active role in inflammation-mediated glucose intolerance during obesity.

A field test of the dilution effect hypothesis in four avian multi-host pathogens.

The Dilution Effect Hypothesis (DEH) argues that greater biodiversity lowers the risk of disease and reduces the rates of pathogen transmission since more diverse communities harbour fewer competent hosts for any given pathogen, thereby reducing host exposure to the pathogen. DEH is expected to operate most intensely in vector-borne pathogens and when species-rich communities are not associated with increased host density. Overall, dilution will occur if greater species diversity leads to a lower contact rate between infected vectors and susceptible hosts, and between infected hosts and susceptible vectors. Field-based tests simultaneously analysing the prevalence of several multi-host pathogens in relation to host and vector diversity are required to validate DEH. We tested the relationship between the prevalence in house sparrows (Passer domesticus) of four vector-borne pathogens-three avian haemosporidians (including the avian malaria parasite Plasmodium and the malaria-like parasites Haemoproteus and Leucocytozoon) and West Nile virus (WNV)-and vertebrate diversity. Birds were sampled at 45 localities in SW Spain for which extensive data on vector (mosquitoes) and vertebrate communities exist. Vertebrate censuses were conducted to quantify avian and mammal density, species richness and evenness. Contrary to the predictions of DEH, WNV seroprevalence and haemosporidian prevalence were not negatively associated with either vertebrate species richness or evenness. Indeed, the opposite pattern was found, with positive relationships between avian species richness and WNV seroprevalence, and Leucocytozoon prevalence being detected. When vector (mosquito) richness and evenness were incorporated into the models, all the previous associations between WNV prevalence and the vertebrate community variables remained unchanged. No significant association was found for Plasmodium prevalence and vertebrate community variables in any of the models tested. Despite the studied system having several characteristics that should favour the dilution effect (i.e., vector-borne pathogens, an area where vector and host densities are unrelated, and where host richness is not associated with an increase in host density), none of the relationships between host species diversity and species richness, and pathogen prevalence supported DEH and, in fact, amplification was found for three of the four pathogens tested. Consequently, the range of pathogens and communities studied needs to be broadened if we are to understand the ecological factors that favour dilution and how often these conditions occur in nature.

Organotin(IV)-Decorated Graphene Quantum Dots as Dual Platform for Molecular Imaging and Treatment of Triple Negative Breast Cancer.

The pharmacological activity of organotin(IV) complexes in cancer therapy is well recognized but their large applicability is hampered by their poor water solubility. Hence, carbon dots, in particular nitrogen-doped graphene quantum dots (NGQDs), may be a promising alternative for the efficient delivery of organotin(IV) compounds as they have a substantial aqueous solubility, a good chemical stability, and non-toxicity as well as a bright photoluminescence that make them ideal for theranostic applications against cancer. Two different multifunctional nanosystems have been synthesized and fully characterized based on two fragments of organotin-based cytotoxic compounds and 4-formylbenzoic acid (FBA), covalently grafted onto the NGQDs surface. Subsequently, an in vitro determination of the therapeutic and theranostic potential of the achieved multifunctional systems was carried out. The results showed a high cytotoxic potential of the NGQDs-FBA-Sn materials against breast cancer cell line (MDA-MB-231) and a lower effect on a non-cancer cell line (kidney cells, HEK293T). Besides, thanks to their optical properties, the dots enabled their fluorescence molecular imaging in the cytoplasmatic region of the cells pointing towards a successful cellular uptake and a release of the metallodrug inside cancer cells (NGQDs-FBA-Sn).

Biological Use of Nanostructured Silica-Based Materials Functionalized with Metallodrugs: The Spanish Perspective.

Since the pioneering work of Vallet-Regí's group on the design and synthesis of mesoporous silica-based materials with therapeutic applications, during the last 15 years, the potential use of mesoporous silica nanostructured materials as drug delivery vehicles has been extensively explored. The versatility of these materials allows the design of a wide variety of platforms that can incorporate numerous agents of interest (fluorophores, proteins, drugs, etc.) in a single scaffold. However, the use of these systems loaded with metallodrugs as cytotoxic agents against different diseases and with distinct therapeutic targets has been studied to a much lesser extent. This review will focus on the work carried out in this field, highlighting both the pioneering and recent contributions of Spanish groups that have synthesized a wide variety of systems based on titanium, tin, ruthenium, copper and silver complexes supported onto nanostructured silica. In addition, this article will also discuss the importance of the structural features of the systems for evaluating and modulating their therapeutic properties. Finally, the most interesting results obtained in the study of the potential therapeutic application of these metallodrug-functionalized silica-based materials against cancer and bacteria will be described, paying special attention to preclinical trials in vivo.

New Carbonate-Based Materials and Study of Cytotoxic Capacity in Cancer Cells.

Calcium carbonate, one of the most commonly found biominerals produced by organisms, has shown great potential for the development of systems with biological applications due to its excellent biocompatibility, biodegradability, and simple chemical composition. Here, we focus on the synthesis of various carbonate-based materials with vaterite phase control and their subsequent functionalization for applications in treating glioblastoma, one of the most limiting tumors currently without effective treatments. The incorporation of l-cysteine into the systems increased cell selectivity while the incorporation of manganese supplied the materials with cytotoxic capacity. Extensive characterization of the systems by infrared spectroscopy, ultraviolet-visible spectroscopy, X-ray diffraction, X-ray fluorescence, and transmission electron microscopy confirmed the incorporation of the different fragments causing selectivity and cytotoxicity to the systems. To verify their therapeutic activity, the vaterite-based materials were tested in the CT2A cell line (murine glioma) and compared to SKBR3 (breast cancer) and HEK-293T (human kidney) cell lines. These studies on the cytotoxicity of the materials have shown promising results that can encourage future in vivo studies in glioblastoma models.

Principles, Advances, and Perspectives of Anaerobic Digestion of Lipids.

Several problems associated with the presence of lipids in wastewater treatment plants are usually overcome by removing them ahead of the biological treatment. However, because of their high energy content, waste lipids are interesting yet challenging pollutants in anaerobic wastewater treatment and codigestion processes. The maximal amount of waste lipids that can be sustainably accommodated, and effectively converted to methane in anaerobic reactors, is limited by several problems including adsorption, sludge flotation, washout, and inhibition. These difficulties can be circumvented by appropriate feeding, mixing, and solids separation strategies, provided by suitable reactor technology and operation. In recent years, membrane bioreactors and flotation-based bioreactors have been developed to treat lipid-rich wastewater. In parallel, the increasing knowledge on the diversity of complex microbial communities in anaerobic sludge, and on interspecies microbial interactions, contributed to extend the knowledge and to understand more precisely the limits and constraints influencing the anaerobic biodegradation of lipids in anaerobic reactors. This critical review discusses the most important principles underpinning the degradation process and recent key discoveries and outlines the current knowledge coupling fundamental and applied aspects. A critical assessment of knowledge gaps in the field is also presented by integrating sectorial perspectives of academic researchers and of prominent developers of anaerobic technology.

Percutaneous vertebroplasty versus conservative treatment and placebo in osteoporotic vertebral fractures: meta-analysis and critical review of the literature.

OBJECTIVES: To assess the current evidence regarding the efficacy of percutaneous vertebroplasty (PVP) over conservative treatment (CT) and placebo in osteoporotic vertebral fractures (OVFs) by performing a meta-analysis of randomized controlled trials (RCTs). MATERIALS AND METHODS: A systematic search was conducted on PubMed, EMBASE, and Cochrane databases. The main outcomes were pain relief, improvement of functional disability, and quality of life at different time points: short-term (1-2 weeks), medium-term (1-3 months), and long-term (≥ 6 months). Subgroup analyses based on time from fracture onset and sham procedure were also performed. RESULTS: A total of 14 RCTs were included in the meta-analysis. PVP showed significant benefits over CT in all outcomes, but slight-to-none clear differences over placebo. Subgroup analyses revealed that PVP performed in fractures < 6 weeks provided superior short-term pain relief than the control group (p = .02), and better quality of life in the medium-term (p = .03) and long-term (p = .006). Placebo based on infiltrating the skin alone was significantly inferior to PVP at most time points in all outcomes, but no significant differences between PVP and placebo were found when the sham procedure consisted of infiltrating both the skin and periosteum. CONCLUSIONS: PVP showed significant advantages over CT in terms of efficacy, but benefits were more limited when compared to placebo. In addition, benefits of PVP are more prominent in recent OVFs. Differences in the sham procedure or criteria regarding patient's selection/allocation seem to be the main causes of disparity in previous RCTs. KEY POINTS: • Previous RCTs showed significant advantages of PVP over CT in terms of efficacy, but benefits were more limited when compared to placebo. • Differences in patient allocation or in the sham procedure might explain the lack of benefits of PVP versus placebo found in previous RCTs. • Despite controversial opinions, PVP should be offered to patients with OVFs as an alternative option to conservative treatment.

Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects.

We have designed and synthesized two novel cobalt coordination compounds using bumetanide (bum) and indomethacin (ind) therapeutic agents. The anti-inflammatory effects of cobalt metal complexes with ind and bum were assayed in lipopolysaccharide stimulated RAW 264.7 macrophages by inhibition of nitric oxide production. Firstly, we determined the cytotoxicity and the anti-inflammatory potential of the cobalt compounds and ind and bum ligands in RAW 264.7 cells. Indomethacin-based metal complex was able to inhibit the NO production up to 35% in a concentration-dependent manner without showing cytotoxicity, showing around 6-37 times more effective than indomethacin. Cell cycle analysis showed that the inhibition of NO production was accompanied by a reversion of the differentiation processes in LPS-stimulated RAW 264.7 cells, due to a decreased of cell percentage in G0/G1 phase, with the corresponding increase in the number of cells in S phase. These two materials have mononuclear structures and show slow relaxation of magnetization. Moreover, both compounds show anti-diabetic activity with low in vitro cell toxicities. The formation of metal complexes with bioactive ligands is a new and promising strategy to find new compounds with high and enhanced biochemical properties and promises to be a field of great interest.

Tacrolimus rescues the signaling and gene expression signature of endothelial ALK1 loss-of-function and improves HHT vascular pathology.

Hereditary hemorrhagic telangiectasia (HHT) is a highly debilitating and life-threatening genetic vascular disorder arising from endothelial cell (EC) proliferation and hypervascularization, for which no cure exists. Because HHT is caused by loss-of-function mutations in bone morphogenetic protein 9 (BMP9)-ALK1-Smad1/5/8 signaling, interventions aimed at activating this pathway are of therapeutic value. We interrogated the whole-transcriptome in human umbilical vein ECs (HUVECs) and found that ALK1 signaling inhibition was associated with a specific pro-angiogenic gene expression signature, which included a significant elevation of DLL4 expression. By screening the NIH clinical collections of FDA-approved drugs, we identified tacrolimus (FK-506) as the most potent activator of ALK1 signaling in BMP9-challenged C2C12 reporter cells. In HUVECs, tacrolimus activated Smad1/5/8 and opposed the pro-angiogenic gene expression signature associated with ALK1 loss-of-function, by notably reducing Dll4 expression. In these cells, tacrolimus also inhibited Akt and p38 stimulation by vascular endothelial growth factor, a major driver of angiogenesis. In the BMP9/10-immunodepleted postnatal retina-a mouse model of HHT vascular pathology-tacrolimus activated endothelial Smad1/5/8 and prevented the Dll4 overexpression and hypervascularization associated with this model. Finally, tacrolimus stimulated Smad1/5/8 signaling in C2C12 cells expressing BMP9-unresponsive ALK1 HHT mutants and in HHT patient blood outgrowth ECs. Tacrolimus repurposing has therefore therapeutic potential in HHT.

Short term comparison between blind and ultrasound guided injection in morton neuroma.

OBJECTIVE: The aim of this work is to compare the effectiveness of blind and ultrasound-guided injection for Morton's neuroma (MN) to determine which is more appropriate as the initial procedure in conservative treatment. METHODS: This is an evaluator-blinded randomised trial. Of the 56 included patients, 27 were assigned to the blind group (A) and 29 to the ultrasound-guided group (B). Injection includes 1 ml of 2% mepivacaine and 40 mg of triamcinolone in each web space with MN. The included patients were assessed clinically by VAS score and the Manchester Foot Pain and Disability Score (MFPDS). The follow-up was performed at 15 days, 1 month, 45 days, 2 months, 3 months and 6 months after the initial injection. RESULTS: No differences in age or clinical measurements were found at presentation between group A and group B. At the follow-up, the ultrasound-guided group showed greater symptomatic relief at several stages of the follow-up: 45 days (VAS 3.0 ± 0.5 versus 5.5 ± 0.5, p = 0.001; MFPDS: 32.2 ± 1.8 versus 38.8 ± 2.0, p = 0.018), 2 months (VAS: 3.1 ± 0.5 versus 5.6 ± 0.5, p = 0.002; MFPDS: 31.5 ± 1.9 versus 38.5 ± 2.1, p = 0.020) and 3 months (VAS: 3.1 ± 0.4 versus 5.2 ± 0.6, p = 0.010; MFPDS: 31.2 ± 1.9 versus 37.7 ± 2.4, p = 0.047). CONCLUSION: Injection of MN under ultrasound guidance provides a statistically significant improvement at some stages of the follow-up (45 days, 2 and 3 months), compared with blind injection. KEY POINTS: • Ultrasound-guided steroid injections in Morton's neuroma provide short-term pain relief to over 60% of the patients. • Ultrasound-guided injections in Morton's neuroma lead to a higher percentage of short-term pain relief than blind injections. • Ultrasound-guided injections in Morton's neuroma lead to a lower percentage of skin side effects than blind injections.

Vertebral metastases from neuroendocrine tumours: How to avoid false positives on 68Ga-DOTA-TOC PET using CT pattern analysis?

OBJECTIVES: To develop criteria to improve discrimination between vertebral metastases from neuroendocrine tumours (NETs) and benign bone lesions on PET combined with CT using DOTA-D-Phe1-Tyr3-octreotide labelled with gallium-68 (68Ga-DOTA-TOC). METHODS: In 535 NET patients, 68Ga-DOTA-TOC PET/CT examinations were reviewed retrospectively for vertebral CT lesions and/or PET foci. For each vertebral PET abnormality, appearance on CT, biological volume (BV), standardized uptake value (SUVmax) and ratios to those of reference organs were determined. All vertebral abnormalities were characterized as a metastasis, a typical vertebral haemangioma (VH) or other benign lesion. RESULTS: In 79 patients (14.8 %), we found 107 metastases, 34 VHs and 31 other benign lesions in the spine. The optimal cut-off values to differentiate metastases from benign lesions were BV ≥0.72 cm3, SUVmax ≥2, SUVmax ratio to a reference vertebra ≥2.1, to liver ≥0.28 and to spleen ≥0.14. They corresponded to lesion-based 68Ga-DOTA-TOC PET/CT sensitivity of 87 %, 98 %, 97 %, 99 % and 94 %, and specificity of 55 %, 100 %, 90 %, 97 %, 100 %, respectively. CONCLUSIONS: The high sensitivity of 68Ga-DOTA-TOC-PET/CT in detecting NET vertebral metastases was confirmed; this study showed that specificity could be improved by combining CT features and quantifying 68Ga-DOTA-TOC uptake. KEY POINTS: • Bone metastases in neuroendocrine tumours correlate with prognosis. • Benign bone lesions may mimic metastases on 68 Ga-DOTA-TOC PET/CT imaging. • The specific polka-dot CT pattern may be missing in some vertebral haemangiomas. • Lesion atypical for haemangiomas can be better characterized by quantifying 68 Ga-DOTA-TOC uptake.

CALHM1 ion channel elicits amyloid-ß clearance by insulin-degrading enzyme in cell lines and in vivo in the mouse brain.

Alzheimer's disease is characterized by amyloid-ß (Aß) peptide accumulation in the brain. CALHM1, a cell-surface Ca(2+) channel expressed in brain neurons, has anti-amyloidogenic properties in cell cultures. Here, we show that CALHM1 controls Aß levels in vivo in the mouse brain through a previously unrecognized mechanism of regulation of Aß clearance. Using pharmacological and genetic approaches in cell lines, we found that CALHM1 ion permeability and extracellular Ca(2+) were required for the Aß-lowering effect of CALHM1. Aß level reduction by CALHM1 could be explained by an increase in extracellular Aß degradation by insulin-degrading enzyme (IDE), extracellular secretion of which was strongly potentiated by CALHM1 activation. Importantly, Calhm1 knockout in mice reduced IDE enzymatic activity in the brain, and increased endogenous Aß concentrations by up to ∼50% in both the whole brain and primary neurons. Thus, CALHM1 controls Aß levels in cell lines and in vivo by facilitating neuronal and Ca(2+)-dependent degradation of extracellular Aß by IDE. This work identifies CALHM1 ion channel as a potential target for promoting amyloid clearance in Alzheimer's disease.

Modified acoustic transmission tube apparatus incorporating an active downstream termination.

Current techniques for measuring normal incidence sound transmission loss with a modified impedance tube, or transmission tube, require setting up two different absorbing termination loads at the end of the downstream tube [ASTM E2611-09, Standard Test Method for Measurement of Normal Incidence Sound Transmission of Acoustical Materials Based on the Transfer Matrix Method (American Society for Testing and Materials, West Conshohocken, 2009)]. The process of physically handling the two required passive absorbing loads is a possible source of measurement errors, which are mainly due to changes in sample test position, or in test setup re-assembly, between measurements. In this paper, a modified transmission tube apparatus is proposed for non-intrusively changing the downstream acoustic load by means of a combined passive-active termination. It provides a controlled variable sound absorption which simplifies the setup of standard two-load techniques, without the need of physically handling the apparatus during the tests. This virtually eliminates the risk of errors associated with the physical manipulation of the two passive terminations. Transmission loss measurements in some representative test conditions are reported, showing improvements over current implementations, in reducing by approximately 50% the measurement variations associated with the setup of the two required absorbing terminations. Measurement results agree within 0.4 dB (maximum difference in high resolution broadband), and 0.04 dB (mean difference in 1/3-octave bands), with those obtained using standard passive two-load methods.

Culex pipiens forms and urbanization: effects on blood feeding sources and transmission of avian Plasmodium.

BACKGROUND: The wide spread mosquito Culex pipiens pipiens have two forms molestus and pipiens which frequently hybridize. The two forms have behavioural and physiological differences affecting habitat requirements and host selection, which may affect the transmission dynamic of Cx. p. pipiens-borne diseases. METHODS: During 2013, blood engorged Cx. p. pipiens mosquitoes were captured in urban, rural and natural areas from Southern Spain. In 120 mosquitoes, we identified the blood meal origin at vertebrate species/genus level and the mosquito form. The presence and molecular lineage identity of avian malaria parasites in the head-thorax of each mosquito was also analysed. RESULTS: Mosquitoes of the form pipiens were more frequently found in natural than in urban areas. The proportion of Cx. pipiens form molestus and hybrids of the two forms did not differ between habitat categories. Any significant difference in the proportion of blood meals on birds between forms was found. Birds were the most common feeding source for the two forms and their hybrids. Among mammals, dogs and humans were the most common hosts. Two Plasmodium and one Haemoproteus lineages were found in mosquitoes, with non-significant differences between forms. CONCLUSION: This study supports a differential distribution of Cx. p. pipiens form pipiens between urban and natural areas. Probably due to the similar feeding sources of both mosquito forms and their hybrids here, all of them may frequently interact with avian malaria parasites playing a role in the transmission of Plasmodium.

Spinal interventions. / Intervencionismo en la columna.

We review the state of the art in imaging-guided percutaneous interventional procedures used to diagnose and/or treat the diverse causes of back pain. These procedures can be used for diagnosis, treatment, or both. They are focused on the vertebral bodies, the facet joints, the intervertebral discs, and the nerve structures.

Comparison of ultrasound and fluoroscopic guidance for injection in CT arthrography and MR arthrography of the hip. / Comparación de las técnicas de inyección ecográfica y radioscópica en artro-TC y artro-RM de cadera.

OBJECTIVE: To evaluate the usefulness of ultrasound-guided versus fluoroscopy-guided injection in CT arthrography and MR arthrography. MATERIAL AND METHODS: We reviewed all CT arthrography and MR arthrography studies done at our center between October 1, 2014 and October 1, 2015. We analyzed 32 studies: 26 with fluoroscopic guidance and 6 with ultrasound guidance. We compared the two techniques on the following parameters: presence of sufficient contrast material in the joint, extravasation or injection of contrast material in the soft tissues (presence of contrast material in the psoas or other soft tissues), and intra-articular gas bubbles. We used SPSS V. 20 to compare the techniques with Pearson's chi-square tests. RESULTS: Contrast material was observed in soft tissues in 56.3% of ultrasound-guided injections, making 6.3% of the procedures invalid for diagnostic purposes. Extravasation of contrast material was observed in 53.8% of fluoroscopy-guided procedures, making 3.8% invalid for diagnostic purposes. Intra-articular gas was observed in 21.9% of ultrasound-guided studies and in 38.5% of fluoroscopy-guided studies. None of the differences between techniques were statistically significant at p<0.05. CONCLUSIONS: Our study shows that ultrasound is as useful as fluoroscopy for injecting contrast material for CT arthroscopy and MR arthroscopy; ultrasound has the advantage of not using ionizing radiation.

Individual identification of endangered species using mosquito blood meals: a proof-of-concept study in Iberian lynx.

Host identification from mosquito blood meals has been routinely used to identify the feeding preferences of insects in studies on transmission of vector-borne pathogens. Here, we identified for the first time the susceptibility of the endangered Iberian lynx (Lynx pardinus) to the attack of a wild mosquito female, the mosquito Anopheles atroparvus. Furthermore, we used 11 microsatellite markers to test for the utility of vertebrate DNA isolated from insect blood meals for individual identification of wildlife. Only the three smallest markers were successfully amplified; however, this genotype did not match with any of the previously genotyped individuals in southern Spain. These results support the use of DNA from mosquito blood meals as a non-invasive source of DNA and a powerful tool on epidemiological and conservation biology studies. However, as may be the case of other non-invasive sampling methods, the utility of this technique is probably limited by the quantity and quality of vertebrate DNA.

Anti-cancer applications of titanocene-functionalised nanostructured systems: an insight into cell death mechanisms.

A series of alkenyl-substituted titanocene compounds have been supported on the mesoporous silica-based material KIT-6. The corresponding functionalised materials were completely characterised by different techniques (solid-state multinuclear NMR spectroscopy, IR spectroscopy, N2 adsorption-desorption isotherms, X-ray fluorescence and diffraction, SEM and TEM) to observe the incorporation of the titanocene derivatives on the external surface of the material KIT-6. Both the titanocene compounds and the materials were tested in vitro against a wide variety of human cancer and normal cell lines. A very high cytotoxicity of the synthesised titanocene derivatives (IC50 values in the range of those described in the literature for the most active cytotoxic titanocene compounds), with selectivity towards cancer cell lines was observed. The cytotoxic activity of the materials is the highest reported to date for titanocene-functionalised materials. In addition, higher Ti uptake (from 4 to 23% of the initial amount of Ti) of the cells treated with materials was observed with respect to those treated with "free" titanocene derivatives (which gave Ti uptake values from 0.4 to 4.6% of the initial amount of Ti). Additional experiments with the titanocene derivatives and the functionalised materials revealed that changes to the morphological and functional dynamics of apoptosis occurred when the active titanocene species were incorporated into mesoporous materials. In addition, the materials could induce programmed cell death in tumour cell populations by impairing the damaged DNA repair mechanisms and by upregulation of intrinsic and extrinsic apoptotic signalling pathways.