Fusion rate following extreme lateral lumbar interbody fusion

Introduction

Lumbar fusion has been found to be a clinically effective procedure in adult patients. The lateral transpsoas approach allows for direct visualization of the intervertebral space, significant support of the vertebral anterior column, while avoiding the complications associated with the posterior procedures. The aim of this study is to determine the fusion rate of inter body fusion using computed tomography in patients treated by extreme lateral intersomatic fusion (XLIF) technique.

Materials and methods

All patients intervened by XLIF procedure between 2009 and 2013 by a single operating team at a single institution were recruited for this study. A clinical evaluation and a CT scan of the involved spinal segments were then performed with at least 1-year follow-up following the standard clinical practice in the center.

Results

A total of 77 patients met inclusion criteria, of which 53 were available for review with a mean follow-up of 34.5 (12–62) months. A total of 68 (87.1 %) of the 78 operated levels were considered as completely fused, 8 (10.2 %) were considered as stable, probably fused, and 2 (2.6 %) of the operated levels were diagnosed as pseudarthrosis. When stratified by type of graft material complete fusion was obtained in 75 % of patients in which autograft was used to fill the cages, compared to 89 % of patients in which calcium triphosphate was used, and 83 % of patients in which Attrax? was used.

Discussion

Reports of XLIF fusion rate in the literature vary from 85 to 93 % at 1-year follow-up. Fusion rate in our series corroborates data from previous publications. The results of this series confirm that anterior inter body fusion by means of XLIF approach is a technique that achieves high fusion rate and satisfactory clinical outcomes.

     

Haplotype tagging reveals parallel formation of hybrid races in two butterfly species

Genetic variation segregates as linked sets of variants or haplotypes. Haplotypes and linkage are central to genetics and underpin virtually all genetic and selection analysis. Yet, genomic data often omit haplotype information due to constraints in sequencing technologies. Here, we present “haplotagging,” a simple, low-cost linked-read sequencing technique that allows sequencing of hundreds of individuals while retaining linkage information. We apply haplotagging to construct megabase-size haplotypes for over 600 individual butterflies (Heliconius erato and H. melpomene), which form overlapping hybrid zones across an elevational gradient in Ecuador. Haplotagging identifies loci controlling distinctive high- and lowland wing color patterns. Divergent haplotypes are found at the same major loci in both species, while chromosome rearrangements show no parallelism. Remarkably, in both species, the geographic clines for the major wing-pattern loci are displaced by 18 km, leading to the rise of a novel hybrid morph in the center of the hybrid zone. We propose that shared warning signaling (Müllerian mimicry) may couple the cline shifts seen in both species and facilitate the parallel coemergence of a novel hybrid morph in both comimetic species. Our results show the power of efficient haplotyping methods when combined with large-scale sequencing data from natural populations.

Understanding how changes in DNA sequence affect traits and shape the evolution of populations and species has been a defining goal in genetics and evolution (1–3). DNA is naturally organized in the genome as long molecules consisting of linked chromosome segments. Linkage is a core concept in genetics: in genetic mapping, geneticists map causal variants not by tracking the actual mutation but through many otherwise neutral and unremarkable linked variants. Likewise, the detection of selection relies on observing hitchhiking of linked variants rather than seeing the mutation itself. This recognition makes it all the more paradoxical that haplotype information is routinely omitted from most genomic studies as a technical compromise. Lacking haplotype information not only complicates analysis and ancestry reconstruction but also precludes detection of allele-specific expression (4) and chromosome rearrangements and reduces power to detect selective sweeps, even entirely missing them when multiple haplotypes sweep together (5). Instead of sequencing genomes as haplotypes, short-read sequencing produces 150-bp reads. Until long-read platforms become sufficiently accurate and affordable, this lack of haplotype context will continue to impact mapping and genomic studies, particularly those in nonmodel organisms.One way to simplify haplotype reconstruction and inference from sequencing data is to avoid discarding haplotype information in the first place. A promising emerging technique is linked-read (LR) sequencing (6–9), which preserves long-range information via molecular barcoding of long DNA molecules before sequencing. Individual short reads can then be linked via a shared barcode to reconstruct the original haplotype. However, existing options all suffer from high cost, poor scalability, and/or require custom sequencing primers or settings that have thus far prevented them from being applied as the default sequencing platform (SI Appendix, Tables S1 and S2). If LR sequencing could become scalable and affordable, it would significantly advance genetics by enabling the “haplotyping” of entire populations (i.e., the sequencing and systematic discovery of genomic variants as haplotypes in hundreds or even thousands of samples in model and nonmodel organisms alike).Here, we describe a solution called “haplotagging,” a simple and rapid protocol for LR sequencing. Importantly, haplotagging maintains full compatibility with standard Illumina sequencing and can easily scale to large populations with no extra costs. We demonstrate this in three steps. First, we show that direct haplotyping using haplotagging is robust in single human and mouse samples with known haplotypes (“phases”). Next, we show the feasibility of population haplotyping in 245 mice, even with very low-coverage LR sequencing. Finally, we apply haplotagging to investigate the emergence of a hybrid morph in a hybrid zone system in Ecuador featuring 670 individuals of two species of Heliconius butterflies.     

Comparative effect of human and Trypanosoma cruzi calreticulin in wound healing

In orthopaedics, the use of factors that enhance granulation tissue formation and prevent or delay new bone regeneration is sometimes desirable. Calreticulin (CRT), a unique endoplasmic reticulum luminal Ca²⁺‐binding chaperone widely distributed in eukaryotic cells, is involved in many cellular functions. Among them, CRT has an important influence in cutaneous wound healing and diverse processes associated with cutaneous repair, inhibition of angiogenesis, promotion of cell adhesion and antitumour effect. One of the molecules involved in several aspects of the host–parasite interplay is Trypanosoma cruzi calreticulin (TcCRT), which is highly homologous to human calreticulin (HuCRT). Here, recombinant (r)HuCRT and rTcCRT are compared on their abilities to affect fibroblast behaviour in a scratch plate assay, and wound healing in in vivo skin rat models. In molar terms, rTcCRT is three orders of magnitude more efficient than rHuCRT in increasing proliferation and migration of human fibroblasts in vitro. A similar effect was observed in vivo on rat skin wounds and inhibition of bone gap bridging in rabbit unicortical bone osteotomies. Copyright © 2012 John Wiley & Sons, Ltd.     

Recommendations from GESIDA/SEFH/PNS to improve adherence to antiviral treatment (2004)

Since the early days of antiretroviral therapy, adherence has emerged as the milestone of success; in fact, it is the most potent predictor of effectiveness. The main factors related to adherence include the complexity of the therapeutic regimen, adverse effects, psychological problems, alcoholism and active addiction to drugs, lack of social and family support and the patient's beliefs and attitudes about the treatment. Adherence monitoring should be part of the HIV patient's regular care, and should be done with feasible, easily applied methods adapted to the different clinical settings. The minimally acceptable measures should include use of a validated questionnaire, together with data from the Pharmacy Department's drug dispensation registry. All patients that begin HAART or undergo a change of treatment should participate in a treatment education program imparted by health professionals with knowledge and experience in the management of patients with HIV infection. The health team (doctors, pharmacists and nursing professionals) should offer maximum availability to solve the doubts and problems that may occur during treatment. When sub-optimal adherence is detected, intervention strategies based on psychological therapy, educational efforts and personal advice should be attempted, in order to adapt the treatment scheme to the patient's habits and provide solutions to the problem of non-compliance. In certain situations, co-morbid conditions will also require attention. Treatment adherence, being a multidimensional problem, needs a multidisciplinary team approach. The choice of therapy, only one aspect of the multidimensional problem of adherence, must be a careful and individualized decision; however, simpler regimens with regard to the number of pills and daily dose are desirable.     

Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment

OBJECTIVES:Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation in a live Escherichia coli-induced sepsis model in rats.METHODS:Male Wistar rats were administered an intravenous suspension of E. coli bacteria or were subjected to a sham procedure. Three hours after bacterial infusion, the rats were randomized into the following groups: a control group without treatment, a group treated with lactated Ringer''s solution (4 mL/kg, i.v.), and a group treated with lactated Ringer''s solution (4 mL/kg, i.v.) plus ethyl pyruvate (50 mg/kg). At 24 h after bacterial infusion, leukocyte-endothelial interactions were investigated using intravital microscopy, and the expression of P-selectin and intercellular adhesion molecule-1 was evaluated via immunohistochemistry. White blood cell and platelet counts were also determined at baseline and 3 h and 24 h after E. coli inoculation.RESULTS:The non-treated and lactated Ringer''s solution-treated groups exhibited increases in the numbers of rolling leukocytes (∼2.5-fold increase), adherent cells (∼3.0-fold), and migrated cells (∼3.5-fold) compared with the sham group. In contrast, treatment with Ringer''s ethyl pyruvate solution reduced the numbers of rolling, adherent and migrated leukocytes to the levels observed in the sham group. Additionally, the expression of P-selectin and intercellular adhesion molecule-1 was significantly increased on mesenteric microvessels in the non-treated group compared with the sham group (p<0.001). The expression of both adhesion molecules was reduced in the other groups, with ethyl pyruvate being more effective than lactated Ringer''s solution. Infusion of bacteria caused significant leukopenia (3 h), followed by leukocytosis with granulocytosis (24 h). There was also an intense and progressive reduction in the number of platelets. However, no differences were observed after treatment with the different solutions.CONCLUSIONS:The presented data suggest that ethyl pyruvate efficiently reduces the inflammatory response in the mesenteric microcirculation in an experimental model of sepsis induced by live E. coli and is associated, at least in part, with down-regulation of P-selectin and intercellular adhesion molecule-1.     

In vitro antiplasmodial activity of some medicinal plants of Burkina Faso

Malaria remains a major public health problem due to the emergence and spread of Plasmodium falciparum drug resistance. There is an urgent need to investigate new sources of antimalarial drugs which are more effective against Plasmodium falciparum. One of the potential sources of antimalarial drugs is traditional medicinal plants. In this work, we studied the in vitro antiplasmodial activity of chloromethylenic, methanolic, and MeOH/H₂O (1/1) crude extracts and decoction obtained from eight medicinal plants collected in Burkina Faso and of total alkaloids for five plants. Extracts were evaluated in vitro for efficacy against Plasmodium falciparum strain K1, which is resistant to chloroquine, pyrimethamine and proguanil using the fluorescence-based SYBR Green I assay. The antiproliferative activity on human-derived hepatoma cell line HepG2 and Chinese hamster ovary (CHO) cells was evaluated using the 3-[4,5-dimethylthyazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test in order to determine the selectivity index. Among the plant extracts tested for in vitro antiplasmodial activity, 16 were considered to be inactive (with IC₅₀?>?10 μg/ml), six showed a moderate activity (5?<?IC₅₀?≤?10 μg/ml), and six were found to have a good in vitro activity with IC₅₀ value?≤?5 μg/ml. The highest antiplasmodial activity was found for extracts from: the alkaloid leaf extract and the chloromethylenic extracts of Combretum fragrans (IC₅₀?=?3 μg/ml, IC₅₀?=?5 μg/ml), the total alkaloids and the chloromethylenic leaf extracts of Combretum collinum (IC₅₀?=?4 μg/ml), the MeOH/H₂O leaf extract of Terminalia avicennioides (IC₅₀?=?3.5 μg/ml), and the alkaloid leaf extract of Pavetta crassipes (IC₅₀?=?5 μg/ml). Three other extracts showed moderate antiplasmodial activity (5?<?IC₅₀?≤?10 μg/ml): Terminalia avicennioides and Combretum fragrans methanolic extracts and Acacia kirkii alkaloid leaf extract (IC₅₀?=?6.5, 9 and 10 μg/ml respectively). The Terminalia avicennioides crude MeOH/H₂O (80:20 v/v) extract of the leaves was submitted to a successive liquid/liquid extraction with ethylacetate and n-butanol respectively. The extracts were investigated for in vitro antiplasmodial activity and antioxidant properties using DPPH^●, ABTS⁺ and FRAP methods. The ethylacetate extract showed the best antiplasmodial activity (7 μg/ml) and the active constituent was isolated as ellagic acid by bioguided fractionation with an IC₅₀?=?0.2 μM on Plasmodium falciparum and SI?=?152. Besides, Terminalia avicennioides leaf extract and ellagic acid showed a good antioxidant activity. Our finding confirms the importance of investigating the antimalarial activity of plant species used in traditional medicine. Overall, two plants belonging to the Combretaceae family, Combretum fragrans and Combretum collinum appeared to be the best candidates and will be further investigated for their antiplasmodial properties, in order to isolate the molecules responsible for the antiplasmodial activity.     

Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome

Prostate cancer is the second leading cause of cancer death among United States men. However, disease aggressiveness is varied, with low-grade disease often being indolent and high-grade cancer accounting for the greatest density of deaths. Outcomes are also disparate among men with high-grade prostate cancer, with upwards of 65% having disease recurrence even after primary treatment. Identification of men at risk for recurrence and elucidation of the molecular processes that drive their disease is paramount, as these men are the most likely to benefit from multimodal therapy. We previously showed that androgen-induced expression profiles in prostate development are reactivated in aggressive prostate cancers. Herein, we report the down-regulation of one such gene, Sparcl1, a secreted protein, acidic and rich in cysteine (SPARC) family matricellular protein, during invasive phases of prostate development and regeneration. We further demonstrate a parallel process in prostate cancer, with decreased expression of SPARCL1 in high-grade/metastatic prostate cancer. Mechanistically, we demonstrate that SPARCL1 loss increases the migratory and invasive properties of prostate cancer cells through Ras homolog gene family, member C (RHOC), a known mediator of metastatic progression. By using models incorporating clinicopathologic parameters to predict prostate cancer recurrence after treatment, we show that SPARCL1 loss is a significant, independent prognostic marker of disease progression. Thus, SPARCL1 is a potent regulator of cell migration/invasion and its loss is independently associated with prostate cancer recurrence.