Effectiveness of surgery for lumbar spinal stenosis

Background: The management of spinal stenosis by surgery has increased rapidly in the past two decades, however, there is still controversy regarding the efficacy of surgery for this condition. Our aim was to investigate the efficacy and comparative effectiveness of surgery in the management of patients with lumbar spinal stenosis. Methods: Electronic searches were performed on MEDLINE, EMBASE, AMED, CINAHL, Web of Science, LILACS and Cochrane Library from inception to November 2014. Hand searches were conducted on included articles and relevant reviews. We included randomised controlled trials evaluating surgery compared to no treatment, placebo/sham, or to another surgical technique in patients with lumbar spinal stenosis. Primary outcome measures were pain, disability, recovery and quality of life. The PEDro scale was used for risk of bias assessment. Data were pooled with a random-effects model, and the GRADE approach was used to summarise conclusions. Results: Nineteen published reports (17 trials) were included. No trials were identified comparing surgery to no treatment or placebo/sham. Pooling revealed that decompression plus fusion is not superior to decompression alone for pain (mean difference -3.7, 95% confidence interval -15.6 to 8.1), disability (mean difference 9.8, 95% confidence interval -9.4 to 28.9), or walking ability (risk ratio 0.9, 95% confidence interval 0.4 to 1.9). Interspinous process spacer devices are slightly more effective than decompression plus fusion for disability (mean difference 5.7, 95% confidence interval 1.3 to 10.0), but they resulted in significantly higher reoperation rates when compared to decompression alone (28% v 7%, P < 0.001). There are no differences in the effectiveness between other surgical techniques for our main outcomes. Conclusions: The relative efficacy of various surgical options for treatment of spinal stenosis remains uncertain. Decompression plus fusion is not more effective than decompression alone. Interspinous process spacer devices result in higher reoperation rates than bony decompression

Anopheles aquasalis Infected by Plasmodium vivax Displays Unique Gene Expression Profiles when Compared to Other Malaria Vectors and Plasmodia

Malaria affects 300 million people worldwide every year and is endemic in 22 countries in the Americas where transmission occurs mainly in the Amazon Region. Most malaria cases in the Americas are caused by Plasmodium vivax, a parasite that is almost impossible to cultivate in vitro, and Anopheles aquasalis is an important malaria vector. Understanding the interactions between this vector and its parasite will provide important information for development of disease control strategies. To this end, we performed mRNA subtraction experiments using A. aquasalis 2 and 24 hours after feeding on blood and blood from malaria patients infected with P. vivax to identify changes in the mosquito vector gene induction that could be important during the initial steps of infection. A total of 2,138 clones of differentially expressed genes were sequenced and 496 high quality unique sequences were obtained. Annotation revealed 36% of sequences unrelated to genes in any database, suggesting that they were specific to A. aquasalis. A high number of sequences (59%) with no matches in any databases were found 24 h after infection. Genes related to embryogenesis were down-regulated in insects infected by P. vivax. Only a handful of genes related to immune responses were detected in our subtraction experiment. This apparent weak immune response of A. aquasalis to P. vivax infection could be related to the susceptibility of this vector to this important human malaria parasite. Analysis of some genes by real time PCR corroborated and expanded the subtraction results. Taken together, these data provide important new information about this poorly studied American malaria vector by revealing differences between the responses of A. aquasalis to P. vivax infection, in relation to better studied mosquito-Plasmodium pairs. These differences may be important for the development of malaria transmission-blocking strategies in the Americas

Has the reporting quality of published randomised controlled trial protocols improved since the SPIRIT statement? A methodological study

OBJECTIVES: To determine the reporting quality of published randomised controlled trial (RCT) protocols before and after the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statemen

Regulation of glucose and fatty acid metabolism in skeletal muscle during contraction

O ciclo glicose-ácido graxo explica a preferência do tecido muscular pelos ácidos graxos durante atividade moderada de longa duração. Em contraste, durante o exercício de alta intensidade, há aumento na disponibilidade e na taxa de oxidação de glicose. A produção de espécies reativas de oxigênio (EROs) durante a atividade muscular sugere que o balanço redox intracelular é importante na regulação do metabolismo de lipídios/carboidratos. As EROs diminuem a atividade do ciclo de Krebs e aumentam a atividade da proteína desacopladora mitocondrial. O efeito oposto é esperado durante a atividade moderada. Assim, as questões levantadas nesta revisão são: Por que o músculo esquelético utiliza preferencialmente os lipídios no estado basal e de atividade moderada? Por que o ciclo glicose-ácido graxo falha em exercer seus efeitos durante o exercício intenso? Como o músculo esquelético regula o metabolismo de lipídios e carboidratos em regime envolvendo o ciclo contração-relaxamento.The glucose-fatty acid cycle explains the preference for fatty acid during moderate and long duration physical exercise. In contrast, there is a high glucose availability and oxidation rate in response to intense physical exercise. The reactive oxygen species (ROS) production during physical exercise suggests that the redox balance is important to regulate of lipids/carbohydrate metabolism. ROS reduces the activity of the Krebs cycle, and increases the activity of mitochondrial uncoupling proteins. The opposite effects happen during moderate physical activity. Thus, some issues is highlighted in the present review: Why does skeletal muscle prefer lipids in the basal and during moderate physical activity? Why does glucose-fatty acid fail to carry out their effects during intense physical exercise? How skeletal muscles regulate the lipids and carbohydrate metabolism during the contraction-relaxation cycle

Structurally Related Monoterpenes p-Cymene, Carvacrol and Thymol Isolated from Essential Oil from Leaves of Lippia sidoides Cham. (Verbenaceae) Protect Mice against Elastase-Induced Emphysema

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes (p-cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). Methods: Mices received porcine pancreatic elastase (PPE) and were treated with p-cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. Results: In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1 beta, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-kappa B-positive cells in lung parenchyma (p < 0.05). All treatments attenuated levels of 8-iso-PGF2 alpha but only thymol was able to reduced exhaled nitric oxide (p < 0.05). Conclusion: Monoterpenes p-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Laboratorio de Investigacao Medica, Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo (LIM)Univ Fed Sao Paulo, Dept Biol Sci, BR-09913030 Diadema, BrazilUniv Sao Paulo, Sch Med, Dept Med, BR-01246903 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Exact Sci & Earth, BR-09913030 Diadema, BrazilFed Univ ABC, Ctr Nat Sci & Humanities, BR-09606045 Santo Andre, SP, BrazilUniv Fed Sao Paulo, Dept Biosci, Campus Baixada Santista, BR-11015020 Santos, SP, BrazilDepartment of Biological Science, Universidade Federal de São Paulo, Diadema 09913-030, BrazilDepartment of Exact Science and Earth, Universidade Federal de São Paulo, Diadema 09913-030, BrazilDepartment of Bioscience, Federal University of São Paulo, Campus Baixada Santista, Santos 11015-020, SP, BrazilCNPq: 300546/2012-2CNPq: 304465/2012-7CNPq: 476877/2012-1CNPq: 306278/2015-4FAPESP: 2011/51739-0FAPESP: 2013/02881-4FAPESP: 2008/55359-5FAPESP: 2015/11936-2FAPESP: 2014/25689-4LIM: LIM20Web of Scienc

Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons

During corticogenesis, pyramidal neurons (~80% of cortical neurons) arise from the ventricular zone, pass through a multipolar stage to become bipolar and attach to radial glia[superscript 1, 2], and then migrate to their proper position within the cortex[superscript 1, 3]. As pyramidal neurons migrate radially, they remain attached to their glial substrate as they pass through the subventricular and intermediate zones, regions rich in tangentially migrating interneurons and axon fibre tracts. We examined the role of lamellipodin (Lpd), a homologue of a key regulator of neuronal migration and polarization in Caenorhabditis elegans, in corticogenesis. Lpd depletion caused bipolar pyramidal neurons to adopt a tangential, rather than radial-glial, migration mode without affecting cell fate. Mechanistically, Lpd depletion reduced the activity of SRF, a transcription factor regulated by changes in the ratio of polymerized to unpolymerized actin. Therefore, Lpd depletion exposes a role for SRF in directing pyramidal neurons to select a radial migration pathway along glia rather than a tangential migration mode.Ruth L. Kirschstein National Research Service Award (grant F32- GM074507)National Institutes of Health (U.S.) (grant # GM068678

Genetic Markers Associated to Dyslipidemia in HIV-Infected Individuals on HAART

This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, and LDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%). APOE (rs429358 and rs7412) genotypes and APOA5 −1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). The APOA5 −1131T>C (rs662799) and SCAP 2386A>G (rs12487736) polymorphisms were significantly associated with high-density-lipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both the APOB SP Ins/Del (rs17240441) and APOB XbaI (rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen

Li-Fraumeni-like syndrome associated with a large BRCA1 intragenic deletion

Background: Li-Fraumeni (LFS) and Li-Fraumeni-like (LFL) syndromes are associated to germline TP53 mutations, and are characterized by the development of central nervous system tumors, sarcomas, adrenocortical carcinomas, and other early-onset tumors. Due to the high frequency of breast cancer in LFS/LFL families, these syndromes clinically overlap with hereditary breast cancer (HBC). Germline point mutations in BRCA1, BRCA2, and TP53 genes are associated with high risk of breast cancer. Large rearrangements involving these genes are also implicated in the HBC phenotype. Methods: We have screened DNA copy number changes by MLPA on BRCA1, BRCA2, and TP53 genes in 23 breast cancer patients with a clinical diagnosis consistent with LFS/LFL; most of these families also met the clinical criteria for other HBC syndromes. Results: We found no DNA copy number alterations in the BRCA2 and TP53 genes, but we detected in one patient a 36.4 Kb BRCA1 microdeletion, confirmed and further mapped by array-CGH, encompassing exons 9-19. Breakpoints sequencing analysis suggests that this rearrangement was mediated by flanking Alu sequences. Conclusion: This is the first description of a germline intragenic BRCA1 deletion in a breast cancer patient with a family history consistent with both LFL and HBC syndromes. Our results show that large rearrangements in these known cancer predisposition genes occur, but are not a frequent cause of cancer susceptibility.Brazilian National Institute of Science and Technology in OncogenomicsBrazilian National Institute of Science and Technology in Oncogenomics [FAPESP 2008/57887-9, CNPq 573589/08-9]Fundo de Incentivo a Pesquisa (FIP)Fundo de Incentivo a Pesquisa (FIPE)Hospital de Clinicas de Porto Alegre [04-081, 09-115]Hospital de Clinicas de Porto AlegreFAPERGS (Brazil)FAPERGS, BrazilCAPES [Process: 2317/10-9]CAPE