Adequate vitamin D level associated with reduced risk of sporadic colorectal cancer

PurposeThe effect of vitamin D level pertinent to colorectal cancer incidence, progression, or mortality risk is complicated, and study findings are mixed. Therefore, we evaluated whether serum vitamin D [25-hydroxyvitamin D, 25(OH)D] is associated with the incidence of sporadic colorectal cancer (CRC).MethodsThis study is a retrospective analysis of the relationship between serum 25(OH)D level and the risk of CRC. Age, sex, body mass index, history of polyp, disease conditions (i.e., diabetes), medications, and other eight vitamins were used as confounding factors. A total of 389 participants were enrolled in this study, including comprising 83 CRC patients without a family history and 306 healthy controls, between January 2020 and March 2021 at the Department of Colorectal Surgery and Endoscope Center at the Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Adjusted smoothing spline plots, subgroup analysis, and multivariate logistic regression analysis were conducted to estimate the relative risk between serum 25(OH)D and sporadic CRC risk.ResultsAfter fully adjusting the confounding factors, it was found that circulating 25(OH)D played a protective role in patients with CRC (OR = 0.76 [0.63, 0.92], p = 0.004) and that an adequate vitamin D level was significantly associated with a reduced CRC risk compared to vitamin D deficiency or sufficiency (OR = 0.31 [0.11, 0.9], p = 0.03). According to this study, statins did not affect the potential protective effects of vitamin D (OR = 1.02 [0.97, 1.08], p = 0.44) and may account for the inverse association between serum 25(OH)D and colorectal cancer.ConclusionAn adequate level of serum 25(OH)D was associated with a reduced CRC risk, especially for the elderly. The finding on the absence of protective effect of vitamin D in the statin use subgroup, suggests it may be one of the substantial contributing confounders, and warrants further investigation

Affirmative action in education and Black Economic Empowerment in the workplace in South Africa since 1994: policies, strengths and limitations

This paper explains the concepts of Affirmative Action (AA) and Black Economic Empowerment (BEE) and the policies developed in post-Apartheid South Africa. It compares it to similar policies adopted in different contexts in Malaysia, India and the U.S.A. It explains and critiques the South African policies on AA and BEE, its history since 1994 and how class has replaced race as the determinant of who succeeds in education and the workplace. It analyses why these policies were essential to address the massive racial divide in education and the workplace at the arrival of democracy in 1994, but also why it has been controversial and racially divisive. The strengths and limitations of these policies are juxtaposed, the way it has benefitted the black and white elites, bolstered the black middle-class but has had little success in addressing the education and job futures of poor, working class black citizens in South Africa. The views of a number of key social analysts in the field are stated to explain the moral, racial, divisive aspects of AA in relation to the international experience and how South Africa is grappling with limited success to bridge the divide between the rich and poor

The interaction between XBP1 and eNOS contributes to endothelial cell migration

Trabalho final de mestrado integrado em Medicina área científica de Urologia, apresentado á Faculdade de Medicina da Universidade de CoimbraINTRODUÇÃO: Nas últimas décadas a nefrectomia parcial tem assumido um papel de destaque no tratamento do carcinoma de células renais. Esta técnica, também denominada cirurgia poupadora de nefrónios, permite remover o tumor na totalidade, preservando o parênquima renal adjacente. As suas indicações tornaram-se mais abrangentes à medida que os resultados se mostraram cada vez mais promissores. Assim, actualmente a nefrectomia parcial é o tratamento padrão do carcinoma de células renais, em detrimento da tradicional nefrectomia radical. Discute-se agora qual das duas, nefrectomia parcial aberta ou laparoscópica, é a melhor opção. OBJECTIVOS: Rever as evidências científicas relativas ao tratamento do carcinoma de células renais pela nefrectomia parcial, aberta e laparoscópica, definindo o papel actual de cada uma delas nesta área. MÉTODOS: Pesquisa na PubMed e Medline de artigos relativos a nefrectomia radical e nefrectomia parcial aberta e laparoscópica, publicados entre 1997 e 2009. Consulta das “Guidelines” da Associação Europeia de Urologia. DESENVOLVIMENTO: A nefrectomia parcial mostra resultados oncológicos semelhantes aos da nefrectomia radical, permitindo uma menor morbilidade renal a longo prazo. A nefrectomia parcial aberta é agora o tratamento recomendado pelas “Guidelines” da Associação Europeia de Urologia para o tratamento de tumores com diâmetro inferior a 4 cm, limitados ao rim, mesmo quando o rim contralateral é normal. As indicações poderão ainda ser alargadas para tumores até 7 cm de diâmetro, dependendo das características do tumor. A nefrectomia parcial laparoscópica, embora tecnicamente mais exigente, é uma boa opção de tratamento em centros com experiência na realização da técnica, revelando bons resultados a curto prazo. CONCLUSÕES: A nefrectomia parcial aberta é actualmente o tratamento padrão do carcinoma de células renais. A nefrectomia parcial laparoscópica revela resultados a curto prazo semelhantes aos da nefrectomia parcial aberta, contudo são necessários estudos confirmando esses resultados a longo prazoINTRODUCTION: In the last decades partial nephrectomy have had an important role in the treatment of renal cell carcinoma. This surgery, also known as nephron-sparing surgery, allows to remove the tumor and to preserve the surrounding healthy renal parenchyma. Moreover, with the evolution of the technique its indications got more comprehensive. So, nowadays, partial nephrectomy is the standard treatment for renal cell carcinoma, instead of the traditional radical nephrectomy. There is now a discussion between which of the two, open or laparoscopic partial nephrectomy, is the best option. OBJECTIVES: Review the scientific evidences related to the treatment of renal cell carcinoma through open and laparoscopic partial nephrectomy, defining the actual role of both in this area. METHODS: Research articles related to radical nephrectomy, open and laparoscopic partial nephrectomies at PubMed and Medline publications between 1997 and 2009. Consult of the Guidelines of European Urology Association. DEVELOPMENT: Partial nephrectomy shows oncological outcomes similar to those of radical nephrectomy with less renal morbidity at long-term follow-up. Open partial nephrectomy is now the recommended treatment by the Guidelines of European Urology Association for the treatment of tumors less than 4 cm, limited to the kidney, even when the other kidney is normal. Indications can also include tumors less than 7 cm, depending on the characteristics of the tumor. Laparoscopic partial nephrectomy, although technically more demanding, is a good option in specialized centers and reveals similar results in a short-term. CONCLUSIONS: Nowadays open partial nephrectomy is the standard treatment of renal cell carcinoma. Laparoscopic partial shows similar results as open surgery in a short-term, however, more studies are needed to confirm this results at long-term. Key-words: Open partial nephrectomy, laparoscopic partial nephrectomy, renal cell carcinoma, indications, results

Increased CD45RA+FoxP3low Regulatory T Cells with Impaired Suppressive Function in Patients with Systemic Lupus Erythematosus

BACKGROUND: The role of naturally occurring regulatory T cells (Treg) in the control of the development of systemic lupus erythematosus (SLE) has not been well defined. Therefore, we dissect the phenotypically heterogeneous CD4(+)FoxP3(+) T cells into subpopulations during the dynamic SLE development. METHODLOGY/PRINCIPAL FINDINGS: To evaluate the proliferative and suppressive capacities of different CD4(+) T cell subgroups between active SLE patients and healthy donors, we employed CD45RA and CD25 as surface markers and carboxyfluorescein diacetatesuccinimidyl ester (CFSE) dilution assay. In addition, multiplex cytokines expression in active SLE patients was assessed using Luminex assay. Here, we showed a significant increase in the frequency of CD45RA(+)FoxP3(low) naive Treg cells (nTreg cells) and CD45RA(-)FoxP3(low) (non-Treg) cells in patients with active SLE. In active SLE patients, the increased proportions of CD45RA(+)FoxP3(low) nTreg cells were positively correlated with the disease based on SLE disease activity index (SLEDAI) and the status of serum anti-dsDNA antibodies. We found that the surface marker combination of CD25(+)CD45RA(+) can be used to defined CD45RA(+)FoxP3(low) nTreg cells for functional assays, wherein nTreg cells from active SLE patients demonstrated defective suppression function. A significant correlation was observed between inflammatory cytokines, such as IL-6, IL-12 and TNFα, and the frequency of nTreg cells. Furthermore, the CD45RA(+)FoxP3(low) nTreg cell subset increased when cultured with SLE serum compared to healthy donor serum, suggesting that the elevated inflammatory cytokines of SLE serum may promote nTreg cell proliferation/expansion. CONCLUSIONS/SIGNIFICANCE: Our results indicate that impaired numbers of functional CD45RA(+)FoxP3(low) naive Treg cell and CD45RA(-)FoxP3(low) non-suppressive T cell subsets in inflammatory conditions may contribute to SLE development. Therefore, analysis of subsets of FoxP3(+) T cells, using a combination of FoxP3, CD25 and CD45RA, rather than whole FoxP3(+) T cells, will help us to better understand the pathogenesis of SLE and may lead to the development of new therapeutic strategies

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Kirby-Bauer disc approximation to detect inducible third-generation cephalosporin resistance in <it>Enterobacteriaceae</it>

Abstract Resistance to β-lactam antibiotics in enteric Gram-negative bacilli may be difficult to detect using standard methods of either Kirby-Bauer disc diffusion (KBDD) or broth dilution for minimal inhibitory concentration (MIC). This difficulty is due to genetic differences in resistance determinants, differences in levels of gene expression, and variation in spectra of enzymatic activity against the substrate β-lactams used for susceptibility testing. We have examined 95 clinical isolates reportedly susceptible to ceftazidime and ceftriaxone, as originally determined by either KBDD or MIC methods. The organisms studied here were isolated in 2002 from two pediatric hospital centers (Seattle, USA and Shanghai, China). They belong to the inducible β-lactamase producing Gram-negative bacilli, such as Enterobacter spp., Citrobacter spp., Serratia spp., Morganella spp., Providencia spp., and Proteus vulgaris. A Kirby-Bauer disc approximation (KBDA) method identified inducible phenotypes of third-generation cephalosporin resistance in 76% of isolates, which would otherwise be considered susceptible by standard KBDD methods.</p

Two Clinical Strains of Klebsiella pneumoniae Carrying Plasmid-Borne blaIMP-4, blaSHV-12, and armA Isolated at a Pediatric Center in Shanghai, China▿

Two cases of pulmonary infection due to strains of multidrug-resistant Klebsiella pneumoniae were investigated. Beta-lactamase determinants, such as blaIMP-4 and blaSHV-12, and the 16S rRNA methyltransferase-encoding gene armA were detected in these plasmid-bearing organisms. The integron-borne blaIMP-4 and armA contained intervening sequences highly related to those of a Vibrio cholerae O139 plasmid found in Hangzhou, China

Rapid detection of carbapenemase activity of Enterobacteriaceae isolated from positive blood cultures by MALDI-TOF MS

Abstract Background Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been proved to be a useful tool for identification of pathogens directly isolated from blood cultures in clinical microbiology laboratories. β-Lactam antibiotics are commonly used for treatment of bloodstream infections caused by Enterobacteriaceae strains, and carbapenem is the superlative class of β-lactam antibiotics. Since the carbapenem resistance rate of Enterobacteriaceae strains raised year by year, efficient detection of carbapenemase activity and timely delivery of carbapenem susceptibility reports of Enterobacteriaceae strains isolated from blood cultures is important for clinicians. Methods We used 64 simulated blood cultures to establish the method of MALDI-TOF MS based ertapenem hydrolysis assay. The cutoff value of logRQ calculated from the peaks intensity of ertapenem and its hydrolysate was first set to identify the strains with carbapenemase activity. Then, we detected and calculated the logRQ values of 385 Enterobacteriaceae strains from positive clinical blood cultures to distinguish the carbapenemase producers and noncarbapenemase producers. Results The mean logRQ value of 32 noncarbapenemase producers was − 0.85 ± 0.14 in simulated blood cultures, while the logRQ value of 32 carbapenemase producers was 0.87 ± 0.55. Thus, the cutoff value of logRQ was set at − 0.45 with sensitivity of 100% and specificity of 100%. In 385 clinical positive blood cultures, the logRQ values of all carbapenem-susceptible Enterobacteriaceae strains (81.3%, 313/385) were < − 0.45. Comparing with the detection of carbapenemase genes, carbapenem-resistant Enterobacteriaceae strains (18.7%, 72/385) were well distinguished by MALDI-TOF MS based ertapenem hydrolysis assay with a sensitivity of 92.5% and specificity of 100%. Conclusions Our data show that MALDI-TOF MS based ertapenem hydrolysis assay is a rapid and accurate method to detect carbapenemase activity of Enterobacteriaceae strains from positive blood cultures, and can be routinely performed in clinical microbiology laboratories