Development and validation of a nomogram predicting recurrence risk in women with symptomatic urinary tract infection

Objectives: To develop and externally validate a novel nomogram predicting recurrence risk probability at 12 months in women after an episode of urinary tract infection. Methods: The study included 768women from Santa Maria Annunziata Hospital, Florence, Italy, affected by urinary tract infections from January 2005 to December 2009. Another 373 women with the same criteria enrolled at Santa Chiara Hospital, Trento, Italy, from January 2010 to June 2012 were used to externally validate and calibrate the nomogram. Univariate and multivariate Cox regression models tested the relationship between urinary tract infection recurrence risk, and patient clinical and laboratory characteristics. The nomogram was evaluated by calculating concordance probabilities, as well as testing calibration of predicted urinary tract infection recurrence with observed urinary tract infections. Nomogram variables included: number of partners, bowel function, type of pathogens isolated (Grampositive/ negative), hormonal status, number of previous urinary tract infection recurrences and previous treatment of asymptomatic bacteriuria. Results: Of the original development data, 261 out of 768 women presented at least one episode of recurrence of urinary tract infection (33.9%). The nomogram had a concordance index of 0.85. The nomogram predictions were well calibrated. This model showed high discrimination accuracy and favorable calibration characteristics. In the validation group (373 women), the overall c-index was 0.83 (P = 0.003, 95% confidence interval 0.51–0.99), whereas the area under the receiver operating characteristic curve was 0.85 (95% confidence interval 0.79–0.91). Conclusions: The present nomogram accurately predicts the recurrence risk of urinary tract infection at 12 months, and can assist in identifying women at high risk of symptomatic recurrence that can be suitable candidates for a prophylactic strategy

TGFβR2 is a major target of miR-93 in nasopharyngeal carcinoma aggressiveness.

BACKGROUND: MiR-17-92 cluster and its paralogues have emerged as crucial regulators of many oncogenes and tumor suppressors. Transforming growth factor-β receptor II (TGFβR2), as an important tumor suppressor, is involved in various cancer types. However, it is in cancer that only two miRNAs of this cluster and its paralogues have been reported so far to regulate TGFβR2. MiR-93 is oncogenic, but its targetome in cancer has not been fully defined. The role of miR-93 in nasopharyngeal carcinoma (NPC) still remains largely unknown. METHODS: We firstly evaluated the clinical signature of TGFβR2 down-regulation in clinical samples, and next used a miRNA expression profiling analysis followed by multi-validations, including Luciferase reporter assay, to identify miRNAs targeting TGFβR2 in NPC. In vitro and in vivo studies were performed to further investigate the effects of miRNA-mediated TGFβR2 down-regulation on NPC aggressiveness. Finally, mechanism studies were conducted to explore the associated pathway and genes influenced by this miRNA-mediated TGFβR2 down-regulation. RESULTS: TGFβR2 was down-regulated in more than 50% of NPC patients. It is an unfavorable prognosis factor contributing to clinical NPC aggressiveness. A cluster set of 4 TGFβR2-associated miRNAs was identified; they are all from miR-17-92 cluster and its paralogues, of which miR-93 was one of the most significant miRNAs, directly targeting TGFβR2, promoting cell proliferation, invasion and metastasis in vitro and in vivo. Moreover, miR-93 resulted in the attenuation of Smad-dependent TGF-β signaling and the activation of PI3K/Akt pathway by suppressing TGFβR2, further promoting NPC cell uncontrolled growth, invasion, metastasis and EMT-like process. Impressively, the knockdown of TGFβR2 by siRNA displayed a consentaneous phenocopy with the effect of miR-93 in NPC cells, supporting TGFβR2 is a major target of miR-93. Our findings were also substantiated by investigation of the clinical signatures of miR-93 and TGFβR2 in NPC. CONCLUSION: The present study reports an involvement of miR-93-mediated TGFβR2 down-regulation in NPC aggressiveness, thus giving extended insights into molecular mechanisms underlying cancer aggressiveness. Approaches aimed at blocking miR-93 may serve as a promising therapeutic strategy for treating NPC patients

A Chinese cave links climate change, social impacts, and human adaptation over the last 500 years.

The collapse of some pre-historical and historical cultures, including Chinese dynasties were presumably linked to widespread droughts, on the basis of synchronicities of societal crises and proxy-based climate events. Here, we present a comparison of ancient inscriptions in Dayu Cave from Qinling Mountains, central China, which described accurate times and detailed impacts of seven drought events during the period of 1520-1920 CE, with high-resolution speleothem records from the same cave. The comparable results provide unique and robust tests on relationships among speleothem δ(18)O changes, drought events, and societal unrest. With direct historical evidences, our results suggest that droughts and even modest events interrupting otherwise wet intervals can cause serious social crises. Modeling results of speleothem δ(18)O series suggest that future precipitation in central China may be below the average of the past 500 years. As Qinling Mountain is the main recharge area of two large water transfer projects and habitats of many endangered species, it is imperative to explore an adaptive strategy for the decline in precipitation and/or drought events.We gratefully acknowledge the NBRPC (2013CB955902), NSFC (41372192; 41290254; 41230524; 41023006), and the WLF-CAS for funding this research. This study was also partially supported by Taiwan MOST (103-2119-M-002-022) and NTU (101R7625) grants. H.C. and R.L.E. received financial support from the U.S. NSF (EAR-0908792 and EAR-1211299), and S.F.M.B. received support from the Swiss NSF (CRSI22_132646/1).This is the final version. It was first published by NPG at http://www.nature.com/srep/2015/150717/srep12284/full/srep12284.html#author-information

Knowledge and risk behaviors related to HIV/AIDS, and their association with information resource among men who have sex with men in Heilongjiang province, China

<p>Abstract</p> <p>Backgroud</p> <p>In Heilongjiang province, the HIV prevalence in men who have sex with men (MSM) is generally lower than other part of China. However, the official perception for their risk of HIV/AIDS infection has been increasing in the province over the years. Moreover, little information on HIV/AIDS was provided to the communities so that we have disadvantage of controlling HIV/AIDS epidemic in the region. The purpose of this study is to investigate the prevalence of HIV among MSM in Heilongjiang province, to assess their knowledge levels and risk behaviors related to HIV/AIDS, and to explore their associations with information resources.</p> <p>Methods</p> <p>A cross-sectional study using a standardized questionnaire and blood test was administered in 2008 by local interviewers to a sample (1353) of MSM in four cities in Heilongjiang province.</p> <p>Results</p> <p>Among 1353 MSM, 2.3% were identified with HIV infection. About 48.7% of the subjects had multiple male sexual partners and only 37.3% of the subjects had consistent condom use (use every time) in the past 6 months. Most had a fair level of knowledge on HIV/AIDS, with the highest mean knowledge score among the MSM from Jiamusi, those with income 2000-3000 RMB/month, those searching sexual partners via internet and those performed HIV testing over 1 year ago). However, some myths regarding viral transmission (e.g., via mosquito bites or sharing kitchen utensils) also existed. Resources of information from which knowledge and risk behaviors related to HIV/AIDS was most available were television (58.6%) among MSM, followed by sexual partner (51.6%), publicity material (51.0%) and internet (48.7%). Significantly statistical differences of mean knowledge score were revealed in favor of book (<it>P </it>= 0.0002), medical staff (<it>P </it>= 0.0007), publicity material (<it>P </it>= 0.005) and sexual partner (<it>P </it>= 0.02). Press (<it>P </it>= 0.04) and book (<it>P </it>= 0.0003) were contributory to the most frequent condom use (condom use every time), while medical staff (<it>P </it>= 0.005) and publicity material (<it>P </it>= 0.04) is associated with moderate rate of condom use (condom use often).</p> <p>Conclusions</p> <p>Although the prevalence of HIV infection is low among MSM in Heilongjiang province, the situation that the risk behaviors were frequent in the population is alarming. The study suggests that some strategies like condom use and education intervention are practical approaches and need to be strengthened.</p

Involvement of Complexin 2 in Docking, Locking and Unlocking of Different SNARE Complexes during Sperm Capacitation and Induced Acrosomal Exocytosis

Acrosomal exocytosis (AE) is an intracellular multipoint fusion reaction of the sperm plasma membrane (PM) with the outer acrosomal membrane (OAM). This unique exocytotic event enables the penetration of the sperm through the zona pellucida of the oocyte. We previously observed a stable docking of OAM to the PM brought about by the formation of the trans-SNARE complex (syntaxin 1B, SNAP 23 and VAMP 3). By using electron microscopy, immunochemistry and immunofluorescence techniques in combination with functional studies and proteomic approaches, we here demonstrate that calcium ionophore-induced AE results in the formation of unilamellar hybrid membrane vesicles containing a mixture of components originating from the two fused membranes. These mixed vesicles (MV) do not contain the earlier reported trimeric SNARE complex but instead possess a novel trimeric SNARE complex that contained syntaxin 3, SNAP 23 and VAMP 2, with an additional SNARE interacting protein, complexin 2. Our data indicate that the earlier reported raft and capacitation-dependent docking phenomenon between the PM and OAM allows a specific rearrangement of molecules between the two docked membranes and is involved in (1) recruiting SNAREs and complexin 2 in the newly formed lipid-ordered microdomains, (2) the assembly of a fusion-driving SNARE complex which executes Ca2+-dependent AE, (3) the disassembly of the earlier reported docking SNARE complex, (4) the recruitment of secondary zona binding proteins at the zona interacting sperm surface. The possibility to study separate and dynamic interactions between SNARE proteins, complexin and Ca2+ which are all involved in AE make sperm an ideal model for studying exocytosis

The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel

An exploration of ambigrammatic sequences in narnaviruses

Narnaviruses have been described as positive-sense RNA viruses with a remarkably simple genome of ~3 kb, encoding only a highly conserved RNA-dependent RNA polymerase (RdRp). Many narnaviruses, however, are 'ambigrammatic' and harbour an additional uninterrupted open reading frame (ORF) covering almost the entire length of the reverse complement strand. No function has been described for this ORF, yet the absence of stops is conserved across diverse narnaviruses, and in every case the codons in the reverse ORF and the RdRp are aligned. The >3 kb ORF overlap on opposite strands, unprecedented among RNA viruses, motivates an exploration of the constraints imposed or alleviated by the codon alignment. Here, we show that only when the codon frames are aligned can all stop codons be eliminated from the reverse strand by synonymous single-nucleotide substitutions in the RdRp gene, suggesting a mechanism for de novo gene creation within a strongly conserved amino-acid sequence. It will be fascinating to explore what implications this coding strategy has for other aspects of narnavirus biology. Beyond narnaviruses, our rapidly expanding catalogue of viral diversity may yet reveal additional examples of this broadly-extensible principle for ambigrammatic-sequence development

Meanings given to algebraic symbolism in problem posing

Some errors in the learning of algebra suggest students have difficulties giving meaning to algebraic symbolism. In this paper, we use problem posing in order to analyze the students’ capacity to assign meaning to algebraic symbolism and the difficulties that students encounter in this process depending on the characteristics of the algebraic statements given. We designed a written questionnaire composed of eight closed algebraic statements expressed symbolically, which was administered to 55 students who had finished their compulsory education and that had some previous experience in problem posing. In our analysis of the data, we examine both syntactic and semantic structures of the problem posed. We note that in most cases students posed problems with syntactic structures different to those given. They did not include computations within variables, and changed the kinds of relationships connecting variables. Students easily posed problems for statements with additive structures. Other differences in the type of problems posed depend on the characteristics of the given statements