Photodynamic Diagnosis of Non-muscle-invasive Bladder Cancer with Hexaminolevulinate Cystoscopy: A Meta-analysis of Detection and Recurrence Based on Raw Data.

BACKGROUND: Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence. OBJECTIVE: To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence. DESIGN, SETTING, AND PARTICIPANTS: This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC). INTERVENTION: A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We studied the detection of NMIBC (intention to treat [ITT]: n=831; six studies) and recurrence (per protocol: n=634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection. RESULTS AND LIMITATIONS: BL cystoscopy detected significantly more Ta tumours (14.7%; p<0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p<0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p<0.001), significant also in patients with primary (20.7%; p<0.001) and recurrent cancer (27.7%; p<0.001), and in patients at high risk (27.0%; p<0.001) and intermediate risk (35.7%; p=0.004). In 26.7% of patients, CIS was detected only by BL (p<0.001) and was also significant in patients with primary (28.0%; p<0.001) and recurrent cancer (25.0%; p<0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p=0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p=0.052; RR: 0.696 [0.482-1.003]), Ta (p=0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p=0.050) and low-risk (p=0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used. CONCLUSIONS: This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.

Comportamento produtivo de caupi em regimes irrigado e de sequeiro em Petrolina e Juazeiro

O caupi (Vigna unguiculata (L.) Walp.) é a cultura de grãos mais importante da região Semi-Árida brasileira. O objetivo deste trabalho foi avaliar a adaptabilidade e a estabilidade produtiva de 18 genótipos de caupi em regimes irrigado e de sequeiro, em quatro anos (1995 a 1998), nos Municípios de Petrolina, PE, e Juazeiro, BA. Os genótipos compuseram dois experimentos repetidos cinco vezes em delineamento de blocos casualizados, com quatro repetições. A produção de grãos foi corrigida por covariância no estande ideal de plantas e submetida a análises estatísticas. A presença de variações na fertilidade do solo, no manejo e no quadro pluviométrico, alterou o comportamento produtivo dos genótipos (P<0,01). O genótipo Balinha, selecionado e mantido por pequenos produtores, produziu 1.779 kg/ha em áreas irrigadas, comportamento, este, superior ou similar ao de cultivares das instituições de pesquisa. Em regime de sequeiro, os resultados indicam genótipos superiores, como a cultivar EPACE 10, com 1.343 kg/ha e a linhagem TE 901781F, com 1.176 kg/ha. A cultivar EPACE 11 apresentou bom comportamento produtivo, tanto em regime de sequeiro como em regime irrigado, com 1.497 kg/ha. Esses resultados indicam a necessidade do desenvolvimento de genótipos de caupi específicos para diferentes ambientes, com ênfase especial para áreas irrigadas.

The role of the NKG2D receptor for tumor immunity.

Natural killer (NK) cells have originally been identified based on their capacity to kill transformed cells in a seemingly non-specific fashion. Over the last 15 years, knowledge on receptor ligand systems used by NK cells to specifically detect transformed cells has been accumulating rapidly. One of these receptor ligand systems, the NKG2D pathway, has received particular attention, and now serves as a paradigm for how the immune system is able to gather information about the health status of autologous host cells. In addition to its significance on NK cells, NKG2D, as well as other NK cell receptors, play significant roles on T cells. This review aims at summarizing recent insights into the regulation of NKG2D function, the control over NKG2D ligand expression and the role of NKG2D in tumor immunity. Finally, we will discuss first attempts to exploit NKG2D function to improve immunity to tumors.

Determinants of maternal sex steroids during the first half of pregnancy.

OBJECTIVE: To examine the associations of maternal and child characteristics with early pregnancy maternal concentrations of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, and estradiol (E2). METHODS: We analyzed these hormones among 1,343 women with singleton pregnancies who donated serum samples to the Finnish Maternity Cohort from 1986 to 2006 during the first half of pregnancy (median 11 weeks). The associations of maternal and child characteristics with hormone concentrations were investigated by correlation and multivariable regression. RESULTS: Women older than age 30 years had lower androgen and E2 but higher progesterone concentrations than women younger than that age. Multiparous women had 14% lower testosterone, 11% lower androstenedione and 17-hydroxyprogesterone, 9% lower progesterone, and 16% lower E2 concentrations compared with nulliparous women (all P<.05). Smoking mothers had 11%, 18%, and 8% higher testosterone, androstenedione, and 17-hydroxyprogesterone levels, respectively, but 10% lower progesterone compared with nonsmoking women (all P<.05). E2 concentrations were 9% higher (P<.05) among women with a female fetus compared with those with a male fetus. CONCLUSION: Parity, smoking, and, to a lesser extent, maternal age and child sex are associated with sex steroid levels during the first half of a singleton pregnancy. The effects of smoking on the maternal hormonal environment and the possible long-term deleterious consequences on the fetus deserve further evaluation. LEVEL OF EVIDENCE: II.

Patient expectations at a multicultural out-patient clinic in Switzerland.

BACKGROUND: Recognizing patient expectation is considered as an important objective for primary care physicians. A number of studies suggest that failure to identify patient expectations can lead to patient dissatisfaction with care, lack of compliance and inappropriate use of medical resources. It has been suggested that identifying patient expectations in multicultural contexts can be especially challenging. OBJECTIVES: The aim of the study was to compare health care expectations of Swiss and immigrant patients attending the out-patient clinic of a Swiss university hospital and to assess physicians' ability to identify their patients' expectations. METHODS: Over a 3-month period, all patients attending the out-patient clinic at a Swiss university hospital were requested to complete pre-consultation surveys. Their physicians were requested to complete post-consultation surveys. Outcome measures were patients' self-rated health, resort to prior home treatment, patients' expectations of the consultation, physicians' perception of their patients' expectations and agreement between patients and physicians. RESULTS: We analysed 343 questionnaires completed by patients prior to their consultation (> 50% immigrants) and 333 questionnaires completed by their physicians after the consultation. Most expectations were shared by all patients. Physicians had inaccurate perceptions of their patients' expectations, regardless of patients' origin. CONCLUSIONS: Our study found no evidence that immigrant patients' expectations differed from those of Swiss patients, nor that physicians had more difficulty identifying expectations of immigrant patients. However, physicians in our study were generally poor at identifying patients' expectations, and therefore inter-group differences may be difficult to detect. Our results point to the need to strengthen physicians' general communication skills which should then serve as a foundation for more specific, cross-cultural communication training.

Política criminal de la seguridad vial y garantías constitucionales

En este trabajo pretendo de poner de manifiesto las consecuencias de los cambios introducidos por LO 15/2007, de 30 de noviembre, en relación con la delincuencia en el tráfico viario, tanto respecto de los delitos contra la seguridad en el tráfico, como en relación con los homicidios y lesiones producidos en este ámbito. Desde una perspectiva formal, se modifica la denominación del Cap. IV del Título XVII, que pasa a denominarse delitos contra la Seguridad Vial, en lugar de delitos contra la Seguridad en el Tráfico.

Alcoholèmies i dret penal. Especial atenció a la pràctica policial

En la actualitat, la circulació de vehicles s'ha convertit en una activitat bàsica per al desenvolupament de l'economia mundial a la vegada que ha comportat una innumerable quantitat d'avantatges per als individus en àmbits tan dispars com són els laborals o els d'oci. Els progressos de la indústria automobilística han estat extraordinaris. No obstant això, ni el procés d'aprenentatge i adaptació per part dels conductors ni la millora del sistema d'infraestructures ha estat tan espectacular com l'augment del parc mòbil. A més, la informació subministrada pels mass media, en general, ha propiciat més que previngut la conducció irresponsable i perillosa. En conseqüència, el número de morts i ferits en accidents de trànsit es tan important que es pot considerar que estem davant un autèntic problema de salut pública mundial. Els poders públics han promogut campanyes publicitàries a favor d'una conducció responsable, han invertit en educació vial, han millorat la xarxa de carreteres i han creat un sistema sancionador administratiu i penal per castigar les infraccions a les normes de trànsit. Els resultats obtinguts han estat positius, reduint-se la mortalitat en Espanya en més d'un 50%. No obstant això, davant la persistència del número d'accidents mortals o amb greus lesions, el legislador ha optat per incrementar el sistema punitiu, limitant principis constitucionals tan bàsics com són els de presumpció d'innocència o de defensa.

Crohn's disease-associated polymorphism within the PTPN2 gene affects muramyl-dipeptide-induced cytokine secretion and autophagy.

BACKGROUND: The single nucleotide polymorphism (SNP) rs2542151 within the gene locus region encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) has been associated with Crohn's disease (CD), ulcerative colitis (UC), type-I diabetes, and rheumatoid arthritis. We have previously shown that PTPN2 regulates mitogen-activated protein kinase (MAPK) signaling and cytokine secretion in human THP-1 monocytes and intestinal epithelial cells (IEC). Here, we studied whether intronic PTPN2 SNP rs1893217 regulates immune responses to the nucleotide-oligomerization domain 2 (NOD2) ligand, muramyl-dipeptide (MDP). MATERIALS AND METHODS: Genomic DNA samples from 343 CD and 663 non-IBD control patients (male and female) from a combined German, Swiss, and Polish cohort were genotyped for the presence of the PTPN2 SNPs, rs2542151, and rs1893217. PTPN2-variant rs1893217 was introduced into T(84) IEC or THP-1 cells using a lentiviral vector. RESULTS: We identified a novel association between the genetic variant, rs1893217, located in intron 7 of the PTPN2 gene and CD. Human THP-1 monocytes carrying this variant revealed increased MAPK activation as well as elevated mRNA expression of T-bet transcription factor and secretion of interferon-γ in response to the bacterial wall component, MDP. In contrast, secretion of interleukin-8 and tumor necrosis factor were reduced. In both, T(84) IEC and THP-1 monocytes, autophagosome formation was impaired. CONCLUSIONS: We identified a novel CD-associated PTPN2 variant that modulates innate immune responses to bacterial antigens. These findings not only provide key insights into the effects of a functional mutation on a clinically relevant gene, but also reveal how such a mutation could contribute to the onset of disease.

Complete nucleotide sequence of Birmingham IncP alpha plasmids. Compilation and comparative analysis.

The IncP alpha promiscuous plasmid (R18, R68, RK2, RP1 and RP4) comprises 60,099 bp of nucleotide sequence, encoding at least 74 genes. About 40 kb of the genome, designated the IncP core and including all essential replication and transfer functions, can be aligned with equivalent sequences in the IncP beta plasmid R751. The compiled IncP alpha sequence revealed several previously unidentified reading frames that are potential genes. IncP alpha plasmids carry genetic information very efficiently: the coding sequences of the genes are closely packed but rarely overlap, and occupy almost 86% of the genome's nucleotide sequence. All of the 74 genes should be expressed, although there is as yet experimental evidence for expression of only 60 of them. Six examples of tandem-in-frame initiation sites specifying two gene products each are known. Two overlapping gene arrangements occupy different reading frames of the same region. Intergenic regions include most of the 25 promoters; transcripts are usually polycistronic. Translation of most of the open reading frames seems to be initiated independently, each from its own ribosomal binding and initiation site, although, a few cases of coupled translation have been reported. The most frequently used initiation codon is AUG but translation for a few open reading frames begins at GUG or UUG. The most common stop-codon is UGA followed by UAA and then UAG. Regulatory circuits are complex and largely dependent on two components of the central control operon. KorA and KorB are transcriptional repressors controlling at least seven operons. KorA and KorB act synergistically in several cases by recognizing and binding to conserved nucleotide sequences. Twelve KorB binding sites were found around the IncP alpha sequence and these are conserved in R751 (IncP beta) with respect to both sequence and location. Replication of IncP alpha plasmids requires oriV and the plasmid-encoded initiator protein TrfA in combination with the host-encoded replication machinery. Conjugative plasmid transfer depends on two separate regions occupying about half of the genome. The primary segregational stability system designated Par/Mrs consists of a putative site-specific recombinase, a possible partitioning apparatus and a post-segregational lethality mechanism, all encoded in two divergent operons. Proteins related to the products of F sop and P1 par partitioning genes are separately encoded in the central control operon.

Iowa Department of Transportation Major Items - Preliminary Quantity Report, February 17, 2015; With Addendums

Weekly letting report.

Dénervation rénale pour le traitement de l'hypertension artérielle résistante: proposition pour une attitude multidisciplinaire commune [Renal denervation in resistant hypertension: proposal for a common multidisciplinary attitude].

The prevalence of resistant hypertension ranges between 5-30%. Patients with resistant hypertension are at increased risk of cardiovascular events. Radiofrequency renal denervation is a recent and promising technique that can be used in the setting of resistant hypertension. However, long-term safety and efficacy data are lacking and evidence to use this procedure outside the strict setting of resistant hypertension is missing. The aim of the article is to propose a common work-up for nephrologists, hypertensiologists, cardiologists and interventional radiologists in order to avoid inappropriate selection of patients and a possible misuse of this procedure.