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INTRODUCTION: High grade, non-muscle invasive bladder cancer (NMIBC) is usually treated with intravesical Bacillus Calmette–Guérin. Chemohyperthermia therapy (CHT) may be a novel alternative therapy for the treatment of NMIBC.OBJECTIVE: To evaluate the recurrence-free survival (RFS) of patients treated with CHT using the Combat bladder recirculation system (BRS) for NMIBC.METHODS: This was a prospective multi-institutional study of 1,028 consecutive patients with NMIBC undergoing CHT between 2012 and 2020. A total of 835 patients were treated with CHT with Mitomycin C (MMC). Disease was confirmed on transurethral resection of bladder tumor (TURBT) prior to starting CHT. Follow-up included cystoscopy and subsequent TURBT if recurrence/progression was suspected. The primary endpoint was RFS. Secondary endpoints were progression-free survival (PFS) and adverse events from CHT.RESULTS AND LIMITATIONS: Median follow up was 22.4 months (Interquartile range (IQR): 12.8 –35.8). Median age was 70.4 years (IQR: 62.1 –78.6). A total of 557 (66.7%), 172 (20.6) and 74 (8.9%) of patients were classified to BCG naïve, BCG unresponsive and BCG failure, respectively. The RFS at 12 months and 24 months for BCG naïve was 87.6% (95% CI 85.0% - 90.4%) and 75.0% (95% CI 71.3% - 78.8%), respectively. The RFS at 12 months and 24 months for BCG unresponsive cohort was 78.1% (95% CI 72.0% - 84.7%) and 57.4% (95% CI 49.7% - 66.3%), respectively. The RFS at 24 months for the BCG unresponsive cohort for CIS with/without papillary disease and papillary only disease were 43.6% (95% CI 31.4% –60.4%) and 64.5% (95% CI 55.4% - 75.1%), respectively. Minor adverse events occurred in 216 (25.6%) patients and severe events occurred in 17 (2.0%) patients.CONCLUSIONS: CHT with MMC using the Combat BRS is effective in the medium term and has a favorable adverse event profile.

Extended food consumption during the rest period perturbs the phase relationship between circadian clocks in the periphery and the brain, leading to adverse health effects. Beyond the liver, how metabolic organs respond to a timed hypocaloric diet is largely unexplored. We investigated how feeding schedules impacted circadian gene expression in epididymal white and brown adipose tissue (eWAT and BAT) compared to the liver and hypothalamus. We restricted food to either daytime or nighttime in C57BL/6J male mice, with or without caloric restriction. Unlike the liver and eWAT, rhythmic clock genes in the BAT remained insensitive to feeding time, similar to the hypothalamus. We uncovered an internal split within the BAT in response to conflicting environmental cues, displaying inverted oscillations on a subset of metabolic genes without modifying its local core circadian machinery. Integrating tissue-specific responses on circadian transcriptional networks with metabolic outcomes may help elucidate the mechanism underlying the health burden of eating at unusual times.

Cultivation of the phytopathogenic fungus Botrytis cinereausing sublethal amounts of copper sulfate yielded a cryptic sesquiterpenoids family, which displayed the basic chemical structure of (+)-4-epi-eremophil-9-ene. The biosynthesis pathway was established, and the route involved the likely transformation of the diphosphate of farnesyl (FDP), to give a cis-fused eudesmane cation, through (S)-hedycaryol, finally yielding the (+)-4-epi-eremophil-9-enol derivatives. An expression study of genes that code for the sesquiterpene cyclases (STC), including the recently reported gene Bcstc7present in the B. cinereagenome, was performed in order to establish the STC involved in this biosynthesis. The results showed a higher expression level for the Bcstc7gene with respect to the other stc1–5genes in both wild-type strains, B05.10 and Botrytis cinereaUCA992. Deletion of the Bcstc7gene eliminated (+)-4-epi-eremophilenol biosynthesis, which could be re-established by complementing the null mutant with the Bcstc7gene. Chemical analysis suggested that STC7 is the principal enzyme responsible for the key step of cyclization of FDP to eremophil-9-en-11-ols. Furthermore, a thorough study of the two wild-types and the complemented mutant revealed four new eremophilenol derivatives whose structures are reported here.

Analizar el uso particular de los smartphones entre los profesionales sanitarios de Atención Primaria durante el acto asistencial y sus consecuencias.

En la urolitiasis intervienen diversos factores genéticos y ambientales. Las 2 anomalías metabólicas más frecuentes son el incremento en la eliminación urinaria de calcio y la reducción en la de citrato. El cociente calculado entre las concentraciones de ambas sustancias es un buen marcador de riesgo de formación de cálculos cálcicos.

Various genetic and environmental factors are involved in urolithiasis. The 2 most common metabolic abnormalities are the increase in urinary calcium and low urinary citrate excretion. The ratio calculated between the concentrations of both substances is a good risk marker for the formation of calcium stones.

Eighty-six specimens representing 7 species of rodents from 9 localities in the state Zacatecas were examined for helminths. Only 5 host species were found to harbor at least 1 species: Chaetodipussp., Dipodomys merriami atronasus, Neotoma mexicana, Otospermophilus variegatus, and Peromyscussp.; in contrast Mus musculusand Reithrodontomyssp., were not parasitized. Three species of cestodes (Catenotaeniidae gen. sp., Hymenolepissp., and Raillietinasp.) and 7 nematodes (Gongylonemasp., Heteromyoxyuris longejector, Lamotheoxyuriscf. ackerti, Mastophorus dipodomis, Rauschtineriasp., Pterygodermatites dipodomis, and Trichuris dipodomis) were recorded. The intestine is the most parasitized (7 taxa) and trematodes were not found. The highest species richness was recorded in D. merriami atronasusfrom Rancho La Barranca (6 taxa), which also had the most sampling effort. H. longejectorin Chaetodipussp. from El Gordillo, showed the greatest mean abundance, and mean intensity values, followed by Rauschtineriasp. in O. variegatusfrom Morelos-Zacatecas Road. All species are new locality records, 14 new host records, and 2 taxa recorded for the first time in Mexico: Rauschtineriasp. and M. dipodomis. This is the first study of helminth parasites of rodents from Zacatecas.

Citrus leaf blotch virus(CLBV) infection has been detected in citrus cultivars from several countries including the USA, Spain, Italy, Japan and New Zealand. To investigate whether CLBV is present in Cuba, a survey was conducted in seven commercial citrus fields of the country during 2007–2013. In all, 1940 trees were inspected and samples of two symptomatic and 18 asymptomatic sources were tested by biological indexing and molecular techniques for virus detection. Bark patches from the two symptomatic Nagami and Round kumquat sources induced chlorotic blotching and vein clearing in Dweet tangor, and only for the Round kumquat inoculums, stem pitting in Etrog citron. RT-PCR assays using specific primers to amplify fragments of polymerase (RdRp), movement (MP) and coat protein (CP) genes of CLBV yielded amplicons with the expected sizes using RNA from both sources as a template. Viral RNA was further detected by a non-radioactive dot-blot hybridization assay using a mixture of specific probes derived from a Spanish isolate of CLBV. Sequences from RdRp, MP, and CP amplicons showed identical nucleotide identities for the two Cuban isolates, and higher than 95.9 % with isolates from Spain, New Zealand and the USA.

The sequencing of the genomes of the B05.10 and T4 strains of the fungus Botrytis cinerearevealed an abundance of novel biosynthetic gene clusters, the majority of which were unexpected on the basis of the previous analyses of the fermentation of these and closely related species. By systematic alteration of easy accessible cultivation parameters, using chemical induction with copper sulfate, we have found a cryptic sesquiterpenoid family with new structures related to eremophil-9-ene, which had the basic structure of the sesquiterpene (+)-5-epiaristolochene ((+)-4-epieremophil-9-ene). An expression study of the sesquiterpene cyclase genes present in the Botrytis cinereagenome, under culture conditions, is reported. In general, a 3 day delay and a higher BcSTCgenes expression were observed when copper (5 ppm) was fed to the fermentation broth. In addition, to the observed effect on the BcBOT2(BcSTC1) gene, involved in the biosynthesis of the botrydial toxin, a higher expression level for BcSTC3and BcSTC4was observed with respect to the control in the strain B05.10. Interestingly, under copper conditions, the BcSTC4gene was the most expressed gene in the Botrytis cinereaUCA992 strain. In vitroevaluation of the biological role of these metabolites indicates that they contributed to the conidial development in B. cinereaand appear to be involved in self-regulation of the production of asexual spores. Furthermore, they promoted the formation of complex appressoria or infection cushions.

ABSTRACTImmunogenic cell death (ICD) has been proposed to be a crucial process for antitumor immunosurveillance. ICD is characterized by the exposure and emission of Damage Associated Molecular Patterns (DAMP), including calreticulin (CRT). A positive correlation between CRT exposure or total expression and improved anticancer immunosurveillance has been found in certain cancers, usually accompanied by favorable patient prognosis. In the present study, we sought to evaluate CRT levels in the plasma membrane of CD38+bone marrow mononuclear cells (BMMCs) isolated from 71 patients with varying degrees of multiple myeloma (MM) disease and examine the possible relationship between basal CRT exposure and the bone marrow immune microenvironment, as well as its connection with different clinical markers. Data show that increased levels of cell surface-CRT were associated with more aggressive clinical features and with worse clinical prognosis in MM. High CRT expression in MM cells was associated with increased infiltration of NK cells, CD8+T lymphocytes and dendritic cells (DC), indicative of an active anti-tumoral immune response, but also with a significantly higher presence of immunosuppressive Treg cells and increased expression of PD-L1 in myeloma cells.

The U-shaped assembly line has received a considerable attention and has been widely used in industry in recent years due to the pressures of the just-in-time (JIT) manufacturing philosophy. However, balancing the U-shaped line is more difficult than balancing the traditional straight line. This study aims at balancing the U-shaped assembly line by introducing a novel heuristic which is based on the simulated annealing (SA) algorithm. The objectives to be optimised in this study are the number of workstations and balance efficiency. The performance of the proposed algorithm is examined by solving a set of standard test problems and a real case study. The results attained by the proposed algorithm were compared against the best known solution in the literature and it was found that the proposed algorithm is able to find good solutions in a reasonably short computational time. [Received 29 December 2012; Revised 28 March 2014; Revised 25 August 2014; Revised 22 May 2015; Accepted 26 May 2015]

Circadian clocks regulate the temporal organization of several biochemical processes, including lipid metabolism, and their disruption leads to severe metabolic disorders. Immortalized cell lines acting as circadian clocks display daily variations in [32P]phospholipid labeling; however, the regulation of glycerophospholipid (GPL) synthesis by internal clocks remains unknown. Here we found that arrested NIH 3T3 cells synchronized with a 2 h-serum shock exhibited temporal oscillations in a) the labeling of total [3H] GPLs, with lowest levels around 28 and 56 h, and b) the activity of GPL-synthesizing and GPL-remodeling enzymes, such as phosphatidate phosphohydrolase 1 (PAP-1) and lysophospholipid acyltransferases (LPLAT), respectively, with antiphase profiles. In addition, we investigated the temporal regulation of phosphatidylcholine (PC) biosynthesis. PC is mainly synthesized through the Kennedy pathway with choline kinase (ChoK) and CTP:phosphocholine cytidylyltranferase (CCT) as key regulatory enzymes. We observed that the PC labeling exhibited daily changes, with the lowest levels every ∼28 h, that were accompanied by brief increases in CCT activity and the oscillation in ChoK mRNA expression and activity. Results demonstrate that the metabolisms of GPLs and particularly of PC in synchronized fibroblasts are subject to a complex temporal control involving concerted changes in the expression and/or activities of specific synthesizing enzymes.

Background/Aims:Idiopathic hypercalciuria (IH) is associated with a decreased bone mineral density (BMD) both in children and adults. It is being increasingly recognized that IH may be a contributing factor to osteopenia and/or osteoporosis in adults. We studied BMD in girls with IH and in their mothers, also affected with IH, in order to evaluate the influence of genetic background on bone mass in the setting of IH. Methods:BMD was evaluated in 40 girls with IH and in their premenopausal mothers from whom they had inherited this disease. Urinary creatinine and calcium were measured by standard laboratory methods. BMD was determined by dual X-ray absorptiometry scanning of the lumbar spine (LS) and the femoral neck (FN), and values are expressed as Z- and T-scores. Results:A Z-score of <–1 at the LS was found in 42.5% of the girls, whilst in the mothers, a Z score of <–1 at the LS and/or FN was observed in 47.5% and a T-score of <–1 at the LS and/or FN in 62.5%. The Z-score at the LS was significantly lower in girls and their mothers compared to controls, although this finding did not apply for the Z-score at the FN in the mothers. Z-scores in the girls of mothers with osteopenia were significantly lower or there was a trend for the score to be lower than in the girls of mothers with normal BMD. There was a significant relationship between the Z-score of the girls and the T-score at the LS in the mothers (r = 0.32, p < 0.05). Conclusion:We have observed a high prevalence of osteopenia in our population affected by IH, both in girls and in their mothers. We suggest that BMD should be measured during the third or fourth decades of life in those individuals with nephrolithiasis or with children diagnosed as having IH.

Este trabajo pretende analizar el grado en que el Partido Revolucionario Institucional (PRI) y el gobierno de México se entrelazan. Si bien estos dos aparatos a menudo perciben como uno solo, es importante desagregar analíticamente sus papeles, funciones y acceso a recursos, así como diferenciar el personal y las carreras seguidas por quienes pertenecen a una u otra institución. El trabajo demuestra que estos dos aparatos son diferentes en muchos aspectos, y discute hasta qué punto la apertura política y la democratización en México pueden estar llevando a una mayor divergencia o convergencia entre las dos estructuras. De manera un tanto paradójica, dada la ortodoxia técnica y neoliberal de la presente administración, los imperativos políticos tienden a llevar al PRI y a las estructuras gubernamentales hacia una vinculación más estrecha y hacia un traslape mayor. Los autores argumentan que esta convergencia va en contra de un proceso de democratización y apertura política genuinas.