Glioblastoma is the most lethal primary malignant brain tumor. Although considerable progress has been made in the treatment of this aggressive tumor, the clinical outcome for patients remains poor. ...Histone deacetylases (HDACs) are recognized as promising targets for cancer treatment. In the past several years, HDAC inhibitors (HDACis) have been used as radiosensitizers in glioblastoma treatment. However, no study has demonstrated the status of global HDAC expression in gliomas and its possible correlation to the use of HDACis. The purpose of this study was to evaluate and compare mRNA and protein levels of class I, II and IV of HDACs in low grade and high grade astrocytomas and normal brain tissue and to correlate the findings with the malignancy in astrocytomas.
Forty-three microdissected patient tumor samples were evaluated. The histopathologic diagnoses were 20 low-grade gliomas (13 grade I and 7 grade II) and 23 high-grade gliomas (5 grade III and 18 glioblastomas). Eleven normal cerebral tissue samples were also analyzed (54 total samples analyzed). mRNA expression of class I, II, and IV HDACs was studied by quantitative real-time polymerase chain reaction and normalized to the housekeeping gene beta-glucuronidase. Protein levels were evaluated by western blotting.
We found that mRNA levels of class II and IV HDACs were downregulated in glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8 genes, p < 0.05). The protein levels of class II HDAC9 were also lower in high-grade astrocytomas than in low-grade astrocytomas and normal brain tissue. Additionally, we found that histone H3 (but not histone H4) was more acetylated in glioblastomas than normal brain tissue.
Our study establishes a negative correlation between HDAC gene expression and the glioma grade suggesting that class II and IV HDACs might play an important role in glioma malignancy. Evaluation of histone acetylation levels showed that histone H3 is more acetylated in glioblastomas than normal brain tissue confirming the downregulation of HDAC mRNA in glioblastomas.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The prognosis of glioblastomas is still extremely poor and the discovery of novel molecular therapeutic targets can be important to optimize treatment strategies. Gene expression analyses comparing ...normal and neoplastic tissues have been used to identify genes associated with tumorigenesis and potential therapeutic targets. We have used this approach to identify differentially expressed genes between primary glioblastomas and non-neoplastic brain tissues. We selected 20 overexpressed genes related to cell cycle, cellular movement and growth, proliferation and cell-to-cell signaling and analyzed their expression levels by real time quantitative PCR in cDNA obtained from microdissected fresh tumor tissue from 20 patients with primary glioblastomas and from 10 samples of non-neoplastic white matter tissue. The gene expression levels were significantly higher in glioblastomas than in non-neoplastic white matter in 18 out of 20 genes analyzed:
P
< 0.00001 for
CDKN2C
,
CKS2
,
EEF1A1
,
EMP3
,
PDPN
,
BNIP2
,
CA12
,
CD34
,
CDC42EP4
,
PPIE
,
SNAI2
,
GDF15
and
MMP23b
; and
NFIA
(
P
: 0.0001),
GPS1
(
P
: 0.0003),
LAMA1
(
P
: 0.002),
STIM1
(
P
: 0.006), and
TASP1
(
P
: 0.01). Five of these genes are located in contiguous loci at 1p31–36 and 2 at 17q24–25 and 8 of them encode surface membrane proteins.
PDPN
and
CD34
protein expression were evaluated by immunohistochemistry and they showed concordance with the PCR results. The present results indicate the presence of 18 overexpressed genes in human primary glioblastomas that may play a significant role in the pathogenesis of these tumors and that deserve further functional investigation as attractive candidates for new therapeutic targets.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Burden of disease is an indicator that relates to health status. United States and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in ...recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx).
To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center.
The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing.
The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37±3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530).
The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease.
Marine Protected Area (MPA) is a fundamental strategy for the maintenance of ocean ecological processes worldwide and, consequently, their associated ecosystem services. Nevertheless, the quality of ...the services provided by MPAs, including cultural services such as recreational activities, depends on the effective management of marine habitats and biodiversity. Here, we performed an ecosystemic assessment in reef environments within a subtropical MPA, modeling the potential risks for their habitats and their recreational activities. The Queimada Grande Island (QGI), southeastern Brazil, was used as the model area since this island encompasses a unique and irreplaceable marine habitat, the Southernmost Atlantic coral reef. We firstly assessed and mapped the habitats, the biodiversity, and the recreational activities associated with QGI reefs. Next, we considered different scenarios of management for the modeling risks across the study area. We found that the coral reef and its adjacent habitats, such as the rhodolith bed, make the sheltered face of the island an important area for the provision of the cultural ecosystem services and overlapping uses such as onboard recreational fishing, spearfishing, and recreational diving. This area was also evaluated as the one under the highest risk of impact, considering the current scenario of management. The most successful scenario modeling to reduce these risks was the hypothetical implementation of a 66% reduction of all activities over all QGI habitats. Despite that, the scenario simulating the application of the regulations present in the MPA management plan was enough to reduce almost half the maximum risk value. Therefore, we concluded that to provide a balance among conservation, uses, and the local economy, the application of these regulations is the better management scenario modeled for the study area. Such results provided useful information and tools for local management and decision-making in this singular marine environment, also being an example for mapping ecosystem services and modeling risks in MPAs worldwide.
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•The use of cultural ecosystem services in MPAs can harm their conservation goals.•We modeled the potential risks for reef environments within a subtropical MPA.•Different uses and scenarios of management were modeled for risks evaluation.•The coral reef and the rhodolith bank had the highest risk of impact by habitat uses.•The regulations of the MPA management plan, if applied, can reduce this risk by half.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The age and growth of three endemic threatened guitarfish species were analysed using vertebrae of Pseudobatos horkelii, P. percellens and Zapteryx brevirostris. Edge and marginal‐increment analyses ...were used to evaluate the periodicity of the formation of the band‐pairs, suggesting deposition of one band‐pair per year, from late winter to late spring. The von Bertalanffy growth model was used to describe the growth of these species with the following parameters, for pooled sexes: P. horkelii
L∞ = 126.93,
k = 0.19 and
t0 = −1.51; P. percellens
L∞ = 109.31,
k = 0.16 and
t0 = −1.78; Z. brevirostris
L∞ = 60.37,
k = 0.24 and
t0 = −1.42. Our results are essential to understanding the resilience and vulnerability of these species to harvest, which can contribute to management and conservation actions of these species.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In the Southwest Atlantic, fisheries and in situ observations suggest that mesophotic reefs occur further south than has been reported in the literature, and a description of these subtropical ...regions is still lacking. We used Baited Remote Underwater stereo-Videos to explore unrevealed patterns in the vertical structure of fish assemblages on subtropical Atlantic reefs, contrasting shallow and mesophotic habitats. Our data on species turnover and light penetration reveal that in the subtropical Atlantic, the boundaries between shallow and mesophotic habitats occur at depths of 18 m, which is shallower than most previous studies have shown. Generalized additive mixed models identified different environmental and management factors as important predictor variables that explain distribution of fish assemblages’ attributes. Besides adding new evidence about mesophotic limits, we described variations in the vertical structure of fish assemblages, providing important information for the description and conservation of mesophotic environments in subtropical regions.
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•Light penetration and species turnover determine boundaries of mesophotic ecosystems.•Shallow and mesophotic zones shelter different species richness and abundance.•Subtropical mesophotic zones do not provide refuge for fishery target species.•Environmental and management factors act in synergy shaping fish assemblages.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Objectives
Investigate the efficacy of caspofungin in participants <3 months of age with invasive Candida infection (ICI).
Methods
This multicentre, randomized, double-blind, ...comparator-controlled, Phase 2 study (protocol MK0991-064; NCT01945281) enrolled participants <3 months of age with culture-confirmed ICI within 96 h of study entry. Participants were randomly assigned 2:1 to once-daily intravenous 2 mg/kg caspofungin or intravenous 1 mg/kg amphotericin B deoxycholate (dAMB). The primary endpoint was fungal-free survival (FFS) 2 weeks after treatment in the full-analysis-set (FAS) population, defined as participants with culture-confirmed ICI who received ≥1 dose of therapy. Planned enrolment was 90 participants.
Results
Fifty-one participants were enrolled; 49 received treatment (caspofungin, n=33; dAMB, n=16); 2 additional participants did not have confirmed infections at study entry. The study was terminated after ∼ 3.5 years because of low enrolment. Forty-seven participants were included in the FAS population (caspofungin, n=31; dAMB, n=16). FFS rate at 2 weeks after treatment was 71.0% (22/31) in the caspofungin arm and 68.8% (11/16) in the dAMB arm difference, stratified by weight, − 0.9% (95% CI, − 24.3%–27.7%). Adverse events developed in 84.8% (28/33) of participants in the caspofungin arm and 100% (16/16) in the dAMB arm.
Conclusions
Among neonates and infants with confirmed ICI, FFS at 2 weeks was similar in the caspofungin and dAMB treatment arms. A smaller proportion of participants who received caspofungin experienced adverse events.
Caprellid material of the present study was collected between 25-3000 m depth from the Campos Basin area, Southwestern Atlantic. As a result, Deutella incerta was found as a new record to the ...Southwestern Atlantic and two new species are described: Liropus guerragarciai sp. nov. and Mayerella sittropiae sp. nov. Besides, Paracaprella pusilla is herein redescribed as a common component of the Campos Basin amphipod community. Caprellids are a diverse and abundant group that can be found among algae and general biological substrates of the continental shelf area. As more deep sea samples are coming into light, they are turning out to be also a common component in this habitat. Including the present data, there are 25 caprellid species recorded in Brazil, being four of them restricted to the slope areas and 14 endemic to the Brazilian coast. A key to the Caprellidae species from Brazil is provided.
Objectives To evaluate the safety and efficacy of different doses of fluconazole used for invasive prophylaxis of fungal infection in neonates. Study design A systematic search was conducted with ...PubMed, Scopus, and Web of Science. A manual search was performed as well. Only randomized controlled trials of neonates in a neonatal intensive care unit (NICU) who received fluconazole prophylaxis for invasive fungal infection, regardless of the dose or therapeutic regimen, were included in this review. Data on baseline characteristics, outcomes incidence of proven invasive Candida infection, overall mortality, and invasive Candida infection-related mortality were extracted. Results Eleven studies were included in the review, with fluconazole doses of 3, 4, or 6 mg/kg. When the incidence of invasive Candida and invasive Candida -related mortality were considered as outcomes, the 3 and 6 mg/kg fluconazole doses were found to be statistically superior to placebo (OR, 5.48 95% credible interval, 1.81-18.94 and 2.63 1.18-7.02, respectively, and 15.32 1.54-54.31 and 9.14 1.26-142.7, respectively), but data for the 3 doses were not statistically significantly different. Conclusions Use of the lowest fluconazole dose (3 mg/kg) should be recommended for Candida prophylaxis in neonates, given that increasing the fluconazole dose is not associated with higher efficacy and has greater potential for toxicity and increased cost.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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