61 mmol/L, P < 0 001) and 13% (−0 34 mmol/L, P = 0 048) compared

61 mmol/L, P < 0.001) and 13% (−0.34 mmol/L, P = 0.048) compared with placebo ( Fig. 1). HDL cholesterol concentrations increased by 11% (0.13 mmol/L, P = 0.013) after fenofibrate treatment, whereas fish oil tended to increase Ipilimumab mouse HDL cholesterol (P = 0.076) compared to placebo.

Compared with fenofibrate treatment, HDL cholesterol (P = 0.737) and triglyceride concentrations (P = 0.133) were comparable after fish oil intake, but total cholesterol (0.91 mmol/L, P < 0.001) and LDL cholesterol (0.78 mmol/L, P < 0.001) were increased. Concentrations of free fatty acids were not affected by either treatment. Fish oil tended to raise fasting plasma glucose concentrations compared to placebo (0.24 mmol/L, P = 0.056) and fenofibrate treatment had no effect (P = 0.721) compared to placebo.

At the end of the intervention period, glucose concentrations between fish oil and fenofibrate treatment (P = 0.250) did not differ. Compared to placebo, fenofibrate significantly reduced total VLDL particle numbers (−23 nmol/L, P = 0.001), in particular large (−2.4 nmol/L, P = 0.003) and medium VLDL particles (−14 nmol/L, P = 0.001). Fish oil reduced the number of large VLDL particles (−3.0 nmol/L, P < 0.001), although the total number of VLDL particles was not affected. It increased however the total number of LDL particles (224 nmol/L, P = 0.005), but decreased the number of IDL particles (−28 nmol/L,

P = 0.016). GSK126 datasheet For HDL, fenofibrate decreased HDL size (−0.11 nm, P = 0.025) and increased the number of medium HDL Interleukin-3 receptor particles (3.1 μmol/L, P = 0.011). Fish oil had no overall effect on HDL size, but increased the number large HDL particles (1.5 μmol/L). Fish oil treatment resulted in higher particle numbers of total VLDL (16 nmol/L, P = 0.02), medium VLDL (13 nmol/L, P = 0.002), total LDL (334 nmol/L, P < 0.001), large LDL (132 nmol/L, P = 0.006) and small LDL (215 nmol/L, P = 0.043) compared to fenofibrate treatment ( Table 3). The number of large HDL particles and HDL size were larger (1.8 nmol/L, P = 0.004 and 0.14 nm, P = 0.004, respectively). The number of medium HDL particles was smaller after fish oil treatment compared to fenofibrate treatment (−4.8 nmol/L, P < 0.001). Concentrations of TNFR1, TNFR2 hsCRP, TNFα, IL6, sICAM1 and sVCAM1 did not differ between the treatments (Table 4). Compared with placebo, the chemokine MCP1, however, increased upon fenofibrate treatment (28 ng/mL, P = 0.034), but remained unaffected after fish oil treatment (P = 0.204) ( Table 4). Further, fenofibrate significantly lowered sE-selectin concentrations compared to both placebo (−4.1 ng/mL, P = 0.034) and fish oil (−5.7 ng/mL, P = 0.014), whereas fish oil treatment had no effect compared to placebo (P = 0.932). Fish oil and micronized fenofibrate were well tolerated by all subjects.

The concentrations in the renal homogenates were determined from

The concentrations in the renal homogenates were determined from standard curves produced with GSH or GSSG standard dilutions. The final results are presented as nanomoles of GSH or GSSG/milligram of protein and the GSH/GSSG ratio (Rahman et al., 2006). Nitric oxide production analyses were done indirectly by the Griess reaction method, which detects nitrite, the NO degradation product (Green et al., 1982). Briefly, the homogenate samples mentioned above were reacted with 1% sulfanilamide for 10 min following reaction with nafitiletilenodiamine. selleck chemicals llc The resultant product was determined by absorbance at 540 nm in a spectrophotometer. The left kidneys of both groups were used for the histological

analyses performed by fixation in 10% formaldehyde and dehydrated in increasing aqueous solutions of ethanol (50%, 70%, 80%, 90%, 95% and 100%) for 30 min each. After dehydration, the NVP-BGJ398 nmr samples

were embedded in paraffin and sectioned (4 and 7 μm) in a microtome (model MRP-03, Lupe Indústria e Comércio Ltda.) These sections were fixed on slides and all tissues were stained with hematoxylin and eosin (H/E) for structural assessment of the tissue, Picrosirius Red to measure the surface density of collagen and periodic acid–Schiff (PAS) to allow visualization of the basement membrane. The sections were mounted on coverslips using Entellan® mounting medium. The fields were photographed randomly. Quantification was obtained using Image-Pro Plus (Media Cybernetics). The percentage of intense red color with the picrosirius red staining was given by comparing it to total renal tissue in the photograph (100%). The percentage of interstitial space was obtained by measuring the spaces in relation to the total area photographed. Right kidneys

were used to obtain membrane-enriched fractions to measure the activities of sodium pumps and protein kinases, and for protein identification. Membrane fractions of kidneys from control rats and rats exposed to MCYST-LR were prepared from the outer cortex (cortex corticis), a region of the kidney in which more than 90% of the cell population corresponds to proximal tubules (Whittembury and Proverbio, 1970; Proverbio and Aspartate Del Castillo, 1981). The external portion of the cortex was carefully removed with a Stadie Riggs microtome and carefully dissected with small scissors to eliminate contamination. The fragments were homogenized in a Teflon and glass homogenizer using 4 ml of solution (250 mM sucrose, 10 mM Hepes–Tris (pH 7.6), 2 μM EDTA, 1 mM phenylmethylsulfonyl fluoride and 0.15 mg/ml of soybean trypsin inhibitor) per gram of kidney slices in an ice bath. The homogenate was centrifuged at 755×g for 10 min at 4 °C. The supernatant was collected and stored at −20 °C or in liquid nitrogen. Protein content was determined by the Folin phenol method ( Lowry et al., 1951).

Post-treatment relapse was confirmed in patients with HCV-RNA lev

Post-treatment relapse was confirmed in patients with HCV-RNA level less than 25 IU/mL at the end of treatment and subsequent HCV-RNA level of 25 IU/mL or greater in 2 consecutive measurements. Efficacy analyses were performed using the intent-to-treat population, defined as all randomized 5-FU supplier HCV genotype 1b–infected patients who received

at least one dose of coformulated ABT-450/ritonavir/ombitasvir. The safety population included all patients who received at least one dose of study drug. A population of 90 patients per treatment arm was calculated to provide greater than 90% power to achieve noninferiority of the active regimen to the historical threshold (64%). SAS software (SAS Institute,

Inc, Cary, NC) for the UNIX operating system was used for all analyses. All statistical tests and all confidence intervals were 2-sided with a significance level of .05. Patient screening began on August 14, 2012, and the final SVR12 data were collected on January 16, 2014. Of 324 patients screened, 187 were randomized and 186 received study drug (91 in group 1, 95 in group 2) (Supplementary Consort Flow Chart). Null responders, partial responders, and relapsers to previous pegIFN/RBV treatment comprised 34.9%, 28.5%, and Protein Tyrosine Kinase inhibitor 36.6% of the study population, respectively,

evenly stratified between treatment arms (Table 1). Reasons for screen failures are provided in the Supplementary Appendix. Seven randomized patients, 3 in group 1 and 4 in group 2, were not included in the intent-to-treat efficacy population. Of these, 6 patients were enrolled before a protocol amendment and received noncoformulated ABT-450/ritonavir/ombitasvir, 3 of whom were genotype 1a; a seventh patient’s HCV subgenotype was not determined. After 12 weeks of treatment, 96.6% (85 of 88; 95% CI, 92.8–100) of group 1 and 100% (91 of 91; 95% CI, 95.9–100) PIK3C2G of group 2 patients achieved SVR12 using the intent-to-treat population for both groups (Figure 1; Table 2, Supplementary Figure 2). For the primary end point, SVR12 rates in both treatment groups were noninferior to the historical SVR rate for telaprevir plus pegIFN/RBV in comparable treatment-experienced patients. Both treatment groups also were superior to the historical rate. Noninferiority of group 2 to group 1 was shown because the treatment difference in SVR12 rates was 3.4% (95% CI, -0.4 to 7.2). No patients from either treatment group experienced on-treatment virologic failure or post-treatment relapse. Of the 3 patients in group 1 who did not achieve SVR12, there were 2 (2.

Both analyses showed that in adults, ROIs across the sensorimotor

Both analyses showed that in adults, ROIs across the sensorimotor cortex with a selective response to tool or animal pictures, tended to show a similar category preference http://www.selleckchem.com/products/DAPT-GSI-IX.html for these picture’s printed names. In contrast, the directions of category-selective response patterns for tool versus animal pictures and tool versus animal names were entirely unrelated in the 7 to 8-year-old and 9 to 10-year-old sensorimotor cortex. Crucially, statistical tests comparing

BOLD-responses derived from type (i) and (ii) ROIs across age, revealed that category-selective responses to printed tool and animal names were significantly more pronounced in the adult cortex than in the child cortex. These results can thus not simply be ascribed to greater increases in BOLD activity in adults than in children. In subgroups of adults

and children matched on scan-to-scan motion and residual noise in the GLM, adults still showed significantly GSK126 manufacturer more ROIs with corresponding category-selectivity for pictures and their printed names than children. Therefore, the age-differences reported here are unlikely to be driven by BOLD-related confounds. It is also unlikely that they are caused by reduced attention or poorer task-performance in children, because accuracy on the one-back task in the scanner was far above chance level and equivalently high across all ages and conditions. In adults, areas in the cortex that were category-selective for

tool versus animal pictures thus clearly showed corresponding category-selectivity for the words describing those pictures in our one-back matching task. This is consistent with the notion that “embodied” category knowledge is activated automatically during reading in the mature cortex (Pulvermueller, 2013). Based on picture-word priming effects in young over readers that suggest automatic co-activation of semantic representation across formats (Ehri, 1976, Rosinski, 1977 and Rosinski et al., 1975), we expected spontaneous picture-like BOLD-responses to printed words to emerge early in reading training. However, we found the opposite, namely that it takes years of training and highly expert reading skills, before familiar printed words give rise to automatic picture-like activations in the cortices of developing readers. Why does sensorimotor cortex engagement during printed word processing take so long to develop? One possibility is that children performed the matching task in the scanner solely by focussing on word shape, without any processing of word content (i.e., without automatic reading). Whilst we cannot fully exclude this possibility because we collected no reading measures in the scanner, we believe this explanation is highly unlikely.

The albumin concentration was determined in all


The albumin concentration was determined in all

admission samples and the concentration of albumin and creatinine was determined in all serial samples. These analyses were conducted by Queensland Health Forensic and Scientific Services at Princess Alexandra Hospital, Brisbane, Australia. This service is accredited by the National Association of Testing Authorities, Australia and certified to International Standards (ISO 9001). The MCPA concentration–time profile in patients providing the most serial samples was Bcl-2 inhibitor constructed using the total and free MCPA concentrations. A plot of the free versus total MCPA concentration was then constructed using data from all admission and serial plasma samples to determine whether protein binding Inhibitor Library research buy was saturable and the approximate concentration at which this occurred. The bound MCPA concentration was calculated as the difference between the free and total concentration at each time point. A Scatchard plot was constructed using the bound and free MCPA concentrations to estimate the number of apparent protein binding sites. Here, following visual inspection, a one-phase (linear) relationship suggests one-site binding,

a two-phase relationship suggests two-site binding, and so on (Kermode, 1989, Molinoff et al., 1981 and Motulsky and Christopoulos, 2005). In the case of two-site binding the relationship between free and bound concentrations is quantified by nonlinear regression using a two-site binding hyperbola model as follows: Bound concentration=Bmax1⋅CuKd1+Cu+Bmax2⋅CuKd2+Cu

Here, Cu is the free (unbound) plasma concentration of MCPA and Kdi and Bmaxi are the affinity constant and maximum density (concentration of saturation) of binding at the ith site ( Molinoff et al., 1981 and Motulsky and Christopoulos, 2005). This analysis was initially conducted using the combined population data. To account for possible inter-individual variability in protein binding, the analysis was also conducted by global fitting. Global fitting is a computational regression method which incorporates best-fit data for individuals when determining the best-fit data for the group as a whole. Finally, because chlorophenoxy compounds Non-specific serine/threonine protein kinase largely bind to albumin ( Braunlich et al., 1989 and Rosso et al., 1998), this regression was also conducted relative to the concentration of albumin (g/L) to determine the extent to which this influenced the fit. When determining the protein binding properties of MCPA it was assumed that binding was at equilibrium at the time of measurement. To determine whether saturation of protein binding influences clearance in humans the plasma apparent elimination half-life was determined prior to and following the concentration where saturation was calculated to occur.

The same template is also used when changes in the shape of the r

The same template is also used when changes in the shape of the radiation field are desired. The template containing this information is given to the physicist to incorporate within the intraoperative treatment planning system. The orientation of the applicator and the template must be established to implement such dose prescriptions correctly. The dose to a larger area (Dose 1) and to the boost region (Dose 2) is determined by the radiation oncologist

and prescribed to 0.5 cm from the applicator’s surface. The HAM applicator is positioned in direct www.selleckchem.com/products/Erlotinib-Hydrochloride.html contact with the area at risk using either sutures or packing to hold the applicator in place (Fig. 3a). Packing is also used to displace normal adjacent organs (e.g., large bowel, bladder, and small intestines) away from the field, as well as lead shields to reduce the dose to normal structures in close contact with the applicator (Fig. 3b). The HAM applicator catheters are then connected to the HDR machine (Fig. 4), the staff leaves the room, and the patient is prepared for treatment via remote afterloader control. Treatment planning is performed while the applicator is secured in the treatment position using

the Abacus HDR planning software Ribociclib chemical structure (GammaMed, Inc., North Jackson, OH). It is especially efficient for planning treatments using applicators with fixed or predefined geometry as it allows the import of the implant geometry. Such a program was developed in-house to interface with Abacus and transfer the treatment geometry as defined in the operating room. The treatment geometry includes source stopping positions and dose reference points, required for dwell-time optimization. A secondary dose calculation algorithm for quality assurance of HDR treatment planning is also performed [5] and [6]. Figure 5 shows a coronal view of dose distribution using the DP for dose-escalation and also dose distribution in an irregular field. After the plan is evaluated and approved by the physician, a second physicist performs an independent check of the treatment plan. The process of planning and checking the plan has been streamlined and takes approximately 5 min. Once the plan is Cediranib (AZD2171) checked and

approved, the treatment proceeds and patient vital signs are monitored remotely. All patients in this study were followed by the surgeon and/or radiation oncologist at 3- to 6-month intervals. All information related to clinical outcome was obtained from the patient electronic medical record system. This was a retrospective study approved by the Institutional Review Board. Treatment-related complications were classified using the Common Toxicity Criteria of Adverse Effects version 3.0. Overall survival (OS) and LC rates were calculated by the Kaplan–Meier method. Local failure was defined as recurrent disease inside of the IORT field and distant failure included any extra-IORT site described by the physician on physical examination, radiographic, and/or pathologic findings.

Recently, Bandyopadhyay et al adapted this approach to reveal ho

Recently, Bandyopadhyay et al. adapted this approach to reveal how cells cope

with DNA damage [ 44••]. They directly compared interactions maps recorded under normal or DNA-damage inducing conditions, a strategy similar to identifying gene expression changes using microarrays. Analyzing each dataset individually recovered mainly ‘housekeeping interactions’ find more between genes involved in chromatin biology (and previously observed in other datasets [ 36•• and 37••]). Focusing on the differences, on the other hand, specifically revealed known DNA repair pathways and pinpointed several new regulators of this well-characterized process. The technical challenges of constructing similar maps in higher organisms are formidable, for example, as the number of possible pairwise gene-combinations grow exponentially with genome size. Our own work has provided a first indication that metazoan interaction maps can be constructed from high-throughput,

combinatorial RNAi approaches [45] (Figure 3). To study the functional interdependencies of signaling pathways in Drosophila cells, we targeted 96 genes – each with two independent RNAi reagents – and generated all ca. 18 000 possible double-knockdown combinations. Recording three distinct quantitative phenotypes (cell growth, nuclear size and DNA content) allowed us to identify more than 600 instances where the double-RNAi phenotype learn more could not be predicted from single perturbations using a multiplicative model [ 46]. Many of these genetic interactions specifically affected only one of the assayed cellular characteristics, highlighting the context-dependence of functional connections ( Figure Baf-A1 nmr 3). Correlating these interaction profiles across different signaling pathways pinpointed Cka/Striatin3 as novel positive regulator of the Ras/MAPK cascade in fruitflies and in human cells [ 45]. The large number of pair-wise – let alone higher order – interactions currently limits

the scope of genetic interaction studies in metazoan cells and further technical innovations are clearly required to experimentally map interactions within mammalian-sized genomes. Future experiments in mammalian cells might, for example, take advantage of novel multiplexing strategies. For example, Muellner et al. molecularly barcoded a panel of 89 engineered isogenic cancer cell lines to survey over 6000 drug–gene interactions in a highly multiplexed format [ 47•] ( Figure 1c). The assay faithfully identified known as well as novel interactions, revealing, for example, that NOTCH1 activation can confer resistance to PI3K inhibitors. Similar multiplex approaches could be applied to the study of gene-gene interactions in the future, and might be expanded further, for example, through next-generation sequencing based quantification strategies [ 48].

Results depicted in Fig 4 indicate that complex I inhibition by

Results depicted in Fig. 4 indicate that complex I inhibition by Ebs, (PhSe)2 and (PhTe)2 was not modified by the addition of SOD (Fig. 4A), CAT (Fig. 4B) or SOD + CAT (Fig. Selleck Daporinad 4C). In order to test the hypothesis that organochalcogens-induced complex I inhibition is mediated by oxidation of thiol groups, we investigated the efficacy of GSH

to reverse the organochalcogens-induced inhibition of complex I. Fig. 5 shows that GSH (500 μM) completely reversed the organochalcogens-induced complex I inhibition in hepatic (Fig. 5A) and in renal (Fig. 5B) membranes. In order to check the inhibitory effect of different organochalcogens in mitochondria complex II activity, we carried out experiments at two different conditions. In brief, in condition 1 the membranes were incubated with the organocompounds (at different concentrations) in the presence of succinate

5 mM for 10 min. The reaction was stopped 3 min after MTT by addition of ethanol. In condition 2, the mitochondrial membranes 3-Methyladenine manufacturer were incubated with various concentrations of organocompounds in the absence of succinate for 10 min. Succinate (5 mM) and MTT were then added and the reaction stopped after 3 min by the addition of ethanol. Statistical analysis indicates that Ebs and (PhTe)2 significantly inhibited both hepatic and renal complex II activity in both conditions (Fig. 6). In contrast, (PhSe)2 did not change the mitochondrial complex II activity from liver (Fig. 6A and B), but inhibited renal complex II activity under condition ioxilan 1 (Fig. 6C), without inhibiting it under experimental condition 2 (Fig. 6D). The IC50 (μM) values for inhibition by organochalcogens of mitochondrial complex II activity, in both conditions, are showed in Table 1. Malonate (8 mM) caused a significant inhibition of the mitochondrial complex II activity that varied from 40% to 70% inhibition (see Fig. 6A–D). GSH (500 μM) completely reversed the organochalcogens-induced complex II inhibition both in hepatic (Fig.

7A) and renal (Fig. 7B) membranes. Ebs and (PhTe)2 inhibited the mitochondrial complexes II–III activity from liver (Fig. 8A) and kidney (Fig. 8B). (PhSe)2 did not inhibit hepatic complexes II–III activity (Fig. 8A), but significantly inhibited renal complexes II–III activity (Fig. 8B). The IC50 (μM) values for inhibition by organochalcogens of mitochondrial complexes II–III activity are showed in Table 1. Statistical analysis revealed that Ebs did not modify the hepatic (Fig. 9A) or renal (Fig. 9B) complex IV activity. (PhSe)2 slightly inhibited complex IV activity from liver and kidney (Fig. 9A and B), whereas (PhTe)2 did not change the renal complex IV activity (Fig. 9B); but it inhibited hepatic complex IV activity at 50 μM (Fig. 9A). The IC50 (μM) value for inhibition by (PhSe)2 of mitochondrial complex IV activity is showed in Table 1.

Neuronal circuits in sensory system are closely connected with ot

Neuronal circuits in sensory system are closely connected with other nerve systems for efficient handling of sensory information.1 For example, taste sensory CHIR-99021 concentration information that reached the nucleus tractus of solitarius is principally relayed to the gustatory

cortex via the parabrachial nucleus, but also targets to the other brain area such as the cerebral cortex, hippocampus, amygdala, hypothalamus and nucleus accumbens for the better storage or recall of taste memory or the innate and instinctive response such as preference and aversion.2, 3 and 4 Thus, it is suggested that the deprivation or disruption of taste sensory relays may affect the function of those brain regions. Taste sensory system is in charge of evaluating the nutritious content of food and preventing the ingestion of toxic substances, and importantly also has the additional value of contributing to the overall pleasure and enjoyment of a meal. Eating has been viewed as a strategy to improve negative mood5 and to mask stress,6 and studies indicate that healthy, normal-weight persons regulate negative emotions by eating.7 and 8 It has been reported that decreased responses

in the reward network including the nucleus accumbens to palatable food may be a trait marker of vulnerability to depression.9 and 10 In rodents, anhedonia, a reduced sensitivity to reward, which is a core symptom of major depression, can be measured by a decreased intake of and preference for sweet solutions. Indeed, sweet solutions have been shown to rapidly calm stress responses in human Dichloromethane dehalogenase newborns,11 and GSK126 in vitro in adults, experimentally induced negative mood is improved

immediately and selectively after eating palatable food,12 suggesting that immediate positive affective reactions elicited by palatable foods diminish the impact of stress. Collectively, it is hypothesized that alterations in oral sensory information can modulate the psycho-emotional status of individuals. Lingual nerve can be damaged by dental surgery or trauma such as physical irritation, radiation, chemotherapy, or viral infection. This study was conducted to define the psycho-emotional effects of the lingual nerve damage in which oral sensory relay to the brain is disrupted, and the rats were tested for anxiety- and depression-like behaviours after bilateral transections of the lingual and chorda tympani nerves. The chorda tympani nerve joins the lingual division of the trigeminal nerve, the lingual nerve, and distributes together to the fungiform papillae on the anterior two thirds of the tongue and may reach also the anterior portion of the foliate papillae. Axons of glossopharyngeal nerve supply both tastes buds and general sensory innervations to the vallate and foliate papillae, and also tastes buds in the pharynx.13 Thus, it is expected that with bilateral transections of the lingual and chorda tympani nerves, rats may lose the sensory information from the anterior two thirds of tongue.

Nestes doentes, o risco clínico de progressão para CHC foi assumi

Nestes doentes, o risco clínico de progressão para CHC foi assumido como idêntico ao do doente com HBC e carga viral indetectável. Quarto, em relação ao risco de progressão da doença foi assumido que doentes em supressão viral não estariam em risco de progressão de HBC para CC e de CC para CD9 and 10. Em doentes com carga viral detectável, o risco de progressão assume-se independente do nível de replicação viral. Tal pressuposto não acautela, portanto, o facto de a progressão poder depender, de forma mais gradual, do nível dessa replicação46. Efetivamente, no estudo REVEAL52, a razão de chances (odds ratio) do número de casos de cirrose, face a doentes

com ADN-VHB http://www.selleckchem.com/products/17-AAG(Geldanamycin).html < 1000 cópias/mL, aumenta proporcionalmente com o nível de ADN-VHB. Acresce que as taxas de progressão utilizadas são também uma aproximação. As taxas de progressão de HBC para CC (de acordo com o padrão de AgHBe) foram assumidas como sendo iguais aos limites superiores reportados por de Francis et al. 31 d. Para as taxas de progressão de CC para CD (assumida como idêntica PLX3397 clinical trial nos 2 padrões de AgHBe) foram utilizados os dados reportados por Idris et al. 3 à semelhança do pressuposto utilizado no estudo de custo-efetividade do tratamento da HBC em Espanha 14. Quinto, em linha com os resultados publicados por Liu et al.53, assume-se que o risco clínico de CHC ou TH é dependente

da carga viral mas independente do padrão de AgHBe. Relativamente à diferenciação do risco clínico de CHC, em função da supressão viral ou ausência desta, deve referir-se que, no estudo recentemente publicado por Papatheodoridis et al.54, não foi encontrada evidência Thalidomide de que a supressão

viral prevenisse o CHC em doentes AgHBe-negativos com cirrose. Apesar das limitações e estimativas necessárias para concretizar este estudo, os resultados alcançados demonstram a dominância de uma das terapêuticas avaliadas. Concretamente, de acordo com a análise realizada o medicamento TDF é uma alternativa dominante, quando comparado com ETV no tratamento oral da HBC, uma vez que gera menores custos e maior efetividade. A análise de sensibilidade confirma este resultado para diferentes cenários em que adotamos variações de grande amplitude dos parâmetros do modelo (custos e efetividade). Assim, os resultados ora produzidos constituem um importante contributo como informação de apoio à decisão terapêutica, numa ótica de valorização e otimização dos recursos disponíveis (e escassos) no sistema de saúde português. O estudo de avaliação económica foi financiado pela empresa Gilead Sciences. O estudo foi desenvolvido de forma independente, sem que lhe tivessem sido impostos quaisquer condicionalismos sobre os resultados por parte do financiador. Assim sendo, as opiniões aqui expressas são fruto da análise e interpretação dos autores e não refletem necessariamente outros pontos de vista. J. Areias, A. Carvalho, G. Macedo, R. Marinho, L.