Intracellular Pathways and Mechanisms of Colored Secondary Metabolites in Cancer Therapy.

Despite the great advancements made in cancer treatment, there are still many unsatisfied aspects, such as the wide palette of side effects and the drug resistance. There is an obvious increasing scientific attention towards nature and what it can offer the human race. Natural products can be used to treat many diseases, of which some plant products are currently used to treat cancer. Plants produce secondary metabolites for their signaling mechanisms and natural defense. A variety of plant-derived products have shown promising anticancer properties in vitro and in vivo. Rather than recreating the natural production environment, ongoing studies are currently setting various strategies to significantly manipulate the quantity of anticancer molecules in plants. This review focuses on the recently studied secondary metabolite agents that have shown promising anticancer activity, outlining their potential mechanisms of action and pathways.

Manufacture of a nothing on insulator nano-structure with two Cr/Au nanowires separated by 18 nm air gap.

Despite the huge number of previous studies of vacuum devices, nanoscale technologies open new paradigms. Vacuum nanodevices bring multiple advantages, such as air instead of a vacuum for the nanometric gap, strong non-linear characteristics, and a metal oxide semiconductor co-integration facility. This paper presents the manufacturing process and measured characteristics of a nano-device that uses a sub-36 nm gap between two Cr/Au nano-wires. In this way, the metal nano-wires replace the semiconductor nano-islands, while an air gap stands for the 'nothing' region of a first-time fabricated variant for a nothing on insulator device. The electron beam lithography mask-less technology is pushed to its technical limit to define a minimum 18 nm-wide gap between two Cr/Au nanowires. The main current-voltage curves are measured for this first real device called a nothing on insulator in the variant metal-air-metal, indicating 10 nA at 10 V as the optimal variant. The main connections between the measurements and technology are emphasized.

Magnetic Resonance Imaging Assessment of Kidney Oxygenation and Perfusion During Sickle Cell Vaso-occlusive Crises.

BACKGROUND: Our understanding of the pathophysiologic processes underlying sickle cell nephropathy remains incomplete. We performed a pilot study to investigate the potential value of magnetic resonance imaging (MRI) for the assessment of kidney oxygenation and detection of potential changes to tissue perfusion and cellular integrity during a vaso-occlusive crisis. STUDY DESIGN: A case-control study. SETTING & PARTICIPANTS: 10 homozygous patients with sickle cell disease (SCD), without kidney disease (based on estimated glomerular filtration rate and albuminuria), underwent renal MRI during a vaso-occlusive crisis episode. The imaging data obtained were compared with those for a second MRI performed at steady state (median, 56 [IQR, 37-72] days after the vaso-occlusive crisis MRI). The control group consisted of 10 apparently healthy individuals. MEASUREMENTS: Deoxyhemoglobin level assessed by R2* value was calculated using the blood oxygen level-dependent technique. The intravoxel incoherent motion diffusion-weighted imaging technique was used to calculate D, D*, and F parameters. RESULTS: Median medullary R2* values on steady-state MRI were significantly higher for patients with SCD than for controls (P=0.01) and did not change significantly during the vaso-occlusive crisis. No significant differences in median cortical R2* values were observed. Both cellular integrity (D) and local perfusion (D* and F) were significantly altered in medullary and cortical areas during vaso-occlusive crises in comparison to steady state in patients with SCD. These parameters did not differ significantly between patients with SCD assessed at steady state and the control group. LIMITATIONS: Small sample size, estimation of glomerular filtration rate according to CKD-EPI creatinine equation without adjustment for race. CONCLUSIONS: Deoxyhemoglobin levels in the medullary area are higher in patients with SCD, during vaso-occlusive crises and at steady state, than in controls. Alterations to the tissue perfusion and cellular integrity of renal parenchyma are a common finding during vaso-occlusive crises that provide additional evidence that a vaso-occlusive crisis may be associated with subclinical kidney injury detectable on MRI.

Integration of Ultrasound in Image-Guided Adaptive Brachytherapy in Cancer of the Uterine Cervix.

Cervical cancer continues to be a public health concern, as it remains the second most common cancer despite screening programs. It is the third most common cause of cancer-related death for women, and the majority of cases happen in developing nations. The standard treatment for locally advanced cervical cancer involves the use of external beam radiation therapy, along with concurrent chemotherapy, followed by an image-guided adaptive brachytherapy (IGABT) boost. The five-year relative survival rate for European women diagnosed with cervical cancer was 62% between 2000 and 2007. Updated cervical cancer treatment guidelines based on IGABT have been developed by the Gynecological working group, which is composed of the Group Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology. The therapeutic strategy makes use of three-dimensional imaging, which can be tailored to the target volume and at-risk organs through the use of computed tomography or magnetic resonance imaging. Under anaesthesia, the brachytherapy implantation is carried out. Ultrasonography is utilised to assess the depth of the uterine cavity and to facilitate the dilation of the uterine canal during the application insertion. In this study, we examine data from the international literature regarding the application of ultrasound in cervical cancer brachytherapy.

Biodegradation Study of Styrene-Butadiene Composites with Incorporated Arthrospira platensis Biomass.

The preparation of polymer composites that incorporate material of a biogenic nature in the polymer matrices may lead to a reduction in fossil polymer consumption and a potentially higher biodegradability. Furthermore, microalgae biomass as biogenic filler has the advantage of fast growth and high tolerance to different types of culture media with higher production yields than those provided by the biomass of terrestrial crops. On the other hand, algal biomass can be a secondary product in wastewater treatment processes. For the present study, an SBS polymer composite (SBSC) containing 25% (w/w) copolymer SBS1 (linear copolymer: 30% styrene and 70% butadiene), 50% (w/w) copolymer SBS2 (linear copolymer: 40% styrene and 60% butadiene), and 25% (w/w) paraffin oil was prepared. Arthrospira platensis biomass (moisture content 6.0 ± 0.5%) was incorporated into the SBSC in 5, 10, 20, and 30% (w/w) ratios to obtain polymer composites with spirulina biomass. For the biodegradation studies, the ISO 14855-1:2012(E) standard was applied, with slight changes, as per the specificity of our experiments. The degradation of the studied materials was followed by quantitatively monitoring the CO2 resulting from the degradation process and captured by absorption in NaOH solution 0.5 mol/L. The structural and morphological changes induced by the industrial composting test on the materials were followed by physical-mechanical, FTIR, SEM, and DSC analysis. The obtained results were compared to create a picture of the material transformation during the composting period. Thus, the collected data indicate two biodegradation processes, of the polymer and the biomass, which take place at the same time at different rates, which influence each other. On the other hand, it is found that the material becomes less ordered, with a sponge-like morphology; the increase in the percentage of biomass leads to an advanced degree of degradation of the material. The FTIR analysis data suggest the possibility of the formation of peptide bonds between the aromatic nuclei in the styrene block and the molecular residues resulting from biomass biodegradation. It seems that in industrial composting conditions, the area of the polystyrene blocks from the SBS-based composite is preferentially transformed in the process.

Influence of Biogenic Material Content on the Biodegradability of Styrene-Butadiene Composites with Incorporated Chlorella vulgaris Biomass.

Bio-fillers are intensively studied for advanced polymer composite circular design and production. In this context, the algal biomass may be considered an important and relatively low-cost resource, when harvested as a by-product from wastewater treatment plants. The biomass of the algal species Chlorella vulgaris is frequently used in this type of environmental process, and its macro constituents' composition ranges from around 15-25% carbohydrates, 10-20% lipids, and 50-60% proteins. Poly (styrene-butadiene-styrene) (SBS) copolymers have a matrix composed of glassy polystyrene domains connected by flexible polybutadiene segments. Although the physical-mechanical properties of SBS copolymers recommend them for many industrial applications, they have the drawback of low biodegradability. This study aimed to assess the aerobic biodegradability of polymer composites by integrating biomass from Chlorella vulgaris at varying mass percentages of 5, 10, and 20% into SBS copolymer composites. Biodegradation tests were conducted under industrial composting conditions (58 °C and 50% relative humidity) for 180 days. The biodegradability of materials was evaluated by measuring the CO2 produced in each vessel during the study period. Potential correlations between the amount of carbon dioxide released and the percentage of biomass added to the polymer matrix were examined. Structural and morphological changes were assessed using Fourier Transform infrared spectroscopy (FTIR), thermal analysis (DSC), and scanning electron microscopy (SEM). Physical and chemical testing revealed a decrease in sample density after the industrial composting test, along with noticeable changes in melt flow index (MFI). The observed physical and chemical changes, coupled with FTIR, SEM, and DSC data, indicate increased cross-linking and higher porosity in biodegraded polymer structures with higher biomass content. This behavior is likely due to the formation of cross-linked connections between polymer chains and polypeptide chains resulting from protein degradation, enhancing connections between polystyrene units facilitated by peptide bonds with the benzene units of the styrene blocks within the polymer matrix.

In vitro evaluation of Axitinib and Sorafenib treatment in glioblastoma cell viability and morphology.

The formation, proliferation, and evolution of glioblastoma (GB) are significantly influenced by pathological angiogenesis. This is supported by several growth factor receptors, such as the vascular endothelial growth factor receptor (VEGFR). In this experiment, we examined how the Food and Drug Administration (FDA) approved VEGFR blockers Sorafenib and Axitinib affect the viability of GB cells in vitro. Cells were cultivated in 96-well culture plates for the experiments, afterwards Sorafenib and Axitinib were administered at doses ranging from 0.3 µM to 80 µM. 2,5-Diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the impact of VEGFR inhibition on high-grade glioma (HGG) cell lines. To observe the morphological changes in cell shape, we used a 10× magnification microscopy. Our results showed that both Axitinib and Sorafenib retarded GB1B culture proliferation in a dose- and time-dependent manner in comparison to control cohorts that had not received any treatment. The half maximal inhibitory concentration (IC50) value for Axitinib was 3.5839 µM after three days of drug administration and 2.2133 µM after seven days of drug administration. The IC50 value for Sorafenib was 3.5152 µM after three days of drug administration and 1.6846 µM after seven days of drug administration. After the treatment with Axitinib or Sorafenib, very few cells became rounded and detached from the support, others remained adherent to the culture substrate, but acquired a larger, flatter shape. Our results indicate that VEGFR might serve as a key target in the treatment of GB. Although it is known that in vitro some drugs block the VEGFR more potently, clinical evidence is required to show whether this actually translates to better clinical outcomes.

Preparation and Characterization of Microalgae Styrene-Butadiene Composites Using Chlorella vulgaris and Arthrospira platensis Biomass.

The food industry is a high consumer of polymer packing materials, sealing materials, and engineering components used in production equipment. Biobased polymer composites used in the food industry are obtained by incorporating different biogenic materials into the structure of a base polymer matrix. Renewable resources such as microalgae, bacteria, and plants may be used as biogenic materials for this purpose. Photoautotrophic microalgae are valuable microorganisms that are able to harvest sunlight energy and capture CO2 into biomass. They are characterized by their metabolic adaptability to environmental conditions, higher photosynthetic efficiency than terrestrial plants, and natural macromolecules and pigments. The flexibility of microalgae to grow in either low-nutrient or nutrient-rich environments (including wastewater) has led to the attention for their use in various biotechnological applications. Carbohydrates, proteins, and lipids are the main three classes of macromolecular compounds contained in microalgal biomass. The content in each of these components depends on their growth conditions. In general, proteins represent 40-70% of microalgae dry biomass, followed by carbohydrates (10-30%) and lipids (5-20%). A distinctive feature of microalgae cells is the presence of light-harvesting compounds such as photosynthetic pigments carotenoids, chlorophylls, and phycobilins, which are also receiving growing interest for applications in various industrial fields. The study comparatively reports on polymer composites obtained with biomass made of two species of green microalgae: Chlorella vulgaris and filamentous, gram-negative cyanobacterium Arthrospira. Experiments were conducted to reach an incorporation ratio of the biogenic material into the matrix in the 5-30% range, and the resulting materials were characterized by their mechanical and physicochemical properties.

A switch from horizontal compression to vertical extension in the Vrancea slab explained by the volume reduction of serpentine dehydration.

The Vrancea slab, Romania, is a subducted remnant of the Tethyan lithosphere characterized by a significant intermediate-depth seismicity (60-170 km). A recent study showed a correlation between this seismicity and major dehydration reactions, involving serpentine minerals up to 130 km depth, and high-pressure hydrated talc deeper. Here we investigate the potential link between the triggering mechanisms and the retrieved focal mechanisms of 940 earthquakes, which allows interpreting the depth distribution of the stress field. We observe a switch from horizontal compression to vertical extension between 100 and 130 km depth, where the Clapeyron slope of serpentine dehydration is negative. The negative volume change within dehydrating serpentinized faults, expected mostly sub-horizontal in the verticalized slab, could well explain the vertical extension recorded by the intermediate-depth seismicity. This apparent slab pull is accompanied with a rotation of the main compressive stress, which could favour slab detachments in active subduction zones.

Dehydration-induced earthquakes identified in a subducted oceanic slab beneath Vrancea, Romania.

Vrancea, Eastern Romania, presents a significant intermediate-depth seismicity, between 60 and 170 km depth, i.e. pressures from 2 to 6.5 GPa. A debate has been lasting for decades regarding the nature of the seismic volume, which could correspond to the remnant of a subducted slab of Tethyan lithosphere or a delamination of the Carpathians lithosphere. Here we compile the entire seismicity dataset (≈ 10,000 events with 2 ≤ Mw ≤ 7.9) beneath Vrancea for P > 0.55 GPa (> 20 km) since 1940 and estimate the pressure and temperature associated with each hypocenter. We infer the pressure and temperature, respectively, from a depth-pressure conversion and from the most recent tomography-based thermal model. Pressure-temperature diagrams show to what extent these hypocentral conditions match the thermodynamic stability limits for minerals typical of the uppermost mantle, oceanic crust and lower continental crust. The stability limits of lawsonite, chloritoid, serpentine and talc minerals show particularly good correlations. Overall, the destabilization of both mantle and crustal minerals could participate in explaining the observed seismicity, but mantle minerals appear more likely with more convincing correlations. Most hypocentral conditions match relatively well antigorite dehydration between 2 and 4.5 GPa; at higher pressures, the dehydration of the 10-Å phase provides the best fit. We demonstrate that the Vrancea intermediate-depth seismicity is evidence of the current dehydration of an oceanic slab beneath Romania. Our results are consistent with a recent rollback of a W-dipping oceanic slab, whose current location is explained by limited delamination of the continental Moesian lithosphere between the Tethyan suture zone and Vrancea.

Optimized Technologies for Cointegration of MOS Transistor and Glucose Oxidase Enzyme on a Si-Wafer.

The biosensors that work with field effect transistors as transducers and enzymes as bio-receptors are called ENFET devices. In the actual paper, a traditional MOS-FET transistor is cointegrated with a glucose oxidase enzyme, offering a glucose biosensor. The manufacturing process of the proposed ENFET is optimized in the second iteration. Above the MOS gate oxide, the enzymatic bioreceptor as the glucose oxidase is entrapped onto the nano-structured TiO2 compound. This paper proposes multiple details for cointegration between MOS devices with enzymatic biosensors. The Ti conversion into a nanostructured layer occurs by anodization. Two cross-linkers are experimentally studied for a better enzyme immobilization. The final part of the paper combines experimental data with analytical models and extracts the calibration curve of this ENFET transistor, prescribing at the same time a design methodology.

Pearson syndrome in the neonatal period: two case reports and review of the literature.

Pearson syndrome is a multiorgan mitochondrial cytopathy that results from defective oxidative phosphorylation owing to mitochondrial DNA deletions. Prognosis is severe and death occurs in infancy or early childhood. This article describes 2 cases with a severe neonatal onset of the disease. A review of the literature reveals the atypical presentation of the disease in the neonatal period, which is often overlooked and underdiagnosed.

Total Reference Air Kerma is Associated with Late Bowel Morbidity in Locally Advanced Cervical Cancer Patients Treated with Image-Guided Adaptive Brachytherapy.

No dose volume parameter has been identified to predict late bowel toxicities in locally advanced cervical cancer (LACC) patients treated with image-guided adaptive brachytherapy. We examined the incidence of bowel toxicities according to the total reference air kerma (TRAK) in 260 LACC patients. In both univariate and multivariate analysis, late morbidity positively correlated with a TRAK ≥2 cGy (centigray) at 1 meter, emphasizing the importance of this parameter in term of late bowel morbidity. Objective: There is no validated dose volume parameter to predict late bowel toxicities in cervical cancer patients treated with image-guided adaptive brachytherapy (IGABT). We examined the incidence of bowel toxicities according to the TRAK, which is proportional to the integral dose to the patients. Material/Methods: Clinical data of 260 LACC patients treated with curative intent from 2004 to 2016 were examined. Patients received chemoradiation plus a pulse-dose rate IGABT boost. The relationship between TRAK and morbidity was assessed by Kaplan-Meier method, log-rank tests, and Cox proportional-hazards model on event-free periods. Results: Median follow-up was 5.2 years (SE (Standard Error): 0.21). Probability of survival without late bowel toxicity Grade ≥ 2 rate for patients without recurrence (n = 227) at 5 years was 66.4% (SE 3.7). In univariate analysis, bowel and/or sigmoid dose/volume parameters were not significant. Late morbidity positively correlated with active smoking, CTVHR volume >25 cm³, and a TRAK ≥2 cGy at 1 meter. In multivariate analysis, the following factors were significant: Active smoking (p < 0.001; HR: 2.6; 95%CI: 1.4⁻5.0), and the TRAK (p = 0.02; HR: 2.4; 95%CI: 1.2⁻5.0). Conclusion: TRAK was associated with late bowel toxicities probability, suggesting that the integral dose should be considered, even in the era of IGABT.

Risk of Late Urinary Complications Following Image Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: Refining Bladder Dose-Volume Parameters.

PURPOSE: To study correlations between dose-volume parameters of the whole bladder and bladder trigone and late urinary toxicity in locally advanced cervical cancer patients treated with pulsed-dose-rate brachytherapy. METHODS AND MATERIALS: Patients with locally advanced cervical cancer treated with chemoradiation therapy and pulsed-dose-rate brachytherapy from 2004 to 2015 were included. Cumulative dose-volume parameters of the whole bladder and bladder trigone were converted into 2-Gy/fraction equivalents (EQD2, with α/ß = 3 Gy); these parameters, as well as clinical factors, were analyzed as predictors of toxicity in patients without local relapse. RESULTS: A total of 297 patients fulfilled the inclusion criteria. The median follow-up period was 4.9 years (95% confidence interval 4.5-5.3 years). In patients without local relapse (n = 251), the Kaplan-Meier estimated grade 2 or higher urinary toxicity rates at 3 years and 5 years were 25.4% and 32.1%, respectively. Minimal dose to the most exposed 2 cm3 of the whole bladder [Formula: see text] , bladder International Commission on Radiation Units & Measurements (ICRU) (BICRU) dose, and trigone dose-volume parameters correlated with grade 2 or higher toxicity. At 3 years, the cumulative incidence of grade 2 or higher complications was 22.8% (standard error, 2.9%) for bladder [Formula: see text]  < 80 GyEQD2 versus 61.8% (standard error, 12.7%) for [Formula: see text]  ≥ 80 GyEQD2 (P = .001). In the subgroup of patients with bladder [Formula: see text]  ≤ 80 GyEQD2, a trigone dose delivered to 50% of the volume (D50%) > 60 GyEQD2 was significant for grade 2 or higher toxicity (P = .027). The probability of grade 3 or higher toxicities increased with bladder [Formula: see text]  > 80 GyEQD2 (16.7% vs 1.6%; hazard ratio [HR], 5.77; P = .039), BICRU dose > 65 GyEQD2 (4.9% vs 1.3%; HR, 6.36; P = .018), and trigone D50% > 60 GyEQD2 (3.1% vs 1.2%; HR, 6.29; P = .028). Pearson correlation coefficients showed a moderate correlation between bladder [Formula: see text] , BICRU dose, and bladder trigone D50% (P < .0001). CONCLUSIONS: These data suggest that [Formula: see text]  ≤ 80 GyEQD2 should be advised for minimizing the risk of severe urinary complications (<15%). Bladder trigone dose was also predictive of severe late urinary toxicity. These constraints need further confirmation in a multicenter prospective setting.

Overcoming Microalgae Harvesting Barrier by Activated Algae Granules.

The economic factor of the microalgae harvesting step acts as a barrier to scaling up microalgae-based technology designed for wastewater treatment. In view of that, this study presents an alternative microalgae-bacteria system, which is proposed for eliminating the economic obstacle. Instead of the microalgae-bacteria (activated algae) flocs, the study aimed to develop activated algae granules comprising the microalgae Chlorella sp. as a target species. The presence of the filamentous microalgae (Phormidium sp.) was necessary for the occurrence of the granulation processes. A progressive decrease in frequency of the free Chlorella sp. cells was achieved once with the development of the activated algae granules as a result of the target microalgae being captured in the dense and tangled network of filaments. The mature activated algae granules ranged between 600 and 2,000 µm, and were characterized by a compact structure and significant settling ability (21.6 ± 0.9 m/h). In relation to the main aim of this study, a microalgae recovery efficiency of higher than 99% was achieved only by fast sedimentation of the granules; this performance highlighted the viability of the granular activated algae system for sustaining a microalgae harvesting procedure with neither cost nor energy inputs.

Costimulatory molecule CD154 in systemic lupus erythematosus and rheumatoid arthritis. Therapeutic perspectives.

SLE is a systemic autoimmune disease characterized by B cell hyperactivity. Evidence from the last years has shown that B cells play a key role in the development of the immune response. The interaction of CD40 on B cells with its ligand CD154 on activated T cells provides a costimulatory signal that induces T dependent B cell proliferation and differentiation with subsequent antibody production. Moreover, CD154 can act as a cytokine, in addition to its main role to mediate the interactions between T and CD40+ target cells. This review focuses on the multiple roles of CD154 in systemic lupus erythematosus and rheumatoid arthritis and its involvement in the humoral immunity disregulation of patients with these diseases. It also takes in consideration the most recent therapeutic perspectives regarding the use of monoclonal antibodies against CD154, which might be a powerful tool in the treatment of these diseases in the future.

EVOLUTION OF SYNCHRONOUS BILATERAL BREAST CARCINOMA IN A YOUNG PATIENT.

Bilateral breast cancer incidence is appreciated to be between 0.3 to 12% and is determined either by a hereditary load associated with chromosomal instability under the effect of environmental factors, or by the evolution in a particular hormonal context which gives biological aggressiveness. We present the case of a patient, aged 38 years, clinically, imagistic and bioptic diagnosed with left axillary lymph node metastases of breast carcinoma NST invasive G3, IHC-RE = 60%, RP = 30%, HER2neu = 2 +, Ki67 = 20%, in August 2013. Patient followed neoadjuvant chemotherapy treatment during September-October 2013. In December 2013 she was clinically and imaging diagnosed with bilateral breast cancer, for which surgical intervention was done which consisted of bilateral radical Madden mastectomy with bilateral axillary lymphadenectomy. BAP-invasive carcinoma NST: left breast-pT2mN3a G2, right breast--pT3mN3a G2, IHC-RE = 90%, RP =70% HER2neu = 2 +, Ki67 = 50%. During the period of January-March 2014, the patient followed adjuvant chemotherapy and Herceptin. Bilateral breast ultrasound assessment in April 2014 revealed: left axilla--liquid blade 29 / 6mm; right axilla--oval ganglion 9/5 mm. Abdominal and pelvic ultrasound: empty uterine cavity, bosselated contour; at left ovary level multiple cystic formations. During the period of May-June 2014, adjuvant radiation therapy and ovarian irradiationwas administered to the patient. Subsequently hormone therapy was initiated. Following CHT / ovarian irradiation patient continues to experience intermittent uterine bleeding, which is why a total hysterectomy with bilateral ovariectomy was done, and BAP: cervical, endometrialand left ovary with tumor multifocal infiltration with histopathological aspect of invasive breast carcinoma NST. Periodic imaging evaluations do not reveal local or distant recurrence. The particularity of this case is synchronous bilateral breast cancer diagnosis in a young patient complicated in its evolution by ovarian metastases. This form of metastasis is rare in young women and occurs in advanced stages of the disease.

THERMOPLASTIC MATERIALS APPLICATIONS IN RADIATION THERAPY.

This is an example of the use of thermoplastic materials in a high-tech medicine field, oncology radiation therapy, in order to produce the rigid masks for positioning and immobilization of the patient during simulation of the treatment procedure, the imaging verification of position and administration of the indicated radiation dose. Implementation of modern techniques of radiation therapy is possible only if provided with performant equipment (CT simulators, linear accelerators of high energy particles provided with multilamellar collimators and imaging verification systems) and accessories that increase the precision of the treatment (special supports for head-neck, thorax, pelvis, head-neck and thorax immobilization masks, compensating materials like bolus type material). The paper illustrates the main steps in modern radiation therapy service and argues the role of thermoplastics in reducing daily patient positioning errors during treatment. As part of quality assurance of irradiation procedure, using a rigid mask is mandatory when applying 3D conformal radiation therapy techniques, radiation therapy with intensity modulated radiation or rotational techninques.

Rosuvastatin Is Effective to Decrease CD8 T-Cell Activation Only in HIV-Infected Patients With High Residual T-Cell Activation Under Antiretroviral Therapy.

OBJECTIVE: The aim of the trial was to evaluate in patients under antiretroviral therapy (ART) the effect of rosuvastatin on cellular and soluble markers of immune activation/inflammation, as well as to identify patients who better benefit from statin administration. METHODS: IMEA-043-CESAR was a phase II open-label pilot trial that enrolled patients under suppressive ART and CD4 <500/mm. Patients received rosuvastatin (20 mg/d) for 12 weeks. The primary outcome was the variation at week 12 (W12) in the proportion of CD38HLA-DRCD8 T lymphocytes. Secondary outcomes included evolution of other markers of T-cell activation and of inflammatory biomarkers between baseline, W12, and W24. RESULTS: Fifty patients were enrolled; end points were available for 43 patients. When considering all patients, the proportion of CD38HLA-DRCD8 T cells did not significantly decline throughout the follow-up. However, the proportion of CD38CD8T cells significantly decreased at W12 [median percentage change of -22.2% (-32.3; +1.4)]. Principal component analysis allowed identification of 3 groups of patients based on their baseline activation/inflammation profiles, 1 group with elevated levels of CD8 T-cell activation, and a small group with high levels of systemic inflammation and low levels of T-cell activation. Half of the patients exhibited relatively low levels of inflammation and activation. The proportion of activated CD8 T cells significantly decreased only in the particular group of patients with high baseline CD8 T-cell activation. CONCLUSIONS: This study shows that combining rosuvastatin with effective ART can result in a sustained decrease in CD8 T-cell activation and highlights the importance of identifying patients who can benefit from specific immunotherapeutic strategies.