One of these signals can remodel a light-signaling network that r

One of these signals can remodel a light-signaling network that regulates the expression of nuclear genes

that encode particular antenna proteins of photosystem II. These findings led us to test whether plastid JQEZ5 nmr signals might impact other light-regulated processes.\n\nPhotomorphogenesis was monitored in genomes uncoupled 1 (gun1), cryptochrome 1 (cry1), and long hypocotyl 5 (hy5), which have defects in light and plastid signaling, by growing Arabidopsis thaliana seedlings under various light conditions and either treating or not treating them with antibiotics that induce chloroplast dysfunction and trigger plastid signaling.\n\nIt was found that plastid signals that depend on GUN1 can affect cotyledon opening and expansion, anthocyanin biosynthesis, and hypocotyl elongation. We also found that plastid signals that depend on CRY1 can regulate cotyledon expansion and development.\n\nOur findings suggest that plastid signals triggered by plastid dysfunction can broadly affect photomorphogenesis and that plastid and light signaling can promote or antagonize each other, depending on the responses studied. Sapitinib These data suggest that GUN1 and cry 1 help to integrate chloroplast

function with photomorphogenesis.”
“Peroxisome proliferator-activated receptors (PPARs) are potentially useful for the treatment of skin diseases, because they stimulate keratinocyte differentiation, exert anti-inflammatory effects and improve barrier function. We examined five PPAR- agonists,

including four thiazolidinediones (ciglitazone, troglitazone, rosiglitazone and pioglitazone) and an angiotensin-II receptor blocker (telmisartan), for their ability to upregulate filaggrin and selleck loricrin expression at both mRNA and protein levels in cultured normal human keratinocytes (NHKs). Troglitazone, rosiglitazone, pioglitazone and telmisartan significantly increased filaggrin expression at both mRNA and protein levels in calcium-induced differentiated NHKs. Rosiglitazone and pioglitazone, but not troglitazone nor telmisartan, also significantly increased loricrin expression at both mRNA and protein levels in differentiated NHKs. These effects were not found in undifferentiated NHKs nor differentiated NHKs treated with ciglitazone. This study revealed differential effects of various PPAR- agonists on epidermal differentiation, and the most potent of those are rosiglitazone and pioglitazone.”
“Entamoeba histolytica is the third-leading cause of parasitic mortality globally. E. histolytica infection generally does not cause symptoms, but the parasite has potent pathogenic potential. The origins, benefits, and triggers of amoebic virulence are complex. Amoebic pathogenesis entails depletion of the host mucosal barrier, adherence to the colonic lumen, cytotoxicity, and invasion of the colonic epithelium. Parasite damage results in colitis and, in some cases, disseminated disease.

Therefore, we next examine the general electronic properties of s

Therefore, we next examine the general electronic properties of single-crystalline 2D MoS2 and study the role of GBs in the electrical transport and photoluminescence properties of its polycrystalline counterparts. These results reveal the important role played by point defects and GBs in affecting charge carrier mobility and excitonic properties of these atomic layers. In addition to the intrinsic defects, growth process induced substrate impurities and strain induced band structure perturbations are revealed as major sources of disorder GSK1904529A research buy in CVD grown 2D MoS2. We further explore substrate defects for

modification and control of electronic and optical properties of 2D MoS2 through interface engineering. Self-assembled monolayer based interface MAPK Inhibitor Library modification, as a versatile technique adaptable to different conventional and flexible substrates, is used to promote

significant tunability in the key MoS2 field-effect device parameters. This approach provides a powerful tool for modification of native substrate defect characteristics and allows for a wide range of property modulations. Our results signify the role of intrinsic and extrinsic defects in the physical properties of MoS2 and unveil strategies that can utilize these characteristics.”
“OBJECTIVE. The purpose of our study was to estimate cancer induction risk and generate risk conversion factors in cardiac CT angiography.\n\nMATERIALS AND METHODS. Under an institutional review board waiver and in compliance with HIPAA, we collected characteristics for a consecutive cohort of 100 patients (60 men and 40 women; mean age, 59 +/- 11 years) who had previously undergone ECG-gated cardiac CT angiography on a 64-slice CT scanner. The volume CT Dose Index (CTDI(vol)) and dose-length Staurosporine product (DLP) were recorded and used with the ImPACT CT Patient

Dosimetry Calculator to compute organ and effective doses in a standard 70 kg phantom. Patient-specific organ and effective doses were obtained by applying a weight-based correction factor. Radiation doses to radiosensitive organs were converted to risks using age-and sex-specific data published in BEIR VII.\n\nRESULTS. Median values were 62 mGy for CTDI(vol), 1,084 mGy-cm for DLP, and 17 cm for scan length. Effective doses ranged from 20 mSv (10th percentile) to 31 mSv (90th percentile). Median cancer induction risks in sensitive organs for men and women were 0.065% and 0.17%, respectively. For men and women, the range of risks was about a factor of 2. In men and women, about three quarters of the cancer risk was from lung cancer. Inclusion of the remaining less sensitive organs exposed during cardiac CT angiography examinations would likely increase the cancer induction risk by similar to 20%.\n\nCONCLUSION.

Dabigatran can be considered in high-risk AF patients who are una

Dabigatran can be considered in high-risk AF patients who are unable or unwilling to comply with the frequent laboratory and clinic visits that are required when receiving treatment with warfarin. Factor Xa inhibitors are another class of new anticoagulants that have been developed. Oral rivaroxaban was non-inferior to warfarin in thromboprophylaxis and with similar bleeding selleck in the ROCKET-AF trial (HR 0.88; p = 0.117). Apixaban, another factor Xa inhibitor, was superior to aspirin in reducing stroke

and systemic embolism in patients with AF in the AVERROES trial (HR 0.45; p < 0.001). The results of the ARISTOTLE trial, which is evaluating apixaban against warfarin in similar to 18 000 patients with AF, are expected to be available later this year. Edoxaban, another oral factor Xa inhibitor, is currently being evaluated against warfarin in the ENGAGE AF-TIMI 48 trial in similar to 20 000 patients with AF. With these new developments, there is a necessity for the clinical practitioner to become familiar with these new and upcoming therapies

and guidelines. This review provides an overview of the available data regarding the clinical usefulness of these agents.”
“Purpose: To determine the possible biological effects GSK1838705A of differently polarised microwave radiation on the chromatin state in human cells. Materials and methods: Isolated human buccal epithelium cells were irradiated by microwaves of frequency f=35 GHz and surface power density E=30 W/cm2. The state of chromatin in human cells was determined by methods of light and electron microscopy. The state of cell membranes was evaluated

by the method of vital indigo carmine staining. Results: The microwave-induced condensation of chromatin in human cells is revealed. Degree of microwave-induced condensation depends on the state of polarisation of electromagnetic wave: In some cases left circularly polarised waves induce less effect than linearly polarised radiation. The linearly polarised electromagnetic waves induce cell membrane damage revealed by increase of cell staining. The data obtained are discussed in connection with mechanisms of biological check details effects of electromagnetic fields. Conclusion: The data obtained in this work demonstrate important biological effects of monochromatic microwave irradiation at 35 GHz. Low-level microwave irradiation induces chromatin condensation in human cells and damages of cell membranes.”
“RNA-binding proteins (RBPs) regulate numerous aspects of gene expression; thus, identification of their endogenous targets is important for understanding their cellular functions. Here we identified transcriptome-wide targets of Rbfox3 in neuronally differentiated P19 cells and mouse brain by using photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CUP).

Twelve patients were treated over 29 months, receiving contralate

Twelve patients were treated over 29 months, receiving contralateral, ventroposterolateral sensory thalamic DBS. Five patients were amputees and 7 had BPAs, all from traumas. A postoperative trial of externalized DBS failed in 1 patient with BPA. Eleven patients proceeded to implantation and gained improvement in pain scores at 12 months. No surgical complications

or stimulation side effects were noted. In the amputation group, SC79 molecular weight after 12 months the mean VAS score improved by 90.0% +/- 10.0% (p = 0.001), SF-36 by 57.5% +/- 97.9% (p = 0.127), UWNPS by 80.4% +/- 12.7% (p < 0.001), and BPI by 79.9% +/- 14.7% (p < 0.001). In the BPA group, after 12 months the mean VAS score improved by 52.7% +/- 30.2% (p < 0.001), SF-36 by 15.6% +/- 30.5% (p = 1.000), UWNPS by 26.2% +/- 40.8% (p = 0.399), and BPI by 38.4% +/- 41.7% (p = 0.018). Mean DBS parameters were 2.5 V, 213 microseconds,

and 25 Hz.\n\nConclusions. Deep brain stimulation demonstrated efficacy at 1 year for chronic neuropathic pain after traumatic amputation and BPA. Clinical trials that retain patients in long-term follow-up are desirable to confirm findings from prospectively assessed case series.”
“Pinch-off syndrome (POS) is a serious complication encountered during the long-term management of totally implantable access ports (TIAPs). The aim of this study was to examine the effect of ultrasound-guided infraclavicular axillary vein puncture to avoid POS in patients with long-term use of a TIAP.\n\nThis was a retrospective review of 207 consecutive TIAPs: one hundred devices implanted using an anatomical landmark technique were used as historical controls (Landmark group), while Adavosertib in vitro 107 devices were implanted THZ1 research buy using an ultrasound (US)-guided puncture method (US group). The pinch-off grade (POG) was determined using chest X-ray findings following the definition of Hinke, and

the progression of POG during the follow-up period of the Landmark and US groups was compared.\n\nSixteen cases in the Landmark group were POG-1 and 3 were POG-2, while all cases in the US group were POG-0 at the time of venipuncture (p < 0.001). Eleven patients in the Landmark group showed some degree of progression of the POG during the follow-up period. In contrast, there were no cases showing progression of the POG in the US group (p = 0.002).\n\nUS-guided infraclavicular axillary vein puncture was found to effectively make it possible to avoid POS for the long-term management of TIAPs, as well as at the time of implantation.”
“Soccer, one of the most popular sports worldwide among young men, can result in a wide range of orthopedic injuries. Although vascular injuries such as dissection occur rarely, they can cause significant mortality if left undiagnosed. We report herein a 31-year-old male who suffered a large middle cerebral artery infarction due to traumatic internal carotid artery dissection after a ball struck his head and neck. He recovered with mild neurologic deficit after decompressive surgery.

British Journal of Cancer (2012) 106, 1406-1414 doi: 10 1038/bjc

British Journal of Cancer (2012) 106, 1406-1414. doi: 10.1038/bjc.2012.103 (C)

2012 Cancer Research UK”
“Studies on comparing the effect of lengthening, isometric and shortening contractions on dystrophin-deficient muscles are unavailable. We hypothesized that different types of contractions lead to different extents to which dystrophin-deficient muscles are injured. For this purpose, we developed protocols for different types of contraction-induced injury to mdx muscles in vitro. Force deficits and percentages of procion orange dye positive fibers were employed to assess the extent of injury to each muscle. Our results revealed that both the lengthening and isometric contractions resulted in significantly greater injury to extensor digitorum longus (EDL) muscles of mdx mice than to that of control (C57BL/6) mice. In contrast, the shortening contractions

induced very mild and identical injury to EDL muscles of mdx and C57BL/6 mice. Then another protocol was carried out in vivo to ascertain the effect of shortening contractions on mdx muscles by achillotenotomy. Histological assessment revealed that the triceps surae muscles with excised Achilles tendon (EAT) displayed little and significantly milder injury than the normal ones did. In conclusions, the unloaded shortening contractions induce little injury to mdx muscles. The in vitro protocol for different types of contraction-induced injury is sensitive see more and reliable.”
“Human papillomavirus (HPV) L1 capsid protein (L1) is associated with the productive phase of HPV infection. However, the expression of L1 and its relationship to p16 expression, a surrogate BIX 01294 cell line marker for HPV infection, are unknown. We examined the relationship between L1 and p16 expression in cervical intraepithelial neoplasia. Tissues were divided into four categories:

regressive lesions (n = 48), progressive lesions (n = 40), and randomly selected CIN1-2 (n = 67) and CIN3 (n = 44). P16 positivity in the progression cases was significantly higher than that in the regression cases, and p16 positivity in the CIN3 cases was significantly higher than that in any other categories. L1 positivity was not significant between each category. The staining pattern was divided into the following four groups: L1-/p16-, L1+/p16-, L1+/p16+, L1-/p16+. The L1-/p16- pattern was significantly associated with the regression nature in CIN1-2. Some CIN3 cases showing a feature of L1+/p16+, which are still HPV-productive, are likely to exist. The combination of both L1 and p16 may be useful in the evaluation of the progression risk of low-grade cervical dysplasia. (c) 2010 Elsevier GmbH. All rights reserved.”
“Objective: The objective of this study was to analyze and identify pancreatic cancer stem cell-specific microRNAs (miRNAs) and messenger RNAs (mRNAs) to investigate their correlations to cancer stem cell biology.

D student (1983-1987) and later as a postdoctoral fellow (1989-1

D. student (1983-1987) and later as a postdoctoral fellow (1989-1993). The preface of this article highlights personal memories of a time that will never come back. (C) 2013 Elsevier B.V. All rights reserved.”
“Context: The administration

of iv glucocorticoid pulses has been advocated as a treatment approach for patients with inflammatory and moderate to severe Graves’ orbitopathy (GO). This review offers an update on this controversial regimen.\n\nEvidence Acquisition: PubMed and the MeSH-Database were searched (with no temporal limit) for the following topics: management AZD8186 order of active and severe GO; glucocorticoid therapy of GO; iv glucocorticoid administration; mechanism and pharmacokinetics of iv glucocorticoids; and adverse events, morbidity, and mortality of iv glucocorticoids. The articles were evaluated according to their setting and study design.\n\nEvidence Synthesis: All randomized and uncontrolled trials, consensus statement, systematic reviews, and meta-analyses dealing with the efficacy and morbidity of iv glucocorticoids in GO were identified.\n\nConclusions: The current

first-line treatment for active, moderate-to-severe GO is a 12-wk course of high-dose iv glucocorticoid pulses. The response rate of this regimen is approximately 80%. Intravenous glucocorticoids have a statistically significant advantage over oral treatment and cause significantly fewer adverse events. However, major side effects related to preexisting diseases, administered dose, and treatment schedule have been reported. The morbidity and mortality of iv glucocorticoid therapy are 6.5 and 0.6%, respectively. Thus, careful patient selection is warranted.

Before iv glucocorticoid administration, patients should be screened for recent hepatitis, liver Sapitinib solubility dmso dysfunction, cardiovascular morbidity, severe hypertension, inadequately managed diabetes, and glaucoma. The cumulative dose should not exceed 8 g, and with the exception of sight-threatening GO the single doses preferably should not be administered on consecutive days. Monthly monitoring during subsequent treatment is warranted. (J Clin Endocrinol Metab 96: 320-332, 2011)”
“Eleven predictions derived from the recalibrational theory of anger were tested. This theory proposes that anger is produced by a neurocognitive program engineered by natural selection to use bargaining tactics to resolve conflicts of interest in favor of the angry individual. The program is designed to orchestrate two interpersonal negotiating tactics (conditionally inflicting costs or conditionally withholding benefits) to incentivize the target of the anger to place greater weight on the welfare of the angry individual. Individuals with enhanced abilities to inflict costs (e.g., stronger individuals) or to confer benefits (e.g.

Immediately after the fireworks display, perchlorate in pond wate

Immediately after the fireworks display, perchlorate in pond waters increased significantly, with concentrations from 30 to 1,480 times higher than the baseline values. Perchlorate concentrations in pond water increased from 0.11 mu g/L to up to 519 mu g/L, following the fireworks display in 2008. Perchlorate concentrations in pond water decreased at a first-order Selleck AG-14699 kinetic degradation rate, with a mean k(obs) value of 0.026 d(-1) and an average half-life of 29 d. The rate of perchlorate deposition into water bodies following fireworks displays was estimated to range from 670 to 2,620 g/ha. We also estimated the perchlorate ingestion rate by the inhalation of aerosols of pond water by people frequently

near the ponds. The

estimated daily intake of perchlorate through the ingestion of aerosols was 32% (226 ng/kg body wt), 13% (92 ng/kg body wt), and 6% (42 ng/kg body wt) of the U. S. Environmental Protection Agency’s reference dose for infants, children, and adults, respectively. Environ. Toxicol. Chem. 2011; 30: 2449-2455. (C) 2011 SETAC”
“A novel method was exploited to use electrospun poly(DL-lactide)(PDLLA) fibers grafted with chitosan as the induction sites for composite fabrication to suit better the mechanical learn more and biological demands for biomedical applications. The amount of chitosan grafted on the fiber surface could be controlled by the aminolysis time, and the kinetic equations of HA growth were drafted YH25448 nmr as a function of the incubation time for fibrous scaffolds with different amounts of grafted chitosan. The introduction of amino groups and

chitosan on electrospun PDLLA fibers enhanced the cell proliferation due to the improved surface wettability and alleviated dimensional shrinkage. Significantly higher cytoviability and alkaline phosphatase levels were detected on mineralized scaffolds from chitosan grafted fibers than those from aminolyzed fibers, and cells interacted and integrated well with the surrounding fibers. The fibrous nanocomposites should have potential applications as functional coatings on medical devices and as scaffolds for bone tissue engineering. (C) 2010 Elsevier Ltd. All rights reserved.”
“Acoustic landscapes, or soundscapes, can vary due to biological (‘biophony’), geophysical (‘geophony’) and anthropogenic (‘anthrophony’) components, and in some environments, such as many coral reefs, biophony dominates the soundscape. We compared 126 sound recordings from 3 different times of day (day, dusk and night) at 42 locations with concurrent fish and habitat surveys to investigate the relationships of acoustic parameters with biological and physical characteristics of coral reefs in the Gambier Archipelago, French Polynesia. Principal Component Analysis revealed that most of the variability in soundscapes could be described using only 4 factors: (1) full bandwidth root mean squared sound pressure level (SPL; 0.01 to 22.

Compared to

expert gastroenterology-adjudicated interpret

Compared to

expert gastroenterology-adjudicated interpretation, the sensitivity to detect blood was 0.94 (95% confidence interval [CI]=0.91 to 0.96) and specificity was 0.87 (95% CI=0.80 to 0.92).\n\nConclusionsAfter brief training, EPs can accurately interpret video capsule endoscopy findings of presence of gross blood or no blood with high sensitivity and specificity. (C) 2013 by the Society for Academic Emergency Medicine”
“Chordal LY2157299 inhibitor transfer from the intact posterior mitral leaflet (PML) to the anterior mitral leaflet (AML) is an effective way to correct anterior leaflet prolapse and provides good long-term results. However, it is difficult to determine the accurate segment of the p38 protein kinase PML which needs to be transferred and the suture point of the leaflets. We describe a modified technique to determine the correct segment that needs to be transferred to effectively correct AMLs with elongated or ruptured chordae. This technique

renders performing chordal transfer easier and more accurate.”
“Unprotected exo,exo-5-norbornene-2,3-dicarboxylic acid and exo,exo-7-oxa-5-norbornene-2,3-dicarboxylic acid were polymerized via ring-opening metathesis polymerization. This reaction yielded polymers with molecular weights (M(n) from GPC) ranging from 31 to 242 kg/mol and polydispersity indices between 1.05 and 1.12, using Grubbs’ third generation catalyst. The water solubility as a function of pH value of the polymers was investigated by dynamic light scattering (DLS). DLS and acid-base titration revealed that the oxanorbornene polymer

was water soluble over a wider pH range than its norbornene analog. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1266-1273, 2009″
“We investigated the influence of breathing motion on radiation therapy according to four-dimensional computed tomography (4D-CT) technology and indicated the registration of 4D-CT images was significant. The demons algorithm in two interpolation modes was compared to the FFD model algorithm to register the different phase images of 4D-CT in tumor tracking, using iodipin as verification. Linear interpolation was used in both mode 1 and mode 2. Mode 1 set outside pixels to nearest pixel, while mode 2 set outside PD0325901 price pixels to zero. We used normalized mutual information (NMI), sum of squared differences, modified Hausdorff-distance, and registration speed to evaluate the performance of each algorithm. The average NMI after demons registration method in mode 1 improved 1.76% and 4.75% when compared to mode 2 and FFD model algorithm, respectively. Further, the modified Hausdorff-distance was no different between demons modes 1 and 2, but mode 1 was 15.2% lower than FFD. Finally, demons algorithm has the absolute advantage in registration speed. The demons algorithm in mode 1 was therefore found to be much more suitable for the registration of 4D-CT images.

Circ Res 98: 962-969, 2006) In this study, we targeted the vascu

Circ Res 98: 962-969, 2006). In this study, we targeted the vascular endothelium by using a lentivirus

construct expressing CYP4A2 under the control of the endothelium-specific promoter VE-cadherin (VECAD-4A2) and examined FK228 the effect of long-term CYP4A2 overexpression on blood pressure and kidney function in SD rats. A bolus injection of VECAD-4A2 increased blood pressure (P < 0.001) by 26, 36, and 30 mmHg 10, 20, and 30 days postinjection, respectively. Arteries from VECAD-4A2-transduced rats produced increased levels of 20-HETE (P < 0.01), expressed lower levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) (P < 0.05), generated higher levels of superoxide anion, and displayed decreased relaxing responsiveness GSK3326595 solubility dmso to acetylcholine (P < 0.05). Proteinuria increased by twofold in VECAD-4A2-transduced rats compared with controls. Treatment of VECAD-4A2-transduced rats with HET0016, an inhibitor of

20-HETE biosynthesis, not only attenuated the increase in blood pressure (P < 0.05) but also improved vascular function (acetylcholine-induced relaxations) and reduced plasma creatinine and proteinuria. HET0016 treatment decreased oxidative stress and increased the phosphorylated state of key proteins that regulate endothelial function, including eNOS, AKT, and AMPK. Collectively, these findings demonstrate that augmentation of vascular endothelial 20-HETE levels results in hypertension, endothelial dysfunction, and renal injury, which is offset by HET0016 through a reduction in vascular 20-HETE coupled with a lessening of oxidative stress and the amplification of pAKT, pAMPK, and p-eNOS levels leading

to normalization of endothelial responses.”
“Background-Vitamin D deficiency is highly prevalent and is associated with dyslipidemia and cardiovascular disease. Stem Cells & Wnt inhibitor The impact of correcting vitamin D deficiency on blood lipids, strong cardiovascular disease prognostic factors, is unknown.\n\nMethods and Results-To determine relationships between 25-hydroxyvitamin D levels and lipids, we analyzed 4.06 million deidentified patient laboratory test results from September 2009 through February 2011. We performed a cross-sectional study of this population to determine associations between 25-hydroxyvitamin D levels and lipids across clinically defined strata. We also conducted a retrospective cohort study of vitamin D deficient patients to investigate how changes in 25-hydroxyvitamin D levels relate to changes in lipid levels. After exclusions, 107 811 patients with serial testing were selected for cross-sectional analysis. Compared with vitamin D deficient patients (<20 ng/mL), those with optimal levels (>= 30 ng/mL) had lower mean total cholesterol (-1.

05; P>0 05 respectively) Conclusions: CRT by high-amplitud

05; P>0.05 respectively).\n\nConclusions: CRT by high-amplitude LV pacing was more effective according to clinical and echocardiographic evaluations. It should be considered as an alternative in non-responsive patients.”
“Objectives: Aspergillus fumigatus is the most common agent of invasive aspergillosis (IA). In recent years, resistance to triazoles, the mainstay of IA therapy, has emerged in different

countries worldwide. IA caused by azole-resistant A. fumigatus (ARAF) shows an exceedingly high mortality. In this study, IA due to ARAF isolates in HSCT recipients in Germany was investigated. Methods: The epidemiology of azole resistance in IA was analysed in two German haematology departments. Between 2012 and 2013, 762 patients received HSCT in Essen (n = 388) and Cologne (n = 374). Susceptibility testing of A. fumigatus isolates was performed by Etest, followed by EUCAST broth microdilution testing if elevated Nepicastat clinical trial MICs were recorded. In all ARAF isolates the cyp51A gene was sequenced and the genotype was determined

by microsatellite typing using nine short tandem repeats. Results: In total, A. fumigatus was recovered from 27 HSCT recipients. 5-Fluoracil Eight patients had azole-resistant IA after HSCT, and seven of the cases were fatal (88%). All except one patient received antifungal prophylaxis (in five cases triazoles). TR34/L98H was the most common mutation (n = 5), followed by TR46/Y121F/T289A (n = 2). In one resistant isolate no cyp51A mutation was detected. Genotyping revealed genetic diversity within the German ARAF isolates

and no clustering with resistant isolates from the Netherlands, this website India and France. Conclusions: This report highlights the emergence of azole-resistant IA with TR34/L98H and TR46/Y121F/T289A mutations in HSCT patients in Germany and underscores the need for systematic antifungal susceptibility testing of A. fumigatus.”
“A series of original quinazolines bearing a 4-thiophenoxy and a 2-trichloromethyl group was synthesized in a convenient and efficient way and was evaluated toward its in vitro antiplasmodial potential. The series revealed global good activity against the K1-multi-resistant Plasmodium falciparum strain, especially with hit compound 5 (IC50 = 0.9 mu M), in comparison with chloroquine and doxycycline chosen as reference-drugs. Both the in vitro cytotoxicity study which was conducted on the human HepG2 cell line and the in vitro antitoxoplasmic screening against Toxoplasma gondii indicate that this series presents an interesting selective antiplasmodial profile. Structure-activity- and toxicity relationships highlight that the trichloromethyl group plays a key role in the antiplasmodial activity and also show that the modulation of the thiophenol moiety influences the toxicity/activity ratio. (C) 2011 Elsevier Ltd. All rights reserved.