Multiple and spectrally robust photonic magic angles in reconfigurable α-MoO3 trilayers.

The emergence of a topological transition of the polaritonic dispersion in twisted bilayers of anisotropic van der Waals materials at a given twist angle-the photonic magic angle-results in the diffractionless propagation of polaritons with deep-subwavelength resolution. This type of propagation, generally referred to as canalization, holds promise for the control of light at the nanoscale. However, the existence of a single photonic magic angle hinders such control since the canalization direction in twisted bilayers is unique and fixed for each incident frequency. Here we overcome this limitation by demonstrating multiple spectrally robust photonic magic angles in reconfigurable twisted α-phase molybdenum trioxide (α-MoO3) trilayers. We show that canalization of polaritons can be programmed at will along any desired in-plane direction in a single device with broad spectral ranges. These findings open the door for nanophotonics applications where on-demand control is crucial, such as thermal management, nanoimaging or entanglement of quantum emitters.

[Clarification of dizziness in old age : Interdisciplinary diagnostic process]. / Schwindelabklärung im Alter : Interdisziplinärer diagnostischer Prozess.

The clinical symptom dizziness encompasses a broad range of complaints. The prevalence among older adults is high. Over the course of 1 year 50% of people over 80 years old, 30% of those between 70-80 years old and 20% between 60-70 years old contact a physician as a result of dizziness. The diagnostic process has to be well organized. The medical history and clinical examination are frequently underestimated but in many cases are crucial. Extensive investigations should only be carried out in cases of a firmly suspected diagnosis. A good interdisciplinary cooperation can positively influence the diagnostic process. The awareness of red flags also helps to detect emergency patients with dizziness. This article discusses the differential diagnosis of dizziness in older adults and provides appropriate recommendations for the diagnostic process.

THE CHALLENGES OF A PROSTATECTOMY IN RURAL AFRICA.

Delayed complications of an established surgical procedure like transvescical prostatectomy can occur in rural settings, where different factors can influence the outcome, beyond appropriate indication for surgery and technical skills of surgeons. Here we present a case that was per se surgically unremarkable, however a number of delayed omplications appeared in the post operative period, including infectious, neurologic, metabolic, hematologic ones, beyond purely post-surgery complications.

Proteomic analysis of the tegument and excretory-secretory products of Dicrocoelium dendriticum (Digenea) adult worms.

Dicrocoeliosis, caused by Dicrocoelium dendriticum, is an important hepatic parasitosis in ruminants, whose immunological diagnosis and control remain unsatisfactory. There are very few studies on the antigens of this trematode and molecular knowledge about it is practically nil. Therefore the aim of this study was to identify the major antigenic proteins in the tegument (TG) and excretory-secretory (ES) antigenic extracts of D. dendriticum. The separation conditions of the protein extracts were optimized using 2-D PAGE; the gels were stained with colloidal Coomassie or transferred to carry out immunodetection with anti-Dicrocoelium dendriticum sera. The proteins of interest excised from the gels were identified by mass spectrometry (MALDI). The proteomic maps of the TG and ES extracts of D. dendriticum were defined first, detecting 332 spots in the TG and 284 in the ES, with a similar distribution in both. A quantity of 29 proteins in the excretion-secretion products and 43 in the teguments were identified first in D. dendriticum, 23 of them antigenic, involved in various processes such as: metabolism, detoxification, chaperone, transport or structural molecules. These results could help us to understand the complex parasite-host relationships, improve the diagnosis of dicroceliosis and help to produce possible vaccines to control it.

Analysis of an expressed sequence tag library from Dicrocoelium dentriticum.

Dicrocoeliosis caused by Dicrocoelium dendriticum is an important liver disease, which affects ruminants all around the world. Despite the significant economic losses caused by this trematode, molecular knowledge is very scarce. In fact, there is no information in the expressed sequence tag (EST) database about the parasite. Furthermore, the immunological diagnosis of dicrocoeliosis remains unsatisfactory, and there aren't available recombinant proteins that could be tested in the diagnosis. For this reason a cDNA library was constructed with mRNA extracted from D. dendriticum adults for first time. A random preliminary screening of 230 phage plaques from the library resulted in the identification of 173 new EST. The deduced proteins expressed by these genes have been described as possible vaccine targets in other trematodes, and/or as relevant diagnosis antigens. Then, our goal was to identify D. dentriticum diagnosis genes to be used as recombinant antigens in the specific immunological diagnosis of the trematodoses. A D. dendriticum cDNA encoding an 8-kDa recombinant protein has been cloned, expressed in Escherichia coli and evaluated in dicrocoeliosis diagnosis using both Western Blot and enzyme-linked immunosorbent assay (ELISA). The recombinant expression molecule has demonstrated its value as a diagnosis antigen of dicrocoeliosis, able to discriminate between positive and controls on day 30 post infection. This is the first research conducted for identification and characterization of D. dendriticum ESTs, which can serve as a starting point for future research on immunodiagnosis and immunoprofilaxis of dicrocoeliosis.

Twist-tunable polaritonic nanoresonators in a van der Waals crystal.

Optical nanoresonators are key building blocks in various nanotechnological applications (e.g., spectroscopy) due to their ability to effectively confine light at the nanoscale. Recently, nanoresonators based on phonon polaritons (PhPs)-light coupled to lattice vibrations-in polar crystals (e.g., SiC, or h-BN) have attracted much attention due to their strong field confinement, high quality factors, and their potential to enhance the photonic density of states at mid-infrared (mid-IR) frequencies, where numerous molecular vibrations reside. Here, we introduce a new class of mid-IR nanoresonators that not only exhibit the extraordinary properties previously reported, but also incorporate a new degree of freedom: twist tuning, i.e., the possibility of controlling their spectral response by simply rotating the constituent material. To achieve this result, we place a pristine slab of the van der Waals (vdW) α-MoO3 crystal, which supports in-plane hyperbolic PhPs, on an array of metallic ribbons. This sample design based on electromagnetic engineering, not only allows the definition of α-MoO3 nanoresonators with low losses (quality factors, Q, up to 200), but also enables a broad spectral tuning of the polaritonic resonances (up to 32 cm-1, i.e., up to ~6 times their full width at half maximum, FWHM ~5 cm-1) by a simple in-plane rotation of the same slab (from 0 to 45°). These results open the door to the development of tunable and low-loss IR nanotechnologies, fundamental requirements for their implementation in molecular sensing, emission or photodetection applications.

Dynamic changes of live/apoptotic circulating tumour cells as predictive marker of response to sunitinib in metastatic renal cancer.

BACKGROUND: Recently, we developed an apoptotic assay for expanding the monitoring capabilities of the circulating tumour cells (CTC) test during therapy. An automated platform for computing CTCs was integrated with a mAb (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 in early apoptosis; we showed that live CTCs were associated with progression, consistent with enhanced cell migration and invasion. The test was first applied here to mRCC. METHODS: Live/apoptotic CTCs changes were measured in mRCC patients receiving first-line Sunitinib and compared with circulating endothelial cell (CEC) levels. RESULTS: The presence of EpCAM-positive, live CTCs predicts progression in individual mRCC patient, being associated with distant metastasis under first-line Sunitinib. Synchronous detection of CTCs and CEC levels discloses for the first time an association between their dynamic changes and outcome: a rapid increase of the CEC number as early as the first cycle of therapy is associated with CTC decrease in non-progressed patients, whereas a delayed response of CECs is related to higher CTC values in the progressed group indicating treatment failure. CONCLUSION: We demonstrated that a delayed response to antiangiogenic treatment indicated by persistent detection of CECs correlates with persistent live CTCs and more aggressive disease.

Optimal dose finding for novel antimalarial combination therapy.

A recent discussion meeting convened by the Medicines for Malaria Venture examined how best to manage the discovery and preclinical pipeline to achieve novel combination therapies which would address the key clinical needs in malaria. It became clear that dose optimisation of components within combination therapy was a key issue in achieving antimalarial efficacy and for preserving that efficacy against parasite resistance emergence. This paper outlines some of the specific issues in malaria that cause dose-ranging and dose-optimisation studies to be particularly challenging and discusses the potential of factorial study design to address such challenges.

Fine needle aspiration of non-small cell lung cancer: current state and future perspective.

AThe emerging treatment revolution determined by the advent of new targeted therapies requires accurate tumour subtyping as a mandatory step in the clinical workup of patients with non-small cell lung carcinoma (NSCLC). As a result of advanced and inoperable disease or poor performance status, in many patients, minimally invasive procedures must be employed to obtain diagnostic material. Fine needle aspiration (FNA) is a valid and widely employed alternative to either tru-cut or open-sky biopsy. Indeed, cytological specimens are suitable for techniques such as immunocytochemistry, mutation and microRNA analysis, and may present advantages over small biopsies especially if cell blocks are prepared and attention is paid to cytomorphology and pre-analytic management of specimens at the time they are collected. These will allow the adequate stratification of patients into different diagnostic and prognostic classes.

Detection of Dicrocoelium dendriticum larval stages in mollusc and ant intermediate hosts by PCR, using mitochondrial and ribosomal internal transcribed spacer (ITS-2) sequences.

The aim of this study was to develop, perfect and validate the PCR (polymerase chain reaction) technique using mitochondrial (mt) and ribosomal (ITS-2) DNA for the accurate identification of Dicrocoelium dendriticum in molluscs and ants, the first and second intermediate hosts, and their early detection. The first primers that were designed amplified a 169 pb mtDNA fragment of D. dendriticum permitted the detection of a single D. dendriticum metacercaria from the Formica rufibarbis and Formica pratensis abdomen, as well as the detection of the brainworm in the head of the ants collected in tetania. Although these primers did not amplify Dicrocoelium chinensis DNA and permitted detected D. dendriticum in the molluscs, they did not discriminate Brachylaimidae metacercariae found in the same mollusc. The PCR that was designed to amplify a 93 bp fragment of the ITS-2 is D. dendriticum specific as it did not amplify D. chinensis, Brachylaimidae and other trematodes. This technique is very sensitive since it permitted the detection of D. dendriticum in the molluscs from the first day post-infection, the brainworm in the head of the ants and only 1 D. dendriticum metacercaria from the abdomen of the ants. Both techniques are important, mainly the latter.

Aromatase mRNA expression in the brain of adult Xenopus laevis exposed to Lambro river water and endocrine disrupting compounds.

Aromatase P450 (P450 arom; Cyp19) is a key enzyme for vertebrate reproduction and brain development that catalyzes the conversion of androgens to estrogens. The aim of this study was to improve the knowledge on EDC effects by analysing their potential impact on brain P450 arom in adult Xenopus laevis exposed for 4 weeks to an environmental sample, the water of the river Lambro (LAM), the most polluted tributary of the Po river in North Italy. Other groups were exposed to individual compounds 10(-8) M tamoxifen (TAM), ethinylestradiol (EE2), flutamide (FLU) and methyldihydrotestosterone (MDHT) known for their (anti)estrogenic and (anti)androgenic modes of action. Expression of CYP19 was evaluated in brain extracts by quantitative RT-PCR, using a pair of primers located in the open reading frame (ORF) that allowed the simultaneous amplification of all transcripts (Aro-ORF) and a pair of primers specific for brain aromatase (Aro-B). Significant increase in Aro-ORF and Aro-B mRNA levels were observed in both females and males exposed to LAM. Different changes were observed for the model compounds using two pairs of primers. Aro-ORF mRNA expression was significantly increased in EE2 and MDHT exposed males and in FLU-exposed females, while it was significantly decreased in TAM exposed females. Aro-B mRNA was significantly increased in both sexes exposed to FLU and decreased in TAM exposed females. In conclusion, aromatase mRNA in the brain of X. laevis was regulated differentially in a gender specific manner by certain (anti)estrogenic and (anti)androgenic EDCs, supporting previous hypotheses that diverse compounds present in the river Lambro may induce feminization and demasculinization effects.

Augmented Reality: Sustaining Autonomous Way-Finding in the Community for Older Persons with Cognitive Impairment.

BACKGROUND: Impairment of autonomous way-finding subsequent to a multitude of neurodegenerative and other diseases impedes independence of older persons and their everyday activities. OBJECTIVE: It was the goal to use augmented reality to aid autonomous way-finding in a community setting. DESIGN: A spatial map and directional information were shown via head-up display to guide patients from the start zone on the hospital campus to a bakery in the nearby community. SETTING: Hospital campus and nearby community. PARTICIPANTS: Patients with mild cognitive impairment (age 63 to 89). INTERVENTIONS: A head-up display was used to help patients find their way. MEASUREMENTS: Time needed to reach goal and number of assists needed. RESULTS: With use of augmented reality device, patients preceded along the correct path in 113 out of 120 intersections. Intermittent reassurance was needed for most patients. Patients affirmed willingness to use such an augmented reality device in everyday life if needed or even pay for it. CONCLUSION: Augmented reality guided navigation is a promising means to sustain autonomous way-finding as a prerequisite for autonomy of older persons in everyday activities. Thus, this study lays ground for a field trial in the community using assistive technology for older persons with cognitive impairment.

Osteogenic activity of cyclodextrin-encapsulated doxycycline in a calcium phosphate PCL and PLGA composite.

Composites of biodegradable polymers and calcium phosphate are bioactive and flexible, and have been proposed for use in tissue engineering and bone regeneration. When associated with the broad-spectrum antibiotic doxycycline (DOX), they could favor antimicrobial action and enhance the action of osteogenic composites. Composites of polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and a bioceramic of biphasic calcium phosphate Osteosynt® (BCP) were loaded with DOX encapsulated in ß-cyclodextrin (ßCD) and were evaluated for effects on osteoblastic cell cultures. The DOX/ßCD composite was prepared with a double mixing method. Osteoblast viability was assessed with methyl tetrazolium (MTT) assays after 1day, 7day, and 14days of composite exposure; alkaline phosphatase (AP) activity and collagen production were evaluated after 7days and 14days, and mineral nodule formation after 14days. Composite structures were evaluated by scanning electron microscopy (SEM). Osteoblasts exposed to the composite containing 25µg/mL DOX/ßCD had increased cell proliferation (p<0.05) compared to control osteoblast cultures at all experimental time points, reaching a maximum in the second week. AP activity and collagen secretion levels were also elevated in osteoblasts exposed to the DOX/ßCD composite (p<0.05 vs. controls) and reached a maximum after 14days. These results were corroborated by Von Kossa test results, which showed strong formation of mineralization nodules during the same time period. SEM of the composite material revealed a surface topography with pore sizes suitable for growing osteoblasts. Together, these results suggest that osteoblasts are viable, proliferative, and osteogenic in the presence of a DOX/ßCD-containing BCP ceramic composite.

p53 gene inactivation in acute lymphoblastic leukemia of B cell lineage associates with chromosomal breakpoints at 11q23 and 8q24.

The clinical heterogeneity of acute lymphoblastic leukemia (ALL) of B cell lineage reflects the presence of distinct molecular pathways leading to well-defined ALL molecular subtypes. These molecular pathways include the formation of the fusion transcripts BCR/ABL and E2A/PBX1, due to t(9;22) and t(1;19), respectively, as well as rearrangements of the MLL gene at 11q23 and of c-MYC at 8q24. Hyperdiploid ALL in the absence of chromosomal structural abnormalities is an additional ALL molecular subtype. Mutations of the RAS family genes and of the p53 tumor suppressor gene represent additional genetic lesions detected in a fraction (10-20%) of ALL cases. RAS activation in ALL may be detected in all molecular subtypes of ALL and denotes poor prognosis. Conversely, little is known regarding the clinical and biological features of ALL cases carrying p53 mutations. In order to help clarify the role of p53 inactivation in ALL development, we have determined the frequency of p53 mutations throughout the molecular spectrum of B cell lineage ALL. We report that p53 inactivation in ALL of B cell lineage is restricted to cases carrying a rearrangement of MLL or c-MYC, whereas it is consistently negative in other molecular subgroups. These data underline the molecular heterogeneity of ALL of B cell lineage and indicate that at least some of the molecular pathways involved in ALL pathogenesis require more than one genetic lesion.

The common TEL/AML1 rearrangement does not represent a frequent event in acute lymphoblastic leukaemia occuring in children with Down syndrome.

Individuals with constitutional trisomy 21 (Down syndrome) are at increased risk of developing acute leukaemias, both of myeloid and lymphoid lineage. Although the cause of leukaemia in Down syndrome (DS) remains unknown, potential candidate genes include the ones on chromosome 21, and in particular AML1, the rearrangement of which in the t(8,21) is associated with the French-American-British (FAB) classification M2 subtype of acute myeloid leukaemia (AML) in the general population and has been described in Down patients with AML-M2. Recently, a new rearrangement involving AML1, the t(12;21), producing the TEL/AML1 hybrid transcript, has been described by molecular analysis as the most recurrent genetic lesion in childhood acute lymphoblastic leukemia (ALL). In order to investigate whether the t(12;21) could give a molecular clue as to the precise basis of the etiologic association between DS and acute lymphoblastic leukemia, we tested a series of 11 consecutive cases of ALL in DS children for the presence of the TEL/AML1 transcript, by RT-PCR analysis. We report absence of the TEL/AML1 rearrangement among the 11 cases tested. This data may be suggestive of alternative pathways involved in the pathogenesis of ALL in children with constitutional trisomy 21.

Partial characterization and isolation of 130 kDa antigenic protein of Dicrocoelium dendriticum adults.

The study focused on characterizing and isolating Dicrocoelium dendriticum antigens or their fractions that could be used for the immunological diagnosis of dicrocoeliosis. Somatic (SoAg) and excretory-secretory antigens (ESAg) were analyzed by SDS-PAGE and their specificity was evaluated by Western blot with homologous and heterologous sera. The antigens were partially purified by chromatographic techniques of gel-filtration (Sephacryl S-300) and ion exchange (Hitrap-DEAE-Sepharose). Western blot analysis using sera of ovine infected with D. dendriticum revealed eight main antigenic polypeptides ranging from 24 to 205 kDa for SoAg and seven for ESAg with apparent molecular mass in the range of 26-205 kDa. We detected a specific parasite protein with an approximate molecular weight of 130 kDa in SDS-PAGE gels, arranged as a 450 kDa tetramer in native conditions. It also showed strong immunoreactivity by Western blot against ovine sera experimentally infected with D. dendriticum. Gel filtration chromatography (Sephacryl S-300) also showed other specific proteins, one of about 24 kDa in SoAg and another of about 42 kDa in ESAg. The elution conditions of 450 kDa protein (130 kDa monomer) by DEAE chromatography were similar to those from the somatic antigen (pH 7.2, 0.1M NaCl, in 29-34 ml fractions) and from the excretion-secretion antigen (pH 8.0, 0.1M NaCl, in 29-35 ml fractions). The suitability of 130 kDa polypeptide for D. dendriticum infection diagnosis was confirmed by Western blot using a pool of sera as well as individual serum samples from experimentally infected sheep. The sequence of amino termini of 130 kDa polypeptide from both fractions was the same and identical to that reported for a peptide from D. dendriticum described as a globin. This sequence also revealed an appreciable similarity with the amino end of globins from some phylogenetically related worms.

Persistence of E2A/PBX1 transcripts in t(1;19) childhood acute lymphoblastic leukemia: correlation with chemotherapy intensity and clinical outcome.

The occurrence of t(1;19) translocation was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) for the E2A/PBX1 hybrid message in a panel of 37 consecutive childhood acute lymphoblastic leukemias (ALLs). Three patients with B-precursor ALL were found to be positive at diagnosis and were re-tested during follow-up to assess the presence of minimal residual disease (MRD). Two of them became PCR-negative during treatment, whereas one remains positive 3 years after diagnosis. Since all three patients are presently in clinical and hematological complete remission, PCR detection of persistent E2A/ PBX1 transcript does not seem to affect significantly the DFS at 3 years. However, the predictivity for an eventual late relapse still remains to be assessed.

Role of acid and bile reflux in development of specialised intestinal metaplasia in distal oesophagus.

BACKGROUND: Barrett's oesophagus is defined as specialised intestinal metaplasia in the distal oesophagus, regardless of extension. AIM: To study distal oesophagus function, and acid and bile exposure in patients with Long Segment (>3 cm), Short Segment (1 to 2 cm) and Ultra-short Segment (<1 cm) Barrett's Oesophagus, and in patients with gastro-oesophageal reflux disease without intestinal metaplasia. PATIENTS: Study population comprised 17 patients with Long, 8 with Short, 9 with Ultra-Short Segment Barrett's oesophagus, 32 with reflux disease and 12 healthy volunteers. METHODS: Patients were evaluated by manometry and by 24-hour pH and bile monitoring. RESULTS: Patients with intestinal metaplasia had greater acid exposure of the distal oesophagus than healthy volunteers. Patients with Long Segment Barrett's oesophagus had a longer history of symptoms, worse lower oesophageal sphincter pressures and longer bile and acid exposure than the other patients. Long Segment Barrett's oesophagus was predicted by low oesophageal pressure and increased bile exposure, age and male sex. CONCLUSION: Acid exposure in the distal oesophagus is probably the aetiological factor behind intestinal metaplasia, but a severely damaged antireflux barrier and bile in the refluxate are necessary for Long Segment Barrett's Oesophagus to develop.

Chemical characterization of sicilian prickly pear (Opuntia ficus indica) and perspectives for the storage of its juice.

In this work, Sicilian cultivars of prickly pear (Opuntia ficus indica) were partially characterized from a chemical point of view, and the possibility of long-term storage of their juice was investigated. The acidity of the prickly pear juice turned out to be very low (0.02%) and the pH very high (6.4-6.5) if compared with values found in other common fruit juices. In the perspective of processing and storage conditions according to Italian law, the acidity has been corrected by adding the proper amount of tartaric and/or phosphoric acid. The sugar content (mainly glucose and fructose) is very high (11-12%), and also L-ascorbic acid is present in considerable amount (31-38 mg/100 g). Among the transition metals, a high content of manganese(II) (1.7-2.9 ppm) and good amounts of iron(III) (0.6-1.2 ppm) and zinc(II) (0.3-0.4 ppm) were found. In particular, such ions appear to be present mainly in the thick skin of the fruit or "trapped" inside the pulp. Pectin methylesterase (PME) seems to be present in very small amount and/or is not highly active. Furthermore, PME activity decreases considerably after the necessary adjustment of the pH and the thermal treatment requested for long-term storage. After approximately 2 months, none of the juices prepared was affected by noticeable sedimentation of the pulp. Finally, different samples of prickly pear juice were sensorially analyzed, employing descriptors such as color, aroma, viscosity, acidity, sweetness, and off-flavors. The results obtained can be considered very satisfactory, and the juice has been widely appreciated when compared with other products commonly available on the market such as pear and peach juices.

Relationship between egg output and parasitic burden in lambs experimentally infected with different doses of Dicrocoelium dendriticum (Digenea).

The relationship between egg elimination and parasitic burden was studied in two groups of 12 lambs experimentally infected with 1000 and 3000 Dicrocoelium dendriticum metacercariae, respectively. Half the animals in each group were slaughtered 2 months post-infection (p.i.) and the other half 6 months p.i. In order to detect and follow elimination of D. dendriticum eggs by the lambs, faeces samples collection started one and a half months p.i. and continued fortnightly until the end of the experiment. Egg elimination was first detected between days 49 and 79 p.i. (mean = 59 +/- 1.6 SE). Mean eggs per gram (epg) was higher in the lambs infected with 3000 metacercariae (347.2 +/- 42.4 epg) than in those infected with 1000 (194.8 +/- 14.4), although no significant differences were detected between both groups using the Student 't' test. Egg elimination was higher in the faeces samples taken in the afternoon (mean = 357.8 +/- 47.6 epg) than in those from the morning (mean = 215.7 +/- 21.3). The percentage of metacercariae which became established as worms was higher in the animals dosed with 1000 metacercariae (21.6%) than in those infected with 3000 (16.3%). The number of worms recovered on necropsy of each animal varied between 30 and 2063 (mean = 346.6 +/- 80.5) and their length between 2.6 and 7.1 mm (mean = 5.2 +/- 0.1). The mean number of parasites for lambs infected with 3000 metacercariae (489.3 +/- 163.1) was higher than that obtained from those dosed with 1000 (215.7 +/- 41.4), although more worms were collected in some cases from the lambs infected with the latter dose than the former. In general there was an increase in the number of epg eliminated as days p.i. and parasitic burden increased. A positive relationship was observed via the correlation coefficient between the number of epg eliminated by each of the lambs throughout the experiment and that of worms recovered. This relationship was more intense on considering only the number of epg eliminated between days 120 and 180 p.i.