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.

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.

[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.

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.

Intestinal Malrotation and Ladd's Bands in a Young Child

The case we present; is an interesting example of intestinal malrotation; which is a well known congenital condition; which tend to manifest early in life. In our case the age of our patient made the diagnosis potentially more challenging; as it was not the most typical age for duodenal stenosis due to Ladd's bands; which is often mostly observed earlier in life. Stenosis of the duodenum is relatively rare; and may represent a surgical challenge; especially in setting with limited diagnostic and treatment facilities. We also discuss implication of language barriers to potentially delay timely diagnosis and optimal management

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.

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.

Development and validation of a mtDNA multiplex PCR for identification and discrimination of Calicophoron daubneyi and Fasciola hepatica in the Galba truncatula snail.

Paramphistomosis and Fasciolosis caused by Calicophoron daubneyi and Fasciola hepatica, respectively, are frequent and important trematodoses in ruminant livestock worldwide. Both parasites use the same snail, Galba truncatula, as intermediate host. The aim of this study was to develop and validate an analytical method based on a mitochondrial DNA (mtDNA) multiplex PCR technique which would allow the early and specific identification, in one step, of C. daubneyi and F. hepatica infection in G. truncatula. First of all, a 1035 bp fragment of mtDNA from adult C. daubneyi worms was obtained. Then two pairs of specific mtDNA primers, which amplified a DNA fragment of 885 pb in the case of C. daubneyi, and of 425 pb in that of F. hepatica, were designed. By means of the multiplex PCR technique developed, there was always a specific amplification in samples from adult F. hepatica and C. daubneyi, but not from Calicophoron calicophorum, Cotylophoron cotylophorum, Cotylophoron batycotyle or Dicrocoelium dendriticum. Likewise, specific amplifications of the expected DNA fragments happened in all samples from snails harbouring larval stages of C. daubneyi or F. hepatica, previously detected by microscopy. However, amplifications were not seen when DNA from snails harbouring other Digenea (Plagiorchiidae, Notocotylidae and furcocercous cercariae) was analysed. Moreover, DNA from G. truncatula molluscs free from infection was not amplified. The multiplex PCR assay permitted infection in the snails experimentally infected with 4 miracidia to be detected as early as day 1 p.i. in the case of F. hepatica and with only 2 miracidia from day 2 p.i. in both, C. daubneyi and F. hepatica. Nevertheless it was necessary to wait until days 29 and 33 p.i. to see C. daubneyi and F. hepatica immature redia, respectively, using microscope techniques. The detection limit of the PCR technique was very low: 0.1 ng of DNA from C. daubneyi and 0.001 ng of DNA from F. hepatica. This allowed infection by either F. hepatica or C. daubneyi to be detected even when pools made up with only 1 µl (60 ng of DNA) from infected snail plus 99 µl from non-infected ones were analyzed. Moreover, simultaneous detection of both parasites was experimentally possible in pools made up with uninfected (98 µl), C. daubneyi infected (1 µl) and F. hepatica infected (1 µl) snails. The most precise and early diagnosis of the infections using the multiplex PCR technique designed will allow more realistic epidemiological models of both infections to be established and consequently a better strategic control.

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.

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.

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.

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.

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.

Manejo de dolor crónico no oncológico en un caso de angina intestinal / Management of chronic non-oncological pain in a case of intestinal angina

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Meat odour and flavour and indoles concentration in ruminal fluid and adipose tissue of lambs fed green herbage or concentrates with or without tannins.

A 2 × 2 factorial experiment was carried out to evaluate the effect of herbage or concentrate feeding system and tannin addition to diet on skatole and indole in ruminal fluid and adipose tissue and meat sensory properties. Twenty-eight male lambs aged 45 days were randomly assigned to one of two feeding systems (vetch green herbage or concentrates, n = 14) and within feeding system to one supplement (quebracho tannins added to the diet or none). Animals were kept in singular pens and slaughtered at the age of 105 days. Indole (P < 0.05) and skatole (P < 0.01) concentrations in ruminal fluid were higher in lambs fed herbage compared to those given concentrates. Skatole in ruminal fluid tended to be present at lower concentrations in animals that received the tannin supplementation (P = 0.07). Indole was also higher in the caudal fat of animals fed green vetch compared to those fed concentrate (P = 0.04). Skatole concentration was lower in the fat of lambs fed concentrates compared to those given herbage (P = 0.05) and was lower in the fat of animals supplemented with tannins compared to the animals not supplemented (P = 0.01). Sheep meat odour was lower in meat from animals supplemented with tannins compared to those not supplemented (P < 0.01). It is concluded that tannins are more effective in reducing skatole formation in ruminants when they are associated with concentrate diets than green herbages.

Preliminary characterization of wild lactic acid bacteria and their abilities to produce flavour compounds in ripened model cheese system.

AIMS: The aim of this work was to preliminary characterize wild lactic acid bacteria (LAB), previously isolated during artisanal Pecorino Siciliano (PS) cheese-making for technological and flavour formation abilities in a model cheese system. METHODS AND RESULTS: Twelve LAB were studied for the ability to grow at 10 and 45 degrees C, to coagulate and acidify both reconstituted skim milk and ewe's milk. Moreover, the capacity of the strains to generate aroma compounds was evaluated in a model cheese system at 30- and 60-day ripening. Flavour compounds were screened by sensory analysis and throughout gas chromatography (GC)-mass spectrometry (MS). Most of the strains were able to grow both at 10 and 45 degrees C and exhibited high ability to acidify and coagulate ewes' milk. Sensory evaluation revealed that the wild strains produced more significant flavour attributes than commercial strains in the 60-day-old model cheese system. GC-MS data confirmed the results of sensory evaluations and showed the ability of wild lactobacilli to generate key volatile compounds. Particularly, three wild lactobacilli strains, belonging to Lactobacillus casei, Lb. rhamnosus and Lb. plantarum species, generated both in 60- and 30-day-old model cheeses system, the 3-methyl butan(al)(ol) compound, which is associated with fruity taste. CONCLUSIONS: The present work preliminarily demonstrated that the technological and flavour formation abilities of the wild strains are strain-specific and that wild lactobacilli, which produced key flavour compounds during ripening, could be used as tailor-made starters. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports the technological characterization and flavour formation ability of wild LAB strains isolated from artisanal Pecorino cheese and highlights that the catabolic activities were highly strain dependent. Hence, wild lactobacilli could be selected as tailor-made starter cultures for the PS cheese manufacture.

Cystic adenomatoid malformation in children: CT histopathological correlation.

PURPOSE: This study was performed to assess the accuracy of computed tomography (CT) in classifying the various types of cystic adenomatoid malformation (CAM) of the lung, as described by Stocker et al., taking histopathology as the gold standard. MATERIALS AND METHODS: We retrospectively reviewed six cases of histologically proven CAM. Chest radiography, chest CT and histopathology results were available for all patients. The CT images were reviewed blinded to the histological findings, and attention was paid to the number and size of cysts so as to classify the lesions into the three groups described by Stocker et al. The classification of lesions based on the CT images was then correlated to the histopathological findings. RESULTS: Areas with small-sized cysts (<2 cm) were detected by CT in two patients (33.3%), areas with large cysts (>2 cm) were seen in three cases (50%) whereas in the remaining case, the diagnosis was mixed type I and type II CAM. In one patient with type I CAM, an area of low-density consolidation around the cysts was interpreted as CAM in a context of pulmonary sequestration. The CT classification based on Stocker et al.'s categories was in agreement with the histopathological findings in four cases, whereas in the remaining two cases, the lesions were classed as type I or II on CT and as mixed (type I and II) lesions at histopathology. In one case, the CT classification was correct, but the histopathology revealed the coexistence of pulmonary sequestration. CONCLUSIONS: In our study, there was concordance between CT and histopathology in 66.7% of cases, whereas in 33.3% histopathology revealed areas with mixed grade lesions. CT proved to be accurate in identifying and characterising CAM and provided important information on lesion site and extension.

Immunohistochemical study of the local immune response in lambs experimentally infected with Dicrocoelium dendriticum (Digenea).

Phenotypic expression of inflammatory cells in liver and hepatic lymph nodes (HLN) has been examined in lambs experimentally infected with Dicrocoelium dendriticum using immunohistochemical techniques. Thirty-two lambs, 12 infected with 1,000 D. dendriticum metacercariae, 12 with 3,000, and 8 controls were used. Half the lambs in each group were slaughtered on days 60 and 180 post-infection (p.i.), respectively. Primary antibodies (Abs) against T cell epitopes (CD3+, CD4+, CD8+ and WC1+ gammadelta), B cell epitopes (CD79alphacy+, CD45R+), immunoglobulin (IgG)-bearing plasma cells, macrophages (CD14+, VPM32+) and major histocompatibility complex (MHC) class IIbeta antigen were used. T lymphocytes (CD3+, CD4+ and CD8+) and B lymphocytes (CD79alphacy+ and CD45R+) with diffuse pattern or forming lymphoid aggregates and follicles surrounded the septal bile ducts (SBD) and inter-lobular bile ducts, whereas the WC1 gammadelta T cells were scattered. Numerous IgG+ plasma cells were observed around SBD. CD14 and VPM32+ macrophages intermingled with lymphocytes were immunostained by the anti-MHC class IIbeta. This Ab also reacted with lymphoid cells. Likewise, increased positive immunostaining for all Abs used was observed in the HLN of infected lambs. There was no qualitative difference regarding the phenotype expression of inflammatory cells between the lambs infected with D. dendriticum. The humoral and cell-mediated local immune responses observed were similar in the two groups of lambs infected with different doses.