TrkB signaling directs the incorporation of newly generated periglomerular cells in the adult olfactory bulb.

In the adult rodent brain, the olfactory bulb (OB) is continuously supplied with new neurons which survival critically depends on their successful integration into pre-existing networks. Yet, the extracellular signals that determine the selection which neurons will be ultimately incorporated into these circuits are largely unknown. Here, we show that immature neurons express the catalytic form of the brain-derived neurotrophic factor receptor TrkB [full-length TrkB (TrkB-FL)] only after their arrival in the OB, at the time when inte-gration commences. To unravel the role of TrkB signaling in newborn neurons, we conditionally ablated TrkB-FL in mice via Cre expression in adult neural stem and progenitor cells. TrkB-deficient neurons displayed a marked impairment in dendritic arborization and spine growth. By selectively manipulating the signaling pathways initiated by TrkB in vivo, we identified the transducers Shc/PI3K to be required for dendritic growth, whereas the activation of phospholipase C-was found to be responsible for spine formation. Further-more, long-term genetic fate mapping revealed that TrkB deletion severely compromised the survival of new dopaminergic neurons, leading to a substantial reduction in the overall number of adult-generated periglomerular cells (PGCs), but not of granule cells (GCs). Surprisingly, this loss of dopaminergic PGCs was mirrored by a corresponding increase in the number of calretinin PGCs, suggesting that distinct subsets of adult-born PGCs may respond differentially to common extracellular signals. Thus, our results identify TrkB signaling to be essential for balancing the incorporation of defined classes of adult-born PGCs and not GCs, reflecting their different mode of integration in the OB. \ua9 2013 the authors

Antibiotic Prophylaxis to Reduce Respiratory Tract Infections and Mortality in Adults Receiving Intensive Care

BACKGROUND: Pneumonia is an important cause of mortality in intensive care units (ICUs). The incidence of pneumonia in ICU patients ranges between 7% and 40%, and the crude mortality from ventilator-associated pneumonia may exceed 50%. Although not all deaths in patients with this form of pneumonia are directly attributable to pneumonia, it has been shown to contribute to mortality in ICUs independently of other factors that are also strongly associated with such deaths. OBJECTIVES: To assess the effects of prophylactic antibiotic regimens, such as selective decontamination of the digestive tract (SDD) for the prevention of respiratory tract infections (RTIs) and overall mortality in adults receiving intensive care. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 1), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register; MEDLINE (January 1966 to March 2009); and EMBASE (January 1990 to March 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) of antibiotic prophylaxis for RTIs and deaths among adult ICU patients. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data and assessed trial quality. MAIN RESULTS: We included 36 trials involving 6914 people. There was variation in the antibiotics used, patient characteristics and risk of RTIs and mortality in the control groups. In trials comparing a combination of topical and systemic antibiotics, there was a significant reduction in both RTIs (number of studies = 16, odds ratio (OR) 0.28, 95% confidence interval (CI) 0.20 to 0.38) and total mortality (number of studies = 17, OR 0.75, 95% CI 0.65 to 0.87) in the treated group. In trials comparing topical antimicrobials alone (or comparing topical plus systemic versus systemic alone) there was a significant reduction in RTIs (number of studies = 17, OR 0.44, 95% CI 0.31 to 0.63) but not in total mortality (number of studies = 19, OR 0.97, 95% CI 0.82 to 1.16) in the treated group. AUTHORS' CONCLUSIONS: A combination of topical and systemic prophylactic antibiotics reduces RTIs and overall mortality in adult patients receiving intensive care. Treatment based on the use of topical prophylaxis alone reduces respiratory infections but not mortality. The risk of resistance occurring as a negative consequence of antibiotic use was appropriately explored only in one trial which did not show any such effect

Time-resolved single-photon detection module based on silicon photomultiplier: A novel building block for time-correlated measurement systems

We present the design and preliminary characterization of the first detection module based on Silicon Photomultiplier (SiPM) tailored for single-photon timing applications. The aim of this work is to demonstrate, thanks to the design of a suitable module, the possibility to easily exploit SiPM in many applications as an interesting detector featuring large active area, similarly to photomultipliers tubes, but keeping the advantages of solid state detectors (high quantum efficiency, low cost, compactness, robustness, low bias voltage, and insensitiveness to magnetic field). The module integrates a cooled SiPM with a total photosensitive area of 1 mm2 together with the suitable avalanche signal read-out circuit, the signal conditioning, the biasing electronics, and a Peltier cooler driver for thermal stabilization. It is able to extract the single-photon timing information with resolution better than 100 ps full-width at half maximum. We verified the effective stabilization in response to external thermal perturbations, thus proving the complete insensitivity of the module to environment temperature variations, which represents a fundamental parameter to profitably use the instrument for real-field applications. We also characterized the single-photon timing resolution, the background noise due to both primary dark count generation and afterpulsing, the single-photon detection efficiency, and the instrument response function shape. The proposed module can become a reliable and cost-effective building block for time-correlated single-photon counting instruments in applications requiring high collection capability of isotropic light and detection efficiency (e.g., fluorescence decay measurements or time-domain diffuse optics systems)

Novel approaches to photon detection and timing for 7-wavelength time domain optical mammography

An 8-channel Silicon Photomultiplier probe and a Time-to-Digital Converter are used to build a higher-throughput, cheaper and compact detection chain for time-resolved optical mammography as compared with conventional PhotoMultiplier Tubes and Time-Correlated Single-Photon Counting boards, still providing comparable performance in the estimation of optical properties, but with higher optical responsivity

Spectrally Resolved Single-Photon Timing of Silicon Photomultipliers for Time-Domain Diffuse Spectroscopy

We characterized the single-photon timing response function of various silicon photomultipliers (SiPMs) over a broad (500-1100 nm) spectral range. We selected two SiPM manufacturers, and we investigated two active areas, i.e., a small (1-1.69 mm2 and a large (9 mm2) one, for each of them. We demonstrate that selected SiPMs are suitable for time-resolved diffuse optics (DO) applications where a very large detection area and sensitivity down to single photons are crucial to detecting the very faint return signal from biological tissues, like the brain, thus allowing replacement of photomultiplier tubes and opening the way to a novel generation of DO multichannel instrumentation. Due to our custom front-end electronics, we show the world's best single-photon timing resolution for SiPMs, namely, 57-ps full-width at half maximum for Hamamatsu 1.69 mm2 and 115 ps for Excelitas 9 mm2. Even further, we provide a thorough spectral investigation of the full single-photon timing response function, also detailing diffusion tails' time constants and dynamic range. The achieved insight and the reported performance open the way to a widespread diffusion of SiPMs not just in many-photon regimes (e.g., PET) but at single-photon counting regimes like DO as well

Voltammetric characterization of gold-based bimetallic (AuPt; AuPd; AuAg) nanoparticles

Bimetallic nanoparticles are nowadays some of the most promising materials for catalytic, electrocatalytic and electroanalytical applications thanks to their novel optical, catalytic, magnetic, and sensing properties. Such novel features, often different and enhanced with respect to the monometallic counterparts, make these systems good candidates to be conveniently applied in a wide range of fields. The possibility to obtain different kinds of bimetallic composites (in terms of composition, structure, metal loading, morphology, etc.) goes in parallel with the need of powerful and accurate characterization tools. Among the commonly involved techniques like Optical Spectroscopy and Dynamic Light Scattering (DLS), also the more powerful Transmission Electron Microscopy (HR-TEM) and Extended X-Ray Absorption Fine Structure (EXAFS) are widely used. However, these analytical tools present some drawbacks in terms of high costs and low accessibility. In this context, electrochemistry and particularly Cyclic Voltammetry, is here proposed as an alternative, low cost, easy to use and simple characterization technique. The possibility to use electrochemical methods to study the final structure of bimetallic nanocomposites was already demonstrated in the Literature [1-2], but there is still lack of information on how such systems change and evolve in time and after aging periods. Therefore, Cyclic Voltammetry is here used, as a complementary technique to HR-TEM and EXAFS not only to investigate the structure of alloyed or core-shell gold-based (Au-Pt; Au-Pd; Au-Ag) systems (by studying the quantity and type of metals present in the materials), but also to elucidate the evolution and growth in time of such bimetallic samples. Time evolution characterization allows to control the morphology and to fix it at the desired point. Finally, the characterized gold-based nanocomposites are used in electrochemical sensing and electrocatalytic applications. A strong improvement in the response, in terms of higher peak currents and electrocatalytic effects, of the bimetallic systems with respect to the monometallic counterparts is evidenced, due to the intimate contact between the two metals, which is responsible of synergistic effects. Also, the effects of an eventual carbonaceous support on the properties of the metal nanoparticles and the possible synergistic effects between composites and supports are investigated [3]. [1] K. Tschulik, K. Ngamchuea, C. Ziegler, M.G. Beier, C. Damm, A. Eychmueller, R.G. Compton, Adv. Funct. Mater., 2015, 25, 5149\u20135158. [2] V. Pifferi, C. Chan-Thaw, S. Campisi, A. Testolin, A. Villa, L. Falciola, L. Prati, Molecules, 2016, 21, 261. [3] A. Testolin, S.Cattaneo, W. Wang, D. Wang, V. Pifferi, L. Prati, L. Falciola, A. Villa, Surfaces, 2019, 2, 205-215

Criteria for the design of tissue-mimicking phantoms for the standardization of biophotonic instrumentation

A lack of accepted standards and standardized phantoms suitable for the technical validation of biophotonic instrumentation hinders the reliability and reproducibility of its experimental outputs. In this Perspective, we discuss general criteria for the design of tissue-mimicking biophotonic phantoms, and use these criteria and state-of-the-art developments to critically review the literature on phantom materials and on the fabrication of phantoms. By focusing on representative examples of standardization in diffuse optical imaging and spectroscopy, fluorescence-guided surgery and photoacoustic imaging, we identify unmet needs in the development of phantoms and a set of criteria (leveraging characterization, collaboration, communication and commitment) for the standardization of biophotonic instrumentation

Large area silicon photomultipliers allow extreme depth penetration in time-domain diffuse optics

We present the design of a novel single-photon timing module, based on a Silicon Photomultiplier (SiPM) featuring a collection area of 9 mm2. The module performs Single-Photon Timing Resolution of about 140 ps, thus being suitable for diffuse optics application. The small size of the instrument (5 cm × 4 cm × 10 cm) allows placing it directly in contact with the sample under investigation, maximizing that way the signal harvesting. Thanks to that, it is possible to increase the source detector distance up to 6 cm or more, therefore enhancing the penetration depth up to an impressive value of 4 cm and paving the way to the exploration of the deepest human body structures in a completely non-invasive approach