Intereleukin-10 Promoter Polymorphism in Mild Cognitive Impairment and in Its Clinical Evolution

Specific proinflammatory alleles are associated with higher risk of Alzheimer disease (AD) in different onset age. The homozygosis for the A allele of −1082 polymorphism (G/A) of interleukin-10 (IL-10) promotes a higher risk of AD and reduced IL-10 generation in peripheral cells after amyloid stimulation. In this paper we analysed genotype and allele frequencies of this polymorphism in 138 subjects with mild cognitive impairment (MCI) diagnosed, respectively, as amnestic (a-MCI) and multiple impaired cognitive domains (mcd-MCI). The genotype frequencies were similar in a-MCI and AD subjects, whereas in mcd-MCI comparable to controls (AA genotype: 50% in a-MCI, 49.2% in AD, 28.7% in mcd-MCI and 31.8% in controls). Consequently, both allele and genotype distributions were significantly different between a-MCI and mcd-MCI (allele: P = .02, genotype: P < .05). These results support the theory that polymorphisms of cytokine genes can affect neurodegeneration and its clinical progression. IL-10 may partly explain the conversion of a-MCI to AD or be a genetic marker of susceptibility

Non-invasive monitoring and control in silicon photonics by CMOS integrated electronics

As photonics breaks away from today's device level toward large scale of integration and complex systems-on-a-chip, concepts like monitoring, control and stabilization of photonic integrated circuits emerge as new paradigms. Here, we show non-invasive monitoring and feedback control of high quality factor silicon photonics resonators assisted by a transparent light detector directly integrated inside the cavity. Control operations are entirely managed by a CMOS microelectronic circuit, hosting many parallel electronic read-out channels, that is bridged to the silicon photonics chip. Advanced functionalities, such as wavelength tuning, locking, labeling and swapping are demonstrated. The non-invasive nature of the transparent monitor and the scalability of the CMOS read-out system offer a viable solution for the control of arbitrarily reconfigurable photonic integrated circuits aggregating many components on a single chip

Automated routing and control of silicon photonic switch fabrics

Automatic reconfiguration and feedback controlled routing is demonstrated in an 8×8 silicon photonic switch fabric based on Mach-Zehnder interferometers. The use of non-invasive Contactless Integrated Photonic Probes (CLIPPs) enables real-time monitoring of the state of each switching element individually. Local monitoring provides direct information on the routing path, allowing an easy sequential tuning and feedback controlled stabilization of the individual switching elements, thus making the switch fabric robust against thermal crosstalk, even in the absence of a cooling system for the silicon chip. Up to 24 CLIPPs are interrogated by a multichannel integrated ASIC wire-bonded to the photonic chip. Optical routing is demonstrated on simultaneous WDM input signals that are labelled directly on-chip by suitable pilot tones without affecting the quality of the signals. Neither preliminary circuit calibration nor lookup tables are required, being the proposed control scheme inherently insensible to channels power fluctuations

Aging, cancer, and cancer vaccines

World population has experienced continuous growth since 1400 A.D. Current projections show a continued increase - but a steady decline in the population growth rate - with the number expected to reach between 8 and 10.5 billion people within 40 years. The elderly population is rapidly rising: in 1950 there were 205 million people aged 60 or older, while in 2000 there were 606 million. By 2050, the global population aged 60 or over is projected to expand by more than three times, reaching nearly 2 billion people [1]. Most cancers are age-related diseases: in the US, 50% of all malignancies occur in people aged 65-95. 60% of all cancers are expected to be diagnosed in elderly patients by 2020 [2]. Further, cancer-related mortality increases with age: 70% of all malignancy-related deaths are registered in people aged 65 years or older [3]. Here we introduce the microscopic aspects of aging, the pro-inflammatory phenotype of the elderly, and the changes related to immunosenescence. Then we deal with cancer disease and its development, the difficulty of treatment administration in the geriatric population, and the importance of a comprehensive geriatric assessment. Finally, we aim to analyze the complex interactions of aging with cancer and cancer vaccinology, and the importance of this last approach as a complementary therapy to different levels of prevention and treatment. Cancer vaccines, in fact, should at present be recommended in association to a stronger cancer prevention and conventional therapies (surgery, chemotherapy, radiation therapy), both for curative and palliative intent, in order to reduce morbidity and mortality associated to cancer progression

+874(T→A) single nucleotide gene polymorphism does not represent a risk factor for Alzheimer's disease

In the recent years, several cytokines have been associated with Alzheimer's disease (AD) development and progression and many studies have correlated this risk with polymorphisms in the genes encoding these molecules. Also the type 1 cytokine interferon (IFN)-γ belongs to a cytokine class that affects the immune function; in fact it plays a major role in defence against viruses and intracellular pathogens but also in the induction of the immune-mediated inflammatory response. The aim of this study was to evaluate the role of IFN-γ in AD by studying the association of +874T→A IFN-γ gene polymorphism with AD. We included in this study 115 AD patients (70 women, 45 men, mean age 80) and 90 sex and age-matched healthy controls (HC, 51 women, 39 men, mean age 82) from northern Italy. Genomic DNA was extracted with the salting-out method from whole blood of all subjects; the genotyping at IFN-γ loci was assessed with ARMS-PCR. The data obtained from the +874T→A IFN-γ gene polymorphism analysis of AD patients and HC lack of any statistically significant differences also when stratified according to gender. In conclusion these results confirm the previous shown lack of association between +874T→A IFN-γ gene polymorphism and the risk of AD. However, other polymorphisms have been demonstrated to influence IFN-γ transcription and since natural killer cells of AD patients show higher production of the cytokine, further analysis will be necessary to clarify the role of this gene in the pathogenesis of the disease

All-optical mode unscrambling on a silicon photonic chip

Propagation of light beams through scattering or multimode systems may lead to randomization of the spatial coherence of the light. Although information is not lost, its recovery requires a coherent interferometric reconstruction of the original signals, which have been scrambled into the modes of the scattering system. Here, we show that we can automatically unscramble four optical beams that have been arbitrarily mixed in a multimode waveguide, undoing the scattering and mixing between the spatial modes through a mesh of silicon photonics Mach-Zehnder interferometers. Using embedded transparent detectors and a progressive tuning algorithm, the mesh self-configures automatically and reset itself after significantly perturbing the mixing, without turning off the beams. We demonstrate the recovery of four separate 10 Gbits/s information channels, with residual cross-talk between beams of -20dB. This principle of self-configuring and self-resetting in optical systems should be applicable in a wide range of optical applications.Comment: 23 pages, 10 figure

Automated routing and control of silicon photonic switch fabrics

Automatic reconfiguration and feedback controlled routing is demonstrated in an 8×8 silicon photonic switch fabric based on Mach-Zehnder interferometers. The use of non-invasive Contactless Integrated Photonic Probes (CLIPPs) enables realtime monitoring of the state of each switching element individually. Local monitoring provides direct information on the routing path, allowing an easy sequential tuning and feedback controlled stabilization of the individual switching elements, thus making the switch fabric robust against thermal crosstalk, even in the absence of a cooling system for the silicon chip. Up to 24 CLIPPs are interrogated by a multichannel integrated ASIC wirebonded to the photonic chip. Optical routing is demonstrated on simultaneous WDM input signals that are labelled directly on-chip by suitable pilot tones without affecting the quality of the signals. Neither preliminary circuit calibration nor lookup tables are required, being the proposed control scheme inherently insensible to channels power fluctuations

Wavelength locking of silicon photonics multiplexer for DML-based WDM transmitter

We present a wavelength locking platform enabling the feedback control of silicon (Si) microring resonators (MRRs) for the realization of a 4 × 10 Gb/s wavelength-division-multiplexing (WDM) transmitter. Four thermally tunable Si MRRs are employed to multiplex the signals generated by four directly modulated lasers (DMLs) operating in the L-band, as well as to improve the quality of the DMLs signals. Feedback control is achieved through a field-programmable gate array controller by monitoring the working point of each MRR through a transparent detector integrated inside the resonator. The feedback system provides an MRR wavelength stability of about 4 pm (0.5 GHz) with a time response of 60 ms. Bit error rate (BER) measurements confirm the effectiveness and the robustness of the locking system to counteract sensitivity degradations due to thermal drifts, even under uncooled operation conditions for the Si chip

Neurocognitive Impairment in HIV-Infected Naïve Patients with Advanced Disease: The Role of Virus and Intrathecal Immune Activation

Objective. To investigate intrathecal immune activation parameters and HIV-RNA in HIV-associated neurocognitive disorders (HAND) of advanced naïve HIV-infected patients and to evaluate their dynamics before and after initiation of antiretroviral therapy (ART). Methods. Cross-sectional and longitudinal analysis of HIV RNA, proinflammatory cytokines (IL-6, IL-10, INF-γ, TNF-α, TGF-β1, and TGF-β2) and chemokines (MIP-1α, MIP-1β, and MCP-1) in plasma and cerebrospinal fluid (CSF) of HIV-infected patients with CD4 <200/μL. Results. HAND was diagnosed at baseline in 6/12 patients. Baseline CSF HIV-RNA was comparable in patients with or without HAND, whereas CSF concentration of IL-6 and MIP-1β, proinflammatory cytokines, was increased in HAND patients. CSF evaluation at 12 weeks was available in 10/12 cases. ART greatly reduced HIV-RNA in all patients. Nevertheless, IL-6 and MIP-1β remained elevated after 12 weeks of therapy in HAND patients, in whom CSF HIV RNA decay was slower than the plasmatic one as well. Conclusion. Immune activation, as indicated by inflammatory cytokines, but not higher levels of HIV-RNA is observed in advanced naïve HIV-infected patients with HAND. In HAND patients, ART introduction resulted in a less rapid clearance of CSF viremia compared to plasma and no modifications of intratechal immune activation