Lymphocyte Subsets and Inflammatory Cytokines of Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Almost all multiple myeloma (MM) cases have been demonstrated to be linked to earlier monoclonal gammopathy of undetermined significance (MGUS). Nevertheless, there are no identified characteristics in the diagnosis of MGUS that have been helpful in differentiating subjects whose cancer may progress to a malignant situation. Regarding malignancy, the role of lymphocyte subsets and cytokines at the beginning of neoplastic diseases is now incontestable. In this review, we have concentrated our attention on the equilibrium between the diverse lymphocyte subsets and the cytokine system and summarized the current state of knowledge, providing an overview of the condition of the entire system in MGUS and MM. In an age where the therapy of neoplastic monoclonal gammopathies largely relies on drugs capable of acting on the immune system (immunomodulants, immunological checkpoint inhibitors, CAR-T), detailed knowledge of the the differences existing in benign and neoplastic forms of gammopathy is the main foundation for the adequate and optimal use of new drugs

An Examination of Manufactured Housing as a Community- and Asset-Building Strategy

An increasing share of lower-income families, the same population targeted by community-development organizations, are opting to live in housing that was built off-site in a factory to meet the performance standards of the national HUD manufactured-housing code. However, most community-development practitioners are just beginning to come to terms with the implications of manufactured housing for their work.This paper explores advantages and disadvantages of manufactured housing for those entities whose mission is community development and asset building. Several challenges are presented for practitioners: First, working to educate consumers while also creating financing processes that ensure manufactured home buyers obtain credit on the best terms for which they can qualify. Second, using the increased scrutiny under the Manufactured Housing Improvement Act of 2000 to advocate for states to enforce more rigorous installation standards and increased accountability. Third, working to overcome land-use controls which prevent manufactured homes from being placed in communities in need of affordable housing, as well as areas with more potential for appreciation. Fourth, working with designers and planners to develop innovative designs and housing developments, while maintaining manufactured housing's affordability advantages.Finally, equal effort must be devoted to address the difficult conditions of many lower-income people -- owners and renters alike -- living in older, and often deteriorating, mobile homes. While a few of these families and individuals could be relocated to new and better quality homes with the help of subsidies, resource limitations suggest the need to create cost-effective methods to eliminate health and safety problems by upgrading or rehabilitating this extremely affordable element of the nation's housing inventory.As a companion to this paper, an exhaustive literature review has been compiled

Single prazosin infusion in prelimbic cortex Fosters extinction of amphetamine-induced conditioned place preference

Exposure to drug-associated cues to induce extinction is a useful strategy to contrast cue-induced drug seeking. Norepinephrine (NE) transmission in medial prefrontal cortex has a role in the acquisition and extinction of conditioned place preference induced by amphetamine. We have reported recently that NE in prelimbic cortex delays extinction of amphetamine-induced conditioned place preference (CPP). A potential involvement of α1-adrenergic receptors in the extinction of appetitive conditioned response has been also suggested, although their role in prelimbic cortex has not been yet fully investigated. Here, we investigated the effects of the α1-adrenergic receptor antagonist prazosin infusion in the prelimbic cortex of C57BL/6J mice on expression and extinction of amphetamine-induced CPP. Acute prelimbic prazosin did not affect expression of amphetamine-induced CPP on the day of infusion, while in subsequent days it produced a clear-cut advance of extinction of preference for the compartment previously paired with amphetamine (Conditioned stimulus, CS). Moreover, prazosin-treated mice that had extinguished CS preference showed increased mRNA expression of brain-derived neurotrophic factor (BDNF) and post-synaptic density 95 (PSD-95) in the nucleus accumbens shell or core, respectively, thus suggesting that prelimbic α1-adrenergic receptor blockade triggers neural adaptations in subcortical areas that could contribute to the extinction of cue-induced drug-seeking behavior. These results show that the pharmacological blockade of α1-adrenergic receptors in prelimbic cortex by a single infusion is able to induce extinction of amphetamine-induced CPP long before control (vehicle) animals, an effect depending on contingent exposure to retrieval, since if infused far from or after reactivation it did not affect preference. Moreover, they suggest strongly that the behavioral effects depend on post-treatment neuroplasticity changes in corticolimbic network, triggered by a possible “priming” effect of prazosin, and point to a potential therapeutic power of the antagonist for maladaptive memories

Recurrent Varicose Veins Following Surgical Treatment: Our Experience with Five Years Follow-up

ObjectiveTo report the 5 year outcome of varicose veins surgery and to establish the factors determining recurrence.Study DesignProspective observational study.Materials and MethodsThis study reports the outcome in 1326 patients treated in a day surgery centre of an institutional referral centre. Patients were investigated clinically and by colour flow duplex scanning before operation. Treatments used included flush ligation of the sapheno-femoral junction (SFJ) and the sapheno-popliteal junction (SPJ). Incompetence of the great saphenous vein (GSV) and small saphenous vein (SSV) were managed by stripping of these veins. Perforating vein ligation and hook phlebectomy were also used. Patients were evaluated 3 weeks and 5 years following treatment by clinical examination and duplex ultrasonography.Results412 patients were excluded from the study because they failed to attend for follow-up or did not wear elastic stockings post-operatively. No residual saphenous truncal reflux was found at the initial assessment 3 weeks following surgery. After 5 years, recurrence of varicose veins occurred in 332 patients out of 1326 (25 %). Recurrences arose at the sapheno-femoral junction in 109 out of 862 patients (13%), at the sapheno-popliteal junction in 39 out of 132 patients (30%), in both saphenous regions 38 out of 107 patients (36%) and in 146 out of 225 subjects (65 %) with secondary varicose veins.ConclusionVaricose veins recurred despite technically correct surgery confirmed on post-operative duplex ultrasonography. The likelihood of recurrence increased in the presence of SSV reflux, perforating vein incompetence and post-thrombotic deep vein incompetence

Pharmacological rescue of adult hippocampal neurogenesis in a mouse model of X-linked intellectual disability

Oligophrenin-1 (OPHN1) is a Rho GTPase activating protein whose mutations cause X-linked intellectual disability (XLID). How loss of function of Ophnl affects neuronal development is only partly understood. Here we have exploited adult hippocampal neurogenesis to dissect the steps of neuronal differentiation that are affected by Ophn1 deletion. We found that mice lacking Ophnl display a reduction in the number of newborn neurons in the dentate gyrus. A significant fraction of the Ophn1-deficient newly generated neurons failed to extend an axon towards CM, and showed an altered density of dendritic protrusions. Since Ophnl-deficient mice display overactivation of Rho-associated protein kinase (ROCK) and protein kinase A (PICA) signaling, we administered a clinically approved ROCK/PICA inhibitor (fasudil) to correct the neurogenesis defects. While administration of fasudil was not effective in rescuing axon formation, the same treatment completely restored spine density to control levels, and enhanced the long-term survival of adult-born neurons in mice lacking Ophn1. These results identify specific neurodevelopmental steps that are impacted by Ophn1 deletion, and indicate that they may be at least partially corrected by pharmacological treatment. (C) 2017 The Authors. Published by Elsevier Inc

The Chemokine CCL2 Mediates the Seizure-enhancing Effects of Systemic Inflammation

Epilepsy is a chronic disorder characterized by spontaneous recurrent seizures. Brain inflammation is increasingly recognized as a critical factor for seizure precipitation, but the molecular mediators of such proconvulsant effects are only partly understood. The chemokine CCL2 is one of the most elevated inflammatory mediators in patients with pharmacoresistent epilepsy, but its contribution to seizure generation remains unexplored. Here, we show, for the first time, a crucial role for CCL2 and its receptor CCR2 in seizure control. We imposed a systemic inflammatory challenge via lipopolysaccharide (LPS) administration in mice with mesial temporal lobe epilepsy. We found that LPS dramatically increased seizure frequency and upregulated the expression of many inflammatory proteins, including CCL2. To test the proconvulsant role of CCL2, we administered systemically either a CCL2 transcription inhibitor (bindarit) or a selective antagonist of the CCR2 receptor (RS102895). We found that interference with CCL2 signaling potently suppressed LPS-induced seizures. Intracerebral administration of anti-CCL2 antibodies also abrogated LPS-mediated seizure enhancement in chronically epileptic animals. Our results reveal that CCL2 is a key mediator in the molecular pathways that link peripheral inflammation with neuronal hyperexcitability

Social housing policy or social policy for housing? The role of the Programa Especial de Realojamento (PER) in the housing/planning nexus in Portugal

Recent (European) comparative studies in the fields of housing policy and spatial planning have been dominated by taxonomical approaches (attempts at categorising systems and temporal stages of state action) and measures of the ‘maturity’ of national systems. In this paper, we adopt a genealogical perspective and consider (national and local) cultures central to the shaping of policy (differences and convergence). We set out a long-term, in-depth exploration of the planning-housing nexus in Portugal – a case that helps adding nuances to mainstream theorisation – and focus on the Programa Especial de Relojamento (PER; Special Programme for Rehousing), a programme that has had changing roles (from a financial instrument to a core component of policies of urban regeneration) in connection with political and planning cultures changing in time and space. Our goal is contributing to making sense of the intersection between planning cultures in transition and changing housing policy, namely the generalised shift toward regeneration and concurrent retrenchment of state action – and the relation among housing as welfare (‘social housing policy’) and housing as urban policy (‘social policy for housing’).info:eu-repo/semantics/publishedVersio

Comparative planning and housing studies beyond taxonomy: a genealogy of the special programme for rehousing (Portugal)

Recent European comparative studies in the fields of housing policy and spatial planning have been dominated by taxonomical and linear approaches, and by normative calls for convergence toward systems considered more ‘mature’ or ‘advanced’. In this article, we adopt a genealogical perspective and consider those cultures that are central to the shaping of policy. We set out a long-term exploration of the intersection between spatial planning and housing policy in Portugal and focus on the Special Programme for Rehousing (Programa Especial de Realojamento, PER), a programme that has had changing roles (from a financial instrument to a core component of policies of urban regeneration) in connection with political and planning cultures changing in time and space. In this way, we provide evidence of the limited capacity of taxonomic and linear approaches to describe planning and housing systems undergoing processes of change and, conversely, show the potential of genealogical research.info:eu-repo/semantics/publishedVersio

Antioxidant Betalains from Cactus Pear (Opuntia Ficus Indica) inhibit endothelial ICAM-1 expression

It has been suggested that some pigments would have antioxidant properties and that their presence in dietary constituents would contribute to reduce the risk of oxidative stress\u2013correlated diseases. Among others, inflammatory response depends on redox status and may implicate oxidative stress. Vascular endothelial cells are a direct target of oxidative stress in inflammation. We have tested the impact of the free radical scavenger and antioxidant properties of betalains from the prickle pear in an in vitro model of endothelial cells. Here we show the capacity of betalains to protect endothelium from cytokine- induced redox state alteration, through ICAM-1 inhibition. KEYWORDS: endothelial cells; ICAM-1; betalains; antiinflammatory drug

Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells

Antioxidant phytochemicals are investigated as novel treatments for supportive therapy in b-thalassemia. The dietary indicaxanthin was assessed for its protective effects on human b-thalassemic RBCs submitted in vitro to oxidative haemolysis by cumene hydroperoxide. Indicaxanthin at 1.0\u201310 mMenhanced the resistance to haemolysis dose-dependently. In addition, it prevented lipid and haemoglobin (Hb) oxidation, and retarded vitamin E and GSH depletion. After ex vivo spiking of blood from thalassemia patients with indicaxanthin, the phytochemical was recovered in the soluble cell compartment of the RBCs. A spectrophotometric study showed that indicaxanthin can reduce perferryl-Hb generated in solution from met-Hb and hydrogen peroxide (H2O2), more effectively than either Trolox or vitamin C. Collectively our results demonstrate that indicaxanthin can be incorporated into the redox machinery of b-thalassemic RBC and defend the cell from oxidation, possibly interfering with perferryl-Hb, a reactive intermediate in the hydroperoxidedependent Hb degradation. Opportunities of therapeutic interest for b-thalassemia may be considered