Lenalidomide, bortezomib and dexamethasone induction therapy for the treatment of newly diagnosed multiple myeloma : a practical review

For patients with newly diagnosed multiple myeloma, survival outcomes continue to improve significantly: however, nearly all patients will relapse following induction treatment. Optimisation of induction therapy is essential to provide longer term disease control and the current standard of care for most patients incorporates an immunomodulatory agent and proteasome inhibitor, most commonly lenalidomide and bortezomib in combination with dexamethasone (RVD), with maintenance until progression. Historically there has been limited access to RVD as an induction strategy outside of the United States; fortunately, there is now increasing access worldwide. This review discusses the rationale for use of RVD as induction therapy and aims to provide guidance in prescribing this regimen in order to optimise efficacy while minimising the toxicities of treatment. We also highlight the increasing evidence for the utility of addition of a monoclonal antibody to the RVD backbone to deepen responses and potentially provide longer disease control.Peer reviewe

Biomimetic Calcium-Silicate Cements Support Differentiation Of Human Orofacial Mesenchymal Stem Cells

Introduction Human orofacial bone mesenchymal stem cells (OFMSCs) from maxilla and mandible have robust osteogenic regenerative properties based on our previous reports that demonstrate phenotypic and functional differences between jaw and axial bone mesenchymal stem cells in same individuals. Furthermore, a combination of OFMSCs with bioactive calcium-releasing cements can potentially improve OFMSC multi-lineage differentiation capacity, but biocompatibility of calcium silicate cements with OFMSCs is still unclear. We tested the hypothesis that material extracts of calcium-releasing calcium-silicate cements support biomimetic microenvironment for survival and differentiation of human OFMSCs. Methods Two experimental calcium-silicate cements 1) calcium-silicate mineral powder (wTC) containing di- and tricalcium-silicate, calcium sulphate, and calcium chloride and 2) wTC doped with alpha-tricalcium phosphate (wTC-αTCP) were designed and prepared. Cement setting times were assessed by Gilmore needles, ability to release calcium and hydroxyl ions was assessed by potentiometric methods and OFMSC attachment to calcium-silicate discs was assessed. Calcium-silicate material extracts were tested for ability to support OFMSCs survival and in vitro/in vivo differentiation. Results Fewer OFMSCs attached to calcium-silicate discs relative to tissue culture plastic (p=0.001). Extracts of calcium-silicate cements sustained OFMSC survival, maintained steady state levels of vascular cell adhesion molecule-1, alkaline phosphatase and bone sialoprotein while upregulating their respective gene transcripts. Adipogenic and in vivo bone regenerative capacities of OFMSCs were also unaffected by calcium-silicate extracts. Conclusions Ion-releasing calcium-silicate cements support a biomimetic microenvironment conducive to survival and differentiation of OFMSCs. Combination of OFMSCs and calcium-silicate cement can potentially promote tissue regeneration in periapical bone defects

Auditory evoked potentials in peripheral vestibular disorder individuals

INTRODUÇÃO: Os sistemas auditivo e vestibular estão localizados no mesmo receptor periférico, porém adentram ao SNC e percorrem caminhos distintos, estabelecendo uma série de conexões e abrangendo uma vasta região do encéfalo. Mesmo percorrendo caminhos diferentes, algumas alterações podem comprometer ambos os sistemas. Testes como os Potenciais Evocados Auditivos podem auxiliar no diagnóstico com alterações vestibulares. OBJETIVO: Caracterizar os resultados dos Potenciais Evocados Auditivos de indivíduos com queixa de tontura ou vertigem com Síndromes Vestibulares Periféricas e com indivíduos normais, com a mesma queixa. MÉTODO: Foram realizados os Potenciais Evocados Auditivos de curta, média e longa latência, sendo um estudo prospectivo transversal. CONCLUSÃO: Indivíduos com queixa de tontura ou vertigem podem apresentar alterações no PEATE, PEAML e P300.INTRODUCTION: The auditory and vestibular systems are located in the same peripheral receptor, however they enter the CNS and go through different ways, thus creating a number of connections and reaching a wide area of the encephalon. Despite going through different ways, some changes can impair both systems. Such tests as Auditory Evoked Potentials can help find a diagnosis when vestibular alterations are seen. OBJECTIVE: describe the Auditory Evoked Potential results in individuals complaining about dizziness or vertigo with Peripheral Vestibular Disorders and in normal individuals having the same complaint. METHODS: Short, middle and long latency Auditory Evoked Potentials were performed as a transversal prospective study. CONCLUSION: individuals complaining about dizziness or vertigo can show some changes in BAEP (Brainstem Auditory Evoked Potential), MLAEP (Medium Latency Auditory Evoked Potential) and P300

Exploring emotional distress, psychological traits and attitudes in patients with chronic migraine undergoing OnabotulinumtoxinA prophylaxis versus withdrawal treatment

This explorative cross-sectional study aims at exploring emotional distress, psychological profiles, and the attitude towards receiving psychological support in eighty-seven patients with chronic migraine (CM) undergoing OnabotulinumtoxinA prophylactic treatment (OBT-A, n = 40) or withdrawal treatment (WT, n = 47). The outcomes were explored through a specific battery of questionnaires. 25% of patients undergoing OBT-A and almost half of the patients undergoing WT reported psychological distress of at least moderate-severe level, respectively. Coping strategies, self-efficacy, and perceived social support were similar in the two groups. Patients undergoing OBT-A presented lower psychological inflexibility than patients undergoing WT. Predictors of higher psychological distress were low perceived social support by friends, low self-efficacy, and higher avoidance strategies. In both groups, most of the patients evaluated receiving psychological support to be useful (79%). The potential beneficial effects of OBT-A on the severity of symptoms and psychological distress might further support its role in the multidisciplinary management of patients with CM. Identifying patients with psychological vulnerabilities who may benefit from psychological support is relevant in patients with CM

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

Genetics of randomly bred cats support the cradle of cat domestication being in the Near East

Cat domestication likely initiated as a symbiotic relationship between wildcats (Felis silvestris subspecies) and the peoples of developing agrarian societies in the Fertile Crescent. As humans transitioned from hunter-gatherers to farmers ~12,000 years ago, bold wildcats likely capitalized on increased prey density (i.e., rodents). Humans benefited from the cats’ predation on these vermin. To refine the site(s) of cat domestication, over 1000 random-bred cats of primarily Eurasian descent were genotyped for single-nucleotide variants and short tandem repeats. The overall cat population structure suggested a single worldwide population with significant isolation by the distance of peripheral subpopulations. The cat population heterozygosity decreased as genetic distance from the proposed cat progenitor’s (F.s. lybica) natural habitat increased. Domestic cat origins are focused in the eastern Mediterranean Basin, spreading to nearby islands, and southernly via the Levantine coast into the Nile Valley. Cat population diversity supports the migration patterns of humans and other symbiotic species