In-situ Raman study of laser-induced graphene oxidation

We present in-situ Raman measurements of laser-induced oxidation in exfoliated single-layer graphene. By using high-power laser irradiation, we can selectively and in a controlled way initiate the oxidation process and investigate its evolution over time. Our results show that the laser-induced oxidation process is divided into two separate stages, namely tensile strain due to heating and subsequent $p$-type doping due to oxygen binding. We discuss the temporal evolution of the $D/G$-mode ratio during oxidation and explain the unexpected steady decrease of the defect-induced $D$ mode at long irradiation times. Our results provide a deeper understanding of the oxidation process in single-layer graphene and demonstrate the possibility of sub-$\mu$m patterning of graphene by an optical method.Comment: 5 pages, 4 figures [submitted as IWEPNM 2015 conference publication to pss(b)

Effects of electrophysical resources in osteoporosis: a review of the literature

OBJECTIVE: The aim of this article was to provide a literature review regarding the impact of the main eletrophysical resources used on the acceleration of bone metabolism and on the osteoporosis treatment. DEFINITION: The OMS defines osteoporosis as a Sistemic esqueletical disease characterized for diminished bone mass and for deterioration of the bone mass microarchitecture, increasing the bone fragility and susceptibility to fracture. Many drug or non-drug treatments are being developed as an attempt to increase the bone mass, and prevent osteoporosis. Within this context, the eletrophysical resources is having a prominence paper, as a resource which presents a osteogenic potencial, capable of stimulating the proliferation of osteoblasts and biomodulate the bone metabolism. RESEARCH STRATEGIES: The data base consulted were: The Cochrane Library, MEDLINE, Embase, LILACS, SciELO, references of indentified articles and contact with laser's especialists, between 1983 and 2009. SELECTION CRITERIA: Were included experimental study and randomized clinical tests on the effects of eletrophysical resources on osteoporosis. RECOMPILATION AND DATA ANALISIS: Two reviewers independently selected the studies, assessed their methodological quality and collected the data. RESULTS: All the eletrophysical resources quoted on this article were effective in stimulation of bone metabolism. However, most of the studies show these effects through in vitro studies and experimental studies with animals. It is important to say that experiments like these are rare in human beings. Based on the findings of this review, it may be suggested that the eletrophysical resources like lasertherapy, ultra-sound, electromagnetic fields and vibration are resources that has osteogenic potencial, but more studies are needed to define the effects of it in humans, as well as more effective treatment protocols. CONCLUSION: With this literature review it is clear that eletrophysical resources have high osteogenic potential, but most of the studies are in vitro. It is needed more studies in vivo, defining therefore, better parameters and doses to be used in the treatment of osteoporosis.OBJETIVO: Fazer uma revisão bibliográfica a respeito dos efeitos dos principais recursos eletrofísicos utilizados na aceleração do metabolismo ósseo e no tratamento da osteoporose. ANTECEDENTES: A Organização Mundial da Saúde (OMS) define a osteoporose como doença esquelética sistêmica caracterizada por diminuição da massa óssea e deterioração microarquitetural do tecido ósseo, com consequente aumento da fragilidade óssea e susceptibilidade à fratura. Vários tratamentos medicamentosos e não medicamentosos vêm sendo desenvolvidos na tentativa de aumentar a massa óssea e prevenir a osteoporose. Dentro desse contexto, os recursos eletrofísicos vêm tendo um papel de destaque, como recursos que apresentam um potencial osteogênico, capazes de estimular a proliferação de osteoblastos e biomodular o metabolismo ósseo. ESTRATÉGIA DE PESQUISA: Foram consultadas as bases de dados: The Cochrane Library, MEDLINE, Embase, LILACS, SciELO, referências dos artigos identificados, e contato com especialisas em laser, entre os anos de 1983 e 2009. CRITÉRIOS DE SELEÇÃO: Foram incluídos estudos experimentais e ensaios clínicos randomizados que avaliaram os efeitos dos recursos eletrofísicos na osteoporose. RECOMPILAÇÃO E ANÁLISE DE DADOS: Dois revisores selecionaram independentemente os estudos, avaliaram sua qualidade metodológica dos estudos e coletaram os dados. RESULTADOS: Todos os recursos eletrofísicos citados neste artigo se mostraram eficazes na estimulação do metabolismo ósseo. No entanto, a grande maioria dos estudos realizados evidenciam esses efeitos através de estudos in vitro e estudos experimentais com cobaias. Cabe ressaltar que trabalhos como esses são raros em seres humanos. Baseado nos achados desta revisão pode ser sugerido que os recursos eletrofísicios como o laser terapêutico, o ultrassom, campos eletromagnéticos e plataformas vibratórias são recursos que tem um potencial osteogênico entretanto mais estudos são necessários para definir os efeitos dos mesmos em humanos, bem como, protocolos mais eficazes de tratamento. CONCLUSÃO: A partir deste levantamento bibliográfico, fica evidente que os recursos eletrofísicos apresentam um grande potencial osteogênico, porém, a maior parte dos estudos é in vitro. São necessários mais estudos in vivo, definindo, assim, melhores parâmetros e doses, para que sejam utilizados no tratamento da osteoporose.Universidade Federal de São Paulo (UNIFESP)Universidade Federal de São CarlosUNIFESPSciEL

Planning and control in construction : analysis and integrations of three methodological approaches. Location-based management system (LBMS), last planner system (LPS) and critical path method (CPM)

LAUREA MAGISTRALETra le cinque principali funzioni manageriali riconosciute universalmente dalla letteratura, pianificazione e controllo occupano i posti di maggior rilevanza. La pianificazione è il momento in cui si sviluppa il piano di progetto e si definiscono le attività e i valori delle variabili necessari al raggiungimento degli obiettivi. Il controllo è la fase operativa in cui è necessario monitorare il corretto procedere del programma, trovare eventuali scostamenti dal piano e adottare adeguate misure correttive. Ad oggi, nel mondo delle costruzioni esistono principalmente tre diversi metodi di pianificazione e controllo chiamati Location-Based Management System (LBMS), Last Planner System (LPS) e Critical Path Method (CPM), sviluppati a partire dalla fine degli anni ‘50. Attraverso un’attenta analisi bibliografica, l’obiettivo di questo elaborato di tesi è quello di, analizzando formalmente e tecnicamente i tre metodi sopra citati ed evidenziando quindi i rispettivi vantaggi e svantaggi, cercare di superare i limiti e le criticità di ciascuno attraverso un’integrazione tra di essi. Inizialmente, il primo tentativo di integrazione proposta sarà a coppie ma, avendo scoperto margine per ulteriore perfezionamento, il culmine della dissertazione si raggiungerà con la proposta di un modello teorico integrato che contemporaneamente consideri tutti i metodi sopra elencati.Among the five main managerial functions universally recognized by the literature, planning and control occupy the most important positions. Planning is the moment in which the project plan is developed and the activities and values of the variables necessary to achieve the objectives are defined. Control is the operational phase in which it is necessary to monitor the correct progress of the program, find any deviations from the plan and take appropriate corrective measures. To date, in the construction world there are mainly three different planning and control methods called Location-Based Management System (LBMS), Last Planner System (LPS) and Critical Path Method (CPM), developed starting from the late 1950s. Through a careful bibliographic analysis, the aim of this thesis is to, by formally and technically analyzing the three methods mentioned above and thus highlighting the respective advantages and disadvantages, trying to overcome the limits and criticalities of each one through a integration between them. Initially, the first attempt of the integration will be in pairs but, having discovered space for further improvement, the culmination of the dissertation will be reached with the proposal of an integrated theoretical model that simultaneously considers all the methods listed above

TREM2 sustains microglial expansion during aging and response to demyelination

Microglia contribute to development, homeostasis, and immunity of the CNS. Like other tissue-resident macrophage populations, microglia express the surface receptor triggering receptor expressed on myeloid cells 2 (TREM2), which binds polyanions, such as dextran sulphate and bacterial LPS, and activates downstream signaling cascades through the adapter DAP12. Individuals homozygous for inactivating mutations in TREM2 exhibit demyelination of subcortical white matter and a lethal early onset dementia known as Nasu-Hakola disease. How TREM2 deficiency mediates demyelination and disease is unknown. Here, we addressed the basis for this genetic association using Trem2(-/-) mice. In WT mice, microglia expanded in the corpus callosum with age, whereas aged Trem2(-/-) mice had fewer microglia with an abnormal morphology. In the cuprizone model of oligodendrocyte degeneration and demyelination, Trem2(-/-) microglia failed to amplify transcripts indicative of activation, phagocytosis, and lipid catabolism in response to myelin damage. As a result, Trem2(-/-) mice exhibited impaired myelin debris clearance, axonal dystrophy, oligodendrocyte reduction, and persistent demyelination after prolonged cuprizone treatment. Moreover, myelin-associated lipids robustly triggered TREM2 signaling in vitro, suggesting that TREM2 may directly sense lipid components exposed during myelin damage. We conclude that TREM2 is required for promoting microglial expansion during aging and microglial response to insults of the white matter

Critical role for prokineticin 2 in CNS autoimmunity

Objective: To investigate the potential role of prokineticin 2 (PK2), a bioactive peptide involved in multiple biological functions including immune modulation, in CNS autoimmune demyelinating disease. Methods: We investigated the expression of PK2 in mice with experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), and in patients with relapsing-remitting MS. We evaluated the biological effects of PK2 on expression of EAE and on development of T-cell response against myelin by blocking PK2 in vivo with PK2 receptor antagonists. We treated with PK2 immune cells activated against myelin antigen to explore the immune-modulating effects of this peptide in vitro. Results: Pk2 messenger RNA was upregulated in spinal cord and lymph node cells (LNCs) of mice with EAE. PK2 protein was expressed in EAE inflammatory infiltrates and was increased in sera during EAE. In patients with relapsing-remitting MS, transcripts for PK2 were significantly increased in peripheral blood mononuclear cells compared with healthy controls, and PK2 serum concentrations were significantly higher. A PK2 receptor antagonist prevented or attenuated established EAE in chronic and relapsing-remitting models, reduced CNS inflammation and demyelination, and decreased the production of interferon (IFN)-γ and interleukin (IL)-17A cytokines in LNCs while increasing IL-10. PK2 in vitro increased IFN-γ and IL-17A and reduced IL-10 in splenocytes activated against myelin antigen. Conclusion: These data suggest that PK2 is a critical immune regulator in CNS autoimmune demyelination and may represent a new target for therapy

Hypomorphic mutation in the RAG2 gene affects dendritic cell distribution and migration.

In Omenn syndrome, altered dendritic cell distribution and impaired migration represent an additional level of immune dysregulation, contributing to the pathogenesis of autoimmunity. OS is a severe combined immunodeficiency characterized by erythrodermia and protracted diarrhea as a result of infiltration of oligoclonal-activated T cells, caused by hypomorphic mutations in RAGs. The RAG2(R229Q) mouse model fully recapitulates the clinical OS phenotype. We evaluated whether T and B cell defects, together with the abnormal lymphoid structure, could affect DC homeostasis and function. High density of LCs was observed in skin biopsies of Omenn patients and in the derma of RAG2(R229Q) mice, correlating with the presence of erythrodermia. In vivo models of cutaneous skin painting and CHS demonstrated a decreased migration of RAG2(R229Q) DCsin particular, LCsinto draining LNs. Interestingly, at steady state, RAG2(R229Q) mice showed a reduction in DC number in all hematopoietic organs except LNs. Analysis of the MHCII marker revealed a diminished expression also upon the LPS-driven inflammatory condition. Despite the decreased number of peripheral DCs, BM pre-cDCs were present in normal number compared with RAG2(+/+) controls, whereas pDCs and monocytes were reduced significantly. Overall, these results point to a secondary defect in the DC compartment, which contributes to clinical manifestations and autoimmunity in OS

Comparison of the effects of low-level laser therapy and low-intensity pulsed ultrasound on the process of bone repair in the rat tibia

BACKGROUND: Electrophysical agents such as Ultrasound (US) and low-level laser therapy (LLLT) have been increasingly used in physical therapy practice. Studies suggest that these devices are able to stimulate osteoblast proliferation and osteogenesis at the fracture site, resulting in a greater deposition of bone mass and speeding up the consolidation process. OBJECTIVE: The aim of this study was to analyze the effects of US and LLLT on the bone healing process, through biomechanical and histological analysis of the bone callus. METHODS: A total of 30 rats were randomly allocated into three groups: control group fracture without treatment (GC); fracture group treated with pulsed US, burst 1.5 MHz, 200us, 1KHz, 30 mW/cm² (GUS) and fracture group treated with laser 830nm, 100mW, 120J/cm² (GL). Bone defects were performed with a circular drill of 2mm in diameter in the animal's tibias. The treatments were carried out after surgery consisting of 7 applications every 48 hours. After 14 days the animals were sacrificed and the tibias were removed to perform the analysis, being the right tibia designated for biomechanical analysis, while the left tibia for histological analysis. RESULTS: The biomechanical analysis showed no statistically significant difference between biomechanical properties of the CG, CL and GUS. In morphometric analysis, both GUS and GL showed a significantly higher woven bone tissue area compared to the control group. However, when the two treatment modalities were compared, there were no statistical differences between them. CONCLUSION: Both devices used in this study were able to accelerate the bone healing process in rats.CONTEXTUALIZAÇÃO: Recursos eletrofísicos, como o ultrassom (US) e a terapia laser de baixa potência (LLLT), vêm sendo cada vez mais utilizados na prática fisioterapêutica. Estudos sugerem que esses recursos são capazes de estimular a proliferação de osteoblastos e a osteogênese no local da fratura, promovendo maior deposição de massa óssea e acelerando o processo de consolidação. OBJETIVO: Analisar os efeitos do US e da LLLT no processo de consolidação óssea por meio das análises biomecânica e histológica do calo ósseo. MÉTODOS: Foram utilizados 30 ratos machos, distribuídos aleatoriamente em três grupos: grupo controle fratura, sem tratamento (GC); grupo fratura tratado com US pulsado com burst de 1,5 MHz, 200us, 1KHz, 30 mW/cm² (GUS) e grupo fratura tratado com laser 830nm, 100mW, 120J/cm² (GL). Foram realizados defeitos ósseos circulares com broca de 2 mm de diâmetro nas tíbias dos animais. Os tratamentos foram realizados a cada 48 horas, totalizando sete aplicações e, no 14º dia, os animais foram sacrificados. A tíbia direita foi designada para análise biomecânica, enquanto a esquerda, para análise histológica. RESULTADOS: A análise biomecânica não mostrou diferença estatisticamente significativa entre as propriedades biomecânicas do GC, GL e GUS. Na análise morfométrica, tanto GUS quanto GL apresentaram área de osso neoformado estatisticamente maior em relação ao GC. No entanto, quando as duas modalidades de tratamento foram comparadas, não foram encontradas diferenças estatísticas entre elas. CONCLUSÃO: Ambos os recursos utilizados neste estudo foram capazes de acelerar o processo de reparo ósseo em ratos.Universidade Federal de São CarlosUFSCar Departamento de Ciências FisiológicasUniversidade Federal de São Paulo (UNIFESP) Departamento de BiociênciasUNIFESP, Depto. de BiociênciasSciEL

Thymus transplantation for complete DiGeorge syndrome: European experience

Background: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). Methods: Twelve patients with cDGS were transplanted with allogeneic cultured thymus. Objective: To confirm and extend the results previously obtained in a single centre. Results: Two patients died of pre-existing viral infections without developing thymopoeisis and one late death occurred from autoimmune thrombocytopaenia. One infant suffered septic shock shortly after transplant resulting in graft loss and the need for a second transplant. Evidence of thymopoeisis developed from 5-6 months after transplantation in ten patients. The median (range) of circulating naïve CD4 counts (x10663 /L) were 44(11-440) and 200(5-310) at twelve and twenty-four months post-transplant and T-cell receptor excision circles were 2238 (320-8807) and 4184 (1582 -24596) per106 65 T-cells. Counts did not usually reach normal levels for age but patients were able to clear pre-existing and later acquired infections. At a median of 49 months (22-80), eight have ceased prophylactic antimicrobials and five immunoglobulin replacement. Histological confirmation of thymopoeisis was seen in seven of eleven patients undergoing biopsy of transplanted tissue including five showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator (AIRE) expression was also demonstrated. Autoimmune complications were seen in 7/12 patients. In two, early transient autoimmune haemolysis settled after treatment and did not recur. The other five suffered ongoing autoimmune problems including: thyroiditis (3); haemolysis (1), thrombocytopaenia (4) and neutropenia (1). Conclusions: This study confirms the previous reports that thymus transplantation can reconstitute T cells in cDGS but with frequent autoimmune complications in survivors

Adult type diffuse gliomas in the new 2021 WHO Classification

Adult-type diffuse gliomas represent a group of highly infiltrative central nervous system tumors with a prognosis that significantly varies depending on the specific subtype and histological grade. Traditionally, adult-type diffuse gliomas have been classified based on their morphological features with a great interobserver variability and discrepancy in patient survival even within the same histological grade. Over the last few decades, advances in molecular profiling have drastically changed the diagnostic approach and classification of brain tumors leading to the development of an integrated morphological and molecular classification endowed with a more clinically relevant value. These concepts were largely anticipated in the revised fourth-edition of WHO classification of central nervous system tumors published in 2016. The fifth-edition (WHO 2021) moved molecular diagnostics forward into a full integration of molecular parameters with the histological features into an integrative diagnostic approach. Diagnosis of adult type diffuse gliomas, IDH mutant and IDH-wildtype has been simplified by introducing revised diagnostic and grading criteria. In this review, we will discuss the most recent updates to the classification of adult-type diffuse gliomas and summarize the essential diagnostic keys providing a practical guidance to pathologists