Hematopoietic stem cell transplantation in chronic lymphoid leukemia: a proposal by the Brazilian Consensus on Bone Marrow Transplantation of the Brazilian Society of Bone Marrow Transplantation, Rio de Janeiro 2009

Portadores de leucemia linfoide crônica (LLC) apresentam curso clínico indolente e prolongado que devem ser diferenciados daqueles que têm doença de evolução agressiva e fatal. Pacientes mais jovens e com critérios de alto risco podem se beneficiar com tratamento mais agressivo como o transplante de células-tronco hemopoéticas (TCTH). O transplante autólogo apresenta casos com remissão citogenética e molecular, baixa taxa de mortalidade, mas não demonstram platô nas curvas de sobrevivência e alta taxa de recaídas. Os transplantes alogênicos com regime mieloablativos têm altos índices de toxicidade e mortalidade, mas evidenciam o efeito enxerto versus leucemia, que aumenta a possibilidade de cura destes indivíduos. Assim, a opção dos transplantes alogênicos está dirigida para os transplantes com regime de condicionamento não mieloablativo, que pode ser aplicado inclusive a pacientes mais idosos ou portadores de comorbidades, e manter o potencial efeito GVL. A identificação dos pacientes que podem ser beneficiados por esses procedimentos, caracterizar e apontar os novos marcadores prognósticos permanece objeto de muitos estudos clínicos e foi o objetivo do grupo responsável em discutir as diretrizes do TCTH no consenso da Sociedade Brasileira de Transplante de Medula Óssea - SBTMO. Assim, consideramos que o TCTH para a leucemia linfoide crônica (LLC) deve seguir, para sua indicação, os critérios do European Group for Blood and Marrow Transplantation (EBMT) e, quando houver disponibilidade de um doador aparentado, a opção deve ser do TCTH alogênico com regime não mieloablativo. O TCTH alogênico não aparentado e o autólogo devem ser considerados como opção secundária de indisponibilidade de doador, situações especiais e ensaios clínicos.Patients with chronic lymphocytic leukemia usually have an indolent and prolonged clinical course and need to be differentiated from those who have an aggressive and fatal disease. Younger patients with high-risk criteria may benefit with a more aggressive treatment that includes hematopoietic stem cell transplantation (HSCT). Autologous transplantation, despite of the encouraging results with cases of molecular and/or cytogenetic remission and low mortality rates, does not present a plateau in survival curves and has a high relapse rate. Allogeneic transplantations using myeloablative regimens, have high toxicity and mortality rates, but also demonstrate the graft-versus-leukemia effect that increases the possibility of cure of these individuals. So the option of allogeneic transplants for patients with CLL is directed to conditioning using non-myeloablative regimens, which can also be applied to older patients or those with comorbidities, and maintain a potential graft-versus-leukemia effect. The identification of patients who may benefit from these procedures and the characterization of new prognostic markers remain the subjects of many clinical studies and were the objective of the group responsible for discussing guidelines for CLL of the consensus on HSCT SBTMO. Thus we believe that HSCT for CLL should follow the criteria of the EBMT. When a sibling donor is available the best option is allogeneic HSCT with a myeloablative regimen. The strategy of unrelated allogeneic or autologous HSCT must be considered as a second option when no donor is available, for special situations and clinical trials

The potential role of G-CSF in stroke

O fator estimulador de colônias granulocitárias (G-CSF) é uma glicoproteína descrita há mais de vinte anos, e é largamente utilizada para tratamento de estados neutropênicos e no transplante de medula óssea. O G-CSF estimula células-tronco hematopoéticas e regula crucialmente a sobrevivência de neutrófilos maduros, pós-mitóticos, através da inibição da apoptose. Além do efeito sistêmico, mais recentemente tem-se demonstrado uma surpreendente atividade do G-CSF no sistema nervoso central. A administração de G-CSF mobiliza células-tronco e progenitoras da medula óssea para o sangue periférico, que, por sua vez, atravessa a barreira hemato-encefálica (BHE) e se dirige à área acometida do cérebro. A atividade do G-CSF no sistema nervoso central tem sido caracterizada como multimodal, pois, além do efeito mobilizador de células da medula óssea, demonstrou uma ação direta neuroprotetora através de diferentes mecanismos, tais como a atividade antiapoptótica em neurônios, regeneração da vascularização, efeito anti-inflamatório e estimulação da neurogênese endógena. Este relato sumariza a ação do G-CSF no sistema nervoso central e aborda seu potencial para o emprego no acidente vascular cerebral.The granulocyte colony-stimulating-factor (G-CSF) is a glycoproteina which has been described for decades, and it is commonly utilized in the treatment of neutropenic states and bone marrow transplants. G-CSF stimulates hematopoietic stem-cels e crucially regulates the survival of mature neutrophils through a mechanism of apoptosis inhibition. Beyond its systemic effect, recently it has been shown its surprising activity in the central nervous system (CNS). G-CSF administration mobilizes bone marrow stem cells para systemic blood, and those cells cross the blood-brain-barrier e target brain's damaged area. G-CSF's activity in the CNS has been defined as multimodal, because additionally it has been demonstrated a direct neuroprotective action through different mechanisms such as antiapoptotic activity, angiogenesis, anti-inflamatory effect, and stimulation of endogenous neurogenesis. This paper sumarizes G-CSF action in the CNS and approaches its potential para use in stroke

Multi-graviton theory, a latticized dimension, and the cosmological constant

Beginning with the Pauli-Fierz theory, we construct a model for multi-graviton theory. Couplings between gravitons belonging to nearest-neighbor ``theory spaces'' lead to a discrete mass spectrum. Our model coincides with the Kaluza-Klein theory whose fifth dimension is latticized. We evaluate one-loop vacuum energy in models with a circular latticized extra dimension as well as with compact continuous dimensions. We find that the vacuum energy can take a positive value, if the dimension of the continuous space time is $6, 10,...$. Moreover, since the amount of the vacuum energy can be an arbitrary small value according to the choice of parameters in the model, our models is useful to explain the small positive dark energy in the present universe.Comment: 10 pages, No figure. Needs REVTeX4. citations are corrected and minor correction

Self-consistent treatment of thermal effects in neutron-star post-mergers: observational implications for third-generation gravitational-wave detectors

We assess the impact of accurate, self-consistent modelling of thermal effects in neutron-star merger remnants in the context of third-generation gravitational-wave detectors. This is done through the usage, in Bayesian model selection experiments, of numerical-relativity simulations of binary neutron star (BNS) mergers modelled through: a) nuclear, finite-temperature (or ``tabulated'') equations of state (EoSs), and b) their simplifed piecewise (or ``hybrid'') representation. These cover four different EoSs, namely SLy4, DD2, HShen and LS220. Our analyses make direct use of the Newman-Penrose scalar $\psi_4$ outputted by numerical simulations. Considering a detector network formed by three Cosmic Explorers, we show that differences in the gravitational-wave emission predicted by the two models are detectable with a natural logarithmic Bayes Factor $\log{\cal{B}}\geq 5$ at average distances of $d_L \simeq 50$Mpc, reaching $d_L \simeq 100$Mpc for source inclinations $\iota \leq 0.8$, regardless of the EoS. This impact is most pronounced for the HShen EoS. For low inclinations, only the DD2 EoS prevents the detectability of such modelling differences at $d_L \simeq 150$Mpc. Our results suggest that the usage a self-consistent treatment of thermal effects is crucial for third-generation gravitational wave detectors.Comment: 9 pages, 3 Figure

Adherence to Mediterranean diet associated with health-related quality of life in children and adolescents: a systematic review

Abstract Background: Health-related quality of life (HRQoL) has become a signifcant outcome in assessing interventions in the pediatric population and could be infuenced by diet patterns. The Mediterranean diet (MD) pattern has been related to multiple positive health outcomes, including decreased cardiovascular risk and better mental health. We aimed to evaluate the association between MD adherence and HRQoL in children and adolescents. Methods: The literature search was conducted in PubMed, Cochrane Library, Scopus, Web of Science, Embase, and Ovid-MEDLINE databases from inception to May 2022. Two researchers independently checked titles and abstracts, evaluated full-text studies, extracted data, and appraised the risk of bias using the Newcastle–Ottawa Scale (NOS). Results: Eleven studies (1 longitudinal and 10 cross-sectional), totaling 6,796 subjects, were included. Ten studies assessed MD adherence with KIDMED index, and one assessed MD adherence with Krece Plus test, while all included studies assessed HRQoL with a KIDSCREEN test. All studies analyzed the association between MD adherence and HRQoL with linear regression, and eight used adjusted models. Five studies found a signifcant positive association of MD adherence with HRQoL, with β-values ranging from 0.13 to 0.26. Two found a nonsignifcant positive relationship, while one found a negative association. According to the NOS criteria, the risk of bias assessment showed four studies with a low risk of bias and seven with a high risk of bias. Conclusion: Our fndings suggest a positive correlation of MD adherence with HRQoL in children and adolescents. However, future research is needed to strengthen the evidence of this relationshi