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1.
J Clin Immunol ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462728

RESUMO

PURPOSE: Use of adoptive immunotherapy with virus-specific T cells (VST) in patients with inborn errors of immunity prior to hematopoietic stem cell transplantation (HSCT) has been reported in few patients. We report our experience, reviewing all the cases previously reported. METHODS: We report four children with inborn errors of immunity who received VST infusion in a pre-HSCT setting in two reference centers in Spain and review all inborn errors of immunity cases previously reported. RESULTS: Taking into account our four cases, nine children have been reported to receive VST prior to HSCT to date: 3 severe combined immunodeficiency, 2 CTPS1 deficiency, 1 dyskeratosis congenital, 1 ORAI1 deficiency, 1 Rothmund-Thomson syndrome, and 1 combined immunodeficiency without confirmed genetic defect. In four patients, immunotherapy resulted in clinical improvement, allowing to proceed to HSCT. In these cases, the infusion was started closely to viral diagnosis [mean time 28 days (IQR; 17-52 days)], and the VST was followed shortly thereafter by HSCT [mean time 28 days (IQR; 10-99 days)]. Viremia was controlled after HSCT in two cases (performed 7 and 36 days after the infusion). Multiple infusions were required in many cases. Five out of nine patients died before receiving HSCT. These patients presented with a prolonged and uncontrolled infection before VST administration [mean time from viral diagnosis to VST infusion was 176 days (IQR; 54-1687)]. CONCLUSIONS: In patients with inborn errors of immunity, the efficacy of VST for treating disseminated viral infections in pre-transplant settings seems to have a limited efficacy. However, this therapy could be used in a pre-emptive setting before severe viral disease occurs or closely to HSCT.

2.
Eur J Haematol ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33296531

RESUMO

OBJECTIVES: The prevalence of sickle cell disease (SCD) in Spain is markedly inferior compared with other European and Mediterranean countries. However, the diagnosis of new patients with SCD is expected to increase. In this multicenter retrospective study we analyze the HSCT results obtained in Spain. METHODS: Forty-five patients who underwent a matched sibling donor (MSD) HSCT between 1999 and 2018 were included. Primary endpoint was event-free survival (EFS) and secondary endpoints included acute and chronic graft versus host disease (GVHD) and overall survival (OS). RESULTS: Bone marrow was the most frequent stem cell source (93.3%). Most patients received a conditioning regimen based on busulfan and cyclophosphamide (69%). Cumulative incidence of grade III-IV acute GvHD and chronic GvHD were 6.8% (95%CI 2.3%-20.1%) and 5.4% (CI95% 1.38-19-9%), respectively. EFS and overall survival OS at 3 years post HSCT were 89.4% (95%CI 73.9%-95.9%) and 92.1% (95%CI 77.2-97.4%), respectively. All patients aged ≤5 presented 100% EFS and OS. CONCLUSIONS: An early referral to HSCT centers should be proposed early in life, before severe complications occur. MSD HSCT should be considered a curative option for all patients aged ≤5 years old and for older pediatric patients who present complications derived from the disease.

3.
BMJ Open ; 10(12): e039723, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33380479

RESUMO

INTRODUCTION: Cognitive and physical declines are frequent causes of disability among older adults (OAs) in Mexico that imposes significant burden on the health system and OAs' families. Programmes to prevent or delay OAs' cognitive and physical decline are scarce. METHODS AND ANALYSIS: A double-blind randomised clinical trial will be conducted. The study will aim to evaluate two 24-week double-task (aerobic and cognitive) square-stepping exercise programmes for OAs at risk of cognitive decline-one programme with and another without caregiver participation-and to compare these with an aerobic-balance-stretching exercise programme (control group). 300 OAs (100 per group) affiliated with the Mexican Institute of Social Security (IMSS) between 60 and 65 years of age with self-reported cognitive concerns will participate. They will be stratified by education level and randomly allocated to the groups. The intervention will last 24 weeks, and the effect of each programme will be evaluated 12, 24 and 52 weeks after the intervention. Participants' demographic and clinical characteristics will be collected at baseline. The outcomes will include: (1) general cognitive function; (2) specific cognitive functions; (3) dual-task gait; (4) blood pressure; (5) carotid intima-media thickness; (6) OAs' health-related quality of life; and (7) caregiver burden. The effects of the interventions on each outcome variable will be examined using a repeated-measures analysis of variance (ANOVA), with study groups as the between-subjects variable and time as the within-subject variable. ETHICS AND DISSEMINATION: The study was approved by the IMSS Ethics and Research Committees (registration number: 2018-785-095). All participants will sign a consent form prior to their participation. The study results will be disseminated to the IMSS authorities, healthcare providers and the research community. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04068376).

4.
Metas enferm ; 23(8): 66-72, oct. 2020. graf, tab
Artigo em Espanhol | IBECS-Express | IBECS | ID: ibc-ET2-7277

RESUMO

OBJETIVO: revisar la evidencia científica referente a los cuidados de la placenta y a la seguridad del recién nacido en el nacimiento Lotus. MÉTODO: revisión narrativa. Se llevaron a cabo diferentes estrategias de búsqueda en las siguientes bases de datos y plataformas: Pubmed, Cochrane, Ovid, Scielo, Cuiden, Clinical key, BMJ, Metas de Enfermería y Google Scholar. Palabras usadas: Lotus birth, umbilical non severance, cord clamping, care, safety, nacimiento Lotus. Filtros: 2016-2020, sobre cuidados placenta y seguridad recién nacido, estudios epidemiológicos. RESULTADOS: se localizaron 169 documentos. Se seleccionaron seis artículos. En dos artículos se trataban los cuidados de la placenta que eran lavadas con agua tibia en las primeras horas, secadas y envueltas en paños de tejidos naturales, usando sales y hierbas aromáticas para acelerar el proceso de secado, y dejándola a la altura del recién nacido. En los otros cuatro documentos se describían seis casos de complicaciones infecciosas que se resolvieron con antibioterapia, en madres que habían presentado bolsa rota prolongada, cultivos vaginales positivos y ausencia de antibioterapia periparto. DISCUSIÓN: el Lotus birth es una práctica infrecuente, asociada tradicionalmente al parto domiciliario, que se va introduciendo en el medio hospitalario. Es escasa la evidencia disponible sobre los cuidados de la placenta en el nacimiento Lotus y la seguridad de esta práctica para los recién nacidos


OBJECTIVE: to review the scientific evidence regarding placenta care and newborn safety in Lotus Birth. METHODS: a narrative review. Different search strategies were conducted in the following databases and platforms: Pubmed, Cochrane, Ovid, Scielo, Cuiden, Clinical key, BMJ, Metas de Enfermería and Google Scholar. Terms used: Lotus Birth, umbilical non severance, cord clamping, care, safety, nacimiento lotus. Filters: 2016-2020, on placenta care and newborn safety, epidemiological studies. RESULTS: in total. 169 documents were located. Six articles were selected. Two articles discussed placenta care: they were washed with warm water during the first hours, dried and wrapped in natural fabric cloths, using salts and aromatic plants to accelerate the drying process, and placed at the same height as the newborn. The other four documents described six cases of infectious complications, which were solved with antibiotic therapy, in mothers who had presented prolonged broken sac, positive vaginal cultures, and lack of peripartal antibiotic therapy. DISCUSSION: Lotus Birth is a rare practice, traditionally associated with home births, which has been increasingly introduced in the hospital setting. There is limited evidence available about placenta care in Lotus Birth, and the safety of this practice for newborns

5.
Eur J Haematol ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084101

RESUMO

OBJECTIVE: Describe the GETH haploidentical stem cell transplantation (haplo-HSCT) activity in non-malignant disease (NMDs). METHODS: We retrospectively analyzed data from children with NMDs who underwent haplo-HSCT. RESULTS: From January 2001 to December 2016, 26 pediatric patients underwent 31 haplo-HSCT through ex vivo T cell-depleted (TCD) graft platforms or post-transplantation cyclophosphamide (PT-Cy) at 7 Spanish centers. Five cases employed unmanipulated PT-Cy haplo-HSCT, 16 employed highly purified CD34+ cells, and 10 employed ex vivo TCD grafts manipulated either with CD3+ CD19+ depletion, TCRαß+ CD19+ selection or naive CD45RA+ T-cell depletion. Peripheral blood stem cells were the sole source for patients following TCD haplo-HSCT, and bone marrow was the source for one PT-Cy haplo-HSCT. The most common indications for transplantation were primary immunodeficiency disorders (PIDs), severe aplastic anemia, osteopetrosis, and thalassemia. The 1-year cumulative incidence of graft failure was 27.4%. The 1-year III-IV acute graft-versus-host disease (GvHD) and 1-year chronic GvHD rates were 34.6% and 16.7%, respectively. The 2-year overall survival was 44.9% for PIDs, and the 2-year graft-versus-host disease-free and relapse-free survival rate was 37.6% for the other NMDs. The transplantation-related mortality at day 100 was 30.8%. CONCLUSION: Although these results are discouraging, improvements will come if procedures are centralized in centers of expertise.

6.
J Biol Chem ; 295(41): 14164-14177, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-32788214

RESUMO

Success or failure of pancreatic beta cell adaptation to ER stress is a determinant of diabetes susceptibility. The ATF6 and IRE1/XBP1 pathways are separate ER stress-response effectors important to beta cell health and function. ATF6α. and XBP1 direct overlapping transcriptional responses in some cell types. However, the signaling dynamics and interdependence of ATF6α and XBP1 in pancreatic beta cells have not been explored. To assess pathway-specific signal onset, we performed timed exposures of primary mouse islet cells to ER stressors and measured the early transcriptional response. Comparing the time course of induction of ATF6 and XBP1 targets suggested that the two pathways have similar response dynamics. The role of ATF6α in target induction was assessed by acute knockdown using islet cells from Atf6α flox/flox mice transduced with adenovirus expressing Cre recombinase. Surprisingly, given the mild impact of chronic deletion in mice, acute ATF6α knockdown markedly reduced ATF6-pathway target gene expression under both basal and stressed conditions. Intriguingly, although ATF6α knockdown did not alter Xbp1 splicing dynamics or intensity, it did reduce induction of XBP1 targets. Inhibition of Xbp1 splicing did not decrease induction of ATF6α targets. Taken together, these data suggest that the XBP1 and ATF6 pathways are simultaneously activated in islet cells in response to acute stress and that ATF6α is required for full activation of XBP1 targets, but XBP1 is not required for activation of ATF6α targets. These observations improve understanding of the ER stress transcriptional response in pancreatic islets.

7.
J Food Sci Technol ; 57(9): 3525-3531, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32713964

RESUMO

Tomato field wastes and industrial by-products represents a valuable source of compounds with nutraceutical potential, and therefore of raw material to obtain food ingredients and additives. The objective of this study was to obtain a flour from tomato industrial by-product and from tomato field waste, dried by a conventional method, that allows to remain important nutraceutical compounds, which in the future, can be used for biotechnological purposes. We found that the drying procedure that allowed to reach an adequate water activity (0.4-0.6) in a forced convection oven were: 55 °C during 120 min. Both, the by-product and the field waste are potential sources for the extraction of phenolic and carotenoid compounds, getting up 11.26 µg/mg dry extract of lycopene and 162.82 µg/mg dry extract of phenolic compounds, highlighting the flavonoids: naringenin, catechin, and rutin. On the other hand, antioxidant analysis showed that oven dried by-product exhibits an inhibition around 80% against hydroxyl and peroxyl radicals, and a positive correlation of both lycopene and ß-carotene with myoglobin protection ratio against these radicals. We concluded that the flour from tomato industrial by-products and field waste have nutraceutical properties attractive to the food industry.

8.
J Pediatr Endocrinol Metab ; 33(7): 865-872, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32634109

RESUMO

Background Physiologic hyperglycemia of puberty is a major contributor to poor glycemic control in youth with type 1 diabetes (T1D). This study's aim was to determine the effectiveness of continuous glucose monitoring (CGM) to improve glycemic control in pubertal youth with T1D compared to a non-CGM cohort after controlling for age, sex, BMI, duration, and insulin delivery methodology. The hypothesis is that consistent CGM use in puberty improves compliance with diabetes management, leading to increased percentage (%) time in range (TIR70-180 mg/dL) of glycemia, and lowering of HbA1c. Methods A longitudinal, retrospective, case-controlled study of 105 subjects consisting of 51 T1D controls (60.8% male) age 11.5 ± 3.8 y; and 54 T1D subjects (48.1% male) age 11.1 ± 5.0 y with confirmed CGM use for 12 months. Pubertal status was determined by Tanner staging. Results were adjusted for baseline HbA1c and diabetes duration. Results HbA1c was similar between the controls and the CGM group at baseline: 8.2 ± 1.1% vs 8.3 ± 1.2%, p=0.48 respectively; but was significantly lower in the CGM group 12 months later, 8.2 ± 1.1% vs. 8.7 ± 1.4%, p=0.035. Longitudinal change in HbA1c was similar in the prepubertal cohort between the control- and CGM groups: -0.17 ± 0.98% vs. 0.38 ± 1.5%, p=0.17. In contrast, HbA1c increased with advancing age and pubertal status in the pubertal controls but not in the pubertal CGM group: 0.55 ± 1.4 vs -0.22 ± 1.1%, p=0.020. Percent TIR was inversely related to HbA1c in the CGM group, r=-0.6, p=0.0004, for both prepubertal and pubertal subjects. Conclusions CGM use significantly improved glycemic control in pubertal youth with T1D compared to non-CGM users.

9.
J Clin Immunol ; 40(6): 901-916, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32638196

RESUMO

Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly with ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory disease fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected in PRF1 in 23 patients (61%), RAB27A in 10 (26%), UNC13D in 3 (8%), LYST in 1 (3%), and STXBP2 in 1 (3%) with a mean interval to diagnosis of 28.3 months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 non-transplanted patients, only 3 improved or had stable disease, one relapsed, and 10 died. Isolated CNS-HLH is a rare and often overlooked cause of inflammatory brain disease. HLH-directed therapy followed by HSCT seems to improve survival and outcome.

10.
Cir Esp ; 2020 Jun 18.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32564875

RESUMO

INTRODUCTION: Compliance to ERAS protocols is a process quality measure that is associated to better outcomes. The main objective of this study is to analyze the association between protocol compliance, surgical stress and functional recovery. The secondary objective is to identify independent factors associated to functional recovery. METHODS: A prospective observational single-centre study was performed. Patients who had scheduled colorectal surgery within an ERAS program from January 2017 to June 2018 were included. We analysed the relationship between protocol compliance percentage and surgical stress (defined by C reactive protein [CRP] blood levels on postoperative 3rd day), and functional recovery (defined by the proportion of patients who meet the discharge criteria on the 5th PO day or before). Multivariate analysis was performed to asses independent factor associated to functional recovery. RESULTS: 313 were included. For every additional percentage point of compliance to the protocol 3rd day C reactive protein plasmatic level decreases 1,46 mg/dL and increases 7% the probability to meet the discharge criteria (p < 0.001 both). Independent factors associated to functional recovery were ASA III-IV (OR 0.26; 0.14-0.48), surgical CR-POSSUM score (OR 0.68; 0.57-0.83), early mobilization (OR 4.22; 1.43-12.4) and removal of urinary catheter (OR 3.35; 1.79-6.27), p < 0,001 each of them. CONCLUSION: Better compliance to ERAS protocol in colorectal surgery decreases surgical stress and accelerates functional recovery.

12.
FASEB J ; 34(5): 6654-6674, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32223018

RESUMO

Angiogenesis, the main mechanism that allows vascular expansion for tissue regeneration or disease progression, is often triggered by an imbalance between oxygen consumption and demand. Here, by analyzing changes in the transcriptomic profile of endothelial cells (ECs) under hypoxia we uncovered that the repression of cell cycle entry and DNA replication stand as central responses in the early adaptation of ECs to low oxygen tension. Accordingly, hypoxia imposed a restriction in S-phase in ECs that is mediated by Hypoxia-Inducible Factors. Our results indicate that the induction of angiogenesis by hypoxia in Embryoid Bodies generated from murine Stem Cells is accomplished by the compensation of decreased S-phase entry in mature ECs and differentiation of progenitor cells. This conditioning most likely allows an optimum remodeling of the vascular network. Identification of the molecular underpinnings of cell cycle arrest by hypoxia would be relevant for the design of improved strategies aimed to suppress angiogenesis in pathological contexts where hypoxia is a driver of neovascularization.

14.
Am J Hematol ; 95(1): 28-37, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625177

RESUMO

A total of 192 pediatric patients, median age 8.6 years, with high-risk hematological malignancies, underwent haploidentical stem cell transplantation (haplo-HSCT) using post-transplantation cyclophosphamide (PT-Cy), or ex vivo T cell-depleted (TCD) graft platforms, from January 1999 to December 2016 in 10 centers in Spain. Some 41 patients received an unmanipulated graft followed by PT-Cy for graft-vs-host disease (GvHD) prophylaxis. A total of 151 patients were transplanted with CD3-depleted peripheral blood stem cells (PBSCs) by either CD34+ selection, CD3+ CD19+ depletion, TCRαß+ CD19+ depletion or CD45RA+ depletion, added to CD34+ selection for GvHD prophylaxis. The PBSCs were the only source in patients following ex vivo TCD haplo-HSCT; bone marrow was the source in 9 of 41 patients following PT-CY haplo-HSCT. Engraftment was achieved in 91.3% of cases. A donor younger than 30 years, and the development of chronic GvHD were positive factors influencing survival, whereas positive minimal residual disease (MRD) before transplant and lymphoid disease were negative factors. The probability of relapse increased with lymphoid malignancies, a donor killer-cell immunoglobulin-like receptor (KIR) haplotype A and positive MRD pretransplant. No difference was found in overall survival, disease-free survival or relapse incidence between the two platforms. Relapse is still of concern in both platforms, and it should be the focus of future efforts. In conclusion, both platforms for haplo-HSCT were effective and could be utilized depending on the comfort level of the center.


Assuntos
Leucemia/terapia , Transplante Haploidêntico , Transplante de Medula Óssea/métodos , Transplante de Medula Óssea/mortalidade , Criança , Ciclofosfamida/uso terapêutico , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia/mortalidade , Depleção Linfocítica , Masculino , Pediatria/métodos , Recidiva , Estudos Retrospectivos , Espanha , Análise de Sobrevida
15.
Sci Signal ; 12(610)2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796630

RESUMO

Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains unknown. We generated a mouse model that enabled the inducible, postnatal deletion of Dhps specifically in postnatal islet ß cells, which function to maintain glucose homeostasis. Removal of Dhps did not have an effect under normal physiologic conditions. However, upon development of insulin resistance, which induces ß cell proliferation, Dhps deletion caused alterations in proteins required for mRNA translation and protein secretion, reduced production of the cell cycle molecule cyclin D2, impaired ß cell proliferation, and induced overt diabetes. We found that hypusine biosynthesis was downstream of protein kinase C-ζ and was required for c-Myc-induced proliferation. Our studies reveal a requirement for DHPS in ß cells to link polyamines to mRNA translation to effect facultative cellular proliferation and glucose homeostasis.


Assuntos
Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Lisina/análogos & derivados , Fatores de Iniciação de Peptídeos/metabolismo , Poliaminas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Idoso , Alelos , Animais , Proliferação de Células , Cruzamentos Genéticos , Ciclina D2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Dieta Hiperlipídica , Feminino , Deleção de Genes , Homeostase , Humanos , Lisina/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Ornitina Descarboxilase/metabolismo , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/metabolismo
16.
Mol Metab ; 27S: S69-S80, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500833

RESUMO

BACKGROUND: A growing body of literature suggests the cell-intrinsic activity of Atf6α during ER stress responses has implications for tissue cell number during growth and development, as well as in adult biology and tumorigenesis [1]. This concept is important, linking the cellular processes of secretory protein synthesis and endoplasmic reticulum stress response with functional tissue capacity and organ size. However, the field contains conflicting observations, especially notable in secretory cell types like the pancreatic beta cell. SCOPE OF REVIEW: Here we summarize current knowledge of the basic biology of Atf6α, along with the pleiotropic roles Atf6α plays in cell life and death decisions and possible explanations for conflicting observations. We include studies investigating the roles of Atf6α in cell survival, death and proliferation using well-controlled methodology and specific validated outcome measures, with a focus on endocrine and metabolic tissues when information was available. MAJOR CONCLUSIONS: The net outcome of Atf6α on cell survival and cell death depends on cell type and growth conditions, the presence and degree of ER stress, and the duration and intensity of Atf6α activation. It is unquestioned that Atf6α activity influences the cell fate decision between survival and death, although opposite directions of this outcome are reported in different contexts. Atf6α can also trigger cell cycle activity to expand tissue cell number through proliferation. Much work remains to be done to clarify the many gaps in understanding in this important emerging field.


Assuntos
Fator 6 Ativador da Transcrição/metabolismo , Morte Celular , Proliferação de Células , Animais , Contagem de Células , Sobrevivência Celular , Humanos
17.
Pediatr Transplant ; 23(8): e13584, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31556188

RESUMO

Cytomegalovirus encephalitis is a challenging life-threatening complication following hematopoietic stem cell transplantation for which medical treatment is usually ineffective or toxic. However, in recent years, adoptive T-cell therapy has been reported to provide a significant chance of cure for patients with viral infections. Herein, two cases of pediatric patients successfully treated with third-party donor-derived virus-specific T cells for CMV meningoencephalitis are reported.


Assuntos
Infecções por Citomegalovirus/terapia , Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Meningoencefalite/terapia , Meningoencefalite/virologia , Complicações Pós-Operatórias/terapia , Complicações Pós-Operatórias/virologia , Criança , Feminino , Humanos , Lactente , Masculino , Indução de Remissão
18.
Dement Geriatr Cogn Disord ; 47(4-6): 243-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31408858

RESUMO

BACKGROUND: Endothelial dysfunction and subsequent inflammation contribute to the development of vascular cognitive impairment (VCI). Soluble intercellular adhesion molecule-1 (sICAM-1) is upregulated in endothelial dysfunction and promotes an inflammatory response; however, the relationship between sICAM-1 and VCI remains equivocal. OBJECTIVE: To determine whether sICAM-1 contributes to the prediction of VCI. METHODS: Community-dwelling older adults (n = 172) from the "Cohort of Obesity, Sarcopenia and Frailty of Older Mexican Adults" (COSFOMA) study were identified as VCI or controls using standard neuropsychological evaluations and neuroimaging. sICAM-1 was quantified using ELISA, and multivariate logistic regression determined the association between sICAM-1 and VCI. RESULTS: A total of 31 VCI cases were identified. sICAM-1 was higher in VCI (VCI: 450.7 [241.6] ng/mL vs. controls: 296.9 [140.9] ng/mL). sICAM-1 concentrations above the 90th percentile (464.1 ng/mL) were associated with VCI group membership in all models (OR: 6.9, 95% CI: 1.1-42.2). The final saturated model explained 64% of the variance in VCI group membership. CONCLUSION: High concentrations of sICAM-1 are independently associated with VCI group membership. Efforts to further characterize the relationship between indices of endothelial dysfunction and pathological changes to the aging brain should be further pursued.


Assuntos
Biomarcadores/sangue , Disfunção Cognitiva/sangue , Demência Vascular/sangue , Molécula 1 de Adesão Intercelular/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Demência Vascular/diagnóstico por imagem , Demência Vascular/psicologia , Feminino , Idoso Fragilizado , Humanos , Vida Independente , Masculino , México , Neuroimagem , Testes Neuropsicológicos , Valor Preditivo dos Testes , Fatores Socioeconômicos , Regulação para Cima
19.
Cell Metab ; 30(1): 10-11, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269421

RESUMO

Genome-wide association studies have identified hundreds of genomic variants associated with human T2D risk, but translating such findings to clinically useful information has proved challenging. A new study in Nature (Flannick et al., 2019) breaks this gridlock, using direct exome sequencing to identify functional coding variants, providing critical complementary gene-level information.


Assuntos
Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla , Exoma , Humanos
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