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1.
AIDS Behav ; 2023 Oct 23.
Article En | MEDLINE | ID: mdl-37870691

The 2022 outbreak of mpox disproportionately impacted men who have sex with men and people living with HIV. As such, HIV organizations were uniquely situated to reach populations affected by mpox. However, the extent to which these organizations pivoted to address mpox, and what form mpox messaging took, is unknown. We conducted a rapid environmental scan of 29 HIV or sexual health organizations to assess the frequency and content of mpox messaging in August 2022, the peak of the mpox outbreak in Miami, FL. Approximately half of the organizations provided mpox messaging, most of which was accurate. Only 5% of the messages were in Spanish and 4% in Spanish and Haitian Creole. Our findings suggest HIV organizations' pivot to mpox messaging may have been delayed overall and in reaching Spanish- and Haitian Creole-speaking communities. Results could inform modifications to mpox messaging campaigns and future outbreaks that disproportionately affect minoritized communities.


RESUMEN: El brote de la viruela del mono en 2022 afectó desproporcionadamente a hombres que tienen relaciones sexuales con hombres y personas que viven con el VIH. Como tal, las organizaciones dedicadas al VIH estaban en una posición única para llegar a las poblaciones afectadas por la viruela del mono. Sin embargo, no se sabe en qué medida estas organizaciones cambiaron su enfoque para abordar la viruela del mono y qué forma tomó la mensajería sobre a la viruela del mono. Realizamos un escaneo ambiental rápido de 29 organizaciones de VIH o salud sexual para evaluar la frecuencia y el contenido de la mensajería sobre la viruela del mono en agosto de 2022, en el pico del brote de la viruela del mono en Miami, Florida. Aproximadamente la mitad de las organizaciones proporcionaron mensajería sobre la viruela del mono, la mayoría de la cual era precisa. Solo el 5% de los mensajes estaban en español y el 4% en español y criollo haitiano. Nuestros hallazgos sugieren que el cambio de enfoque de las organizaciones de VIH hacia la mensajería sobre la viruela del mono puede haber sido en general demorado y que no llegó adecuadamente a las comunidades de habla hispana y criollo haitiano. Los resultados podrían informar modificaciones en las campañas de mensajería sobre la viruela del mono y en futuros brotes que afecten desproporcionadamente a comunidades minorizadas.

3.
Bol. pediatr ; 63(264): 99-103, 2023. tab
Article Es | IBECS | ID: ibc-230679

Objetivo. Analizar las características clínicas y analíticas de los pacientes diagnosticados de síndrome inflamatorio multisistémico pediátrico vinculado a SARS-CoV-2 (SIM-PedS) en la Comunidad Autónoma del Principado de Asturias, durante su ingreso y en los seis meses posteriores. Material y métodos. Estudio descriptivo, observacional, prospectivo (diciembre 2020 - junio 2022). Se incluyeron los pacientes menores de 18 años diagnosticados de SIM-PedS en la Comunidad Autónoma del Principado de Asturias. Se recogieron datos demográficos, clínicos y analíticos durante el ingreso y en los seis meses posteriores. Resultados. Durante el periodo de estudio, se incluyeron 16 pacientes (11 varones, edad mediana 10,6 años). Todos los pacientes tuvieron fiebre, 12 clínica gastrointestinal y 12 exantema. Todos los pacientes presentaron elevación de reactantes de fase aguda, 13 elevación de la porción N-terminal del pro-péptido natriurético tipo B, 10 linfopenia y 6 trombopenia. En la evaluación cardiológica durante el ingreso se encontraron alteraciones en seis pacientes. Todos los pacientes recibieron inmunoglobulinas, 14 corticoides y 6 inotrópicos. Nueve pacientes precisaron ingreso en la Unidad de Cuidados Intensivos Pediátricos (UCIP), con una estancia mediana de cuatro días. Un paciente falleció. No se han observado alteraciones reseñables ni en la clínica ni en la analítica ni en la evaluación cardiaca durante los seis meses posteriores al alta. Conclusiones. Los casos recogidos han mostrado las características clínicas y analíticas descritas en la literatura sobre el SIM-PedS, requiriendo más de la mitad ingreso en UCIP y recibiendo en todos los casos tratamiento con inmunoglobulinas. Presentaron frecuentemente afectación cardiológica, falleciendo un paciente. A los seis meses del episodio, ningún paciente ha mostrado afectación clínica, analítica ni de la función cardiaca (AU)


Aim. To analyze the clinical and analytical characteristics of patients diagnosed with Multisystem Inflammatory Syndrome in Children associated with SARS-CoV-2 (MIS-C) in the autonomous community of the Principality of Asturias, during their admission and in the subsequent six months. Material and methods. Descriptive, observational, prospective study (December 2020 - June 2022). Patients under 18 years of age diagnosed with MIS-C in the autonomous community of the Principality of Asturias were included. Demographic, clinical and analytical data were collected during admission and in the following six months. Results. During the study period, 16 patients were included (11 males, median age 10.6 years). All patients had fever, 12 had gastrointestinal symptoms and 12 had rash. All patients presented elevation of acute phase reactants, 13 elevation of the N-terminal portion of B-type natriuretic pro-peptide, 10 lymphopenia and 6 thrombopenia. In the cardiological evaluation during admission, alterations were found in six patients. All patients received immunoglobulins, 14 corticosteroids and 6 inotropes. Nine patients required admission to the Pediatric Intensive Care Unit (PICU), with a median stay of four days. One patient died. No notable alterations have been observed either in clinical symptoms, laboratory tests or cardiac evaluation during the six months after discharge. Conclusions. The cases collected have shown the clinical and analytical characteristics described in the literature on MIS-C, with more than half requiring admission to the PICU and receiving treatment with immunoglobulins in all cases. They frequently presented cardiological involvement, with one patient dying. Six months after the episode, no patient has shown clinical, analytical or cardiac function impairment (AU)


Humans , Male , Female , Child , /rehabilitation , /complications , Child Health Services , Prospective Studies
4.
Biotechnol Bioeng ; 119(4): 1129-1141, 2022 04.
Article En | MEDLINE | ID: mdl-34984673

The search for new rapid diagnostic tests for malaria is a priority for developing an efficient strategy to fight this endemic disease, which affects more than 3 billion people worldwide. In this study, we characterize systematically an easy-to-operate lab-on-chip, designed for the magnetophoretic capture of malaria-infected red blood cells (RBCs). The method relies on the positive magnetic susceptibility of infected RBCs with respect to blood plasma. A matrix of nickel posts fabricated in a silicon chip placed face down is aimed at attracting infected cells, while healthy cells sediment on a glass slide under the action of gravity. Using a model of infected RBCs, that is, erythrocytes with methemoglobin, we obtained a capture efficiency of about 70% after 10 min in static conditions. By proper agitation, the capture efficiency reached 85% after just 5 min. Sample preparation requires only a 1:10 volume dilution of whole blood, previously treated with heparin, in a phosphate-buffered solution. Nonspecific attraction of untreated RBCs was not observed in the same time interval.


Erythrocytes , Malaria , Humans , Magnetics , Malaria/diagnosis
5.
Eur J Cancer ; 160: 72-79, 2022 01.
Article En | MEDLINE | ID: mdl-34785111

BACKGROUND: The outcome of infants with KMT2A-germline acute lymphoblastic leukaemia (ALL) is superior to that of infants with KMT2A-rearranged ALL but has been inferior to non-infant ALL patients. Here, we describe the outcome and prognostic factors for 167 infants with KMT2A-germline ALL enrolled in the Interfant-06 study. METHODS: Univariate analysis on prognostic factors (age, white blood cell count at diagnosis, prednisolone response and CD10 expression) was performed on KMT2A-germline infants in complete remission at the end of induction (EOI; n = 163). Bone marrow minimal residual disease (MRD) was measured in 73 patients by real-time quantitative polymerase chain reaction at various time points (EOI, n = 68; end of consolidation, n = 56; and before OCTADAD, n = 57). MRD results were classified as negative, intermediate (<5∗10-4), and high (≥5∗10-4). RESULTS: The 6-year event-free and overall survival was 73.9% (standard error [SE] = 3.6) and 87.2% (SE = 2.7). Relapses occurred early, within 36 months from diagnosis in 28 of 31 (90%) infants. Treatment-related mortality was 3.6%. Age <6 months was a favourable prognostic factor with a 6-year disease-free survival (DFS) of 91% (SE = 9.0) compared with 71.7% (SE = 4.2) in infants >6 months of age (P = 0.04). Patients with high EOI MRD ≥5 × 10-4 had a worse outcome (6-year DFS 61.4% [SE = 12.4], n = 16), compared with patients with undetectable EOI MRD (6-year DFS 87.9% [SE = 6.6], n = 28) or intermediate EOI MRD <5 × 10-4 (6-year DFS 76.4% [SE = 11.3], n = 24; P = 0.02). CONCLUSION: We conclude that young age at diagnosis and low EOI MRD seem favourable prognostic factors in infants with KMT2A-germline ALL and should be considered for risk stratification in future clinical trials.


Neoplasm, Residual/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Female , Germ Cells , Humans , Infant , Male , Neoplasm, Residual/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prognosis , Survival Analysis , Treatment Outcome
6.
Animal ; 15(11): 100382, 2021 Nov.
Article En | MEDLINE | ID: mdl-34653786

Primiparous female rabbits have high nutritional requirements and, while it is recommended that they are subjected to an extensive reproductive rhythm, this could lead to overweight, affecting reproductive outcomes. We hypothesised that restricting food intake during the less energetic period of gestation could improve reproductive outcome without impairing offspring viability. This study compares two groups of primiparous rabbit does in an extensive reproductive programme, one in which feed was restricted from Day 0 to Day 21 of gestation (R021), and another in which does were fed ad libitum (control) throughout pregnancy. The mother and offspring variables compared were (1) mother reproductive outcomes at the time points pre-implantation (Day 3 postartificial insemination [AI]), preterm (Day 28 post-AI) and birth; and (2) the prenatal offspring characteristic IGF system gene expression in foetal liver, liver fibrosis and foetus sex ratio, and postnatal factor viability and growth at birth, and survival and growth until weaning. Feed restriction did not affect the conception rate, embryo survival, or the number of morulae and blastocysts recovered at Day 3 post-AI. Preterm placenta size and efficiency were similar in the two groups. However, both implantation rate (P < 0.001) and the number of foetuses (P = 0.05) were higher in the R021 mothers than controls, while there was no difference in foetal viability. Foetal size and weight, the weights of most organs, organ weight/BW ratios and sex ratio were unaffected by feed restriction; these variables were only affected by uterine position (P < 0.05). Conversely, in the R021 does, foetal liver IGBP1 and IGF2 gene expression were dysregulated despite no liver fibrosis and a normal liver structure. No effects of restricted feed intake were produced on maternal fertility, prolificacy, or offspring birth weight, but control females weaned more kits. Litter weight and mortality rate during the lactation period were also unaffected. In conclusion, pre-implantation events and foetal development were unaffected by feed restriction. While some genes of the foetal hepatic IGF system were dysregulated during pregnancy, liver morphology appeared normal, and the growth of foetuses and kits until weaning was unmodified. This strategy of feed restriction in extensive reproductive rhythms seems to have no significant adverse effects on dam reproductive outcome or offspring growth and viability until weaning.


Lactation , Reproduction , Animals , Body Weight , Female , Fetus , Gene Expression , Liver , Pregnancy , Rabbits
7.
Malays Orthop J ; 15(2): 43-46, 2021 Jul.
Article En | MEDLINE | ID: mdl-34429821

INTRODUCTION: Isometric shoulder strength is vital in the management of individuals suffering from shoulder diseases such as rotator cuff tears. Normal values for the working Filipino population who are at risk of developing shoulder problems are lacking. The objective of this study was to determine the isometric baseline isometric shoulder strengths in scaption of healthy Filipino individuals aged 20-30 years old without a history of a shoulder injury. MATERIAL AND METHODS: This is a cross-sectional descriptive study measuring the isometric strength values using the handheld IDO isometer of dominant and non-dominant shoulder of healthy Filipino individuals aged 20 to 30 years old. RESULTS: There is no significant difference in the mean isometric shoulder strength between the dominant and non-dominant arm for both sexes. The male gender scored higher values compared to the female gender and is statistically significant. CONCLUSION: There is no difference in isometric shoulder strength between the dominant and non-dominant shoulder. Strength differences favour the male gender.

11.
Theriogenology ; 150: 321-328, 2020 Jul 01.
Article En | MEDLINE | ID: mdl-32088037

Rabbit does are reflex ovulators such that coitus is needed to release GnRH and elicit the LH surge that triggers the ovulation of mature oocytes. However, the mechanisms eliciting ovulation in this species remain unclear. One of the most promising recently discovered candidates with a role in female reproductive physiology is nerve growth factor beta (ß-NGF). This neurotrophin and its high-affinity receptor TrkA and low affinity receptor p75, is present in all compartments of the ovary, oviduct and uterus suggesting a physiologic role in ovarian folliculogenesis, steroidogenesis, ovulation, luteogenesis and embryo development. Besides, evidence exists that ß-NGF found in seminal plasma could exert a modulatory role in the female hypothalamus-pituitary-ovarian axis contributing to the adrenergic and cholinergic neuronal stimulus of GnRH neurons in an endocrine manner during natural mating. Probably, the paracrine and local roles of the neurotrophin in steroidogenesis and ovulation reinforce the neuroendocrine pathway that leads to ovulation. This review updates knowledge of the role of ß-NGF in rabbit reproduction, including its possible contribution to the mechanisms of action that induce ovulation, and discusses perspectives for the future applications of this neurotrophin on rabbit farms.


Nerve Growth Factor/metabolism , Ovary/metabolism , Pregnancy, Animal , Rabbits , Uterus/metabolism , Animals , Female , Gene Expression Regulation/physiology , Pregnancy
12.
Microsyst Nanoeng ; 6: 50, 2020.
Article En | MEDLINE | ID: mdl-34567662

The poor gas selectivity problem has been a long-standing issue for miniaturized chemical-resistor gas sensors. The electronic nose (e-nose) was proposed in the 1980s to tackle the selectivity issue, but it required top-down chemical functionalization processes to deposit multiple functional materials. Here, we report a novel gas-sensing scheme using a single graphene field-effect transistor (GFET) and machine learning to realize gas selectivity under particular conditions by combining the unique properties of the GFET and e-nose concept. Instead of using multiple functional materials, the gas-sensing conductivity profiles of a GFET are recorded and decoupled into four distinctive physical properties and projected onto a feature space as 4D output vectors and classified to differentiated target gases by using machine-learning analyses. Our single-GFET approach coupled with trained pattern recognition algorithms was able to classify water, methanol, and ethanol vapors with high accuracy quantitatively when they were tested individually. Furthermore, the gas-sensing patterns of methanol were qualitatively distinguished from those of water vapor in a binary mixture condition, suggesting that the proposed scheme is capable of differentiating a gas from the realistic scenario of an ambient environment with background humidity. As such, this work offers a new class of gas-sensing schemes using a single GFET without multiple functional materials toward miniaturized e-noses.

13.
J Periodontal Res ; 54(4): 444-452, 2019 Aug.
Article En | MEDLINE | ID: mdl-30802957

BACKGROUND AND OBJECTIVE: Both chronic and aggressive periodontal disease are associated with vitamin D deficiency. The active form of vitamin D, 1,25(OH)2 D3 , induces the expression of the antimicrobial peptide LL-37 and innate immune mediators in cultured human gingival epithelial cells (GECs). The aim of this study was to further delineate the mechanism by which vitamin D enhances the innate defense against the development of periodontal disease (PD). MATERIALS AND METHODS: Wild-type C57Bl/6 mice were made deficient in vitamin D by dietary restriction. Cultured primary and immortalized GEC were stimulated with 1,25(OH)2 D3 , followed by infection with Porphyromonas gingivalis, and viable intracellular bacteria were quantified. Conversion of vitamin D3 to 25(OH)D3 and 1,25(OH)2 D3 was quantified by ELISA. Effect of vitamin D on basal IL-1α expression in mice was determined by topical administration to the gingiva of wild-type mice, followed by qRT-PCR. RESULTS: Dietary restriction of vitamin D led to alveolar bone loss and increased inflammation in the gingiva in the mouse model. In primary human GEC and established human cell lines, treatment of GEC with 1,25(OH)2 D3 inhibited the intracellular growth of P. gingivalis. Cultured GEC expressed two 25-hydroxylases (CYP27A1 and CYP2R1), as well as 1-α hydroxylase, enabling conversion of vitamin D to both 25(OH)D3 and 1,25(OH)2 D3 . Topical application of both vitamin D3 and 1,25(OH)2 D3 to the gingiva of mice led to rapid inhibition of IL-1α expression, a prominent pro-inflammatory cytokine associated with inflammation, which also exhibited more than a 2-fold decrease from basal levels in OKF6/TERT1 cells upon 1,25(OH)2 D3 treatment, as determined by RNA-seq. CONCLUSION: Vitamin D deficiency in mice contributes to PD, recapitulating the association seen in humans, and provides a unique model to study the development of PD. Vitamin D increases the activity of GEC against the invasion of periodontal pathogens and inhibits the inflammatory response, both in vitro and in vivo. GEC can convert inactive vitamin D to the active form in situ, supporting the hypothesis that vitamin D can be applied directly to the gingiva to prevent or treat periodontal disease.


Alveolar Bone Loss/physiopathology , Calcifediol/pharmacology , Gingiva/physiology , Inflammation/physiopathology , Vitamin D/pharmacology , Alveolar Bone Loss/immunology , Animals , Cells, Cultured , Humans , Inflammation/immunology , Interleukin-1alpha/immunology , Mice , Mice, Inbred C57BL , Porphyromonas gingivalis , Vitamins/pharmacology
14.
Leukemia ; 32(10): 2306, 2018 10.
Article En | MEDLINE | ID: mdl-30218009

The original version of this Article contained an error in the spelling of the author Juan Carlos Rodriguez-Manzaneque, which was incorrectly given as J Carlos Rodríguez-Manzaneque. This has now been corrected in both the PDF and HTML versions of the Article.

15.
Reprod Fertil Dev ; 30(12): 1728-1738, 2018 Nov.
Article En | MEDLINE | ID: mdl-29966585

The developmental competence of invitro maturation (IVM) oocytes can be enhanced by antioxidant agents. The present study investigated, for the first time in the rabbit model, the effect of adding α-tocopherol (0, 100, 200 and 400µM) during IVM on putative transcripts involved in antioxidant defence (superoxide dismutase 2, mitochondrial (SOD2), glutathione peroxidase 1 (GPX1), catalase (CAT)), cell cycle regulation and apoptosis cascade (apoptosis tumour protein 53 (TP53), caspase 3, apoptosis-related cysteine protease (CASP3)), cell cycle progression (cellular cycle V-Akt murine thymoma viral oncogene homologue 1 (AKT1)), cumulus expansion (gap junction protein, alpha 1, 43 kDa (GJA1) and prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclo-oxygenase) (PTGS2)) and metabolism (glucose-6-phosphate dehydrogenase (G6PD)). Meiotic progression, mitochondrial reallocation, cumulus cell apoptosis and the developmental competence of oocytes after IVF were also assessed. Expression of SOD2, CAT, TP53, CASP3 and GJA1 was downregulated in cumulus-oocyte complexes (COCs) after IVM with 100µM α-tocopherol compared with the group without the antioxidant. The apoptotic rate and the percentage of a non-migrated mitochondrial pattern were lower in COCs cultured with 100µM α-tocopherol, consistent with better-quality oocytes. In fact, early embryo development was improved when 100µM α-tocopherol was included in the IVM medium, but remained low compared with invivo-matured oocytes. In conclusion, the addition of 100µM α-tocopherol to the maturation medium is a suitable approach to manage oxidative stress and apoptosis, as well as for increasing the in vitro developmental competence of rabbit oocytes.


Antioxidants/pharmacology , Apoptosis/drug effects , Gene Expression/drug effects , Oocytes/drug effects , Oxidative Stress/drug effects , alpha-Tocopherol/pharmacology , Animals , Caspase 3/genetics , Caspase 3/metabolism , Embryonic Development/drug effects , Female , In Vitro Oocyte Maturation Techniques , Oocytes/metabolism , Rabbits , Reactive Oxygen Species/metabolism
16.
Front Neurol ; 9: 381, 2018.
Article En | MEDLINE | ID: mdl-29899725

Treatment outcomes from pallidal deep brain stimulation are highly heterogeneous reflecting the phenotypic and etiologic spectrum of dystonia. Treatment stratification to neurostimulation therapy primarily relies on the phenotypic motor presentation; however, etiology including genetic factors are increasingly recognized as modifiers of treatment outcomes. Here, we describe a 53 year-old female patient with a progressive generalized dystonia since age 25. The patient underwent deep brain stimulation of the globus pallidus internus (GPi-DBS) at age 44. Since the clinical phenotype included mobile choreo-dystonic features, we expected favorable therapeutic outcome from GPi-DBS. Although mobile dystonia components were slightly improved in the long-term outcome from GPi-DBS the overall therapeutic response 9 years from implantation was limited when comparing "stimulation off" and "stimulation on" despite of proper electrode localization and sufficient stimulation programming. In order to further understand the reason for this limited motor symptom response, we aimed to clarify the etiology of generalized dystonia in this patient. Genetic testing identified a novel heterozygous pathogenic SLC2A1 mutation as cause of glucose transporter type 1 deficiency syndrome (GLUT1-DS). This case report presents the first outcome of GPi-DBS in a patient with GLUT1-DS, and suggests that genotype relations may increasingly complement phenotype-based therapy stratification of GPi-DBS in dystonia.

17.
Animal ; 12(10): 2080-2088, 2018 Oct.
Article En | MEDLINE | ID: mdl-29332610

This work attempts to confirm the effect of an enriched diet with n-3 polyunsaturated fatty acids (PUFA) trying to mitigate the reproductive performances issues such as low conception rate of primiparous rabbits. A total of 127 does were fed ad libitum throughout their two first cycles with two diets with different fat sources: mixed fat in the control and salmon oil in the enriched one, with 3.19 g/100 g (n=63 does) and 28.77 g/100 g (n=64 does) of n-3 of the total fatty acid, respectively. Feed intake was similar between groups (P>0.05). Plasma progesterone concentration was higher in the enriched females than in control ones at 7 (30.9±2.18 v. 23.9±2.30 ng/ml, respectively; P=0.029) and 14 (38.7±2.18 v. 28.2±2.30 ng/ml, respectively; P=0.001) days of first gestation. Considering both cycles, reproductive parameters of mothers (fertility, duration of gestation and prolificacy) and litter parameters (weight at parturition and weaning, mortality and average daily gain (ADG) of kits during lactation) were similar in both groups. However, individual measurements of neonates of enriched group improved 5.87%, 7.10% and 18.01% (P0.05), but embryo apoptosis rate was higher in control group than in enriched one (31.1±4.56% v. 17.1±3.87%, respectively; P<0.05). In conclusion, dietary PUFA enrichment from the rearing and throughout two productive cycles improved plasma progesterone during pregnancy, fertility, milk fatty acid profile and neonates development of primiparous supporting the beneficial effect of n-3 PUFA supplementation in rabbit does.


Animal Feed , Fatty Acids, Omega-3 , Rabbits , Animals , Diet , Dietary Supplements , Fatty Acids , Female , Lactation , Milk , Pregnancy , Rabbits/physiology , Reproduction
18.
Leukemia ; 32(3): 633-644, 2018 03.
Article En | MEDLINE | ID: mdl-28943635

Mixed-lineage leukemia (MLL)-rearranged (MLLr) infant B-cell acute lymphoblastic leukemia (iMLLr-B-ALL) has a dismal prognosis and is associated with a pro-B/mixed phenotype, therapy refractoriness and frequent central nervous system (CNS) disease/relapse. Neuron-glial antigen 2 (NG2) is specifically expressed in MLLr leukemias and is used in leukemia immunophenotyping because of its predictive value for MLLr acute leukemias. NG2 is involved in melanoma metastasis and brain development; however, its role in MLL-mediated leukemogenesis remains elusive. Here we evaluated whether NG2 distinguishes leukemia-initiating/propagating cells (L-ICs) and/or CNS-infiltrating cells (CNS-ICs) in iMLLr-B-ALL. Clinical data from the Interfant cohort of iMLLr-B-ALL demonstrated that high NG2 expression associates with lower event-free survival, higher number of circulating blasts and more frequent CNS disease/relapse. Serial xenotransplantation of primary MLL-AF4+ leukemias indicated that NG2 is a malleable marker that does not enrich for L-IC or CNS-IC in iMLLr-B-All. However, NG2 expression was highly upregulated in blasts infiltrating extramedullar hematopoietic sites and CNS, and specific blockage of NG2 resulted in almost complete loss of engraftment. Indeed, gene expression profiling of primary blasts and primografts revealed a migratory signature of NG2+ blasts. This study provides new insights on the biology of NG2 in iMLLr-B-ALL and suggests NG2 as a potential therapeutic target to reduce the risk of CNS disease/relapse and to provide safer CNS-directed therapies for iMLLr-B-ALL.

19.
Int J Obes (Lond) ; 42(4): 618-624, 2018 04.
Article En | MEDLINE | ID: mdl-29158541

BACKGROUND/OBJECTIVES: We aimed to evaluate mitochondrial biogenesis (MB), structure, metabolism and dysfunction in abdominal adipose tissue from male pediatric patients with obesity. SUBJECTS/METHODS: Samples were collected from five children with obesity (percentile ⩾95) and five eutrophic boys (percentile ⩾5/⩽85) (8-12 years old) following parental informed consent. We analyzed the expression of key genes involved in MB (sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor-γ (PPARγ), PPARγ coactivator-1α (PGC1α), nuclear respiratory factors 1 and 2 (NRF1, NRF2) and mitochondrial transcription factor A (TFAM) and surrogates for mitochondrial function/structure/metabolism (porin, TOMM20, complex I and V, UCP1, UCP2, SIRT3, SOD2) by western blot. Citrate synthase (CS), complex I (CI) activity, adenosine triphosphate (ATP) levels, mitochondrial DNA (mtDNA) content and oxidative stress end points were also determined. RESULTS: Most MB proteins were significantly decreased in samples from children with obesity except complex I, V and superoxide dismutase-2 (SOD2). Similarly, CS and CI activity showed a significant reduction, as well as ATP levels and mtDNA content. PPARγ, PGC1α, complex I and V and SOD2 were hyperacetylated compared with lean samples. Concurrently, in samples from children with obesity, we found decreased SOD2 activity and redox state imbalance highlighted by decreased reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and significant increases in protein carbonylation. CONCLUSIONS: Adipose tissue from children with obesity demonstrates a dysregulation of key modulators of MB and organelle structure, and displays hyperacetylation of key proteins and altered expression of upstream regulators of cell metabolism.


Adipose Tissue/physiopathology , Mitochondria/physiology , Organelle Biogenesis , Pediatric Obesity/physiopathology , Acetylation , Adipose Tissue/cytology , Adipose Tissue/metabolism , Child , DNA, Mitochondrial/metabolism , Humans , Male , Mitochondrial Proteins/analysis , Mitochondrial Proteins/chemistry , Mitochondrial Proteins/metabolism , Oxidative Stress/physiology , Pediatric Obesity/metabolism
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