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INTRODUCTION: Deep brain stimulation (DBS) has shown remarkable success treating neurological and psychiatric disorders including Parkinsons disease, essential tremor, dystonia, epilepsy, and obsessive-compulsive disorder. DBS is now being explored to improve cognitive and functional outcomes in other psychiatric conditions, such as those characterized by reduced N-methyl-D-aspartate (NMDA) function (i.e., schizophrenia). While DBS for movement disorders generally involves high-frequency (>100 Hz) stimulation, there is evidence that low-frequency stimulation may have beneficial and persisting effects when applied to cognitive brain networks. METHODS: In this study, we utilize a novel technology, functional ultrasound imaging (fUSI), to characterize the cerebrovascular impact of medial septal nucleus (MSN) DBS under conditions of NMDA antagonism (pharmacologically using Dizocilpine [MK-801]) in anesthetized male mice. RESULTS: Imaging from a sagittal plane across a variety of brain regions within and outside of the septohippocampal circuit, we find that MSN theta-frequency (7.7 Hz) DBS increases hippocampal cerebral blood volume (CBV) during and after stimulation. This effect was not present using standard high-frequency stimulation parameters [i.e., gamma (100 Hz)]. DISCUSSION: These results indicate the MSN DBS increases circuit-specific hippocampal neurovascular activity in a frequency-dependent manner and does so in a way that continues beyond the period of electrical stimulation.

Introduction: Both ketamine (KET) and medial prefrontal cortex (mPFC) deep brain stimulation (DBS) are emerging therapies for treatment-resistant depression, yet our understanding of their electrophysiological mechanisms and biomarkers is incomplete. This study investigates aperiodic and periodic spectral parameters, and the signal complexity measure sample entropy, within mPFC local field potentials (LFP) in a chronic corticosterone (CORT) depression model after ketamine and/or mPFC DBS. Methods: Male rats were intraperitoneally administered CORT or vehicle for 21 days. Over the last 7 days, animals receiving CORT were treated with mPFC DBS, KET, both, or neither; then tested across an array of behavioral tasks for 9 days. Results: We found that the depression-like behavioral and weight effects of CORT correlated with a decrease in aperiodic-adjusted theta power (5-10 Hz) and an increase in sample entropy during the administration phase, and an increase in theta peak frequency and a decrease in the aperiodic exponent once the depression-like phenotype had been induced. The remission-like behavioral effects of ketamine alone correlated with a post-treatment increase in the offset and exponent, and decrease in sample entropy, both immediately and up to eight days post-treatment. The remission-like behavioral effects of mPFC DBS alone correlated with an immediate decrease in sample entropy, an immediate and sustained increase in low gamma (20-50 Hz) peak width and aperiodic offset, and sustained improvements in cognitive function. Failure to fully induce remission-like behavior in the combinatorial treatment group correlated with a failure to suppress an increase in sample entropy immediately after treatment. Conclusion: Our findings therefore support the potential of periodic theta parameters as biomarkers of depression-severity; and periodic low gamma parameters and cognitive measures as biomarkers of mPFC DBS treatment efficacy. They also support sample entropy and the aperiodic spectral parameters as potential cross-modal biomarkers of depression severity and the therapeutic efficacy of mPFC DBS and/or ketamine. Study of these biomarkers is important as objective measures of disease severity and predictive measures of therapeutic efficacy can be used to personalize care and promote the translatability of research across studies, modalities, and species. [ABSTRACT FROM AUTHOR]

The role of malnutrition at diagnosis as a predictor of early mortality in Mexican leukemia children remains controversial. The objective of present study was to investigate whether malnutrition was a predictor of early mortality during the first year of treatment in Mexican acute lymphoblastic leukemia (ALL) children through the first population-based study. A total of 794 newly diagnosed ALL pediatric patients from public hospitals of Mexico City were enrolled. A multivariate Cox proportional hazards regression model was constructed and adjusted by patient’s age at diagnosis, gender, hospital of treatment, and socioeconomic status. Early mortality was high (12.1%) and malnutrition by different indicators was not associated with mortality at induction phase and at 6th month; a high risk of dying (RR = 2.08; 95% CI: 1.08–4.01) was observed in the group of malnourished children with a high-risk ALL. [ABSTRACT FROM AUTHOR]

Background. Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. The impact of chemotherapy has resulted in improved survival, although results have not been the same for all countries. methods. We reviewed the available medical literature in Medline on reports of overall and disease-free survival in children with ALL from the late 1970s to 2007. Survival was analyzed according to economic development (developed and developing countries) and according to age, sex, cell type and leukocyte count at diagnosis. Results. In developed countries there has been an increase in overall 5-year survival from 60% in 1984 to 83.5% in 2007 and for diseasefree survival from 48.5% to 83.5%. This was not registered in developing countries where until 2006 the average overall survival and disease-free survival was ~60%. At diagnosis, prognostic factors related with higher survival rates are age (1 to 9 years), sex (females), type of leukemia (B-cell leukemia) and leukocyte count <10,000 mm³. Information regarding survival rates is very scarce. Conclusions. Survival of children with ALL is increasing, particularly disease-free survival rates. Prognostic factors related to survival are age, sex, cell type and leukocyte count. Further studies are needed in developing countries. [ABSTRACT FROM AUTHOR]

Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a wide range of biological properties. Among them are Δ 12 -prostaglandin J 2 (Δ 12 -PGJ 2 ) and Δ 12 -prostaglandin J 3 (Δ 12 -PGJ 3 ), whose unusual structural motifs and potent cytotoxicities present unique opportunities for chemical and biological investigations. Herein, we report a short olefin-metathesis-based total synthesis of Δ 12 -PGJ 2 and its application to the construction of a series of designed analogues possessing monomeric, dimeric, trimeric, and tetrameric macrocyclic lactones consisting of units of this prostaglandin. Biological evaluation of these analogues led to interesting structure-activity relationships and trends and the discovery of a number of more potent antitumor agents than their parent naturally occurring molecules.

Introduction: Acute myeloid leukemias represent the second most common childhood leukemia subtype. In Mexico, there are few studies on descriptive epidemiology for this disease., Aims: To report acute myeloid leukemia incidence for children less than 15 years of age in the Metropolitan Area of the Valley of Mexico for a period of five years (2010-2014) and to analyze whether there are differences in the incidence of acute myeloid leukemia by regions., Material and Methods: A descriptive study was conducted in nine public hospitals in Mexico City. The crude annual average incidence rate and adjusted average annual incidence rate were calculated., Results: A total of 190 patients with diagnosis of de novo acute myeloid leukemia were analyzed. Male sex (57.2%) and acute myeloid leukemia-M3 subtype (25.3%) were more frequent. The adjusted average annual incidence rates for Mexico City and for the Metropolitan Area of the Valley of Mexico were 8.18 and 7.74 per million children under 15 years old, respectively., Conclusions: It seems that childhood acute myeloid leukemia incidence is increasing in Mexico City, which makes the identification of associated risk factors imperative.