Design of a Stem Cell-Based Therapy for Ependymal Repair in Hydrocephalus Associated With Germinal Matrix Hemorrhages.

BACKGROUND: In preterm birth germinal matrix hemorrhages (GMHs) and the consequent posthemorrhagic hydrocephalus (PHH), the neuroepithelium/ependyma development is disrupted. This work is aimed to explore the possibilities of ependymal repair in GMH/PHH using a combination of neural stem cells, ependymal progenitors (EpPs), and mesenchymal stem cells. METHODS: GMH/PHH was induced in 4-day-old mice using collagenase, blood, or blood serum injections. PHH severity was characterized 2 weeks later using magnetic resonance, immunofluorescence, and protein expression quantification with mass spectrometry. Ependymal restoration and wall regeneration after stem cell treatments were tested in vivo and in an ex vivo experimental approach using ventricular walls from mice developing moderate and severe GMH/PHH. The effect of the GMH environment on EpP differentiation was tested in vitro. Two-tailed Student t or Wilcoxon-Mann-Whitney U test was used to find differences between the treated and nontreated groups. ANOVA and Kruskal-Wallis tests were used to compare >2 groups with post hoc Tukey and Dunn multiple comparison tests, respectively. RESULTS: PHH severity was correlated with the extension of GMH and ependymal disruption (means, 88.22% severe versus 19.4% moderate). GMH/PHH hindered the survival rates of the transplanted neural stem cells/EpPs. New multiciliated ependymal cells could be generated from transplanted neural stem cells and more efficiently from EpPs (15% mean increase). Blood and TNFα (tumor necrosis factor alpha) negatively affected ciliogenesis in cells committed to ependyma differentiation (expressing Foxj1 [forkhead box J1] transcription factor). Pretreatment with mesenchymal stem cells improved the survival rates of EpPs and ependymal differentiation while reducing the edematous (means, 18% to 0.5% decrease in severe edema) and inflammatory conditions in the explants. The effectiveness of this therapeutical strategy was corroborated in vivo (means, 29% to 0% in severe edema). CONCLUSIONS: In GMH/PHH, the ependyma can be restored and edema decreased from either neural stem cell or EpP transplantation in vitro and in vivo. Mesenchymal stem cell pretreatment improved the success of the ependymal restoration.

Body Composition Evaluation and Clinical Markers of Cardiometabolic Risk in Patients with Phenylketonuria.

Cardiovascular diseases are the main cause of mortality worldwide. Patients with phenylketonuria (PKU) may be at increased cardiovascular risk. This review provides an overview of clinical and metabolic cardiovascular risk factors, explores the connections between body composition (including fat mass and ectopic fat) and cardiovascular risk, and examines various methods for evaluating body composition. It particularly focuses on nutritional ultrasound, given its emerging availability and practical utility in clinical settings. Possible causes of increased cardiometabolic risk in PKU are also explored, including an increased intake of carbohydrates, chronic exposure to amino acids, and characteristics of microbiota. It is important to evaluate cardiovascular risk factors and body composition in patients with PKU. We suggest systematic monitoring of body composition to develop nutritional management and hydration strategies to optimize performance within the limits of nutritional therapy.

Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi.

Neglected diseases caused by kinetoplastid parasites are a health burden in tropical and subtropical countries. The need to create safe and effective medicines to improve treatment remains a priority. Microbial natural products are a source of chemical diversity that provides a valuable approach for identifying new drug candidates. We recently reported the discovery and bioassay-guided isolation of a novel family of macrolides with antiplasmodial activity. The novel family of four potent antimalarial macrolides, strasseriolides A-D, was isolated from cultures of Strasseria geniculata CF-247251, a fungal strain obtained from plant tissues. In the present study, we analyze these strasseriolides for activity against kinetoplastid protozoan parasites, namely, Trypanosoma brucei brucei, Leishmania donovani and Trypanosoma cruzi. Compounds exhibited mostly low activities against T. b. brucei, yet notable growth inhibition and selectivity were observed for strasseriolides C and D in the clinically relevant intracellular T. cruzi and L. donovani amastigotes with EC50 values in the low micromolar range. Compound C is fast-acting and active against both intracellular and trypomastigote forms of T. cruzi. While cell cycle defects were not identified, prominent morphological changes were visualized by differential interference contrast microscopy and smaller and rounded parasites were visualized upon exposure to strasseriolide C. Moreover, compound C lowers parasitaemia in vivo in acute models of infection of Chagas disease. Hence, strasseriolide C is a novel natural product active against different forms of T. cruzi in vitro and in vivo. The study provides an avenue for blocking infection of new cells, a strategy that could additionally contribute to avoid treatment failure.

Antiparasitic Meroterpenoids Isolated from Memnoniella dichroa CF-080171.

Memnoniella is a fungal genus from which a wide range of diverse biologically active compounds have been isolated. A Memnoniella dichroa CF-080171 extract was identified to exhibit potent activity against Plasmodium falciparum 3D7 and Trypanosoma cruzi Tulahuen whole parasites in a high-throughput screening (HTS) campaign of microbial extracts from the Fundación MEDINA's collection. Bioassay-guided isolation of the active metabolites from this extract afforded eight new meroterpenoids of varying potencies, namely, memnobotrins C-E (1-3), a glycosylated isobenzofuranone (4), a tricyclic isobenzofuranone (5), a tetracyclic benzopyrane (6), a tetracyclic isobenzofuranone (7), and a pentacyclic isobenzofuranone (8). The structures of the isolated compounds were established by (+)-ESI-TOF high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Compounds 1, 2, and 4 exhibited potent antiparasitic activity against P. falciparum 3D7 (EC50 0.04-0.243 µM) and T. cruzi Tulahuen (EC50 0.266-1.37 µM) parasites, as well as cytotoxic activity against HepG2 tumoral liver cells (EC50 1.20-4.84 µM). The remaining compounds (3, 5-8) showed moderate or no activity against the above-mentioned parasites and cells.

Touchscreen-Based Cognitive Training Alters Functional Connectivity Patterns in Aged But Not Young Male Rats.

Age-related cognitive decline is related to cellular and systems-level disruptions across multiple brain regions. Because age-related cellular changes within different structures do not show the same patterns of dysfunction, interventions aimed at optimizing function of large-scale brain networks may show greater efficacy at improving cognitive outcomes in older adults than traditional pharmacotherapies. The current study aimed to leverage a preclinical rat model of aging to determine whether cognitive training in young and aged male rats with a computerized paired-associates learning (PAL) task resulted in changes in global resting-state functional connectivity. Moreover, seed-based functional connectivity was used to examine resting state connectivity of cortical areas involved in object-location associative memory and vulnerable in old age, namely the medial temporal lobe (MTL; hippocampal cortex and perirhinal cortex), retrosplenial cortex (RSC), and frontal cortical areas (prelimbic and infralimbic cortices). There was an age-related increase in global functional connectivity between baseline and post-training resting state scans in aged, cognitively trained rats. This change in connectivity following cognitive training was not observed in young animals, or rats that traversed a track for a reward between scan sessions. Relatedly, an increase in connectivity between perirhinal and prelimbic cortices, as well as reduced reciprocal connectivity within the RSC, was found in aged rats that underwent cognitive training, but not the other groups. Subnetwork activation was associated with task performance across age groups. Greater global functional connectivity and connectivity between task-relevant brain regions may elucidate compensatory mechanisms that can be engaged by cognitive training.

Cholinergic Boutons are Distributed Along the Dendrites and Somata of VIP Neurons in the Inferior Colliculus.

Cholinergic signaling shapes sound processing and plasticity in the inferior colliculus (IC), the midbrain hub of the central auditory system, but how cholinergic terminals contact and influence individual neuron types in the IC remains largely unknown. Using pharmacology and electrophysiology, we recently found that acetylcholine strongly excites VIP neurons, a class of glutamatergic principal neurons in the IC, by activating α3ß4* nicotinic acetylcholine receptors (nAChRs). Here, we confirm and extend these results using tissue from mice of both sexes. First, we show that mRNA encoding α3 and ß4 nAChR subunits is expressed in many neurons throughout the IC, including most VIP neurons, suggesting that these subunits, which are rare in the brain, are important mediators of cholinergic signaling in the IC. Next, by combining fluorescent labeling of VIP neurons and immunofluorescence against the vesicular acetylcholine transporter (VAChT), we show that individual VIP neurons in the central nucleus of the IC (ICc) are contacted by a large number of cholinergic boutons. Cholinergic boutons were distributed adjacent to the somata and along the full length of the dendritic arbors of VIP neurons, positioning cholinergic signaling to affect synaptic computations arising throughout the somatodendritic compartments of VIP neurons. In addition, cholinergic boutons were occasionally observed in close apposition to dendritic spines on VIP neurons, raising the possibility that cholinergic signaling also modulates presynaptic release onto VIP neurons. Together, these results strengthen the evidence that cholinergic signaling exerts widespread influence on auditory computations performed by VIP neurons and other neurons in the IC.

Home-delivered meals as an adjuvant to improve volume overload and clinical outcomes in hemodialysis.

Patients on chronic hemodialysis are counseled to reduce dietary sodium intake to limit their thirst and consequent interdialytic weight gain (IDWG), chronic volume overload and hypertension. Low-sodium dietary trials in hemodialysis are sparse and mostly indicate that dietary education and behavioral counseling are ineffective in reducing sodium intake and IDWG. Additional nutritional restrictions and numerous barriers further complicate dietary adherence. A low-sodium diet may also reduce tissue sodium, which is positively associated with hypertension and left ventricular hypertrophy. A potential alternative or complementary approach to dietary counseling is home delivery of low-sodium meals. Low-sodium meal delivery has demonstrated benefits in patients with hypertension and congestive heart failure but has not been explored or implemented in patients undergoing hemodialysis. The objective of this review is to summarize current strategies to improve volume overload and provide a rationale for low-sodium meal delivery as a novel method to reduce volume-dependent hypertension and tissue sodium accumulation while improving quality of life and other clinical outcomes in patients undergoing hemodialysis.

Inosine triphosphate pyrophosphatase from Trypanosoma brucei cleanses cytosolic pools from deaminated nucleotides.

Inosine triphosphate pyrophosphatases (ITPases) are ubiquitous house-cleaning enzymes that specifically recognize deaminated purine nucleotides and catalyze their hydrolytic cleavage. In this work, we have characterized the Trypanosoma brucei ITPase ortholog (TbITPA). Recombinant TbITPA efficiently hydrolyzes (deoxy)ITP and XTP nucleotides into their respective monophosphate form. Immunolocalization analysis performed in bloodstream forms suggests that the primary role of TbITPA is the exclusion of deaminated purines from the cytosolic nucleoside triphosphate pools. Even though ITPA-knockout bloodstream parasites are viable, they are more sensitive to inhibition of IMP dehydrogenase with mycophenolic acid, likely due to an expansion of IMP, the ITP precursor. On the other hand, TbITPA can also hydrolyze the activated form of the antiviral ribavirin although in this case, the absence of ITPase activity in the cell confers protection against this nucleoside analog. This unexpected phenotype is dependant on purine availability and can be explained by the fact that ribavirin monophosphate, the reaction product generated by TbITPA, is a potent inhibitor of trypanosomal IMP dehydrogenase and GMP reductase. In summary, the present study constitutes the first report on a protozoan inosine triphosphate pyrophosphatase involved in the removal of harmful deaminated nucleotides from the cytosolic pool.

The spatiotemporal control of expert tennis players when returning first serves: A perception-action perspective.

The aim of the current experiment was to examine the spatiotemporal control of expert tennis players while executing first service returns within a representative experimental setting. We recruited and tested 12 male expert tennis players in hard courts. A comprehensive analysis of the timing (eleven temporal variables analysed at 300 Hz) and performance success of the return actions were carried out, while simultaneously considering task constraints such as the accuracy and the speed of the serves. Temporal organisation of return actions were scaled relative to the server's racket-ball contact (5 ms), an adaptation of fly-time of the split-step, which resulted in consistent landings (133 ms), and initiation of lateral movements towards the ball - with no response errors - after the server's stroke (around 177 ms). Poorer returns occurred when responding to accurate serves accompanied by late trunk movements towards the ball. Returners scaled the timing of the response to the unfolding action of the serve in order to support both spatial and temporal accuracy. These novel findings highlight the significance of the study of fast-ball sports in representative settings and offer further detail on the spatiotemporal control of skilful perception-action.

Preclinical evaluation of strasseriolides A-D, potent antiplasmodial macrolides isolated from Strasseria geniculata CF-247,251.

BACKGROUND: Malaria is a global health problem for which novel therapeutic compounds are needed. To this end, a recently published novel family of antiplasmodial macrolides, strasseriolides A-D, was herein subjected to in vivo efficacy studies and preclinical evaluation in order to identify the most promising candidate(s) for further development. METHODS: Preclinical evaluation of strasseriolides A-D was performed by MTT-based cytotoxicity assay in THLE-2 (CRL-2706) liver cells, cardiotoxicity screening using the FluxOR™ potassium assay in hERG expressed HEK cells, LC-MS-based analysis of drug-drug interaction involving CYP3A4, CYP2D6 and CYP2C9 isoforms inhibition and metabolic stability assays in human liver microsomes. Mice in vivo toxicity studies were also accomplished by i.v. administration of the compounds (vehicle: 0.5% HPMC, 0.5% Tween 80, 0.5% Benzyl alcohol) in mice at 25 mg/kg dosage. Plasma were prepared from mice blood samples obtained at different time points (over a 24-h period), and analysed by LC-MS to quantify compounds. The most promising compounds, strasseriolides C and D, were subjected to a preliminary in vivo efficacy study in which transgenic GFP-luciferase expressing Plasmodium berghei strain ANKA-infected Swiss Webster female mice (n = 4-5) were treated 48 h post-infection with an i.p. dosage of strasseriolide C at 50 mg/kg and strasseriolide D at 22 mg/kg for four days after which luciferase activity was quantified on day 5 in an IVIS® Lumina II imager. RESULTS: Strasseriolides A-D showed no cytotoxicity, no carditoxicity and no drug-drug interaction problems in vitro with varying intrinsic clearance (CLint). Only strasseriolide B was highly toxic to mice in vivo (even at 1 mg/kg i.v. dosage) and, therefore, discontinued in further in vivo studies. Strasseriolide D showed statistically significant activity in vivo giving rise to lower parasitaemia levels (70% lower) compared to the controls treated with vehicle. CONCLUSIONS: Animal efficacy and preclinical evaluation of the recently discovered potent antiplasmodial macrolides, strasseriolides A-D, led to the identification of strasseriolide D as the most promising compound for further development. Future studies dealing on structure optimization, formulation and establishment of optimal in vivo dosage explorations of this novel compound class could enhance their clinical potency and allow for progress to later stages of the developmental pipeline.

α3ß4∗ Nicotinic Acetylcholine Receptors Strongly Modulate the Excitability of VIP Neurons in the Mouse Inferior Colliculus.

The inferior colliculus (IC), the midbrain hub of the central auditory system, receives extensive cholinergic input from the pontomesencephalic tegmentum. Activation of nicotinic acetylcholine receptors (nAChRs) in the IC can alter acoustic processing and enhance auditory task performance. However, how nAChRs affect the excitability of specific classes of IC neurons remains unknown. Recently, we identified vasoactive intestinal peptide (VIP) neurons as a distinct class of glutamatergic principal neurons in the IC. Here, in experiments using male and female mice, we show that cholinergic terminals are routinely located adjacent to the somas and dendrites of VIP neurons. Using whole-cell electrophysiology in brain slices, we found that acetylcholine drives surprisingly strong and long-lasting excitation and inward currents in VIP neurons. This excitation was unaffected by the muscarinic receptor antagonist atropine. Application of nAChR antagonists revealed that acetylcholine excites VIP neurons mainly via activation of α3ß4∗ nAChRs, a nAChR subtype that is rare in the brain. Furthermore, we show that acetylcholine excites VIP neurons directly and does not require intermediate activation of presynaptic inputs that might express nAChRs. Lastly, we found that low frequency trains of acetylcholine puffs elicited temporal summation in VIP neurons, suggesting that in vivo-like patterns of cholinergic input can reshape activity for prolonged periods. These results reveal the first cellular mechanisms of nAChR regulation in the IC, identify a functional role for α3ß4∗ nAChRs in the auditory system, and suggest that cholinergic input can potently influence auditory processing by increasing excitability in VIP neurons and their postsynaptic targets.

World-Class Long-Distance Running Performances Are Best Predicted by Volume of Easy Runs and Deliberate Practice of Short-Interval and Tempo Runs.

ABSTRACT: Casado, A, Hanley, B, Santos-Concejero, J, and Ruiz-Pérez, LM. World-class long-distance running performances are best predicted by volume of easy runs and deliberate practice of short-interval and tempo runs. J Strength Cond Res 35(9): 2525-2531, 2021-The aim of this novel study was to analyze the effect of deliberate practice (DP) and easy continuous runs completed by elite-standard and world-class long-distance runners on competitive performances during the first 7 years of their sport careers. Eighty-five male runners reported their best times in different running events and the amounts of different DP activities (tempo runs and short- and long-interval sessions) and 1 non-DP activity (easy runs) after 3, 5, and 7 years of systematic training. Pearson's correlations were calculated between performances (calculated using the International Association of Athletics Federations' scoring tables) and the distances run for the different activities (and overall total). Simple and multiple linear regression analysis calculated how well these activities predicted performance. Pearson's correlations showed consistently large effects on performance of total distance (r ≥ 0.75, p < 0.001), easy runs (r ≥ 0.68, p < 0.001), tempo runs (r ≥ 0.50, p < 0.001), and short-interval training (r ≥ 0.53, p < 0.001). Long-interval training was not strongly correlated (r ≥ 0.22). Total distance accounted for significant variance in performance (R2 ≥ 0.57, p < 0.001). Of the training modes, hierarchical regression analysis showed that easy runs and tempo runs were the activities that accounted for significant variance in performance (p < 0.01). Although DP activities, particularly tempo runs and short-interval training, are important for improving performance, coaches should note that the non-DP activity of easy running was crucial in better performances, partly because of its contribution to total distance run.

Pilot study to reduce interdialytic weight gain by provision of low-sodium, home-delivered meals in hemodialysis patients.

INTRODUCTION: Patients with kidney failure undergoing maintenance hemodialysis (HD) therapy are routinely counseled to reduce dietary sodium intake to ameliorate sodium retention, volume overload, and hypertension. However, low-sodium diet trials in HD are sparse and indicate that dietary education and behavioral counseling are ineffective in reducing sodium intake. This study aimed to determine whether 4 weeks of low-sodium, home-delivered meals in HD patients reduces interdialytic weight gain (IDWG). Secondary outcomes included changes in dietary sodium intake, thirst, xerostomia, blood pressure, volume overload, and muscle sodium concentration. METHODS: Twenty HD patients (55 ± 12 years, body mass index [BMI] 40.7 ± 16.6 kg/m2 ) were enrolled in this study. Participants followed a usual (control) diet for the first 4 weeks followed by 4 weeks of three low-sodium, home-delivered meals per day. We measured IDWG, hydration status (bioimpedance), standardized blood pressure (BP), food intake (3-day dietary recall), and muscle sodium (magnetic resonance imaging) at baseline (0 M), after the 4-week period of usual diet (1 M), and after the meal intervention (2 M). FINDINGS: The low-sodium meal intervention significantly reduced IDWG when compared to the control period (-0.82 ± 0.14 kg; 95% confidence interval, -0.55 to -1.08 kg; P < 0.001). There were also 1 month (1 M) to 2 month (2 M) reductions in dietary sodium intake (-1687 ± 297 mg; P < 0.001); thirst score (-4.4 ± 1.3; P = 0.003), xerostomia score (-6.7 ± 1.9; P = 0.002), SBP (-18.0 ± 3.6 mmHg; P < 0.001), DBP (-5.9 ± 2.0 mmHg; P = 0.008), and plasma phosphorus -1.55 ± 0.21 mg/dL; P = 0.005), as well as a 0 M to 2 M reduction in absolute volume overload (-1.08 ± 0.33 L; P = 0.025). However, there were no significant changes in serum or tissue sodium (all P > 0.05). DISCUSSION: Low-sodium, home-meal delivery appears to be an effective method for improving volume control and blood pressure in HD patients. Future studies with larger sample sizes are needed to examine the long-term effects of home-delivered meals on these outcomes and to assess cost-effectiveness.

Contextual experience modifies functional connectome indices of topological strength and efficiency.

Stimuli presented at short temporal delays before functional magnetic resonance imaging (fMRI) can have a robust impact on the organization of synchronous activity in resting state networks. This presents an opportunity to investigate how sensory, affective and cognitive stimuli alter functional connectivity in rodent models. In the present study we assessed the effect on functional connectivity of a familiar contextual stimulus presented 10 min prior to sedation for imaging. A subset of animals were co-presented with an unfamiliar social stimulus in the same environment to further investigate the effect of familiarity on network topology. Rats were imaged at 11.1 T and graph theory analysis was applied to matrices generated from seed-based functional connectivity data sets with 144 brain regions (nodes) and 10,152 pairwise correlations (after excluding 144 diagonal edges). Our results show substantial changes in network topology in response to the familiar (context). Presentation of the familiar context, both in the absence and presence of the social stimulus, strongly reduced network strength, global efficiency, and altered the location of the highest eigenvector centrality nodes from cortex to the hypothalamus. We did not observe changes in modular organization, nodal cartographic assignments, assortative mixing, rich club organization, and network resilience. We propose that experiential factors, perhaps involving associative or episodic memory, can exert a dramatic effect on functional network strength and efficiency when presented at a short temporal delay before imaging.

Left ventricular dyssynchrony as result of right ventricular permanent apical pacing.

La estimulación apical permanente del ventrículo derecho (VD) puede producir asincronía del ventrículo izquierdo (VI) desde los puntos de vista eléctrico y mecánico. Este fenómeno es efecto de una alteración de la activación normal del VI que lleva al deterioro de la función sistólica y la aparición de insuficiencia cardíaca y sus efectos deletéreos relacionados. Para el estudio de la asincronía eléctrica del VI se ha propuesto en fecha reciente el nuevo sistema electrocardiográfico no invasivo Synchromax, que puede cuantificar el grado de asincronía eléctrica que causa una subsecuente asincronía mecánica. Esta última se ha estudiado casi siempre mediante la ecocardiografía transtorácica bidimensional (ETT2D) a través del Doppler tisular y la deformación miocárdica y ahora con la ecocardiografía tridimensional transtorácica en tiempo real (E3DTR). La relación entre estos fenómenos ha sido motivo de estudio a fin de identificar a los pacientes que se benefician de la transición a un tratamiento de resincronización cardíaca. Conclusiones: La estimulación artificial permanente del VD produce asincronía eléctrica del VI que puede cuantificarse mediante el nuevo sistema electrocardiográfico Synchromax y desencadenar asincronía mecánica estudiada mediante la ecocardiografía transtorácica para reconocer a los pacientes que pueden beneficiarse de un tratamiento de resincronización cardíaca.Permanent apical pacing of right ventricle (RV) can produce dyssynchrony of the left ventricle (LV) from an electrical and mechanical point of view. This phenomenon is caused by an alteration in the normal activation of LV leading to a deterioration of systolic function and the appearance of heart failure and its associated deleterious effects. For the study of the electrical asynchrony of the LV, a new noninvasive electrocardiographic system Synchromax has recently been proposed, being able to quantify the degree of electrical asynchrony that leads to a subsequent mechanical dyssynchrony. Th e latter has been traditionally studied by two-dimensional transthoracic echocardiography (2DTTE) through tissue Doppler and myocardial deformation and lately by real-time 3-dimensional echocardiography (RT3DE). The relationship between these phenomena has been the subject of study to predict those patients who benefit from an "upgrade" to cardiac resynchronization therapy. Conclusions: Permanent apical pacing of the RV produces electrical dyssynchrony of the LV that can be quantified using a new electrocardiographic system Synchromax and trigger mechanical asynchrony studied through transthoracic echocardiography allowing to predict those patients who benefit from cardiac resynchronization therapy.

La asincronía ventricular izquierda como resultado de la estimulación apical permanente por dispositivos en el ventrículo derecho / Left ventricular dyssynchrony as result of right ventricular permanent apical pacing

Resumen La estimulación apical permanente del ventrículo derecho (VD) puede producir asincronía del ventrículo izquierdo (VI) desde los puntos de vista eléctrico y mecánico. Este fenómeno es efecto de una alteración de la activación normal del VI que lleva al deterioro de la función sistólica y la aparición de insuficiencia cardíaca y sus efectos deletéreos relacionados. Para el estudio de la asincronía eléctrica del VI se ha propuesto en fecha reciente el nuevo sistema electrocardiográfico no invasivo Synchromax, que puede cuantificar el grado de asincronía eléctrica que causa una subsecuente asincronía mecánica. Esta última se ha estudiado casi siempre mediante la ecocardiografía transtorácica bidimensional (ETT2D) a través del Doppler tisular y la deformación miocárdica y ahora con la ecocardiografía tridimensional transtorácica en tiempo real (E3DTR). La relación entre estos fenómenos ha sido motivo de estudio a fin de identificar a los pacientes que se benefician de la transición a un tratamiento de resincronización cardíaca. Conclusiones: La estimulación artificial permanente del VD produce asincronía eléctrica del VI que puede cuantificarse mediante el nuevo sistema electrocardiográfico Synchromax y desencadenar asincronía mecánica estudiada mediante la ecocardiografía transtorácica para reconocer a los pacientes que pueden beneficiarse de un tratamiento de resincronización cardíaca.

Abstract Permanent apical pacing of right ventricle (RV) can produce dyssynchrony of the left ventricle (LV) from an electrical and mechanical point of view. This phenomenon is caused by an alteration in the normal activation of LV leading to a deterioration of systolic function and the appearance of heart failure and its associated deleterious effects. For the study of the electrical asynchrony of the LV, a new noninvasive electrocardiographic system Synchromax has recently been proposed, being able to quantify the degree of electrical asynchrony that leads to a subsequent mechanical dyssynchrony. The latter has been traditionally studied by two-dimensional transthoracic echocardiography (2DTTE) through tissue Doppler and myocardial deformation and lately by real-time 3-dimensional echocardiography (RT3DE). The relationship between these phenomena has been the subject of study to predict those patients who benefit from an “upgrade” to cardiac resynchronization therapy. Conclusions: Permanent apical pacing of the RV produces electrical dyssynchrony of the LV that can be quantified using a new electrocardiographic system Synchromax and trigger mechanical asynchrony studied through transthoracic echocardiography allowing to predict those patients who benefit from cardiac resynchronization therapy.

Strasseriolides A-D, A Family of Antiplasmodial Macrolides Isolated from the Fungus Strasseria geniculata CF-247251.

A novel family of four potent antimalarial macrolides, strasseriolides A-D (1-4), has been isolated from cultures of Strasseria geniculata CF-247251, a fungal strain obtained from plant tissues. The structures of these compounds, including their absolute configurations, were elucidated by HRMS, NMR spectroscopy, and X-ray single-crystal diffraction. The four compounds gave respective IC50 values of 9.810, 0.013, 0.123, and 0.128 µM against Plasmodium falciparum 3D7 parasites with no significant cytotoxicity against the HepG2 cell line.

Differential Effect of Repeated Lipopolysaccharide Treatment and Aging on Hippocampal Function and Biomarkers of Hippocampal Senescence.

Markers of brain aging and cognitive decline are thought to be influenced by peripheral inflammation. This study compared the effects of repeated lipopolysaccharide (LPS) treatment in young rats to age-related changes in hippocampal-dependent cognition and transcription. Young Fischer 344 X Brown Norway hybrid rats were given intraperitoneal injections once a week for 7 weeks with either LPS or vehicle. Older rats received a similar injection schedule of vehicle. Old vehicle and young LPS rats exhibited a delay-dependent impairment in spatial memory. Further, LPS treatment reduced the hippocampal CA3-CA1 synaptic response. RNA sequencing, performed on CA1, indicated an increase in genes linked to neuroinflammation in old vehicle and young LPS animals. In contrast to an age-related decrease in transcription of synaptic genes, young LPS animals exhibited increased expression of genes that support the growth and maintenance of synapses. We suggest that the increased expression of genes for growth and maintenance of synapses in young animals represents neuronal resilience/recovery in response to acute systemic inflammation. Thus, the results indicate that repeated LPS treatment does not completely recapitulate the aging phenotype for synaptic function, possibly due to the chronic nature of systemic inflammation in aging and resilience of young animals to acute treatments.