Acetate Does Not Affect Palmitate Oxidation and AMPK Phosphorylation in Human Primary Skeletal Muscle Cells.

Our recent in vivo human studies showed that colonic administration of sodium acetate (SA) resulted in increased circulating acetate levels, which was accompanied by increments in whole-body fat oxidation in overweight-obese men. Since skeletal muscle has a major role in whole-body fat oxidation, we aimed to investigate effects of SA on fat oxidation and underlying mechanisms in human primary skeletal muscle cells (HSkMC). We investigated the dose (0-5 mmol/L) and time (1, 4, 20, and 24 h) effect of SA on complete and incomplete endogenous and exogenous oxidation of 14C-labeled palmitate in HSkMC derived from a lean insulin sensitive male donor. Both physiological (0.1 and 0.25 mmol/L) and supraphysiological (0.5, 1 and 5 mmol/L) concentrations of SA neither increased endogenous nor exogenous fat oxidation over time in HSkMC. In addition, no effect of SA was observed on Thr172-AMPKα phosphorylation. In conclusion, our previously observed in vivo effects of SA on whole-body fat oxidation in men may not be explained via direct effects on HSkMC fat oxidation. Nevertheless, SA-mediated effects on whole-body fat oxidation may be triggered by other mechanisms including gut-derived hormones or may occur in other metabolically active tissues.

Short-term impacts of COVID-19 on food security and nutrition in rural Guatemala: Phone-based farm household survey evidence.

This article examines the short-term effects of the COVID-19 lockdown on food security and nutrition in rural Guatemala. We rely on a comprehensive panel dataset of 1,824 small agricultural households collected over two survey rounds, on November-December 2019 and May-June 2020. We place special emphasis on changes in agricultural and nonagricultural income sources, including remittances, and changes in dietary diversity, including consumption of animal source foods (ASF) and fruits and vegetables (F&V). We find that COVID-19 affected the incomes, food security, and dietary patterns of households, with a decrease in ASF diversity and an increase in F&V diversity, and an overall net decrease in dietary diversity across all food groups. Dietary diversity among women in reproductive age, however, remained unchanged, and increased among children under 2 years old. Interestingly, households with relatively higher incomes appear to have reduced their dietary diversity to a larger extent than lower income ones, as well as households located in communities with more severe access restrictions. The focus of the study in a region with a high prevalence of poverty and chronic malnutrition provides an important perspective into the consequences of the lockdown in complex rural contexts with vulnerable populations and contributes to inform eventual recovery measures.

The Relationship between Circulating Acetate and Human Insulin Resistance before and after Weight Loss in the DiOGenes Study.

Microbially-produced acetate has been reported to beneficially affect metabolic health through effects on satiety, energy expenditure, insulin sensitivity, and substrate utilization. Here, we investigate the association between sex-specific concentrations of acetate and insulin sensitivity/resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), circulating insulin and Matsuda Index) in the Diet, Obesity and Genes (DiOGenes) Dietary study at baseline and after a low-calorie diet (LCD, 800 kcal/d). In this analysis, 692 subjects (Body Mass Index >27 kg/m2) were included, who underwent an LCD for 8 weeks. Linear mixed models were performed, which were adjusted for mean acetate concentration, center (random factor), age, weight loss, and fat-free mass (FFM). At baseline, no associations between plasma acetate and insulin sensitivity/resistance indices were found. We found a slight positive association between changes in acetate and changes in HOMA-IR (std 0.130, p = 0.033) in women, but not in men (std -0.072, p = 0.310) independently of age, weight loss and FFM. We were not able to confirm previously reported associations between acetate and insulin sensitivity in this large European cohort. The mechanisms behind the sex-specific relationship between LCD-induced changes in acetate and insulin sensitivity require further study.

Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans.

Microbial-derived short-chain fatty acids (SCFA) acetate, propionate and butyrate may provide a link between gut microbiota and whole-body insulin sensitivity (IS). In this cross-sectional study (160 participants, 64% male, BMI: 19.2-41.0 kg/m2, normal or impaired glucose metabolism), associations between SCFA (faecal and fasting circulating) and circulating metabolites, substrate oxidation and IS were investigated. In a subgroup (n = 93), IS was determined using a hyperinsulinemic-euglycemic clamp. Data were analyzed using multiple linear regression analysis adjusted for sex, age and BMI. Fasting circulating acetate, propionate and butyrate concentrations were positively associated with fasting GLP-1 concentrations. Additionally, circulating SCFA were negatively related to whole-body lipolysis (glycerol), triacylglycerols and free fatty acids levels (standardized (std) ß adjusted (adj) -0.190, P = 0.023; std ß adj -0.202, P = 0.010; std ß adj -0.306, P = 0.001, respectively). Circulating acetate and propionate were, respectively, negatively and positively correlated with IS (M-value: std ß adj -0.294, P < 0.001; std ß adj 0.161, P = 0.033, respectively). We show that circulating rather than faecal SCFA were associated with GLP-1 concentrations, whole-body lipolysis and peripheral IS in humans. Therefore, circulating SCFA are more directly linked to metabolic health, which indicates the need to measure circulating SCFA in human prebiotic/probiotic intervention studies as a biomarker/mediator of effects on host metabolism.

The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity.

The interplay of gut microbiota, host metabolism, and metabolic health has gained increased attention. Gut microbiota may play a regulatory role in gastrointestinal health, substrate metabolism, and peripheral tissues including adipose tissue, skeletal muscle, liver, and pancreas via its metabolites short-chain fatty acids (SCFA). Animal and human data demonstrated that, in particular, acetate beneficially affects host energy and substrate metabolism via secretion of the gut hormones like glucagon-like peptide-1 and peptide YY, which, thereby, affects appetite, via a reduction in whole-body lipolysis, systemic pro-inflammatory cytokine levels, and via an increase in energy expenditure and fat oxidation. Thus, potential therapies to increase gut microbial fermentation and acetate production have been under vigorous scientific scrutiny. In this review, the relevance of the colonically and systemically most abundant SCFA acetate and its effects on the previously mentioned tissues will be discussed in relation to body weight control and glucose homeostasis. We discuss in detail the differential effects of oral acetate administration (vinegar intake), colonic acetate infusions, acetogenic fiber, and acetogenic probiotic administrations as approaches to combat obesity and comorbidities. Notably, human data are scarce, which highlights the necessity for further human research to investigate acetate's role in host physiology, metabolic, and cardiovascular health.

Short-Chain Fatty Acids Differentially Affect Intracellular Lipolysis in a Human White Adipocyte Model.

BACKGROUND AND AIMS: Gut-derived short-chain fatty acids (SCFA), formed by microbial fermentation of dietary fibers, are believed to be involved in the etiology of obesity and diabetes. Previous data from our group showed that colonic infusions of physiologically relevant SCFA mixtures attenuated whole-body lipolysis in overweight men. To further study potential mechanisms involved in the antilipolytic properties of SCFA, we aimed to investigate the in vitro effects of SCFA incubations on intracellular lipolysis and signaling using a human white adipocyte model, the human multipotent adipose tissue-derived stem (hMADS) cells. METHODS: hMADS adipocytes were incubated with mixtures of acetate, propionate, and butyrate or single SCFA (acetate, propionate and butyrate) in concentrations ranging between 1 µmol/L and 1 mmol/L. Glycerol release and lipase activation was investigated during basal conditions and following ß-adrenergic stimulation. RESULTS: SCFA mixtures high in acetate and propionate decreased basal glycerol release, when compared to control (P < 0.05), while mixtures high in butyrate had no effect. Also, ß-adrenergic receptor mediated glycerol release was not significantly altered following incubation with SCFA mixtures. Incubation with only acetate decreased basal (1 µmol/L) and ß-adrenergically (1 µmol/L and 1 mmol/L) mediated glycerol release when compared with control (P < 0.05). In contrast, butyrate (1 µmol/L) slightly increased basal and ß-adrenergically mediated glycerol release compared with control (P < 0.05), while propionate had no effect on lipolysis. The antilipolytic effect of acetate was accompanied by a reduced phosphorylation of hormone-sensitive lipase (HSL) at serine residue 650. In addition, inhibition of Gi G proteins following pertussis toxin treatment prevented the antilipolytic effect of acetate. CONCLUSION: The present data demonstrated that acetate was mainly responsible for the antilipolytic effects of SCFA and acts via attenuation of HSL phosphorylation in a Gi-coupled manner in hMADS adipocytes. Therefore, the modulation of colonic and circulating acetate may be an important target to modulate human adipose tissue lipid metabolism.

CT-Guided Microwave Ablation of 45 Renal Tumors: Analysis of Procedure Complexity Utilizing a Percutaneous Renal Ablation Complexity Scoring System.

PURPOSE: To develop a scoring system that stratifies complexity of percutaneous ablation of renal tumors. MATERIALS AND METHODS: Analysis was performed of 36 consecutive patients (mean age, 64 y; range, 30-89 y) who underwent CT-guided microwave (MW) ablation of 45 renal tumors (mean tumor diameter, 2.4 cm; range, 1.2-4.0 cm). Technical success and effectiveness were determined based on intraprocedural and follow-up imaging studies. The RENAL score and the proposed percutaneous renal ablation complexity (P-RAC) score were calculated for each tumor. RESULTS: Technical success was 93.3% (n = 42). Biopsy of 38 of 45 renal tumors revealed 23 renal cell carcinomas. Median follow-up period was 9.7 months (range, 2.9-46.8 months). There were no tumor recurrences. One major complication, ureteropelvic junction stricture, occurred (2.6%). The P-RAC score was found to differ statistically from the RENAL score (t = 3.754, df = 44, P = .001). A positive correlation was found between the P-RAC score and number of antenna insertions (r = .378, n = 45, P = .011) and procedure duration (r = .328, n = 45, P = .028). No correlation was found between the RENAL score and number of MW antenna insertions (r = .110, n = 45, P = .472) or procedure duration (r = .263, n = 45, P = .081). Hydrodissection was significantly more common in the P-RAC high-complexity category than in low-complexity category (χ2 = 12.073, df = 2, P = .002). CONCLUSIONS: The P-RAC score may be useful in stratifying percutaneous renal ablation complexity. Further studies with larger sample sizes are necessary to validate the P-RAC score and to determine if it can predict risk of complications.

Bariatric CT Imaging: Challenges and Solutions.

The obesity epidemic in the adult and pediatric populations affects all aspects of health care, including diagnostic imaging. With the increasing prevalence of obese and morbidly obese patients, bariatric computed tomographic (CT) imaging is becoming common in day-to-day radiology practice, and a basic understanding of the unique problems that bariatric patients pose to the imaging community is crucial in any setting. Because larger patients may not fit into conventional scanners, having a CT scanner with an adequate table load limit, a large gantry aperture, a large scan field of view, and a high-power generator is a prerequisite for bariatric imaging. Iterative reconstruction methods, high tube current, and high tube voltage can reduce the image noise that is frequently seen in bariatric CT images. Truncation artifacts, cropping artifacts, and ring artifacts frequently complicate the interpretation of CT images of larger patients. If recognized, these artifacts can be easily reduced by using the proper CT equipment, scan acquisition parameters, and postprocessing options. Lastly, because of complex contrast material dynamics, contrast material-enhanced studies of bariatric patients require special attention. Understanding how the rate of injection, the scan timing, and the total mass of iodine affect vascular and parenchymal enhancement will help to optimize contrast-enhanced studies in the bariatric population. This article familiarizes the reader with the challenges that are frequently encountered at CT imaging of bariatric patients, beginning with equipment selection and ending with a review of the most commonly encountered obesity-related artifacts and the technical considerations in the acquisition of contrast-enhanced images. (©)RSNA, 2016.

Do natural disasters cause an excessive fear of heights? Evidence from the Wenchuan earthquake.

This paper uses the 2008 Wenchuan earthquake in China to examine if the occurrence of a natural disaster can cause an excessive fear of living in upper floors. We rely on potential variations in earthquake risk perceptions by floor level to assess whether the pricing of apartments in lower versus upper floors is consistent with a disproportionate fear of heights. We use a unique transaction dataset for new apartment units in the affected area. We find that the relative price of low to high floor units, particularly units located in the first and second floor, considerably increased for several months after the earthquake and then returned back to the levels observed prior to the tremor. This temporal increase in relative prices is in line with a higher risk perception and fear, triggered after the earthquake, of living in upper floors, which gradually dissipated over time. The results are robust to alternative model estimations.

Pathophysiology of perinatal asphyxia: can we predict and improve individual outcomes?

Perinatal asphyxia occurs still with great incidence whenever delivery is prolonged, despite improvements in perinatal care. After asphyxia, infants can suffer from short- to long-term neurological sequelae, their severity depend upon the extent of the insult, the metabolic imbalance during the re-oxygenation period and the developmental state of the affected regions. Significant progresses in understanding of perinatal asphyxia pathophysiology have achieved. However, predictive diagnostics and personalised therapeutic interventions are still under initial development. Now the emphasis is on early non-invasive diagnosis approach, as well as, in identifying new therapeutic targets to improve individual outcomes. In this review we discuss (i) specific biomarkers for early prediction of perinatal asphyxia outcome; (ii) short and long term sequelae; (iii) neurocircuitries involved; (iv) molecular pathways; (v) neuroinflammation systems; (vi) endogenous brain rescue systems, including activation of sentinel proteins and neurogenesis; and (vii) therapeutic targets for preventing or mitigating the effects produced by asphyxia.

Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins.

Delivery is a stressful and risky event menacing the newborn. The mother-dependent respiration has to be replaced by autonomous pulmonary breathing immediately after delivery. If delayed, it may lead to deficient oxygen supply compromising survival and development of the central nervous system. Lack of oxygen availability gives rise to depletion of NAD(+) tissue stores, decrease of ATP formation, weakening of the electron transport pump and anaerobic metabolism and acidosis, leading necessarily to death if oxygenation is not promptly re-established. Re-oxygenation triggers a cascade of compensatory biochemical events to restore function, which may be accompanied by improper homeostasis and oxidative stress. Consequences may be incomplete recovery, or excess reactions that worsen the biological outcome by disturbed metabolism and/or imbalance produced by over-expression of alternative metabolic pathways. Perinatal asphyxia has been associated with severe neurological and psychiatric sequelae with delayed clinical onset. No specific treatments have yet been established. In the clinical setting, after resuscitation of an infant with birth asphyxia, the emphasis is on supportive therapy. Several interventions have been proposed to attenuate secondary neuronal injuries elicited by asphyxia, including hypothermia. Although promising, the clinical efficacy of hypothermia has not been fully demonstrated. It is evident that new approaches are warranted. The purpose of this review is to discuss the concept of sentinel proteins as targets for neuroprotection. Several sentinel proteins have been described to protect the integrity of the genome (e.g. PARP-1; XRCC1; DNA ligase IIIα; DNA polymerase ß, ERCC2, DNA-dependent protein kinases). They act by eliciting metabolic cascades leading to (i) activation of cell survival and neurotrophic pathways; (ii) early and delayed programmed cell death, and (iii) promotion of cell proliferation, differentiation, neuritogenesis and synaptogenesis. It is proposed that sentinel proteins can be used as markers for characterising long-term effects of perinatal asphyxia, and as targets for novel therapeutic development and innovative strategies for neonatal care.

Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors.

2,5-Dimethoxy-4-substituted phenylisopropylamines and phenethylamines are 5-hydroxytryptamine (serotonin) (5-HT)(2A/2C) agonists. The former are partial to full agonists, whereas the latter are partial to weak agonists. However, most data come from studies analyzing phospholipase C (PLC)-mediated responses, although additional effectors [e.g., phospholipase A(2) (PLA(2))] are associated with these receptors. We compared two homologous series of phenylisopropylamines and phenethylamines measuring both PLA(2) and PLC responses in Chinese hamster ovary-K1 cells expressing human 5-HT(2A) or 5-HT(2C) receptors. In addition, we assayed both groups of compounds as head shake inducers in rats. At the 5-HT(2C) receptor, most compounds were partial agonists for both pathways. Relative efficacy of some phenylisopropylamines was higher for both responses compared with their phenethylamine counterparts, whereas for others, no differences were found. At the 5-HT(2A) receptor, most compounds behaved as partial agonists, but unlike findings at 5-HT(2C) receptors, all phenylisopropylamines were more efficacious than their phenethylamine counterparts. 2,5-Dimethoxyphenylisopropylamine activated only the PLC pathway at both receptor subtypes, 2,5-dimethoxyphenethylamine was selective for PLC at the 5-HT(2C) receptor, and 2,5-dimethoxy-4-nitrophenethylamine was PLA(2)-specific at the 5-HT(2A) receptor. For both receptors, the rank order of efficacy of compounds differed depending upon which response was measured. The phenylisopropylamines were strong head shake inducers, whereas their phenethylamine congeners were not, in agreement with in vitro results and the involvement of 5-HT(2A) receptors in the head shake response. Our results support the concept of functional selectivity and indicate that subtle changes in ligand structure can result in significant differences in the cellular signaling profile.

[Autologous bone marrow transplantation as a treatment for autoimmune disease: mechanisms and results]. / Trasplante autólogo de médula ósea como tratamiento de enfermedades autoinmunes: mecanismos y resultados.

Autoimmune diseases are characterized by immune response against self antigens. One of the current research interests in this field is oriented toward development of tolerance. One of the newest options in the search for tolerance is autologous bone marrow transplantation: a variant of bone marrow transplant in which the patient's own hematopoietic stem cells are reinfused after myeloablative therapy. The idea of using bone marrow transplant in treatment of autoimmune diseases derived from observing remission in autoimmune diseases in patients transplanted due to coexisting neoplastic disease. Although an isolated initial report of bone marrow transplant as treatment for autoimmune disease questioned the utility of this procedure, over all, results are encouraging. To compile information in a programmed and systematic manner, it is necessary to send more patients in all stages of immune diseases to specialized centers to be included in large multicenter randomized trials. In time, the role for this procedure in autoimmune diseases will become clear.

Trasplante autólogo de médula ósea como tratamiento de enfermedades autoinmunes: mecanismos y resultados / Autologous Bone Marrow Transplantation as a Treatment for Autoimmune Disease: Mechanisms and Results

Las enfermedades autoinmunes se caracterizan por una respuesta del sistema inmune del individuo hacia tejidos propios. Una línea de investigación actual es el tratamiento de estas enfermedades y el desarrollo de tolerancia. Una de las opciones en la búsqueda del desarrollo de tolerancia es el trasplante autólogo de médula ósea: la variantes del trasplante de médula ósea que hace uso de células progenitoras hematopoyéticas propias. La posibilidad de usar este tipo de trasplante como tratamiento de enfermedades autoinmunes se originó en los hallazgos de remisiones de enfermedades autoinmunes coexistentes, en pacientes que eran trasplantados por enfermedades oncológicas. En esta revisión presentemos el fundamento teórico de este tratamiento, así como una recopilación de los estudios preclínicos y clínicos más relevantes en esta materia. Aunque algún reporte inicial puso en duda la utilidad de dicho procedimiento, en general, los resultados son alentadores. Es necesario que más pacientes en diversos estadios de las enfermedades autoinmunes sean referidos a centros especializados de manera que sea posible recopilar la información de manera ordenada y sistemática, y se pueda arribar a un conocimiento sobre el papel que juega este tipo de tratamiento en las enfermedades autoinmunes.

Autoimmune diseases are characterized by immune response against self antigens. One of the current research interests in this field is oriented toward development of tolerance. One of the newest options in the search for tolerance is autologous bone marrow transpiantation: a variant of bone marrow transplant in which the patient's own hematopoietic stem cells are reinfused after myeloablative therapy. The idea of using bone marrow transplant in treatment of autoimmune diseases derived from observing remission in autoinmune diseases in patients transplanted due to coexisting neoplastic disease. Although an isolated initial report of bone marrow transplant as treatment for autoimmune disease questioned the utility of this procedure, over all, results are encouraging. To compile information in a programmed and systematic manner, it is necessary to send more patients in all stages of immune diseases to specialized centers to be included in large multicenter randomized trials. In time, the role for this procedure in autoimmune diseases will become clear.

A randomized trial of dexamethasone before remission induction, in de novo childhood acute lymphoblastic leukemia.

We evaluated the impact of adding dexamethasone before chemotherapy in 95 children with de novo standard-risk acute lymphoblastic leukemia (ALL). The children were randomly divided into 2 groups: one group was given dexamethasone, the other was not. The initial characteristics and mean follow-up of both groups were similar. Day +14 blast percentage was significantly lower in the dexamethasone group. Disease-free survival at 40-months follow-up was better (almost significantly so) in the dexamethasone group.

Infección y neutropenia: pefloxacina versus amikacina-ceftazidima como terapia antimicrobiana empírica inicial / Infection and neutropenia, pefloxacine vs. amikacine-ceftazidime as an initial antimicrobial empirical therapy

Objetivo. Comparar la eficacia y eficiencia de la pefloxacina vs la amika-cina-ceftazidima, seguidas de vancomicina, como terapia empírica en episodios de infección y neutropenia. Material y métodos. El estudio fue prospectivo. Se incluyeron pacientes mayores de 15 años, con temperatura superior a 38ºC y concentración de neutrófilos menor de 1 x 10 a la 9/L. La asignación a la ramas de tratamiento se hizo al azar. Un grupo recibió pefloxacina, el otro amikacina y ceftazidima. En ambas rama, si la fiebre persistió por 72 h se agregó vancomicina; si la fiebre persistió por 10 días, se agregó anfotericina B. Resultados. 38 pacientes evaluables (17/21) en ambas ramas fueron comparables en patología básica, aplicación de quimioterapia, neutrófilos iniciales, neutropenia máxima, neutrófilos finales, focos infecciosos y gérmenes aislados. La curación se observó en 87 y 89 por ciento de los casos, respectivamente (p=0.52). La duración promedio de la fiebre fue de 6.1 y 5.8 días (p=0.84). Conclusión. La pefloxacina y la amikacina-ceftazidima tienen eficacia y eficiencia comparables como antibióticos iniciales en episodios de infección y neutropenia, usados como tratamiento antimicrobiana empírica

¿Conviene realizar plasmaféresis en el preoperatorio de timectomía? / Is it advisable the realization of plasmapheresis in the preoperative of thymectomy?

El objetivo de este trabajo fue evaluar el beneficio de la plasmaféresis en la preparación para timectomía de los enfermos con miastenia gravis generalizada (MGG). Se evaluaron 21 pacientes de enero de 1988 a enero de 1995, con diagnóstico confirmado de MGG, quienes fueron sometidos a timectomía y se les realizó plasmaféresis previa al procemiento; se compararon con un grupo control histórico de 21 enfermos; ambos grupos eran comparables en sexo, edad, tiempo de enfermedades, en el manejo prequirúrgico y posoperatorio; la diferencia entre ellos fue la realización de plasmaféresis. El grupo tratado mostró diferencias significativas en una reducción del tiempo de asistencia ventilatoria (p < 0.008), menor requerimiento de piridostigmina (p< 0.0006) y mejores condiciones clínicas evaluadas a través de la clasificación de Osserman (p < 0.0075) durante el posoperatorio. Concluimos que el grupo tratado tuvo morbilidad en el posoperatorio inmediato y mediato, por lo que deberá realizarse este procedimiento en el manejo preoperatorio a timectomía en pacientes con MGG cuando sea posible