Acute ketone supplementation in the absence of muscle glycogen utilization: Insights from McArdle disease.

BACKGROUND & AIMS: Ketone supplementation is gaining popularity. Yet, its effects on exercise performance when muscle glycogen cannot be used remain to be determined. McArdle disease can provide insight into this question, as these patients are unable to obtain energy from muscle glycogen, presenting a severely impaired physical capacity. We therefore aimed to assess the effects of acute ketone supplementation in the absence of muscle glycogen utilization (McArdle disease). METHODS: In a randomized cross-over design, patients with an inherited block in muscle glycogen breakdown (i.e., McArdle disease, n = 8) and healthy controls (n = 7) underwent a submaximal (constant-load) test that was followed by a maximal ramp test, after the ingestion of a placebo or an exogenous ketone ester supplement (30 g of D-beta hydroxybutyrate/D 1,3 butanediol monoester). Patients were also assessed after carbohydrate (75 g) ingestion, which is currently considered best clinical practice in McArdle disease. RESULTS: Ketone supplementation induced ketosis in all participants (blood [ketones] = 3.7 ± 0.9 mM) and modified some gas-exchange responses (notably increasing respiratory exchange ratio, especially in patients). Patients showed an impaired exercise capacity (-65 % peak power output (PPO) compared to controls, p < 0.001) and ketone supplementation resulted in a further impairment (-11.6 % vs. placebo, p = 0.001), with no effects in controls (p = 0.268). In patients, carbohydrate supplementation resulted in a higher PPO compared to ketones (+21.5 %, p = 0.001) and a similar response was observed vs. placebo (+12.6 %, p = 0.057). CONCLUSIONS: In individuals who cannot utilize muscle glycogen but have a preserved ability to oxidize blood-borne glucose and fat (McArdle disease), acute ketone supplementation impairs exercise capacity, whereas carbohydrate ingestion exerts the opposite, beneficial effect.

Ceratonia siliqua L. Pod Extract: From Phytochemical Characterization to Liposomal Formulation and Evaluation of Behaviour in Cells.

The formulation of plant extracts in phospholipid vesicles is a promising strategy to exploit their biological properties while solving problems related to poor solubility in water, high instability, and low skin permeation and retention time. In this study, Ceratonia siliqua ripe pods were used for the preparation of a hydro-ethanolic extract, which showed antioxidant properties owing to the presence of biologically active compounds identified by liquid chromatography-mass spectrometry (e.g., hydroxybenzoic acid and flavonoid derivatives). To improve the applicability of the extract in therapy, a topical formulation based on liposomes was explored. The vesicles were characterized by small size (around 100 nm), negative charge (-13 mV), and high entrapment efficiency (>90%). Furthermore, they displayed both spherical and elongated shapes, with oligolamellar structure. Their biocompatibility was demonstrated in cells, including erythrocytes and representative skin cell lines. The antioxidant activity of the extract was proved by the scavenging of free radicals, the reduction of ferric ions, and the protection of skin cells from oxidative damage.

Phenolic Fingerprint, Bioactivity and Nanoformulation of Prunus spinosa L. Fruit Extract for Skin Delivery.

The nanoformulation of plant extracts in phospholipid vesicles is a promising strategy to exploit the biological properties of natural bioactive substances and overcome drawbacks such as poor aqueous solubility, chemical instability, low skin permeation and retention time, which strongly limit their topical application. In this study, Prunus spinosa berries were used for the preparation of a hydro-ethanolic extract, which showed antioxidant and antibacterial properties owing to the presence of phenolic compounds. Two types of phospholipid vesicles were developed to improve the applicability as topical formulations. Liposomes and Penetration Enhancer-containing Vesicles were characterized for mean diameter, polydispersity, surface charge, shape, lamellarity, and entrapment efficiency. Additionally, their safety was assayed with different cell models, including erythrocytes and representative skin cell lines.

High-dose oral glutamine supplementation reduces elevated glutamate levels in cerebrospinal fluid in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome.

BACKGROUND AND PURPOSE: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA mutations. There are no disease-modifying therapies, and treatment remains mainly supportive. It has been shown previously that patients with MELAS syndrome have significantly increased cerebrospinal fluid (CSF) glutamate and significantly decreased CSF glutamine levels compared to controls. Glutamine has many metabolic fates in neurons and astrocytes, and the glutamate-glutamine cycle couples with many metabolic pathways depending on cellular requirements. The aim was to compare CSF glutamate and glutamine levels before and after dietary glutamine supplementation. It is postulated that high-dose oral glutamine supplementation could reduce the increase in glutamate levels. METHOD: This open-label, single-cohort study determined the safety and changes in glutamate and glutamine levels in CSF after 12 weeks of oral glutamine supplementation. RESULTS: Nine adult patients with MELAS syndrome (66.7% females, mean age 35.8 ± 3.2 years) were included. After glutamine supplementation, CSF glutamate levels were significantly reduced (9.77 ± 1.21 vs. 18.48 ± 1.34 µmol/l, p < 0.001) and CSF glutamine levels were significantly increased (433.66 ± 15.31 vs. 336.31 ± 12.92 µmol/l, p = 0.002). A side effect observed in four of nine patients was a mild sensation of satiety. One patient developed mild and transient elevation of transaminases, and another patient was admitted for an epileptic status without stroke-like episode. DISCUSSION: This study demonstrates that high-dose oral glutamine supplementation significantly reduces CSF glutamate and increases CSF glutamine levels in patients with MELAS syndrome. These findings may have potential therapeutic implications in these patients. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT04948138. Initial release 24 June 2021, first patient enrolled 1 July 2021. https://clinicaltrials.gov/ct2/show/NCT04948138.

To list or not to list? The value and detriment of freelisting in ethnobotanical studies.

Although freelisting and semi-structured interviews are widespread methods in ethnobotany, few studies quantitatively examine how these methods may bias results. Using a comprehensive ethnobotanical inventory of palm species, uses and names in the Chácobo tribe of Bolivia, we show that interviews elicit more items than freelists, but the effect is sensitive to sample size, item type and data categorization. This implies that even subtle methodological choices may greatly affect reported results.

Who should conduct ethnobotanical studies? Effects of different interviewers in the case of the Chácobo Ethnobotany project, Beni, Bolivia.

BACKGROUND: That the answers elicited through interviews may be influenced by the knowledge of the interviewer is accepted across disciplines. However, in ethnobotany, there is little evidence to quantitatively assess what impact this effect may have. We use the results of a large study of traditional ecological knowledge (TEK) of plant use of the Chácobo and Pacahuara of Beni, Bolivia, to explore the effects of interviewer identity and knowledge upon the elicited plant species and uses. METHODS: The Chácobo are a Panoan speaking tribe of about 1000 members (300+ adults) in Beni, Bolivia. Researchers have collected anthropological and ethnobotanical data from the Chácobo for more than a century. Here, we present a complete ethnobotanical inventory of the entire adult Chácobo population, with interviews and plant collection conducted directly by Chácobo counterparts, with a focus on the effects caused by external interviewers. RESULTS: Within this large study, with a unified training for interviewers, we did find that different interviewers did elicit different knowledge sets, that some interviewers were more likely to elicit knowledge similar to their own, and that participants interviewed multiple times often gave information as different as that from two randomly chosen participants. CONCLUSIONS: Despite this, we did not find this effect to be overwhelming-the amount of knowledge an interviewer reported on the research subject had comparatively little effect on the amount of knowledge that interviewer recorded from others, and even those interviewers who tended to elicit similar answers from participants also elicited a large percentage of novel information.

Traditional knowledge hiding in plain sight - twenty-first century ethnobotany of the Chácobo in Beni, Bolivia.

BACKGROUND: The Chácobo are a Panoan speaking tribe of about 1000 members (300+ adults) in Beni, Bolivia. Originally nomadic, the Chácabo were relocated to their current main location in the 1960s. Researchers have visited the Chácabo since 1911. A first more detailed anthropological report exists from the late 1960s, and ecological-ethnobotanical studies were conducted in the 1980s and 1990s. The presented work represents a complete ethnobotanical inventory of the entire adult Chácobo population, with interviews and plant collection conducted directly by Chácobo counterparts. METHODS: Based on previous reports and our preliminary studies, we hypothesized that twenty-first century Chácobo plant use centered on income generation, and that traditional plant use related to household utensils, medicine and traditional crop varieties had almost disappeared. To test this hypothesis, we started the "Chácobo Ethnobotany Project," training 10 indigenous Chácobo participants in ethnobotanical interview and plant collection techniques, in order to more fully document Chácobo knowledge and avoid the influence of foreign interviewers. RESULTS: Our study found 331 useful plant species in 241genera of 95 plant families, with leaves, roots and bark being the most commonly used plant parts The comprehensive documentation that these methods enabled completely nullified our initial hypothesis of knowledge loss. Traditional crop varieties are still widely grown and traditional knowledge is alive. Moreover, it is being actively recuperated in certain domains by the younger generation. Most Chácobo know, and can name, traditional utensils and tools, although only the older generation has still the skills to manufacture them. While many Chácobo still know the names and uses of medicinal species, the younger generation is however often unsure how to identify them. CONCLUSIONS: In this paper we illustrate the complexity of perspectives on knowledge at different ages, and the persistence of knowledge over almost a century. We found that traditional knowledge was only partially affected by the processes of exposure to a market economy, and that different knowledge domains experienced different trends as a result of these changes. Overall knowledge was widely distributed, and we did not observe a directional knowledge loss. We stress the importance to not directly conclude processes of knowledge loss, cultural erosion or acculturation when comparing the knowledge of different age groups.

Benefits of skeletal-muscle exercise training in pulmonary arterial hypertension: The WHOLEi+12 trial.

BACKGROUND: Pulmonary arterial hypertension is often associated with skeletal-muscle weakness. The purpose of this randomized controlled trial was to determine the effects of an 8-week intervention combining muscle resistance, aerobic and inspiratory pressure-load exercises on upper/lower-body muscle power and other functional variables in patients with this disease. METHODS: Participants were allocated to a control (standard care) or intervention (exercise) group (n=20 each, 45±12 and 46±11years, 60% women and 10% patients with chronic thromboembolic pulmonary hypertension per group). The intervention included five, three and six supervised (inhospital) sessions/week of aerobic, resistance and inspiratory muscle training, respectively. The primary endpoint was peak muscle power during bench/leg press; secondary outcomes included N-terminal pro-brain natriuretic peptide levels, 6-min walking distance, five-repetition sit-to-stand test, maximal inspiratory pressure, cardiopulmonary exercise testing variables (e.g., peak oxygen uptake), health-related quality of life, physical activity levels, and safety. RESULTS: Adherence to training sessions averaged 94±0.5% (aerobic), 98±0.3% (resistance) and 91±1% (inspiratory training). Analysis of variance showed a significant interaction (group×time) effect for leg/bench press (P<0.001/P=0.002), with both tests showing an improvement in the exercise group (P<0.001) but not in controls (P>0.1). We found a significant interaction effect (P<0.001) for five-repetition sit-to-stand test, maximal inspiratory pressure and peak oxygen uptake (P<0.001), indicating a training-induced improvement. No major adverse event was noted due to exercise. CONCLUSIONS: An 8-week exercise intervention including aerobic, resistance and specific inspiratory muscle training is safe for patients with pulmonary arterial hypertension and yields significant improvements in muscle power and other functional variables.

Cellular pathophysiological consequences of BCS1L mutations in mitochondrial complex III enzyme deficiency.

Mutations in BCS1L, an assembly factor that facilitates the insertion of the catalytic Rieske Iron-Sulfur subunit into respiratory chain complex III, result in a wide variety of clinical phenotypes that range from the relatively mild Björnstad syndrome to the severe GRACILE syndrome. To better understand the pathophysiological consequences of such mutations, we studied fibroblasts from six complex III-deficient patients harboring mutations in the BCS1L gene. Cells from patients with the most severe clinical phenotypes exhibited slow growth rates in glucose medium, variable combined enzyme deficiencies, and assembly defects of respiratory chain complexes I, III, and IV, increased H(2)O(2) levels, unbalanced expression of the cellular antioxidant defenses, and apoptotic cell death. In addition, all patients showed cytosolic accumulation of the BCS1L protein, suggestive of an impaired mitochondrial import, assembly or stability defects of the BCS1L complex, fragmentation of the mitochondrial networks, and decreased MFN2 protein levels. The observed structural alterations were independent of the respiratory chain function and ROS production. Our results provide new insights into the role of pathogenic BCS1L mutations in mitochondrial function and dynamics.

Anterior medial temporal lobe activation during encoding of words: FMRI methods to optimize sensitivity.

The existence of a rostrocaudal gradient of medial temporal lobe (MTL) activation during memory encoding has historically received support from positron emission tomography studies, but less so from functional MRI (FMRI) studies. More recently, FMRI studies have demonstrated that characteristics of the stimuli can affect the location of activation seen in the MTL when those stimuli are encoded. The current study tested the hypothesis that MTL activation during memory encoding is related to the modality of stimulus presentation. Subjects encoded auditorily or visually presented words in an FMRI novelty paradigm. Imaging and analysis parameters were optimized to minimize susceptibility artifact in the anterior MTL. Greater activation was observed in the anterior than posterior MTL for both modalities of stimulus presentation. The results indicate that anterior MTL activation occurred during encoding, independent of stimulus modality and provide support for the hypothesis that verbal-semantic memory processing occurs in anterior MTL. The authors suggest that technical factors are critical for observing the rostrocaudal gradient in MTL memory activation.

[Pulmonary hypertension during exercise in toxic oil syndrome]. / Hipertensión pulmonar con el ejercicio en el síndrome del aceite tóxico.

BACKGROUND AND OBJECTIVE: Toxic oil syndrome is a risk factor for pulmonary arterial hypertension (PAH) and new cases of this entity are emerging after more than 20 years since the initial toxic oil epidemic. Abnormal elevation of pulmonary systolic pressure with exercise may be considered an early marker of PAH in populations at risk. We aimed to analyze the pulmonary systolic pressure with exercise echocardiography in toxic oil syndrome patients. PATIENTS AND METHOD: 50 toxic oil syndrome patients (cases), and 20 healthy control subjects were submitted to rest and peak exercise echocardiography (semi supine cycloergometer) measuring pulmonary systolic pressure. In toxic oil syndrome patients, pulmonary carbon monoxide diffusion capacity was also analyzed. RESULTS: Peak exercise pulmonary systolic pressure was statistically similar in cases and controls. Nevertheless, 8% of cases reached a pulmonary systolic pressure > or = 80 mmHg and this fact was associated with mild pulmonary arterial hypertension, reduced right ventricular function and abnormal pulmonary diffusion capacity in the rest study. A rest pulmonary systolic pressure cut-off value > or = 27 mmHg had a 100% sensitivity and 71% specificity to predict a peak exercise systolic pulmonary pressure > or = 80 mmHg. CONCLUSIONS: A minority of toxic oil syndrome patients develop severe pulmonary arterial hypertension during exercise. This abnormal response is associated with other markers of pulmonary vasculopathy. Further studies are needed to elucidate the relation between these findings and the likelihood to develop pulmonary arterial hypertension in the future.

Mineral content of the honey produced in Zulia state, Venezuela.

The mineral content of the honey produced in five zones of the Zulia state, Venezuela, during dry and rainy seasons was determined. The analyzed elements were: sodium, potassium (by emission spectroscopy), calcium, magnesium, copper, iron, manganese (by atomic absorption spectroscopy), phosphorus (phosphate ions, by colorimetric method), and ash content of raw honey samples directly collected from different beekeepers. The mean values for Na, K, Ca, Mg, Cu, Fe, Mn, and P were 353+84; 1774+138; 237+66; 52+24; 0.76+0.43; 13.5+10.23; 0.92+0.42 and 1642+323 mg/kg respectively. The mean ash content was 0.431+0.15%. Potassium was the most abundant of the elements determined. This results confirm that Zulian honey can be considered a good source of minerals.