[Clinical characteristics and related factors analysis of adrenal crisis occurred in children with primary nephrotic syndrome].

Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P>0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month,U=25.50, P=0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U=27.00,P=0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L,t=-6.22,P<0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×109 vs. (11±5)×109/L,t=4.26,P=0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19,t=2.56,P=0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0,P=0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.

Clinical characteristics and related factors analysis of adrenal crisis occurred in children with primary nephrotic syndrome / 中华儿科杂志

Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P>0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month,U=25.50, P=0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U=27.00,P=0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L,t=-6.22,P<0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×109 vs. (11±5)×109/L,t=4.26,P=0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19,t=2.56,P=0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0,P=0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.

Neuronally-enriched exosomal microRNA-27b mediates acute effects of ibuprofen on reward-related brain activity in healthy adults: a randomized, placebo-controlled, double-blind trial.

This double-blind, randomized, within-subjects design evaluated whether acute administration of an anti-inflammatory drug modulates neuron-specific, inflammation-modulating microRNAs linked to macroscopic changes in reward processing. Twenty healthy subjects (10 females, 10 males) underwent a functional magnetic resonance imaging scan while performing a monetary incentive delay (MID) task and provided blood samples after administration of placebo, 200 mg, or 600 mg of ibuprofen. Neuronally-enriched exosomal microRNAs were extracted from serum and sequenced. Results showed that: (1) 600 mg of ibuprofen exhibited higher miR-27b-3p, miR-320b, miR-23b and miR-203a-3p expression than placebo; (2) higher mir-27b-3p was associated with lower insula activation during MID loss anticipation; and (3) there was an inverse relationship between miR-27b-3p and MID gain anticipation in bilateral putamen during placebo, a pattern attenuated by both 200 mg and 600 mg of ibuprofen. These findings are consistent with the hypothesis that miR-27b could be an important messaging molecule that is associated with regulating the processing of positive or negative valenced information.

The effects of roflumilast, a phosphodiesterase type-4 inhibitor, on EEG biomarkers in schizophrenia: A randomised controlled trial.

BACKGROUND: Patients with schizophrenia have significant cognitive deficits, which may profoundly impair quality of life. These deficits are also evident at the neurophysiological level with patients demonstrating altered event-related potential in several stages of cognitive processing compared to healthy controls; within the auditory domain, for example, there are replicated alterations in Mismatch Negativity, P300 and Auditory Steady State Response. However, there are no approved pharmacological treatments for cognitive deficits in schizophrenia. AIMS: Here we examine whether the phosphodiesterase-4 inhibitor, roflumilast, can improve neurophysiological deficits in schizophrenia. METHODS: Using a randomised, double-blind, placebo-controlled, crossover design study in 18 patients with schizophrenia, the effect of the phosphodiesterase-4 inhibitor, roflumilast (100 µg and 250 µg) on auditory steady state response (early stage), mismatch negativity and theta (intermediate stage) and P300 (late stage) was examined using electroencephalogram. A total of 18 subjects were randomised and included in the analysis. RESULTS: Roflumilast 250 µg significantly enhanced the amplitude of both the mismatch negativity (p=0.04) and working memory-related theta oscillations (p=0.02) compared to placebo but not in the other (early- or late-stage) cognitive markers. CONCLUSIONS: The results suggest that phosphodiesterase-4 inhibition, with roflumilast, can improve electroencephalogram cognitive markers, which are impaired in schizophrenia, and that phosphodiesterase-4 inhibition acts at an intermediate rather than early or late cognitive processing stage. This study also underlines the use of neurophysiological measures as cognitive biomarkers in experimental medicine.

Cannabis points to the synaptic pathology of mental disorders: how aberrant synaptic components disrupt the highest psychological functions
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Cannabis can elicit an acute psychotic reaction, and its long-term use is a risk factor for schizophrenia. The main active psychoactive ingredient ∆9-tetrahydrocannabinol (Δ9-THC) activates cannabinoid 1 (CB1) receptors, which are localized to the terminals of glutamate and GABA neurons in the brain. The endogenous cannabinoids are involved in information processing and plasticity at synapses in the hippocampus, basal ganglia, and cerebral cortex. Exogenously applied CB1 receptor agonists disrupt neuronal dynamics and synaptic plasticity, resulting in cognitive deficits and impairment of the highest psychological functions. Various other pro-psychotic drugs, such as ketamine and methamphetamine, exert their effects in the same microdomain of synaptic spines as Δ9-THC. Additionally, many of the most robust findings in psychiatric genetics include components that localize to dendritic spines and have important roles in information processing and plasticity.
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La cannabis puede provocar una reacción psicótica aguda y su empleo a largo plazo es un factor de riesgo para esquizofrenia. El principal componente psicoactivo ∆9-tetrahidrocannabinol (Δ9-THC) estimula los receptores cannabinoides CB1, que se localizan en las terminales de las neuronas de glutamato y de GABA cerebrales. Los cannabinoides endógenos participan en el procesamiento de la información y la plasticidad en las sinapsis del hipocampo, los ganglios basales y la corteza cerebral. Los agonistas de CB1 administrados de forma exógena interrumpen la dinámica neuronal y la plasticidad sináptica, lo que se traduce en déficits cognitivos y deterioro de las funciones psicológicas más altas. Varias otras drogas propsicóticas, como la ketamina y la metanfetamina, ejercen sus efectos en el mismo microdominio de espinas sinápticas que el Δ9-THC. Además, muchos de los hallazgos más consistentes en genética psiquiátrica incluyen componentes que se localizan en las espinas dendríticas y tienen funciones importantes en el procesamiento y la plasticidad de la información.

Le cannabis peut provoquer une réaction psychotique aiguë et sa consommation à long terme est un facteur de risque de schizophrénie. Le ∆9-tétrahydrocannabinol (Δ9-THC), principal ingrédient psychoactif, active les récepteurs cannabinoïdes CB1 situés aux extrémités des neurones glutamatergiques et GABAergiques dans le cerveau. Les cannabinoïdes endogènes participent au traitement de l'information et à la plasticité des synapses dans l'hippocampe, les ganglions de la base et le cortex cérébral. Les agonistes CB1 exogènes perturbent la dynamique neuronale et la plasticité synaptique, entraînant des déficits cognitifs et une altération des fonctions psychologiques les plus hautes. D'autres drogues propsychotiques, telles la kétamine et la méthamphétamine, agissent dans le même micro-domaine des épines synaptiques que le Δ9-THC. De plus, de nombreuses recherches en génétique psychiatrique ont mis en évidence des composés qui jouent un rôle important dans le traitement de l'information et la plasticité en se fixant sur les épines dendritiques.

Benefits and Adverse Effects of Histidine Supplementation.

Histidine is a nutritionally essential amino acid with many recognized benefits to human health, while circulating concentrations of histidine decline in pathologic conditions [e.g., chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)]. The purpose of this review is to examine the existing literature regarding the benefits of histidine intake, the adverse effects of excess histidine, and the upper tolerance level for histidine. Supplementation with doses of 4.0-4.5 g histidine/d and increased dietary histidine intake are associated with decreased BMI, adiposity, markers of glucose homeostasis (e.g., HOMA-IR, fasting blood glucose, 2-h postprandial blood glucose), proinflammatory cytokines, and oxidative stress. It is unclear from the limited number of studies in humans whether the improvements in glucoregulatory markers, inflammation, and oxidative stress are due to reduced BMI and adiposity, increased carnosine (a metabolic product of histidine with antioxidant effects), or both. Histidine intake also improves cognitive function (e.g., reduces appetite, anxiety, and stress responses and improves sleep) potentially through the metabolism of histidine to histamine; however, this relation is ambiguous in humans. At high intakes of histidine (>24 g/d), studies report adverse effects of histidine such as decreased serum zinc and cognitive impairment. There is limited research on the effects of histidine intake at doses between 4.5 and 24 g/d, and thus, a tolerable upper level has not been established. Determining tolerance to histidine supplementation has been limited by small sample sizes and, more important, a lack of a clear biomarker for histidine supplementation. The U-shaped curve of circulating zinc concentrations with histidine supplementation could be exploited as a relevant biomarker for supplemental histidine tolerance. Histidine is an important amino acid and may be necessary as a supplement in some populations; however, gaps in knowledge, which this review highlights, need to be addressed scientifically.

Effects of HIV infection, antiretroviral therapy, and immune status on the speed of information processing and complex motor functions in adult Cameroonians.

HIV-associated neurocognitive deficits include impaired speed-of-information processing (SIP) and motor functions. There is lack of Cameroonian adult norms for assessing SIP or motor functions. This study of 683 Cameroonians (320 HIV+, 363 HIV-) establishes demographically-adjusted norms for six SIP [Wechsler-Adult-Intelligence-Scale (WAIS)-III Digit Symbol (WAIS-IIIDS) and Symbol Search (WAIS-IIISS), Stroop Color-Naming, Stroop Word-Reading, Trail-Making Test-A (TMT-A), Color Trails-1 (CTT1)], and two motor function [Grooved Pegboard-dominant (GP-DH) and non-dominant (GP-NDH) hands] tests. We assessed viral effects on SIP and motor functions. HIV-infected persons had significantly lower (worse) T scores on GP-DH, WAIS-IIIDS, Stroop Word-Reading, TMT-A; lower motor and SIP summary T scores. Significantly higher proportion of cases (20.7%) than controls (10.3%) had impaired SIP. Male cases had better T scores than female cases on GP-NDH, WAIS-IIIDS, WAIS-IIISS, TMT-A, CTT1; better SIP summary T scores. Antiretroviral therapy (ART) was associated with significantly better T scores on GP-NDH, WAIS-IIIDS, Stroop Color-Naming; better motor and SIP summary T scores. Cases with higher CD4 had better T scores on WAIS-IIIDS, TMT-A, CTT1; better SIP summary T scores. Overall, we demonstrate that HIV infection in Cameroon is associated with deficits in SIP and motor functions; ART and higher CD4 are associated with better cognitive performance. We provide SIP and psychomotor functions normative standards, which will be useful for neurobehavioral studies in Cameroon of diseases affecting the brain.

Testosterone administration in human social neuroendocrinology: Past, present, and future.

Over the past 20 years, social neuroendocrinology researchers have developed pharmacological challenge paradigms to assess the extent to which testosterone plays a causal role in human psychological and behavioural processes. The current paper provides a brief summary of this research and offers recommendations for future research examining the neuroendocrine mechanisms underlying human behaviour.

Caffeine improves text reading and global perception.

BACKGROUND: Reading is a unique human skill. Several brain networks involved in this complex skill mainly involve the left hemisphere language areas. Nevertheless, nonlinguistic networks found in the right hemisphere also seem to be involved in sentence and text reading. These areas do not deal with phonological information, but are involved in verbal and nonverbal pattern information processing. The right hemisphere is responsible for global processing of a scene, which is needed for developing reading skills. AIMS: Caffeine seems to affect global pattern processing specifically. Consequently, our aim was to discover if it could enhance text reading skill. METHODS: In two mechanistic studies (n=24 and n=53), we tested several reading skills, global and local perception, alerting, spatial attention and executive functions, as well as rapid automatised naming and phonological memory, using a double-blind, within-subjects, repeated-measures design in typical young adult readers. RESULTS: A single dose of 200 mg caffeine improved global processing, without any effect on local information processing, alerting, spatial attention and executive or phonological functions. This improvement in global processing was accompanied by faster text reading speed of meaningful sentences, whereas single word/pseudoword or pseudoword text reading abilities were not affected. These effects of caffeine on reading ability were enhanced by mild sleep deprivation. CONCLUSIONS: These findings show that a small quantity of caffeine could improve global processing and text reading skills in adults.

How high-dose alcohol intoxication affects the interplay of automatic and controlled processes.

Binge drinking is an increasingly prevalent pattern of alcohol consumption that impairs top-down cognitive control to a much stronger degree than automatic response generation. Even though an imbalance of those two antagonistic processes fosters the development and maintenance of alcohol use disorders (AUDs), it has never been directly investigated how binge drinking affects the interaction of those two processes. We therefore assessed a sample of n = 35 healthy young men who were asked to perform a newly developed Simon Nogo paradigm once sober and once intoxicated (~1.2‰) in a balanced within-subject design. Additionally, an EEG was recorded to dissociate controlled and automatic cognitive subprocesses. The results demonstrate that alcohol seems to reduce top-down cognitive control. This control impairment was associated with changes in S-R mapping (reflected by a reduced parietal P3 amplitude), top-down response selection (reflected by modulations of lateralized readiness potentials), and (the evaluation of) response inhibition (reflected by modulations of the Nogo P3). In sharp contrast to this, automatic processing does not seem to be equally altered, as we found neither increases nor decreases in this domain. Most importantly, we also found that the interaction between control and automatisms might be less impaired by alcohol than control alone, which may help to overcome alcohol-induced response inhibition deficits. These "carryover" effects of control from one domain to the other could potentially prove beneficial in AUDs.

An abundance of seafood consumption studies presents new opportunities to evaluate effects on neurocognitive development.

The relationship between seafood eaten during pregnancy and neurocognition in offspring has been the subject of considerable scientific study for over 25 years. Evaluation of this question led two scientific advisory committees to the Dietary Guidelines for Americans (DGAC), the Food and Agriculture Organization of the United Nations with the World Health Organization (FAO/WHO), Health Canada, the European Food Safety Authority (EFSA), and the U.S. Food and Drug Administration (FDA) to conclude through 2014 that seafood consumed by pregnant women is likely to benefit the neurocognitive development of their children. The evidence they reviewed included between four and ten studies of seafood consumption during pregnancy that reported beneficial associations. In contrast there are now 29 seafood consumption studies available describing over 100,000 mothers-child pairs and 15 studies describing over 25,000 children who ate seafood. A systematic review of these studies using Nutrition Evaluation Systematic Review methodology is warranted to determine whether recent research corroborates, builds on, or significantly alters the previous conclusions. Studies that evaluate the integrated effects of seafood as a complete food more directly and completely evaluate impacts on neurocognition as compared to studies that evaluate individual nutritients or toxicological constituents in isolation. Here we address how the findings could add to our understanding of whether seafood consumed during pregnancy and early childhood affects neurocognition, including whether such effects are clinically meaningful, lasting, related to amounts consumed, and affected by any neurotoxicants that may be present, particularly mercury, which is present at varying levels in essentially all seafood. We provide the history, context and rationale for reexamining these questions in light of currently available data.

Relationships between seafood consumption during pregnancy and childhood and neurocognitive development: Two systematic reviews.

Abundant data are now available to evaluate relationships between seafood consumption in pregnancy and childhood and neurocognitive development. We conducted two systematic reviews utilizing methodologies detailed by the Dietary Guidelines for Americans Scientific Advisory Committee 2020-2025. After reviewing 44 publications on 106,237 mother-offspring pairs and 25,960 children, our technical expert committee developed two conclusion statements that included the following: "Moderate and consistent evidence indicates that consumption of a wide range of amounts and types of commercially available seafood during pregnancy is associated with improved neurocognitive development of offspring as compared to eating no seafood. Overall, benefits to neurocognitive development began at the lowest amounts of seafood consumed (∼4 oz/wk) and continued through the highest amounts, above 12 oz/wk, some range up to >100 oz/wk.", "This evidence does not meet the criteria for "strong evidence" only due to a paucity of randomized controlled trials that may not be ethical or feasible to conduct for pregnancy" and "Moderate and consistent evidence indicates that consumption of >4 oz/wk and likely >12 oz/wk of seafood during childhood has beneficial associations with neurocognitive outcomes." No net adverse neurocognitive outcomes were reported among offspring at the highest ranges of seafood intakes despite associated increases in mercury exposures. Data are insufficient for conclusive statements regarding lactation, optimal amounts, categories or specific species characterized by mercury content and neurocognitive development; although there is some evidence that dark/oily seafood may be more beneficial. Research was conducted in healthy women and children and is generalizable to US populations. Assessment of seafood as a whole food integrates inherently integrates any adverse effects from neurotoxicants, if any, and benefits to neurocognition from omega-3 fats, as well as other nutrients critical to optimal neurological development. Understanding of the effects of seafood consumption on neurocognition can have significant public health implications.

Increased frequency of mind wandering in healthy women using oral contraceptives.

Oral contraceptive (OC) is the most common type of contraceptive method used in industrialized countries. A recent epidemiological study showed that OC use was associated with the onset of depression in young women. Mind wandering, a cognitive process associated with spontaneous thoughts unrelated to the task at-hand, has previously been associated with depressive thinking. Consequently, mind wandering might be a precursor for cognitive vulnerability in individuals who are at-risk for mood disorders. The purpose of this study was to examine the frequency and nature of mind wandering in women using OC in comparison to two control groups: naturally cycling women and men. We recruited 71 participants (28 women currently using OC, 14 naturally cycling women in the luteal phase of their menstrual cycle and 29 men) aged between 18 and 35 years, and measured the frequency and nature (guilt/fear oriented and positive) of mind wandering using the short version of the Imaginal Process Inventory. In all analyses, we controlled for depressive symptoms to delineate the unique association between OC use and mind wandering. We also measured estradiol, progesterone and testosterone to confirm expected group differences in sex hormones concentrations. Results show that women using OC presented increased frequency of mind wandering when compared to naturally cycling women and men who did not differ between each other. The three groups did not differ in terms of the nature of mind wandering. These results show that OC use is associated with increased frequency of mind wandering and suggest that the association between OC use and dysphoric mood described in previous studies may be partially explained by the impact of OC use on cognitive processes underlying mind wandering.

Positive psychology in the investigation of psychedelics and entactogens: A critical review.

RATIONALE: We reviewed the concepts and empirical findings in studies with psychedelics and entactogens related to positive psychology - the study of healthy human functioning, well-being and eudaemonia. It is an unresolved question how beneficial effects of psychedelics and entactogens are related to the potential risks of these substances - particularly in non-clinical settings. METHODS: We searched in PubMed, PsychINFO and the Cochrane Library for controlled clinical and epidemiological studies which applied concepts from positive psychology. We included N = 77 eligible studies with 9876 participants published before November 1st, 2017: (1) quantitative studies (N = 54), (2) preliminary or exploratory studies and reviews not including meta-analyses (N = 17), and (3) studies evidencing primarily negative results (N = 6). RESULTS: Positive psychology concepts have been applied for measuring effects of clinical trials, recreational and ceremonial use of psychedelics and entactogens. Psychedelics and entactogens were shown to produce acute and long-term effects on mood, well-being, prosocial behaviours, empathy, cognitive flexibility, creativity, personality factors like openness, value orientations, nature-relatedness, spirituality, self-transcendence and mindfulness-related capabilities. CONCLUSIONS: There is preliminary evidence for beneficial effects of psychedelics and entactogens on measures of positive psychology in clinical and healthy populations, however their sustainability remains largely unresolved. The reported results must be considered preliminary due to methodological restrictions. Since longitudinal data on both positive and adverse effects of psychedelics are lacking, more rigorous and standardized measures from positive psychology should be applied in less biased populations with prospective longitudinal designs to carefully assess the benefit-risk-ratio. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.

Influence of Rhodiola rosea on the heat acclimation process in young healthy men.

The adaptogen Rhodiola rosea (RR) may mitigate stress responses and have beneficial effects on endurance capacity (EC) and mental performance. Heat acclimation (HA) improves EC in the heat, but the potential impact of RR on the HA process is unknown. Therefore, our intent was to determine if RR has a positive impact on HA. Twenty male subjects (age, 22.5 ± 3.0 years) completed 2 EC tests involving walking (6 km·h-1) until volitional exhaustion in a climate chamber (air temperature, 42 °C; relative humidity, 18%) before (H1) and after (H2) an 8-day HA period. One group (SHR; n = 10) ingested standardised extract SHR-5 of RR (a single daily dose of 432 mg), while a second group (PLC; n = 10) administered a placebo prior to each HA session. Efficacy of HA was evaluated on the basis of changes that occurred from H1 to H2 in the time to exhaustion (TTE), exercise heart rate (HR), core and skin temperatures (Tc, Tsk), stress hormones, ratings of perceived exertion (RPE) and fatigue (RPF), and thermal sensation (TS). HA significantly increased TTE (133.1 ± 44.1 min in H1; 233.4 ± 59.8 min in H2; p < 0.0001) and decreased (p < 0.0001) HR, Tc, Tsk, stress hormones as well as RPE, RPF, and TS. However, the magnitude of all these changes was similar (p > 0.05) in the SHR and PLC groups. These results suggest that the use of RR during HA has no beneficial performance, physiological, or perceptual effects in young healthy males.

Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study.

Rodent studies demonstrate that supplementing the maternal diet with choline during pregnancy produces life-long cognitive benefits for the offspring. In contrast, the two experimental studies examining cognitive effects of maternal choline supplementation in humans produced inconsistent results, perhaps because of poor participant adherence and/or uncontrolled variation in intake of choline or other nutrients. We examined the effects of maternal choline supplementation during pregnancy on infant cognition, with intake of choline and other nutrients tightly controlled. Women entering their third trimester were randomized to consume, until delivery, either 480 mg choline/d ( n = 13) or 930 mg choline/d ( n = 13). Infant information processing speed and visuospatial memory were tested at 4, 7, 10, and 13 mo of age ( n = 24). Mean reaction time averaged across the four ages was significantly faster for infants born to mothers in the 930 ( vs. 480) mg choline/d group. This result indicates that maternal consumption of approximately twice the recommended amount of choline during the last trimester improves infant information processing speed. Furthermore, for the 480-mg choline/d group, there was a significant linear effect of exposure duration (infants exposed longer showed faster reaction times), suggesting that even modest increases in maternal choline intake during pregnancy may produce cognitive benefits for offspring.-Caudill, M. A., Strupp, B. J., Muscalu, L., Nevins, J. E. H., Canfield, R. L. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study.

Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment.

BACKGROUND: Oxidative stress is one of the causative factors in the pathogenesis of neurodegenerative diseases including mild cognitive impairment (MCI) and dementia. We previously reported that molecular hydrogen (H2) acts as a therapeutic and preventive antioxidant. OBJECTIVE: We assess the effects of drinking H2-water (water infused with H2) on oxidative stress model mice and subjects with MCI. METHODS: Transgenic mice expressing a dominant-negative form of aldehyde dehydrogenase 2 were used as a dementia model. The mice with enhanced oxidative stress were allowed to drink H2-water. For a randomized double-blind placebo-controlled clinical study, 73 subjects with MCI drank ~300 mL of H2-water (H2-group) or placebo water (control group) per day, and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores were determined after 1 year. RESULTS: In mice, drinking H2-water decreased oxidative stress markers and suppressed the decline of memory impairment and neurodegeneration. Moreover, the mean lifespan in the H2-water group was longer than that of the control group. In MCI subjects, although there was no significant difference between the H2- and control groups in ADAS-cog score after 1 year, carriers of the apolipoprotein E4 (APOE4) genotype in the H2-group were improved significantly on total ADAS-cog score and word recall task score (one of the sub-scores in the ADAS-cog score). CONCLUSION: H2-water may have a potential for suppressing dementia in an oxidative stress model and in the APOE4 carriers with MCI.

[Lacosamide (vimpat). Prospects for clinical application]. / Lakosamid (vimpat). Perspektivy klinicheskogo primeneniia.

This article presents the review of the most significant studies of the efficacy and tolerability of lacosamide (LCM) in treatment of patients with focal epilepsy. The review includes the results of the main studies which preceded the official approval of LCM use in mono- and polytherapy. Results on the efficacy of LCM in long-term use and treatment retention in clinical practice, most effective LCM combinations, tolerability, an influence on cognitive and mental functions, advantages in treatment of elderly patients are presented. Characteristics of LCM in comparison with other sodium channel-blocking antiepileptic drugs and selection priorities are shown. The authors assess perspectives of further use of LCM in clinical practice.

Breakdown of local information processing may underlie isoflurane anesthesia effects.

The disruption of coupling between brain areas has been suggested as the mechanism underlying loss of consciousness in anesthesia. This hypothesis has been tested previously by measuring the information transfer between brain areas, and by taking reduced information transfer as a proxy for decoupling. Yet, information transfer is a function of the amount of information available in the information source-such that transfer decreases even for unchanged coupling when less source information is available. Therefore, we reconsidered past interpretations of reduced information transfer as a sign of decoupling, and asked whether impaired local information processing leads to a loss of information transfer. An important prediction of this alternative hypothesis is that changes in locally available information (signal entropy) should be at least as pronounced as changes in information transfer. We tested this prediction by recording local field potentials in two ferrets after administration of isoflurane in concentrations of 0.0%, 0.5%, and 1.0%. We found strong decreases in the source entropy under isoflurane in area V1 and the prefrontal cortex (PFC)-as predicted by our alternative hypothesis. The decrease in source entropy was stronger in PFC compared to V1. Information transfer between V1 and PFC was reduced bidirectionally, but with a stronger decrease from PFC to V1. This links the stronger decrease in information transfer to the stronger decrease in source entropy-suggesting reduced source entropy reduces information transfer. This conclusion fits the observation that the synaptic targets of isoflurane are located in local cortical circuits rather than on the synapses formed by interareal axonal projections. Thus, changes in information transfer under isoflurane seem to be a consequence of changes in local processing more than of decoupling between brain areas. We suggest that source entropy changes must be considered whenever interpreting changes in information transfer as decoupling.

Subjective and physiological effects, and expired carbon monoxide concentrations in frequent and occasional cannabis smokers following smoked, vaporized, and oral cannabis administration.

BACKGROUND: Although smoking is the most common cannabis administration route, vaporization and consumption of cannabis edibles are common. Few studies directly compare cannabis' subjective and physiological effects following multiple administration routes. METHODS: Subjective and physiological effects, and expired carbon monoxide (CO) were evaluated in frequent and occasional cannabis users following placebo (0.001% Δ9-tetrahydrocannabinol [THC]), smoked, vaporized, and oral cannabis (6.9% THC, ∼54mg). RESULTS: Participants' subjective ratings were significantly elevated compared to placebo after smoking and vaporization, while only occasional smokers' ratings were significantly elevated compared to placebo after oral dosing. Frequent smokers' maximum ratings were significantly different between inhaled and oral routes, while no differences in occasional smokers' maximum ratings between active routes were observed. Additionally, heart rate increases above baseline 0.5h after smoking (mean 12.2bpm) and vaporization (10.7bpm), and at 1.5h (13.0bpm) and 3h (10.2bpm) after oral dosing were significantly greater than changes after placebo, with no differences between frequent and occasional smokers. Finally, smoking produced significantly increased expired CO concentrations 0.25-6h post-dose compared to vaporization. CONCLUSIONS: All participants had significant elevations in subjective effects after smoking and vaporization, but only occasional smokers after oral cannabis, indicating partial tolerance to subjective effects with frequent exposure. There were no differences in occasional smokers' maximum subjective ratings across the three active administration routes. Vaporized cannabis is an attractive alternative for medicinal administrations over smoking or oral routes; effects occur quickly and doses can be titrated with minimal CO exposure. These results have strong implications for safety and abuse liability assessments.