Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts.

BACKGROUND: Single doses of exogenous ketone salts (KS) transiently increase circulating beta-hydroxybutyrate (BHB) (∼1 mM; 1-2 h) regardless of starting levels of ketosis; however, no studies have explored how sustained use of KS influences measures of ketonemia and glycemia. OBJECTIVES: To determine the response to a hypocaloric, well-formulated ketogenic diet (KD), with and without the inclusion of two daily racemic KS doses (6 g R-BHB + 6 g S-BHB per serving) on 1) daily fasting capillary R-BHB and glucose (R-BHB/GLUfast), 2) bi-weekly 13 h diurnal BHB and glucose (R-BHB/GLUdiur), 3) three-hours post-KS ingestion kinetics (R-BHBKS), and 4) bi-weekly fasting plasma enantiomer-specific BHB (R/S-BHBplasma). METHODS: Non-diabetic adults with overweight and obesity were randomized to receive a precisely measured hypocaloric KD (∼75 %en of maintenance) for six weeks, supplemented twice-daily with KS or placebo (PL). A non-randomized comparison group was provided an isonitrogenous/isoenergetic low-fat diet (LFD). All meals were provided to subjects. Capillary blood was collected daily to measure R-BHB/GLUfast and hourly for R-BHB/GLUdiur. Plasma was collected to measure R/S-BHBplasma, insulin, fasting glucose, and insulin resistance (HOMA-IR). Total AUC was calculated using the trapezoidal method. RESULTS: Mean R-BHBfast increased significantly during KD + PL (1.0 mM BHB), an effect enhanced 26% during KD + KS. GLUfast AUC was -6% lower during KD + KS versus LFD. Mean R-BHBdiur increased 40% in KD + KS versus KD + PL, whereas GLUdiur decreased 13% during both KDs versus LFD. R-BHBKS peaked (Δ: ∼1 mM) 1 h after the morning KS dose, but not following the afternoon dose. Both R/S-BHBplasma increased during KD independent of KS inclusion. R-BHBplasma was 50-times greater compared to S-BHBplasma, and the KS augmented S-BHBplasma 50% more than PL. Fasting insulin and HOMA-IR decreased after 14 days independent of diet. CONCLUSIONS: A hypocaloric KD was effective at reducing diurnal glucose compared to a LFD independent of weight loss, but twice-daily racemic KS ingestion during KD augmented ketonemia, both as R- and S-BHB, and decreased mean fasting glucose beyond a KD alone. The hypoglycemic effects of KD in combination with exogenous ketones merit further investigation.

The Royal College of Psychiatrists' Leadership and Management Fellow Scheme.

The Royal College of Psychiatrists' Leadership and Management Fellow Scheme aims to develop and support a new cohort of leaders within psychiatry. This article provides an introduction to the scheme, which is accessible to all higher trainees with the support of their host organisation. We explore its development, structure and how it is evolving to provide a strong platform for achieving the College's ambition to benefit patient care by embedding a culture of medical leadership within mental health services.

Detection of Autism Spectrum Disorder in Children Using Machine Learning Techniques.

Autism Spectrum Disorder (ASD) is a neurological disorder which might have a lifelong impact on the language learning, speech, cognitive, and social skills of an individual. Its symptoms usually show up in the developmental stages, i.e., within the first two years after birth, and it impacts around 1% of the population globally [https://www.autism-society.org/whatis/facts-and-statistics/. Accessed 25 Dec 2019]. ASD is mainly caused by genetics or by environmental factors; however, its conditions can be improved by detecting and treating it at earlier stages. In the current times, clinical standardized tests are the only methods which are being used, to diagnose ASD. This not only requires prolonged diagnostic time but also faces a steep increase in medical costs. To improve the precision and time required for diagnosis, machine learning techniques are being used to complement the conventional methods. We have applied models such as Support Vector Machines (SVM), Random Forest Classifier (RFC), Naïve Bayes (NB), Logistic Regression (LR), and KNN to our dataset and constructed predictive models based on the outcome. The main objective of our paper is to thus determine if the child is susceptible to ASD in its nascent stages, which would help streamline the diagnosis process. Based on our results, Logistic Regression gives the highest accuracy for our selected dataset.

The Efficacy of MDMA (3,4-Methylenedioxymethamphetamine) for Post-traumatic Stress Disorder in Humans: A Systematic Review and Meta-Analysis.

Background: 3,4-methylenedioxymethamphetamine (MDMA), known recreationally as "Molly" or "Ecstasy", is a triple monoamine reuptake inhibitor. MDMA specifically acts as a weak 5-HT1 and 5-HT2 receptor agonist, targeting 5-HT2A, 5-HT2B, and 5-HT2C receptors. Its potential use for therapeutic purposes with these pharmacological profiles remains a controversial subject. Studies have shown the potential benefits in clinical trials for post-traumatic stress disorder (PTSD). A larger amount of data has been provided for the push in support of MDMA-assisted psychotherapy in these patients.  Objective: The aim of this article is to compute a meta-analysis and conduct a systematic review of the effects of MDMA on PTSD, discussing the potential benefits and adverse events relative to dosing and stability of treatment. Methods: Articles were collected and analyzed for systematic review: 16 articles were included in the systematic review that met the criteria for the use of MDMA in the treatment of PTSD as well as assessing the safety and efficacy of the drug in human participants. Ten studies were used for the meta-analysis, with a cumulative sample size of 168 patients. The significance of the findings on dosing and efficacy of MDMA in healthy human participants was quantified based on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD symptom scores. Results: The disorders for which MDMA demonstrated a net positive or net negative effect on symptoms are presented separately. Adverse events in patients across all disease classes are presented. The therapeutic index for patients who demonstrated a benefit is also presented. An odds ratio for beneficial and adverse events is used to determine treatment-resistant patients who may benefit from clinical trials of MDMA. Discussion: Findings show promising evidence for the potential therapeutic use of MDMA alongside psychotherapy in the treatment of PTSD. The pharmacological profile of MDMA may provide direction for future drug developments to treat patients with treatment-resistant psychiatric disorders.

A Pre-Workout Supplement of Ketone Salts, Caffeine, and Amino Acids Improves High-Intensity Exercise Performance in Keto-Naïve and Keto-Adapted Individuals.

Background: Acute ingestion of ketone supplements alters metabolism and potentially exercise performance. No studies to date have evaluated the impact of co-ingestion of ketone salts with caffeine and amino acids on high intensity exercise performance, and no data exists in Keto-Adapted individuals.Methods: We tested the performance and metabolic effects of a pre-workout supplement containing beta-hydroxybutyrate (BHB) salts, caffeine, and amino acids (KCA) in recreationally-active adults habitually consuming a mixed diet (Keto-Naïve; n = 12) or a ketogenic diet (Keto-Adapted; n = 12). In a randomized and balanced manner, subjects consumed either the KCA consisting of ∼7 g BHB (72% R-BHB and 28% S-BHB) with ∼100 mg of caffeine, and amino acids (leucine and taurine) or Water (control condition) 15 minutes prior to performing a staged cycle ergometer time to exhaustion test followed immediately by a 30 second Wingate test.Results: Circulating total BHB concentrations increased rapidly after KCA ingestion in KN (154 to 732 µM) and KA (848 to 1,973 µM) subjects and stayed elevated throughout recovery in both groups. Plasma S-BHB increased >20-fold 15 minutes after KCA ingestion in both groups and remained elevated throughout recovery. Compared to Water, KCA ingestion increased time to exhaustion 8.3% in Keto-Naïve and 9.8% in Keto-Adapted subjects (P < 0.001). There was no difference in power output during the Wingate test between trials. Peak lactate immediately after exercise was higher after KCA (∼14.9 vs 12.7 mM).Conclusion: These results indicate that pre-exercise ingestion of a moderate dose of R- and S-BHB salts combined with caffeine, leucine and taurine improves high-intensity exercise performance to a similar extent in both Keto-Adapted and Keto-Naïve individuals.

Prevalence, risk factors, circumstances for falls and level of functional independence among geriatric population - A descriptive study.

BACKGROUND: Falls is one of the common problems faced by elderly population and in preventing falls in India, research has largely focused on identification and management of risk factors, but the circumstances of the fall and its associated factors are sparsely researched. OBJECTIVES: The primary objective is to find the prevalence of fall, investigate risk factors, and its circumstances for falls and level of functional independence in elderly population. The secondary objective is to find out fear of fall (FOF) and its association of demographic factors on elderly population. METHODS: This was a cross-sectional study; 2049 elderly population of 60 years and above were recruited by one-stage cluster sampling technique within Mumbai, Panvel, and Thane cities, Maharashtra. Data were collected using a questionnaire, Fall Efficacy Scale-International, Barthel Index, and Kuppuswamy Scale. Obtained responses were analyzed using SPSS software; descriptive statistics and Chi-square test were applied. RESULTS: The prevalence of falls in this study found as 24.98%. Demographic factors such as age group, education, marital status, and socio-economic status had demonstrated a significant association with older adults (P < 0.05); 44.92% of falls occurred in the morning, the majority of falls (65.43%) occurred indoors, 56.45% of the fallers reported to had slips, and 60.55% of the fallers had sustained injuries. From the total participants, 34.70% of the fallers reported FOF, 23.67% of the fallers expressed reduced functional activities, and 18.06% of the fallers demonstrated affection in activities of daily living. CONCLUSION: This study reveals fall as a significant health problem and provides insight into the influencing risk factors for falls among older adults.

Synthesis, structural characterisation and stereochemical investigation of chiral sulfur-functionalised N-heterocyclic carbene complexes of palladium and platinum.

Palladium and platinum complexes containing a sulfur-functionalised N-heterocyclic carbene (S-NHC) chelate ligand have been synthesised. The absolute conformations of these novel organometallic S-NHC chelates were determined by X-ray structural analyses and solution-phase 2D (1)H-(1)H ROESY NMR spectroscopy. The structural studies revealed that the phenyl substituents on the stereogenic carbon atoms invariably take up the axial positions on the Pd-C-S coordination plane to afford a skewed five-membered ring structure. All of the chiral complexes are structurally rigid and stereochemically locked in a chiral ring conformation that is either (Rs ,S,R)-λ or (Ss ,R,R)-δ in both the solid state and solution.

Simultaneous quantitative determination of metoprolol, atorvastatin and ramipril in capsules by a validated stability-indicating RP-UPLC method.

A simple ultra performance liquid chromatographic (UPLC) method has been developed for the simultaneous estimation of Metoprolol (MT), Atorvastatin (AT) and Ramipril (RM) from capsule dosage form. The method was developed using Zorbax XDB-C18 (4.6 mm à 50 mm, 1.8 Îm) column with a mobile phase consisting of 0.06% ortho phosphoric acid in Milli Q water having an ion pair reagent, 0.0045 M Sodium lauryl sulphate as buffer, at ratio of buffer: Acetonitrile (50:50 v/v), at 55ÂC column temperature with a flow rate of 1.0 ml/min. Detection was carried out with ultra-violet detection at 210 nm for RM, MT and AT respectively. The retention times were about 1.3, 2.1 and 2.6 min for MT, AT and RM respectively, the method was validated for linearity, accuracy, precision, specificity, robustness and ruggedness. The % mean recoveries are 101.9, 102.1 and 101.4 for MT, AT and RM respectively. The method was found to be rugged and robust and can be successfully used to determine the three drugs and its combinations.

Controllable synthesis of P-chiral 1,2- and 1,3-diphosphines via asymmetric Diels-Alder reactions involving functionalized allylic phosphines as dienophiles.

Optically pure P-chiral 1,2- and 1,3-diphosphines were synthesized chemoselectively and stereoselectively from the chiral organopalladium complex promoted asymmetric Diels-Alder reaction between 3,4-dimethyl-1-phenylphosphole (DMPP) and cis- and trans-ester substituted allylic phosphines.