The thermodynamics of metabolism, cardiovascular performance and exercise, in health and diabetes: The objective of clinical markers

Extensive experience in UK National Health Service metabolic syndrome/type 2 diabetes clinics highlights the need for convenient clinical marker(s) which can be readily used to indicate the success or otherwise of alternative therapies. In this paper we study the metabolic context of the healthy and diseased states, which points to the haemodynamics being a possible key in identifying candidate markers. Human metabolism relates to two elemental thermodynamic systems, the individual cell and the human body in its entirety. The fundamental laws of thermodynamics apply to humans, animals, and their individual cells for both healthy and diseased conditions. as they are to classic heat engines. In compliance with the second law enhanced levels of heat are generated under exercise, heat itself being another factor modulating the cardiovascular response to physical exercise. Nutrients and oxygen uptake occurs via the digestive system and lungs, respectively, leading to ATP production by the established metabolic pathways: this is controlled by insulin. These are then delivered to the cells via the haemodynamic system to satisfy local metabolic need. The supply and demand of oxygen are finely regulated, in part, via oxygen-dependent release of ATP from the circulating erythrocytes. Energy supply and demand are regulated to sustain muscle activity resulting in the body’s output of measurable thermodynamic work—i.e. exercise. Recently a dynamic pathway model allowing quantification of ATP release from the erythrocytes and its contribution to oxygen supply regulation has been published. However, metabolic uptake is well known to be greatly affected by disease such as the highly prevalent diabetes type 2 with insulin resistance and beta cell dysfunction having mechanistic roles. In 2010, over 25% of residents above 65 in the USA had diabetes 2. The complexity of the metabolic pathways means that monitoring of patient-specific treatment would be beneficial from a diabetic marker which may be haemodynamic-related and traceable via the local fluid dynamics

Combined mirror visual and auditory feedback therapy for upper limb phantom pain: a case report

<p>Abstract</p> <p>Introduction</p> <p>Phantom limb sensation and phantom limb pain is a very common issue after amputations. In recent years there has been accumulating data implicating 'mirror visual feedback' or 'mirror therapy' as helpful in the treatment of phantom limb sensation and phantom limb pain.</p> <p>Case presentation</p> <p>We present the case of a 24-year-old Caucasian man, a left upper limb amputee, treated with mirror visual feedback combined with auditory feedback with improved pain relief.</p> <p>Conclusion</p> <p>This case may suggest that auditory feedback might enhance the effectiveness of mirror visual feedback and serve as a valuable addition to the complex multi-sensory processing of body perception in patients who are amputees.</p

Quantum thermodynamics at critical points during melting and solidification processes

We systematically explore and show the existence of finite-temperature continuous quantum phase transition (CTQPT) at a critical point, namely, during solidification or melting such that the first-order thermal phase transition is a special case within CTQPT. Infact, CTQPT is related to chemical reaction where quantum fluctuation (due to wavefunction transformation) is caused by thermal energy and it can occur maximally for temperatures much higher than zero Kelvin. To extract the quantity related to CTQPT, we use the ionization energy theory and the energy-level spacing renormalization group method to derive the energy-level spacing entropy, renormalized Bose-Einstein distribution and the time-dependent specific heat capacity. This work unambiguously shows that the quantum phase transition applies for any finite temperatures.Comment: To be published in Indian Journal of Physics (Kolkata

The need for a marker predicting benefit following cardiovascular disease risk reduction treatment

Developing a robust method to study characteristics of vascular flow using ultrasound may be useful to assess endothelial function and vasodilatation. There are four stages in this proposal. 1.The first stage is to standardise and validate the methodology to enable computational risk flow data and other flow characteristics to be used clinically. (Current Study). Further development of fluid modelling methods will enable particulate haemodynamics to be investigated, and incorporate detailed endothelial structure together with cellular pathways. 2. This should be followed up by studies in different patient groups investigating the association between the derived values and estimated risk (using other methods such as Framingham risk score). 3. Then, associated with underlying cardiovascular risk, prospective studies would be made to establish whether computational flow dynamic data can predict outcome. If successful it could prove to be a very useful marker of benefit following treatment in a clinical setting

Klinefelters Syndrome: Change in T-Scores with Testosterone, Bisphosphonate, and Vitamin D Treatment over 6 Years

Background: Klinefelter's syndrome (KS) is characterized by extra X chromosomes and features of primary hypogonadism including osteopenia and osteoporosis. Testosterone therapy (TTh) is widely used to treat men with KS and low serum testosterone/hypogonadal symptoms, though studies on its efficacy in improving bone density show varied outcomes. Materials and Methods: We studied the effects of TTh, bisphosphonates, and vitamin D/calcium in 38 men with KS and low testosterone, hypogonadal symptoms, and T-scores consistent with osteoporosis. Our aim was to investigate at the end of follow-up (median: 87 months, range: 27-147 months), associations between age, baseline total testosterone, and T-scores, and change in T-scores after treatment. Results: At final assessment, all men had T-score values outside the osteoporotic range (-1.1 standard deviation [SD],-1.8 SD). Baseline age but not median baseline testosterone appeared associated with change in T-score and T-score at final assessment. All men had dual-energy X-ray absorptiometry every 6 months and demonstrated continued improvement in T-scores after 3 months and up to 72 months. Baseline age and T-scores (stratified by median) were associated with change in T-score at final assessment. Compared with men ≥51 years, those aged <51 years showed significantly greater improvement in T-scores between 6 and 30 months. Men with worse T-score values (<3.7 SD) showed significantly greater improvement at every time point up to 36 months. Our results indicate that TTh, bisphosphonates, and vitamin D/calcium improve osteoporosis although there is a need to better understand the effects of the individual therapies, age, and baseline T-score on treatment efficacy

Age and the Residual Risk of Cardiovascular Disease following Low Density Lipoprotein-Cholesterol Exposure

Copyright © 2023 by the authors. We believe that there is sufficient evidence from basic science, longitudinal cohort studies and randomised controlled trials which validates the low-density lipoprotein cholesterol (LDL-C) or lipid hypothesis. It is important that we can communicate details of the cardiovascular disease (CVD) risk reduction that the average patient could expect depending on the scale of LDL-C decrease following lipid lowering therapy. It is also essential that residual risk (ResR) of CVD be highlighted. To achieve this aim by using existing trial evidence, we developed mathematical models initially for relative risk reduction (RRR) and absolute risk (AR) reduction and then showed that despite optimising LDL-C levels, a considerable degree of ResR remains that is dependent on AR. Age is significantly associated with AR (odds ratio: 1.02, 95% confidence intervals: 1.01–1.04) as was previously demonstrated by analysing the Whickham study cohort using a logistic regression model (age remaining significant even when all the other significant risk factors such as sex, smoking, systolic blood pressure, diabetes and family history were included in the regression model). A discussion of a paper by Ference et al. provided detailed evidence of the relationship between age and AR, based on lifetime LDL-C exposure. Finally, we discussed non-traditional CVD risk factors that may contribute to ResR based on randomised controlled trials investigating drugs improving inflammation, thrombosis, metabolic and endothelial status.This work received no external funding

Watch your step!: a frustrated total internal reflection approach to forensic footwear imaging

Forensic image retrieval and processing are vital tools in the fight against crime e.g. during fingerprint capture. However, despite recent advances in machine vision technology and image processing techniques (and contrary to the claims of popular fiction) forensic image retrieval is still widely being performed using outdated practices involving inkpads and paper. Ongoing changes in government policy, increasing crime rates and the reduction of forensic service budgets increasingly require that evidence be gathered and processed more rapidly and efficiently. A consequence of this is that new, low-cost imaging technologies are required to simultaneously increase the quality and throughput of the processing of evidence. This is particularly true in the burgeoning field of forensic footwear analysis, where images of shoe prints are being used to link individuals to crime scenes. Here we describe one such approach based upon frustrated total internal reflection imaging that can be used to acquire images of regions where shoes contact rigid surfaces

Testosterone replacement therapy: association with mortality in high-risk patient subgroups

Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.[Correction added on 12 January 2024, after first online publication: Figure 1 updated in this version.]Copyright © 2023 The Authors. Objectives: We describe studies determining the association between testosterone therapy (TTh) and mortality. Materials & methods: We used a registry database of 737 men with adult-onset testosterone deficiency defined as presenting with low serum total testosterone (TT) levels ≤12.1 nmol/L and associated symptoms over a near 10-year follow-up. We compared associations between testosterone undecanoate (TU), cardio-metabolic risk factors and mortality using non-parametric statistics followed by separate Cox regression models to determine if any association between TU and morality was independent of age and cardio-metabolic risk factors. Finally, the association between TU and mortality was studied in men stratified by cardio-metabolic risk. Results: During a median follow-up interquartile range (IQR) of 114 (84–132) months, 94 of the 737 men died. TU (ref: non-treatment) was associated with mortality; hazard ratio = 0.23, 95% confidence intervals = 0.14–0.40. Cox's regression models showed the above association to be independent of baseline age, waist circumference, hemoglobin A1c, lipids, blood pressure, smoking, and type 2 diabetes. These variables remained associated with mortality. We finally stratified the men by the high-risk baseline variables and established that the association between mortality and TU was only evident in men at higher risk. A possible explanation could lie with the “law of initial value,” where greater improvements are evident following treatment in patients with worse baseline values. Conclusions: This study with long follow-up confirms that TTh is associated with lower mortality in men with adult-onset TD. This association was evident only in men with greater cardio-metabolic risk factors who demonstrated greater benefit.North Staffordshire Medical Institute. Grant Number: PID-200078

Testosterone Therapy in Adult-Onset Testosterone Deficiency: Hematocrit and Hemoglobin Changes

Objective: Hematocrit (HCT)/hemoglobin (Hb) ratio in (%/g/dL) is around 3, with high fidelity between measured and derived Hb (applying the conversion using HCT) in various pathologies. We examined changes in HCT and Hb values and HCT/Hb, compared with baseline, in men with adult-onset testosterone deficiency (TD) given testosterone therapy (TTh). Materials and Methods: Data were analyzed from an observational, prospective registry study at various time points in 353 men with adult-onset TD receiving testosterone undecanoate (median follow-up: 105 months). After establishing baseline HCT/Hb, we compared (cf. baseline) changes in HCT, Hb, and HCT/Hb at 12, 48, 72, and 96 months. Regression analyses determined predictors of HCT and Hb change. Results: TTh was associated with ( p < 0.0001) increases in median HCT and Hb; 44% to 49% and 14.5 to 14.9 g/dL at final assessment, respectively. Regression analyses showed that HCT change was associated with baseline HCT and testosterone levels, while Hb change was associated with baseline Hb, HCT, and testosterone levels. In the total cohort and subgroups, HCT/Hb increased significantly at all time points ( p < 0.0001, cf. baseline) with over 90% of men demonstrating increases. Linear regression showed that the ratio of HCT change/Hb change (i.e., difference between HCT at the various time points and baseline value/difference between Hb at the various time points and baseline value), following TTh at each time point was higher than the baseline HCT/Hb ratio. Conclusion: HCT increase was greater than we anticipated from the established HCT/Hb of 3. We speculate that increased erythrocyte life span with associated higher Hb loss via vesiculation could account for our observation. This could have a bearing when using HbA1c as an indicator in men with adult-onset TD on TTh