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Advances in Genetics 2024Modern humans evolved in Africa some 200,000 years ago, and since then, human populations have expanded and diversified to occupy a broad range of habitats and use... (Review)
Review
Modern humans evolved in Africa some 200,000 years ago, and since then, human populations have expanded and diversified to occupy a broad range of habitats and use different subsistence modes. This has resulted in different adaptations, such as differential responses to diseases and different abilities to digest or tolerate certain foods. The shift from a subsistence strategy based on hunting and gathering during the Palaeolithic to a lifestyle based on the consumption of domesticated animals and plants in the Neolithic can be considered one of the most important dietary transitions of Homo sapiens. In this text, we review four examples of gene-culture coevolution: (i) the persistence of the enzyme lactase after weaning, which allows the digestion of milk in adulthood, related to the emergence of dairy farming during the Neolithic; (ii) the population differences in alcohol susceptibility, in particular the ethanol intolerance of Asian populations due to the increased accumulation of the toxic acetaldehyde, related to the spread of rice domestication; (iii) the maintenance of gluten intolerance (celiac disease) with the subsequent reduced fitness of its sufferers, related to the emergence of agriculture and (iv) the considerable variation in the biosynthetic pathway of long-chain polyunsaturated fatty acids in native populations with extreme diets.
Topics: Humans; Diet; Biological Evolution; Animals; Cultural Evolution; Adaptation, Physiological; Lactase
PubMed: 38908898
DOI: 10.1016/bs.adgen.2024.01.004 -
Nature Aging Jan 2024Skeletal muscle plays a central role in the regulation of systemic metabolism during lifespan. With aging, this function is perturbed, initiating multiple chronic...
Skeletal muscle plays a central role in the regulation of systemic metabolism during lifespan. With aging, this function is perturbed, initiating multiple chronic diseases. Our knowledge of mechanisms responsible for this decline is limited. Glycerophosphocholine phosphodiesterase 1 (Gpcpd1) is a highly abundant muscle enzyme that hydrolyzes glycerophosphocholine (GPC). The physiological functions of Gpcpd1 remain largely unknown. Here we show, in mice, that the Gpcpd1-GPC metabolic pathway is perturbed in aged muscles. Further, muscle-specific, but not liver- or fat-specific, inactivation of Gpcpd1 resulted in severely impaired glucose metabolism. Western-type diets markedly worsened this condition. Mechanistically, Gpcpd1 muscle deficiency resulted in accumulation of GPC, causing an 'aged-like' transcriptomic signature and impaired insulin signaling in young Gpcpd1-deficient muscles. Finally, we report that the muscle GPC levels are markedly altered in both aged humans and patients with type 2 diabetes, displaying a high positive correlation between GPC levels and chronological age. Our findings reveal that the muscle GPCPD1-GPC metabolic pathway has an important role in the regulation of glucose homeostasis and that it is impaired during aging, which may contribute to glucose intolerance in aging.
Topics: Aged; Animals; Humans; Mice; Aging; Diabetes Mellitus, Type 2; Glucose; Metabolic Networks and Pathways; Muscle, Skeletal; Phospholipases; Glycerylphosphorylcholine
PubMed: 38238601
DOI: 10.1038/s43587-023-00551-6 -
Journal of Health Psychology Jul 2023The COVID-19 pandemic continues to impact global psychological wellbeing. To investigate the sustained impact of COVID-19 on wellbeing, the current study longitudinally...
The COVID-19 pandemic continues to impact global psychological wellbeing. To investigate the sustained impact of COVID-19 on wellbeing, the current study longitudinally assessed fear of COVID-19, anxiety, depression, intolerance of uncertainty, worry, sleep quality, loneliness and alcohol use during the pandemic in the United Kingdom. Timepoint 1 (T1; = 445) took place in February 2021 following the highest number of pandemic-related deaths in the UK. Timepoint 2 (T2, = 198) took place in June 2021 when pandemic-related deaths had declined considerably, and many had been vaccinated. At T1, COVID-19 fear predicted elevated levels of anxiety, depression, intolerance of uncertainty, worry, sleep quality and loneliness. At T2, we observed that levels of COVID-19 fear, depression, loneliness and sleep quality decreased. However, COVID-19 fear continued to predict elevated intolerance of uncertainty, worry and impaired sleep quality. These findings demonstrate the longitudinal impact of COVID-19 fear on psychological wellbeing.
Topics: Humans; Pandemics; COVID-19; Fear; Anxiety; United Kingdom; Depression
PubMed: 36397647
DOI: 10.1177/13591053221134848 -
Expert Review of Clinical Immunology 2023
Topics: Humans; Anaphylaxis; Food Hypersensitivity; Allergens; Epinephrine
PubMed: 37753864
DOI: 10.1080/1744666X.2023.2265069 -
Drug and Alcohol Dependence Jul 2023Sleep disturbance, clinically significant pain, and depressive symptoms commonly occur together among individuals with substance use disorders. The purposes of the...
AIM
Sleep disturbance, clinically significant pain, and depressive symptoms commonly occur together among individuals with substance use disorders. The purposes of the present study were to 1) identify subgroups of individuals with heterogenous patterns of pain, sleep disturbance, and depressive symptoms, and 2) identify demographic and clinical correlates of profile membership.
MATERIAL AND METHODS
The present study assessed a sample (N = 8621) of individuals seeking residential substance use treatment in 2020 and 2021 in the United States. We examined whether unique sub-groups could be identified based on patterns of sleep disturbance, pain impact, and depressive symptoms during the first four weeks of treatment, using longitudinal latent profile analysis. Next, we explored demographic, substance use, and clinical correlates (i.e., distress intolerance) of profile membership, as well as whether profile membership was associated with treatment attrition.
RESULTS
The identified classes were: 1) Low sleep disturbance, pain impact, and depressive symptoms, 2) High pain, remitting depressive symptoms, and mild sleep disturbance, 3) High depressive symptoms, low pain, and remitting sleep disturbance, and 4) High sleep disturbance, pain impact, and depressive symptoms. Individuals with high pain, depressive symptoms, and sleep disturbance were more likely to be older, use opioids as their primary substance, have high distress intolerance, and discontinue treatment.
CONCLUSION
Results highlight the importance of comprehensive care and management of physical health conditions, particularly among older adults. Further, results highlight that distress intolerance may be a modifiable risk factor for co-occurring sleep disturbance, pain impact, and depressive symptoms.
Topics: Humans; Aged; Depression; Pain; Risk Factors; Sleep Wake Disorders; Sleep
PubMed: 37182354
DOI: 10.1016/j.drugalcdep.2023.109903 -
Substance Use & Misuse 2024: Existing work proposes that people with higher social anxiety symptoms and sociability alcohol expectancies believe alcohol can lower their anxiety. However, studies...
: Existing work proposes that people with higher social anxiety symptoms and sociability alcohol expectancies believe alcohol can lower their anxiety. However, studies have primarily analyzed retrospective reports, not anticipatory motives. Since predictions of future emotion (i.e., affective forecasts) strongly influence behavior, it is critical to understand how people predict alcohol will influence their anxiety. Additionally, intolerance of uncertainty (IU) is related to the use of alcohol as a coping tool, but there is a dearth of work testing whether IU influences alcohol-related forecasts. : Utilizing a novel affective forecasting task, we tested the prediction that social anxiety symptoms, sociability alcohol expectancies, and IU would relate to predictions about alcohol use. In an initial study and preregistered replication, participants imagined themselves in stressful social scenarios and forecasted how anxious they would feel when drinking and when sober. In the replication, participants also forecasted whether they would drink in the imagined scenarios. : Contrary to hypotheses, social anxiety symptoms and IU did not significantly predict higher forecasted anxiety across studies, nor did they predict forecasted drinking. Exploratory analyses showed that participants with higher sociability alcohol expectancies forecasted being more likely to drink, and forecasted feeling less anxious when drinking (versus being sober). Even after statistically controlling for social anxiety, the effect of sociability expectancies remained significant in predicting forecasted anxiety and forecasted drinking. : Clinicians could consider specifically targeting sociability expectancies for alcohol use difficulties, and future research should continue utilizing affective forecasting paradigms to test links between social anxiety, alcohol expectancies, and alcohol-use problems.
Topics: Humans; Alcohol Drinking; Retrospective Studies; Anxiety; Social Behavior; Anxiety Disorders; Motivation
PubMed: 38233360
DOI: 10.1080/10826084.2024.2302133 -
ANZ Journal of Surgery Nov 2023The frequency of oxycodone adverse reactions, subsequent opioid prescription, effect on pain and patient care in general surgery patients are not well known. This study...
BACKGROUND
The frequency of oxycodone adverse reactions, subsequent opioid prescription, effect on pain and patient care in general surgery patients are not well known. This study aimed to determine prevalence of documented oxycodone allergy and intolerances (independent variables) in a general surgical cohort, and association with prescribing other analgesics (particularly opioids), subjective pain scores, and length of hospital stay (dependent variables).
METHODS
This retrospective cohort study included general surgery patients from two South Australian hospitals between April 2020 and March 2022. Multivariable logistic regression evaluated associations between previous oxycodone allergies and intolerances, prescription records, subjective pain scores, and length of hospital stay.
RESULTS
Of 12 846 patients, 216 (1.7%) had oxycodone allergies, and 84 (0.7%) oxycodone intolerances. The 216 oxycodone allergy patients had lower odds of receiving oxycodone (OR 0.17, P < 0.001), higher odds of tramadol (OR 3.01, P < 0.001) and tapentadol (OR 2.87, P = 0.001), but 91 (42.3%) still received oxycodone and 19 (8.8%) morphine. The 84 with oxycodone intolerance patients had lower odds of receiving oxycodone (OR 0.23, P < 0.001), higher odds of fentanyl (OR 3.6, P < 0.001) and tramadol (OR 3.35, P < 0.001), but 42 (50%) still received oxycodone. Patients with oxycodone allergies and intolerances had higher odds of elevated subjective pain (OR 1.60, P = 0.013; OR 2.36, P = 0.002, respectively) and longer length of stay (OR 1.36, P = 0.038; OR 2.24, P = 0.002, respectively) than patients without these.
CONCLUSIONS
General surgery patients with oxycodone allergies and intolerances are at greater risk of worse postoperative pain and longer length of stay, compared to patients without. Many still receive oxycodone, and other opioids that could cause cross-reactivity.
Topics: Humans; Analgesics, Opioid; Oxycodone; South Australia; Length of Stay; Tramadol; Retrospective Studies; Practice Patterns, Physicians'; Australia; Pain, Postoperative; Hypersensitivity
PubMed: 37837230
DOI: 10.1111/ans.18722 -
ESC Heart Failure Feb 2024Ivabradine, a medical treatment for heart failure (HF), reduces heart rate (HR) and prolongs diastolic perfusion time. It is frequently prescribed to patients with HF... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ivabradine, a medical treatment for heart failure (HF), reduces heart rate (HR) and prolongs diastolic perfusion time. It is frequently prescribed to patients with HF who have a suboptimal response or intolerance to beta-blockers. Degenerative mitral regurgitation (MR) is a valvular heart disease often associated with the development of HF and atrial fibrillation (AF). However, studies comparing the effects of ivabradine and beta-blockers on MR are lacking. Therefore, this study aimed to explore the potential therapeutic effects of ivabradine and carvedilol on MR using a rat model.
METHODS AND RESULTS
Using a novel echo-guided mini-invasive surgery, MR was created in 12-weeks-old Sprague-Dawley rats. After 2 weeks, the rats were randomized to receive either ivabradine or carvedilol for 4 weeks. Echocardiography was performed at baseline and at two-week intervals. Following haemodynamic studies, postmortem tissues were analysed. Notably, the MR-induced myocardial dysfunction did not improve considerably after treatment with ivabradine or carvedilol. However, in haemodynamic studies, pharmacological therapies, particularly carvedilol, mitigated MR-induced chamber dilatation (end-systolic volume and end-diastolic volume; MR vs. MR + Carvedilol; P < 0.05) and decreased compliance (end-systolic pressure-volume relationship; MR vs. MR + Carvedilol; P < 0.05). Compared with ivabradine, a shorter duration (MR vs. MR + Carvedilol; P < 0.05) and reduced inducibility (MR vs. MR + Carvedilol and MR vs. MR + Ivabradine; P < 0.05) of AF were observed in MR rats treated with carvedilol. Similarly, reduced cardiac fibrosis and apoptosis were observed in the MR rat model in the treatment groups, especially in those treated with carvedilol (MR vs. MR + Carvedilol; P < 0.01).
CONCLUSIONS
Although both ivabradine and carvedilol, at least in part, mitigated MR-induced chamber dilatation and decreased compliance, carvedilol had a better effect on reversing MR-induced cardiac fibrosis, apoptosis, and arrhythmogenesis than ivabradine. When compared with Ivabradine, MR rats treated with carvedilol exhibited a shorter duration and reduced inducibility of AF, thus providing more effective suppression of HCN4. Further investigations are required to validate our findings.
Topics: Humans; Rats; Animals; Carvedilol; Ivabradine; Mitral Valve Insufficiency; Rats, Sprague-Dawley; Adrenergic beta-Antagonists; Heart Failure; Atrial Fibrillation; Fibrosis
PubMed: 37963437
DOI: 10.1002/ehf2.14577 -
Biomedicines Jan 2024Ventricular tachycardia is a potentially life-threatening arrhythmia associated with an overall high morbi-mortality, particularly in patients with structural heart... (Review)
Review
Ventricular tachycardia is a potentially life-threatening arrhythmia associated with an overall high morbi-mortality, particularly in patients with structural heart disease. Despite their pivotal role in preventing sudden cardiac death, implantable cardioverter-defibrillators, although a guideline-based class I recommendation, are unable to prevent arrhythmic episodes and significantly alter the quality of life by delivering recurrent therapies. From open-heart surgical ablation to the currently widely used percutaneous approach, catheter ablation is a safe and effective procedure able to target the responsible re-entry myocardial circuit from both the endocardium and the epicardium. There are four main mapping strategies, activation, entrainment, pace, and substrate mapping, each of them with their own advantages and limitations. The contemporary guideline-based recommendations for VT ablation primarily apply to patients experiencing antiarrhythmic drug ineffectiveness or those intolerant to the pharmacological treatment. Although highly effective in most cases of scar-related VTs, the traditional approach may sometimes be insufficient, especially in patients with nonischemic cardiomyopathies, where circuits may be unmappable using the classic techniques. Alternative methods have been proposed, such as stereotactic arrhythmia radioablation or radiotherapy ablation, surgical ablation, needle ablation, transarterial coronary ethanol ablation, and retrograde coronary venous ethanol ablation, with promising results. Further studies are needed in order to prove the overall efficacy of these methods in comparison to standard radiofrequency delivery. Nevertheless, as the field of cardiac electrophysiology continues to evolve, it is important to acknowledge the role of artificial intelligence in both the pre-procedural planning and the intervention itself.
PubMed: 38397868
DOI: 10.3390/biomedicines12020266 -
MBio Nov 2023is an alpha-proteobacterium that is a promising platform for industrial scale production of biofuels due to its efficient ethanol fermentation and low biomass...
is an alpha-proteobacterium that is a promising platform for industrial scale production of biofuels due to its efficient ethanol fermentation and low biomass generation. is aerotolerant and encodes a complete respiratory electron transport chain, but the benefit of respiration for growth in oxic conditions has never been confirmed, despite decades of research. Growth and ethanol production of wild-type is poor in oxic conditions indicating that it does not benefit from oxidative phosphorylation. Additionally, in previous studies, aerobic growth improved significantly when respiratory genes were disrupted () or acquired point mutations ( and ), even if respiration was significantly reduced by these changes. Here, we obtained clean deletions of respiratory genes and , individually and in combination, and showed, for the first time, that deletion of completely inhibited O respiration and dramatically reduced growth in oxic conditions. Both respiration and aerobic growth were restored by expressing a heterologous, water-forming NADH oxidase, . Oxygen can have many negative effects, including formation of reactive oxygen species (ROS) or directly inactivating oxygen sensitive enzymes. Our results suggest that the effect of molecular oxygen on enzymes had a greater negative impact on than formation of ROS. This result shows that the main role of the electron transport chain in is reducing the intracellular concentration of molecular oxygen, helping to explain why it is beneficial for to use electron transport chain complexes that have little capacity to contribute to oxidative phosphorylation. IMPORTANCE A key to producing next-generation biofuels is to engineer microbes that efficiently convert non-food materials into drop-in fuels, and to engineer microbes effectively, we must understand their metabolism thoroughly. is a bacterium that is a promising candidate biofuel producer, but its metabolism remains poorly understood, especially its metabolism when exposed to oxygen. Although respires with oxygen, its aerobic growth is poor, and disruption of genes related to respiration counterintuitively improves aerobic growth. This unusual result has sparked decades of research and debate regarding the function of respiration in . Here, we used a new set of mutants to determine that respiration is essential for aerobic growth and likely protects the cells from damage caused by oxygen. We conclude that the respiratory pathway of should not be deleted from chassis strains for industrial production because this would yield a strain that is intolerant of oxygen, which is more difficult to manage in industrial settings.
PubMed: 37909744
DOI: 10.1128/mbio.02043-23