Journal of Physiology-London最新文献

{"title":"Enhancing stroke risk stratification in atrial fibrillation through non-Newtonian blood modelling and Gaussian process emulation.","authors":"Paolo Melidoro, Abdel Rahman Amr Sultan, Ahmed Qureshi, Magdi H Yacoub, Khalil L Elkhodary, Gregory Y H Lip, Natalie Montarello, Nishant Lahoti, Ronak Rajani, Magdalena Klis, Steven E Williams, Oleg Aslanidi, Adelaide De Vecchi","doi":"10.1113/JP287283","DOIUrl":"https://doi.org/10.1113/JP287283","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is the most common heart arrhythmia, linked to a five-fold increase in stroke risk. The left atrial appendage (LAA), prone to blood stasis, is a common thrombus formation site in AF patients. The LAA can be classified into four morphologies: broccoli, cactus, chicken wing and windsock. Stroke risk prediction in AF typically relies on demographic characteristics and comorbidities, often overlooking blood flow dynamics. We developed patient-specific non-Newtonian models of blood flow, dependent on fibrinogen and haematocrit, to predict changes in LAA viscosity, aiming to predict stroke in AF patients. We conducted 480 computational fluid dynamics (CFD) simulations using the non-Newtonian model across the four LAA morphologies for four virtual patient cohorts: AF + Covid-19, AF + pathological fibrinogen, AF + normal fibrinogen, and healthy controls. Gaussian process emulators (GPEs) were trained on this in silico cohort to predict average LAA viscosity at near-zero computational cost. GPEs demonstrated high accuracy in AF cohorts but lower accuracy when the chicken wing GPE was applied to other morphologies. Global sensitivity analysis showed fibrinogen significantly influenced blood viscosity in all AF cohorts. The chicken wing morphology exhibited the highest viscosity, while the AF + Covid-19 cohort had the highest viscosity. Our non-Newtonian model in CFD simulations confirmed fibrinogen's substantial impact on blood viscosity at low shear rates in the LAA, suggesting that combining blood values and geometric parameters of the LAA into GPE training could enhance stroke risk stratification accuracy. KEY POINTS: Fibrinogen has a significant effect on blood viscosity in the left atrial appendage (LAA) at low shear rates. Gaussian process emulators (GPEs) can predict the viscosity of blood in the LAA at near-zero computational cost. Out of all LAA morphologies, the chicken wing morphology exhibited the highest average blood viscosity. High average blood viscosity in the LAA of atrial fibrilation + Covid-19 patients was observed due to high fibrinogen levels in this cohort. Combining blood values and geometric parameters of the LAA into GPE training could enhance stroke risk stratification accuracy.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Grip force control under sudden change of friction","authors":"Laurence Willemet,&nbsp;Felix Roël,&nbsp;David Abbink,&nbsp;Ingvars Birznieks,&nbsp;Michaël Wiertlewski","doi":"10.1113/JP286486","DOIUrl":"10.1113/JP286486","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;A task as simple as holding a cup between your fingers generates complex motor commands to finely regulate the forces applied by muscles. These fine force adjustments ensure the stability and integrity of the object by preventing it from slipping out of grip during manipulation and by reacting to perturbations. To do so, our sensorimotor system constantly monitors tactile and proprioceptive information about the force object exerts on fingertips and the friction of the surfaces to determine the optimal grip force. While the literature describes the transient responses, humans can generate to react to perturbations in load force, it is yet to be determined if humans can also react to abrupt changes in friction while already holding an object. Only recently technology using imperceivable ultrasonic vibrations became available to modulate friction in real time to investigate this question. In this study, we used an object with an integrated friction modulation device suspended in a pulley system controlling the load. With this device, we explored the rapid adaptation of the sensorimotor system to changes in friction alone and in combination with changes in load. When load force and friction changed simultaneously, the grip force response was regulated based on the grip safety requirements. Participants increased their grip force in response to decrease in friction. However, they did not adjust their grip force when the friction increased, which is expected based on our biomechanical model of friction sensing mechanisms.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Simple tasks like pouring water into a glass mobilize intricate interactions between fingertip sensory inputs and motor commands to account for the weight change and friction.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;It has been investigated how humans react to force perturbations when holding an object, but very little is known about how frictional changes are sensed and acted upon while holding an object, for example, due to sweating or condensation.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We engineered a unique experimental object that utilizes imperceivable ultrasonic vibrations to change the frictional properties of the surface in a few milliseconds. This apparatus enabled us to study how human subjects react to change of friction when gripping or holding an object.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We showed that humans adjust the strength of their grasp when forces in the dire","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 2","pages":"411-422"},"PeriodicalIF":4.7,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined inhibition of atrial-specific potassium currents as a possible anti-arrhythmic drug therapy: A match made in silico.","authors":"Vladimír Sobota","doi":"10.1113/JP287950","DOIUrl":"https://doi.org/10.1113/JP287950","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal investment, body condition and calf growth in humpback whales","authors":"Martin van Aswegen,&nbsp;Andy Szabo,&nbsp;Jens J. Currie,&nbsp;Stephanie H. Stack,&nbsp;Lewis Evans,&nbsp;Janice Straley,&nbsp;Janet Neilson,&nbsp;Christine Gabriele,&nbsp;Kelly Cates,&nbsp;Debbie Steel,&nbsp;Lars Bejder","doi":"10.1113/JP287379","DOIUrl":"10.1113/JP287379","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;Given recent declines in North Pacific humpback whale (&lt;i&gt;Megaptera novaeangliae&lt;/i&gt;) reproductive output and calf survival, there is additional urgency to better understand how mother–calf pairs allocate energy resources across their migratory cycle. Here, unoccupied aerial system (UAS; or drone) photogrammetry was used to quantify the body size and condition (BC) of humpback whales on their Hawaiʻi (HI) breeding and Southeast Alaska (SEAK) feeding grounds. Between 2018 and 2022, we collected 2410 measurements of 1659 individuals. Rates of change in body volume (BV) and length (BL) were quantified using 803 repeat measurements of 275 individuals. On average, HI mothers lost 0.106 m&lt;sup&gt;3&lt;/sup&gt; or 96.84 kg day&lt;sup&gt;−1&lt;/sup&gt; while fasting, equivalent to 2641 MJ day&lt;sup&gt;−1&lt;/sup&gt; or 830 kg of krill and 424 kg of Pacific herring daily. HI calf BV and BL increased by 0.035 m&lt;sup&gt;3&lt;/sup&gt; and 2.6 cm day&lt;sup&gt;−1&lt;/sup&gt;, respectively. In SEAK, maternal BV increased by 0.015 m&lt;sup&gt;3&lt;/sup&gt; or 14.54 kg day&lt;sup&gt;−1&lt;/sup&gt; (367 MJ day&lt;sup&gt;−1&lt;/sup&gt;), while calf BV and BL increased by 0.039 m&lt;sup&gt;3&lt;/sup&gt; and 0.93 cm day&lt;sup&gt;−1&lt;/sup&gt;, respectively. Maternal investment in calf growth correlated with both female BL and BC, with larger females producing larger, faster-growing calves. Finally, using 330 measurements from 156 females, we quantified differences in BC increase over four feeding seasons. Lactating females exhibited an average BC increase of 6.10%, half that of unclassified females (13.51%) and six times lower than pregnant females (37%). These findings represent novel insights into the life history of humpback whales across their migratory cycle, providing key baseline data for bioenergetic models elucidating the effects of anthropogenic disturbance and rapidly changing ocean ecosystems.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;On average, Hawaiʻi (HI) mothers lost 0.106 m&lt;sup&gt;3&lt;/sup&gt; or 96.84 kg day&lt;sup&gt;−1&lt;/sup&gt;, equivalent to 2641 MJ day&lt;sup&gt;−1&lt;/sup&gt;. Over a 60 day period, this corresponded to an estimated mean energetic cost of 158 GJ, or ≈50 tons of krill or ≈25 tons of Pacific herring, surpassing the total energetic cost of gestation estimated for humpback whales of similar length.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;In Southeast Alaska (SEAK), maternal body volume (BV) increased by just 0.015 m&lt;sup&gt;3&lt;/sup&gt; or 14.54 kg day&lt;sup&gt;−1&lt;/sup&gt; (367 MJ day&lt;sup&gt;−1&lt;/sup&gt;). Further, SEAK lactating females showed the slowest rates of growth in body width and condition over a 150 day period compared to non-lactating females.&lt;/li&gt;\u0000 \u0000 ","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 2","pages":"551-578"},"PeriodicalIF":4.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Energetic cost of gestation and prenatal growth in humpback whales","authors":"Martin van Aswegen,&nbsp;Andy Szabo,&nbsp;Jens J. Currie,&nbsp;Stephanie H. Stack,&nbsp;Kristi L. West,&nbsp;Nicholas Hofmann,&nbsp;Fredrik Christiansen,&nbsp;Lars Bejder","doi":"10.1113/JP287304","DOIUrl":"10.1113/JP287304","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;Improving our understanding of energy allocation in reproduction is key for accurately parameterizing bioenergetic models to assess population responses to environmental perturbations and anthropogenic disturbance. We quantified the energetic cost of gestation in humpback whales (&lt;i&gt;Megaptera novaeangliae&lt;/i&gt;) using historical whaling records, non-invasive unoccupied aerial system (UAS) photogrammetry and &lt;i&gt;post mortem&lt;/i&gt; tissue samples. First, we estimated relative birth size using body length measurements of 678 mother–fetus pairs from historical whaling records and 987 mother–calf pairs measured &lt;i&gt;in situ&lt;/i&gt; using UAS-photogrammetry. The total energetic cost of gestation includes fetal growth (FG), heat increment of gestation and placental tissue development. FG was modelled from conception to birth, with fetal volume and mass estimated using the volume-to-length relationship of perinatal calves and published humpback whale tissue composition estimates. Tissue-specific energy content was quantified using &lt;i&gt;post mortem&lt;/i&gt; bone, muscle, viscera and blubber samples from a neonatal humpback whale. Placental tissue development was estimated using humpback whale placental tissue and published equations. Relative birth length was found to be 33.75% (95% CI: 32.10–34.61) of maternal length. FG rates and absolute birth size increased with maternal length, with exponential growth in fetal length, volume and mass resulting in minimal energetic costs over the first two quadmesters (0.01–1.08%) before increasing significantly in the final quadmester (98.92%). Gestational heat constituted the greatest energetic cost (90.42–94.95%), followed by fetal (4.58–7.76%) and placental (0.37–1.83%) tissue growth. Our findings highlight the energetic costs endured by capital breeding females preceding parturition, with the most substantial energetic costs of gestation coinciding with migration and fasting.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;We quantified the energetic cost of gestation using body length measurements of mother–fetus pairs from historical whaling records, length estimates of mother–calf pairs measured &lt;i&gt;in situ&lt;/i&gt; using aerial photogrammetry and &lt;i&gt;post mortem&lt;/i&gt; tissue samples.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Fetal growth rates and birth size increased with maternal length, with fetal length, volume and mass increasing exponentially over gestation.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Energetic costs over the first two quadmesters were negligible (0.01–1.08%) before increasing significantly in the final qua","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 2","pages":"529-550"},"PeriodicalIF":4.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive analysis of ratio-based metrics in physiology.","authors":"Peter L M Kerkhof, Rienzi A Diaz-Navarro, Neal Handly","doi":"10.1113/JP287889","DOIUrl":"https://doi.org/10.1113/JP287889","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An endogenous aryl hydrocarbon receptor ligand induces preeclampsia-like phenotypes in rats","authors":"Ying-Jie Zhao,&nbsp;Chi Zhou,&nbsp;Si-Yan Zhang,&nbsp;Jay S. Mishra,&nbsp;Hui-Hui Li,&nbsp;Wei Lei,&nbsp;Kai Wang,&nbsp;Sathish Kumar,&nbsp;Jing Zheng","doi":"10.1113/JP287503","DOIUrl":"10.1113/JP287503","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;Preeclampsia (PE) is a hypertensive disorder during human pregnancy. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor. Exogenous and endogenous AhR ligands can induce hypertension in male rats and mice. Herein, using rats as a model, we tested the hypothesis that over-regulation of endogenous AhR ligands during pregnancy impairs vascular functions by disrupting the transcriptome in the placenta, contributing to the development of PE. Pregnant rats were injected daily with an endogenous AhR ligand, 2-(1′&lt;i&gt;H&lt;/i&gt;-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), from gestational day (GD) 10 to 19. Maternal mean blood pressure was measured on GD16–20. Proteinuria and uteroplacental blood flow were monitored on GD20. Placentas collected on GD20 were used to determine changes in vascular density and transcriptome. Compared with the vehicle control, ITE elevated maternal mean blood pressure by 22% and 16% on GD16 and 17, respectively. ITE increased proteinuria by 50% and decreased uteroplacental blood flow by 26%. ITE reduced the placental vascular density by 18%. RNA sequencing analysis revealed that ITE induced 1316 and 2020 differentially expressed genes (DEGs) in female and male placentas, respectively. These DEGs were enriched in pathways relevant to heart diseases, vascular functions and inflammation. Bioinformatics analysis also predicted that ITE altered immune cell infiltration in placentas depending on fetal sex. These data suggest that over-regulation of endogenous AhR ligands may lead to PE with impaired vascular functions and disrupted fetal sex-specific transcriptomes and immune cell infiltration in placentas. These AhR ligand-induced DEGs and pathways may represent promising therapeutic targets for PE-induced cardiovascular dysfunctions.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;An endogenous AhR ligand (ITE) elevated maternal blood pressure and proteinuria in pregnant rats, and decreased uteroplacental blood flow and fetal and placental growth, all of which are hallmarks of preeclampsia.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;ITE reduced vascular density and altered immune cell distribution in rat placentas.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;ITE dysregulated transcriptomes in rat placentas in a fetal sex-specific manner. These ITE-dysregulated genes and pathways are highly relevant to diseases of heart, vascular functions and inflammatory responses.&lt;/li&gt;\u0000 &lt;/ul&gt;\u0000 ","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 2","pages":"579-594"},"PeriodicalIF":4.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise intolerance in pulmonary hypertension: robbing Peter to pay Paul","authors":"Ken D. O'Halloran","doi":"10.1113/JP288081","DOIUrl":"10.1113/JP288081","url":null,"abstract":"&lt;p&gt;The diaphragm is a remarkable striated muscle. As the principal muscle of inspiration, it is cyclically active facilitating airflow into the lungs from the first breath that we draw to our last. High force-dependent actions such as airway clearance and cough require powerful contractions of the diaphragm. Moreover, the diaphragm is critical to the development of raised intra-abdominal pressures subserving a range of functions. Notwithstanding its critical importance, the diaphragm is inherently vulnerable. Structural and functional plasticity, as seen in all striated muscle, affords advantages in the face of stressors but it can also provide a substrate for aberrant remodelling in circumstances that drive maladaptation. It is established that clinically relevant diaphragm weakness emerges in a wide range of scenarios such as critical care, muscle wasting diseases, undernutrition and endocrine disorders. It is also established that diaphragm weakness presents in both systemic and pulmonary hypertension.&lt;/p&gt;&lt;p&gt;Pulmonary hypertension (PH) is a progressive disease associated with limited exercise capacity and dyspnoea, relating to cardiac dysfunction, and peripheral and inspiratory muscle dysfunction. Humans and rats with PH show evidence of diaphragm muscle atrophy and weakness before the development of limb muscle dysfunction. PH-induced diaphragm weakness is partly attributable to sarcomeric dysfunction (Manders et al., &lt;span&gt;2012&lt;/span&gt;), which may relate to redox stress amenable to rescue by chronic antioxidant treatment (Himori et al., &lt;span&gt;2017&lt;/span&gt;). Maximum inspiratory pressure is reduced in people with PH, with evidence of decreased force in permeabilised diaphragm slow fibres and decreased calcium sensitivity in fast fibres, rescued by a fast troponin activator (Manders et al., &lt;span&gt;2016&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;The work of breathing is increased in PH, necessitating greater blood flow to meet increased oxygen demand. PH impairs vasomotor function in diaphragm arterioles, alters blood flow distribution and impairs the hyperaemic response to electrically induced contractions of the &lt;i&gt;in situ&lt;/i&gt; diaphragm (Schulze et al., &lt;span&gt;2023&lt;/span&gt;). These findings suggest that vascular dysfunction may precede and contribute to diaphragm dysfunction in PH due to a mismatch in oxygen delivery and demand.&lt;/p&gt;&lt;p&gt;In this issue of &lt;i&gt;The Journal of Physiology&lt;/i&gt;, Schulze et al. (&lt;span&gt;2024&lt;/span&gt;) extend their recent work to assess limb and respiratory muscle blood flow during aerobic exercise in rats with PH to determine the relative distribution of cardiac output to working muscles in PH, and in the light of previous findings (Schulze et al., &lt;span&gt;2023&lt;/span&gt;), assess bulk and regional blood flow distribution in the diaphragm during dynamic sub-maximal exercise. In essence, the study sought to determine if altered haemodynamics between and within muscles predicates exercise intolerance in PH.&lt;/p&gt;&lt;p&gt;Studies were performed in control and monocrotaline-in","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 2","pages":"243-244"},"PeriodicalIF":4.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Past the limits of pain: placebo and nocebo effects in visual processing reveal novel behavioural and brain markers of the twin phenomena","authors":"Lewis S. Crawford","doi":"10.1113/JP287678","DOIUrl":"10.1113/JP287678","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"602 24","pages":"6639-6640"},"PeriodicalIF":4.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESSION OF CONCERN: Insulin relaxes bladder via PI3K/AKT/eNOS pathway activation in mucosa: unfolded protein response-dependent insulin resistance as a cause of obesity-associated overactive bladder","authors":"","doi":"10.1113/tjp.16446","DOIUrl":"10.1113/tjp.16446","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"602 24","pages":"7113"},"PeriodicalIF":4.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}