Person-Centered Coordinated Care Experience of People With Long-Term Conditions in the Balearic Islands Measured by the P3CEQ.

Objective: This study aimed to use the Person-Centered Coordinated Care Experience Questionnaire (P3CEQ) to assess the experience of person-centered coordinated care among people with long-term conditions in the Balearic Islands, Spain. Methods: Over 1300 participants receiving treatment for chronic conditions or HIV pre-exposure prophylaxis were invited to complete the P3CEQ and a socio-demographic questionnaire, both administered electronically via the Naveta app. The P3CEQ assesses the key domains of the P3C through an 11-item questionnaire. Items 1, 2, 3, 4, 5, 8, 9 and 10 assess specifically person-centredness (PC subscale), while items 5, 6, 7, 8 and 9 measure care coordination (CC subscale; question 7 includes 4 sub-questions to specifically assess care plans). Descriptive statistics were used to summarize patient characteristics and P3CEQ items scores. Data analysis included chi-squared test of independence, Student's t-test and analysis of variance test. Pairwise comparisons were adjusted by Bonferroni correction. Results: The P3CEQ and a socio-demographic questionnaire were sent to 1313 individuals (651 men, 657 women, 5 'other gender'). A response rate of 35.34% was achieved, with 464 P3CEQ responders (223 men and 241 women). Significant differences in response rates were observed by age, smoking status, alcohol consumption, membership of patient organizations, and use of alternative medicine. Care planning was rated significantly lower than other measured domains. Women experienced less person-centered care than men (16.64 vs 17.91) and rated care coordination worse than their male counterparts (9.18 vs 10.23). There were also differences in scores between medical condition types, with cancer and inflammatory bowel disease patients rating highest for both person-centered care (21.20 and 19.13, respectively) and care coordination (10.70 vs 10.88, respectively). Patients with skin and rheumatic diseases rated lowest their experience of person-centered care. People with higher education and those employed or studying experienced better person-centeredness. Conclusion: Using the P3CEQ, we detected significant differences in the care experiences of people with chronic conditions, suggesting the need to address potential gender biases, social inequalities, and the poorer ratings observed for certain conditions in the study population.

Implementing Systematic Patient-Reported Measures for Chronic Conditions Through the Naveta Value-Based Telemedicine Initiative: Observational Retrospective Multicenter Study.

BACKGROUND: Patient-reported outcome and experience measures can play a critical role in providing patient-centered and value-based health care to a growing population of patients who are chronically ill. Value-based telemedicine platforms such as the Naveta initiative may facilitate the effective integration of these tools into health care systems. OBJECTIVE: This study aims to evaluate the response rate to electronic patient-reported outcome measures (ePROMs) and electronic patient-reported experience measures (ePREMs) among patients participating in the Naveta telemedicine initiative and its correlations with sociodemographic and clinical characteristics, as well as the evolution of the response rates over time. METHODS: Between January 1, 2021, and June 30, 2023, a total of 53,364 ePREMs and ePROMs for 20 chronic conditions were administered through the Naveta-Phemium platform. Descriptive statistics were used to summarize continuous and categorical variables. Differences in response rates within each sociodemographic variable were analyzed using logistic regression models, with significance assessed via chi-square and post hoc Tukey tests. Two-way ANOVA was used to examine the interaction between time interval and disease type on response rate evolution. RESULTS: A total of 3372 patients with severe chronic diseases from 64 public hospitals in Spain participated in the Naveta health questionnaire project. The overall response rate to ePROMs and ePREMs during the first 2.5 years of the Naveta initiative was 46.12% (24,704/53,364), with a baseline rate of 53.33% (7198/13,496). Several sociodemographic factors correlated with lower response rates, including male gender, older age, lower education level, frequent alcohol use, being a student, and not being physically active. There were also significant variations in response rates among different types of chronic conditions (P<.001), with the highest rates being for respiratory (433/606, 71.5%), oncologic (200/319, 62.7%), digestive (2247/3601, 62.4%), and rheumatic diseases (7506/12,982, 57.82%) and the lowest being for HIV infection (7473/22,695, 32.93%). During the first 6 months of follow-up, the response rates decreased in all disease types, except in the case of the group of patients with oncologic disease, among whom the response rate increased up to 100% (6/6). Subsequently, the overall response rate approached baseline levels. CONCLUSIONS: Recognizing the influence of sociodemographic factors on response rates is critical to identifying barriers to participation in telemonitoring programs and ensuring inclusiveness in patient-centered health care practices. The observed decline in response rates at follow-up may be due to survey fatigue, highlighting the need for strategies to mitigate this effect. In addition, the variation in response rates across chronic conditions emphasizes the importance of tailoring telemonitoring approaches to specific patient populations.

Astrocytes adjust the dynamic range of cortical network activity to control modality-specific sensory information processing.

Cortical neuron-astrocyte communication in response to peripheral sensory stimulation occurs in a topographic-, frequency-, and intensity-dependent manner. However, the contribution of this functional interaction to the processing of sensory inputs and consequent behavior remains unclear. We investigate the role of astrocytes in sensory information processing at circuit and behavioral levels by monitoring and manipulating astrocytic activity in vivo. We show that astrocytes control the dynamic range of the cortical network activity, optimizing its responsiveness to incoming sensory inputs. The astrocytic modulation of sensory processing contributes to setting the detection threshold for tactile and thermal behavior responses. The mechanism of such astrocytic control is mediated through modulation of inhibitory transmission to adjust the gain and sensitivity of responding networks. These results uncover a role for astrocytes in maintaining the cortical network activity in an optimal range to control behavior associated with specific sensory modalities.

TREK channels in Mechanotransduction: a Focus on the Cardiovascular System.

Mechano-electric feedback is one of the most important subsystems operating in the cardiovascular system, but the underlying molecular mechanism remains rather unknown. Several proteins have been proposed to explain the molecular mechanism of mechano-transduction. Transient receptor potential (TRP) and Piezo channels appear to be the most important candidates to constitute the molecular mechanism behind of the inward current in response to a mechanical stimulus. However, the inhibitory/regulatory processes involving potassium channels that operate on the cardiac system are less well known. TWIK-Related potassium (TREK) channels have emerged as strong candidates due to their capacity for the regulation of the flow of potassium in response to mechanical stimuli. Current data strongly suggest that TREK channels play a role as mechano-transducers in different components of the cardiovascular system, not only at central (heart) but also at peripheral (vascular) level. In this context, this review summarizes and highlights the main existing evidence connecting this important subfamily of potassium channels with the cardiac mechano-transduction process, discussing molecular and biophysical aspects of such a connection.

Effects of transcranial static magnetic field stimulation over the left dorsolateral prefrontal cortex on random number generation.

OBJECTIVE: Focal application of transcranial static magnetic field stimulation (tSMS) is a neuromodulation technique, with predominantly inhibitory effects when applied to the motor, somatosensory or visual cortex. Whether this approach can also transiently interact with dorsolateral prefrontal cortex (DLPFC) function remains unclear. The suppression of habitual or competitive responses is one of the core executive functions linked to DLPFC function. This study aimed to assess the impact of tSMS on the prefrontal contributions to inhibitory control and response selection by means of a RNG task. METHODS: We applied 20 min of tSMS over the left DLPFC of healthy subjects, using a real/sham cross-over design, during performance of a RNG task. We used an index of randomness calculated with the measures of entropy and correlation to assess the impact of stimulation on DLPFC function. RESULTS: The randomness index of the sequences generated during the tSMS intervention was significantly higher compared to those produced in the sham condition. CONCLUSIONS: Our results indicate that application of tSMS transiently modulates specific functional brain networks in DLPFC, which indicate a potential use of tSMS for treatment of neuropsychiatric disorders. SIGNIFICANCE: This study provides evidence for the capacity of tSMS for modulating DLPFC function.

Effects of Glucagon-like peptide 1 (GLP-1) analogs in the hippocampus.

The glucagon-like peptide-1 (GLP-1) is a pleiotropic hormone very well known for its incretin effect in the glucose-dependent stimulation of insulin secretion. However, GLP-1 is also produced in the brain, and it displays critical roles in neuroprotection by activating the GLP-1 receptor signaling pathways. GLP-1 enhances learning and memory in the hippocampus, promotes neurogenesis, decreases inflammation and apoptosis, modulates reward behavior, and reduces food intake. Its pharmacokinetics have been improved to enhance the peptide's half-life, enhancing exposure and time of action. The GLP-1 agonists are successfully in clinical use for the treatment of type-2 diabetes, obesity, and clinical evaluation for the treatment of neurodegenerative diseases.

Are TREK Channels Temperature Sensors?

Internal human body normal temperature fluctuates between 36.5 and 37.5°C and it is generally measured in the oral cavity. Interestingly, most electrophysiological studies on the functioning of ion channels and their role in neuronal behavior are carried out at room temperature, which usually oscillates between 22 and 24°C, even when thermosensitive channels are studied. We very often forget that if the core of the body reached that temperature, the probability of death from cardiorespiratory arrest would be extremely high. Does this mean that we are studying ion channels in dying neurons? Thousands of electrophysiological experiments carried out at these low temperatures suggest that most neurons tolerate this aggression quite well, at least for the duration of the experiments. This also seems to happen with ion channels, although studies at different temperatures indicate large changes in both, neuron and channel behavior. It is known that many chemical, physical and therefore physiological processes, depend to a great extent on body temperature. Temperature clearly affects the kinetics of numerous events such as chemical reactions or conformational changes in proteins but, what if these proteins constitute ion channels and these channels are specifically designed to detect changes in temperature? In this review, we discuss the importance of the potassium channels of the TREK subfamily, belonging to the recently discovered family of two-pore domain channels, in the transduction of thermal sensitivity in different cell types.

Tetrodotoxin: A New Strategy to Treat Visceral Pain?

Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly defined, the implication of both the central and peripheral nervous systems in visceral hypersensitivity is well established. The role of several pathways in visceral nociception has been explored, as well as the influence of specific receptors on afferent neurons, such as voltage-gated sodium channels (VGSCs). VGSCs initiate action potentials and dysfunction of these channels has recently been associated with painful GI conditions. Current treatments for visceral pain generally involve opioid based drugs, which are associated with important side-effects and a loss of effectiveness or tolerance. Hence, efforts have been intensified to find new, more effective and longer-lasting therapies. The implication of VGSCs in visceral hypersensitivity has drawn attention to tetrodotoxin (TTX), a relatively selective sodium channel blocker, as a possible and promising molecule to treat visceral pain and related diseases. As such, here we will review the latest information regarding this toxin that is relevant to the treatment of visceral pain and the possible advantages that it may offer relative to other treatments, alone or in combination.

Contribution of K2P Potassium Channels to Cardiac Physiology and Pathophysiology.

Years before the first two-pore domain potassium channel (K2P) was cloned, certain ion channels had already been demonstrated to be present in the heart with characteristics and properties usually attributed to the TREK channels (a subfamily of K2P channels). K2P channels were later detected in cardiac tissue by RT-PCR, although the distribution of the different K2P subfamilies in the heart seems to depend on the species analyzed. In order to collect relevant information in this regard, we focus here on the TWIK, TASK and TREK cardiac channels, their putative roles in cardiac physiology and their implication in coronary pathologies. Most of the RNA expression data and electrophysiological recordings available to date support the presence of these different K2P subfamilies in distinct cardiac cells. Likewise, we show how these channels may be involved in certain pathologies, such as atrial fibrillation, long QT syndrome and Brugada syndrome.

Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress.

Glucagon like-peptide 1 (GLP-1) within the brain is produced by a population of preproglucagon neurons located in the caudal nucleus of the solitary tract. These neurons project to the hypothalamus and another forebrain, hindbrain, and mesolimbic brain areas control the autonomic function, feeding, and the motivation to feed or regulate the stress response and the hypothalamic-pituitary-adrenal axis. GLP-1 receptor (GLP-1R) controls both food intake and feeding behavior (hunger-driven feeding, the hedonic value of food, and food motivation). The activation of GLP-1 receptors involves second messenger pathways and ionic events in the autonomic nervous system, which are very relevant to explain the essential central actions of GLP-1 as neuromodulator coordinating food intake in response to a physiological and stress-related stimulus to maintain homeostasis. Alterations in GLP-1 signaling associated with obesity or chronic stress induce the dysregulation of eating behavior. This review summarized the experimental shreds of evidence from studies using GLP-1R agonists to describe the neural and endocrine integration of stress responses and feeding behavior.

Contribution of KCNQ and TREK Channels to the Resting Membrane Potential in Sympathetic Neurons at Physiological Temperature.

The ionic mechanisms controlling the resting membrane potential (RMP) in superior cervical ganglion (SCG) neurons have been widely studied and the M-current (IM, KCNQ) is one of the key players. Recently, with the discovery of the presence of functional TREK-2 (TWIK-related K+ channel 2) channels in SCG neurons, another potential main contributor for setting the value of the resting membrane potential has appeared. In the present work, we quantified the contribution of TREK-2 channels to the resting membrane potential at physiological temperature and studied its role in excitability using patch-clamp techniques. In the process we have discovered that TREK-2 channels are sensitive to the classic M-current blockers linopirdine and XE991 (IC50 = 0.310 ± 0.06 µM and 0.044 ± 0.013 µM, respectively). An increase from room temperature (23 °C) to physiological temperature (37 °C) enhanced both IM and TREK-2 currents. Likewise, inhibition of IM by tetraethylammonium (TEA) and TREK-2 current by XE991 depolarized the RMP at room and physiological temperatures. Temperature rise also enhanced adaptation in SCG neurons which was reduced due to TREK-2 and IM inhibition by XE991 application. In summary, TREK-2 and M currents contribute to the resting membrane potential and excitability at room and physiological temperature in the primary culture of mouse SCG neurons.

PIP2 Mediated Inhibition of TREK Potassium Currents by Bradykinin in Mouse Sympathetic Neurons.

Bradykinin (BK), a hormone inducing pain and inflammation, is known to inhibit potassium M-currents (IM) and to increase the excitability of the superior cervical ganglion (SCG) neurons by activating the Ca2+-calmodulin pathway. M-current is also reduced by muscarinic agonists through the depletion of membrane phosphatidylinositol 4,5-biphosphate (PIP2). Similarly, the activation of muscarinic receptors inhibits the current through two-pore domain potassium channels (K2P) of the "Tandem of pore-domains in a Weakly Inward rectifying K+ channel (TWIK)-related channels" (TREK) subfamily by reducing PIP2 in mouse SCG neurons (mSCG). The aim of this work was to test and characterize the modulation of TREK channels by bradykinin. We used the perforated-patch technique to investigate riluzole (RIL) activated currents in voltage- and current-clamp experiments. RIL is a drug used in the palliative treatment of amyotrophic lateral sclerosis and, in addition to blocking voltage-dependent sodium channels, it also selectively activates the K2P channels of the TREK subfamily. A cell-attached patch-clamp was also used to investigate TREK-2 single channel currents. We report here that BK reduces spike frequency adaptation (SFA), inhibits the riluzole-activated current (IRIL), which flows mainly through TREK-2 channels, by about 45%, and reduces the open probability of identified single TREK-2 channels in cultured mSCG cells. The effect of BK on IRIL was precluded by the bradykinin receptor (B2R) antagonist HOE-140 (d-Arg-[Hyp3, Thi5, d-Tic7, Oic8]BK) but also by diC8PIP2 which prevents PIP2 depletion when phospholipase C (PLC) is activated. On the contrary, antagonizing inositol triphosphate receptors (IP3R) using 2-aminoethoxydiphenylborane (2-APB) or inhibiting protein kinase C (PKC) with bisindolylmaleimide did not affect the inhibition of IRIL by BK. In conclusion, bradykinin inhibits TREK-2 channels through the activation of B2Rs resulting in PIP2 depletion, much like we have demonstrated for muscarinic agonists. This mechanism implies that TREK channels must be relevant for the capture of information about pain and visceral inflammation.

Ion Channels and Thermosensitivity: TRP, TREK, or Both?

Controlling body temperature is a matter of life or death for most animals, and in mammals the complex thermoregulatory system is comprised of thermoreceptors, thermosensors, and effectors. The activity of thermoreceptors and thermoeffectors has been studied for many years, yet only recently have we begun to obtain a clear picture of the thermosensors and the molecular mechanisms involved in thermosensory reception. An important step in this direction was the discovery of the thermosensitive transient receptor potential (TRP) cationic channels, some of which are activated by increases in temperature and others by a drop in temperature, potentially converting the cells in which they are expressed into heat and cold receptors. More recently, the TWIK-related potassium (TREK) channels were seen to be strongly activated by increases in temperature. Hence, in this review we want to assess the hypothesis that both these groups of channels can collaborate, possibly along with other channels, to generate the wide range of thermal sensations that the nervous system is capable of handling.

Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons.

Two-pore domain potassium channels (K2P) constitute major candidates for the regulation of background potassium currents in mammalian cells. Channels of the TREK subfamily are also well positioned to play an important role in sensory transduction due to their sensitivity to a large number of physiological and physical stimuli (pH, mechanical, temperature). Following our previous report describing the molecular expression of different K2P channels in the vagal sensory system, here we confirm that TREK channels are functionally expressed in neurons from the mouse nodose ganglion (mNG). Neurons were subdivided into three groups (A, Ah and C) based on their response to tetrodotoxin and capsaicin. Application of the TREK subfamily activator riluzole to isolated mNG neurons evoked a concentration-dependent outward current in the majority of cells from all the three subtypes studied. Riluzole increased membrane conductance and hyperpolarized the membrane potential by approximately 10 mV when applied to resting neurons. The resting potential was similar in all three groups, but C cells were clearly less excitable and showed smaller hyperpolarization-activated currents at -100 mV and smaller sustained currents at -30 mV. Our results indicate that the TREK subfamily of K2P channels might play an important role in the maintenance of the resting membrane potential in sensory neurons of the autonomic nervous system, suggesting its participation in the modulation of vagal reflexes.