Motor network gamma oscillations in chronic home recordings predict dyskinesia in Parkinson's disease.

In Parkinson's disease, imbalances between 'antikinetic' and 'prokinetic' patterns of neuronal oscillatory activity are related to motor dysfunction. Invasive brain recordings from the motor network have suggested that medical or surgical therapy can promote a prokinetic state by inducing narrowband gamma rhythms (65-90 Hz). Excessive narrowband gamma in the motor cortex promotes dyskinesia in rodent models, but the relationship between narrowband gamma and dyskinesia in humans has not been well established. To assess this relationship, we used a sensing-enabled deep brain stimulator system, attached to both motor cortex and basal ganglia (subthalamic or pallidal) leads, paired with wearable devices that continuously tracked motor signs in the contralateral upper limbs. We recorded 984 h of multisite field potentials in 30 hemispheres of 16 subjects with Parkinson's disease (2/16 female, mean age 57 ± 12 years) while at home on usual antiparkinsonian medications. Recordings were done 2-4 weeks after implantation, prior to starting therapeutic stimulation. Narrowband gamma was detected in the precentral gyrus, subthalamic nucleus or both structures on at least one side of 92% of subjects with a clinical history of dyskinesia. Narrowband gamma was not detected in the globus pallidus. Narrowband gamma spectral power in both structures co-fluctuated similarly with contralateral wearable dyskinesia scores (mean correlation coefficient of ρ = 0.48 with a range of 0.12-0.82 for cortex, ρ = 0.53 with a range of 0.5-0.77 for subthalamic nucleus). Stratification analysis showed the correlations were not driven by outlier values, and narrowband gamma could distinguish 'on' periods with dyskinesia from 'on' periods without dyskinesia. Time lag comparisons confirmed that gamma oscillations herald dyskinesia onset without a time lag in either structure when using 2-min epochs. A linear model incorporating the three oscillatory bands (beta, theta/alpha and narrowband gamma) increased the predictive power of dyskinesia for several subject hemispheres. We further identified spectrally distinct oscillations in the low gamma range (40-60 Hz) in three subjects, but the relationship of low gamma oscillations to dyskinesia was variable. Our findings support the hypothesis that excessive oscillatory activity at 65-90 Hz in the motor network tracks with dyskinesia similarly across both structures, without a detectable time lag. This rhythm may serve as a promising control signal for closed-loop deep brain stimulation using either cortical or subthalamic detection.

Capsaicin: Emerging Pharmacological and Therapeutic Insights.

Capsaicin, the most prominent pungent compound of chilli peppers, has been used in traditional medicine systems for centuries; it already has a number of established clinical and industrial applications. Capsaicin is known to act through the TRPV1 receptor, which exists in various tissues; capsaicin is hepatically metabolised, having a half-life correlated with the method of application. Research on various applications of capsaicin in different formulations is still ongoing. Thus, local capsaicin applications have a pronounced anti-inflammatory effect, while systemic applications have a multitude of different effects because their increased lipophilic character ensures their augmented bioavailability. Furthermore, various teams have documented capsaicin's anti-cancer effects, proven both in vivo and in vitro designs. A notable constraint in the therapeutic effects of capsaicin is its increased toxicity, especially in sensitive tissues. Regarding the traditional applications of capsaicin, apart from all the effects recorded as medicinal effects, the application of capsaicin in acupuncture points has been demonstrated to be effective and the combination of acupuncture and capsaicin warrants further research. Finally, capsaicin has demonstrated antimicrobial effects, which can supplement its anti-inflammatory and anti-carcinogenic actions.

Betamethasone improved near-term neonatal lamb lung maturation in experimental maternal asthma.

Maternal asthma is associated with increased rates of neonatal lung disease, and fetuses from asthmatic ewes have fewer surfactant-producing cells and lower surfactant-protein B gene (SFTPB) expression than controls. Antenatal betamethasone increases lung surfactant production in preterm babies, and we therefore tested this therapy in experimental maternal asthma. Ewes were sensitised to house dust mite allergen, and an asthmatic phenotype induced by fortnightly allergen lung challenges; controls received saline. Pregnant asthmatic ewes were randomised to receive antenatal saline (asthma) or 12 mg intramuscular betamethasone (asthma+beta) at 138 and 139 days of gestation (term = 150 days). Lambs were delivered by Caesarean section at 140 days of gestation and ventilated for 45 min before tissue collection. Lung function and structure were similar in control lambs (n = 16, 11 ewes) and lambs from asthma ewes (n = 14, 9 ewes). Dynamic lung compliance was higher in lambs from asthma+beta ewes (n = 12, 8 ewes) compared to those from controls (P = 0.003) or asthma ewes (P = 0.008). Lung expression of surfactant protein genes SFTPA (P = 0.048) and SFTPB (P < 0.001), but not SFTPC (P = 0.177) or SFTPD (P = 0.285), was higher in lambs from asthma+beta than those from asthma ewes. Female lambs had higher tidal volume (P = 0.007), dynamic lung compliance (P < 0.001), and SFTPA (P = 0.037) and SFTPB gene expression (P = 0.030) than males. These data suggest that betamethasone stimulates lung maturation and function of near-term neonates, even in the absence of impairment by maternal asthma.

Relationship Between Chronic Obstructive Pulmonary Disease and Osteoporosis: A Scoping Review.

INTRODUCTION: Potential associations between Chronic Obstructive Pulmonary Disease (COPD) and osteoporosis have been studied, but areas of uncertainty remain. OBJECTIVE: This scoping review aimed to identify the published evidence on the epidemiological relationships between COPD and osteoporosis. METHODS: Experimental and observational evidence evaluating relationships between COPD and osteoporosis on epidemiology, clinical manifestations, risk factors (RFs), therapeutic management and quality of life (QoL) was searched on PubMed and Embase (until May 2023). The studies were categorized according to their objectives and characteristics. Data were analyzed using descriptive statistics. RESULTS: Ninety-nine studies were selected, namely 33 (33%) reporting epidemiologic measures, 11 (11%) clinical manifestations, 74 (75%) RFs (45 ones, of which body mass index [BMI; n = 22 studies], corticosteroids' use [n = 20], and COPD severity [n = 15] were the most studied), 7 (7%) therapeutic management, and 3 (3%) QoL. Twenty-seven (27.6%) studies evaluated ≥2 domains. Most studies followed a cross-sectional design (n = 37; 37.4%). Eighty-nine studies (90%) assessed patients with COPD at baseline and studied its relationship with osteoporosis. CONCLUSION: There are well-established features linking COPD and osteoporosis, including shared RFs, such as smoking, elderly, physical inactivity, or low BMI. Others deserve clarification, including the impact of COPD severity, or the use of inhaled corticosteroids on the incidence of osteoporosis and fractures, as well as the value of performing routine imaging tests, or prescribing anti-resorptive medications in COPD to prevent osteoporotic-related outcomes. QoL studies are also lacking. Investigating such issues is needed to propose clinical guidelines for managing osteoporosis in patients with COPD.

The Relevance, Predictability, and Utility of Annexin A5 for Human Physiopathology.

As an important functional protein molecule in the human body, human annexin A5 (hAnxA5) is widely found in human cells and body fluids. hAnxA5, the smallest type of annexin, performs a variety of biological functions by reversibly and specifically binding phosphatidylserine (PS) in a calcium-dependent manner and plays an important role in many human physiological and pathological processes. The free state hAnxA5 exists in the form of monomers and usually forms a polymer in a specific self-assembly manner when exerting biological activity. This review systematically discusses the current knowledge and understanding of hAnxA5 from three perspectives: physiopathological relevance, diagnostic value, and therapeutic utility. hAnxA5 affects the occurrence and development of many physiopathological processes. Moreover, hAnxA5 can be used independently or in combination as a biomarker of physiopathological phenomena for the diagnosis of certain diseases. Importantly, based on the properties of hAnxA5, many novel drug candidates have been designed and prepared for application in actual medical practice. However, there are also some gaps and shortcomings in hAnxA5 research. This in-depth study will not only expand the understanding of structural and functional relationships but also promote the application of hAnxA5 in the field of biomedicine.

Hypertriglyceridemia: Molecular and Genetic Landscapes.

Lipid disorders represent one of the most worrisome cardiovascular risk factors. The focus on the impact of lipids on cardiac and vascular health usually concerns low-density lipoprotein cholesterol, while the role of triglycerides (TGs) is given poor attention. The literature provides data on the impact of higher plasma concentrations in TGs on the cardiovascular system and, therefore, on the outcomes and comorbidities of patients. The risk for coronary heart diseases varies from 57 to 76% in patients with hypertriglyceridemia. Specifically, the higher the plasma concentrations in TGs, the higher the incidence and prevalence of death, myocardial infarction, and stroke. Nevertheless, the metabolism of TGs and the exact physiopathologic mechanisms which try to explain the relationship between TGs and cardiovascular outcomes are not completely understood. The aims of this narrative review were as follows: to provide a comprehensive evaluation of the metabolism of triglycerides and a possible suggestion for understanding the targets for counteracting hypertriglyceridemia; to describe the inner physiopathological background for the relationship between vascular and cardiac damages derived from higher plasma concentrations in TGs; and to outline the need for promoting further insights in therapies for reducing TGs plasma levels.

Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications.

Takotsubo syndrome is a condition characterized by acute transient left ventricular systolic dysfunction, which at presentation can be challenging to distinguish from acute myocardial infarction. Although previously thought to be a benign, self-limiting condition, recent studies have confirmed that patients with takotsubo syndrome have persistent subtle ongoing cardiac dysfunction, and many continue to have limiting symptoms despite restoration of left ventricular ejection fraction. Moreover, these patients have a substantial burden of morbidity and mortality, as well, with high rates of subsequent major adverse cardiovascular events that approach those of patients with acute coronary syndrome. The mechanisms behind this condition remain elusive. Despite substantial research, the medical community continues to have an incomplete understanding of its underlying pathogenesis and pathophysiology. Catecholamine-induced myocardial injury is the most established and well-known theory, but this does not explain all the clinical features and presentations of the condition, and numerous other pathways and abnormalities are emerging. Because of the poor understanding of its underlying pathophysiology, there is a lack of evidence-based interventions to treat the acute episode, to avoid recurrences, and to prevent major adverse cardiovascular events. This highlights the need for further research to gain a better understanding of the underlying pathophysiology to inform appropriate randomized controlled trials of interventions targeting the causative pathways. Only then can evidence-based management strategies be established to improve clinical outcomes of this potentially lethal condition.

Atrial Fibrillation in Endurance Training Athletes: Scoping Review.

Background: Moderate regular physical activity is indicated to avoid atrial fibrillation (AF), whereas athletes should be counseled that long-lasting vigorous sports engagement may cause AF, according to the 2016 European Society of Cardiology (ESC) recommendations for AF treatment. Exercise and AF are complex. Objectives: To evaluate the relationship between Endurance training and AF, in addition to the starting point/trigger by which Endurance Training causes impairment of cardiac function and AF, considering the time and intensity of Endurance training. Materials and Methods: We synthesized evidence from articles published in the PubMed, EMBASE, and SciELO databases using their respective Boolean operators. A total of 112 original articles related to AF and endurance athletes published up to the year 2023 were reviewed. Results: Our study verified multiples aspects of the genesis of AF in athletes, such as cardiac adaptations to exercise, disturbances in cardiac injury biomarkers, sex differences in cardiac adaptations and their role in AF risk, and the relationship between body composition (height, weight, and physical fitness) and AF pathogenesis. Conclusions: Variations in cardiac structure (increased atrial thickness and size in addition to myocardial fibrosis) and significant increases in vagal tone (sinus bradycardia and imbalances in sympathetic and parasympathetic activation) shorten the refractory period shortening in athletes, induce the onset of re-entrance mechanisms, and serve as ectopic triggers that can lead to AF.

Central and Peripheral Nervous System Complications of Vasculitis Syndromes from Pathology to Bedside: Part 2-Peripheral Nervous System.

PURPOSE OF REVIEW: Peripheral nervous system vasculitides (PNSV) are a heterogeneous group of disorders with a clinical subset that may differ in prognosis and therapy. We provide a comprehensive update on the clinical assessment, diagnosis, complications, treatment, and follow-up of PNSV. RECENT FINDINGS: Progress in neuroimaging, molecular testing, and peripheral nerve biopsy has improved clinical assessment and decision-making of PNSV, also providing novel insights on how to prevent misdiagnosis and increase diagnostic certainty. Advances in imaging techniques, allowing to clearly display the vessel walls, have also enhanced the possibility to differentiate inflammatory from non-inflammatory vascular lesions, while recent histopathology data have identified the main morphological criteria for more accurate diagnosis and differential diagnoses. Overall, the identification of peculiar morphological findings tends to improve diagnostic accuracy by defining a clearer boundary between systemic and non-systemic neuropathies. Therefore, the definition of epineurium vessel wall damage, type of vascular lesion, characterization of lymphocyte populations, antibodies, and inflammatory factors, as well as the identification of direct nerve damage or degeneration, are the common goals for pathologists and clinicians, who will both benefit for data integration and findings translation. Nevertheless, to date, treatment is still largely empiric and, in some cases, unsatisfactory, thus often precluding precise prognostic prediction. In this context, new diagnostic techniques and multidisciplinary management will be essential in the proper diagnosis and prompt management of PNSV, as highlighted in the present review. Thirty to fifty percent of all patients with vasculitis have signs of polyneuropathy. Neuropathies associated with systemic vasculitis are best managed according to the guidelines of the underlying disease because appropriate workup and initiation of treatment can reduce morbidity. Steroids, or in severe or progressive cases, cyclophosphamide pulse therapy is the standard therapy in non-systemic vasculitic neuropathies. Some patients need long-term immunosuppression. The use of novel technologies for high-throughput genotyping will permit to determine the genetic influence of related phenotypes in patients with PNSV.

Amyloid-ß levels and cognitive trajectories in non-demented pTau181-positive subjects without amyloidopathy.

Phosphorylated Tau181 (pTau181) in CSF and recently in plasma has been associated with Alzheimer's disease. In the absence of amyloidopathy, individuals with increased total Tau levels and/or temporal lobe atrophy experience no or only mild cognitive decline compared with biomarker-negative controls, leading to the proposal to categorize this constellation as suspected non-Alzheimer's disease pathophysiology (SNAP). We investigated whether the characteristics of SNAP also applied to individuals with increased CSF-pTau181 without amyloidopathy. In this long-term observational study, 285 non-demented individuals, including 76 individuals with subjective cognitive impairment and 209 individuals with mild cognitive impairment, were classified based on their CSF levels of pTau181 (T), total Tau (N), amyloid-ß42 (Aß42) and Aß42/Aß40 ratio (A) into A+T+N±, A+T-N±, A-T+N±, and A-T-N-. The longitudinal analysis included 154 subjects with a follow-up of more than 12 months who were followed to a median of 4.6 years (interquartile range = 4.3 years). We employed linear mixed models on psychometric tests and region of interest analysis of structural MRI data. Cognitive decline and hippocampal atrophy rate were significantly higher in A+T+N± compared to A-T+N±, whereas there was no difference between A-T+N± and A-T-N-. Furthermore, there was no significant difference between A-T+N± and controls in dementia risk [hazard ratio 0.3, 95% confidence interval (0.1, 1.9)]. However, A-T+N± and A-T-N- could be distinguished based on their Aß42 and Aß40 levels. Both Aß40 and Aß42 levels were significantly increased in A-T+N± compared to controls. Long term follow-up of A-T+N± individuals revealed no evidence that this biomarker constellation was associated with dementia or more severe hippocampal atrophy rates compared to controls. However, because of the positive association of pTau181 with Aß in the A-T+N± group, a link to the pathophysiology of Alzheimer's disease cannot be excluded in this case. We propose to refer to these individuals in the SNAP group as 'pTau and Aß surge with subtle deterioration' (PASSED). The investigation of the circumstances of simultaneous elevation of pTau and Aß might provide a deeper insight into the process under which Aß becomes pathological.

Novel subgroups in acute respiratory failure based on the trajectories of three endotheliopathy biomarkers: A cohort study.

Baseline levels of endotheliopathy are associated with worse respiratory outcomes and mortality in undifferentiated acute respiratory failure (ARF), but knowledge is lacking on the development of endotheliopathy over time in ARF. We, therefore, aimed to evaluate the prognostic significance of trajectories of endotheliopathy during the first days of ARF. We performed a secondary, exploratory analysis of a single-center prospective cohort including 459 patients requiring mechanical ventilation. Based on Days 1-3 Syndecan-1, soluble Thrombomodulin (sTM), and Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1), we divided patients into subgroups using latent class mixed modeling and correlated subgroups with clinical outcomes using Cox regression. Based on Syndecan-1 and sTM, respectively, we identified two subgroups. Based on PECAM-1, we identified three subgroups. Subgroups based on Syndecan-1 and sTM were identifiable from the baseline levels, but subgroups based on PECAM-1 were not. Patients with persistently high levels of both sTM and PECAM-1 were liberated from mechanical ventilation more slowly (Group high vs. Group low, sTM: hazard ratio [HR]: 0.66, 95% confidence interval [CI]: 0.50-0.88, p = .01, PECAM-1: HR: 0.59, 95% CI: 0.37-0.93, p = .02) and had higher 30-day mortality (sTM: HR: 1.90, 95% CI: 1.20-3.01, p = .01, PECAM-1: HR: 4.25, 95% CI: 1.99-9.07, p < .01). In ARF requiring mechanical ventilation, patients in subgroups with persistently high levels of sTM and PECAM-1 had lower rates of liberation from mechanical ventilation and higher 30-day mortality. However, patients with persistently high levels of sTM were identifiable based on the baseline level, and only the trajectory of PECAM-1 added information to that of the baseline level.

Understanding the Relationship between Nonalcoholic Fatty Liver Disease and Thyroid Disease.

The prevalence of hypothyroidism in patients with nonalcoholic fatty liver disease (NAFLD) is high (22.4%). Thyroid hormones (THs) regulate many metabolic activities in the liver by promoting the export and oxidation of lipids, as well as de novo lipogenesis. They also control hepatic insulin sensitivity and suppress hepatic gluconeogenesis. Because of its importance in lipid and carbohydrate metabolism, the involvement of thyroid dysfunction in the pathogenesis of NAFLD seems plausible. The mechanisms implicated in this relationship include high thyroid-stimulating hormone (TSH) levels, low TH levels, and chronic inflammation. The activity of the TH receptor (THR)-ß in response to THs is essential in the pathogenesis of hypothyroidism-induced NAFLD. Therefore, an orally active selective liver THR-ß agonist, Resmetirom (MGL-3196), was developed, and has been shown to reduce liver fat content, and as a secondary end point, to improve nonalcoholic steatohepatitis. The treatment of NAFLD with THR-ß agonists seems quite promising, and other agonists are currently under development and investigation. This review aims to shine a light on the pathophysiological and epidemiological evidence regarding this relationship and the effect that treatment with THs and selective liver THR-ß agonists have on hepatic lipid metabolism.

Kaempferol: A Review of Current Evidence of Its Antiviral Potential.

Kaempferol and its derivatives are flavonoids found in various plants, and a considerable number of these have been used in various medical applications worldwide. Kaempferol and its compounds have well-known antioxidant, anti-inflammatory and antimicrobial properties among other health benefits. However, the antiviral properties of kaempferol are notable, and there is a significant number of experimental studies on this topic. Kaempferol compounds were effective against DNA viruses such as hepatitis B virus, viruses of the alphaherpesvirinae family, African swine fever virus, and pseudorabies virus; they were also effective against RNA viruses, namely feline SARS coronavirus, dengue fever virus, Japanese encephalitis virus, influenza virus, enterovirus 71, poliovirus, respiratory syncytial virus, human immunodeficiency virus, calicivirus, and chikungunya virus. On the other hand, no effectiveness against murine norovirus and hepatitis A virus could be determined. The antiviral action mechanisms of kaempferol compounds are various, such as the inhibition of viral polymerases and of viral attachment and entry into host cells. Future research should be focused on further elucidating the antiviral properties of kaempferol compounds from different plants and assessing their potential use to complement the action of antiviral drugs.

The Immunological Microenvironment and the Emerging Role of Stem Cells Therapy in Peyronie's Disease: A Systematic Narrative Review.

Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.

Management of Neonatal Isolated and Combined Growth Hormone Deficiency: Current Status.

Congenital growth hormone deficiency (GHD) is a rare disease caused by disorders affecting the morphogenesis and function of the pituitary gland. It is sometimes found in isolation but is more frequently associated with multiple pituitary hormone deficiency. In some cases, GHD may have a genetic basis. The many clinical signs and symptoms include hypoglycaemia, neonatal cholestasis and micropenis. Diagnosis should be made by laboratory analyses of the growth hormone and other pituitary hormones, rather than by cranial imaging with magnetic resonance imaging. When diagnosis is confirmed, hormone replacement should be initiated. Early GH replacement therapy leads to more positive outcomes, including reduced hypoglycaemia, growth recovery, metabolic asset, and neurodevelopmental improvements.

Retinal vessels as a window on amyotrophic lateral sclerosis pathophysiology: A systematic review.

Amyotrophic lateral sclerosis (ALS) is a rare fatal motor neuron disease. Although many potential mechanisms have been proposed, the pathophysiology of the disease remains unknown. Currently available treatments can only delay the progression of the disease and prolong life expectancy by a few months. There is still no definitive cure for ALS, and the development of new treatments is limited by a lack of understanding of the underlying biological processes that trigger and promote neurodegeneration. Several scientific results suggest a neurovascular impairment in ALS providing perspectives for the development of new biomarkers and treatments. In this article, we performed a systematic review using PRISMA guidelines including PubMed, EmBase, GoogleScholar, and Web of Science Core Collection to analyze the scientific literature published between 2000 and 2021 discussing the neurocardiovascular involvement and ophthalmologic abnormalities in ALS. In total, 122 articles were included to establish this systematic review. Indeed, microvascular pathology seems to be involved in ALS, affecting all the neurovascular unit components. Retinal changes have also been recently highlighted without significant alteration of the visual pathways. Despite the peripheral location of the retina, it is considered as an extension of the central nervous system (CNS) as it displays similarities to the brain, the inner blood-retinal barrier, and the blood-brain barrier. This suggests that the eye could be considered as a 'window' into the brain in many CNS disorders. Thus, studying ocular manifestations of brain pathologies seems very promising in understanding neurodegenerative disorders, mainly ALS. Optical coherence tomography angiography (OCT-A) could therefore be a powerful approach for exploration of retinal microvascularization allowing to obtain new diagnostic and prognostic biomarkers of ALS.

[Traumatic brain injury]. / Schädel-Hirn-Trauma.

Traumatic brain injury (TBI) describes parenchymal brain damage caused by external forces to the head. It has a massive personal and socioeconomic impact, as it is a disease with high morbidity and mortality. Both young and old people are affected, as a result of traffic or sports accidents as well as due to falls at home. The term TBI encompasses various clinical pictures, differing considerably in cause, prognosis and therapy. What they all have in common is the pathophysiological cascade that develops immediately after the initial trauma and which can persist for several days and weeks. In this phase, medical treatment, whether surgical or pharmacological, attempts to reduce the consequences of the primary damage. The aim is to maintain adequate cerebral perfusion pressure and to reduce intracranial pressure.

[Complex regional pain syndrome]. / Syndrome douloureux régional complexe.

Complex regional pain syndrome is a clinical entity that usually occurs following trauma, surgery, or other triggering event. Patients complain of pain described as burning, associated with sensory, vasomotor, sudomotor, motor and/or trophic disorders. The pain appears disproportionate to the initial lesion. The diagnosis is purely clinical and based on the Budapest criteria. It is a diagnosis of exclusion. The pathophysiology is still poorly understood and is thought to be multifactorial. Several mechanisms have been described: an inflammatory state, an overactivation of the sympathetic autonomic nervous system and a poor perception of pain at the central level. The management of signs and symptoms is therefore global. It involves physiotherapy and occupational therapy, often combined with analgesic medications. Psychological treatment may be proposed in certain circumstances. The natural evolution is rather favourable.

Le syndrome douloureux régional complexe constitue une entité clinique survenant habituellement suite à un traumatisme, une chirurgie ou un autre événement déclencheur. Les patients se plaignent d'une douleur décrite comme une brûlure, associée à des troubles sensoriels, vasomoteurs, sudomoteurs, moteurs et/ou trophiques. La douleur apparaît disproportionnée par rapport à la lésion initiale. Le diagnostic est purement clinique et repose sur les critères de Budapest. Il s'agit d'un diagnostic d'exclusion. La physiopathologie est encore peu connue, et serait multifactorielle. Plusieurs mécanismes sont décrits : un état inflammatoire, une suractivation du système nerveux autonome sympathique et une mauvaise perception de la douleur au niveau central. La prise en charge des signes et symptômes est donc globale. Elle fait intervenir une rééducation en kinésithérapie et ergothérapie, souvent associée à un traitement antalgique médicamenteux. Une prise en charge en psychologie peut être proposée dans certaines circonstances. L'évolution naturelle est plutôt favorable.

Role of miR-185-5p as modulator of periostin synthesis and smooth muscle contraction in asthma.

Asthma is a chronic respiratory disease produced by an aberrant immune response that originates with breathing difficulties and cough, through airway remodeling. The above pathophysiological events of asthma emerge the regulators of effectors, like epigenetics, which include microRNAs (miRNAs) who perform post-transcriptional regulation, controlling diverse pathways in respiratory diseases. The objective of the study was to determine how miR-185-5p regulates the secretion of periostin by airway structural cells, and smooth muscle cells contraction, both related to airway remodeling in asthma. We used miR-185-5p mimic and inhibitors in bronchial smooth muscle cells (BSMCs) and small airway epithelial cells (SAECs) from healthy subjects. Gene expression and protein levels of periostin (POSTN), CDC42, and RHOA were analyzed by RT-PCR and ELISA/Western blot, respectively. BSMC contractility was analyzed using cell-embedded collagen gels and measurement of intracellular calcium was performed using Fura-2. Additionally, miR-185-5p and periostin expression were evaluated in sputum from healthy and asthmatics. From these experiments, we observed that miR-185-5p modulation regulates periostin mRNA and protein in BSMCs and SAECs. A tendency for diminished miR-185-5p expression and higher periostin levels was seen in sputum cells from asthmatics compared to healthy, with an inverse correlation observed between POSTN and miR-185-5p. Inhibition of miR-185-5p produced higher BSMCs contraction induced by histamine. Calcium mobilization was not modified by miR-185-5p, showing that miR-185-5p role in BSMC contractility is performed by regulating CDC42 and RhoA pro-contractile factors instead. In conclusion, miR-185-5p is a modulator of periostin secretion by airway structural cells and of smooth muscle contraction, which can be related to asthma pathophysiology, and thus, might be a promising therapeutic target.

Refractory Hypertension: a Narrative Systematic Review with Emphasis on Prognosis.

PURPOSE OF REVIEW: To perform a narrative systematic review on refractory hypertension (RfHT) with particular emphasis on prognosis. RECENT FINDINGS: There were 37 articles on RfHT, 13 non-systematic reviews, and 24 original studies. RfHT, a recently described extreme phenotype of anti-hypertensive treatment failure, shall be defined as uncontrolled out-of-office blood pressure (BP) levels despite the use of at least 5 anti-hypertensive drugs, including a long-acting diuretic and a mineraloreceptor antagonist. Its prevalence ranges from 0.5 to 4.3% of general treated hypertensives and between 3.6 and 51.4% of patients with resistant hypertension (RHT). RfHT is associated with younger age, African ancestry, obesity, hypertension-mediated organ damage and clinical cardiovascular diseases, and with some comorbidities, such as diabetes and obstructive sleep apnea. Its physiopathological mechanisms probably involve sympathetic overactivity and not volume overload. Patients with RfHT have a worse prognosis than non-refractory RHT individuals, with higher risks of adverse cardiovascular and renal outcomes and of mortality. RfHT represents a rare but true extreme phenotype of anti-hypertensive treatment failure distinct from RHT and with a significantly worse prognosis. Identifying such individuals is important to tailor specific interventions.