Molecular aspects of regeneration in insects.

Regeneration is a fascinating phenomenon observed in various organisms across the animal kingdom. Different orders of class Insecta are reported to possess comprehensive regeneration abilities. Several signalling molecules, such as morphogens, growth factors, and others trigger a cascade of events that promote wound healing, blastema formation, growth, and repatterning. Furthermore, epigenetic regulation has emerged as a critical player in regulating the process of regeneration. This report highlights the major breakthrough research on wound healing and tissue regeneration. Exploring and reviewing the molecular basis of regeneration can be helpful in the area of regenerative medicine advancements. The understanding gathered from this framework can potentially contribute to hypothesis designing with implications in the field of synthetic biology and human health.

2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia). METHODS: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate. STRUCTURE: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.

Distinct gene expression dynamics in developing and regenerating crustacean limbs.

Regenerating animals have the ability to reproduce body parts that were originally made in the embryo and subsequently lost due to injury. Understanding whether regeneration mirrors development is an open question in most regenerative species. Here, we take a transcriptomics approach to examine whether leg regeneration shows similar temporal patterns of gene expression as leg development in the embryo, in the crustacean Parhyale hawaiensis. We find that leg development in the embryo shows stereotypic temporal patterns of gene expression. In contrast, the dynamics of gene expression during leg regeneration show a higher degree of variation related to the physiology of individual animals. A major driver of this variation is the molting cycle. We dissect the transcriptional signals of individual physiology and regeneration to obtain clearer temporal signals marking distinct phases of leg regeneration. Comparing the transcriptional dynamics of development and regeneration we find that, although the two processes use similar sets of genes, the temporal patterns in which these genes are deployed are different and cannot be systematically aligned.

Juvenile hormone signaling is indispensable for late embryogenesis in ametabolous and hemimetabolous insects.

BACKGROUND: Juvenile hormone (JH) is an insect-exclusive hormone involved in regulating diverse aspects of insect physiology, and the evolution of its diverse function is widely interesting. Studying embryogenesis in basal wingless insects is important to understand the functional evolution of JH; however, experimental studies in this regard are scarce. In this study, we conducted CRISPR/Cas9-mediated knockout (KO) of genes involved in JH biosynthesis and signaling cascades in the ametabolous firebrat, Thermobia domestica. Additionally, we investigated whether the primitive action of JH is conserved in the hemimetabolous cricket, Gryllus bimaculatus. RESULTS: We observed that KO of JHAMT, CYP15A1, Met, and Kr-h1 resulted in embryonic lethality in T. domestica. Deprivation of JH or JH signaling arrested the progression of extraembryonic fluid resorption after dorsal closure and hatching, which is consistent with the gene expression pattern showing high Kr-h1 expression in the late embryos of T. domestica. The embryos deficient in JH signaling displayed wrinkled and weak legs. Comparative transcriptome analysis revealed that JH signaling promotes embryonic leg maturation through inducing energy supply and muscle activity, as validated by transmission electron microscopy (TEM). In addition, JH signaling exhibited similar embryonic effects in G. bimaculatus. CONCLUSIONS: This study reveals the indispensable role of JH signaling in facilitating the maturation of terminal tissues during late embryogenesis, as demonstrated by the regulation of leg development, in ametabolous and hemimetabolous insects. These findings further indicate that the embryonic functions of JH evolved earlier than its anti-metamorphic functions during postembryonic development.

Controversies in the pathophysiology of leg ulcers in sickle cell disease.

Patients with sickle cell disease (SCD) often experience painful vaso-occlusive crises and chronic haemolytic anaemia, as well as various acute and chronic complications, such as leg ulcers. Leg ulcers are characterized by their unpredictability, debilitating pain and prolonged healing process. The pathophysiology of SCD leg ulcers is not well defined. Known risk factors include male gender, poor social conditions, malnutrition and a lack of compression therapy when oedema occurs. Leg ulcers typically start with spontaneous pain, followed by induration, hyperpigmentation, blister formation and destruction of the epidermis. SCD is characterized by chronic haemolysis, increased oxidative stress and decreased nitric oxide bioavailability, which promote ischaemia and inflammation and consequently impair vascular function in the skin. This cutaneous vasculopathy, coupled with venostasis around the ankle, creates an ideal environment for local vaso-occlusive crises, which can result in the development of leg ulcers that resemble arterial ulcers. Following the development of the ulcer, healing is hindered as a result of factors commonly observed in venous ulceration, including venous insufficiency, oedema and impaired angiogenesis. All of these factors are modulated by genetic factors. However, our current understanding of these genetic factors remains limited and does not yet enable us to accurately predict ulceration susceptibility.

Impaired microvascular function in patients with sickle cell anemia and leg ulcers improved with healing.

Leg Ulcer (LU) pathophysiology is still not well understood in sickle cell anaemia (SCA). We hypothesised that SCA patients with LU would be characterised by lower microvascular reactivity. The aim of the present study was to compare the microcirculatory function (transcutaneous oxygen pressure (TcPO2) on the foot and laser Doppler flowmetry on the arm) and several blood biological parameters between nine SCA patients with active LU (LU+) and 56 SCA patients with no positive history of LU (LU-). We also tested the effects of plasma from LU+ and LU- patients on endothelial cell activation. We observed a reduction of the TcPO2 in LU+ compared to LU- patients. In addition, LU+ patients exhibited lower cutaneous microvascular vasodilatory capacity in response to acetylcholine, current and local heating compared to LU- patients. Inflammation and endothelial cell activation in response to plasma did not differ between the two groups. Among the nine patients from the LU+ group, eight were followed and six achieved healing in 4.4 ± 2.5 months. Among thus achieving healing, microvascular vasodilatory capacity in response to acetylcholine, current and local heating and TcPO2 improved after healing. In conclusion, microcirculatory function is impaired in patients with LU, and improves with healing.

Statin therapy improves locomotor muscle microvascular reactivity in patients with heart failure with preserved ejection fraction.

Peripheral microvascular dysfunction has been documented in patients with heart failure with preserved ejection fraction (HFpEF), which may be related to elevated levels of inflammation and oxidative stress. Unfortunately, few strategies have been identified to effectively ameliorate this disease-related derangement. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10 mg daily) on lower limb microvascular reactivity, functional capacity, and biomarkers of inflammation and oxidative stress in patients with HFpEF (statin, n = 8, 76 ± 6 yr; placebo, n = 8, 68 ± 9 yr). The passive limb movement (PLM)-induced hyperemic response and 6-min walk test (6MWT) distance were evaluated to assess ambulatory muscle microvascular function and functional capacity, respectively. Circulating biomarkers were also measured to assess the contribution of changes in inflammation and redox balance to these outcomes. The total hyperemic response to PLM, assessed as leg blood flow area under the curve (LBFAUC), increased following the statin intervention (pre, 60 ± 68 mL; post, 164 ± 90 mL; P < 0.01), whereas these variables were unchanged in the placebo group (P = 0.99). There were no significant differences in 6MWT distance following statin or placebo intervention. Malondialdehyde (MDA), a marker of lipid peroxidation, was significantly reduced following the statin intervention (pre, 0.68 ± 0.10; post, 0.51 ± 0.11; P < 0.01) while other circulating biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to a diminution in oxidative stress.NEW & NOTEWORTHY This was the first study to investigate the impact of statin administration on locomotor muscle microvascular function in patients with HFpEF. In support of our hypothesis, the total hyperemic response to PLM, assessed as leg blood flow area under the curve, increased, and malondialdehyde, a marker of oxidative damage, was reduced following the statin intervention. Together, these data provide new evidence for the efficacy of statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to reduced oxidative stress.

Sitting leg vasculopathy: potential adaptations beyond the endothelium.

Increased sitting time, the most common form of sedentary behavior, is an independent risk factor for all-cause and cardiovascular disease mortality; however, the mechanisms linking sitting to cardiovascular risk remain largely elusive. Studies over the last decade have led to the concept that excessive time spent in the sitting position and the ensuing reduction in leg blood flow-induced shear stress cause endothelial dysfunction. This conclusion has been mainly supported by studies using flow-mediated dilation in the lower extremities as the measured outcome. In this review, we summarize evidence from classic studies and more recent ones that collectively support the notion that prolonged sitting-induced leg vascular dysfunction is likely also attributable to changes occurring in vascular smooth muscle cells (VSMCs). Indeed, we provide evidence that prolonged constriction of resistance arteries can lead to modifications in the structural characteristics of the vascular wall, including polymerization of actin filaments in VSMCs and inward remodeling, and that these changes manifest in a time frame that is consistent with the vascular changes observed with prolonged sitting. We expect this review will stimulate future studies with a focus on VSMC cytoskeletal remodeling as a potential target to prevent the detrimental vascular ramifications of too much sitting.

Cation Modulation in AgSbTe2 Realizes Carrier Optimization, Defect Engineering, and a 7% Single-Leg Thermoelectric Efficiency.

AgSbTe2 plays a pivotal role in mid-temperature thermoelectric generators (TEGs). Leveraging the seminal advances in cation manipulation within AgSbTe2, this study demonstrates an enhanced TE power factor (PF = S2σ) of 1.5 mWm-1 K-2 and a peak zT of 1.5 at 583 K in an off-stoichiometric Ag1.04Sb0.96Te2 crystal. The introduction of Ge in place of Ag leads to an increased nH as evidenced by the detection of trace Ge4+ through XPS analysis. Further chemical state analysis reveals the simultaneous presence of Ag+, Sb3+, and Ge4+, elucidating the effect of cation modulations. TEM characterizations validate the presence of superlattice structure, and the linear defects discerned within the AgSbTe2 matrix. Consequently, the lattice thermal conductivity κL is substantially reduced in the Ag1.02Ge0.02Sb0.96Te2 crystal, yielding a peak zT of 1.77 at 623 K. This notable advancement is attributed to the counterbalance achieved between the enhanced PF and the reduced κL, facilitated by cation modulation. Additionally, a single-leg TE device incorporating Ag1.02Ge0.02Sb0.96Te2 demonstrates a conversion efficiency of 7% across a temperature gradient (ΔT) of 350 K. This study corroborates the efficacy of cation modulation through thermodynamic approaches and establishes a relationship between transport properties and the presence of defects.

Multi-Level Structural Enhancement Mechanism of the Excellent Mechanical Properties of Dung Beetle Leg Joint.

The multi-level structure is a strategy to enhance the mechanical properties of dung beetle leg joints. Under external loads, the microstructure facilitates energy dissipation and prevents crack extension. The macrostructure aids in transferring the load to more reliable parts. The connection established by the two hemispheres is present in the dung beetle leg joint. The micron-layered and nanoscale crystal structures further constitute the leg joint with excellent mechanical properties. The maximum compression fracture force is ≈101000 times the weight of the leg. Here, the structural design within the dung beetle leg joints and reveal the resulting mechanical response and enhancement mechanisms is determined. A series of beetle leg joints where the macrostructure and microstructure of the dung beetle leg provide mechanical strength at critical strains while avoiding catastrophic failure by transferring the load from the joint to the exoskeleton of the femur is highlighted. Nanocrystalline structures and fiber layers contribute to crack propagation of the exoskeleton. Based on this, the bionic joint with multi-level structures using resin and conducted a series of tests to verify their effectiveness is prepared. This study provides a new idea for designing and optimizing high-load joints in engineering.

Neuronal mechanisms regulating locomotion in adult Drosophila.

The coordinated action of multiple leg joints and muscles is required even for the simplest movements. Understanding the neuronal circuits and mechanisms that generate precise movements is essential for comprehending the neuronal basis of the locomotion and to infer the neuronal mechanisms underlying several locomotor-related diseases. Drosophila melanogaster provides an excellent model system for investigating the neuronal circuits underlying motor behaviors due to its simple nervous system and genetic accessibility. This review discusses current genetic methods for studying locomotor circuits and their function in adult Drosophila. We highlight recently identified neuronal pathways that modulate distinct forward and backward locomotion and describe the underlying neuronal control of leg swing and stance phases in freely moving flies. We also report various automated leg tracking methods to measure leg motion parameters and define inter-leg coordination, gait and locomotor speed of freely moving adult flies. Finally, we emphasize the role of leg proprioceptive signals to central motor circuits in leg coordination. Together, this review highlights the utility of adult Drosophila as a model to uncover underlying motor circuitry and the functional organization of the leg motor system that governs correct movement.

Hypertension Restricts Leg Blood Flow and Aggravates Neuromuscular Fatigue during Human Locomotion in Males.

Patients with hypertension (HTN) are characterized by exaggerated vascular resistance and mean arterial pressure (MAP), and a compromised leg blood flow (QL) response to exercise recruiting a small muscle mass. However, the impact of hypertension on peripheral hemodynamics and the development of neuromuscular fatigue during locomotor activities, which critically depends on QL, remain unknown. Eight HTN (143±11mmHg / 95±6mmHg; 45±13years) and 8 matched (age, activity) controls (120±6mmHg / 77±7mmHg; CTRL) performed constant-load cycling exercise at 25, 50, and 75W (for 4-min each), and at 165±41W (for 5-min). Exercise-induced locomotor muscle fatigue was quantified as the pre- to post-exercise change in quadriceps twitch-torque (∆Qtw, peripheral fatigue) and voluntary activation (∆VA%, central fatigue). QL (Doppler-ultrasound) and leg vascular conductance (LVC) were determined during cycling at 25, 50, and 75W. Heart Rate and ventilatory responses were recorded during all intensities. MAP during exercise was, on average, ~21mmHg higher (P=0.002) and LVC ~39% lower (P=0.001) in HTN compared to CTRL. QL was consistently between 20-30% lower (P=0.004) and heart rate was significantly higher in HTN. Exercise-induced peripheral (∆Qtw: -53±19% vs -25±23%) and central (∆VA%: -7±5% vs -3±2%) fatigue were significantly greater in HTN compared to CTRL. In addition to an exaggerated MAP, LVC and QL were lower during exercise in HTN compared to CTRL. Given the critical role of QL in determining the development of neuromuscular fatigue, these hemodynamic impairments likely accounted for the faster development of neuromuscular fatigue characterizing hypertensive individuals during locomotor exercise.

Human lower leg muscles grow asynchronously.

Muscle volume must increase substantially during childhood growth to generate the power required to propel the growing body. One unresolved but fundamental question about childhood muscle growth is whether muscles grow at equal rates; that is, if muscles grow in synchrony with each other. In this study, we used magnetic resonance imaging (MRI) and advances in artificial intelligence methods (deep learning) for medical image segmentation to investigate whether human lower leg muscles grow in synchrony. Muscle volumes were measured in 10 lower leg muscles in 208 typically developing children (eight infants aged less than 3 months and 200 children aged 5 to 15 years). We tested the hypothesis that human lower leg muscles grow synchronously by investigating whether the volume of individual lower leg muscles, expressed as a proportion of total lower leg muscle volume, remains constant with age. There were substantial age-related changes in the relative volume of most muscles in both boys and girls (p < 0.001). This was most evident between birth and five years of age but was still evident after five years. The medial gastrocnemius and soleus muscles, the largest muscles in infancy, grew faster than other muscles in the first five years. The findings demonstrate that muscles in the human lower leg grow asynchronously. This finding may assist early detection of atypical growth and allow targeted muscle-specific interventions to improve the quality of life, particularly for children with neuromotor conditions such as cerebral palsy.

Sex-Specific Association Patterns of Bone Microstructure and Lower Leg Arterial Calcification.

In conversations about bone loss and the importance of calcium homeostasis, patients frequently inquire about the association with arterial calcifications. Although a relationship between bone loss and the occurrence of vascular calcifications is suspected, it is not yet fully investigated and understood. This study aims to analyze associations between bone mineralization, structure, and vascular calcification at the lower leg in patients with low bone mineral density in HR-pQCT. We retrospectively analyzed 774 high-resolution quantitative computed tomography (HR-pQCT) scans of the distal tibia for the presence of vascular calcifications. After sex-specific propensity score matching for age and BMI to account for confounders, 132 patients remained for quantification of bone microstructure, bone density, lower leg arterial calcification (LLAC), and laboratory parameters of bone turnover. The interactions between bone parameters and vascular calcification were quantified by regression analyses. The calcium metabolism was not different between individuals with and without LLAC, nor oral calcium supplementation. Female patients with LLAC had a higher cortical perimeter (p = 0.016) compared to female patients without LLAC, whereas male patients with LLAC had lower cortical pore diameter than male patients without LLAC (p = 0.027). The appearance of LLAC was sex specifically associated with bone parameters. In female patients, only plaque density was associated with HR-pQCT bone parameters and age, whereas in male patients, plaque volume was associated with HR-pQCT parameters of the distal tibia. Female patients exhibit an increasing plaque density depended on age and trabecular thinning. Decreasing cortical pore diameter and trabecular number along with increasing bone mineralization are linked to increasing plaque volume in male patients.

Skipping without and with hurdles in bipedal macaque: global mechanics.

Macaques trained to perform bipedally used running gaits across a wide range of speeds. At higher speeds they preferred unilateral skipping (galloping). The same asymmetric stepping pattern was used while hurdling across two low obstacles placed at the distance of a stride within our experimental track. In bipedal macaques during skipping, we expected a differential use of the trailing and leading legs. The present study investigated global properties of the effective and virtual leg, the location of the virtual pivot point (VPP), and the energetics of the center of mass (CoM), with the aim of clarifying the differential leg operation during skipping in bipedal macaques. When skipping, macaques displayed minor double support and aerial phases during one stride. Asymmetric leg use was indicated by differences in leg kinematics. Axial damping and tangential leg work did not influence the indifferent peak ground reaction forces and impulses, but resulted in a lift of the CoM during contact of the leading leg. The aerial phase was largely due to the use of the double support. Hurdling amplified the differential leg operation. Here, higher ground reaction forces combined with increased double support provided the vertical impulse to overcome the hurdles. Following CoM dynamics during a stride, skipping and hurdling represented bouncing gaits. The elevation of the VPP of bipedal macaques resembled that of human walking and running in the trailing and leading phases, respectively. Because of anatomical restrictions, macaque unilateral skipping differs from that of humans, and may represent an intermediate gait between grounded and aerial running.

Patient-reported lymphedema after sentinel lymph node mapping in women with low-grade endometrial cancer.

BACKGROUND: Sentinel lymph node mapping is a minimally invasive surgical staging procedure that allows identification of macro- and micrometastases. The implementation of sentinel lymph node mapping to women with low-grade endometrial cancer allows detection of lymph node metastases and avoids the morbidity of radical pelvic lymphadenectomy. The extent of myometrial invasion is highly predictive of lymph node metastases but is hard to determine precisely preoperatively. The exact rate of lymph node metastases in the large group of women with <50% myometrial invasion is low but unknown. The benefit of detecting metastases in this group should balance the risk of lymphedema. There is limited knowledge of early and late lymphedema and its impact on the quality of life in women with low-grade endometrial cancer following sentinel lymph node mapping. OBJECTIVE: The primary objective was to investigate the risk of patient-reported lymphedema after sentinel lymph node mapping in women with low-grade endometrial cancer. In addition, we aimed to evaluate risk factors for lymphedema and the condition-specific quality of life (QoL) among women who reported lymphedema 12 months after surgery. STUDY DESIGN: Women with presumed stage I low-grade endometrial cancer were included in a national prospective cohort study on sentinel lymph node mapping from March 2017 to February 2022. Women completed a package of validated patient-reported outcome measures before surgery, 3 and 12 months after surgery. The primary outcome was the leg lymphedema domain score from the European Organisation for Research and Treatment of Cancer-Endometrial Cancer Module (EORTC QLQ-EN24). The lymphedema assessment was further supplemented by 7 validated single items from the European Organisation for Research and Treatment of Cancer item library addressing lymphedema of legs, genitals, and groin. The disease-specific quality of life was assessed using the validated Lymphedema Quality of Life Tool. Scores were linearly transformed to 0 to 100. A change from baseline of 8 points in leg lymphedema sum-score was considered clinically important. Mean difference scores over time with 95% confidence interval were estimated. Multiple linear regression models evaluated baseline predictors associated with the 12 months postoperative lymphedema score, and if early lymphedema predicted lymphedema at 12 months after surgery. Lymphedema condition-specific quality of life was evaluated for women with lymphedema. RESULTS: Seventy-nine % (486/617) completed patient-reported outcome measures at baseline and 12 months. The mean difference score of leg lymphedema from baseline to 12 months was 5.0, confidence interval [3.3, 6.8], that is, below the threshold for clinical importance. Baseline leg lymphedema score and body mass index were positively associated with the leg lymphedema score at 12 months. The leg lymphedema score at 3 months was associated with a higher 12-month score. High scores of lymphedema at 12 months were negatively associated with the women's daily activities, appearance, emotional functioning, and global quality of life and increased their subjective symptom burden. CONCLUSION: Women with low-grade endometrial cancer have a low risk of lymphedema after sentinel lymph node mapping. Leg swelling at baseline and body mass index predicted more lymphedema at 12 months after surgery. Early lymphedema at 3 months predicted persistent lymphedema. A high leg lymphedema score at 12 months is associated with impairment in several aspects of quality of life.

The role of point-of-care ultrasound to monitor response of fluid replacement therapy in pregnancy.

Fluid management in obstetrical care is crucial because of the complex physiological conditions of pregnancy, which complicate clinical manifestations and fluid balance management. This expert review examined the use of point-of-care ultrasound to evaluate and monitor the response to fluid therapy in pregnant patients. Pregnancy induces substantial physiological changes, including increased cardiac output and glomerular filtration rate, decreased systemic vascular resistance, and decreased plasma oncotic pressure. Conditions, such as preeclampsia, further complicate fluid management because of decreased intravascular volume and increased capillary permeability. Traditional methods for assessing fluid volume status, such as physical examination and invasive monitoring, are often unreliable or inappropriate. Point-of-care ultrasound provides a noninvasive, rapid, and reliable means to assess fluid responsiveness, which is essential for managing fluid therapy in pregnant patients. This review details the various point-of-care ultrasound modalities used to measure dynamic changes in fluid status, focusing on the evaluation of the inferior vena cava, lung ultrasound, and left ventricular outflow tract. Inferior vena cava ultrasound in spontaneously breathing patients determines diameter variability, predicts fluid responsiveness, and is feasible even late in pregnancy. Lung ultrasound is crucial for detecting early signs of pulmonary edema before clinical symptoms arise and is more accurate than traditional radiography. The left ventricular outflow tract velocity time integral assesses stroke volume response to fluid challenges, providing a quantifiable measure of cardiac function, which is particularly beneficial in critical care settings where rapid and accurate fluid management is essential. This expert review synthesizes current evidence and practice guidelines, suggesting the integration of point-of-care ultrasound as a fundamental aspect of fluid management in obstetrics. It calls for ongoing research to enhance techniques and validate their use in broader clinical settings, aiming to improve outcomes for pregnant patients and their babies by preventing complications associated with both under- and overresuscitation.

Sex-based disparities in dopamine agonist response in patients with restless legs syndrome.

This study aimed to investigate sex-related differences in the response to ropinirole and pramipexole in patients with restless legs syndrome (RLS). By analysing clinical parameters and polysomnographic (PSG) findings, we sought to elucidate the potential factors related to sex disparities modulating treatment responses and sleep quality in RLS. A total of 41 drug-free patients with RLS, aged ≥18 years, underwent two consecutive nocturnal PSG recordings, without medication at baseline; before the second night, 26 patients received an oral dose of 0.25 mg pramipexole whereas 15 received 0.5 mg ropinirole. After each PSG recording, patients self-evaluated the severity of their previous night symptoms by means of an ad hoc visual analogue scale (VAS). At baseline, sleep efficiency and percentage of Stage N2 tended to be higher in females while wakefulness after sleep onset was significantly higher in males. After treatment, total leg movements during sleep (LMS), periodic LMS (PLMS), and periodicity indexes were significantly lower in females than in males. The VAS score was lower after treatment in all patients, without differences between the two sexes. This study demonstrates a higher acute responsiveness of PLMS to dopamine agonists (pramipexole and ropinirole) in females than in males with RLS. These findings might be explained by differential sex-related expression of dopamine receptors, especially D3, within the central nervous system. In addition, our findings provide translational hints toward a better tailored and sex-specific approach to the treatment of RLS associated with PLMS, with dopamine agonist possibly associated with a better outcome in females than in males.

An expedited model for identifying potential patients with periodic leg movements.

Periodic leg movements during sleep (PLMS) may have crucial consequences in adults. This study aimed to identify baseline characteristics, symptoms, or questionnaires that could help to identify sleep-disordered breathing patients with significant PLMS. Patients aged 20-80 years who underwent polysomnography for assessing sleep disturbance were included. Various factors such as sex, age, body measurements, symptoms, apnea-hypopnea index (AHI), and sleep quality scales were analysed to determine the presence of PLMS. The study included 1480 patients with a mean age of 46.4 ± 13.4 years, among whom 110 (7.4%) had significant PLMS with a PLM index of 15 or higher. There were no significant differences observed in terms of sex or BMI between patients with and without significant PLMS. However, the odds ratios (OR) for PLMS were 4.33, 4.41, and 4.23 in patients who were aged over 50 years, had insomnia, or had an ESS score of less than 10, respectively. Notably, the OR increased up to 67.89 times in patients who presented with all three risk factors. Our analysis identified significant risk factors for PLMS: age over 50, self-reported insomnia, and lower daytime sleepiness levels. These findings aid in identifying potential PLMS patients, facilitating confirmatory examinations and managing associated comorbidities.

The dynamics of cyclic-periodic phenomena during non-rapid and rapid eye movement sleep.

Sleep is a complex physiological state characterized by distinct stages, each exhibiting unique electroencephalographic patterns and physiological phenomena. Sleep research has unveiled the presence of intricate cyclic-periodic phenomena during both non-rapid eye movement and rapid eye movement sleep stages. These phenomena encompass a spectrum of rhythmic oscillations and periodic events, including cyclic alternating pattern, periodic leg movements during sleep, respiratory-related events such as apneas, and heart rate variability. This narrative review synthesizes empirical findings and theoretical frameworks to elucidate the dynamics, interplay and implications of cyclic-periodic phenomena within the context of sleep physiology. Furthermore, it invokes the clinical relevance of these phenomena in the diagnosis and management of sleep disorders.