Emergent order in hydrodynamic spin lattices.

Macroscale analogues1-3 of microscopic spin systems offer direct insights into fundamental physical principles, thereby advancing our understanding of synchronization phenomena4 and informing the design of novel classes of chiral metamaterials5-7. Here we introduce hydrodynamic spin lattices (HSLs) of 'walking' droplets as a class of active spin systems with particle-wave coupling. HSLs reveal various non-equilibrium symmetry-breaking phenomena, including transitions from antiferromagnetic to ferromagnetic order that can be controlled by varying the lattice geometry and system rotation8. Theoretical predictions based on a generalized Kuramoto model4 derived from first principles rationalize our experimental observations, establishing HSLs as a versatile platform for exploring active phase oscillator dynamics. The tunability of HSLs suggests exciting directions for future research, from active spin-wave dynamics to hydrodynamic analogue computation and droplet-based topological insulators.

Minimal Quantization Model in Pilot-Wave Hydrodynamics.

Investigating how classical systems may manifest dynamics analogous to those of quantum systems is a broad subject of fundamental interest. Walking droplets, which self-propel through a resonant interaction with their own wave field, provide a unique macroscopic realization of wave-particle duality that exhibits behaviors previously thought exclusive to quantum particles. Despite significant efforts, elucidating the precise origin and form of the wave-mediated forces responsible for the walker's quantumlike behavior remained elusive. Here, we demonstrate that, owing to wave interference, the force responsible for orbital quantization originates from waves excited near stationary points on the walker's past trajectory. Moreover, we derive a minimal model with the essential ingredients to capture quantized orbital dynamics, including quasiperiodic and chaotic orbits. Notably, this minimal model provides an explicit distinction between local forces, which account for the walker's preferred speed and wave-induced added mass, and spatiotemporal nonlocal forces responsible for quantization. The quantization mechanism revealed here is generic, and will thus play a role in other hydrodynamic quantum analogs.

Walking droplets in a circular corral: Quantisation and chaos.

A millimetric liquid droplet may walk across the surface of a vibrating liquid bath through a resonant interaction with its self-generated wavefield. Such walking droplets, or "walkers," have attracted considerable recent interest because they exhibit certain features previously believed to be exclusive to the microscopic, quantum realm. In particular, the intricate motion of a walker confined to a closed geometry is known to give rise to a coherent wave-like statistical behavior similar to that of electrons confined to quantum corrals. Here, we examine experimentally the dynamics of a walker inside a circular corral. We first illustrate the emergence of a variety of stable dynamical states for relatively low vibrational accelerations, which lead to a double quantisation in angular momentum and orbital radius. We then characterise the system's transition to chaos for increasing vibrational acceleration and illustrate the resulting breakdown of the double quantisation. Finally, we discuss the similarities and differences between the dynamics and statistics of a walker inside a circular corral and that of a walker subject to a simple harmonic potential.

Improved lipid-lowering treatment and reduction in cardiovascular disease burden in homozygous familial hypercholesterolemia: The SAFEHEART follow-up study.

AIM: We aimed to describe clinical and genetic characteristics, lipid-lowering treatment and atherosclerotic cardiovascular disease (ASCVD) outcomes over a long-term follow-up in homozygous familial hypercholesterolemia (HoFH). METHODS: SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is a long-term study in molecularly diagnosed FH. Data analyzed in HoFH were prospectively obtained from 2004 until 2022. ASCVD events, lipid profile and lipid-lowering treatment were determined. RESULTS: Thirty-nine HoFH patients were analyzed. The mean age was 42 ± 20 years and nineteen (49%) were women. Median follow-up was 11 years (IQR 6,18). Median age at genetic diagnosis was 24 years (IQR 8,42). At enrolment, 33% had ASCVD and 18% had aortic valve disease. Patients with new ASCVD events and aortic valve disease at follow-up were six (15%), and one (3%), respectively. Median untreated LDL-C levels were 555 mg/dL (IQ 413,800), and median LDL-C levels at last follow-up was 122 mg/dL (IQR 91,172). Most patients (92%) were on high intensity statins and ezetimibe, 28% with PCSK9i, 26% with lomitapide, and 23% with lipoprotein-apheresis. Fourteen patients (36%) attained an LDL-C level below 100 mg/dL, and 10% attained an LDL-C below 70 mg/dL in secondary prevention. Patients with null/null variants were youngers, had higher untreated LDL-C and had the first ASCVD event earlier. Free-event survival is longer in patients with defective variant compared with those patients with at least one null variant (p=0.02). CONCLUSIONS: HoFH is a severe life threating disease with a high genetic and phenotypic variability. The improvement in lipid-lowering treatment and LDL-C levels have contributed to reduce ASCVD events.

Piperacillin-Tazobactam as an Adjuvant in the Mechanical Treatment of Patients with Periodontitis: A Randomized Clinical Study.

In this study, the aim was to evaluate the effects of the adjuvant piperacillin-tazobactam solution in the mechanical treatment of periodontitis. A single-blind split-mouth randomized study, it included 24 participants. All of them presented periodontitis stage III according to the 2018 World Workshop classification and the presence of at least one of the following periodontal pathogens: Aggregatibacter actinomycetemcomitans; Porphyromona gingivalis; Treponema denticola; Tannerella forsythia; Prevotella intermedia. The study established two groups: a control group (SRP: scaling and root planing) and a test group (SRP plus local piperacillin-tazobactam). The final recruitment included 11 women (45.8%) and 13 men (54.2%). The age range was between 25 and 72 years, and the mean age was 57 ± 10.20 years. Clinical controls were performed at 2 weeks, 3 months, and 6 months, repeating the SRP and applying the piperacillin-tazobactam solution again at the 3-month appointment. The clinical attachment level decreased by a mean of 2.13 ± 0.17 mm from the baseline to 6 months in the test group versus 1.63 ± 0.18 mm in the control group. The mean probing pocket depth decreased from 1.32 ± 0.09 mm in the test group, versus from 0.96 ± 0.14 mm on the control side. The plaque index in the test group decreased by 0.46 ± 0.04, while it decreased by an average of 0.31 ± 0.04 in the control group. In conclusion, the local use of piperacillin-tazobactam as complementary therapy produces better clinical results in patients with periodontitis. However, these results are not maintained over time, and so a more persistent local application is necessary.

Analysis of the Radiological Changes of the Sinus Membrane Using Cone Beam Computed Tomography and Its Relationship with Dental Treatments. A Retrospective Study.

The aim of this study was to identify the most relevant dental factors and iatrogenic causes in the development of pathological changes to the sinus membrane and to analyse their possible influence on the development of odontogenic sinusitis. A descriptive, observational study was designed, with 276 patients who had been evaluated via cone beam computed tomography, analysing possible sinus thickening factors, such as apical infections, endodontic treatments, periodontitis, radicular cysts and impacted teeth, as well as iatrogenic factors caused by implant treatments or the development of oroantral communications produced during tooth extraction manoeuvres. Among the dental factors, periodontitis (47.1%), apical pathology (23.5%) and endodontic treatments (23.1%) were the predominant causes of sinus membrane thickening that most frequently produced an occupancy between 2 and 10 mm. Regarding the implant treatments, the placement of implants through the floor of the maxillary sinus was the main cause (9.8%), followed by sinus elevation techniques (6.2%). Dental extraction was the first cause of oroantral communication (5.0%), being the procedure that caused the greatest thickening of the sinus membrane. This study highlights the importance of dental treatments and iatrogenic factors in sinus pathology, and the need for diagnostic interrelations between the different specialists who address this pathology.

Dental Transmigration: An Observational Retrospective Study OF52 Mandibular Canines.

The aim of this study was to analyze the prevalence of transmigrated canines in a Spanish population by evaluating their clinical and radiological characteristics. The descriptive observational study obtained 6840 orthopantomographs from all patients seeking dental care in the years 2017-21 via the Patient Reception Service and Dentistry Service at the Faculty of Dentistry at the Complutense University of Madrid and the Central Hospital of the Red Cross of Madrid (Spain). In total, 52 patients presented transmigrated canines, establishing a prevalence of 0.76%. This sample comprised 28 women and 24 men. Whenever a transmigrated canine was identified, a CBCT scan was obtained and used to evaluate the clinical and radiological variables associated with canine transmigration. The predominant side of the transmigration was the left (57.69%) compared to the right side (42.30%). The position of the canine, in order of frequency, according to the Mupparapu classification, corresponded to type IV (42.30%), type II (36.53%), type I (15.38%), and type V (5.76%), with no type III transmigrations found. Clinical manifestations were only recorded in 17.30% of cases, and 11.53% of the radiological findings showed the presence of tooth cysts that were confirmed by histopathological studies. Other impactions, in addition to the transmigrated canine, were found in five patients (9.61%), with the majority being the presence of third molars.

A hydrodynamic analog of Friedel oscillations.

We present a macroscopic analog of an open quantum system, achieved with a classical pilot-wave system. Friedel oscillations are the angstrom-scale statistical signature of an impurity on a metal surface, concentric circular modulations in the probability density function of the surrounding electron sea. We consider a millimetric drop, propelled by its own wave field along the surface of a vibrating liquid bath, interacting with a submerged circular well. An ensemble of drop trajectories displays a statistical signature in the vicinity of the well that is strikingly similar to Friedel oscillations. The droplet trajectories reveal the dynamical roots of the emergent statistics. Our study elucidates a new mechanism for emergent quantum-like statistics in pilot-wave hydrodynamics and so suggests new directions for the nascent field of hydrodynamic quantum analogs.

Molecular basis of the familial chylomicronemia syndrome in patients from the National Dyslipidemia Registry of the Spanish Atherosclerosis Society.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is an extremely rare lipoprotein disorder caused by mutations in at least 5 genes of the lipoprotein lipase (LPL) complex. OBJECTIVE: This work shows the molecular analysis of patients diagnosed with FCS, who attended the Spanish Arteriosclerosis Society lipid units and were included in the National Dyslipidemia Registry. METHODS: Among the 238 patients registered with severe hypertriglyceridemia (fasting triglycerides >1000 mg/dL), 26 were diagnosed with FCS as they had confirmed postheparin plasma LPL activity deficiency and/or homozygosity for loss-of-function mutations in LPL, GPIHBP1, APOC2, LMF1, or Apolipoprotein A5 (APOA5). RESULTS: Among the 26 FCS cases, 23 had mutations in the homozygous state: 19 in LPL and 4 in the GPIHBP1 gene. The molecular analysis revealed 3 novel mutations: 2 in LPL, in 2 unrelated patients (c.312delA; p.Asp105Thrfs*66 and c.629A>G; p.His210Arg), and 1 in GPHIBP1 in a third patient (c.502delC; p.Leu168Serfs*83). These 3 patients had confirmed lack of LPL activity. Three additional patients with confirmed LPL activity deficiency were heterozygous carriers of mutations in the genes analyzed. Among these, we found 2 novel mutations in APOA5 (c.50-1G>A and c.326_327insC; p.Tyr110Leufs*158). CONCLUSION: We have identified 5 novel pathogenic mutations: 2 in LPL, 1 in GPIHBP1, and 2 in the APOA5 gene. The genetic defaults accounting for the LPL activity deficiency of 23 of them have been clearly identified and 3 patients, who harbored mutations in heterozygosity, were diagnosed based on LPL activity deficiency, which raises the question of the involvement of new genes in the manifestation of FCS.

Clinical and molecular characteristics of homozygous familial hypercholesterolemia patients: Insights from SAFEHEART registry.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder associated with very high levels of cholesterol, accelerated atherosclerosis and very premature death, often secondary to occlusion of the coronary ostia by supravalvular atheroma in untreated individuals. OBJECTIVE: To describe molecular and clinical characteristics of HoFH enrolled at SAFEHEART registry and to evaluate the role of the type of mutation in clinical expression. METHODS: SAFEHEART is a registry of molecularly defined familial hypercholesterolemia patients. A standardized phone call is made every year for the follow-up. Patients with confirmed HoFH were selected. Molecular and clinical characteristics were analyzed. RESULTS: Thirty-four HoFH patients (27 true HoFH, 4 compound heterozygous familial hypercholesterolemia, and 3 autosomal recessive hypercholesterolemia) have been enrolled in the period 2004-2015. Twenty different mutations in LDLR gene have been detected. Sixteen patients carry defective mutations (DMs), and 15 carry null mutations (NMs). Only patients with NMs met low-density lipoprotein cholesterol (LDL-C) criteria for clinical diagnosis. Patients with NMs had higher untreated LDL-C levels (P < .0001), more aortic valve stenosis (P < .05), and lower age at first cardiovascular event (P < .05) compared to patients with DMs. In the follow-up, 1 liver transplant patient died and 3 cases underwent revascularization procedures. Eight cases started LDL apheresis and 1 case had a liver transplant. CONCLUSIONS: HoFH phenotypic expression is highly variable. These patients have high atherosclerotic coronary artery disease risk including aortic valve stenosis and do not achieve the LDL-C treatment goals with standard therapy.

Attainment of LDL-Cholesterol Treatment Goals in Patients With Familial Hypercholesterolemia: 5-Year SAFEHEART Registry Follow-Up.

BACKGROUND: Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data on attainment of treatment targets; large registries that reflect real-life clinical practice can uniquely provide this information. OBJECTIVES: We sought to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients enrolled in a large national registry. METHODS: The SAFEHEART study (Spanish Familial Hypercholesterolemia Cohort Study) is a large, ongoing registry of molecularly defined patients with heterozygous FH treated in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was investigated in relation to use of lipid-lowering therapy (LLT). RESULTS: The study recruited 4,132 individuals (3,745 of whom were ≥18 years of age); 2,752 of those enrolled were molecularly diagnosed FH cases. Mean follow-up was 5.1 ± 3.1 years; 71.8% of FH cases were on maximal LLT, and an LDL-C treatment target <100 mg/dl was reached by only 11.2% of patients. At follow-up, there was a significant increase in the use of ezetimibe, drug combinations with statins, and maximal LLT. The presence of type 2 diabetes mellitus, a defective allele mutation, ezetimibe use, and the absence of previous ASCVD were predictors of the attainment of LDL-C goals. CONCLUSIONS: Despite the use of intensified LLT, many FH patients continue to experience high plasma LDL-C levels and, consequently, do not achieve recommended treatment targets. Type of LDL-receptor mutation, use of ezetimibe, coexistent diabetes, and ASCVD status can bear significantly on the likelihood of attaining LDL-C treatment goals.

Molecular characterization of familial hypercholesterolemia in Spain: identification of 39 novel and 77 recurrent mutations in LDLR.

Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), an autosomal dominant inherited disorder associated with an increased risk of premature atherosclerosis. The aim of this study was to characterize the LDLR mutations in a group of 476 apparently non-related Spanish FH patients. The promoter region and the 18 exons with their flanking intron sequences of the LDLR gene were screened by PCR-SSCP analysis and DNA sequencing. In addition, we tested for the presence of the mutation p.R3500Q in the gene coding for apolipoprotein B-100 (apo B-100). We found 77 mutations previously described, and 39 novel mutations affecting the LDLR gene: 8 missense, 5 nonsense, 15 frameshift, 5 splicing, 4 in frame, one nucleotide change in the non-coding sequence of exon 1, and one silent variant. We have identified al least one of these LDLR gene mutations in 329 subjects (69%). Four patients were homozygous, 4 patients were compound heterozygous, 48 patients were found to carry two different sequence variants in the same allele and 4 patients carried three different sequence variants in the same allele. Additionally, 4 subjects were carriers of the p.R3500Q mutation in the apo B gene. All of these findings indicate that there is a broad spectrum of mutations and sequence variants in the LDLR gene causing FH in Spain.