Determining the changes in morphology and loading status following medial displacement calcaneal osteotomy for flatfoot using patient-specific finite element models.

Medial displacement calcaneal osteotomy (MDCO) is the standard procedure for flatfoot. We investigated the effect of MDCO on the foot using a finite element analysis. Foot models were created from computed tomography data of 8 patients with flat feet. MDCO was performed on each model with bone translation distance of 4, 8, and 12 mm. The morphological changes, plantar pressures, and stress percentage on the talocrural and subtalar joints were evaluated before and after surgery. Morphological evaluation showed improvement in the medial longitudinal arch. The stress percentage of plantar pressure in the medial area decreased, and the stress percentage of plantar pressure in the mid- and lateral forefoot area increased. At the talocrural joint, the medial and middle stress percentage increased, while the lateral and posterior stress percentage decreased. In the subtalar joint, the stress percentage in the middle subtalar joint increased and that in the posterior subtalar joint decreased. Within the posterior subtalar joint, the anterior and medial stress percentage increased, while the posterior and lateral stress percentage decreased. Preoperative simulation using the finite element analysis may be useful in understanding postoperative morphological changes and loading conditions to perform patient-specific surgery.

Whole-Exome Sequencing Revealed a Pathogenic Germline Variant in the Fumarate Hydratase Gene, Leading to the Diagnosis of Hereditary Leiomyomatosis and Renal Cell Cancer.

The diagnosis of hereditary skin tumors is difficult for "old" diagnostic tools such as immunohistochemistry. Whole-exome sequencing analysis as a "new" diagnostic tool enables us to make a final diagnosis in spite of unknown hereditary diseases in the past. Hereditary leiomyomatosis and renal cell cancer are autosomal dominant hereditary cancer syndromes characterized by uterine myomas, cutaneous leiomyomas, and aggressive renal cell cancer. The syndrome is associated with pathogenic germline variants in the fumarate hydratase gene. Herein, we demonstrate a pathogenic germline variant of the fumarate hydratase gene in a 60-year-old woman with multiple cutaneous leiomyomas, leading to the diagnosis of hereditary leiomyomatosis and renal cell cancer. Whole-exome sequencing analysis using genomic DNA extracted from peripheral blood leukocytes revealed one germline variant in the FH gene on chromosome 1 (c.290G>A, p.Gly97Asp). She received total hysterectomy due to uterine myoma, which strongly supported the diagnosis. No tumor was detected in her kidney by computed tomography and ultrasound examination. Genetic examination for the mutation of the fumarate hydratase gene is important in order to reach the correct diagnosis and to detect renal cancer at its early stage.

[Neural Mechanisms of Visual Search and Working Memory].

Visual search is a useful experimental paradigm investigating various aspects of attention. For efficient search, participants must avoid revisiting previously viewed objects. Inhibitory tagging and inhibition of return are phenomena related to this process, but their neural mechanisms are yet to be elucidated. Recent studies have shown that the rate of revisit behavior during visual search correlates with working memory capacity. This suggests that top-down signals from the frontal executive system alter the priority map that guides attention and eye movements. With this in mind, we have developed a novel visual search paradigm with many identical distractors and an evaluation model that assesses multiple parameters of working memory. The model incorporated memory capacity, memory decay, and utility rate, and when applied to data obtained from experimental animals, these parameters could be reliably evaluated. Furthermore, using the behavioral paradigm and model, we found that systemic administration of subanesthetic dose of ketamine decreased utility rate and memory capacity, while nicotine administration increased utility rate. Since our behavioral paradigm does not require complex instruction, it can be applied to a variety of patients in future clinical studies.

Preparation of Waterborne Silicone-Modified Polyurethane Nanofibers and the Effect of Crosslinking Agents on Physical Properties.

Silicone-modified polyurethane (PUSX) refers to the introduction of a silicone short chain into the polyurethane chain to make it have the dual properties of silicone and polyurethane (PU). It can be used in many fields, such as coatings, films, molding products, adhesives, and so on. The use of organic solvents to achieve the fiberization of silicone-modified polyurethane has been reported. However, it is challenging to achieve the fiberization of silicone-modified polyurethane based on an environmentally friendly water solvent. Herein, we report a simple and powerful strategy to fabricate environmentally friendly waterborne silicone-modified polyurethane nanofiber membranes through the addition of polyethylene glycol (PEG) with different molecular weights using electrospinning technology and in situ doping with three crosslinking agents with different functional groups (a polyoxazoline crosslinking agent, a polycarbodiimide crosslinking agent, and a polyisocyanate crosslinking agent) combined with various heating treatment conditions. The influence of PEG molecular weight on fiber formation was explored. The morphology, structure, water resistance, and mechanical properties were analyzed regarding the effect of the introduction of silicone into PU. The effects of the type and content of crosslinking agent on the morphology and physical properties of PUSX nanofiber membranes are discussed. These results show that the introduction of silicone can improve the water resistance and high temperature resistance of waterborne PU, and the addition of a crosslinking agent can further improve the water resistance of the sample, so that the sample can maintain good morphology after immersion. Crosslinking agents with different functional groups had different effects on the mechanical properties of PUSX nanofiber membranes due to different reactions. Among them, the oxazoline crosslinking agent had a significant effect on improving tensile strength, while the isocyanate crosslinking agent had a significant effect on improving the elongation at break. The PUSX nanofiber membrane prepared in this work did not use organic solvents that were harmful to humans and the environment, and it can be used in outdoor textiles, oil-water separation, medical health, and other fields.

Temporal Information Processing in the Cerebellum and Basal Ganglia.

Temporal information processing in the range of a few hundred milliseconds to seconds involves the cerebellum and basal ganglia. In this chapter, we present recent studies on nonhuman primates. In the studies presented in the first half of the chapter, monkeys were trained to make eye movements when a certain amount of time had elapsed since the onset of the visual cue (time production task). The animals had to report time lapses ranging from several hundred milliseconds to a few seconds based on the color of the fixation point. In this task, the saccade latency varied with the time length to be measured and showed stochastic variability from one trial to the other. Trial-to-trial variability under the same conditions correlated well with pupil diameter and the preparatory activity in the deep cerebellar nuclei and the motor thalamus. Inactivation of these brain regions delayed saccades when asked to report subsecond intervals. These results suggest that the internal state, which changes with each trial, may cause fluctuations in cerebellar neuronal activity, thereby producing variations in self-timing. When measuring different time intervals, the preparatory activity in the cerebellum always begins approximately 500 ms before movements, regardless of the length of the time interval being measured. However, the preparatory activity in the striatum persists throughout the mandatory delay period, which can be up to 2 s, with different rate of increasing activity. Furthermore, in the striatum, the visual response and low-frequency oscillatory activity immediately before time measurement were altered by the length of the intended time interval. These results indicate that the state of the network, including the striatum, changes with the intended timing, which lead to different time courses of preparatory activity. Thus, the basal ganglia appear to be responsible for measuring time in the range of several hundred milliseconds to seconds, whereas the cerebellum is responsible for regulating self-timing variability in the subsecond range. The second half of this chapter presents studies related to periodic timing. During eye movements synchronized with alternating targets at regular intervals, different neurons in the cerebellar nuclei exhibit activity related to movement timing, predicted stimulus timing, and the temporal error of synchronization. Among these, the activity associated with target appearance is particularly enhanced during synchronized movements and may represent an internal model of the temporal structure of stimulus sequence. We also considered neural mechanism underlying the perception of periodic timing in the absence of movement. During perception of rhythm, we predict the timing of the next stimulus and focus our attention on that moment. In the missing oddball paradigm, the subjects had to detect the omission of a regularly repeated stimulus. When employed in humans, the results show that the fastest temporal limit for predicting each stimulus timing is about 0.25 s (4 Hz). In monkeys performing this task, neurons in the cerebellar nuclei, striatum, and motor thalamus exhibit periodic activity, with different time courses depending on the brain region. Since electrical stimulation or inactivation of recording sites changes the reaction time to stimulus omission, these neuronal activities must be involved in periodic temporal processing. Future research is needed to elucidate the mechanism of rhythm perception, which appears to be processed by both cortico-cerebellar and cortico-basal ganglia pathways.

Bodily maps of uncertainty and surprise in musical chord progression and the underlying emotional response.

Music has profoundly shaped the human experience across cultures and generations, yet its impact on our minds and bodies remains elusive. This study examined how the perception of musical chord elicits bodily sensations and emotions through the brain's predictive processing. By deploying body-mapping tests and emotional evaluations on 527 participants exposed to chord progressions, we unveiled the intricate interplay between musical uncertainty, prediction error in eliciting specific bodily sensations and emotions. Our results demonstrated that certain chord progressions elicit cardiac and abdominal sensations, linked to interoception, and associated with aesthetic appreciation and positive valence. These findings highlight the crucial role of musical uncertainty and prediction error in emotional response and sound embodiment. This study offers insight into the potential connection between music-induced interoception and mental well-being, underscoring the musical effects on our minds and bodies.

Enhancing Wear Resistance in Functionally Graded Metallic Components: Insights from Nanoindentation and Mechanical Analysis.

To manufacture metallic components with high wear resistance, treatments such as nitriding and carburising followed by quenching and tempering (NQT and CQT, respectively) are applied to various types of steel to increase the hardness (H) of the friction surface. However, the wear mechanism of the resulting functionally graded materials has not been fully understood. In this study, specimens of industrial 99.82% pure iron treated with NQT at 913 and 1033 K, and CQT at 1203 K, as well as hot-rolled sheets without heat treatment were examined by performing nanoindentation tests to measure changes in their H, reduced Young's moduli (Er), elastic deformation energies (We), and plastic deformation energies (Wp) along the depth direction. The relationship between Wp/We and the elastic strain resistance (H/Er) can be expressed for all specimens via the equation Wp/We = -1.0 + 0.16 (H/Er)-1. Furthermore, the obtained H/Er av measured at 5 µm intervals based on the specimen profile and wear volume has a good correlation depending to the sliding distance, as confirmed by the results of the ring-on-plate sliding tests conducted for the carbon-treated, nitrogen-treated, and hot-rolled specimens. This study provides a new approach, using H/Er parameters to identify the dominant factors affecting wear resistance at the initial stage of wear that may contribute to the development of wear-resistant materials.

Histological analysis of neuronal changes in the olfactory cortex during pregnancy.

Fluctuations in olfactory sensitivity are widely known to occur during pregnancy and may be responsible for hyperemesis gravidarum. These changes are thought to be caused by structural and functional alterations in neurons in response to marked changes of the hormonal milieu. In this study, we examined changes in neurons in the olfactory cortex during pregnancy and after delivery in rats. Dendritic spine densities were measured in the piriform cortex (PIR) and posterolateral cortical amygdala (COApl), which are involved in olfaction. The results showed increased numbers of dendritic spines in the PIR in mid-pregnancy and in the COApl during early and late pregnancy, but not in the motor area of the cerebral cortex, indicating a correlation with changes in olfactory sensitivity during pregnancy. Immunohistochemical analysis of expression of ovarian hormone receptors in these brain regions revealed a decrease in the number of estrogen receptor α-positive cells during pregnancy in the PIR and during pregnancy and the postpartum period in the COApl. Regarding pregnancy-related peptide hormones, oxytocin receptors were expressed in the PIR and COApl, while prolactin receptors were not found in these regions. Accordingly, oxytocin-containing neurites were distributed in both regions. These results suggest that the balance of these hormonal signals has an effect on olfactory sensitivity in pregnant females.

Detection of biomagnetic signals from induced pluripotent stem cell-derived cardiomyocytes using deep learning with simulation data.

The detection of spontaneous magnetic signals can be used for the non-invasive electrophysiological evaluation of induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs). We report that deep learning with a dataset that combines magnetic signals estimated using numerical simulation and actual noise data is effective in the detection of weak biomagnetic signals. To verify the feasibility of this method, we measured artificially generated magnetic signals that mimic cellular magnetic fields using a superconducting quantum interference device and attempted peak detection using a long short-term memory network. We correctly detected 80.0% of the peaks and the method achieved superior detection performance compared with conventional methods. Next, we attempted peak detection for magnetic signals measured from mouse iPS-CMs. The number of detected peaks was consistent with the spontaneous beats counted using microscopic observation and the average peak waveform achieved good similarity with the prediction. We also observed the synchronization of peak positions between simultaneously measured field potentials and magnetic signals. Furthermore, the magnetic measurements of cell samples treated with isoproterenol showed potential for the detection of chronotropic effects. These results suggest that the proposed method is effective and has potential application in the safety assessment of regenerative medicine and drug screening.

Validation of Wistar-Kyoto rats kept in solitary housing as an animal model for depression using voxel-based morphometry.

Major depressive disorder is a common psychiatric condition often resistant to medication. The Wistar-Kyoto (WKY) rat has been suggested as an animal model of depression; however, it is still challenging to translate results from animal models into humans. Solitary housing is a mild stress paradigm that can simulate the environment of depressive patients with limited social activity due to symptoms. We used voxel-based morphometry to associate the solitary-housed WKY (sWKY) rat model with data from previous human studies and validated our results with behavioural studies. As a result, atrophy in sWKY rats was detected in the ventral hippocampus, caudate putamen, lateral septum, cerebellar vermis, and cerebellar nuclei (p < 0.05, corrected for family-wise error rate). Locomotor behaviour was negatively correlated with habenula volume and positively correlated with atrophy of the cerebellar vermis. In addition, sWKY rats showed depletion of sucrose consumption not after reward habituation but without reward habituation. Although the application of sWKY rats in a study of anhedonia might be limited, we observed some similarities between the regions of brain atrophy in sWKY rats and humans with depression, supporting the translation of sWKY rat studies to humans.

Diurnal Variation of Brain Activity in the Human Suprachiasmatic Nucleus.

The suprachiasmatic nucleus (SCN) is the central clock for circadian rhythms. Animal studies have revealed daily rhythms in the neuronal activity in the SCN. However, the circadian activity of the human SCN has remained elusive. In this study, to reveal the diurnal variation of the SCN activity in humans, we localized the SCN by employing an areal boundary mapping technique to resting-state functional images and investigated the SCN activity using perfusion imaging. In the first experiment (n = 27, including both sexes), we scanned each participant four times a day, every 6 h. Higher activity was observed at noon, while lower activity was recorded in the early morning. In the second experiment (n = 20, including both sexes), the SCN activity was measured every 30 min for 6 h from midnight to dawn. The results showed that the SCN activity gradually decreased and was not associated with the electroencephalography. Furthermore, the SCN activity was compatible with the rodent SCN activity after switching off the lights. These results suggest that the diurnal variation of the human SCN follows the zeitgeber cycles of nocturnal and diurnal mammals and is modulated by physical lights rather than the local time.

Asymptomatic subarachnoid hemorrhage following carotid endarterectomy: illustrative case.

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting are common surgical interventions for internal carotid artery stenosis. Cerebral hyperperfusion syndrome (CHS) is a well-known complication of both procedures that can lead to intracranial hemorrhage and worsen clinical outcomes. Here, the authors report a rare case of non-aneurysmal subarachnoid hemorrhage (SAH) following CEA and review the relevant literature. OBSERVATIONS: A 70-year-old woman with hypertension and diabetes presented with progressive visual loss in the right eye and was diagnosed with ocular ischemic syndrome. Imaging revealed severe right cervical carotid artery stenosis. CEA was performed with no complications. Postoperatively, the patient's blood pressure was tightly controlled, with no evidence of CHS. However, an asymptomatic SAH was detected on postoperative day 7. Careful observation and blood pressure control were maintained. Since follow-up magnetic resonance imaging (MRI) showed no enlarging of the SAH and the patient was asymptomatic, she was discharged on postoperative day 15 with a modified Rankin scale score of 0. LESSONS: This case highlights the potential occurrence of non-aneurysmal SAH as a rare complication of CEA, even in asymptomatic patients. Repeated postoperative MRI is necessary to detect such complications. It is crucial to carefully control blood pressure after CEA regardless of symptoms.

Roles of Stress Response in Autophagy Processes and Aging-Related Diseases.

The heat shock factor 1 (HSF1)-mediated stress response pathway and autophagy processes play important roles in the maintenance of proteostasis. Autophagy processes are subdivided into three subtypes: macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy. Recently, molecular chaperones and co-factors were shown to be involved in the selective degradation of substrates by these three autophagy processes. This evidence suggests that autophagy processes are regulated in a coordinated manner by the HSF1-mediated stress response pathway. Recently, various studies have demonstrated that proteostasis pathways including HSF1 and autophagy are implicated in longevity. Furthermore, they serve as therapeutic targets for aging-related diseases such as cancer and neurodegenerative diseases. In the future, these studies will underpin the development of therapies against various diseases.

A Single Intradermal Injection of Autologous Adipose-Tissue-Derived Stem Cells Rejuvenates Aged Skin and Sharpens Double Eyelids.

Facial skin aging is the most visible manifestation of aging in the body. In this study, we aimed to rejuvenate aging skin via a one-time intradermal injection of autologous adipose-derived stem cells (ADSCs). Eight patients were enrolled for study. Photographs of patients taken immediately before and 1, 3, 6, and 12 months after ADSC injections were comparatively evaluated for visible skin manifestations. ADSCs were cultured from the abdominal-skin-derived subcutaneous fat tissue, and 1 × 108 cultured ADSCs were injected intradermally into the facial skin. Cultured myoblasts were incubated with the supernatant derived from ADSCs, and the effect was evaluated via glucose consumption and lactic acid production in the medium. Eight cases showed the shallowing and disappearance of wrinkles, including those of the glabella, lower eyelids, crow`s feet, and forehead and nasolabial grooves, a month to several months after treatment. Double eyelids became prominent, and facial pores significantly reduced in size. These effects lasted for over one year. Myoblasts cultured in the presence of an ADSC-derived exosome were activated compared to that of ADSCs cultured without supernatant. The result supports the role of muscle in ADSC skin rejuvenation. The present study first reports that a single intradermal administration of cultured ADSCs rejuvenates aged facial skin over the course of one year. Further, patients exhibited definite double eyelids and pore shrinkage, strongly indicating the active involvement of muscle, which was supported by an in vitro study. Our study also suggested the important role of biological factors delivered from injected stem cells, although the detailed mechanism of rejuvenation effects of ADSC skin injection remains to be clarified.

Sensory and motor representations of internalized rhythms in the cerebellum and basal ganglia.

Both the cerebellum and basal ganglia are involved in rhythm processing, but their specific roles remain unclear. During rhythm perception, these areas may be processing purely sensory information, or they may be involved in motor preparation, as periodic stimuli often induce synchronized movements. Previous studies have shown that neurons in the cerebellar dentate nucleus and the caudate nucleus exhibit periodic activity when the animals prepare to respond to the random omission of regularly repeated visual stimuli. To detect stimulus omission, the animals need to learn the stimulus tempo and predict the timing of the next stimulus. The present study demonstrates that neuronal activity in the cerebellum is modulated by the location of the repeated stimulus and that in the striatum (STR) by the direction of planned movement. However, in both brain regions, neuronal activity during movement and the effect of electrical stimulation immediately before stimulus omission were largely dependent on the direction of movement. These results suggest that, during rhythm processing, the cerebellum is involved in multiple stages from sensory prediction to motor control, while the STR consistently plays a role in motor preparation. Thus, internalized rhythms without movement are maintained as periodic neuronal activity, with the cerebellum and STR preferring sensory and motor representations, respectively.

Origin of Unexpected Ir3+ in a Superconducting Candidate Sr2IrO4 System Analyzed by Photoelectron Holography.

The reason for the absence of superconductivity in Sr2IrO4 was estimated by photoelectron spectra and photoelectron holograms. The analysis of the La photoelectron hologram concluded that La atoms are substituted to Sr sites. Two O 1s peaks were observed and were identified as the oxygens in the IrO2 and SrO planes by photoelectron holography and density functional theory (DFT) calculations. In the Ir 4f spectrum of Sr2IrO4, an unexpected Ir3+ peak was observed as much as 50% of all of the Ir. The photoelectron hologram of Ir3+ showed a displacement of about 0.15 Å. This displacement is thought to be due to the oxygen vacancies in the IrO2 plane. These oxygen vacancies and the associated local displacement of the atoms might inhibit superconductivity in spite of sufficient electron doping.

High-dose ubiquinol supplementation in multiple-system atrophy: a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial.

Background: Functionally impaired variants of COQ2, encoding an enzyme in biosynthesis of coenzyme Q10 (CoQ10), were found in familial multiple system atrophy (MSA) and V393A in COQ2 is associated with sporadic MSA. Furthermore, reduced levels of CoQ10 have been demonstrated in MSA patients. Methods: This study was a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial. Patients with MSA were randomly assigned (1:1) to either ubiquinol (1500 mg/day) or placebo. The primary efficacy outcome was the change in the unified multiple system atrophy rating scale (UMSARS) part 2 at 48 weeks. Efficacy was assessed in all patients who completed at least one efficacy assessment (full analysis set). Safety analyses included patients who completed at least one dose of investigational drug. This trial is registered with UMIN-CTR (UMIN000031771), where the drug name of MSA-01 was used to designate ubiquinol. Findings: Between June 26, 2018, and May 27, 2019, 139 patients were enrolled and randomly assigned to the ubiquinol group (n = 69) or the placebo group (n = 70). A total of 131 patients were included in the full analysis set (63 in the ubiquinol group; 68 in the placebo group). This study met the primary efficacy outcome (least square mean difference in UMSARS part 2 score (-1.7 [95% CI, -3.2 to -0.2]; P = 0.023)). The ubiquinol group also showed better secondary efficacy outcomes (Barthel index, Scale for the Assessment and Rating of Ataxia, and time required to walk 10 m). Rates of adverse events potentially related to the investigational drug were comparable between ubiquinol (n = 15 [23.8%]) and placebo (n = 21 [30.9%]). Interpretation: High-dose ubiquinol was well-tolerated and led to a significantly smaller decline of UMSARS part 2 score compared with placebo. Funding: Japan Agency for Medical Research and Development.

Candida Pneumonia in a Young Vegan Man with Diabetic Ketoacidosis.

A 39-year-old vegan man was admitted with diabetic ketoacidosis. He had also developed pneumonia that was unresponsive to antibiotics. Based on bronchoscopy findings, the diagnosis of Candida pneumonia was made, and the pulmonary shadow disappeared rapidly after antifungal therapy. Candida pneumonia has been mostly reported in severely immunocompromised patients. This is a rare case of Candida pneumonia that was found in a young vegan man with diabetes mellitus (DM). Although malnutrition caused by DM or an unbalanced diet is often underestimated as a cause of immunodeficiency, these conditions can be risk factors for serious opportunistic infections, including Candida pneumonia.

Phenotypic screening using waveform analysis of synchronized calcium oscillations in primary cortical cultures.

At present, in vitro phenotypic screening methods are widely used for drug discovery. In the field of epilepsy research, measurements of neuronal activities have been utilized for predicting efficacy of anti-epileptic drugs. Fluorescence measurements of calcium oscillations in neurons are commonly used for measurement of neuronal activities, and some anti-epileptic drugs have been evaluated using this assay technique. However, changes in waveforms were not quantified in previous reports. Here, we have developed a high-throughput screening system containing a new analysis method for quantifying waveforms, and our method has successfully enabled simultaneous measurement of calcium oscillations in a 96-well plate. Features of waveforms were extracted automatically and allowed the characterization of some anti-epileptic drugs using principal component analysis. Moreover, we have shown that trajectories in accordance with the concentrations of compounds in principal component analysis plots were unique to the mechanism of anti-epileptic drugs. We believe that an approach that focuses on the features of calcium oscillations will lead to better understanding of the characteristics of existing anti-epileptic drugs and allow to predict the mechanism of action of novel drug candidates.

A novel homozygous nonsense variant of LMF1 in pregnancy-induced hypertriglyceridemia with acute pancreatitis.

Hypertriglyceridemia (HTG)-induced pancreatitis during pregnancy could lead to maternal and fetal death. However, its genetic bases are not fully understood, and its treatment strategies are yet to be established. Here we report a case with a novel homozygous nonsense variant of LMF1 in pregnancy-associated HTG with acute pancreatitis. Our patient had childhood-onset severe HTG that had been well-controlled by dietary management in the non-pregnant period with plasma triglyceride (TG) levels at around 200 mg/dL. Milky plasma was noted at the first-trimester pregnancy checkup, followed by a severe increase in plasma TG (10,500 mg/dL) that resulted in pancreatitis in the last trimester. The implementation of strict dietary fat restriction (less than 4 grams per day) reduced plasma TG levels and led to successful delivery. Exome sequencing revealed a novel homozygous nonsense variant in LMF1 (c.697C>T, p.Arg233Ter). The activities of lipoprotein lipase (LPL) and hepatic lipase in post-heparin plasma were not abolished but reduced. The use of pemafibrate decreased plasma TG levels with a concomitant increase in LPL activity. HTG in childhood or early pregnancy is commonly assumed to be polygenic in origin but should be regarded as a feature suggestive of monogenic hyperchylomicronemia. Adequate TG monitoring and dietary fat restriction should be implemented to prevent potentially lethal events of pancreatitis.