RESUMEN
Pathologic roles of innate immunity in neurologic disorders are well described, but their beneficial aspects are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induce inflammation. Here, we report that Dectin-1 limited experimental autoimmune encephalomyelitis (EAE), while its downstream signaling molecule, Card9, promoted the disease. Myeloid cells mediated the pro-resolution function of Dectin-1 in EAE with enhanced gene expression of the neuroprotective molecule, Oncostatin M (Osm), through a Card9-independent pathway, mediated by the transcription factor NFAT. Furthermore, we find that the Osm receptor (OsmR) functioned specifically in astrocytes to reduce EAE severity. Notably, Dectin-1 did not respond to heat-killed Mycobacteria, an adjuvant to induce EAE. Instead, endogenous Dectin-1 ligands, including galectin-9, in the central nervous system (CNS) were involved to limit EAE. Our study reveals a mechanism of beneficial myeloid cell-astrocyte crosstalk regulated by a Dectin-1 pathway and identifies potential therapeutic targets for autoimmune neuroinflammation.
Asunto(s)
Astrocitos/inmunología , Encéfalo/patología , Proteínas Adaptadoras de Señalización CARD/metabolismo , Encefalomielitis Autoinmune Experimental/inmunología , Lectinas Tipo C/metabolismo , Esclerosis Múltiple/inmunología , Células Mieloides/inmunología , Inflamación Neurogénica/inmunología , Receptores Mitogénicos/metabolismo , Animales , Comunicación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Galectinas/metabolismo , Regulación de la Expresión Génica , Lectinas Tipo C/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Glicoproteína Mielina-Oligodendrócito/inmunología , Oncostatina M/genética , Oncostatina M/metabolismo , Subunidad beta del Receptor de Oncostatina M/metabolismo , Fragmentos de Péptidos/inmunología , Receptores Mitogénicos/genética , Transducción de SeñalRESUMEN
The balance of myeloid populations and lymphoid populations must be well controlled. Here we found that osteopontin (OPN) skewed this balance during pathogenic conditions such as infection and autoimmunity. Notably, two isoforms of OPN exerted distinct effects in shifting this balance through cell-type-specific regulation of apoptosis. Intracellular OPN (iOPN) diminished the population size of myeloid progenitor cells and myeloid cells, and secreted OPN (sOPN) increase the population size of lymphoid cells. The total effect of OPN on skewing the leukocyte population balance was observed as host sensitivity to early systemic infection with Candida albicans and T cell-mediated colitis. Our study suggests previously unknown detrimental roles for two OPN isoforms in causing the imbalance of leukocyte populations.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Candidiasis/inmunología , Colitis/inmunología , Infecciones/inmunología , Linfocitos/inmunología , Células Mieloides/inmunología , Osteopontina/inmunología , Animales , Apoptosis , Candida albicans , Proliferación Celular , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Linfopoyesis/inmunología , Ratones , Ratones Noqueados , Mielopoyesis/inmunología , Osteopontina/genética , Isoformas de Proteínas , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos TRESUMEN
The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.
RESUMEN
Estrogen is a disease-modifying factor in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) via estrogen receptor alpha (ERα). However, the mechanisms by which ERα signaling contributes to changes in disease pathogenesis have not been completely elucidated. Here, we demonstrate that ERα deletion in dendritic cells (DCs) of mice induces severe neurodegeneration in the central nervous system in a mouse EAE model and resistance to interferon beta (IFNß), a first-line MS treatment. Estrogen synthesized by extragonadal sources is crucial for controlling disease phenotypes. Mechanistically, activated ERα directly interacts with TRAF3, a TLR4 downstream signaling molecule, to degrade TRAF3 via ubiquitination, resulting in reduced IRF3 nuclear translocation and transcription of membrane lymphotoxin (mLT) and IFNß components. Diminished ERα signaling in DCs generates neurotoxic effector CD4+ T cells via mLT-lymphotoxin beta receptor (LTßR) signaling. Lymphotoxin beta receptor antagonist abolished EAE disease symptoms in the DC-specific ERα-deficient mice. These findings indicate that estrogen derived from extragonadal sources, such as lymph nodes, controls TRAF3-mediated cytokine production in DCs to modulate the EAE disease phenotype.
Asunto(s)
Encefalomielitis Autoinmune Experimental , Receptor alfa de Estrógeno , Ratones , Animales , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Linfotoxina/genética , Receptor beta de Linfotoxina/metabolismo , Factor 3 Asociado a Receptor de TNF/genética , Factor 3 Asociado a Receptor de TNF/metabolismo , Estrógenos/farmacología , Fenotipo , Células Dendríticas/metabolismo , Ratones Endogámicos C57BLRESUMEN
The external carotid artery (ECA) plays a major role in supplying blood to the head and neck. Although impeded blood flow in the ECA is expected to affect orofacial functions, few studies have shown how blood flow obstruction in the ECA contributes to impairment of these functions, including chewing and swallowing. This study was performed to investigate the effects of ECA ligation (ECAL) on immediate and long-term changes in masticatory and swallowing functions as well as the jaw-opening reflex evoked in the digastric muscle. The experiments were carried out using male Sprague-Dawley rats. In the acute experiment, the digastric reflex evoked by low-threshold electrical stimulation of the inferior alveolar nerve and the swallow reflex, identified by digastric and thyrohyoid electromyographic (EMG) bursts, were compared between before and 1 h after ECAL. The chronic experiment was conducted on freely moving rats. EMGs of the masseter, digastric, and thyrohyoid muscles were chronically recorded. The long-term effects of ECAL on behavior and muscle histology were compared between rats with an intact ECA and rats with ECAL. In the acute experiment, the peak amplitude of the digastric reflex on the ECAL side was significantly decreased 1 h after ECAL. In the chronic experiment, although most parameters of the masticatory and swallowing EMGs were not significantly different between the groups, the results suggest wide variation of the effect of ECAL on the muscles. Blood supply compensation from collaterals of the internal carotid artery may be permanent in some animals.NEW & NOTEWORTHY The inhibitory effect of unilateral external carotid artery ligation (ECAL) on the ipsilateral digastric reflex was small but evident. Most parameters of masticatory and swallowing muscle activity were not significantly different after ECAL. Wide variation was noted in the effect of ECAL on the ipsilateral muscle activity. Blood supply compensation from collaterals of the internal carotid artery may occur in response to the impaired blood flow.
Asunto(s)
Arteria Carótida Externa , Reflejo , Ratas , Animales , Masculino , Ratas Sprague-Dawley , Electromiografía , Reflejo/fisiología , Masticación/fisiologíaRESUMEN
The sternohyoid muscle depresses the hyoid bone, but it is unclear whether the muscle contributes to respiratory and swallowing mechanisms. This study aimed to clarify whether the sternohyoid muscle participates in the respiration and swallowing reflex and how the activity is modulated in two conditions: with airway stenosis and with a fixed sternohyoid muscle length. Electromyographic activity in the sternohyoid, digastric, thyrohyoid, and diaphragm muscles was recorded in anesthetized rats. The sternohyoid muscle activity was observed in the inspiratory phase and during swallowing, and was well coordinated with digastric and thyrohyoid muscle activity. With airway stenosis, the respiratory activity per respiratory cycle was facilitated in all assessed muscles but the facilitation of activity per second occurred only in the digastric, thyrohyoid, and sternohyoid muscles. With airway stenosis, the swallowing activity was facilitated only in the digastric muscle but not in the thyrohyoid and sternohyoid muscles. Swallowing activity was not observed in the sternohyoid muscle in the condition with the sternohyoid muscle length fixed, although increased inspiratory activity remained. The current results suggest that (1) the sternohyoid muscle is slightly activated in the inspiratory phase, (2) the effect of airway stenosis on respiratory function may differ between the upper airway muscles and diaphragm, and (3) swallowing activity in the sternohyoid muscle is not dominantly controlled by the swallowing central pattern generator but instead occurs as a myotatic reflex.
RESUMEN
Japanese males belong to the Y chromosome C1a1, C2, D1a2a, D1a2a-12f2b, O1b2, O1b2a1a1, O2a2b1, and O2a1b haplogroups. Notably, the regional frequency of each haplogroup is homogeneous. Owing to recent developments in genome sequencing technology, the phylogenetic tree of Y chromosome haplogroups is updated annually. Therefore, in this study, we aimed to provide an update on the Y chromosome haplogroups of modern Japanese males and examine their regional distributions. Using 1,640 samples of Japanese males from seven Japanese cities (Nagasaki, Fukuoka, Tokushima, Osaka, Kanazawa, Kawasaki, and Sapporo), haplogroups C1a1, C2, D1a2a, D1a2a-12f2b, O1b2, and O1b2a1a1 were updated based on the latest phylogenetic tree. Haplogroup C1a1 was mainly classified into C1a1a1a and C1a1a1b subgroups; C1a1a1b was more common in Tokushima and Osaka than in the other regions. Haplogroup C2 was mainly classified into C2a, C2b1a1a, C2b1a1b, C2b1a2, and C2b1b subgroups and exhibited frequency differences in Osaka. Haplogroup D1a2a was classified into D1a2a1c1 and D1a2a2 subgroups, and its frequency varied between Tokushima and Osaka. Haplogroup D1a2a-12f2b was classified into D1a2a1a2b1a1a and D1a2a1a3 subgroups; however, no significant frequency differences were observed. Haplogroup O1b2 was classified into O1b2a1a2a1a, O1b2a1a2a1b, and O1b2a1a3 subgroups, with frequency differences between Nagasaki and Kanazawa. Haplogroup O1b2a1a1 was mainly classified into O1b2a1a1a, O1b2a1a1b, and O1b2a1a1c subgroups; however, no significant frequency differences were observed. Our findings suggest that gene flow in the Kinki region is caused by human migration.
Asunto(s)
Cromosomas Humanos Y , Masculino , Humanos , Japón , Filogenia , Haplotipos , Mapeo CromosómicoRESUMEN
Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system driven by peripheral immune cell infiltration and glial activation. The pathological hallmark of MS is demyelination, and mounting evidence suggests neuronal damage in gray matter is a major contributor to disease irreversibility. While T cells are found in both gray and white matter of MS tissue, they are typically confined to the white matter of the most commonly used mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Here, we used a modified EAE mouse model (Type-B EAE) that displays severe neuronal damage to investigate the interplay between peripheral immune cells and glial cells in the event of neuronal damage. We show that CD4+ T cells migrate to the spinal cord gray matter, preferentially to ventral horns. Compared to CD4+ T cells in white matter, gray matter-infiltrated CD4+ T cells were mostly immobilized and interacted with neurons, which are behaviors associated with detrimental effects to normal neuronal function. T cell-specific deletion of CXCR2 significantly decreased CD4+ T cell infiltration into gray matter in Type-B EAE mice. Further, astrocyte-targeted deletion of TAK1 inhibited production of CXCR2 ligands such as CXCL1 in gray matter, successfully prevented T cell migration into spinal cord gray matter, and averted neuronal damage and motor dysfunction in Type-B EAE mice. This study identifies astrocyte chemokine production as a requisite for the invasion of CD4+T cell into the gray matter to induce neuronal damage.
Asunto(s)
Astrocitos/patología , Linfocitos T CD4-Positivos/metabolismo , Sustancia Gris/patología , Esclerosis Múltiple/patología , Receptores de Interleucina-8B/metabolismo , Animales , Astrocitos/metabolismo , Linfocitos T CD4-Positivos/patología , Quimiocina CXCL1/metabolismo , Quimiocina CXCL5/metabolismo , Quimiocinas/metabolismo , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/patología , Femenino , Quinasas Quinasa Quinasa PAM/genética , Quinasas Quinasa Quinasa PAM/metabolismo , Masculino , Ratones Endogámicos C57BL , Asta Ventral de la Médula Espinal/patología , Imagen de Lapso de TiempoRESUMEN
Mastication is controlled by central pattern generator in the brainstem and can be modulated by volition. The aim of this study was to investigate the effect of chewing well on swallowing. Twenty-six healthy participants were instructed to eat 8, 12, and/or 16 g of steamed rice with barium sulphate under the following two conditions: chewing freely task (CF; chewing naturally in their usual manner) and chewing well task (CW; chewing the food with a request to "chew well"). We evaluated bolus transport and swallowing movement using videofluoroscopy and electromyography of the masseter, suprahyoid and thyrohyoid muscles. The chewing time and pharyngeal transit time (PTT) at the first swallow showed high reproducibility in both CF and CW. PTT for CW was significantly shorter and longer than CF in 12 and 16 g, respectively. In 12 g, CW increased the pharyngeal bolus velocity and decreased thyrohyoid EMG activity during swallowing compared with CF. In 16 g, the difference between CW and CF in the estimated swallowed bolus volume was positively correlated with that in upper esophageal sphincter transit duration. We speculate that CW modulates PTT during swallowing depending on the mouthful volume.
RESUMEN
BACKGROUND: Lingual pressure (LP) generation is cooperatively controlled not only by the intrinsic tongue (I-ton) muscles but also by hyoid muscle activation. However, the measurement of endurance and fatigue properties of I-ton muscles is difficult due to the instability of electrodes. OBJECTIVE: The purpose of this study was to apply suction electrodes to measure electromyograms (EMGs) of I-ton muscle and to evaluate integrated EMG amplitude (iEMG) and mean power frequency (MPF) of EMG in the I-ton and hyoid muscles performing continuous LP. METHODS: Twenty healthy adult volunteers (10 males, 10 females, mean age 28.8 years) were instructed to perform 10-s LP generation tasks at 25%, 50%, 75% and 100% of maximum LP in randomised order with visual feedback. During each task, EMGs of the I-ton, suprahyoid (S-hyo), infrahyoid (I-hyo) and masseter (Mass) muscles were simultaneously recorded. The iEMG and MPF of EMG burst during 10-s LP tasks were compared. The recording period was divided into three substages to analyse temporal changes with the Friedman test. RESULTS: During the 10-s task, the iEMG significantly increased as the LP strength increased (p < .001). There was no time-dependent change in the I-ton iEMG; however, the MPF of the I-ton EMG burst decreased in all tasks (p < .05). The S-hyo and I-hyo iEMGs gradually increased, especially with strong LP (p < .01). CONCLUSION: While I-ton muscles may easily fatigue during 10-s LP generation, S-hyo and I-hyo muscles may help compensate for the weakened I-ton muscle activity by increasing their activity to maintain LP.
Asunto(s)
Músculos Faciales , Lengua , Masculino , Adulto , Femenino , Humanos , Succión , Músculo Masetero , Músculos del Cuello , Electromiografía , Contracción MuscularRESUMEN
BACKGROUND: Liquid modification is a widely established strategy of treatment for patients with dysphagia. The modification of liquid particularly by thickening or carbonation is a common approach to promote safe swallowing. OBJECTIVE: This study sought to investigate how carbonated and/or thickened water modulates swallowing behaviours during swallowing in healthy young individuals. METHODS: Thirty-one healthy volunteers (9 men, 22 women; mean age ± standard deviation [SD], 25.7 ± 6.2 years) were instructed to swallow 20 mL of water, carbonated water and carbonated juice with and without added thickening agent. Electromyograms (EMGs) of the suprahyoid (S-hyo) muscles were recorded to evaluate swallowing behaviours. Obtained S-hyo EMG bursts was analysed using the following outcome parameters: onset latency, the time between swallowing que to onset of EMG burst; rising time and falling time, defined as the time between onset and peak, and between peak and offset, respectively; duration, defined as the time between onset and offset of EMG burst; and area integral value under the waveform. RESULTS: Effects of thickening demonstrated the extended onset latency, EMG burst duration including falling time and the larger area of EMG in thickened liquid compared to thin liquid, but there was not much difference between thin and thickened carbonated liquids. Carbonation significantly decreased the duration including falling time for thickened but not for thin liquids. CONCLUSION: Patients with dysphagia can benefit from use of carbonated or thickened water while the effects on swallowing physiology may differ between carbonation and thickening.
RESUMEN
BACKGROUND: Modification of foods or liquids is commonly administered as part of dysphagia treatment. However, no consensus exists on the parameters for defining texture-modified food for patients with dysphagia. OBJECTIVES: The aim of this study was to evaluate the effect of food/liquid material on swallowing physiology in patients with dysphagia and to discuss the optimal food choice for direct swallowing therapy. MATERIALS AND METHODS: A total of 140 patients underwent a videofluoroscopic swallowing study using three test foods/liquids: 3 mL of mildly thick liquid (Thick liquid), jelly made of agar and polysaccharide (Jelly) and jelly made of pectin (Reset gel). Outcome measures of videofluoroscopic images, bolus transit time and hyoid movements were compared. RESULTS: The frequency of chewing movements was highest for Jelly, followed by Reset gel and Thick liquid. While the probability of oral residue was the highest for Reset gel, pharyngeal residue after swallowing was high for Thick liquid as compared to Jelly and Reset gel. Oral transit time and pharyngeal transit time for Thick liquid were significantly smaller than that for Jelly and Reset gel. Pharyngeal delay time was significantly smaller for Thick liquid than that for Jelly and Reset gel. There was no difference in hyoid elevation time and hyoid movement time among the conditions. CONCLUSION: Mildly thick liquid material may be optimal for patients with primarily oral motor function impairment and jelly, such as Reset gel, may be more suitable for patients with primarily pharyngeal motor function impairment or oral and pharyngeal coordinative motor function decline.
Asunto(s)
Trastornos de Deglución , Deglución , Humanos , Trastornos de Deglución/fisiopatología , Femenino , Masculino , Deglución/fisiología , Anciano , Persona de Mediana Edad , Fluoroscopía , Masticación/fisiología , Anciano de 80 o más Años , Grabación en Video , Hueso Hioides/fisiopatología , Hueso Hioides/diagnóstico por imagen , Adulto , AlimentosRESUMEN
BACKGROUND: It remains unclear how the salivary flow and the fat content of food affect bolus formation during mastication. OBJECTIVES: We aimed to clarify: (1) how hyposalivation affects jaw-closing and hyoid-elevating muscle activities in bolus formation, and (2) if the effect of hyposalivation on muscle activity depends on the fat content of food. METHODS: Eighteen healthy male volunteers were instructed to freely ingest four test foods: Plain, Fat without seasoning, Fat with seasoning, and Soft rice crackers. Masseter and suprahyoid electromyographic activities were recorded before and 30 min after the administration of atropine sulfate, a muscarinic receptor antagonist that induces hyposalivation. RESULTS: Hyposalivation extended the masticatory duration significantly in all the test foods except Fat with seasoning. Masticatory cycle time was significantly longer with vs without hyposalivation for the Soft (p = .011). Suprahyoid activity/cycle was significantly greater with vs without hyposalivation (p = .013). Masticatory cycle time was significantly longer at the late stage with vs without hyposalivation for the Soft (p < .001). Suprahyoid activity/cycle was significantly greater at the middle (p = .045) and late stages (p = .002) with vs without hyposalivation for the Soft and greater at the late stage with vs without hyposalivation for the Plain (p = .043). Changes in masticatory cycle time and suprahyoid activity/cycle for these foods had significantly positive relationship (p < .001). CONCLUSION: Hyposalivation-induced changes in masticatory behaviours resulted from the middle and late stage suprahyoid activity. Fat content and seasoning compensate for salivary flow inhibition.
Asunto(s)
Electromiografía , Voluntarios Sanos , Masticación , Saliva , Humanos , Masculino , Masticación/fisiología , Adulto , Saliva/química , Xerostomía/fisiopatología , Adulto Joven , Salivación/efectos de los fármacos , Salivación/fisiología , Músculo Masetero/fisiología , Músculo Masetero/efectos de los fármacos , Grasas de la Dieta , Atropina/farmacologíaRESUMEN
Anticholinergic medication causes impaired swallowing with hyposalivation. However, the underlying mechanisms by which these drugs modulate the swallowing reflex remain unclear. This study investigated the effects of the muscarinic acetylcholine receptor (mAChR) nonspecific antagonist atropine on the initiation of swallowing. Experiments were performed on 124 urethane-anesthetized rats. A swallow was evoked by either topical laryngeal application of a small amount of distilled water (DW), saline, citric acid, or capsaicin; upper airway distention with a continuous airflow; electrical stimulation of the superior laryngeal nerve (SLN); or focal microinjection of N-methyl-d-aspartate (NMDA) into the lateral region of the nucleus of the solitary tract (L-nTS). Swallows were identified by electromyographic bursts of the digastric and thyrohyoid muscles. Either atropine, the peripheral mAChR antagonist methylatropine, or antagonists of mAChR subtypes M1-M5 were intravenously delivered. Atropine at a dose of 1 mg/kg increased the number of DW-evoked swallows compared with baseline and did not affect the number of swallows evoked by saline, citric acid, capsaicin, or upper airway distention. Methylatropine and M1-M5 antagonists did not significantly change the number of DW-evoked swallows. Bilateral SLN transection completely abolished DW-evoked swallows, and atropine decreased the swallowing threshold of SLN electrical stimulation. Finally, microinjection of NMDA receptor antagonist AP-5 into the L-nTS inhibited DW-evoked swallows, and atropine facilitated the initiation of swallowing evoked by NMDA microinjection into this region. These results suggest that atropine facilitates DW-evoked swallows via central mAChR actions.NEW & NOTEWORTHY Atropine facilitated the distilled water (DW)-evoked swallows in anesthetized rats. Atropine decreased the swallowing threshold evoked by electrical stimulation of the superior laryngeal nerve, which is a primary sensory nerve for the initiation of DW-evoked swallows. Atropine facilitated the swallows evoked by N-methyl-d-aspartate microinjection into the lateral region of the nucleus of the solitary tract, which is involved in the DW-evoked swallows. We speculate that atropine facilitates the DW-evoked swallows via central muscarinic receptor actions.
Asunto(s)
Atropina , N-Metilaspartato , Ratas , Animales , Ratas Sprague-Dawley , Atropina/farmacología , N-Metilaspartato/farmacología , Agua/farmacología , Capsaicina/farmacología , Derivados de Atropina/farmacología , Deglución/fisiología , Estimulación Eléctrica , Receptores Muscarínicos , Ácido Cítrico/farmacología , Reflejo/fisiologíaRESUMEN
The number of patients with end-stage renal failure is increasing annually worldwide and the problem is compounded by a shortage of renal transplantation donors. In our previous research, we have shown that transplantation of renal progenitor cells into the nephrogenic region of heterologous fetuses can induce the development of nephrons. We have also developed transgenic mice in which specific renal progenitor cells can be removed by drugs. By combining these two technologies, we have succeeded in generating human-mouse chimeric kidneys in fetal mice. We hope to apply these technologies to regenerative medicine. The quality of nephron progenitor cells (NPCs) derived from human pluripotent stem cells is important for the generation of chimeric kidneys, but there is currently no simple evaluation system for the chimerogenic potential of human NPCs. In this study, we focused on the fact that the re-aggregation of mouse renal progenitor cells can be used for nephron formation, even when merged into single cells. First, we examined the conditions under which nephron formation is likely to occur in mice during re-aggregation. Next, to improve the differentiation potential of human NPCs derived from pluripotent stem cells, NPCs were sorted using Integrin subunit alpha 8 (ITGA8). Finally, we demonstrated chimera formation between different species by mixing mouse cells with purified, selectively-induced human NPCs under optimum conditions. We observed these chimeric organoids at different time points to learn about these human-mouse chimeric structures at various stages of renal development. We found that the rate of chimera formation was affected by the purity of the human NPCs and the cell ratios used. We demonstrated that chimeric nephrons can be generated using a simple model, even between distant species. We believe that this admixture of human and mouse renal progenitor cells is a promising technology with potential application for the evaluation of the chimera formation abilities of NPCs.
Asunto(s)
Riñón , Nefronas , Humanos , Ratones , Animales , Células Madre Embrionarias , Diferenciación Celular , Ratones Transgénicos , OrganoidesRESUMEN
PURPOSE: The study aims to determine the effectiveness of bridging sutures in preventing iris capture and a subsequent reverse pupillary block after an intrascleral fixation of an implanted intraocular lens (IOL). METHODS: We studied 6 eyes that had an iris capture with reverse pupillary block due to a dislocated IOL after an intrascleral fixation. After the dislocated IOL was repositioned, 10-0 polypropylene sutures were inserted 1.5 mm posterior to the limbus and directed to run between the iris and the IOL. The sutures were placed orthogonal to the haptics of the IOL. Anterior segment optical coherence tomography (AS-OCT) was used in 4 eyes to evaluate the degree of iridodonesis before and after the bridging sutures. The heights of the temporal and nasal sectors of the middle iris from the iris plane (the line between anterior chamber angles) were compared for each 0.2-s AS-OCT image taken immediately after the eye moved from a lateral to a primary position. RESULTS: None of the eyes had a recurrence of the iris capture after the bridging sutures. The refractive error, anterior chamber depth, and vision were not significantly altered after the bridging sutures were placed. The AS-OCT images showed that the height of the nasal iris was decreased more at 0 s postoperatively blocking the excessive downward movement of the nasal iris but not the iridodonesis. CONCLUSION: Bridging sutures were effective in preventing iris capture and subsequent reverse pupillary block after an intrascleral fixation of an IOL.
Asunto(s)
Enfermedades del Iris , Lentes Intraoculares , Trastornos de la Pupila , Humanos , Implantación de Lentes Intraoculares/métodos , Esclerótica/cirugía , Iris/cirugía , Suturas , Estudios Retrospectivos , Técnicas de SuturaRESUMEN
PURPOSE: To compare the effects of macular intraretinal hemorrhage (IRH) and macular hole (MH) on best-corrected visual acuity (BCVA) after displacement of submacular hemorrhage (SMH) due to retinal arterial macroaneurysm (RAM) rupture. METHODS: This multicenter retrospective study included 48 eyes with SMH due to RAM rupture. Cases underwent vitrectomy to displace SMH and were followed up for 6 months. We classified cases according to the presence of IRH and MH and compared the postoperative BCVA among the groups. RESULTS: We classified the eyes into IRH(+)MH(+) group (10 eyes), IRH(+)MH(-) group (23 eyes), and IRH(-)MH(-) group (15 eyes). The postoperative BCVA was significantly worse in the IRH(+)MH(+) and IRH(+)MH(-) groups than in the IRH(-)MH(-) group (0.91 ± 0.41 in logarithm of the minimal angle of resolution units, Snellen equivalent 20/163, 0.87 ± 0.45, 20/148, and 0.18 ± 0.21, 20/30, respectively; P < 0.001). The postoperative central retinal thickness was significantly lower in the IRH(+) group (IRH(+)MH(+) and IRH(+)MH(-) groups combined) than in the IRH(-) group (IRH(-)MH(-) group) (121.4 ± 70.1 µ m and 174.3 ± 32.9 µ m, respectively, P = 0.008). The postoperative external limiting membrane and ellipsoid zone continuities were significantly discontinuous in the IRH(+) group ( P < 0.001, P = 0.001, respectively). The multiple linear regression analysis showed that both IRH(+)MH(+) and IRH(+)MH(-) were associated with the postoperative BCVA (regression coefficient, 0.799 and 0.711, respectively; P < 0.001 for both). CONCLUSION: Both IRH and MH were poor prognostic indicators in cases with SMH due to RAM rupture.
Asunto(s)
Macroaneurisma Arterial de Retina , Perforaciones de la Retina , Humanos , Perforaciones de la Retina/diagnóstico , Perforaciones de la Retina/etiología , Perforaciones de la Retina/cirugía , Estudios Retrospectivos , Macroaneurisma Arterial de Retina/complicaciones , Macroaneurisma Arterial de Retina/diagnóstico , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/etiología , Hemorragia Retiniana/cirugía , Pronóstico , Vitrectomía , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To report on the feasibility of 27-gauge (G) vitrectomy for pediatric patients. METHODS: This study is an international, multicenter, retrospective, interventional case series. Participants were patients 17 years or younger who underwent 27-G vitrectomy for various indications. RESULTS: The records of 56 eyes from 47 patients were reviewed. Mean age was 5.7 ± 5.2 years. Diagnoses included retinopathy of prematurity (Stages 3 with vitreous hemorrhage, 4A, 4B, and 5), Terson's syndrome, traumatic macular hole, posterior capsular opacification, endophthalmitis, and others. Instruments used were the 27-G infusion, 27-G vitreous cutter, 27-G light pipe, and 27-G internal limiting membrane forceps. Instrument bending was noted in one (1.8%) case. There were no cases with intraoperative complications, infusion issues, or postoperative endophthalmitis. There were 67/145 (46%) sclerotomies that required suturing, of which most (51/145) were sutured out of precaution. There were four cases (7.1%) that required conversion to a larger gauge and three cases (5.3%) that developed postoperative hypotony. Mean visual acuity improved from logarithm of the minimum angle of resolution 1.32 (20/420) to 0.72 (20/105), after a mean follow-up of 125.1 days (P = 0.01). Anatomic success was achieved in 96.4% of eyes after a single surgery. CONCLUSION: Twenty-seven-gauge vitrectomy was safe and feasible in selected pediatric vitreoretinopathies. Further studies are warranted to examine indications and outcomes.
Asunto(s)
Endoftalmitis , Degeneración Retiniana , Cirugía Vitreorretiniana , Recién Nacido , Humanos , Niño , Lactante , Preescolar , Vitrectomía , Estudios Retrospectivos , Resultado del Tratamiento , Hemorragia Vítrea/cirugía , Endoftalmitis/etiología , Endoftalmitis/cirugía , Retina , Complicaciones Posoperatorias/cirugía , Degeneración Retiniana/cirugíaRESUMEN
BACKGROUND: To determine the incidence and characteristics of the multiple subretinal particles (SRPs) present after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). METHODS: The medical records of 224 eyes of 224 patients that underwent PPV for RRD were reviewed. The presence of SRPs in the subretinal fluid blebs and the presence of subretinal deposits were determined by optical coherence tomography (OCT) and fundus autofluorescence (FAF). The characteristics of the FAF and infrared reflectance (IR) images of a scanning laser ophthalmoscope in eyes with SRPs (SRPs group) were compared to that of eyes without SRPs (control group). RESULTS: SRPs were observed in 27 eyes (12%), and they were completely resolved in 20 eyes (74%) after 6 months. The incidence of macula-off RRD (85%) and preoperative precipitates (41%) were significantly higher in the SRPs group than that in the control group (64%, P = 0.046; 12%, P = 0.002). The axial length was significantly shorter in the SRPs group than that in the control group (25.04 ± 1.54 mm, 26.00 ± 1.78 mm, P = 0.012). The preoperative and postoperative best-corrected visual acuity were not significantly different between the two groups (P = 0.702, P = 0.337). The subretinal fluid bleb determined by OCT were hyperfluorescent in the FAF images in 24 eyes (89%), and the subretinal deposits were hypofluorescent with solid appearance by OCT other than fluid in 3 eyes (11%). The hypofluorescent subretinal deposits in the FAF images were bright in the IR images in 2 eyes. CONCLUSIONS: The SRPs consist of lipofuscin-related hyperfluorescent subretinal fluid and the subretinal deposits containing bright IR melanin particles of proliferating retinal pigment epithelial cells.
Asunto(s)
Desprendimiento de Retina , Humanos , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/cirugía , Vitrectomía/métodos , Estudios Retrospectivos , Agudeza Visual , Retina , Tomografía de Coherencia Óptica/métodosRESUMEN
The effects of head and neck alignment and pharyngeal anatomy on epiglottic inversion remain unclear. This study investigated the factors involved in epiglottic inversion, including head and neck alignment and pharyngeal anatomy, in patients with dysphagia. Patients with a chief complaint of dysphagia and who underwent videofluoroscopic swallowing study at our hospital from January to July 2022 were enrolled. They were divided into three groups based on the degree of epiglottic inversion as the complete-inversion (CI), partial-inversion (PI), and non-inversion group (NI) groups. Data were compared among the three groups; a total of 113 patients were analyzed. The median age was 72.0 (IQR: 62.0-76.0) years; 41 (36.3%) and 72 (63.7%) were women and men, respectively. There were in 45 (39.8%) patients in the CI, 39 (34.5%) in the PI, and 29 (25.7%) in the NI groups, respectively. Single-variable analysis revealed significant relation to epiglottic inversion of Food Intake LEVEL Scale score, penetration-aspiration score with 3-mL thin liquid bolus, epiglottic vallecula and pyriform sinus residue, hyoid position and displacement during swallowing, pharyngeal inlet angle (PIA), epiglottis to posterior pharyngeal wall distance, and body mass index. Logistic regression analysis with complete epiglottic inversion as the dependent variable revealed the X coordinate at maximum hyoid elevation position during swallowing and PIA as significant explanatory variables. These results suggest that epiglottic inversion is constrained in patients with dysphagia who have poor head and neck alignment or posture and a narrow pharyngeal cavity just before swallowing.