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1.
J Neurosci ; 43(9): 1530-1539, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36669887

RESUMO

The velocity-storage circuit participates in the vestibulopostural reflex, but its role in the postural reflex requires further elucidation. The velocity-storage circuit differentiates gravitoinertial information into gravitational and inertial cues using rotational cues. This implies that a false rotational cue can cause an erroneous estimation of gravity and inertial cues. We hypothesized the velocity-storage circuit is a common gateway for all vestibular reflex pathways and tested that hypothesis by measuring the postural and perceptual responses from a false inertial cue estimated in the velocity-storage circuit. Twenty healthy human participants (40.5 ± 8.2 years old, 6 men) underwent two different sessions of earth-vertical axis rotations at 120°/s for 60 s. During each session, the participants were rotated clockwise and then counterclockwise with two different starting head positions (head-down and head-up). During the first (control) session, the participants kept a steady head position at the end of rotation. During the second (test) session, the participants changed their head position at the end of rotation, from head-down to head-up or vice versa. The head position and inertial motion perception at the end of rotation were aligned with the inertia direction anticipated by the velocity-storage model. The participants showed a significant correlation between postural and perceptual responses. The velocity-storage circuit appears to be a shared neural integrator for the vestibulopostural reflex and vestibular perception. Because the postural responses depended on the inertial direction, the postural instability in vestibular disorders may be the consequence of the vestibulopostural reflex responding to centrally estimated false vestibular cues.SIGNIFICANCE STATEMENT The velocity-storage circuit appears to participate in the vestibulopostural reflex, which stabilizes the head and body position in space. However, it is still unclear whether the velocity-storage circuit for the postural reflex is in common with that involved in eye movement and perception. We evaluated the postural and perceptual responses to a false inertial cue estimated by the velocity-storage circuit. The postural and perceptual responses were consistent with the inertia direction predicted in the velocity-storage model and were correlated closely with each other. These results show that the velocity-storage circuit is a shared neural integrator for vestibular-driven responses and suggest that the vestibulopostural response to a false vestibular cue is the pathomechanism of postural instability clinically observed in vestibular disorders.


Assuntos
Sinais (Psicologia) , Percepção de Movimento , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Movimentos Oculares , Postura/fisiologia , Reflexo , Percepção de Movimento/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia
2.
Br J Haematol ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39104032

RESUMO

The optimal treatment strategy for newly diagnosed primary central nervous system lymphoma (PCNSL) has yet to be established, especially in the elderly. In the current study, we conducted a phase II study to evaluate the efficacy and safety of rituximab plus high-dose MTX followed by rituximab plus cytarabine in patients aged ≥60 years newly diagnosed with PCNSL. Patients received an induction treatment of high-dose methotrexate plus rituximab followed by two cycles of a consolidation treatment of cytarabine plus rituximab. The primary end-point was a 2-year progression-free survival (PFS) rate. A total of 35 patients were recruited, and their median age was 73 (range: 60-81). After induction treatment, the complete and partial responses (PRs) were 56% and 20% respectively. Twenty-six patients proceeded to the consolidation treatment; the complete and PRs were 59% and 9% respectively. After a median follow-up duration of 36.0 months, the 2-year PFS rate was 58.7%. Treatment was generally well-tolerated as only three patients were withdrawn from the study due to toxicity, and no treatment-related mortality was reported. The 2-year overall survival rate was 77.9%. The current study may suggest the feasibility of administering high-dose MTX plus cytarabine in PCNSL patients aged ≥60 years and the potential role of additive rituximab.

3.
Biochem Biophys Res Commun ; 710: 149892, 2024 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-38581951

RESUMO

Chlorination is a potent disinfectant against various microorganisms, including bacteria and viruses, by inducing protein modifications and functional changes. Chlorine, in the form of sodium hypochlorite, stands out as the predominant sanitizer choice due to its cost-effectiveness and powerful antimicrobial properties. Upon exposure to chlorination, proteins undergo modifications, with amino acids experiencing alterations through the attachment of chloride or oxygen atoms. These modifications lead to shifts in protein function and the modulation of downstream signaling pathways, ultimately resulting in a bactericidal effect. However, certain survival proteins, such as chaperones or transcription factors, aid organisms in overcoming harsh chlorination conditions. The expression of YabJ, a highly conserved protein from Staphylococcus aureus, is regulated by a stress-activated sigma factor called sigma B (σB). This research revealed that S. aureus YabJ maintains its structural integrity even under intense chlorination conditions and harbors sodium hypochlorite molecules within its surface pocket. Notably, the pocket of S. aureus YabJ is primarily composed of amino acids less susceptible to chlorination-induced damage, rendering it resistant to such effects. This study elucidates how S. aureus YabJ evades the detrimental effects of chlorination and highlights its role in sequestering sodium hypochlorite within its structure. Consequently, this process enhances resilience and facilitates adaptation to challenging environmental conditions.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Cloretos/metabolismo , Hipoclorito de Sódio/farmacologia , Hipoclorito de Sódio/metabolismo , Proteínas de Bactérias/metabolismo , Aminoácidos/metabolismo
4.
Haematologica ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38841794

RESUMO

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

5.
Cerebellum ; 23(2): 856-860, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37227606

RESUMO

Opsoclonus refers to saccadic oscillations without an intersaccadic interval occurring in multiple planes. Opsoclonus mostly indicates dysfunction of the brainstem or cerebellum. We report opsoclonus induced by horizontal head-shaking without other signs of brainstem or cerebellar dysfunction in two patients with vestibular migraine (VM). The development of opsoclonus after horizontal head-shaking indicates unstable or hyperactive neural circuits between the excitatory and inhibitory saccadic premotor burst neurons in these patients with VM.


Assuntos
Transtornos de Enxaqueca , Transtornos da Motilidade Ocular , Humanos , Movimentos Sacádicos , Tronco Encefálico , Cerebelo , Vertigem
6.
Cerebellum ; 23(5): 1892-1898, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38498146

RESUMO

Paroxysmal positional nystagmus frequently occurs in lesions involving the cerebellum, and has been ascribed to disinhibition and enhanced canal signals during positioning due to cerebellar dysfunction. This study aims to elucidate the mechanism of central positional nystagmus (CPN) by determining the effects of baclofen on the intensity of paroxysmal positional downbeat nystagmus due to central lesions. Fifteen patients with paroxysmal downbeat CPN were subjected to manual straight head-hanging before administration of baclofen, while taking baclofen 30 mg per day for at least one week, and two weeks after discontinuation of baclofen. The maximum slow phase velocity (SPV) and time constant (TC) of the induced paroxysmal downbeat CPN were analyzed. The positional vertigo was evaluated using an 11-point numerical rating scale (0 to 10) in 9 patients. After treatment with baclofen, the median of the maximum SPV of paroxysmal downbeat CPN decreased from 30.1°/s [interquartile range (IQR) = 19.6-39.0°/s] to 15.2°/s (IQR = 11.2-22.0°/s, Wilcoxon signed rank test, p < 0.001) with the median decrement ratio at 40.2% (IQR = 28.2-50.6%). After discontinuation of baclofen, the maximum SPV re-increased to 24.6°/s (IQR = 13.1-34.4°/s, Wilcoxon signed rank test, p = 0.001) with the median increment ratio at 23.5% (IQR = 5.2-87.9%). In contrast, the TCs of paroxysmal downbeat CPN remained unchanged at approximately 3.0 s throughout the evaluation. The positional vertigo also decreased with the medication (Wilcoxon signed rank test, p = 0.020), and remained unchanged even after discontinuation of medication (Wilcoxon signed rank test, p = 0.737). The results of this study support the prior presumption that paroxysmal CPN is caused by enhanced responses of the semicircular canals during positioning due to cerebellar disinhibition. Baclofen may be tried in symptomatic patients with paroxysmal CPN.


Assuntos
Baclofeno , Nistagmo Patológico , Humanos , Baclofeno/uso terapêutico , Baclofeno/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Nistagmo Patológico/tratamento farmacológico , Nistagmo Patológico/fisiopatologia , Adulto , Relaxantes Musculares Centrais/uso terapêutico , Agonistas dos Receptores de GABA-B/uso terapêutico , Agonistas dos Receptores de GABA-B/farmacologia
7.
Cerebellum ; 23(5): 2003-2011, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38702560

RESUMO

Two vestibular signals, rotational and inertial cues, converge for the perception of complex motion. However, how vestibular perception is built on neuronal behaviors and decision-making processes, especially during the simultaneous presentation of rotational and inertial cues, has yet to be elucidated in humans. In this study, we analyzed the perceptual responses of 20 participants after pairwise rotational experiments, comprised of four control and four test sessions. In both control and test sessions, participants underwent clockwise and counterclockwise rotations in head-down and head-up positions. The difference between the control and test sessions was the head re-orientation relative to gravity after rotations, thereby providing only rotational cues in the control sessions and both rotational and inertial cues in the test sessions. The accuracy of perceptual responses was calculated by comparing the direction of rotational and inertial cues acquired from participants with that predicted by the velocity-storage model. The results showed that the accuracy of rotational perception ranged from 80 to 95% in the four control sessions but significantly decreased to 35 to 75% in the four test sessions. The accuracy of inertial perception in the test sessions ranged from 50 to 70%. The accuracy of rotational perception improved with repetitive exposure to the simultaneous presentation of both rotational and inertial cues, while the accuracy of inertial perception remained steady. The results suggested a significant interaction between rotational and inertial perception and implied that vestibular perception acquired in patients with vestibular disorders are potentially inaccurate.


Assuntos
Percepção de Movimento , Vestíbulo do Labirinto , Humanos , Rotação , Masculino , Feminino , Percepção de Movimento/fisiologia , Adulto Jovem , Adulto , Vestíbulo do Labirinto/fisiologia , Sinais (Psicologia) , Movimentos da Cabeça/fisiologia , Orientação/fisiologia
8.
Cell Commun Signal ; 22(1): 518, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39449023

RESUMO

Although the efficacy of trastuzumab deruxtecan (T-DXd) against HER2-positive gastric cancers (GCs) has driven its clinical application, the precise mechanisms governing its immunomodulatory role remain unclear. In this study, we examined the immune-related mechanisms of action of T-DXd in GC cells. T-DXd exhibited potent antitumor effects in GC cells across diverse HER2 expression levels by inducing DNA damage and apoptosis. Activation of the DNA damage response by T-DXd led to increased PD-L1 expression. RNA-Seq analysis revealed that T-DXd modulated immune-related pathways, resulting in the upregulation of genes associated with inflammation and IFN signaling. Importantly, T-DXd activated the cGAS-STING pathway, inducing an IFN-I response in HER2-positive GC cells. Furthermore, T-DXd activated dendritic cells via the cancer cell-intrinsic cGAS-STING-IFN axis and enhanced PBMC-mediated tumor cell killing by activating CD8+ T cells. These findings provide valuable insights into the role of the cytosolic DNA sensing pathway in the action of T-DXd and offer a compelling rationale for combining T-DXd with immune checkpoint blockade therapies in GC treatment.


Assuntos
Proteínas de Membrana , Nucleotidiltransferases , Transdução de Sinais , Neoplasias Gástricas , Trastuzumab , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Células Dendríticas/imunologia , Animais , Apoptose/efeitos dos fármacos , Dano ao DNA , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Camundongos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Camptotecina/análogos & derivados , Imunoconjugados
9.
Eur J Neurol ; 31(6): e16261, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38411317

RESUMO

BACKGROUND AND PURPOSE: The etiological distribution of oculomotor nerve palsy has varied amongst the studies. This study aimed to define the clinical features and underlying etiologies of isolated oculomotor nerve palsy by recruiting patients from all departments in a referral-based university hospital. METHODS: The medical records of 672 patients who had a confirmed diagnosis of isolated oculomotor nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, South Korea, from 2003 to 2020 were reviewed. A proportion of the etiology of isolated oculomotor nerve palsy was also compared with that of patients pooled from the previous studies that were searched on PubMed in May 2022. RESULTS: The most common etiology was microvascular (n = 168, 26.5%), followed by vascular anomalies (n = 110, 17.4%), neoplastic (n = 86, 13.6%), inflammatory (n = 79, 12.5%), idiopathic (n = 60, 9.5%) and traumatic (n = 53, 8.4%). Neurologists were mainly involved in the management of microvascular and inflammatory oculomotor nerve palsies whilst ophthalmologists mainly participated in the care of idiopathic, neoplastic and traumatic palsies. Neurosurgeons mostly took care of oculomotor nerve palsy due to vascular anomalies. CONCLUSIONS: The proportion of etiologies of isolated oculomotor nerve palsy may differ according to the specialties involved in the management. The results of previous studies on the etiological distribution of isolated oculomotor nerve palsy should be interpreted with this consideration.


Assuntos
Doenças do Nervo Oculomotor , Humanos , Doenças do Nervo Oculomotor/etiologia , Doenças do Nervo Oculomotor/epidemiologia , Pessoa de Meia-Idade , Adulto , Masculino , Feminino , Idoso , Adolescente , Adulto Jovem , Criança , Idoso de 80 Anos ou mais , Pré-Escolar , República da Coreia/epidemiologia
10.
Eur J Neurol ; 31(5): e16242, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38344918

RESUMO

BACKGROUND AND PURPOSE: Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma. METHODS: A retrospective search of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed. RESULTS: Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain. CONCLUSIONS: This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.


Assuntos
Diplopia , Transtornos da Motilidade Ocular , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Transtornos da Motilidade Ocular/diagnóstico , Movimentos Oculares , Cerebelo , Paralisia
11.
Bioorg Chem ; 143: 107070, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38190796

RESUMO

Three new fusidane-type nortriterpenoids, simplifusinolide A, 24-epi simplifusinolide A, and simplifusidic acid L (1-3), were isolated from the EtOAc extract of the Arctic marine-derived fungus Simplicillium lamellicola culture medium, together with fusidic acid (4) and 16-O-deacetylfusicid acid (5). The structures of the isolated compounds were elucidated by NMR and MS analyses. The absolute configurations of compounds 1-3 were established by the quantum mechanical calculations of electronic circular dichroism and gauge-including atomic orbital NMR chemical shifts, followed by DP4 + analysis. Benign prostatic hyperplasia (BPH) is a major urological disorder in men worldwide. The anti-BPH potentials of the isolated compounds were evaluated using BPH-1 and WPMY-1 cells. Treatment with simplifusidic acid L (3) and fusidic acid (4) significantly downregulated the mRNA levels of the androgen receptor (AR) and its downstream effectors, inhibiting the proliferation of BPH-1 cells. Specifically, treatment with 24-epi simplifusinolide A (2) significantly suppressed the cell proliferation of both BPH-1 and DHT-stimulated WPMY-1 cells by inhibiting AR signaling. These results suggest the potential of 24-epi simplifusinolide A (2), simplifusidic acid L (3) and fusidic acid (4) as alternative agents for BPH treatment by targeting AR signaling.


Assuntos
Hypocreales , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/tratamento farmacológico , Ácido Fusídico/farmacologia , Extratos Vegetais/farmacologia , Proliferação de Células
12.
BMC Pulm Med ; 24(1): 69, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308277

RESUMO

BACKGROUND: Viral infection is a risk factor for asthma exacerbation (AE). However, bacterial infections related to AE in adults are poorly known. On the other hand, obese patients with asthma have their own clinical and biological characteristics compared with non-obese patients. METHODS: We investigated the differences in isolated pathogens for AE between obese and non-obese patients with asthma. We included 407 patients with AE from 24 medical centers in Korea. Microorganisms isolated from culture, RT-PCR or serologic tests using lower respiratory tract specimens were retrospectively investigated. RESULTS: A total of 171 obese and 236 non-obese patients with asthma were included for analysis. Compared to non-obese patients, obese patients were associated with women (77.2% vs. 63.6%), never smoker (82.5% vs. 73.9%), shorter duration of asthma (7.9 ± 8.4 vs. 10.5 ± 10.1 years), less history of pulmonary tuberculosis (8.8% vs. 17.4%), and more comorbidity of allergic rhinitis (48.5% vs. 0.8%). Viral and/or bacterial infections were detected in 205 patients (50.4%) with AE. The numbers of patients with viral only, bacterial only, or both infections were 119, 49, and 37, respectively. The most commonly isolated bacterium was Streptococcus pneumoniae, followed by Pseudomonas aeruginosa and Chlamydia pneumoniae. Obese patients showed a lower incidence of Chlamydia pneumoniae infection. In the non-obese group, bacterial infection, especially Chlamydia pneumoniae infection, was significantly associated with the duration of systemic corticosteroid use (13.6 ± 19.8 vs. 9.7 ± 6.7 days, p = 0.049). CONCLUSION: Bacterial infection was associated with a longer period of corticosteroid use in the non-obese group. Acute Chlamydia pneumoniae infection was less associated with obese patients with AE. Further well-designed studies are needed to evaluate microorganisms and the efficacy of antibiotics in patients with AE.


Assuntos
Asma , Infecções Bacterianas , Infecções por Chlamydophila , Infecções Respiratórias , Adulto , Humanos , Feminino , Infecções Respiratórias/complicações , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Estudos Retrospectivos , Asma/complicações , Asma/epidemiologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/complicações , Obesidade/complicações , Obesidade/epidemiologia , Sistema Respiratório , Infecções por Chlamydophila/complicações , Corticosteroides
13.
J Korean Med Sci ; 39(29): e214, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39079683

RESUMO

BACKGROUND: Dizziness/vertigo is one of the most common symptoms for which people seek healthcare. However, the healthcare expenditure attributable to dizziness/vertigo in South Korea remains poorly understood. We investigated the healthcare costs due to six major disorders causing dizziness/vertigo using claims data. METHODS: The healthcare costs were evaluated using all the claims data submitted to the Health Insurance Review and Assessment Service from January 1 to December 31, 2022. The six major vestibular disorders included for analysis were benign paroxysmal positional vertigo (BPPV), psychogenic/persistent postural perceptual dizziness (PPPD), vascular vertigo/dizziness (VVD), vestibular migraine (VM), Meniere's disease (MD), and vestibular neuritis (VN). RESULTS: During the 1-year study period, 4.1% of adults aged 20 or older visited hospitals due to dizziness/vertigo in South Korea. Compared to the general population, the patients with dizziness/vertigo were more often elderly, female, and residents of small towns. The total healthcare cost for the six major vestibular disorders was ₩547.8 billion (approximately $406.5 million). BPPV incurred the highest annual healthcare cost (₩183.5 billion, 33.5%), followed by VVD (₩158.8 billion, 29.0%), MD (₩82.2 billion, 15.0%), psychogenic/PPPD (₩60.3 billion, 11.0%), VN (₩32.9 billion, 6.0%), and VM (₩30.1 billion, 5.5%). The mean healthcare cost per hospital visit due to dizziness/vertigo was ₩96,524 (95% confidence interval, ₩96,194-₩96,855), 30% higher than the average (₩73,948) of the overall healthcare cost per hospital visit over the same period. CONCLUSION: Owing to higher healthcare costs for dizziness/vertigo and increased prevalence of dizziness/vertigo in the aged population, healthcare costs due to dizziness/vertigo will increase rapidly in South Korea. Thus, a guideline for cost-effective management of dizziness/vertigo should be established to reduce the healthcare costs due to these common symptoms.


Assuntos
Tontura , Custos de Cuidados de Saúde , Vertigem , Humanos , República da Coreia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Vertigem Posicional Paroxística Benigna , Doença de Meniere/economia , Neuronite Vestibular , Transtornos de Enxaqueca/economia , Revisão da Utilização de Seguros
14.
Int J Mol Sci ; 25(17)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39273456

RESUMO

Gastric cancer (GC) is the fifth most common cause of cancer-related death worldwide. Early detection is crucial for improving survival rates and treatment outcomes. However, accurate GC-specific biomarkers remain unknown. This study aimed to identify the metabolic differences between intestinal metaplasia (IM) and GC to determine the pathways involved in GC. A metabolic analysis of IM and tissue samples from 37 patients with GC was conducted using ultra-performance liquid chromatography with tandem mass spectrometry. Overall, 665 and 278 significant features were identified in the aqueous and 278 organic phases, respectively, using false discovery rate analysis, which controls the expected proportion of false positives among the significant results. sPLS-DA revealed a clear separation between IM and GC samples. Steroid hormone biosynthesis, tryptophan metabolism, purine metabolism, and arginine and proline metabolism were the most significantly altered pathways. The intensity of 11 metabolites, including N1, N2-diacetylspermine, creatine riboside, and N-formylkynurenine, showed significant elevation in more advanced GC. Based on pathway enrichment analysis and cancer stage-specific alterations, we identified six potential candidates as diagnostic biomarkers: aldosterone, N-formylkynurenine, guanosine triphosphate, arginine, S-adenosylmethioninamine, and creatine riboside. These metabolic differences between IM and GC provide valuable insights into gastric carcinogenesis. Further validation is needed to develop noninvasive diagnostic tools and targeted therapies to improve the outcomes of patients with GC.


Assuntos
Biomarcadores Tumorais , Metaplasia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Metaplasia/metabolismo , Metaplasia/patologia , Masculino , Feminino , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Idoso , Metaboloma , Metabolômica/métodos , Redes e Vias Metabólicas , Espectrometria de Massas em Tandem/métodos
15.
BMC Oral Health ; 24(1): 1186, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39369200

RESUMO

BACKGROUND: Toothbrushing is the most commonly used method to physically remove dental plaque. However, there are many areas of the mouth that are difficult to reach with a toothbrush. The type of toothbrush is a critical factor influencing the effectiveness of oral care. The purpose of the study was to evaluate a toothbrush with a thin head, slender-neck and super-tapered bristles to target hard-to-reach areas in the oral cavity for reducing dental plaque and gingivitis. METHODS: This crossover study included 58 adults aged 20 years and older. All participants were randomly assigned to use test and control toothbrushes (the latter had a normal head and round bristles) for two 4-week phases. Participants brushed their teeth twice daily in their habitual manner. At the start and end of each phase the Silness-LÓ§e plaque index (PI), LÓ§e -Silness gingival index (GI) and bleeding-on-probing index (BOP) were assessed and performed plaque fluorescence tests using quantitative light-induced fluorescence technology. RESULTS: After using the test toothbrush, PI, GI and BOP decreased by 25%, 30% and 48%, respectively (P < 0.05). For the rearmost molars, PI, GI and BOP decreased by 18%, 26% and 47%, respectively (P < 0.05). For the implants, GI and BOP decreased by 31% and 57%, respectively (P < 0.05). The plaque fluorescence tests indicated that after using the test toothbrush, the dental plaque area for the anterior teeth and the simple plaque score for the rearmost molars decreased by 25% (P < 0.05) and 14% (P = 0.527), respectively. CONCLUSIONS: The test toothbrush was markedly better than the control toothbrush at reducing dental plaque and gingivitis. In particular, the test toothbrush produced an excellent reduction in dental plaque and gingivitis for the rearmost molars and the implants. TRIAL REGISTRATION: KCT0009669, retrospectively registered 02/08/2024.


Assuntos
Estudos Cross-Over , Placa Dentária , Gengivite , Escovação Dentária , Humanos , Escovação Dentária/instrumentação , Masculino , Feminino , Adulto , Placa Dentária/prevenção & controle , Gengivite/prevenção & controle , Pessoa de Meia-Idade , Índice de Placa Dentária , Desenho de Equipamento , Índice Periodontal , Adulto Jovem , Dispositivos para o Cuidado Bucal Domiciliar
16.
Medicina (Kaunas) ; 60(9)2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39336550

RESUMO

Background and Objectives: With increases in cancer incidence and the number of cancer survivors, the demand for cancer management is growing. However, studies on dental prosthetic treatment for patients with cancer are rare. We aim to investigate the dental prosthetic treatment in patients with cancer aged ≥65 years after expanded health insurance coverage. Materials and Methods: This retrospective study included patients who were treated with implants and removable dentures at Ulsan University Hospital in South Korea between June 2015 and June 2023. Data on age, sex, cancer location, comorbid systemic diseases, number of remaining teeth, dental prosthetic treatment history, type of dental prosthetic treatment, and insurance coverage status were extracted from patient medical records and panoramic radiographs. The influence of multiple variables on dental prosthetic treatment was analyzed using the Chi-square and Fisher's exact tests. Results: The study included 61 patients with cancer (32 men, 29 women; average age: 70.9 years). Among them, 56 (91.8%) had insurance coverage benefits, and 34 (55.7%) received treatments such as implants, removable partial dentures, or complete dentures for the first time. Treatment types included 37 (60.7%) cases of implant prostheses and 24 (39.3%) conventional removable dentures. No statistical differences were observed in the type of dental prosthetic treatment according to sex, age, cancer location, number of systemic diseases, and dental prosthetic treatment history (p > 0.05). Patients with <10 remaining teeth received treatment with conventional removable dentures, which was statistically significant (p < 0.001). Conclusions: Of the 61 patients, 56 (91.8%) received insurance benefits, and 34 (55.7%) underwent dental prosthetic treatment for the first time. Within the limitations of this retrospective study, the expanded health insurance coverage alleviated the unmet demand for dental prosthetic treatment. As cancer prevalence continues to increase, expanding customized health insurance coverage is crucial to meet this demand.


Assuntos
Cobertura do Seguro , Neoplasias , Humanos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Neoplasias/terapia , República da Coreia , Idoso de 80 Anos ou mais , Cobertura do Seguro/estatística & dados numéricos , Prótese Dentária/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos
17.
Medicina (Kaunas) ; 60(5)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38792863

RESUMO

Introduction: Basicervical femoral neck fracture (FNF) is an uncommon type of femoral neck fracture and is associated with an increased risk of fixation failure due to its inherent instability. The purpose of this study was to compare the surgical parameters and reoperation rate between the use of a multiple cannulated screw (MCS) and fixed angle device (FAD) in treating basicervical FNFs. Methods: We retrospectively reviewed the records of 885 patients who underwent internal fixation between May 2004 and August 2019 to determine basicervical FNF with at least 12 months of follow-up. Among the identified 77 patients with basicervical FNF, 17 patients who underwent multiple cannulated screw (MCS) fixation and 36 patients who underwent fixed angle device (FAD) fixation were included. We compared the rates of fracture-site collapse and reoperations according to the fixation device. Results: Among the 53 patients with basicervical FNF, 13 patients (24.5%) sustained surgical complications (8 collapses of fracture site and 5 reoperations). The reoperation rate in the MCS group was significantly higher than that in the FAD group (23.5% vs. 2.8%, p = 0.016), without any significant difference in the collapse of the fracture site (11.8% vs. 16.7%, p = 0.642). Conclusions: Although basicervical FNF was rare among hip fractures, fracture site collapse was prevalent and prone to fixation failure. Surgeons should keep this in mind, and consider FAD for basicervical FNF.


Assuntos
Parafusos Ósseos , Fraturas do Colo Femoral , Fixação Interna de Fraturas , Humanos , Fraturas do Colo Femoral/cirurgia , Feminino , Masculino , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/estatística & dados numéricos , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Reoperação/estatística & dados numéricos , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/epidemiologia
18.
Am J Gastroenterol ; 118(8): 1373-1380, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36728217

RESUMO

INTRODUCTION: This prospective study aimed to investigate the efficacy and safety of preemptive antiviral therapy with tenofovir disoproxil fumarate (TDF) for HBsAg-positive patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. METHODS: We enrolled 73 patients from 20 institutions. The primary end point was the absolute risk of hepatitis B virus (HBV)-related hepatitis during preemptive TDF therapy and for 24 weeks after withdrawal from TDF. Hepatitis was defined as a more than 3-fold increase in serum alanine aminotransferase from baseline or an alanine aminotransferase level of ≥100 U/L. HBV-related hepatitis was defined as hepatitis with an increase in serum HBV-DNA to >10 times that of the pre-exacerbation baseline or an absolute increase of ≥20,000 IU/mL compared with the baseline. RESULTS: No patient developed HBV reactivation or HBV-related hepatitis during preemptive antiviral therapy (until 48 weeks after completion of R-CHOP chemotherapy) with TDF. All adverse events were grade 1 or 2. HBV reactivation was reported in 17 (23.3%) patients. All HBV reactivation was developed at a median of 90 days after withdrawal from TDF (range, 37-214 days). Six (8.2%) patients developed HBV-related hepatitis at a median of 88 days after withdrawal from TDF (range, 37-183 days). DISCUSSION: Preemptive TDF therapy in HBsAg-positive patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy was safe and effective for preventing HBV-related hepatitis. However, a long-term maintenance strategy of preemptive TDF therapy should be recommended because of the relatively high rate of HBV-related hepatitis after withdrawal from TDF ( ClinicalTrials.gov ID: NCT02354846).


Assuntos
Hepatite B Crônica , Linfoma Difuso de Grandes Células B , Humanos , Tenofovir/efeitos adversos , Rituximab/efeitos adversos , Vincristina/efeitos adversos , Prednisona/uso terapêutico , Antígenos de Superfície da Hepatite B , Estudos Prospectivos , Alanina Transaminase , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Vírus da Hepatite B , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/induzido quimicamente , Antivirais/uso terapêutico , DNA Viral
19.
Cerebellum ; 22(1): 1-13, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34993890

RESUMO

Differentiation of spinocerebellar ataxia type 17 (SCA17) from Huntington's disease (HD) is often challenging since they share the clinical features of chorea, parkinsonism, and dystonia. The ocular motor findings remain to be elucidated in SCA17, and may help differentiating SCA17 from HD. We retrospectively compared the ocular motor findings of 11 patients with SCA17 with those of 10 patients with HD. In SCA17, abnormal ocular motor findings included impaired smooth pursuit (9/11, 82%), dysmetric saccades (9/11, 82%), central positional nystagmus (CPN, 7/11, 64%), abnormal head-impulse tests (4/11, 36%), and horizontal gaze-evoked nystagmus (GEN, 3/11, 27%). Among these, CPN was more frequently observed in SCA17 than in HD (7/11 (64%) vs. 0/10 (0%), p = 0.004) while saccadic slowing was more frequently observed in HD than in SCA17 (8/10 (80%) vs. 2/11 (18%), p = 0.009). Of six patients with follow-up evaluation, five later developed bilateral saccadic hypermetria (n = 4), GEN (n = 1), CPN (n = 1), bilaterally abnormal smooth pursuit (n = 1), and hyperactive head-impulse responses (n = 1) along with a clinical decline. Ocular motor abnormalities can be utilized as a diagnostic marker for differentiation of SCA17 from HD as well as a surrogate marker for clinical decline in SCA17.


Assuntos
Doença de Huntington , Nistagmo Patológico , Transtornos da Motilidade Ocular , Ataxias Espinocerebelares , Humanos , Doença de Huntington/diagnóstico , Estudos Retrospectivos , Ataxias Espinocerebelares/diagnóstico , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/etiologia
20.
Eur J Neurol ; 30(8): 2471-2480, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37154347

RESUMO

BACKGROUND AND PURPOSE: The etiologies of abducens nerve palsy have shown a large variability among studies. This study aimed to establish the clinical features and underlying etiologies of isolated abducens nerve palsy by recruiting patients from all departments in a referral-based university hospital. METHODS: We reviewed the medical records of 807 patients with a confirmed diagnosis of isolated abducens nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, Republic of Korea, from 2003 to 2020. We also compared the proportion of etiology with that of the patients pooled from the previous studies. RESULTS: The most common etiology was microvascular (n = 296, 36.7%), followed by idiopathic (n = 143, 17.7%), neoplastic (n = 115, 14.3%), vascular anomalies (n = 82, 10.2%), inflammatory (n = 76, 9.4%), and traumatic (n = 35, 4.3%). Patients were mostly managed by ophthalmologists (n = 576, 71.4%), followed by neurologists (n = 479, 59.4%), emergency physicians (n = 278, 34.4%), neurosurgeons (n = 191, 23.7%), and others (n = 72, 8.9%). The proportion of etiology significantly differed according to the age and sex of the patients and the specialties involved in the management (p < 0.001). Compared to the pooled data from the previous reports, the current study showed a higher prevalence of microvascular cause but a lower occurrence of traumatic and neoplastic causes. CONCLUSIONS: The results of previous studies on etiologic distribution of isolated abducens nerve palsy should be interpreted with consideration of the demographic features of patients recruited and the specialties involved.


Assuntos
Doenças do Nervo Abducente , Humanos , Doenças do Nervo Abducente/epidemiologia , Doenças do Nervo Abducente/etiologia , Doenças do Nervo Abducente/diagnóstico , Causalidade , República da Coreia/epidemiologia , Neurologistas
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