Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 711
Filtrar
1.
Cell Genom ; 4(3): 100510, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38447574

RESUMO

CRISPR-Cas9 short guide RNA (sgRNA) library screening is a powerful approach to understand the molecular mechanisms of biological phenomena. However, its in vivo application is currently limited. Here, we developed our previously established in vitro revival screening method into an in vivo one to identify factors involved in spermatogenesis integrity by utilizing sperm capacitation as an indicator. By introducing an sgRNA library into testicular cells, we successfully pinpointed the retinal degeneration 3 (Rd3) gene as a significant factor in spermatogenesis. Single-cell RNA sequencing (scRNA-seq) analysis highlighted the high expression of Rd3 in round spermatids, and proteomics analysis indicated that Rd3 interacts with mitochondria. To search for cell-type-specific signaling pathways based on scRNA-seq and proteomics analyses, we developed a computational tool, Hub-Explorer. Through this, we discovered that Rd3 modulates oxidative stress by regulating mitochondrial distribution upon ciliogenesis induction. Collectively, our screening system provides a valuable in vivo approach to decipher molecular mechanisms in biological processes.


Assuntos
RNA Guia de Sistemas CRISPR-Cas , Sêmen , Masculino , Humanos , Testículo , Espermátides , Espermatogênese/genética
2.
Kyobu Geka ; 77(3): 169-172, 2024 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-38465487

RESUMO

BACKGROUND: Lung segment anatomy is complex and difficult for medical students to comprehend, so education is a challenging issue. Three-dimensional (3D) models may be a more effective teaching tool for medical students. We evaluated the usefulness of 3D models in education for segmentectomy. METHODS: Sixty-six students who participated in clinical training for thoracic surgery from November 2020 to March 2022 were included in the study. Computed tomography (CT) images, 3D-CT images, and 3D models were used to investigate students' level of understanding for each lung segment. Levels of understanding were assessed using a questionnaire administered using the interview method. The results of the questionnaire were tabulated and analyzed using the Kruskal-Wallis test. RESULTS: The response rate was 100%. Comprehension scores for all questions were highest for 3D models, followed by 3D-CT and CT. These results suggest that use of a 3D entity model may have a high educational effect. CONCLUSION: Although it is unclear whether students' comprehension was directly related to their understanding of correct anatomy, our results suggest that 3D models may be an effective way for medical students to understand lung segmentectomy.


Assuntos
Estudantes de Medicina , Humanos , Pneumonectomia , Avaliação Educacional , Imageamento Tridimensional/métodos , Simulação por Computador
3.
Intern Med ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38494719

RESUMO

Objective To survey the epidemiology of respiratory pathogens during the COVID-19 pandemic using multiplex polymerase chain reaction (PCR). Methods Specimens were assayed using multiplex nested PCR. Patients and Materials Specimens were obtained from outpatients who presented with symptoms of upper respiratory tract infection and asymptomatic outpatients who had contact with patients with SARS-CoV-2 infection at Tohoku Medical and Pharmaceutical University Hospital in Sendai, Japan, from November 1, 2020, to May 31, 2023. The analysis included multiple specimens collected from the same patients at different time-points. Data were collected from the electronic records after testing. Results This study included 8,335 patients (4,311 men) with a median age of 59 years old, and 11,741 total specimens were collected. At least 1 positive SARS-CoV-2 result was obtained for 1,710 (14.6%) specimens. Furthermore, 15 pathogens were identified in the positive specimens, and rhinovirus/enterovirus was detected more frequently than other viruses. We identified a larger number of SARS-CoV-2-positive specimens in patients ≥10 years old. In contrast, in patients 0-9 years old, we identified a larger number of specimens positive for rhinovirus/enterovirus than for other viruses. Conclusions In this study, we examined the epidemiology of circulating respiratory pathogens during the COVID-19 pandemic era.

4.
Acta Otolaryngol ; : 1-5, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38469861

RESUMO

BACKGROUND: The effect of wearing masks on olfaction remains unclear. OBJECTIVES: This study aimed to clarify the differences between the effects of no masks, surgical masks, and N95 respirator masks by conducting both identification and threshold olfaction tests. METHODS: Young, healthy volunteers aged ≥ 18 years and < 30 years without awareness of apparent olfactory disorder were included. All participants filled out a questionnaire on olfaction and completed an acuity smell identification test (Open Essence test) and an olfactory threshold test (T&T olfactometry) while wearing no masks, surgical masks, or N95 respirator masks. RESULTS: In the Open Essence tests, the no-mask group score was significantly higher than those of the surgical- and N95-mask groups. Using T&T olfactometry, the median-detection threshold of the no-mask group was significantly lower than that of the surgical-mask group, and the surgical-mask group threshold was significantly lower than that of the N95-mask group. Similar patterns were observed for the median-recognition threshold. CONCLUSIONS: Wearing masks, especially an N95 mask, reduces the ability to detect and identify odors. This disadvantage should be considered by professionals such as healthcare workers, who require proper olfaction to perform appropriate tasks.

5.
Int J Pediatr Otorhinolaryngol ; 178: 111904, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38432029

RESUMO

OBJECTIVE: The purpose of this study is to compare patient trends in otitis media with effusion (OME) symptoms and diagnoses before and after the COVID-19 pandemic in order to investigate the effects of the coronavirus disease of 2019 (COVID-19). METHODS: A retrospective, multi-center, observational study was carried out between January 2018 and December 2022 at hospitals in the Iwate Prefecture with full-time doctors. All patients were initially separated into two groups, one for the pre-COVID-19 era (from January 2018 to June 2020), and the other for the COVID-19 era (from July 2020 to December 2022). RESULTS: In the pre-COVID-19 era, 132 patients had tympanostomy tubes (TT) placed, while 64 patients had them placed in the COVID-19 era. Between the pre-COVID-19 and COVID-19 eras, there were no statistically significant differences in terms of age, sex, side, craniofacial deformity, or adenoidectomy. Children in elementary school showed a greater decline than those in preschool (42-11 patients in elementary school (74%) and 49 to 32 patients in preschool school (35%); p = 0.025). CONCLUSIONS: The percentage of TT placements for OME dropped to roughly half during the COVID-19 epidemic. This was particularly obvious in elementary school students.


Assuntos
COVID-19 , Otite Média com Derrame , Criança , Pré-Escolar , Humanos , Japão/epidemiologia , Ventilação da Orelha Média , Otite Média com Derrame/epidemiologia , Otite Média com Derrame/cirurgia , Pandemias , Estudos Retrospectivos , Masculino , Feminino
6.
Eur J Cancer ; 201: 113951, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417299

RESUMO

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.


Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos , Neoplasias do Sistema Nervoso Central , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/uso terapêutico , Japão , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/tratamento farmacológico , Receptores ErbB/genética , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/cirurgia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Mutação , Recidiva , Sistema Nervoso Central/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos
7.
Vet Res ; 55(1): 17, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321502

RESUMO

Streptococcus suis is a gram-positive bacterium that causes meningitis, septicemia, endocarditis, and other disorders in pigs and humans. We obtained 42 and 50 S. suis isolates from lesions of porcine endocarditis and palatine tonsils, respectively, of clinically healthy pigs in Japan; we then determined their sequence types (STs) by multilocus sequence typing (MLST), cps genotypes, serotypes, and presence of classical major virulence-associated marker genes (mrp, epf, and sly). The 42 isolates from endocarditis lesions were assigned to a limited number of STs and clonal complexes (CCs). On the other hand, the 50 isolates from tonsils were diverse in these traits and seemingly in the degree of virulence, suggesting that tonsils can accommodate a variety of S. suis isolates. The goeBURST full algorithm using tonsil isolates obtained in this study and those retrieved from the database showed that major CCs as well as many other clusters were composed of isolates originating from different countries, and some of the STs were very similar to each other despite the difference in country of origin. These findings indicate that S. suis with not only different but also similar mutations in the genome have survived in tonsils independently across different geographical locations. Therefore, unlike the lesions of endocarditis, the tonsils of pigs seemingly accommodate various S. suis lineages. The present study suggests that S. suis acquired its diversity by natural mutations during colonization and persistence in the tonsils of pigs.


Assuntos
Endocardite , Infecções Estreptocócicas , Streptococcus suis , Doenças dos Suínos , Humanos , Suínos , Animais , Tipagem de Sequências Multilocus/veterinária , Tonsila Palatina/microbiologia , Streptococcus suis/genética , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/veterinária , Doenças dos Suínos/microbiologia , Endocardite/veterinária
8.
Radiol Phys Technol ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413510

RESUMO

This study aimed to assess the subjective and objective image quality of low-dose computed tomography (CT) images processed using a self-supervised denoising algorithm with deep learning. We trained the self-supervised denoising model using low-dose CT images of 40 patients and applied this model to CT images of another 30 patients. Image quality, in terms of noise and edge sharpness, was rated on a 5-point scale by two radiologists. The coefficient of variation, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were calculated. The values for the self-supervised denoising model were compared with those for the original low-dose CT images and CT images processed using other conventional denoising algorithms (non-local means, block-matching and 3D filtering, and total variation minimization-based algorithms). The mean (standard deviation) scores of local and overall noise levels for the self-supervised denoising algorithm were 3.90 (0.40) and 3.93 (0.51), respectively, outperforming the original image and other algorithms. Similarly, the mean scores of local and overall edge sharpness for the self-supervised denoising algorithm were 3.90 (0.40) and 3.75 (0.47), respectively, surpassing the scores of the original image and other algorithms. The CNR and SNR for the self-supervised denoising algorithm were higher than those for the original images but slightly lower than those for the other algorithms. Our findings indicate the potential clinical applicability of the self-supervised denoising algorithm for low-dose CT images in clinical settings.

9.
Surg Infect (Larchmt) ; 25(2): 147-154, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38381952

RESUMO

Background: Video-assisted thoracoscopic surgery is a widely recommended treatment for empyema in advanced stages. However, only a few studies have evaluated prognostic factors among patients with empyema who underwent video-assisted thoracoscopic surgery. Furthermore, no studies have evaluated predictors of direct discharge home. Patients and Methods: This multicenter retrospective cohort study included 161 patients with empyema who underwent video-assisted thoracoscopic surgery in five acute-care hospitals. The primary outcome was the probability of direct discharge home. The secondary outcome was the length of hospital stay after surgery. We broadly assessed pre-operative factors and performed univariable logistic regression for the direct discharge home and univariable gamma regression for the length of hospital stay after surgery. Results: Of the 161 included patients, 74.5% were directly discharged home. Age (>70 years; -24.3%); altered mental status (-33.4%); blood urea nitrogen (>22.4 mg/dL; -19.4%); and pleural pH (<7.2; -17.6%) were associated with high probabilities of not being directly discharged home. Fever (15.2%) and albumin (> 2.7 g/dL; 20.2%) were associated with high probabilities of being directly discharged home. The median length of stay after surgery was 19 days. Age (>70 years; 6.2 days); altered mental status (5.6 days); purulence (2.7 days); pleural thickness (>2 cm; 5.1 days); bronchial fistula (14.6 days); albumin (>2.7 g/dL; 3.1 days); and C-reactive protein (>20 mg/dL; 3.6 days) were associated with a longer post-operation hospital stay. Conclusions: Physicians should consider using these prognostic factors to predict non-direct discharge to the home for patients with empyema.


Assuntos
Empiema Pleural , Alta do Paciente , Humanos , Idoso , Empiema Pleural/cirurgia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Cirurgia Torácica Vídeoassistida/efeitos adversos , Albuminas
10.
Surg Today ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38356076

RESUMO

PURPOSE: Saliva is often used as a tool for identifying systemic diseases because of the noninvasive nature of its collection. Moreover, salivary metabolites can be potential predictive factors for postoperative survival. We conducted the present study to establish whether salivary metabolites can function as predictive biomarkers for lung surgery complications. METHODS: Unstimulated salivary samples were collected from 412 patients before lung surgery. Salivary metabolites were analyzed comprehensively by capillary electrophoresis mass spectrometry. Clinical data with the discriminatory ability of biomarkers were assessed to predict lung surgery complications using multivariate logistic regression analysis. The primary endpoint was the risk factors for postoperative complications of Clavien-Dindo grade ≥ III. RESULTS: Postoperative complications of Clavien-Dindo grade ≥ III developed in 36 patients (8.7%). There was no postoperative 30-day mortality. Male sex (odds ratio [OR], 3.852; 95% confidence interval CI 1.455-10.199; p = 0.007) and salivary gamma-butyrobetaine (OR, 0.809; 95% CI 0.694-0.943; p = 0.007) were identified as significant risk factors for postoperative complications of Clavien-Dindo grade ≥ III. CONCLUSION: Salivary metabolites are potential noninvasive biomarkers for predicting postoperative complications of lung surgery.

11.
Nanomaterials (Basel) ; 14(2)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38251139

RESUMO

This study investigates the nanostructural properties of pseudo-binary Al-1.0Mg2Si (mass%) alloys with and without 0.5Cu using transmission electron microscopy (TEM) and small-angle neutron scattering (SANS). The TEM results show that both alloys exhibit extra electron diffraction spots related to MgSiMg second clusters at peak-aged conditions. High-resolution TEM images have revealed that the second cluster exists as a needle-shaped precipitate that is shorter and thicker than the ß″ phase. We found that the second cluster, which we referred to as the R phase in this paper, is more likely to form partially along the longitudinal axis of a random-type precipitate. Thus, the atomic arrangement in the random-type precipitate is not completely random. SANS is used to quantify the size and volume fraction of the observed needle-shaped precipitates since the R phase is difficult to observe with TEM. The R phase forms even in the Cu-free alloy, but the volume fraction is low, and the growth and formation are retarded near the peak-aged conditions. Undoubtedly, the Cu addition has the effect of stabilizing the growth of the R phase and also promoting its formation. Therefore, the R phase also contributes to the increase in hardness at both under- and peak-aged conditions in the Cu-containing alloy in addition to the strengthening ß″ phases.

12.
Sci Rep ; 14(1): 110, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167633

RESUMO

Non-alcoholic fatty liver disease is a common liver disease worldwide, and is associated with dysregulation of lipid metabolism, leading to inflammation and fibrosis. Acanthopanax senticosus Harms (ASH) is widely used in traditional medicine as an adaptogen food. We examined the effect of ASH on steatohepatitis using a high-fat diet mouse model. Mice were fed a choline-deficient, L-amino acid-defined, high-fat diet with ASH extract (ASHE). After 6 weeks, liver RNA transcriptome sequencing (RNA-Seq) was performed, followed by Ingenuity Pathway Analysis (IPA). Our findings revealed that mice fed a high-fat diet with 5% ASHE exhibited significantly reduced liver steatosis. These mice also demonstrated alleviated inflammation and reduced fibrosis in the liver. IPA of RNA-Seq indicated that hepatocyte nuclear factor 4 alpha (HNF4 alpha), a transcription factor, was the activated upstream regulator (P-value 0.00155, z score = 2.413) in the liver of ASHE-fed mice. Adenosine triphosphate binding cassette transporter 8 and carboxylesterase 2, downstream targets of HNF4 alpha pathway, were upregulated. Finally, ASHE-treated HepG2 cells exposed to palmitate exhibited significantly decreased lipid droplet contents. Our study provides that ASHE can activate HNF4 alpha pathway and promote fat secretion from hepatocytes, thereby serving as a prophylactic treatment for steatohepatitis in mice.


Assuntos
Eleutherococcus , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Eleutherococcus/química , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Inflamação/patologia , Modelos Animais de Doenças , Fibrose , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos
13.
Parasitol Int ; 99: 102832, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38040112

RESUMO

A case of suspected food poisoning related to the consumption of raw meat from a common minke whale (Balaenoptera acutorostrata) was reported in Tokyo, Japan, in June 2020. Microscopic analysis revealed tissue cysts of Toxoplasma gondii and sarcocysts of Sarcocystis sp. in whale meat. The SAG2 and ITS1 region sequences of T. gondii were detected in the DNA extracted from the meat. Genotyping of the multilocus nested PCR-RFLP using the genetic markers SAG1, SAG2 (5'- SAG2, 3'-SAG2, and alt. SAG2), SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico revealed that the genotype of T. gondii was type II, with a type I pattern for the L358 locus. In the phylogenetic analyses of the six loci (GRA6, GRA7, SAG1, HP2, UPRT1, and UPRT7), these sequences clustered into haplogroup 2. Moreover, the sequences of the virulence-related genes ROP5 and ROP18 of T. gondii isolated from whale meat were similar to those of the type II ME49 reference strain. Sequence analyses of the mtDNA cox1 gene, 18S rRNA gene, and ITS1 region indicated the highest similarity of sarcocyst isolated from whale meat to Sarcocystis species that infect birds or carnivores as intermediate hosts; however, the species could not be identified. To our knowledge, this is the first report of T. gondii and Sarcocystis spp. being detected in same whale meat ingested by patients involved in a suspected food poisoning case in Japan.


Assuntos
Doenças Transmitidas por Alimentos , Baleia Anã , Sarcocystis , Toxoplasma , Toxoplasmose Animal , Animais , Humanos , Sarcocystis/genética , Filogenia , Japão , Toxoplasmose Animal/diagnóstico , Carne , Genótipo , Polimorfismo de Fragmento de Restrição
14.
Gen Thorac Cardiovasc Surg ; 72(5): 346-354, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38143254

RESUMO

OBJECTIVES: Although several societies recommend regular chest computed tomography (CT) scans for the surveillance of surgically resected non-small cell lung cancer (NSCLC), there is paucity of evidence to support these statements. This study aimed to clarify whether regular CT scans improved the prognosis of patients with surgically resected NSCLC based on TNM 8th classification. METHODS: Patients with pathologic Stage 0-III NSCLC who underwent complete surgical resection other than sublobar resection procedures were enrolled in the study. For these patients, clinicopathological data and postoperative surveillance data were collected by the retrospective review of medical records. Patients were categorized into the chest X-ray (CXR) group or the CT group according to whether they were followed-up with basic examinations including CXR or basic examinations plus regular chest CT. Postoperative overall survival was compared between the two groups. RESULTS: Six hundred sixty five patients were categorized into the CXR (n = 245) and CT (n = 420) groups. The clinicopathological backgrounds did not differ to a statistically significant extent. Recurrence was seen in 68 (27.3%) patients in the CXR group and 117 (27.8%) patients in the CT group. The 5-year overall survival rates of the two groups did not differ to a statistically significant extent (CXR, 76.5%; CT, 78.3%, P = 0.22). CONCLUSION: Regular chest CT scans may not improve the prognosis of surgically resected NSCLC. Further study is warranted to precisely evaluate the benefit of CT-based postoperative surveillance of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Tomografia Computadorizada por Raios X , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
15.
Rev Bras Parasitol Vet ; 32(4): e011923, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38055438

RESUMO

In vitro excystation of cysts of microscopically identified Chilomastix mesnili and Retortamonas sp. isolated from Japanese macaques and Retortamonas sp. isolated from small Indian mongooses could be induced using an established protocol for Giardia intestinalis and subsequently by culturing with H2S-rich Robinson's medium supplemented with Desulfovibrio desulfuricans. Excystation usually began 2 h after incubation in Robinson's medium. DNA was isolated from excysted flagellates after 4 h of incubation or from cultured excysted flagellates. Phylogenetic analysis based on their 18S rRNA genes revealed that two isolates of C. mesnili from Japanese macaques belonged to the same cluster as a C. mesnili isolate from humans, whereas a mammalian Retortamonas sp. isolate from a small Indian mongoose belonged to the same cluster as that of an amphibian Retortamonas spp. isolate from a 'poison arrow frog' [sequence identity to AF439347 (94.9%)]. These results suggest that the sequence homology of the 18S rRNA gene of the two C. mesnili isolates from Japanese macaques was similar to that of humans, in addition to the morphological similarity, and Retortamonas sp. infection of the amphibian type in the small Indian mongoose highlighted the possibility of the effect of host feeding habitats.


Assuntos
Herpestidae , Parasitos , Retortamonadídeos , Humanos , Animais , Filogenia , Retortamonadídeos/genética , Herpestidae/genética , Macaca fuscata/genética , RNA Ribossômico 18S/genética
16.
Sci Rep ; 13(1): 21494, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057582

RESUMO

Fatty acid-binding protein 7 (FABP7) is vital for uptake and trafficking of fatty acids in the nervous system. To investigate the involvement of FABP7 in noise-induced hearing loss (NIHL) pathogenesis, we used Fabp7 knockout (KO) mice generated via CRISPR/Cas9 in the C57BL/6 background. Initial auditory brainstem response (ABR) measurements were conducted at 9 weeks, followed by noise exposure at 10 weeks. Subsequent ABRs were performed 24 h later, with final measurements at 12 weeks. Inner ears were harvested 24 h after noise exposure for RNA sequencing and metabolic analyses. We found no significant differences in initial ABR measurements, but Fabp7 KO mice showed significantly lower thresholds in the final ABR measurements. Hair cell survival was also enhanced in Fabp7 KO mice. RNA sequencing revealed that genes associated with the electron transport chain were upregulated or less impaired in Fabp7 KO mice. Metabolomic analysis revealed various alterations, including decreased glutamate and aspartate in Fabp7 KO mice. In conclusion, FABP7 deficiency mitigates cochlear damage following noise exposure. This protective effect was supported by the changes in gene expression of the electron transport chain, and in several metabolites, including excitotoxic neurotransmitters. Our study highlights the potential therapeutic significance of targeting FABP7 in NIHL.


Assuntos
Perda Auditiva Provocada por Ruído , Audição , Camundongos , Animais , Proteína 7 de Ligação a Ácidos Graxos/genética , Proteína 7 de Ligação a Ácidos Graxos/metabolismo , Camundongos Endogâmicos C57BL , Audição/fisiologia , Ruído/efeitos adversos , Perda Auditiva Provocada por Ruído/genética , Cóclea/metabolismo , Camundongos Knockout , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Limiar Auditivo/fisiologia
17.
Open Forum Infect Dis ; 10(12): ofad571, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38075018

RESUMO

Background: Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic. Although systemic steroids play an important role in treating patients with severe COVID-19, the role of inhaled corticosteroids in non-critically ill, hospitalized patients with COVID-19 remains unclear. Methods: We analyzed findings in non-critically ill, hospitalized patients with COVID-19 who were >18 years old and were admitted to 64 Japanese hospitals between January and September 2020. We performed propensity score matching analysis to evaluate 28-day and in-hospital mortality rates with or without inhaled ciclesonide within 2 days of admission. Sensitivity analyses using inverse probability weighting analysis, and generalized estimating equation method were also performed. Results: Eligible patients (n = 3638) were divided into ciclesonide (n = 290) and control (n = 3, 393) groups. The 1-to-4 propensity score matching analysis included 271 ciclesonide users and 1084 nonusers. There were no significant differences between the 2 groups for 28-day (3.3% vs 2.3%; risk difference, 1.0% [95% confidence interval, -1.2 to 3.3]) or in-hospital (4.8% vs 2.6%; risk difference, 2.2 [-.5 to 4.9]) mortality rates. The sensitivity analysis showed similar outcomes. Conclusions: From this multicenter observational study in Japan, inhaled ciclesonide did not decrease 28-day or in-hospital mortality rates in non-critically ill, hospitalized patients with COVID-19. Future large, multinational, randomized trials are required to confirm our results.

18.
JMIR Res Protoc ; 12: e52565, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37962941

RESUMO

BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted pathogen associated with increasing antibiotic resistance. The current treatment guidelines recommend moxifloxacin-sequential therapy for macrolide-resistant Mgenitalium or strains with unknown resistance profiles. However, it is unclear whether sitafloxacin, a 4th-generation fluoroquinolone antibiotic, is effective against resistant strains. OBJECTIVE: This study aims to assess and compare the efficacy and safety of sitafloxacin- and moxifloxacin-based treatment regimens for managing Mgenitalium infections. METHODS: We will conduct this randomized controlled trial at multiple centers in Japan. Eligible participants include adults aged 18 years or older with a confirmed Mgenitalium infection, as determined through the nucleic acid amplification test. Patients will be randomly assigned using a stratified approach based on the treatment facility and infection site. The interventions comprise oral sitafloxacin (200 mg) daily for 7 days (with optional pretreatment of oral doxycycline, 200 mg, daily for up to 7 days), with a control group receiving oral doxycycline (200 mg) daily for 7 days followed by moxifloxacin (400 mg) daily for another 7 days. The primary outcome is the treatment success rate with a superiority margin of 10%, as confirmed through the nucleic acid amplification test. Secondary outcomes encompass changes in the bacterial load at the urogenital or rectal sites and the emergence of posttreatment-resistant mutant strains. RESULTS: Enrollment commenced in June 2023 and will conclude in December 2024, with findings anticipated by 2025. The expected success rates fall within the range of 80% for sitafloxacin and 42% for moxifloxacin against Mgenitalium carrying the G248T (S83I) mutation, based on previous studies. Accordingly, with a 5% significance level (2-sided) and 80% statistical power, we aim to recruit 50 participants per group, factoring in a 10% expected dropout rate. CONCLUSIONS: This study will provide valuable insights into the efficacy and safety of sitafloxacin- versus moxifloxacin-based sequential therapy in treating Mgenitalium infections. These findings have the potential to influence clinical guidelines, favoring more effective therapeutic choices. The multicenter approach enhances the robustness of this study. However, a limitation is the potential insufficiency of statistical power to detect posttreatment-resistant mutant strains in each group, rendering posttreatment-resistance mutations a notable concern. In the future, we may need to increase the sample size to enhance power. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs031230111); https://jrct.niph.go.jp/en-latest-detail/jRCTs031230111. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52565.

19.
Biomed Hub ; 8(1): 72-78, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920726

RESUMO

Introduction: Early detection of dysphagia risk, initiating rehabilitation, and resumption of appropriate diet based on swallowing function is important during deep neck infection (DNI) control. This study aimed to evaluate the extent of cervical abscess development, particularly in the deep neck space, and its relationship to postoperative swallowing function. Methods: A retrospective chart review was performed for all DNI cases treated between April 2015 and April 2021. Deep neck spaces were divided into categories based on computed tomography findings. Functional Oral Intake Scale (FOIS) scores of 4 or higher was defined as normal or slight swallowing disorder and 3 or lower as dysphagia. Results: Seventeen cases were included in the analysis. Based on FOIS, 14 cases were classified into the dysphagia group at 2 weeks after surgery, 11 cases at 4 weeks, and 8 cases at 8 weeks. There was no significant difference between the location of the abscess and dysphagia at 2 weeks after surgery. Patients with anterior cervical space abscess significantly increased dysphagia 4 weeks (p = 0.018) and 8 weeks (p = 0.036) after surgery. Conclusion: Abscess formation in the anterior cervical space may be associated with prolonged dysphagia after treatment due to inflammation and scarring of the muscles associated with swallowing.

20.
Int J Pediatr Otorhinolaryngol ; 174: 111747, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37820571

RESUMO

OBJECTIVE: Children with cleft palate (CP) are at high risk of developing otitis media with effusion (OME) due to Eustachian tube (ET) dysfunction. Palatoplasty has been reported to decrease the frequency of middle ear disease and improve ET function, and although various techniques have been developed, there is no consensus on the differences in the impact of different techniques on the middle ear. The purpose of this study was to determine the differential effects of palatoplasty on middle ear function and hearing. METHODS: We performed a retrospective observational survey of pediatric patients who underwent palatoplasty for CP between June 2010 and October 2018 at Tohoku University Hospital. Cases were divided into three groups depending on the palatoplasty procedures performed: the push-back palatoplasty group, the two-flap palatoplasty group, and the Furlow double-opposing Z-plasty group. We examined the differences in clinical characteristics between patients who underwent each procedure. The primary outcome variable was tympanic membrane (TM) findings, and the secondary outcome was hearing test results. RESULTS: Children who underwent the two-flap palatoplasty had a higher tympanostomy tube (TT) insertion rate and a higher total number of TT insertions than those who underwent the Furlow double-opposing Z-plasty or the push-back palatoplasty. The TM retraction rate tended to be lower in the Furlow double-opposing Z-plasty group than in the push-back palatoplasty group or the two-flap palatoplasty group. The hearing test results at the last visit were not significantly different among the three groups. CONCLUSIONS: Children who underwent the two-flap palatoplasty had a higher rate of TT insertions, potentially increasing the risk of TM perforation. In contrast, the Furlow double-opposing Z-plasty group had a lower tendency for TM regression, possibly due to improved ET function and reduced incidence of OME. It is important to understand the advantages and disadvantages of each technique before selecting one suitable for the child's cleft and arch width. Additionally, it is important to conduct regular follow-up of TM findings and hearing test results even after palatoplasty.


Assuntos
Fissura Palatina , Otopatias , Otite Média com Derrame , Criança , Humanos , Fissura Palatina/cirurgia , Fissura Palatina/complicações , Otopatias/cirurgia , Audição , Testes Auditivos , Ventilação da Orelha Média , Otite Média com Derrame/diagnóstico , Otite Média com Derrame/cirurgia , Otite Média com Derrame/etiologia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Membrana Timpânica/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...