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1.
Z Orthop Unfall ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38604232

RESUMO

Elderly people are prone to falls. We established the Falls Prevention Working Group (FPWG) at our hospital in 2015 to reduce the number of falls during hospitalization. This study compared the trend of in-hospital falls in the elderly in two time periods (2008/9 and 2018/9) and determined the effects of FPWG-implemented measures. Using medical records, we counted the monthly number of falls suffered by patients during hospitalization in April 2008-March 2009 and April 2018-March 2019. We also categorized the falls according to the severity of fall-related complications.A total of 3609 hospital falls were recorded during the 2008-2019 period (2008/9: n = 433, 2018/9: n = 324). Falls were more common in patients aged 70-79 in 2008/9 but were noted in those aged ≥ 80 in 2018/9. The mean number of falls/month (27.3 ± 6.4, range: 12-45) was stable throughout the year. The incidence of falls in 2018/9 (1.90/1000 per persons per day) was significantly lower than in 2008/9 (2.30/1000, p = 0.006). Level ≥ 3b accidents, reflecting serious accidents with complications, were encountered in 12 of 433 accidents in 2008/9 compared with significantly fewer accidents (2 of the same severity among 324 accidents) in 2018/9 (p = 0.030).Our results showed a decrease in in-hospital falls in 2018/9 and that the sufferers were older relative to 10 years earlier. A multidisciplinary team should recommend measures to prevent falls and an environment "resilient" to falls, and encourage patients to be aware of possible falls.

2.
Anal Sci ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478357

RESUMO

Hypoxia is involved in various diseases, such as cancers. Pimonidazole has often been used as the gold-standard marker to visualize hypoxic regions. Pimonidazole labels hypoxic regions by forming a covalent bond with a neighboring protein under hypoxic conditions in the body, which is detected by immunohistochemistry performed on tissue sections. To date, some pimonidazole-fluorophore conjugates have been reported as fluorescent probes for hypoxia imaging that do not require immunostaining. They are superior to pimonidazole because immunostaining can produce high background signals. However, large fluorophores in the conjugates may alter the original biodistribution and reactivity. Here, we report a new hypoxia marker, Pimo-yne, as a pimonidazole-alkyne conjugate. Pimo-yne has a similar hypoxia detection capability as pimonidazole because the alkyne tag is small and can be detected by Cu-catalyzed click reaction with azide-tagged fluorescent dyes. We successfully visualized hypoxic regions in tumor tissue sections using Pimo-yne with reduced background signals. The detected regions overlapped well with those detected by pimonidazole immunohistochemistry. To further reduce the background, we employed a turn-on azide-tagged fluorescent dye.

3.
ACS Nano ; 18(6): 5167-5179, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38301048

RESUMO

Elucidation of biological phenomena requires imaging of microenvironments in vivo. Although the seamless visualization of in vivo hypoxia from the level of whole-body to single-cell has great potential to discover unknown phenomena in biological and medical fields, no methodology for achieving it has been established thus far. Here, we report the whole-body and whole-organ imaging of hypoxia, an important microenvironment, at single-cell resolution using activatable covalent fluorescent probes compatible with tissue clearing. We initially focused on overcoming the incompatibility of fluorescent dyes and refractive index matching solutions (RIMSs), which has greatly hindered the development of fluorescent molecular probes in the field of tissue clearing. The fluorescent dyes compatible with RIMS were then incorporated into the development of activatable covalent fluorescent probes for hypoxia. We combined the probes with tissue clearing, achieving comprehensive single-cell-resolution imaging of hypoxia in a whole mouse body and whole organs.


Assuntos
Corantes Fluorescentes , Imageamento Tridimensional , Animais , Camundongos , Imageamento Tridimensional/métodos , Sondas Moleculares , Hipóxia/diagnóstico por imagem , Imagem Óptica/métodos
4.
Epileptic Disord ; 26(1): 139-143, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38009673

RESUMO

Dynamin-1 (DNM1) is involved in synaptic vesicle recycling, and DNM1 mutations can lead to developmental and epileptic encephalopathy. The neuroimaging of DNM1 encephalopathy has not been reported in detail. We describe a severe phenotype of DNM1 encephalopathy showing characteristic neuroradiological features. In addition, we reviewed previously reported cases who have DNM1 pathogenic variants with white matter abnormalities. Our case presented drug-resistant seizures from 1 month of age and epileptic spasms at 2 years of age. Brain MRI showed no progression of myelination, progression of diffuse cerebral atrophy, and a thin corpus callosum. Proton magnetic resonance spectroscopy showed a decreased N-acetylaspartate peak and diffusion tensor imaging presented with less pyramidal decussation. Whole-exome sequencing revealed a recurrent de novo heterozygous variant of DNM1. So far, more than 50 cases of DNM1 encephalopathy have been reported. Among these patients, delayed myelination occurred in two cases of GTPase-domain DNM1 encephalopathy and in six cases of middle-domain DNM1 encephalopathy. The neuroimaging findings in this case suggest inadequate axonal development. DNM1 is involved in the release of synaptic vesicles with the inhibitory transmitter GABA, suggesting that GABAergic neuron dysfunction is the mechanism of refractory epilepsy in DNM1 encephalopathy. GABA-mediated signaling mechanisms play important roles in axonal development and GABAergic neuron dysfunction may be cause of white matter abnormalities in DNM1 encephalopathy.


Assuntos
Encefalopatias , Epilepsia , Espasmos Infantis , Humanos , Dinamina I/genética , Imagem de Tensor de Difusão , Epilepsia/genética , Espasmos Infantis/genética , Mutação , Fenótipo , Ácido gama-Aminobutírico/genética
5.
J Reprod Dev ; 70(1): 49-54, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38008463

RESUMO

Pre-ovulatory follicles are cooler than the neighboring reproductive organs in cows. Thus, measuring the temperature of reproductive organs could be a useful method for predicting estrus and ovulation in cows, and the establishment of a non-invasive technique is required. In this study, we used infrared thermography (IRT) to measure ocular surface temperature as a potential surrogate for reproductive organ temperature. Five Japanese Black cows with synchronized estrus were subjected to temperature measurements in five regions of the ocular surface, including the nasal conjunctiva, nasal limbus, center cornea, temporal limbus, and temporal conjunctiva, twice a day (0800 h and 1600 h) during the experimental period. The temperatures in the five regions significantly declined in cows from estrus to ovulation. To the best of our knowledge, this study is the first to use IRT to show a temperature decrease in the ocular surface along with estrus to ovulation in Japanese Black cows.


Assuntos
Ovulação , Termografia , Feminino , Bovinos , Animais , Temperatura , Termografia/veterinária , Termografia/métodos , Temperatura Corporal , Estro , Sincronização do Estro
6.
Brain Dev ; 46(1): 57-61, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37778966

RESUMO

BACKGROUND: Some patients with ATP1A3 variant-associated polymicrogyria have recurrent transient heart failure. However, effective treatment for the transient cardiac condition remains to be elucidated. CASE REPORT: The patient started experiencing focal motor onset seizures in 12 h after birth, revealing bilateral diffuse polymicrogyria. The patient also experienced transient bradycardia (sinus bradycardia) attacks from 15 days old. Echocardiography revealed a reduced ejection fraction; however, no obvious electrocorticogram or electroencephalogram abnormalities were observed during the attacks. Initially, the attacks occurred in clusters daily. They later decreased in frequency, occurring at monthly intervals. Repeated episodes of transient bradycardia attacks and polymicrogyria indicated possible ATP1A3 gene abnormality and genetic testing revealed a novel heterozygous ATP1A3 variant (NM_152296: exon22:c.2977_2982del:p.(Glu993_Ile994del)), which was not found in the patient's parents. Cilostazol was administered at 3 months old for recurrent transient bradycardia attacks. Cilostazol significantly shortened the duration of bradycardia episodes and prolonged the interval between attacks. Cilostazol also effectively treats transient symptomatic bradycardia. CONCLUSION: Cilostazol could be a treatment option for recurrent transient bradycardia attacks associated with ATP1A3 gene abnormalities and polymicrogyria.


Assuntos
Insuficiência Cardíaca , Polimicrogiria , Humanos , Lactente , Cilostazol , Bradicardia/tratamento farmacológico , Bradicardia/genética , Polimicrogiria/tratamento farmacológico , Polimicrogiria/genética , Polimicrogiria/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/complicações , Convulsões/complicações , ATPase Trocadora de Sódio-Potássio/genética
7.
Vaccine ; 42(2): 239-245, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38087713

RESUMO

PURPOSE: To investigate individual and environmental vaccination-related factors among the older adults in Japan, using administrative data. METHODS: We conducted a cohort study and included people who reached the relevant age (≥65 years) for routine pneumococcal vaccination of older adults between April 2015 and March 2020. Monthly data of residents in the two municipalities from April 2014 to March 2020 and vaccination records from April 2015 to March 2020 were used. We defined five cohorts according to the year in which routine vaccinations were available. Each cohort was followed for a total of two years, with the first year being the "baseline period" and second year being the "vaccine follow-up period." Pneumococcal vaccination data was extracted from vaccination records at "first dose." Age, sex, socioeconomic status, comorbidities, hospital visit history, hospitalization history, Specific Health Check-ups participation, and information on contracted hospitals for pneumococcal vaccination were used as covariates. A multivariate logistic regression model was used to investigate the relationship between pneumococcal vaccination and vaccination-related factors. Odds ratios (OR) and 95 % confidence intervals (95 % CI) were calculated. RESULTS: Analysis included 17,991 patients. Vaccination coverage was 33.6 % for all subjects. Multivariate analysis found the following as significant vaccination-related factors: female (OR: 1.18, 95 % CI: 1.11-1.26), not low income (1.76, 1.17-2.76), hospital visits: ≥once/month (1.27, 1.19-1.35), and Specific Health Check-ups participation (2.10, 1.95-2.27). No significant results were found for hospitals that contracted pneumococcal vaccination. CONCLUSIONS: Individual factors, such as sex and Specific Health Check-ups participation, were found to be important factors affecting pneumococcal vaccination among older adults in Japan. Environmental factors, such as the characteristics of residential areas, should be evaluated in further investigations.


Assuntos
Infecções Pneumocócicas , Cobertura Vacinal , Humanos , Feminino , Idoso , Japão , Estudos de Coortes , Infecções Pneumocócicas/prevenção & controle , Vacinação , Streptococcus pneumoniae , Vacinas Pneumocócicas
9.
J Med Case Rep ; 17(1): 478, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907963

RESUMO

BACKGROUND: Few reports have described multidisciplinary treatment, including extracorporeal shock wave therapy, for patients with refractory chronic tension-type headache. In this study, we conducted multidisciplinary treatment for a patient with chronic tension-type headache who suffered from chronic headache refractory to treatment. CASE PRESENTATION: The patient was a 45-year-old Japanese male suffering from 20 years of headache. As his headache had worsened recently, he visited a local clinic. With the diagnosis of suspected tension-type headache, its treatment was unsuccessful and he was referred to our hospital. The neurology department confirmed the tension-type headache and prescribed another medication, but he showed no improvement. Then, the patient was referred to the rehabilitation medicine department for consultation. At the initial visit, we identified multiple myofascial trigger points in his bilateral posterior neck and upper back regions. At the initial visit, he was prescribed 10 mL of 1% lidocaine injected into the muscles in these areas. In addition, he received 2000 extracorporeal shock wave therapy into bilateral trapezius muscles, and was instructed to take oral Kakkonto extract granules, benfotiamine, pyridoxine hydrochloride, and cyanocobalamin. Cervical muscle and shoulder girdle stretches and exercises were also recommended. At follow-up treatment visits, we used extracorporeal shock wave therapy to bilateral trapezius muscles, which led to immediate pain relief. After 11 weeks, he was not taking any medication and his headache was subjectively improved and his medical treatment ended. CONCLUSION: A patient with chronic tension-type headache refractory to regular treatment was successfully treated with a multimodal approach including extracorporeal shock wave therapy in addition to standard treatment. For patients with tension-type headache accompanied by myofascial trigger points, it may be recommended to promptly consider aggressive multimodal treatment that includes extracorporeal shock wave therapy.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas , Síndromes da Dor Miofascial , Cefaleia do Tipo Tensional , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Combinada , Cefaleia , Síndromes da Dor Miofascial/complicações , Síndromes da Dor Miofascial/diagnóstico , Síndromes da Dor Miofascial/terapia , Cefaleia do Tipo Tensional/terapia , Cefaleia do Tipo Tensional/diagnóstico , Cefaleia do Tipo Tensional/etiologia
10.
J Vet Med Sci ; 85(12): 1355-1365, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-37914278

RESUMO

The composition of the gut microbiome varies due to dietary habits. We investigated influences of diet on the composition of the gut microbiome using the feces of 11 avian species, which consumed grain-, fish- and meat-based diets. We analyzed gut microbiome diversity and composition by next-generation sequencing (NGS) of 16S ribosomal RNA. The grain-diet group had higher gut microbiome diversity than the meat- and fish-diet group. The ratio of Bacteroidetes and Firmicutes phyla was higher in the grain-diet group than in the meat- and fish-diet groups. The grain-diet group had a higher ratio of Veillonellaceae than the meat-diet group and a higher ratio of Eubacteriaceae than the fish-diet habit group. To clarify the influence of diet within the same species, white-tailed eagles (Haliaeetus albicilla, n=6) were divided into two groups, and given only deer meat or fish for approximately one month. The composition of the gut microbiome of individuals in both groups were analyzed by NGS. There were indications of fluctuation in the levels of some bacteria (Lactobacillus, Coriobacteriales, etc.) in each diet group. Moreover, one individual for each group which switched each diet in last week changed to each feature of composition of bacterial flora. The above results show that the composition of the gut microbiome differ depending on diet, even within the same species.


Assuntos
Cervos , Águias , Microbioma Gastrointestinal , Animais , Microbioma Gastrointestinal/genética , Cervos/genética , Bactérias/genética , Dieta/veterinária , Fezes/microbiologia , Comportamento Alimentar , RNA Ribossômico 16S/genética
11.
QJM ; 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37878823

RESUMO

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated a) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or b) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

12.
Photodiagnosis Photodyn Ther ; 44: 103861, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37879425

RESUMO

BACKGROUND: We previously developed a site-specific transvascular drug delivery system (DDS) based on photomechanical waves (PMWs) or laser-induced stress/shock waves (LISWs). In this study, we investigated the validity of this method to deliver a clinical photosensitizer, talaporfin sodium (TS), to subcutaneous tumors in mice and to enhance the efficacy of photodynamic therapy (PDT). METHODS: TS solution (2.5 mg/kg) was intravenously injected into mice. Immediately thereafter, PMWs were applied to the tumor by irradiating a laser target with a Q-switched ruby laser pulse (0.8 J/cm2). Five hours after TS administration, some tumors were excised to evaluate the depth distribution of the delivered TS under a fluorescence microscope. Other tumors were subjected to PDT by irradiating the tissues with a 665 nm continuous-wave laser diode (75 mW/cm2, 667 s) at this timepoint. The effects of PDT were evaluated on the basis of the two primary therapeutic mechanisms of TS-mediated PDT: i) damage to tumor cells and ii) damage to endothelial cells of tumor vessels, i.e., the vascular shutdown effect on tumors. RESULTS: PMW application significantly increased the accumulation of TS in the tumor parenchyma but not in the tumor vessel walls; the endothelial cell junctions of tumor vessels should be the route of TS delivery enhanced by PMWs. Thus, as a result of PMW application followed by PDT, while the vascular shutdown effect on the tumors was not enhanced, direct damage to the tumor cells was increased, resulting in significant tumor growth retardation without body weight loss for 7 days after treatment.


Assuntos
Fotoquimioterapia , Porfirinas , Camundongos , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Células Endoteliais , Lasers
13.
Eur J Cardiothorac Surg ; 64(3)2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37725388

RESUMO

OBJECTIVES: Ventricular tachycardia (VT) originating from the left ventricular summit region, the most superior region of the left ventricle surrounded by the major coronary arteries and veins, is frequently refractory to pharmacological therapies and endocardial and epicardial catheter ablation. METHODS: Eleven patients with an age from 31 to 79 (median 56) years old, underwent map-guided surgery for left ventricular summit VT. All patients had undergone 1-5 unsuccessful sessions of catheter ablation for incessant VT, preoperatively. Five patients had suffered VT storm and 1 had a history of cardiopulmonary resuscitation. Four patients had implanted with a defibrillator. Epicardium to endocardium transmural cryothermia was applied at the VT origin determined by intraoperative epicardial mapping with electro-anatomical mapping system. Harmonic scalpel was used to remove the epicardial fat and cryothermia was applied directly to the myocardium, avoiding thermal or mechanical injuries to the coronary vessels. Additional endocardial cryothermia at the VT origin was performed by a cryoprobe introduced into the left ventricular cavity through an aortotomy. RESULTS: There was no surgical mortality or long-term mortality related to VT during a median follow-up period of 60 months (interquartile range: 34-82). Five-year freedom from preoperatively documented left ventricular summit VT and non-documented VT was 91% and 73%, respectively. All the patients with postoperative VT underwent successful catheter ablation. Other patients were free from VT during the follow-up period. CONCLUSIONS: Epicardial to endocardial transmural cryothermia at the VT origin guided by intraoperative electro-anatomical mapping with a close collaboration with electrophysiologists was crucial in successful surgery for left ventricular summit VT.


Assuntos
Reanimação Cardiopulmonar , Ablação por Cateter , Taquicardia Ventricular , Humanos , Pessoa de Meia-Idade , Ventrículos do Coração/cirurgia , Taquicardia Ventricular/cirurgia , Tecido Adiposo
15.
J Med Invest ; 70(1.2): 115-122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37164706

RESUMO

BACKGROUND AND PURPOSE: Jumping to conclusion (JTC)-a cognitive bias in thinking processes-leads to drawing conclusions based on little information, and could be related to psychosis and paranoia. While it has recently been pointed out that it could accompany the autism spectrum disorder (ASD), no interventions targeting this bias in adolescents with ASD have been reported. Therefore, this exploratory study investigated the effects of a group social cognition program on JTC bias in adolescents with ASD. PATIENTS AND METHODS: Group rehabilitation using social cognition and interaction training (SCIT) was conducted for 12- to 18-year-old adolescents with ASD. An SCIT program comprehensively targets social cognitive functions, including interventions for JTC bias, and examines changes before and after the SCIT intervention, social cognitive functioning tasks, and subjective quality of life (QOL). RESULTS: Thirteen adolescents with ASD participated in this program ; 10 (76.9%) stayed through it. The proportion of participants with JTC bias decreased significantly before and after SCIT (before : 7/10 ; after : 1/10 ; p = 0.041), and subjective QOL increased significantly (p=0.014). CONCLUSION: The results show that a group social cognition program with a JTC bias approach improves the JTC bias and increases subjective QOL in adolescents with ASD. J. Med. Invest. 70 : 115-122, February, 2023.


Assuntos
Transtorno do Espectro Autista , Psicoterapia de Grupo , Humanos , Adolescente , Criança , Qualidade de Vida , Transtorno do Espectro Autista/terapia , Cognição
16.
J Clin Psychopharmacol ; 43(4): 365-368, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37216369

RESUMO

BACKGROUND: Although several guidelines recommend monotherapy with antipsychotics for the treatment of schizophrenia, patients who receive long-acting injectable antipsychotics (LAIs) are frequently treated with oral antipsychotics (OAPs). In the present study, we investigated the detailed use of psychotropic medications among patients throughout Japan with schizophrenia who received LAIs or OAPs. METHODS: The present study used data from the project for the Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment from 94 facilities in Japan. The LAI group included patients who received any LAI, and the non-LAI group included patients who took only OAP medications at discharge. The participants of this study were 2518 schizophrenia patients (263 in the LAI group and 2255 in the non-LAI group) who received inpatient treatment and had prescription information at discharge between 2016 and 2020. RESULTS: This study revealed significantly higher rates of polypharmacy antipsychotics, number of antipsychotics, and chlorpromazine equivalents in the LAI group than in the non-LAI group. In contrast, the LAI group showed lower rate of concomitant use of hypnotic and/or antianxiety medication than the non-LAI group. CONCLUSIONS: Presenting these real-world clinical results, we want to encourage clinicians to keep monotherapy in mind for the treatment of schizophrenia, especially by reducing concomitant use of antipsychotics in the LAI group and reducing hypnotic and/or antianxiety medication in the non-LAI group.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Japão , Injeções , Administração Oral , Hipnóticos e Sedativos , Preparações de Ação Retardada/uso terapêutico
17.
Drug Metab Pharmacokinet ; 50: 100497, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37037169

RESUMO

Caco-2 cells are widely used as an in vitro intestinal model. However, the expression levels of the drug-metabolizing enzymes CYP3A4 and UGT1A1 are lower in these cells than in intestinal cells. Furthermore, the majority of prodrugs in use today are ester-containing, and carboxylesterase (CES) 1 and CES2 are among the enzymes that process the prodrugs into drugs. In the human small intestine, CES1 is hardly expressed while CES2 is highly expressed, but the CES expression pattern in Caco-2 cells is the opposite. In this study, we generated CYP3A4-POR-UGT1A1-CES2 knock-in (KI) and CES1 knock-out (KO) Caco-2 (genome-edited Caco-2) cells using a PITCh system. Genome-edited Caco-2 cells were shown to express functional CYP3A4, POR, UGT1A1 and CES2 while the expression of the CES1 protein was completely knocked out. We performed transport assays using temocapril. The Papp value of temocapril in genome-edited Caco-2 cells was higher than that in WT Caco-2 cells. Interestingly, the amount of temocaprilat on the apical side in genome-edited Caco-2 cells was lower than that in WT Caco-2 cells. These results suggest that genome-edited Caco-2 cells are more suitable than WT Caco-2 cells as a model for predicting intestinal drug absorption and metabolism.


Assuntos
Carboxilesterase , Pró-Fármacos , Humanos , Células CACO-2 , Carboxilesterase/genética , Carboxilesterase/metabolismo , Citocromo P-450 CYP3A/genética , Pró-Fármacos/metabolismo
18.
Molecules ; 28(6)2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36985707

RESUMO

A novel algorithm for covalent bond dissociation is developed to accurately predict fracture behavior of thermosetting polymers via molecular dynamics simulation. This algorithm is based on the Monte Carlo method that considers the difference in local strain and bond-dissociation energies to reproduce a thermally activated process in a covalent bond dissociation. This study demonstrates the effectiveness of this algorithm in predicting the stress-strain relationship of fully crosslinked thermosetting polymers under uniaxial tensile conditions. Our results indicate that the bond-dissociation energy plays an important role in reproducing the brittle fracture behavior of a thermosetting polymer by affecting the number of covalent bonds that are dissociated simultaneously.

19.
Clin Neurol Neurosurg ; 226: 107620, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36805253

RESUMO

BACKGROUND: Some patients with post-stroke claw toe respond well to botulinum toxin (BoNT) treatment while others do not. This study was designed to assess the impact of stroke type (cerebral hemorrhage and cerebral infarction) on the outcome of BoNT treatment for claw toe. METHODS: We retrospectively examined the medical records of patients who received local BoNT (onabotulinumtoxin A) injections into the flexor hallucis longus (FHL) and flexor digitorum longus (FDL) muscles. All patients suffered stroke-related leg paralysis and spasticity. RESULTS: The study participants were 58 patients (mean age, 61.4 ± 10.3 years, ± SD) with time since stroke of 6.7 ± 4.4 years. The stroke type was cerebral hemorrhage (n = 38) and cerebral infarction (n = 20). After a total of 124 BoNT administrations with medical records entries on the subjective symptoms, the odds for symptomatic improvement was approximately 5.8 times higher in patients of the infarction group compared with the hemorrhage group (OR = 5.787, 95% CI = 2.369-14.134, p = 0. 000). Fifty-one patients (32 with cerebral hemorrhage, 19 with cerebral infarction) received the first local BoNT injection and had available medical records, analysis of which showed a significantly higher rate of symptomatic improvement in patients of the infarction group than those of the hemorrhage group (p = 0.006). After adjustment by factors known to influence treatment outcome (degree of spasticity and paralysis, BoNT dosage, and extent of FDL muscle control of toe movements), the treatment effect was predominantly higher in patients with cerebral infarction. CONCLUSION: The BoNT treatment response was better for claw toes in cerebral infarction patients than in hemorrhage patients, possibly suggesting that claw toe is associated with more severe spasticity in this group of patients.


Assuntos
Toxinas Botulínicas Tipo A , Síndrome do Dedo do Pé em Martelo , Fármacos Neuromusculares , Acidente Vascular Cerebral , Humanos , Pessoa de Meia-Idade , Idoso , Síndrome do Dedo do Pé em Martelo/complicações , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Espasticidade Muscular , Paralisia , Hemorragia Cerebral/complicações , Resultado do Tratamento , Infarto Cerebral/complicações , Infarto/complicações
20.
Children (Basel) ; 10(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36670685

RESUMO

BACKGROUND: Outdoor play (OP), which is considered important for children's development, is declining every year. Perceived physical competence (PPC) is a vital factor that promotes physical activity such as OP, sports clubs, etc., but the relationship between PPC and OP was unknown. The purpose of this research was to investigate the relationship between PPC and OP in children and consider whether there were any sex-specific changes. METHODS: A cross-sectional study was conducted in Japan with 288 children (134 girls, age: 10.6 ± 1.01 years). OP was assessed using an original self-report questionnaire. Each weekday, the children reported the time of OP and were classified as "high" if they played outside for at least an hour three times. PPC was evaluated with a self-report questionnaire developed by Okazawa et al. (1996). It has 12 questions and was assessed on a 5-point Likert scale. After adjusting for age, sex, BMI, screen time, sports club participation, and the number of friends, logistic regression analyses were carried out. RESULTS: Children with better PPC were significantly more likely to be classified as "high" [crude odds ratio (OR): 1.04; 95% confidence interval (CI): 1.00-1.08; adjusted OR: 1.04; 95% CI: 1.00-1.08]. Only girls with better PPC were significantly more likely to be classified as "high" in a sex-based stratified analysis [crude OR: 1.08; 95% CI: 1.01-1.15, adjusted OR 1.09; 95% CI: 1.02-1.17]. CONCLUSIONS: Particularly among girls, OP could be promoted as a voluntary physical activity with improved PPC.

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