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1.
J Hum Genet ; 68(12): 849-857, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37731132

RESUMO

Numerous variants of unknown significance (VUSs) exist in hereditary breast and ovarian cancers. Although multiple methods have been developed to assess the significance of BRCA1/2 variants, functional discrepancies among these approaches remain. Therefore, a comprehensive functional evaluation system for these variants should be established. We performed conventional homologous recombination (HR) assays for 50 BRCA1 and 108 BRCA2 VUSs and complementarily predicted VUSs using a statistical logistic regression prediction model that integrated six in silico functional prediction tools. BRCA1/2 VUSs were classified according to the results of the integrative in vitro and in silico analyses. Using HR assays, we identified 10 BRCA1 and 4 BRCA2 VUSs as low-functional pathogenic variants. For in silico prediction, the statistical prediction model showed high accuracy for both BRCA1 and BRCA2 compared with each in silico prediction tool individually and predicted nine BRCA1 and seven BRCA2 variants to be pathogenic. Integrative functional evaluation in this study and the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines strongly suggested that seven BRCA1 variants (p.Glu272Gly, p.Lys1095Glu, p.Val1653Leu, p.Thr1681Pro, p.Phe1761Val, p.Thr1773Ile, and p.Gly1803Ser) and four BRCA2 variants (p.Trp31Gly, p.Ser2616Phe, p.Tyr2660Cys, and p.Leu2792Arg) were pathogenic. This study demonstrates that integrative evaluation using conventional HR assays and optimized in silico prediction comprehensively classified the significance of BRCA VUSs for future clinical applications.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Humanos , Feminino , Proteína BRCA1/genética , Predisposição Genética para Doença , Proteína BRCA2/genética , Recombinação Homóloga , Neoplasias da Mama/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
2.
Nihon Koshu Eisei Zasshi ; 70(9): 544-553, 2023 Sep 30.
Artigo em Japonês | MEDLINE | ID: mdl-37286491

RESUMO

Objectives In Japan, schools of public health (SPH) have engaged in professional education focusing on five core disciplines: epidemiology, biostatistics, social and behavioral science, health policy and management, and occupational and environmental health. However, empirical information is lacking regarding the current state of this education and its associated challenges in Japan. In this article, we showcase this issue, using the master of public health (MPH) course at Teikyo University Graduate School of Public Health (Teikyo SPH) as an example.Methods We summarized the current objectives and classes required to complete the MPH course at Teikyo SPH, using the course guideline published in 2022. Current issues and possible future directions in the course were summarized based on the opinions of Teikyo SPH faculty members.Results For epidemiology, lectures and exercises were designed to focus on how to formulating public health issues, collecting and evaluating data, and causal inference. Issues related to the design included ensuring that students had the necessary skills to apply epidemiology to emerging issues, and catching the course up with evolving techniques. For biostatistics, lectures and exercise classes focused on understanding data and statistics, as well as performing analyses. Issues included the understanding of theories, setting the course level, and a lack of appropriate education materials for emerging analytical methods. For social and behavioral science, lectures and exercise classes focused on understanding human behaviors and actions for problem solving. Issues included learning various behavioral theories in a limited timeframe, the gap between the lectures and various needs, and nurturing professionals who had the skills to perform in practical settings. For health policy and management, lectures, exercise classes, and practical training classes focused on identifying and solving problems in the community and around the world, and on integrating the disparate viewpoints of health economics and policy. Issues included few alumni who actually found work globally, a lack of students working in local or central administrations, and insufficient perspectives on rational/economic thinking and macro-economic transitions. For occupational and environmental health, lectures, exercise classes, and practical training classes focused on learning the occupational and environmental impacts of public health issues, and their countermeasures. Challenges included enriching the topics with regard to advanced technologies, environmental health, and socially vulnerable populations.Conclusion Through these reflections on MPH education at Teikyo SPH, the following recommendations are considered essential in order to prepare improvements to the program: reorganizing the curriculum to meet the needs of the day, accepting students with various backgrounds, addressing the increasing knowledge and skills that need to be acquired by the students, and enhancing the powers of professors to implement changes.


Assuntos
Educação Profissional em Saúde Pública , Saúde Pública , Humanos , Universidades , Escolaridade , Currículo , Educação Profissional em Saúde Pública/métodos
3.
Invest New Drugs ; 40(1): 142-150, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34417913

RESUMO

Background The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) was established in 2004. Since then, various pieces of legislation, notices, and guidelines have been issued, and the regulatory approval pathways for domestic drugs have been diversified. However, the effects of these measures have not been fully examined. We examined the impact of these measures on the approval of antineoplastic drugs and the design of pivotal clinical trials for efficacy assessment by the PMDA. Methods We collected data on the antineoplastic drugs approved by the PMDA in fiscal years 2004-2019. We extracted the approval review pathways and the pivotal clinical trial designs from the PMDA review reports, and analyzed them to identify patterns. Results In total, 387 indications in oncology were approved by the PMDA in fiscal years 2004-2019, or 365 indications excluding multiple regulatory pathways. The number of approved indications generally increased year on year (p < 0.001). The largest number of approved indications was under the Orphan Drug Designation (31%, 114/365) and this continues to increase (p < 0.001). In the 288 indications for which clinical trial data were submitted for review, the pivotal clinical trial designs changed significantly (p < 0.001) after the guideline on clinical evaluation for antineoplastic drugs was revised in 2006. Conclusion The number of indications in oncology approved by the PMDA has been increasing over the past 16 years, alongside changes in regulatory pathways. The 2006 guideline on clinical evaluation had a particular impact on pivotal clinical trial designs.


Assuntos
Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto/organização & administração , Ensaios Clínicos como Assunto/estatística & dados numéricos , Aprovação de Drogas/organização & administração , Aprovação de Drogas/estatística & dados numéricos , Humanos , Japão , Produção de Droga sem Interesse Comercial/estatística & dados numéricos
4.
BMC Vet Res ; 18(1): 296, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918681

RESUMO

BACKGROUND: Communication skills are a necessary competency in veterinary medicine, and shared decision-making (SDM) between practitioners and patients is becoming increasingly important in veterinary practice as in human medicine. There are few studies that have quantitatively measured SDM in veterinary health care, and the relationship between SDM and consultation satisfaction is unknown. The purpose of this study was to investigate the status of SDM implementation in veterinary hospitals and the relationship between SDM implementation and consultation satisfaction among pet owners. We conducted a cross-sectional study using self-administered questionnaires among pet owners and veterinarians. In total, 77 pet owners who visited a veterinary clinic and 14 veterinarians at the clinics participated in this study. After a veterinary clinic visit, owners were asked to rate their decision-making preferences using the Shared Decision Making Questionnaire for patients (SDM-Q-9) adapted for veterinary medicine, as well as their satisfaction with the consultation. The corresponding veterinarians were asked to complete the veterinary version of the survey (SDM-Q-Doc). RESULTS: Most pet owners (64.9%) preferred SDM in veterinary consultations. Cronbach's alpha coefficient of 0.84 for the veterinary SDM-Q-9 and 0.89 for the veterinary SDM-Q-Doc both confirmed high reliability. The Spearman's correlation coefficient between the SDM-Q-9 and consultation satisfaction was 0.526 (p < 0.001), which was significant. The SDM-Q-Doc was not significantly correlated with either the SDM-Q-9 or pet owner consultation satisfaction. We conducted a sensitivity analysis of correlations among veterinarians; responses on the SDM-Q-Doc to examine the association between the SDM-Q-Doc and SDM-Q-9 and owner satisfaction; the results remained the same and no association was found. CONCLUSIONS: Our findings suggest that evaluation of SDM among pet owners was associated with their satisfaction with veterinary consultation. Veterinarians may be able to improve the satisfaction level of pet owners by adopting a consultation method that increases SDM. We did not consider the content of veterinary care or the number of visits to the veterinary clinic; future studies should be conducted to confirm the validity of our results.


Assuntos
Tomada de Decisão Compartilhada , Médicos Veterinários , Animais , Estudos Transversais , Tomada de Decisões , Humanos , Participação do Paciente , Satisfação Pessoal , Encaminhamento e Consulta , Reprodutibilidade dos Testes , Inquéritos e Questionários
5.
BMC Public Health ; 22(1): 461, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35255866

RESUMO

BACKGROUND: Dietary and lifestyle modifications to reduce subjective psychosomatic symptoms (SPS) have become an important topic worldwide. We developed a school-based dietary and lifestyle education programme that involved parents/guardians in reducing SPS in adolescents (SPRAT). The programme encouraged parents/guardians to participate in adolescents' healthy dietary and lifestyle modifications to reduce SPS, increase enjoyment of school life, and foster appropriate dietary intake. This study evaluated the effectiveness of SPRAT in reducing SPS and in altering dietary behaviour among adolescents. METHODS: A 6-month cluster randomised controlled trial using SPRAT and the usual school programme (control) was performed. Participants were middle school students in Japan who provided informed consent. Outcomes were SPS scores assessed at baseline and 2, 4, and 6 months after baseline and the proportions of dietary and lifestyle factors achieved such as enjoyment of school life and dietary intakes assessed by FFQW82. Change from baseline (CFB) at 6 months was the primary endpoint. A linear mixed-effects model was applied. As for dietary intake, the treatment effect was estimated as an interaction term between baseline and treatment "baseline*treatment". RESULTS: The intention-to treat analysis included 951 (94.7%) and 1035 (89.8%) individuals in the SPRAT and control groups, respectively. The CFB in the 6-month SPS score adjusted for baseline was lower in the SPRAT group (-0.29) than in the control group (0.62), but the difference was not statistically significant -0.91 (p = 0.093). CONCLUSIONS: Although the primary endpoint tended to denote improvement in the SPRAT group compared to the control group, the improvement was not significant. Favourable effects were observed in some secondary outcomes and statistically significant treatment*baseline interactions were observed for several dietary intakes. These results imply that CFBs of dietary intake were increased or decreased in a favourable direction depending on the baseline intake, especially in the SPRAT group. TRIAL REGISTRATION: UMIN000026715. (27/03/2017).


Assuntos
Dieta , Estilo de Vida , Adolescente , Comportamento Alimentar , Humanos , Transtornos Psicofisiológicos/prevenção & controle , Instituições Acadêmicas
6.
Chembiochem ; 20(22): 2862-2875, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31180162

RESUMO

Y257 of Oryza sativa parkeol synthase (OsOSC2) corresponds to H234 of Saccharomyces cerevisiae lanosterol cyclase (ScLAS), which is believed to be responsible for the final deprotonation reaction. An Ala mutant afforded nine tetracyclic skeletons as the main products; they consisted of protostadienol scaffolds with both 17R and 17S configurations and both 20R and 20S configurations, as well as a pair of 20R- and 20S-configured parkeols. The production of 20R- and 20S-configured tetracycles (59:40 ratio) through the action of the Y257A mutant indicated that the substrate folding had been altered from a chair-boat-chair-chair (a normal folding pattern) to a chair-boat-chair-boat structure (an unusual folding pattern). Other mutants with different steric bulks also yielded both 20R- and 20S-configured tetracycles. Thus, the primary function of Y257 appears to be to impose a normal chair structure at the D-ring site through having appropriate steric bulk. In contrast, mutations at H234 of ScLAS were reported to cause no conformational changes. The OsOSC2 Phe mutant also yielded 20R- and 20S-configured parkeols (25:33 ratio), thus suggesting that the OH group of Y257 can form hydrogen bonds with other amino acids to force a chair conformation at the D-ring site, and this variant also gave 20R- and 20S-configured parkeols in a high yield (60 %). Y257 is unlikely to act as a base to abstract H-11 and stabilize the transient cation through cation-π interactions. Thus, the catalytic roles of Y257 are significantly different from those of H234 of ScLAS.


Assuntos
Transferases Intramoleculares/química , Oryza/enzimologia , Proteínas de Plantas/química , Tirosina/química , Sequência de Aminoácidos , Domínio Catalítico , Ciclização , Transferases Intramoleculares/genética , Lanosterol/análogos & derivados , Lanosterol/síntese química , Conformação Molecular , Mutagênese Sítio-Dirigida , Mutação , Proteínas de Plantas/genética , Prótons , Esqualeno/análogos & derivados , Esqualeno/química
7.
JMIR Pediatr Parent ; 7: e48478, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38623727

RESUMO

Background: Recently, digital media, including internet websites and smartphone apps, have become popular resources for parents in searching for child health care information. Higher health literacy among parents in obtaining adequate health care information and making proper decisions may lead to improved child health outcomes and a reduction in the burden on health care professionals. However, few studies have examined the association between the provision of child health care information apps and parents' health literacy. Objective: This study aims to evaluate whether parents' use of an app that provides child health care information is associated with their health care knowledge, their health literacy, and emergency room visits for their children. Methods: Participants were recruited during checkups for their 1.5-year-old children at health centers within Saku City in 2022. Parents who agreed to participate were included in this study; individuals were excluded if they were not the mother or father of the child or did not have a smartphone. Participants were asked if they had used the Oshiete-Doctor app, which was distributed by Saku City free of charge to improve the home nursing skills of parents and guardians. Sociodemographic data of parents and children, data on health care knowledge about children, data on the frequency of emergency room visits in the past 6 months, and health literacy scores (HLSs) of parents (measured with the HLS-EU-Q47 [European Health Literacy Survey Questionnaire]) were collected from participants in this cross-sectional survey. Univariable and multivariable analyses were conducted to examine the associations of app use with health care knowledge, health literacy, and emergency room visits. Results: In total, 251 respondents completed the survey (response rate: 251/267, 94%). Although the proportion of health care workers was significantly higher among app users than among non-app users (P=.005), no other participant attributes were significantly associated with the use of the app. The proportions of participants with higher health care knowledge and participants with higher total HLSs were significantly higher among app users than among non-app users (P=.001 and P=.003, respectively). After adjusting for potentially confounding covariates, these proportions were still significantly higher among app users than among non-app users (P=.02 and P=.007, respectively). Emergency room visits were significantly more frequent among app users than among non-app users (P=.007) in the univariable analysis, but the association was not significant (P=.07) after adjusting for sociodemographic variables. Conclusions: This study showed a significant association between parents' use of a child health care information app and higher child health care knowledge and health literacy. The use of the app may lead to more appropriate health decisions and behaviors in children's health care. Future studies are needed to evaluate the association between app use and emergency room visits.

8.
Cureus ; 16(1): e52123, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38344613

RESUMO

Autoimmune polyendocrine syndrome (APS) type 3B is characterized by presence of autoimmune thyroid disease, chronic atrophic gastritis and pernicious anemia. In this report, we present a rare case of APS type 3B with neuropathy by thiamine deficiency. A 65-year-old man had a history with hypothyroidism, gastritis, gastrectomy for gastric cancer and subacute combined degeneration of the spinal cord. Patient developed polyneuropathy with not mecobalamin but thiamine deficiency. Serum anti-thyroglobin (TG), anti-thyroid peroxidase (TPO), and anti-gastric parietal cell antibodies were positive. He was treated with thiamine supplementation and improved muscle weakness, sensory impairment and gait disturbance. Classically, it is reported gastric cancer related to hypothyroidism. Additionally, thiamine deficiency can be caused by gastrectomy. Here, his thiamine deficiency was related to APS type 3B, leading to polyneuropathy.

9.
Cureus ; 16(2): e54390, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38505443

RESUMO

There are various causes of unilateral finger palsy. Its potential etiologies include peripheral neuropathy, carpal tunnel syndrome, and nerve root disorder due to myelopathy. In addition to them, similar paralysis has been reported in localized lesions of the cerebrum, classically referred to as pseudoperipheral palsy. In this report, we describe a case of an 80-year-old man who developed sudden clumsiness of the right fingers. Neurological examination showed muscle weakness mainly in the 1st and 2nd fingers (Medical Research Council grade 1-4) and normal reflexes in the extremities. The affected muscles were innervated by the median nerve, ulnar nerve, and radial nerve, and their nerve root levels ranged from C6 to T1. All the Phalen's, Tinel's, and flick signs were negative. Diffusion-weighted brain magnetic resonance imaging showed hyperintensity limited in the precentral knob on the left precentral gyrus. The etiology was diagnosed as cardiogenic embolism due to atrial fibrillation. In this report, we provide key findings for diagnosing pure motor isolated finger palsy by cerebral infarction through neurological examination.

10.
Traffic Inj Prev ; 25(1): 27-35, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37773056

RESUMO

OBJECTIVES: Few studies have examined motor function in determining the suitability of patients with stroke to resume driving a car. Patients with hemiplegia usually control car pedals with the unaffected lower limb. However, motor control on the unaffected side is also impaired in patients with stroke. This study aimed to clarify the neurophysiological characteristics of pedal switching control during emergency braking in patients with hemiplegia. METHODS: The study participants consisted of 10 drivers with left hemiplegia and 10 age-matched healthy drivers. An experimental pedal was used to measure muscle activity and kinematic data during braking, triggered by the light from a light-emitting diode placed in front of the drivers. RESULTS: The patient group took the same reaction time as the healthy group. However, from the visual stimulus to the release of the accelerator pedal, the patient group had higher muscle activity in the tibialis anterior and rectus femoris and had faster angular velocities of hip and knee flexion than the healthy group. In addition, the patient group had higher co-contraction activities between flexors and extensors. From the accelerator pedal release to brake contact, the patient group had slower angular velocities of hip adduction, internal rotation, ankle dorsiflexion, internal return, and internal rotation than the healthy group. CONCLUSIONS: Patients with hemiplegia exhibited poor control of pedal switching using their unaffected side throughout the pedal-switching task. These results indicate that the safety related to car-pedal control should be carefully evaluated while deciding whether a patient can resume driving a car after a stroke.


Assuntos
Condução de Veículo , Acidente Vascular Cerebral , Humanos , Hemiplegia/etiologia , Automóveis , Acidentes de Trânsito , Músculo Esquelético , Extremidade Inferior , Acidente Vascular Cerebral/complicações
11.
Cureus ; 16(1): e53130, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38420055

RESUMO

Myotonic dystrophy type 1 (DM1) is one of the monogenic neurological diseases that neurologists most often experience. DM1 can develop several symptoms, including muscle weakness, gait disturbance, urinary incontinence, and cognitive decline. Other hand, normal pressure hydrocephalus (NPH) is more frequent in the elderly population and is characterized by a triad of symptoms, gait disturbance, urinary urge incontinence, and cognitive decline. Therefore, some symptoms overlap between DM1 and NPH. In this report, we described a case of DM1 that presented with a triad of NPH, and NPH-like changes in brain images. A 54-year-old man with DM1 visited our hospital for rehabilitation. He had a history of dyslipidemia, diabetes, and cataracts. He developed muscle weakness, blepharoptosis, and dysarthria at 43 years. Neuro-exam revealed percussion and grip myotonia, distal muscle weakness and atrophy, broad-based gait, and urinary incontinence. The mini-mental state examination score was 18. Brain magnetic resonance imaging revealed enlarged lateral and third ventricles and Evans index was 0.38 (NPH criterion; >0.3), which was mimicking for NPH. Tap test (TT) was evaluated twice. First TT improved clinical symptoms slightly, but second was unremarkable. Based on the second TT result, we could not diagnose with NPH and could prevent unnecessary surgical shunting. Brain imaging of DM1 can show an NPH-like appearance in patients older than 50. Although TT is the gold standard for diagnosing NPH, its sensitivity and specificity vary among reports. TT results should be interpreted with caution before performing a surgical shunt. If necessary, multiple TTs should be considered in DM1 patients.

12.
Cureus ; 16(2): e54492, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38516483

RESUMO

Lateral medullary infarction (LMI), or Wallenberg syndrome, can develop various symptoms, but it is rare that ipsilateral axial lateropulsion (or body lateropulsion, BL) or atonic bladder (AB) are caused by LMI. This report describes a case of LMI with both BL and AB. A 77-year-old man, with a history of hypertension and diabetes, developed acute left BL and anuresis. A neurological exam showed right gaze nystagmus, slight dysarthria and dysphagia, right dysesthesia in the trunk, and ataxia in the left limbs and trunk. Horner's syndrome and paralysis were unremarkable. Brain magnetic resonance imaging revealed hyperintensity in the lateral medulla oblongata. Cystometry revealed AB, although the patient had the urge to urinate. Owing to acute therapy, although trunk ataxia was presented for several months, BL and anuresis were recovered on day 15 and day 35, respectively. Here, we describe the potential mechanisms of BL and AB caused by LMI.

13.
Cureus ; 16(2): e54988, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38550435

RESUMO

Behçet's disease (BD) is a multisystemic vasculitis disorder. Neuro-Behçet's disease (NBD) is a set of neurologic symptoms imputable to an underlying Behçet vasculitis. Among the wide range of vascular abnormalities secondary to BD, a dural arteriovenous fistula (dAVF) is not classically described. Whether a dAVF is associated with BD or dAVF is a chance occurrence is still a matter of debate. Herein, we describe an NBD case of a 48-year-old male, presenting with headache and fever, where a dAVF was seen on imaging. He was treated with prednisolone and colchicine, followed by the surgical resection for dAVF. Then, we discuss the possible association between BD and dAVF based on the latest literature.

14.
Cureus ; 16(3): e56232, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618350

RESUMO

Apraxia of eyelid opening (AEO) is occasionally seen in Parkinson's disease (PD) or related diseases. However, many clinicians have trouble with the management of AEO by Parkinsonism. In this report, we describe a case of AEO in Parkinsonism improved by trihexyphenidyl (THP). The patient was a 64-year-old woman, who was previously healthy but developed bradykinesia. She was clinically diagnosed as PD due to an L-dopa challenge test, but no other detailed tests were performed. She started antiparkinsonian medications and her symptoms were improved at an early phase. However, her motor symptoms were gradually exacerbated over time, and antiparkinsonian medications were dosed up. At 69 years old, blepharospasm and AEO developed. Although other antiparkinsonian medications did not improve her AEO, THP cured AEO dramatically at 73 years old. In this report, we discuss a mechanism of AEO by Parkinsonism and the pathway of THP for the improvement of AEO.

15.
Cureus ; 16(3): e56064, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618457

RESUMO

Miller-Fisher syndrome (MFS), characterized by ophthalmoplegia, ataxia, and areflexia, is a Guillain-Barré syndrome (GBS) variant. It is well-known that the causative antibody for MFS is anti-GQ1b antibody. This report describes a rare case of MFS with not only anti-GQ1b antibodies but also anti-GT1a antibodies following Influenza A infection. The patient, a 47-year-old woman, contracted Influenza A three weeks before admission. She complained of double vision followed by areflexia, ataxia in the four extremities, and complete gaze palsy. She was treated with intravenous methylprednisolone pulse and intravenous immunoglobulin therapies. Her neurological symptoms were recovered after these immunotherapies.

16.
Cureus ; 16(4): e57892, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38725779

RESUMO

The double skull sign (DSS) is a unique image on the outside of the brain that looks like two skulls. Whereas congenital and acquired types of DSS have been reported, the etiology of both of them is calcified hematomas. We encountered a case of a 46-year-old woman with a history of subarachnoid hemorrhage followed by cranioplasty at 43 years old. She developed right hemiparalysis and motor aphasia suddenly. Brain computed tomography and magnetic resonance imaging revealed not only cerebral infarction but also DSS incidentally. After detailed analysis, we concluded that the DSS in this case was not due to calcification of the hematoma but was related to the cranioplasty. In this report, we present an interesting case and discuss etiologies of the development of DSS after cranioplasty.

17.
Pharmacol Res Perspect ; 12(3): e1203, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38682818

RESUMO

Interference in cell cycle progression has been noted as one of the important properties of anticancer drugs. In this study, we developed the cell cycle prediction model using high-content imaging data of recipient cells after drug exposure and DNA-staining with a low-toxic DNA dye, SiR-DNA. For this purpose, we exploited HeLa and MCF7 cells introduced with a fluorescent ubiquitination-based cell cycle indicator (Fucci). Fucci-expressing cancer cells were subjected to high-content imaging analysis using OperettaCLS after 36-h exposure to anticancer drugs; the nuclei were segmented, and the morphological and intensity properties of each nucleus characterized by SiR-DNA staining were calculated using imaging analysis software, Harmony. For the use of training, we classified cells into each phase of the cell cycle using the Fucci system. Training data (n = 7500) and validation data (n = 2500) were randomly sampled and the binary classification prediction models for G1, early S, and S/G2/M phases of the cell cycle were developed using four supervised machine learning algorithms. We selected random forest as the model with the best performance through 10-fold cross-validation; the accuracy rate was approximately 75%-87%. Regarding feature importance, variables expected to be biologically related to the cell cycle, for example, signal intensity and nuclear size, were highly ranked, suggesting the validity of the model. These results showed that the cell cycle can be predicted in cancer cells by simply exploiting the current prediction model using fluorescent images of DNA-staining dye, and the model could be applied for the use of future ex vivo drug sensitivity diagnosis.


Assuntos
Antineoplásicos , Ciclo Celular , Corantes Fluorescentes , Humanos , Ciclo Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Células HeLa , Células MCF-7 , DNA , Aprendizado de Máquina , Coloração e Rotulagem/métodos , Núcleo Celular
18.
Nat Commun ; 15(1): 4351, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806498

RESUMO

Low-cost detection systems are needed for the identification of microplastics (MPs) in environmental samples. However, their rapid identification is hindered by the need for complex isolation and pre-treatment methods. This study describes a comprehensive sensing platform to identify MPs in environmental samples without requiring independent separation or pre-treatment protocols. It leverages the physicochemical properties of macroporous-mesoporous silver (Ag) substrates templated with self-assembled polymeric micelles to concurrently separate and analyze multiple MP targets using surface-enhanced Raman spectroscopy (SERS). The hydrophobic layer on Ag aids in stabilizing the nanostructures in the environment and mitigates biofouling. To monitor complex samples with multiple MPs and to demultiplex numerous overlapping patterns, we develop a neural network (NN) algorithm called SpecATNet that employs a self-attention mechanism to resolve the complex dependencies and patterns in SERS data to identify six common types of MPs: polystyrene, polyethylene, polymethylmethacrylate, polytetrafluoroethylene, nylon, and polyethylene terephthalate. SpecATNet uses multi-label classification to analyze multi-component mixtures even in the presence of various interference agents. The combination of macroporous-mesoporous Ag substrates and self-attention-based NN technology holds potential to enable field monitoring of MPs by generating rich datasets that machines can interpret and analyze.

19.
Cureus ; 16(3): e55590, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38576684

RESUMO

Melodic intonation therapy (MIT) is one of the rehabilitation methods for patients with non-fluent or dysfluent aphasia, mainly caused by stroke or brain injury. Although MIT is conducted in various languages, reports on the Japanese version of MIT (MIT-J) are limited. In this report, we describe a case about the efficacy of MIT-J in the subacute phase after stroke on subcortical aphasia. Our case was a 60-year-old right-handed woman who suffered from left putaminal hemorrhage. She was treated with acute therapy, including medications and rehabilitation, but non-fluent aphasia was preserved. Regardless of general speech therapies, her aphasia was not improved. In the subacute phase, we started MIT-J (protocol: 20 minutes per day, five days per week for two weeks). The effect of MIT-J was remarkable and in particular, speech intelligibility was improved. It is required to accumulate more cases to reveal the effect of MIT-J.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36673846

RESUMO

PURPOSE: To prevent frailty, it is necessary to focus on pre-frailty and consider preventive interventions that incorporate social aspects. This study aimed to explore socio-demographic associations with pre-frailty, focusing on modifiable social factors among community-dwelling older adults in a rural Japanese city. METHODS: We conducted a self-administered survey on social, physical, and mental factors, and basic attributes, in September 2021. Respondents were classified as frail, pre-frail, or healthy according to their The Kihon Checklist scores. Of the 494 valid responses, 93 respondents classified as pre-frail and 110 as healthy were analyzed. The socio-demographic associations with pre-frailty were investigated by multiple logistic regression, and interactions between gender and other factors were examined. RESULTS: The analysis identified that for both genders, no-community participation in middle age (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.16-2.92) was found to be a social factor associated with pre-frailty. Having friends who listen to one's concerns (OR, 2.54; 95% CI, 1.26-5.10) was a factor for women. CONCLUSIONS: This study showed that modifiable social factors associated with pre-frailty were community involvement and being able to share concerns with friends. The findings suggest the need for support that emphasizes social aspects to prevent pre-frailty.


Assuntos
Fragilidade , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , População do Leste Asiático , Idoso Fragilizado , Fragilidade/epidemiologia , Avaliação Geriátrica , Vida Independente , Fatores Sexuais , Japão
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