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1.
Asian J Endosc Surg ; 17(4): e13387, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39340128

RESUMO

Extraperitoneal colostomy is often selected to reduce the risk of parastomal hernia. However, its closure surgery is rare and seldom reported. Here, we report our unique experience with robotic left hemicolectomy and extraperitoneal colostomy closure. An 83-year-old female was diagnosed with descending colon cancer with stenosis. She had previously undergone abdominoperineal resection with extraperitoneal colostomy. After improving the intestinal obstruction with a self-expanding stent, we performed robotic left hemicolectomy and extraperitoneal colostomy closure. Thanks to the multijoint function of the robot, which enables the forceps to be angled up to 90° in all directions, we could dissect the stoma from the abdominal wall up to just beneath the rectus abdominis in an intra-abdominal procedure without enlarging the skin incision. This case suggests that robotic surgery with the articulating function is beneficial for procedures near the abdominal wall ceiling and effective for extraperitoneal colostomy closure.


Assuntos
Colectomia , Neoplasias do Colo , Colostomia , Procedimentos Cirúrgicos Robóticos , Humanos , Feminino , Idoso de 80 Anos ou mais , Colectomia/métodos , Neoplasias do Colo/cirurgia , Colostomia/métodos , Colo Descendente/cirurgia , Protectomia/métodos , Estomas Cirúrgicos/efeitos adversos
2.
Artigo em Inglês | MEDLINE | ID: mdl-39196683

RESUMO

Mutations in proline-rich transmembrane protein 2 (PRRT2) cause paroxysmal kinesigenic dyskinesia (PKD). Recently, we reported that a Prrt2 mutation exacerbated L-dopa-induced motor deficits in mice, suggesting that the basal ganglia might contribute to PKD pathology. Here, we demonstrated that the Prrt2 mutation enhanced depolarization stimuli-induced extracellular dopamine levels in the mouse striatum, which were attenuated by repeated stimulation. L-dopa administration maintained high dopamine levels in Prrt2-KI mice even during repetitive stimuli but did not affect dopamine levels in wild-type mice. Thus, the enhanced and prolonged responsiveness of dopamine release in nigrostriatal dopaminergic neurons to sequential excitation may be partially implicated in Prrt2-related dyskinesia.

3.
Surg Case Rep ; 10(1): 164, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951358

RESUMO

BACKGROUND: In laparoscopic colorectal surgery, accurate localization of a tumor is essential for ensuring an adequate ablative margin. Therefore, a new method, near-infrared laparoscopy combined with intraoperative colonoscopy, was developed for visualizing the contour of a cecal tumor from outside of the bowel. The method was used after it was verified on a model that employed a silicone tube. CASE PRESENTATION: The patient was a 77-year-old man with a cecal tumor near the appendiceal orifice. Laparoscopy was used to clamp of the terminal ileum, and a colonoscope was then inserted through the anus to the cecum. The laparoscope in the normal light mode could not be used to identify the cecal tumor. However, a laparoscope in the near-infrared ray mode could clearly visualize the contour of the cecal tumor from outside of the bowel, and the tumor could be safely resected by a stapler. The histopathological diagnosis of the resected specimen was adenocarcinoma with an invasion depth of M and a clear negative margin. CONCLUSIONS: This is the first report of the laparoscopic detection of the contour of a cecal tumor from outside the bowel. This technique is useful and safe for contouring tumors in laparoscopic colorectal surgery and can be used in various surgeries that combine endoscopy and laparoscopy.

4.
Glob Health Med ; 6(2): 149-155, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38690132

RESUMO

Postpartum women live with a low quality of life due to pain caused by episiotomy and perineal laceration. In particular, they endure pain when sitting for long periods of time to breastfeed. The purpose of this study is to develop a sitting aid to alleviate postpartum vulvodynia. This study was conducted in the following four phases from July 2017 to May 2019. They are: material selection and molding, cleaning and disinfection testing, pressure distribution measurement testing, and trial testing by postpartum women. The main material was a 100% polypropylene object with a three-dimensional reticular fiber spring structure and fiber density of 3.8 kg/m2. As a result, a sitting aid that withstands washing and disinfection well in the medical field and is breathable. It had moderate resilience and elasticity and reduced pressure on the seating surface for women weighing approximately 45 kg and 55 kg, but we were skeptical about its use for women weighing more than that. The completed sitting aid is noninvasively effective in improving the quality of life of many postpartum women, but the density and thickness of the main material should be reexamined to meet the needs of women in a wider weight range. In addition, a self-administered questionnaire survey of trial users revealed that some women did not experience relief from vulvodynia even after using the sitting aid. Such women also had physical problems such as discomfort in the lower back, difficulty breastfeeding, and difficulty standing up. For women with multiple physical problems, individual causes should be addressed.

5.
Surg Case Rep ; 10(1): 105, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691233

RESUMO

BACKGROUND: The standard treatment for colorectal cancer consists of surgery and chemotherapy, which can be combined to improve outcomes. Immune checkpoint inhibitors (ICI) are a significant advancement in the standard treatment of metastatic, unresectable colorectal cancer with deficient mismatch repair (dMMR). However, limited data are available about the use of ICI in the neoadjuvant and conversion settings. Here, we present two cases treated with ICI. CASE PRESENTATION: Case 1: A 75-year-old male with a large, borderline resectable rectal cancer diagnosed as cT4bN1bM0 who underwent neoadjuvant chemotherapy, followed by combination ICI consisting of ipilimumab and nivolumab. After four courses of ICI, the tumor significantly shrank, but positron emission tomography still showed a positive result and R0 resection was performed. Pathological analysis revealed no residual cancer cells. The patient has been monitored without adjuvant chemotherapy, and no recurrences have occurred after one year. Case 2: A 60-year-old male with locally advanced sigmoid colon cancer who received neoadjuvant treatment with pembrolizumab. The tumor partially shrank after three courses, and continued pembrolizumab monotherapy resulted in further tumor shrinkage which still showed positive positron emission tomography. Curative sigmoidectomy with partial resection of the ileum and bladder was performed, and the pathological outcome was pCR. There was no viable tumor in the specimen. The patient has been monitored without adjuvant chemotherapy for six months, and no recurrence has been observed. CONCLUSIONS: The present study reports two cases, including a large, borderline resectable rectal cancer after failure of chemotherapy followed by combination treatment with nivolumab and ipilimumab and one case of sigmoid colon cancer after pembrolizumab treatment, which resulted in pathological complete response. However, it remains unknown whether ICI therapy can replace surgery or diminish the optimal extent of resection, or whether adjuvant chemotherapy is needed after surgery in the case of achieving pCR after ICI therapy. Overall, this case report suggests that ICI before colorectal surgery can be effective and potentially a 'watch-and-wait" strategy could be used for cases in which ICI is effective.

6.
J Anus Rectum Colon ; 8(1): 43-47, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313748

RESUMO

Although robotic rectal resections are now widely performed, there are few robotic suction tools that can be easily used by console surgeons. It can therefore be difficult to maintain a clear visual field in the pelvis when there is effusion and bleeding from either a highly advanced cancer or from preoperative cancer treatment. In this report, we introduce our unique surgical technique that uses a soft catheter with a small gauze ball attached, inserted through the assistant port. This simple and inexpensive "instrument" can be used by the console surgeon as a retractor as well as a reliable suction device to secure their view of the operative field in the pelvis. This technique can be used in a narrow surgical field and does not rely on an assistant surgeon, making it potentially applicable to all types of surgery.

7.
JMA J ; 7(1): 30-39, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38314423

RESUMO

Introduction: Cervical cancer is the fourth most common cancer among women worldwide. Most cervical cancers are caused by persistent infection with human papillomavirus (HPV) acquired through sexual contact. Decision-making is the process of choosing among several options, and a better decision is one that the people engaged in the decision-making process express satisfaction with. Despite that HPV infection is associated with sexual behavior, no studies in Japan on HPV vaccination decision-making that include perspectives on sexuality exist. This study aimed to determine the factors that influence satisfaction with decision-making concerning HPV vaccination among female university students in Japan. Methods: The cross-sectional study was carried out by an anonymous self-administered questionnaire mail survey of 1988 female university students in Japan between April and July 2021. Of them, 301 agreed to participate in the survey. After the exclusion of those with missing data, the analysis included 252 (12.7%) students. We summarized descriptive statistics in terms of characteristics, satisfaction with decision-making regarding HPV vaccination, HPV vaccination behavior, knowledge, attitude about HPV vaccination, influencing factors, and perceptions and behaviors related to sexuality. Furthermore, we conducted multivariate analyses to investigate factors that influence satisfaction with decision-making regarding HPV vaccination. Results: Of the 252 participants, 102 (40.5%) were satisfied with their decisions regarding HPV vaccination. After adjustment for confounding factors, the multivariable-adjusted odds ratios (95% confidence intervals) for factors associated with satisfaction in decision-making regarding HPV vaccination were as follows: being vaccinated (vs. non-vaccinated) 5.46 (2.51-11.89), having high knowledge scores (vs. per 1 point) 1.09 (1.01-1.17), and having awareness about the risk of contracting sexually transmitted infections (STIs) via sexual intercourse (vs. per 1 point) 0.83 (0.72-0.96). Conclusions: Being vaccinated, having higher knowledge scores, and having lower awareness regarding the risk of STIs were associated with satisfied decision-making concerning HPV vaccination. Providing younger people with correct information about cervical cancer, HPV vaccines, and STI prevention contributes to increased satisfaction with their HPV vaccination decisions.

8.
Biol Pharm Bull ; 47(2): 509-517, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38403661

RESUMO

(-)-Epigallocatechin-3-gallate (EGCg), a major constituent of green tea extract, is well-known to exhibit many beneficial actions for human health by interacting with numerous proteins. In this study we identified synaptic vesicle membrane protein VAT-1 homolog (VAT1) as a novel EGCg-binding protein in human neuroglioma cell extracts using a magnetic pull-down assay and LC-tandem mass spectrometry. We prepared recombinant human VAT1 and analyzed its direct binding to EGCg and its alkylated derivatives using surface plasmon resonance. For EGCg and the derivative NUP-15, we measured an association constant of 0.02-0.85 ×103 M-1s-1 and a dissociation constant of nearly 8 × 10-4 s-1. The affinity Km(affinity) of their binding to VAT1 was in the 10-20 µM range and comparable with that of other EGCg-binding proteins reported previously. Based on the common structure of the compounds, VAT1 appeared to recognize a catechol or pyrogallol moiety around the B-, C- and G-rings of EGCg. Next, we examined whether VAT1 mediates the effects of EGCg and NUP-15 on expression of neprilysin (NEP). Treatments of mock cells with these compounds upregulated NEP, as observed previously, whereas no effect was observed in the VAT1-overexpressing cells, indicating that VAT1 prevented the effects of EGCg or NUP-15 by binding to and inactivating them in the cells overexpressing VAT1. Further investigation is required to determine the biological significance of the VAT1-EGCg interaction.


Assuntos
Catequina , Proteínas de Transporte Vesicular , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Vesículas Sinápticas/metabolismo , Chá/química , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
9.
Gan To Kagaku Ryoho ; 51(1): 90-92, 2024 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-38247102

RESUMO

The patient was a 68-year-old woman who was on hemodialysis due to systemic amyloidosis and nephrotic syndrome. Biopsy revealed amyloid deposition in the stomach, duodenum, and colon. A transverse colon tumor was found on a follow- up CT after the aortic dissection surgery. We performed lower gastrointestinal endoscopy and contrast-enhanced CT and diagnosed transverse colon cancer with gastric wall infiltration(cStage Ⅲc). We considered that transverse colon resection was oncologically sufficient. However, due to concurrent gastrointestinal amyloidosis, which increased the risk of anastomotic leakage we performed laparoscopic extended right hemicolectomy to avoid colon-colon anastomosis with partial gastrectomy. Additionally intraoperative indocyanine green(ICG)fluorescence imaging showed that the fluorescence signal in the small intestinal wall was satisfactory, while it was weak in the colon wall. As a result, we suspected of impaired blood flow of colon wall due to an amyloidosis, so we additionally created a loop ileostomy. It is said that gastrointestinal amyloidosis raises the risk of anastomotic leakage. A case of transverse colon cancer complicated by gastrointestinal amyloidosis in which we successfully prevented anastomotic leakage through a multidimensional evaluation and approach is reported, along with a literature review.


Assuntos
Amiloidose , Colo Transverso , Neoplasias do Colo , Gastroenteropatias , Feminino , Humanos , Idoso , Fístula Anastomótica , Colo Transverso/cirurgia , Amiloidose/complicações , Amiloidose/cirurgia , Neoplasias do Colo/complicações , Neoplasias do Colo/cirurgia
10.
Surg Today ; 54(3): 282-287, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37777607

RESUMO

It has been pointed out that robotic surgery is more time-consuming than laparoscopic surgery, and a major challenge for the future is educating young surgeons while maintaining the surgical quality. To solve these problems, we report a role-sharing surgery (RSS) approach in which the surgery is divided into several areas and timetabled, with roles shared by several operators. We performed RSS for 19 standard colorectal cancer surgeries. The surgery was completed within + 28 min of the scheduled operation time, and a beginner robotic surgeon (BRS) was able to perform approximately 66% of the total surgery. There were no statistically significant differences in the short-term outcomes between the RSS and conventional surgery groups. Based on these findings, RSS has the potential to be the best practice for educating BRSs in robotic surgery, the use of which is expected to increase steadily in the future.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Cirurgiões , Humanos , Procedimentos Cirúrgicos Robóticos/educação , Cirurgiões/educação , Laparoscopia/educação
11.
J Obstet Gynaecol Res ; 50(3): 313-321, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38037733

RESUMO

AIM: Prediction of labor progression is important for maternal and fetal health, as improved accuracy can lead to more timely intervention and improved outcomes. This review aims to outline the importance of predicting the progression of spontaneous parturition, detail the various methods employed to enhance this prediction and provide recommendations for future research. METHODS: We searched articles relating to labor progression and systematic review articles on Artificial Inteligence (AI) in childbirth management using PubMed. To supplement, Google Scholar was used to find recent guidelines and related documents. RESULTS: Traditional methods like vaginal examinations, criticized for subjectivity and inaccuracy, are gradually being replaced by ultrasound, considered a more objective and accurate approach. Further advancements have been observed with machine learning and artificial intelligence techniques, which promise to surpass the accuracies of conventional methods. The Friedman curve, developed in 1954, is the standard for assessing labor progress, but its application to Asian women, in particular, remains controversial, and various studies have reported that the actual rate of labor was slower than that indicated by the Friedman curve. CONCLUSION: There is a need to innovate methodologies for predicting delivery tailored to modern pregnant women, especially when they have different genetic and cultural backgrounds than their Western counterparts, such as Asians. Future research should develop predictive models of labor progression that aim to enhance medical intervention and improve the safety and well-being of both mother and child.


Assuntos
Trabalho de Parto , Gestantes , Criança , Gravidez , Feminino , Humanos , Inteligência Artificial , Ultrassonografia , Feto
12.
Intern Med ; 63(1): 101-106, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37225490

RESUMO

A man who was an inactive hepatitis B virus (HBV) carrier with positive hepatitis B surface antigen (HBs antigen) and undetectable HBV-DNA under anti-viral treatment developed nephrotic syndrome at 52 years old, and a renal biopsy revealed advanced membranous nephropathy (MN) with focal cellular crescents, interstitial hemorrhaging, and peritubular capillaritis. Immunofluorescence studies demonstrated granular IgG deposition and HBs antigen-positivity along the capillaries. Glomeruli were negative for phospholipase A2 receptor 1. There were no clinical findings of systemic vasculitis. We considered MN combined with small-vessel vasculitis due to HBV infection. These results suggest that HBV-related kidney disease should be considered even in patients with an inactive HBV carrier status under treatment.


Assuntos
Glomerulonefrite Membranosa , Hepatite B , Masculino , Humanos , Pessoa de Meia-Idade , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/tratamento farmacológico , Vírus da Hepatite B/genética , Antígenos de Superfície da Hepatite B , Hepatite B/complicações , Hepatite B/tratamento farmacológico , DNA , Antivirais/uso terapêutico
13.
J Biochem ; 174(6): 561-570, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37793168

RESUMO

Mutations of proline-rich transmembrane protein 2 (PRRT2) lead to dyskinetic disorders such as paroxysmal kinesigenic dyskinesia (PKD), which is characterized by attacks of involuntary movements precipitated by suddenly initiated motion, and some convulsive disorders. Although previous studies have shown that PKD might be caused by cerebellar dysfunction, PRRT2 has not been sufficiently analyzed in some motor-related regions, including the basal ganglia, where dopaminergic neurons are most abundant in the brain. Here, we generated several types of Prrt2 knock-in (KI) mice harboring mutations, such as c.672dupG, that mimics the human pathological mutation c.649dupC and investigated the contribution of Prrt2 to dopaminergic regulation. Regardless of differences in the frameshift sites, all truncating mutations abolished Prrt2 expression within the striatum and cerebral cortex, consistent with previous reports of similar Prrt2 mutant rodents, confirming the loss-of-function nature of these mutations. Importantly, administration of l-dopa, a precursor of dopamine, exacerbated rotarod performance, especially in Prrt2-KI mice. These findings suggest that dopaminergic dysfunction in the brain by the PRRT2 mutation might be implicated in a part of motor symptoms of PKD and related disorders.


Assuntos
Dopamina , Distonia , Animais , Humanos , Camundongos , Distonia/genética , Proteínas de Membrana/genética , Mutação
14.
Surg Case Rep ; 9(1): 64, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37095273

RESUMO

BACKGROUND: Spontaneous regression (SR) of cancer occurs in 1 in 60,000-100,000 patients. This phenomenon has been reported in almost all cancer types, most commonly neuroblastoma, renal cell carcinoma, malignant melanoma, and lymphoma/leukemia. However, SR in colorectal cancer (CRC) is extremely rare, particularly in advanced cases. Hence, this report describes a very rare case of spontaneous regression of advanced transverse colon cancer. CASE PRESENTATION: A 76-year-old female with anemia was diagnosed with a type II well-differentiated adenocarcinoma in the middle transverse colon. Two months later, a second colonoscopy examination was performed for preoperative marking, and it revealed tumor shrinkage and a shift to type 0-IIc morphology. Endoscopic tattooing was then performed, followed by a laparoscopic partial resection of the transverse colon with D3 lymph node dissection. However, the resected specimen contained no tumor, and colonoscopy showed no tumor remnants in the remaining colon. Histopathological examination revealed mucosal regeneration and a mucus nodule in between the submucosal and muscular layers, with no cancer cells detected. Immunohistochemical analysis revealed the loss of MutL homolog 1 (MLH1) and postmeiotic segregation increased 2 (PMS2) expression in the cancer cells of biopsied specimens, suggesting deficient mismatch repair (dMMR). The patient continues to be followed up until 6 years postoperatively, and no recurrence has been observed. In this study, we also reviewed similar reported cases of spontaneous regression of cancer involving dMMR. CONCLUSION: This study presents a rare case of spontaneous regression of advanced transverse colon cancer wherein dMMR is strongly involved. However, further accumulation of similar cases is needed to elucidate this phenomenon and to develop new treatment strategies for CRC.

15.
Biol Pharm Bull ; 46(3): 446-454, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36858574

RESUMO

The onset of Alzheimer's disease (AD) is characterized by accumulation of amyloid ß peptide (Aß) in the brain. Neprilysin (NEP) is one of the major Aß-degrading enzymes. Given findings that NEP expression in the brain declines from the early stage of AD before apparent neuronal losses are observed, enhancement of NEP activity and expression may be a preventive and therapeutic strategy relevant to disease onset. We screened for compounds that could enhance the activity and expression of NEP using a polyphenol library previously constructed by our research group and investigated the structure-activity relationships of the identified polyphenols. We found that amentoflavone, apigenin, kaempferol, and chrysin enhanced the activity and expression of NEP, suggesting that chemical structures involving a double bond between positions 2 and 3 in the C ring of flavones are important for NEP enhancement, while catechol or pyrogallol structures, except for the galloyl group of catechins, abolished these effects. Moreover, natural compounds, such as quercetin, were not effective per se, but were changed to effective compounds by adding a lipophilic moiety. Using our study findings, we propose improvements for dietary habits with experimental evidence, and provide a basis for the development of novel small molecules as disease-modifying drugs for AD.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Neprilisina , Apigenina , Encéfalo
16.
Oncol Rep ; 49(3)2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36734271

RESUMO

Ataxia telangiectasia and Rad3­related (ATR) is a kinase that repairs DNA damage. Although inhibitors that selectively target ATR have been developed, their effectiveness in colorectal cancer has not been widely reported. The present study hypothesized that anticancer agents that effectively act in the S phase before the G2/M checkpoint may be ideal agents for concomitant use with ATR inhibitors, which act at the G2/M checkpoint. Therefore, the present study examined the combined effects of AZD6738, an ATR inhibitor, and trifluridine (FTD), which acts in the S phase and has a high DNA uptake rate. In vitro cell viability assays, flow cytometry and western blotting were performed to evaluate cell viability, and changes in cell cycle localization and protein expression. The results revealed that in colorectal cancer cells, the combination of AZD6738 and FTD inhibited cell viability, cell cycle arrest at the G2/M checkpoint and Chk1 phosphorylation, and increased apoptotic protein expression levels more than that when treated with FTD alone. HT29, a BRAF­mutant cell line known to be resistant to anticancer drugs, was used to induce tumors in vivo. Since FTD does not have sufficient efficacy when administered orally, it was mixed with tipiracil to prevent degradation; this mixture is known as TAS­102. TAS­102 alone exerted minimal tumor suppressive effects; however, when used in combination with AZD6738, tumor suppression was observed, suggesting that AZD6738 may increase the effectiveness of a weakly effective drug. Although ATR inhibitors are effective against p53 mutants, the present study demonstrated that these inhibitors were also effective against the p53 wild­type HCT116 colorectal cancer cell line. In conclusion, combination therapy with AZD6738 and FTD enhanced the inhibition of tumor proliferation in vitro and in vivo. In the future, we aim to investigate the potentiating effect of AZD6738 on 5­fluouracil­resistant cell lines that are difficult to treat.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Demência Frontotemporal , Humanos , Linhagem Celular Tumoral , Trifluridina/farmacologia , Trifluridina/uso terapêutico , Proteína Supressora de Tumor p53/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Quinase 1 do Ponto de Checagem/metabolismo
17.
Genes Cells ; 28(4): 319-325, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36719634

RESUMO

We investigated the alterations in autophagy-related molecules in neurons differentiated from induced pluripotent stem cells obtained from patients with Alzheimer's disease (AD). Consistent with our previous microarray data, ATG4A protein was upregulated in the neurons derived from a familial AD patient with an APP-E693Δ mutation who showed accumulation of intracellular amyloid ß peptide (Aß). This upregulation was reversed by inhibiting Aß production, suggesting that the intracellular Aß may be responsible for the upregulation of ATG4A. The LC3B-II/LC3B-I ratio, an index of autophagosome formation, was lower in the neurons derived from the AD patient with APP-E693Δ as well as the neurons derived from other familial and sporadic AD patients. These findings indicate that dysregulation of autophagy-related molecules may accelerate the pathogenesis of AD.


Assuntos
Doença de Alzheimer , Células-Tronco Pluripotentes Induzidas , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Mutação , Neurônios/metabolismo
18.
Elife ; 122023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36647607

RESUMO

Nutrition in early life has profound effects on an organism, altering processes such as organogenesis. However, little is known about how specific nutrients affect neuronal development. Dendrites of class IV dendritic arborization neurons in Drosophila larvae become more complex when the larvae are reared on a low-yeast diet compared to a high-yeast diet. Our systematic search for key nutrients revealed that the neurons increase their dendritic terminal densities in response to a combined deficiency in vitamins, metal ions, and cholesterol. The deficiency of these nutrients upregulates Wingless in a closely located tissue, body wall muscle. Muscle-derived Wingless activates Akt in the neurons through the receptor tyrosine kinase Ror, which promotes the dendrite branching. In larval muscles, the expression of wingless is regulated not only in this key nutrient-dependent manner, but also by the JAK/STAT signaling pathway. Additionally, the low-yeast diet blunts neuronal light responsiveness and light avoidance behavior, which may help larvae optimize their survival strategies under low-nutritional conditions. Together, our studies illustrate how the availability of specific nutrients affects neuronal development through inter-organ signaling.


Assuntos
Dendritos , Proteínas de Drosophila , Animais , Dendritos/fisiologia , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Neurônios/fisiologia , Nutrientes , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
19.
Front Microbiol ; 13: 728831, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386684

RESUMO

In Japan, major mumps outbreaks still occur every 4-5 years because of low mumps vaccine coverage (30-40%) owing to the voluntary immunization program. Herein, to prepare for a regular immunization program, we aimed to reveal the nationwide and long-term molecular epidemiological trends of the mumps virus (MuV) in Japan. Additionally, we performed whole-genome sequencing (WGS) using next-generation sequencing to assess results from conventional genotyping using MuV sequences of the small-hydrophobic (SH) gene. We analyzed 1,064 SH gene sequences from mumps clinical samples and MuV isolates collected from 25 prefectures from 1986 to 2017. The results showed that six genotypes, namely B (110), F (1), G (900), H (3), J (41), and L (9) were identified, and the dominant genotypes changed every decade in Japan since the 1980s. Genotype G has been exclusively circulating since the early 2000s. Seven clades were identified for genotype G using SH sequence-based classification. To verify the results, we performed WGS on 77 representative isolates of genotype G using NGS and phylogenetically analyzed them. Five clades were identified with high bootstrap values and designated as Japanese clade (JPC)-1, -2, -3, -4, -5. JPC-1 and -3 accounted for over 80% of the total genotype G isolates (68.3 and 13.8%, respectively). Of these, JPC-2 and -5, were newly identified clades in Japan through this study. This is the first report describing the nationwide and long-term molecular epidemiology of MuV in Japan. The results provide information about Japanese domestic genotypes, which is essential for evaluating the mumps elimination progress in Japan after the forthcoming introduction of the mumps vaccine into Japan's regular immunization program. Furthermore, the study shows that WGS analysis using NGS is more accurate than results obtained from conventional SH sequence-based classification and is a powerful tool for accurate molecular epidemiology studies.

20.
PLoS One ; 17(11): e0277174, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36355760

RESUMO

The COVID-19 pandemic has been affecting the mental health of hospital workers. During the prolonged pandemic, hospital workers may experience much more severe psychological distress, leading to an increased risk of suicide. This study aimed to investigate changes in psychological effects on hospital workers over 12 months from the beginning of the pandemic and clarify factors associated with psychological distress and suicide-related ideation 1-year after the pandemic's beginning. These repeated, cross-sectional surveys collected demographic, mental health, and stress-related data from workers in 2 hospitals in Yokohama, Japan. The first survey, conducted in March-April 2020, contained the 12-item General Health Questionnaire (GHQ-12) assessing general distress and the Impact of Event Scale-Revised (IES-R) assessing event-related distress. In the second survey in March 2021, hospital workers at the same two hospitals were reassessed using the same questionnaire, and Item 9 of the Patient Health Questionnaire (PHQ-9) was added to assess their suicide-related ideation. The findings of the first and second surveys revealed that the average score of GHQ-12 (3.08 and 3.73, respectively), the IES-R total score (6.8 and 12.12, respectively), and the prevalence rates of severe general distress (35.0% and 44.0%, respectively) and severe event-related distress (7.0% and 17.1%, respectively) deteriorated. The second survey showed that 8.6% of the hospital workers were experiencing suicide-related ideation. Both the general and event-related distress were associated with suicide-related ideation. In these surveys, mental health outcomes among the hospital workers deteriorated over one year from the pandemic's beginning, and their severe psychological distress was the risk factor for the suicide-related ideation. Further studies are needed to compare the psychological effects on hospital workers during and after the prolonged pandemic and to explore appropriate measures to support hospital workers' mental health.


Assuntos
COVID-19 , Angústia Psicológica , Suicídio , Humanos , COVID-19/epidemiologia , Pandemias , Estudos Transversais , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Inquéritos e Questionários , Hospitais
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