Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.506
Filtrar
1.
Front Oncol ; 14: 1445375, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220653

RESUMO

Background: Although microbiota in prostatic tissues of patients with prostate cancer have been studied, results of different studies have been inconsistent. Different ethnicity of study subjects, different study designs, and potential contaminations during sample collection and experiments might have influenced microbiome results of prostatic tissues. In this study, we analyzed microbiota and their potential functions in benign and malignant tissues of prostate cancer considering possible contaminants and host variables. Materials and methods: A total of 118 tissue samples (59 benign tissues and 59 malignant tissues) obtained by robot-assisted laparoscopic radical prostatectomy were analyzed and 64 negative controls (from sampling to sequencing processes) were included to reduce potential contaminants. Results: Alteration of the microbiome in prostate tissues was detected only in patients with diabetes. Furthermore, the influence of diabetes on microbiome was significant in malignant tissues. The microbiome in malignant tissues of patients with diabetes was influenced by pathologic stages. The relative abundance of Cutibacterium was reduced in the high pathologic group compared to that in the intermediate group. This reduction was related to microbial pathways increased in the high pathologic group. Conclusion: Results of this study indicate that diabetes can influence the progression of prostate cancer with microbiome alteration in prostate tissues. Although further studies are necessary to confirm findings of this study, this study can help us understand tissue microbiome in prostate cancer and improve clinical therapy strategies.

2.
Food Nutr Res ; 682024.
Artigo em Inglês | MEDLINE | ID: mdl-39239457

RESUMO

Background: Previous research has demonstrated the anti-obesity effects of kimchi in 3T3-L1 adipocytes and mice with diet-induced obesity by assessing the expression of obesity-associated genes. Additionally, recent studies have identified mechanisms involving thermogenesis that support these effects. Objective: This study aims to further investigate the anti-obesity properties of kimchi, focusing on its impact on thermogenic activity in differentiated T37i brown adipocytes. Design: The study first evaluated the antioxidant potential of kimchi using total antioxidant capacity (TAC) and ferric reducing antioxidant power (FRAP) assays. Optimal differentiation conditions for T37i adipocytes were established before proceeding with evaluations of cell viability, intracellular triglyceride (TG) content, lipid accumulation, and the expression of genes and proteins related to obesity and thermogenesis. Results: Kimchi maintained over 90% cell viability in T37i adipocytes at concentrations up to 1,000 µg/mL. Efficient differentiation of T37i preadipocytes was achieved using a medium containing 10% calf serum, 2 nM 3,3',5-triiodo-L-thyronin (T3), and 100 nM insulin. Kimchi significantly reduced intracellular TG levels and lipid accumulation, compared to the control group, and enhanced the expression of genes and proteins related to thermogenesis while reducing the expression of obesity-related genes. Discussion: The findings suggest that kimchi exerts its anti-obesity effects by modulating thermogenic and obesity-related pathways in brown adipocytes, which may be partially attributed to its antioxidant properties. Conclusions: Kimchi shows promise as a preventive measure against obesity by influencing metabolic pathways associated with both obesity and thermogenesis in T37i brown adipocytes.

3.
Plant Dis ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39254850

RESUMO

Chili (Capsicum annuum L.) is an economically important crop worldwide, valued for its culinary uses. In South Korea, anthracnose caused by Colletotrichum spp. including C. truncatum, C. gloeosporioides, C. coccodes, C. acutatum, and C. scovillei incurs on substantial economic loss (Kim et al. 2008; Oo and Oh 2020). In August 2022, somewhat different types of symptoms that was not typical on chilli fruits were observed in a field in Yereonggwang (GPS: 35.2579° N, 126.4742° E), South Korea. The disease symptoms appeared as sunken, necrotic lesions with dense black spore masses forming in concentric rings. The estimated disease incidence the 0.2 ha field showing up to 1% of fruits affected. To isolate the pathogen, six symptomatic chilli fruits were collected. Small pieces (5 mm²) were cut from the margins of the lesions, surface-sterilized in 70% ethanol for 30 sec, followed by 1% sodium hypochlorite for 1 minute, and then rinsed three times in sterile distilled water. The tissue pieces were placed on potato dextrose agar (PDA) plates and incubated at 25°C in the dark. After 3 to 5 days, emerging fungal colonies were sub-cultured to obtain pure isolates. A total of five isolates were obtained and initially identified as Colletotrichum spp. based on morphological characteristics. Seven-day old colonies were initially white, turning light orange with age on PDA. Setae (observed on lesion) were dark brown, verruculose and septate. Conidia were cylindrical, hyaline, and measured 14.8 to 19.9 × 4.2 to 6.5 µm (mean 16.7 × 5.6 µm, n = 70) in size; appressoria were brown to dark brown and irregularly shaped. These morphological characteristics of the isolates agree with those reported for the morphology of C. sojae by Damm et al. (2019). To confirm the identity of the isolates, DNA was extracted and specific gene regions were amplified and sequenced using the following primer sets: ITS (ITS1 and ITS4), GAPDH (GDF1 and GDR1), ACT (ACT-512F and ACT-783R), TUB (T1 and Bt2b), HIS3 (CYLH3F and CYLH3R), and CHS-1 (CHS-79F and CHS-345R). The resulting sequences were deposited in the NCBI GenBank with accession numbers (LC830742 to LC830766). Maximum likelihood phylogenetic analysis using combine sequences of ITS, GAPDH, ACT, TUB, HIS3 and CHS-1 in MEGA X confirmed the isolates as C. sojae, marking the first report of this pathogen on chilli in South Korea, previously known to infect soybean. Pathogenicity tests were conducted on wound and nonwounded healthy and mature-green chili fruits (cv. Bicksita) to confirm the pathogenicity of the isolated C. sojae. The fruits were surface-sterilized using 70% ethanol and then rinsed with sterile distilled water. The fruits were wounded using a sterile needle to facilitate infection. A conidial suspension (1x106 conidia/mL) was prepared from 7-day-old PDA cultures. Each fruit was inoculated by placing a 10 µL drop of the conidial suspension onto the wounded and nonwounded sites (4 to 5) of the wound and unwound fruits, respectively. Control fruits were inoculated with sterile water. A total of 40 fruits per treatment were used and the experiment repeated twice. The fruits were placed in plastic box lined with moist paper towels to maintain high humidity and incubated at 25°C. Anthracnose symptoms developed on the inoculated fruits within 7 days, while control and unwounded fruits remained symptom-free. Colletotrichum sojae was successfully reisolated from the symptomatic fruits, fulfilling Koch's postulates and confirming its role as the causal agent of the disease. Colletotrichum sojae is known to infect Fabaceae species worldwide such as Glycine max, Medicago sativa, Phaseolus vulgaris, Atractylodes ovata and Vigna unguiculata (Damm et al. 2019; Talhinhas and Baroncelli 2021), Atractylodes ovata in South Korea (Hassan et al. 2021) and chili pepper in China (Zhanget al. 2023). The first report of C. sojae causing chili anthracnose in South Korea represents a new challenge for chili growers. Integrated disease management strategies need to be developed and implemented to mitigate its impact.

4.
Lancet ; 404(10456): 937-948, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39226909

RESUMO

BACKGROUND: Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation. METHODS: A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y12 inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan-Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083). FINDINGS: A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31-92) after intervention, with a median duration of treatment of 334 days (329-365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan-Meier estimate 2·8%) with ticagrelor monotherapy and 332 (Kaplan-Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78-1·07]; p=0·0039 for non-inferiority; τ2<0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan-Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34-0·54]; p<0·0001 for superiority; τ2=0·079) and all-cause death (Kaplan-Meier estimate 0·9% vs 1·2%; 0·76 [0·59-0·98]; p=0·034 for superiority; τ2<0·0001) were lower with ticagrelor monotherapy. Trial sequential analysis showed strong evidence of non-inferiority for MACCE and superiority for bleeding among the overall and ACS populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p interaction=0·041) and all-cause death (p interaction=0·050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p interaction=0·022), indicating a benefit in ACS with ticagrelor monotherapy. INTERPRETATION: Our study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding, especially in patients with ACS. Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation. FUNDING: Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale.


Assuntos
Síndrome Coronariana Aguda , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Ensaios Clínicos Controlados Aleatórios como Assunto , Ticagrelor , Humanos , Ticagrelor/uso terapêutico , Ticagrelor/administração & dosagem , Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Terapia Antiplaquetária Dupla/métodos , Hemorragia/induzido quimicamente , Stents Farmacológicos , Resultado do Tratamento
5.
Korean J Intern Med ; 39(5): 783-792, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39252488

RESUMO

BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) is a promising therapy for inducing and maintaining remission in patients with ulcerative colitis (UC). However, FMT has not been approved for UC treatment in Korea. Our study aimed to investigate patient perceptions of FMT under the national medical policy. METHODS: This was a prospective, multicenter study. Patients with UC ≥ 19 years of age were included. Patients were surveyed using 22 questions on FMT. Changes in perceptions of FMT before and after education were also compared. RESULTS: A total of 210 patients with UC were enrolled. We found that 51.4% of the patients were unaware that FMT was an alternative treatment option for UC. After reading the educational materials on FMT, more patients were willing to undergo this procedure (27.1% vs. 46.7%; p < 0.001). The preferred fecal donor was the one recommended by a physician (41.0%), and the preferred transplantation method was the oral capsule (30.4%). A large proportion of patients (50.0%) reported that the national medical policy influenced their choice of FMT treatment. When patients felt severe disease activity, their willingness to undergo FMT increased (92.3% vs. 43.1%; p = 0.001). CONCLUSION: Education can increase preference for FMT in patients with UC. When patients have severe disease symptoms or their quality of life decreases their willingness to undergo FMT increases. Moreover, national medical policies may influence patient choices regarding FMT.


Assuntos
Colite Ulcerativa , Transplante de Microbiota Fecal , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Colite Ulcerativa/terapia , Colite Ulcerativa/microbiologia , Colite Ulcerativa/diagnóstico , Masculino , Feminino , Adulto , República da Coreia , Pessoa de Meia-Idade , Estudos Prospectivos , Educação de Pacientes como Assunto , Preferência do Paciente , Resultado do Tratamento , Aceitação pelo Paciente de Cuidados de Saúde , Adulto Jovem , Idoso , Percepção
6.
Materials (Basel) ; 17(17)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39274824

RESUMO

The purpose of this study was to investigate the optimization of computer-aided design/computer-aided manufacturing (CAD/CAM) patient-specific implants for mandibular facial bone defects and compare the biocompatibility and osseointegration of machined titanium (Ma), Sandblasted/Large-grit/Acid-etched (SLA) titanium, and polyetherketoneketone (PEKK) facial implants. We hypothesized that the facial implants made of SLA titanium had superior osseointegration when applied to the gonial angle defect and prevented the senile atrophy of the bone. Histologic findings of the soft-tissue reaction, hard-tissue reaction, and bone-implant contact (BIC (%) of 24 Ma, SLA, and PEKK facial implants at 8 and 12 weeks were investigated. There was no statistical difference in the soft tissue reaction. Bone was formed below the periosteum in all facial implants at 12 weeks and the BIC values were significantly different at both 8 and 12 weeks (p < 0.05). Ma, SLA, and PEKK facial implants are biocompatible with osseointegration properties. SLA can enhance osseointegration and provoke minimal soft tissue reactions, making them the most suitable choice. They provide an excellent environment for bone regeneration and, over the long term, may prevent atrophy caused by an aging mandible. The bone formation between the lateral surface of the facial implant and periosteum may assist in osseointegration and stabilization.

7.
Lancet ; 404(10457): 1029-1039, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39236729

RESUMO

BACKGROUND: Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year. METHODS: This investigator-initiated, multicentre, randomised, open-label, superiority trial conducted at 20 hospitals in South Korea enrolled patients aged 19-85 years for whom PCI with drug-eluting stents was clinically indicated. After diagnostic angiography, clinical and angiographic findings were assessed to identify patients who met the criterion of having one or more complex lesions. Patients were randomly assigned 1:1 to receive PCI with OCT guidance (OCT-guidance group) or angiography guidance without OCT (angiography-guidance group). Web-response permuted-block randomisation (mixed blocks of four or six) was used at each participating site to allocate patients. The allocation sequence was computer-generated by an external programmer who was not involved in the rest of the trial. Outcome assessors were masked to group assignment. Patients, follow-up health-care providers, and data analysers were not masked. PCI was done according to conventional standard methods with everolimus-eluting stents. The primary endpoint was major adverse cardiac events (a composite of cardiac death, myocardial infarction, stent thrombosis, or ischaemia-driven target-vessel revascularisation), 1 year after PCI. The primary analysis was done in the intention-to-treat population. The margin used to establish superiority was 1·0 as a hazard ratio. This trial is registered with ClinicalTrials.gov (NCT03625908) and is completed. FINDINGS: Between Jan 9, 2019, and Sept 22, 2022, 1604 patients requiring PCI with drug-eluting stents for complex lesions were randomly assigned to receive either OCT-guided PCI (n=803) or angiography-guided PCI (n=801). 1290 (80%) of 1604 patients were male and 314 (20%) were female. The median age of patients at randomisation was 64 years (IQR 57-70). 1588 (99%) patients completed 1-year follow-up. The primary endpoint occurred in 37 (5%) of 803 patients in the OCT-guided PCI group and 59 (7%) of 801 patients in the angiography-guided PCI group (absolute difference -2·8% [95% CI -5·1 to -0·4]; hazard ratio 0·62 [95% CI 0·41 to 0·93]; p=0·023). Rates of stroke, bleeding events, and contrast-induced nephropathy were not significantly different across the two groups. INTERPRETATION: Among patients who required drug-eluting stent implantation for complex lesions, OCT guidance resulted in a lower incidence of major adverse cardiac events at 1 year compared with angiography guidance. These findings indicate the existence of a therapeutic benefit of OCT as an intravascular imaging technique for PCI guidance in patients with complex coronary lesions. FUNDING: Abbott Vascular and Cardiovascular Research Center. TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.


Assuntos
Angiografia Coronária , Stents Farmacológicos , Intervenção Coronária Percutânea , Tomografia de Coerência Óptica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea/métodos , República da Coreia , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento
8.
Investig Clin Urol ; 65(5): 442-450, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39249916

RESUMO

PURPOSE: We evaluated the feasibility, safety, and learning curve of extraperitoneal single-port robot-assisted radical prostatectomy (SP-RARP) and introduced innovative surgical techniques to maintain the instrument positions during the procedures. MATERIALS AND METHODS: A cohort of 100 patients underwent extraperitoneal SP-RARP at our institution from December 2021 to April 2023. The procedures were performed by an experienced urology surgeon utilizing two surgical techniques for dissecting the posterior aspect of the prostate-"changing instrument roles" and "using camera inversion"-to prevent positional shifts between the camera and instruments. RESULTS: The mean operation time for SP-RARP was 93.58 minutes, and the mean console time was 65.16 minutes. The mean estimated blood loss during the procedures was 109.30 mL. No cases necessitated conversion to multi-port robot, laparoscopy, or open surgery, and there were no major complications during the hospital stay or in the short-term follow-up. Early outcomes of post-radical prostatectomy indicated a biochemical recurrence rate of 4.0% over a mean follow-up duration of 6.40 months, with continence and potency recovery rates of 92.3% and 55.8%, respectively. Analysis of the learning curve showed no significant differences in operation time, console time, and positive surgical margin rates between the initial and latter 50 cases. CONCLUSIONS: Extraperitoneal SP-RARP is a feasible and safe option for the treatment of localized prostate cancer in skilled hands. Continued accrual of cases is essential for future comparisons of SP-RARP with multiport approaches.


Assuntos
Estudos de Viabilidade , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Prostatectomia/métodos , Masculino , Procedimentos Cirúrgicos Robóticos/métodos , Pessoa de Meia-Idade , Neoplasias da Próstata/cirurgia , Idoso , Resultado do Tratamento , Curva de Aprendizado , Fatores de Tempo , Estudos Retrospectivos , Duração da Cirurgia
9.
Clin Ther ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39289057

RESUMO

PURPOSE: A fixed-dose combination (FDC) of proton pump inhibitors (PPIs) and antacid salts enables rapid acid suppression through the neutralizing effect of the antacid salt and the rapid absorption of PPIs. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of a recently formulated FDC of esomeprazole and magnesium hydroxide to the enteric-coated esomeprazole in healthy subjects. METHODS: A randomized, open-label, multiple-dose, two-treatment, two-way crossover design was conducted in healthy subjects. Forty-nine subjects were randomized to one of the two treatment sequences and received either the test drug (esomeprazole/magnesium hydroxide 40/350 mg) or reference drug (enteric-coated esomeprazole 40 mg) for 7 days in the first period and the alternative in the second period with a 14-day washout period. Blood samples were collected for up to 24 hours for PK assessment, and 24-hour gastric pH monitoring was conducted for PD assessment both before and after a single administration, as well as at a steady state after seven consecutive days of administration. The PK and PD parameters were compared between the two drugs. FINDINGS: After multiple administrations, the median value of time to reach maximum concentration was faster in the test drug than in the reference drug, with a difference of 1.68 hours. The overall systemic exposure of the test drug was similar to that of the reference drug, and the PK parameter fell within the equivalence criteria. The test drug demonstrated a shorter time to reach gastric pH ≥ 4 compared to the reference drug (P = 0.0463). A decrease from baseline in integrated gastric acidity over 24 hours, which represents the degree of inhibition of gastric acid secretion, was equivalent between the two drugs. IMPLICATIONS: The fixed-dose combination of esomeprazole and magnesium hydroxide showed rapid absorption and quicker gastric acid suppression than enteric-coated esomeprazole with comparable PK and PD properties. CLINICALTRIALS: gov identifier: NCT04324905 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT04324905).

10.
Front Microbiol ; 15: 1429808, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39268541

RESUMO

Introduction: African swine fever (ASF) is a lethal and highly contagious transboundary animal disease with the potential for rapid international spread. In the absence of a widely available and definitively proven vaccine, rapid and early detection is critical for ASF control. The quick and user-friendly lateral flow assay (LFA) can easily be performed by following simple instructions and is ideal for on-site use. This study describes the development and validation of two LFAs for the rapid detection of ASF virus (ASFV) in pig serum. Methods: The highly immunogenic antigens (p30 and p72) of ASFV Georgia 2007/1 (genotype II) were expressed in plants (Nicotiana benthamiana) and were used to immunize BALB/c mice to generate specific monoclonal antibodies (mAbs) against the p30 and p72 proteins. mAbs with the strongest binding ability to each protein were used to develop p30_LFA and p72_LFA for detecting the respective ASFV antigens. The assays were first evaluated using a spike-in test by adding the purified p30 or p72 protein to a serum sample from a healthy donor pig. Further validation of the tests was carried out using serum samples derived from experimentally infected domestic pigs, field domestic pigs, and feral pigs, and the results were compared with those of ASFV real-time PCR. Results: p30_LFA and p72_LFA showed no cross-reaction with common swine viruses and delivered visual results in 15 min. When testing with serially diluted proteins in swine serum samples, analytical sensitivity reached 10 ng/test for p30_LFA and 20 ng/test for p72_LFA. Using real-time PCR as a reference, both assays demonstrated high sensitivity (84.21% for p30_LFA and 100% for p72_LFA) with experimentally ASFV-infected pig sera. Specificity was 100% for both LFAs using a panel of PBS-inoculated domestic pig sera. Excellent specificity was also shown for field domestic pig sera (100% for p30_LFA and 93% for p72_LFA) and feral pig sera (100% for both LFAs). Conclusion: The results obtained in this study suggest that p30_LFA and p72_LFA hold promise as rapid, sensitive, user-friendly, and field-deployable tools for ASF control, particularly in settings with limited laboratory resources.

11.
Transl Stroke Res ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39294532

RESUMO

Impaired cerebral circulation, induced by blood vessel constrictions and microthrombi, leads to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). 12/15-Lipooxygenase (12/15-LOX) overexpression has been implicated in worsening early brain injury outcomes following SAH. However, it is unknown if 12/15-LOX is important in delayed pathophysiological events after SAH. Since 12/15-LOX produces metabolites that induce inflammation and vasoconstriction, we hypothesized that 12/15-LOX leads to microvessel constriction and microthrombi formation after SAH, and thus, 12/15-LOX is an important target to prevent delayed cerebral ischemia. SAH was induced in C57BL/6 and 12/15-LOX-/- mice of both sexes by endovascular perforation. Expression of 12/15-LOX was assessed in brain tissue slices and in vitro. C57BL/6 mice were administered either ML351 (12/15-LOX inhibitor) or vehicle. Mice were evaluated for daily neuroscore and euthanized on day 5 to assess cerebral 12/15-LOX expression, vessel constrictions, platelet activation, microthrombi, neurodegeneration, infarction, cortical perfusion, and development of delayed deficits. Finally, the effect of 12/15-LOX inhibition on platelet activation was assessed in SAH patient samples using a platelet spreading assay. In SAH mice, 12/15-LOX was upregulated in brain vascular cells, and there was an increase in 12-S-HETE. Inhibition of 12/15-LOX improved brain perfusion on days 4-5 and attenuated delayed pathophysiological events, including microvessel constrictions, microthrombi, neuronal degeneration, and infarction. Additionally, 12/15-LOX inhibition reduced platelet activation in human and mouse blood samples. Cerebrovascular 12/15-LOX overexpression plays a major role in brain dysfunction after SAH by triggering microvessel constrictions and microthrombi formation, which reduces brain perfusion. Inhibiting 12/15-LOX may be a therapeutic target to improve outcomes after SAH.

12.
JAMA Dermatol ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39230899

RESUMO

This case report describes a patient with severe generalized recessive dystrophic epidermolysis bullosa who presented with an unhealed ulcer that had persisted for the past 3 years.

13.
Med ; 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39153473

RESUMO

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT). METHODS: Individual patient data were pooled from randomized clinical trials that included STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3 months) DAPT versus ticagrelor-based 12-month DAPT in terms of centrally adjudicated clinical outcomes. The co-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding Academic Research Consortium type 3 or 5 bleeding) at 1 year. FINDINGS: The pooled cohort contained 2,253 patients with STEMI. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based DAPT group (1.8% versus 2.0%; hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.49-1.61; p = 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR = 0.89; 95% CI = 0.32-2.46; p = 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%; HR = 0.56; 95% CI = 0.35-0.92; p = 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups. CONCLUSIONS: In patients with STEMI treated with DES implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients. FUNDING: This study was funded by Biotronik (Bülach, Switzerland).

14.
Int J Implant Dent ; 10(1): 38, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101986

RESUMO

PURPOSE: To retrospectively evaluate peri-implant bone loss and health status associated with the long-term use of laser surface-treated implants. METHODS: For control study, total of 23 titanium ASTM F136 grade 23 implants were placed in the edentulous molar area of the mandible. When the Implant Stability Quotient (ISQ) ≥ 70 and insertion torque value (ITV) ≥ 35-50 Ncm at the insertion site, an immediate provisional restoration was connected to the implant within a week after surgery. The definitive restorations were placed 2 months after surgery for all implants. 13 implants were immediately loaded, while 10 implants were conventionally loaded. For comparative study, Radiographs were taken from third years for and then annually for the subsequent eight years to monitor marginal bone loss. RESULTS: After eight year of implant installation, the average change in vertical bone loss was 0.009 mm (P < 0.001), while the average change in horizontal bone loss 8 year after implant placement was 0.026 mm (P < 0.001). The mean marginal bone loss was < 0.2 mm on average. CONCLUSIONS: In this retrospective study, laser-treated implants exhibit a low rate of bone absorption around the implants.


Assuntos
Perda do Osso Alveolar , Implantes Dentários , Estudos Retrospectivos , Humanos , Implantes Dentários/efeitos adversos , Masculino , Feminino , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/diagnóstico por imagem , Pessoa de Meia-Idade , Resultado do Tratamento , Lasers , Idoso , Propriedades de Superfície , Adulto , Mandíbula/cirurgia , Planejamento de Prótese Dentária , Carga Imediata em Implante Dentário/métodos
15.
Food Sci Biotechnol ; 33(12): 2901, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39184981

RESUMO

[This corrects the article DOI: 10.1007/s10068-023-01471-2.].

16.
J Clin Med ; 13(16)2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39201083

RESUMO

Background: It has been reported in many previous studies that the lack of auditory input due to hearing loss (HL) can induce changes in the brain. However, most of these studies have focused on individuals with pre-lingual HL and have predominantly compared the characteristics of those with normal hearing (NH) to cochlear implant (CI) users in children. This study examined the visual and auditory evoked potential characteristics in NH listeners, individuals with bilateral HL, and CI users, including those with single-sided deafness. Methods: A total of sixteen participants (seven NH listeners, four individuals with bilateral sensorineural HL, and five CI users) completed speech testing in quiet and noise and evoked potential testing. For speech testing, the Korean version of the Hearing in Noise Test was used to assess individuals' speech understanding ability in quiet and in noise (noise from the front, +90 degrees, and -90 degrees). For evoked potential testing, visual and auditory (1000 Hz, /ba/, and /da/) evoked potentials were measured. Results: The results showed that CI users understood speech better than those with HL in all conditions except for the noise from +90 and -90 degrees. In the CI group, a decrease in P1 amplitudes was noted across all channels after implantation. The NH group exhibited the highest amplitudes, followed by the HL group, with the CI group (post-CI) showing the lowest amplitudes. In terms of auditory evoked potentials, the smallest amplitude was observed in the pre-CI condition regardless of the type of stimulus. Conclusions: To the best of our knowledge, this is the first study that examined visual and auditory evoked potentials based on various hearing profiles. The characteristics of evoked potentials varied across participant groups, and further studies with CI users are necessary, as there are significant challenges in collecting and analyzing evoked potentials due to artifact issues on the CI side.

17.
Int J Mol Sci ; 25(15)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39126108

RESUMO

Damage to the central nervous system (CNS) often leads to irreversible neurological deficits, and there are currently few effective treatments available. However, recent advancements in regenerative medicine have identified CNS organoids as promising therapeutic options for addressing CNS injuries. These organoids, composed of various neurons and supporting cells, have shown potential for direct repair at injury sites. CNS organoids resemble the structure and function of actual brain tissue, which allows them to adapt and function well within the physiological environment when transplanted into injury sites. Research findings suggest that CNS organoids can replace damaged neurons, form new neural connections, and promote neural recovery. This review highlights the emerging benefits, evaluates preclinical transplantation outcomes, and explores future strategies for optimizing neuroregeneration using CNS organoids. With continued research and technological advancements, these organoids could provide new hope for patients suffering from neurological deficits.


Assuntos
Sistema Nervoso Central , Organoides , Humanos , Organoides/citologia , Organoides/transplante , Regeneração Nervosa , Animais , Neurônios/citologia , Neurônios/fisiologia , Medicina Regenerativa/métodos
18.
Nat Commun ; 15(1): 6901, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134533

RESUMO

The aberrant expression of specific long noncoding RNAs (lncRNAs) has been associated with cognitive and psychiatric disorders. Although a growing number of lncRNAs are now known to regulate neural cell development and function, relatively few lncRNAs have been shown to underlie animal behavior. Pnky is an evolutionarily conserved, neural lncRNA that regulates brain development. Using mouse genetic strategies, we show that Pnky has sex-specific roles in mouse behavior and that this lncRNA can underlie specific behavior by functioning in trans. Male Pnky-knockout mice have decreased context generalization in a paradigm of associative fear learning and memory. In female Pnky-knockout mice, there is an increase in the acoustic startle response, a behavior that is altered in affective disorders. Remarkably, expression of Pnky from a bacterial artificial chromosome transgene decreases the acoustic startle response in female Pnky-knockout mice, demonstrating that Pnky can modulate specific animal behavior by functioning in trans. More broadly, these studies illustrate how specific lncRNAs can underlie cognitive and mood disorders.


Assuntos
Comportamento Animal , Medo , Camundongos Knockout , RNA Longo não Codificante , Reflexo de Sobressalto , Animais , Feminino , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Masculino , Comportamento Animal/fisiologia , Camundongos , Reflexo de Sobressalto/fisiologia , Medo/fisiologia , Memória/fisiologia , Camundongos Endogâmicos C57BL , Fatores Sexuais
19.
Sci Rep ; 14(1): 18482, 2024 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-39122842

RESUMO

A low arousal threshold (LAT) is a pathophysiological trait of obstructive sleep apnea (OSA) that may be associated with brainstem ascending reticular activating system-cortical functional connectivity changes. We evaluated resting-state connectivity between the brainstem nuclei and 105 cortical/subcortical regions in OSA patients with or without a LAT and healthy controls. Twenty-five patients with moderate to severe OSA with an apnea-hypopnea index between 20 and 40/hr (15 with and 10 without a LAT) and 15 age- and sex-matched controls were evaluated. Participants underwent functional magnetic resonance imaging after overnight polysomnography. Three brainstem nuclei-the locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), and ventral tegmental area (VTA)-associated with OSA in our previous study were used as seeds. Functional connectivity values of the two brainstem nuclei (LC and LDTg) significantly differed among the three groups. The connectivity of the LC with the precuneus was stronger in OSA patients than in controls regardless of the concomitant LAT. The connectivity between the LDTg and the posterior cingulate cortex was also stronger in OSA patients regardless of the LAT. Moreover, OSA patients without a LAT showed stronger LDTg-posterior cingulate cortex connectivity than those with a LAT (post hoc p = 0.013), and this connectivity strength was negatively correlated with the minimum oxygen saturation in OSA patients (r = - 0.463, p = 0.023). The LAT in OSA patients was associated with altered LDTg-posterior cingulate cortex connectivity. This result may suggested that cholinergic activity may play a role in the LAT in OSA patients.


Assuntos
Nível de Alerta , Tronco Encefálico , Imageamento por Ressonância Magnética , Polissonografia , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/diagnóstico por imagem , Masculino , Nível de Alerta/fisiologia , Feminino , Pessoa de Meia-Idade , Adulto , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/fisiopatologia , Estudos de Casos e Controles
20.
Clin Orthop Surg ; 16(4): 594-601, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39092311

RESUMO

Background: The purpose of this study was to identify the changes in untreated subscapularis in patients who underwent supraspinatus repair and to evaluate the factors related to the changes in the subscapularis. Methods: A cohort of patients who underwent isolated supraspinatus repair with preservation of the subscapularis was reviewed. Changes in the subscapularis, including any newly formed lesion and aggravation of an existing lesion, were evaluated 12 months postoperatively on magnetic resonance imaging along with an examination to identify causative factors after supraspinatus repair. Clinical scores were compared between patients with and without subscapularis changes. Results: A total of 528 patients were reviewed. Changes in the subscapularis, including newly formed lesions and aggravation of an existing lesion, were shown in 90 patients (17.0%). Upon regression analysis, changes in the subscapularis were associated with the initial existence of a subscapularis lesion (grade I: p = 0.042, grade II: p = 0.025), an accompanying biceps lesion (p = 0.038), and a retear of the repaired supraspinatus (p = 0.024). No significant differences were shown in clinical scores between patients with and without subscapularis changes after supraspinatus repair. Conclusions: Untreated asymptomatic subscapularis may undergo morphological changes even after repair of the torn supraspinatus. Preoperative subscapularis lesions, biceps long head pathology, and retears of the repaired supraspinatus were associated with subscapularis pathology in patients who underwent supraspinatus repair.


Assuntos
Artroscopia , Lesões do Manguito Rotador , Manguito Rotador , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Lesões do Manguito Rotador/cirurgia , Lesões do Manguito Rotador/diagnóstico por imagem , Adulto , Manguito Rotador/cirurgia , Manguito Rotador/diagnóstico por imagem , Idoso , Imageamento por Ressonância Magnética , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA