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1.
J Med Food ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828543

RESUMO

Acorus gramineus has a number of beneficial effects, including protective effects against age-related disorders. In this study, the effects of A. gramineus on testosterone production and andropause symptoms were evaluated. We first treated TM3 mouse Leydig cells, responsible for testosterone production, with A. gramineus aqueous extract at different concentrations. In TM3 cells, the testosterone concentration increased in a concentration-dependent manner compared with those in the control. In addition, at 400 µg/mL extract, the mRNA expression level of the steroidogenic enzyme CYP11A1 was increased. Subsequently, 23-week-old Sprague-Dawley (SD) rats exhibiting an age-related reduction in serum testosterone (approximately 80% lower than that in 7-week-old SD rats) were administered A. gramineus aqueous extract for 8 weeks. Serum total testosterone and free testosterone levels were higher and serum estradiol, prostate-specific antigen levels, and total cholesterol levels were lower in the AG50 group (A. gramineus aqueous extract 50 mg/kg of body weight/day) than in the OLD (control group). The AG50 group also showed significant elevations in sperm count, grip strength, and mRNA expression of StAR, CYP11A1, 17ß-HSD, and CYP17A1 compared with those in the OLD group. In conclusion, A. gramineus aqueous extract facilitated steroidogenesis in Leydig cells, elevated testosterone levels, lowered serum estradiol and total cholesterol levels, and increased muscle strength and sperm count, thus alleviating the symptoms of andropause. These findings suggest that A. gramineus aqueous extract is a potentially effective therapeutic agent against various symptoms associated with andropause.

2.
Adv Healthc Mater ; : e2303781, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828846

RESUMO

Tissue biopsy for early diagnosis and monitoring comes with several challenges, such as its invasiveness, and issues related to tissue heterogeneity in sampling. To address these issues, researchers have proposed a non-invasive approach called liquid biopsy, which uses blood samples to detect specific non-coding RNA (miRNA). However, the current process of isolating and amplifying miRNA can be time-consuming and yield non-specific results. In this study, we introduce a new super-resolution imaging tool that utilizes a thin, hydrogel-based liquid view (LV) film. This film can undergo a 9-fold expansion and allows the analysis of cells obtained from liquid biopsy. We have validated the potential of the LV film as a tool for early diagnosis and prognosis by testing biofluids derived from a variety of diseases. This method has been confirmed to accurately analyze a greater number of miRNAs with higher sensitivity in a shorter time compared to other analytical methods. Our findings suggest that the LV film provides high specificity, and multiplexing in detecting small amounts of miRNAs within cells, making it suitable for three-dimensional implementation. We propose that liquid biopsy with LV films could be a solution to limitations related to the invasiveness, cost, and time-consuming nature of molecular analysis. This article is protected by copyright. All rights reserved.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38857116

RESUMO

Polypyrrole (Ppy) is a biologically compatible polymer that is used as a matrix, in which drugs and enzymes can be incorporated by doping. Here, we suggest an inventive application of Ppy as a biorecognition film encapsulated with an antibody (Ab) as an alternative strategy for the on-site multistep functionalization of thiol-based self-assembled monolayers. The fabrication steps of the recognition films were followed by dropping pyrrole and Ab mixed solutions onto the electrode and obtaining a thin film by direct current electropolymerization. The efficiency of Ab immobilization was studied by using fluorescence microscopy and electrochemical (EC) methods. Finally, the Ab density was increased and immobilized in 1 min, and the sensing performance as an EC immunosensor was demonstrated using α-fetoprotein with a limit of detection of 3.13 pg/mL and sensing range from 1 pg/mL to 100 ng/mL. This study demonstrates the potential for electrochemical functionalization of biomolecules with high affinity and rapidity.

4.
Jpn J Ophthalmol ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739252

RESUMO

PURPOSE: To provide an updated analysis of the long-term outcomes of patients with acute primary angle closure (APAC) and to investigate the risk factors for visual field (VF) loss progression. STUDY DESIGN: Retrospective, clinical cohort study METHODS: One hundred and forty-six APAC patients with a minimum of 1-year follow-up were included. The presenting features and the treatment utilized were recorded. The visual and intraocular pressure (IOP) outcomes were analyzed. The main outcome measures were the proportion of blindness and IOP at the final visit. A subset of patients with sufficient VF results was divided into a stable and progressive group based on mean deviation (MD) loss rate. Univariate and multivariate logistic regression analyses were performed to identify predictors of progression. RESULTS: Nine patients (6.2%) were blind, and 76.0% (111/146) had final decimal visual acuity greater than or equal to 0.5. All patients had normal final IOP, and 65.1% (95/146) were medication-free. 64.4% (94/146) underwent cataract surgery at a median 4 months after their APAC attack. The use of topical hypotensive medications (OR = 8.029, P = 0.012) was the only significant predictor of fast MD loss in the multivariate regression. CONCLUSIONS: The long-term outcomes of APAC in recent years have been more promising. All patients maintained normal IOP several years following their APAC attack, and fewer than half required hypotensive agents. The incidence of blindness was low. These findings suggest that current practice patterns in the management of APAC are beneficial.

5.
ACS Appl Mater Interfaces ; 16(22): 28093-28103, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38775441

RESUMO

Bacteria-assisted chemotherapeutics have been highlighted as an alternative or supplementary approach to treating cancer. However, dynamic cancer-microbe studies at the in vitro level have remained a challenge to show the impact and effectiveness of microbial therapeutics due to the lack of relevant coculture models. Here, we demonstrate a hydrogel-based compartmentalized system for prodrug activation of a natural ingredient of licorice root, glycyrrhizin, by microbial ß-glucuronidase (GUS). Hydrogel containment with Lactococcus lactis provides a favorable niche to encode GUS enzymes with excellent permeability and can serve as an independent ecosystem in the transformation of pro-apoptotic materials. Based on the confinement system of GUS expressing microbes, we quantitatively evaluated chemotherapeutic effects enhanced by microbial GUS enzyme in two dynamic coculture models in vitro (i.e., 2D monolayered cancer cells and 3D tumor spheroids). Our findings support the processes of prodrug conversion mediated by bacterial GUS enzyme which can enhance the therapeutic efficacy of a chemotherapy drug under dynamic coculture conditions. We expect our in vitro coculture platforms can be used for the evaluation of pharmacological properties and biological activity of xenobiotics as well as the potential impact of microbes on cancer therapeutics.


Assuntos
Glucuronidase , Hidrogéis , Pró-Fármacos , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Humanos , Glucuronidase/metabolismo , Hidrogéis/química , Hidrogéis/farmacologia , Lactococcus lactis/enzimologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral
6.
Artigo em Inglês | MEDLINE | ID: mdl-38650430

RESUMO

Objective: Spinal intramedullary hemangioblastoma is a rare and highly vascularized benign tumor. The characteristics of the tumor, its corresponding location, and surgical outcomes remain unknown. The purpose of this study was to identify risk factors and strategies for neurologic deterioration following hemangioblastoma surgery. Methods: A comprehensive retrospective analysis was undertaken to evaluate patients who underwent surgical intervention for intramedullary hemangioblastoma at our institution from 1993 to 2022. Patients with at least one year of follow-up data were included. The analysis covered patient demographics, pre- and post-operative Modified McCormick Scale (MMCS), tumor location, and tumor size. Results: This study included 25 cases. One-year after surgery, neurological deterioration was observed in 5 (20.0%) cases, and neurological improvement was found in 9 (36.0%) cases. Five cases were ventrally located, and twelve cases were dorsally located. Ventrally located cases were larger in tumor axial size (p = 0.029) than dorsal location tumors, resulting in poorer follow-up MMCS and a higher prevalence of von Hippel-Lindau syndrome (VHL) (p = 0.042). Three of them were confirmed to be supplied by the anterior spinal artery. In the case of dorsally located cases, there was no neurologic deterioration. Conclusion: In intramedullary spinal cord hemangioblastomas, cases located ventrally had a higher incidence of neurological deterioration following surgery than those located dorsally or in intramedullary extramedullary cases. Ventrally located hemangioblastomas were larger than those in other locations. They were mainly supplied by the anterior spinal artery in VHL patients.

7.
Front Pharmacol ; 15: 1339486, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655186

RESUMO

Background: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of East Asian herbal medicine (HM) for iron deficiency anemia (IDA) in children and adolescents. Methods: Twelve electronic databases were searched in 28 May 2023 for randomized controlled trials (RCTs) evaluating the efficacy of HM in children with IDA. The primary outcome measures for treatment included blood hemoglobin and serum ferritin levels, whereas the secondary outcomes included the total effective rate (TER), incidence of adverse events (AEs), average healing time, and hematologic indicators related to IDA. Meta-analysis was performed using Review Manager 5.4 and R studio 4.3 software, and subgroup analyses were performed according to the different groups (type of intervention and duration of treatment). The effect size measures used were the risk ratio, mean difference, and standardized mean difference with 95% confidence intervals. The risk of bias was assessed using a revised Cochrane risk of bias tool for randomized trials, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation tools. Results: The meta-analysis included 28 studies. Five studies compared the efficacy of HM alone with that of oral iron alone, whereas 23 compared the efficacy of a combination of HM and oral iron with that of oral iron alone. The meta-analysis revealed that the HM treatment group showed significant improvements in all outcome measures compared to those observed in the oral iron group. Moreover, HM significantly reduced the incidence of gastrointestinal AE, compared to that associated with oral iron. Among the 28 studies, the most commonly used HM prescription was Xingpi Yanger Granules, and the most commonly used botanical drug was Astragali Radix, followed by Atractylodis Rhizoma Alba and Angelicae Sinensis Radix. Conclusion: This meta-analysis identified evidence of the efficacy and safety of HM in children with IDA. Compared to conventional oral iron therapy, HM improved IDA-related blood markers and TER, with fewer AEs and shorter mean healing times. However, further well-designed, large-scale clinical trials are necessary to strengthen the evidence of the efficacy and safety of botanical drugs. Systematic Review Registration: PROSPERO 2022 CRD42022334670. (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022334670).

8.
J Microbiol ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689047

RESUMO

Adenovirus (Ad) is a ubiquitous pathogen capable of infecting a wide range of animals and humans. Human Adenovirus (HAdV) can cause severe infection, particularly in individuals with compromised immune systems. To date, over 110 types of HAdV have been classified into seven species from A to G, with the majority belonging to the human adenovirus species D (HAdV-D). In the HAdV-D, the most significant factor for the creation of new adenovirus types is homologous recombination between viral genes involved in determining the virus tropism or evading immune system of host cells. The E4 gene, consisting of seven Open Reading Frames (ORFs), plays a role in both the regulation of host cell metabolism and the replication of viral genes. Despite long-term studies, the function of each ORF remains unclear. Based on our updated information, ORF2, ORF3, and ORF4 have been identified as regions with relatively high mutations compared to other ORFs in the E4 gene, through the use of in silico comparative analysis. Additionally, we managed to visualize high mutation sections, previously undetectable at the DNA level, through a powerful amino acid sequence analysis tool known as proteotyping. Our research has revealed the involvement of the E4 gene in the evolution of human adenovirus, and has established accurate sequence information of the E4 gene, laying the groundwork for further research.

9.
Neurospine ; 21(1): 83-94, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38569633

RESUMO

OBJECTIVE: This study aimed to compare the accuracy of robotic spine surgery and conventional pedicle screw fixation in lumbar degenerative disease. We evaluated clinical and radiological outcomes to demonstrate the noninferiority of robotic surgery. METHODS: This study employed propensity score matching and included 3 groups: robot-assisted mini-open posterior lumbar interbody fusion (PLIF) (robotic surgery, RS), c-arm guided minimally invasive surgery transforaminal lumbar interbody fusion (C-arm guidance, CG), and freehand open PLIF (free of guidance, FG) (54 patients each). The mean follow-up period was 2.2 years. The preoperative spine condition was considered. Accuracy was evaluated using the Gertzbein-Robbins scale (GRS score) and Babu classification (Babu score). Radiological outcomes included adjacent segmental disease (ASD) and mechanical failure. Clinical outcomes were assessed based on the visual analogue scale, Oswestry Disability Index, 36-item Short Form health survey, and clinical ASD rate. RESULTS: Accuracy was higher in the RS group (p < 0.01) than in other groups. The GRS score was lower in the CG group, whereas the Babu score was lower in the FG group compared with the RS group. No significant differences were observed in radiological and clinical outcomes among the 3 groups. Regression analysis identified preoperative facet degeneration, GRS and Babu scores as significant variables for radiological and clinical ASD. Mechanical failure was influenced by the GRS score and patients' age. CONCLUSION: This study showed the superior accuracy of robotic spine surgery compared with conventional techniques. When combined with minimally invasive surgery, robotic surgery is advantageous with reduced ligament and muscle damage associated with traditional open procedures.

10.
Clin Spine Surg ; 37(4): 131-137, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38637933

RESUMO

STUDY DESIGN: Single-center retrospective study. OBJECTIVE: The objective of this study is to identify the factors leading to repeat surgery in patients with cervical ossification of the longitudinal ligament (OPLL) during a minimal 8-year follow-up after the initial surgery. SUMMARY OF BACKGROUND DATA: The long-term effects of cervical OPLL are well known, but it's not always clear how many patients need to have surgery again because their neurological symptoms get worse. METHODS: This study is included 117 patients who underwent surgery for cervical OPLL and had a follow-up of at least 8 years. OPLL type, surgical extent, surgical method, and sagittal radiological parameters were measured, and OPLL characteristics were analyzed. RESULTS: The average age of patients at the time of surgery was 53.2 years, with a male-to-female ratio of 78:39. The median follow-up duration was 122 months (96-170 mo). Out of the total, 20 cases (17.1%) necessitated repeat surgery, among which 8 cases required surgery at the same site as the initial operation. The highest rate of repeat surgery was observed in patients who underwent total laminectomy without fusion (TL), where 6 out of 21 patients (29%) needed a second surgery, and 5 of these (23%) involved the same surgical site. Patients who underwent repeat surgery at the same site exhibited a greater range of motion (ROM) one year postsurgery (16.4 ± 8.5° vs. 23.1 ± 12.7°, P =0.041). In addition, the ROM at 1 year was higher in patients who underwent TL compared with those who had laminoplasty. Furthermore, the recurrence rate for hill-shape OPLL was higher at 30.8% compared to 10% for plateau-shape OPLL ( P = 0.05). CONCLUSION: Larger cervical ROM 1 year after surgery is related to repeat surgery at the same level as previous surgery, especially in laminectomy without fusion surgery.


Assuntos
Vértebras Cervicais , Ossificação do Ligamento Longitudinal Posterior , Reoperação , Humanos , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Seguimentos , Idoso , Laminectomia , Adulto , Estudos Retrospectivos , Resultado do Tratamento
11.
J Microbiol ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451451

RESUMO

Human adenoviruses (HAdVs) can infect various epithelial mucosal cells, ultimately causing different symptoms in infected organ systems. With more than 110 types classified into seven species (A-G), HAdV-D species possess the highest number of viruses and are the fastest proliferating. The emergence of new adenovirus types and increased diversity are driven by homologous recombination (HR) between viral genes, primarily in structural elements such as the penton base, hexon and fiber proteins, and the E1 and E3 regions. A comprehensive analysis of the HAdV genome provides valuable insights into the evolution of human adenoviruses and identifies genes that display high variation across the entire genome to determine recombination patterns. Hypervariable regions within genetic sequences correlate with functional characteristics, thus allowing for adaptation to new environments and hosts. Proteotyping of newly emerging and already established adenoviruses allows for prediction of the characteristics of novel viruses. HAdV-D species evolved in a direction that increased diversity through gene recombination. Bioinformatics analysis across the genome, particularly in highly variable regions, allows for the verification or re-evaluation of recombination patterns in both newly introduced and pre-existing viruses, ultimately aiding in tracing various biological traits such as virus tropism and pathogenesis. Our research does not only assist in predicting the emergence of new adenoviruses but also offers critical guidance in regard to identifying potential regulatory factors of homologous recombination hotspots.

13.
Proc Natl Acad Sci U S A ; 121(14): e2318039121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38536750

RESUMO

Melanosomes are specific organelles dedicated to melanin synthesis and accumulation in melanocytes. Autophagy is suggestively involved in melanosome degradation, although the potential underlying molecular mechanisms remain elusive. In selective autophagy, autophagy receptors and E3-ligases are the key factors conferring cargo selectivity. In B16F10 cells, ß-mangostin efficiently induced melanosome degradation without affecting other organelles such as mitochondria, peroxisomes, and the endoplasmic reticulum. Among various autophagy receptors, optineurin (OPTN) contributes TANK-binding kinase 1 (TBK1)-dependently to melanosome degradation and its knockdown inhibited ß-mangostin-mediated melanosome degradation. OPTN translocation to melanosomes was dependent on its ubiquitin-binding domain. Moreover, OPTN-mediated TBK1 activation and subsequent TBK1-mediated S187 OPTN phosphorylation were essential for melanosome degradation. ß-mangostin increased K63-linked melanosome ubiquitination. Finally, the E3-ligase RCHY1 knockdown inhibited the melanosome ubiquitination required for OPTN- and TBK1-phosphorylation as well as melanosome degradation. This study suggests that melanophagy, melanosome-selective autophagy, contributes to melanosome degradation, and OPTN and RCHY1 are an essential autophagy receptor and a E3-ligase, respectively, conferring cargo selectivity in melanophagy.


Assuntos
Autofagia , Melanossomas , Melanossomas/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Xantonas , Melanoma Experimental , Animais , Camundongos
14.
Neurointervention ; 19(1): 24-30, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38321887

RESUMO

PURPOSE: Cutting balloon-percutaneous transluminal angioplasty (CB-PTA) is a feasible treatment option for in-stent restenosis (ISR) after carotid artery stenting (CAS). However, the longterm durability and safety of CB-PTA for ISR after CAS have not been well established. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with ISR after CAS who had been treated with CB-PTA from 2012 to 2021 in our center. Detailed information of baseline characteristics, periprocedural and long-term outcomes, and follow-up imaging was collected. RESULTS: During 2012-2021, a total of 301 patients underwent CAS. Of which, CB-PTA was performed on 20 lesions exhibiting severe ISR in 18 patients following CAS. No patient had any history of receiving carotid endarterectomy or radiation therapy. These lesions were located at the cervical segment of the internal carotid artery (n=16), proximal external carotid artery (n=1), and distal common carotid artery (n=1). The median time interval between initial CAS and detection of ISR was 390 days (interquartile range 324-666 days). The follow-up period ranged from 9 months to 9 years with a median value of 21 months. Four patients (22.2%) were symptomatic. The average of stenotic degree before and after the procedure was 79.2% and 34.7%, respectively. Out of the 18 patients receiving CB-PTA, 16 (88.9%) did not require additional stenting, and 16 (88.9%) did not experience recurrent ISR during the follow-up period. Two patients who experienced recurrent ISR were successfully treated with CB-PTA and additional stenting. No periprocedural complication was observed in any case. CONCLUSION: Regarding favorable periprocedural and long-term outcomes in our single-center experience, CB-PTA was a feasible and safe option for the treatment of severe ISR after CAS.

15.
Eur J Neurol ; 31(6): e16261, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38411317

RESUMO

BACKGROUND AND PURPOSE: The etiological distribution of oculomotor nerve palsy has varied amongst the studies. This study aimed to define the clinical features and underlying etiologies of isolated oculomotor nerve palsy by recruiting patients from all departments in a referral-based university hospital. METHODS: The medical records of 672 patients who had a confirmed diagnosis of isolated oculomotor nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, South Korea, from 2003 to 2020 were reviewed. A proportion of the etiology of isolated oculomotor nerve palsy was also compared with that of patients pooled from the previous studies that were searched on PubMed in May 2022. RESULTS: The most common etiology was microvascular (n = 168, 26.5%), followed by vascular anomalies (n = 110, 17.4%), neoplastic (n = 86, 13.6%), inflammatory (n = 79, 12.5%), idiopathic (n = 60, 9.5%) and traumatic (n = 53, 8.4%). Neurologists were mainly involved in the management of microvascular and inflammatory oculomotor nerve palsies whilst ophthalmologists mainly participated in the care of idiopathic, neoplastic and traumatic palsies. Neurosurgeons mostly took care of oculomotor nerve palsy due to vascular anomalies. CONCLUSIONS: The proportion of etiologies of isolated oculomotor nerve palsy may differ according to the specialties involved in the management. The results of previous studies on the etiological distribution of isolated oculomotor nerve palsy should be interpreted with this consideration.


Assuntos
Doenças do Nervo Oculomotor , Humanos , Doenças do Nervo Oculomotor/etiologia , Doenças do Nervo Oculomotor/epidemiologia , Pessoa de Meia-Idade , Adulto , Masculino , Feminino , Idoso , Adolescente , Adulto Jovem , Criança , Idoso de 80 Anos ou mais , Pré-Escolar , República da Coreia/epidemiologia
16.
Eur J Neurol ; 31(5): e16242, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38344918

RESUMO

BACKGROUND AND PURPOSE: Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma. METHODS: A retrospective search of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed. RESULTS: Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain. CONCLUSIONS: This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.


Assuntos
Diplopia , Transtornos da Motilidade Ocular , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Transtornos da Motilidade Ocular/diagnóstico , Movimentos Oculares , Cerebelo , Paralisia
17.
ACS Biomater Sci Eng ; 10(3): 1461-1472, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38315631

RESUMO

The presence of ß-lactamase positive microorganisms imparts a pharmacological effect on a variety of organisms that can impact drug efficacy by influencing the function or composition of bacteria. Although studies to assess dynamic intra- and interspecies communication with bacterial communities exist, the efficacy of drug treatment and quantitative assessment of multiorganism response is not well understood due to the lack of technological advances that can be used to study coculture interactions in a dynamic format. In this study, we investigate how ß-lactamase positive microorganisms can neutralize the effect of ß-lactam antibiotics in a dynamic format at the inter- and intraspecies level using microbial bead technology. Three interactive models for the biological compartmentalization of organisms were demonstrated to evaluate the effect of ß-lactam antibiotics on coculture systems. Our model at the intraspecies level attempts to mimic the biofilm matrix more closely as a community-level feature of microorganisms, which acknowledges the impact of nondrug-resistant species in shaping the dynamic response. In particular, the results of intraspecies studies are highly supportive of the biofilm mode of bacterial growth, which can provide structural support and protect the bacteria from an assault on host or environmental factors. Our findings also indicate that ß-lactamase positive bacteria can neutralize the cytotoxic effect of ß-lactam antibiotics at the interspecies level when cocultured with cancer cells. Results were validated using ß-lactamase positive bacteria isolated from environmental niches, which can trigger phenotypical alteration of ß-lactams when cocultured with other organisms. Our compartmentalization strategy acts as an independent ecosystem and provides a new avenue for multiscale studies to assess intra- and interspecies interactions.


Assuntos
Antibacterianos , Ecossistema , Antibacterianos/química , beta-Lactamases/química , beta-Lactamas/farmacologia , beta-Lactamas/química , Monobactamas , Bactérias , Antibióticos beta Lactam
18.
Am Heart J ; 268: 45-52, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38006908

RESUMO

BACKGROUND: Hypertension adds to the pressure overload on the left ventricle (LV) in combination with aortic valve (AV) disease, but the optimal blood pressure (BP) targets for patients with AV disease remain unclear. We tried to investigate whether intensive BP control reduces LV hypertrophy in asymptomatic patients with aortic stenosis (AS) or aortic regurgitation (AR). METHODS: A total of 128 hypertensive patients with mild to moderate AS (n = 93) or AR (n = 35) were randomly assigned to intensive therapy, targeting a systolic BP <130 mm Hg, or standard therapy, targeting a systolic BP <140 mm Hg. The primary end point was the change in LV mass from baseline to the 24-month follow-up. Secondary end points included changes in severity of AV disease, LV volumes, ejection fraction and global longitudinal strain (GLS). RESULTS: The treatment groups were generally well balanced regarding the baseline characteristics. The mean (±SD) age of the patients was 68 ± 8 years and 48% were men. The mean BP was 145 ± 12/81 ± 10 mm Hg at baseline. Medication at baseline was similar between the 2 groups. The 2 treatment strategies resulted in a rapid and sustained difference in systolic BP (P < .05). At 24-month, the mean systolic BP was 129 ± 12 mm Hg in the intensive therapy group and 135 ± 14 mm Hg in the standard therapy group. No patient died or underwent AV surgery during follow-up in either of the groups. LV mass was changed from 189.5 ± 41.3 to 185.6 ± 41.5 g in the intensive therapy group (P = .19) and from 183.8 ± 38.3 to 194.0 ± 46.4 g in the standard therapy group (P < .01). The primary end point of change in LV mass was significantly different between the intensive therapy and the standard therapy group (-3.9 ± 20.2 g vs 10.3 ± 20.4 g; P = .0007). The increase in LV mass index was also significantly greater in the standard therapy group (P = .01). No significant differences in secondary end points (changes in severity of AV disease, LV volumes, ejection fraction and GLS) were observed between the treatment groups. CONCLUSIONS: Among hypertensive patients with AV disease, intensive hypertensive therapy resulted in a significant reduction in LV hypertrophy, although progression of AV disease was similar between the treatment groups. CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.gov (Number NCT03666351).


Assuntos
Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Hipertensão , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Hipertrofia Ventricular Esquerda/complicações , Volume Sistólico , Pressão Sanguínea , Fatores de Risco , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Função Ventricular Esquerda , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia
19.
J Glaucoma ; 33(1): 40-46, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37671496

RESUMO

PRCIS: Among children with unilateral glaucoma associated with Sturge-Weber syndrome (SWS), 7 of 47 demonstrated involvement in the fellow eye, and that group had had earlier first-eye surgery relative to the noninvolvement group. PURPOSE: The aim of this study was to determine the incidence of and risk factors for fellow-eye involvement in children with unilateral SWS-associated glaucoma. MATERIALS AND METHODS: Children diagnosed with a unilateral facial port-wine stain and ipsilateral glaucoma before the age of 5 and followed up for at least 5 years were enrolled. The incidence rates of fellow-eye glaucoma involvement were estimated per 100 person-years, and factors associated with a higher incidence of fellow-eye involvement were investigated. RESULTS: A total of 47 children [24 (51.1%) girls] with unilateral SWS-associated glaucoma were included. All of them had facial port-wine stain involving ophthalmic division of the trigeminal nerve, and 18 (38.3%) had neurological comorbidities. The mean age at glaucoma diagnosis was 0.8±1.2 years [range, 0.08 (1 mo)-4.0 y]. Over a median follow-up of 8.4 years, glaucoma was diagnosed in the fellow eye of 7 of the children (14.9%; incidence rate of 1.8 per 100 person-years), 6 of whom were girls ( P =0.097) and 5 of whom were diagnosed before the age of 4 years ( P =0.508). The fellow-eye-involvement group showed significantly higher mean follow-up intraocular pressure in the fellow eye, older age at first-eye surgery (both P <0.005), and higher frequency of choroidal hemangioma both at first onset and in fellow eyes ( P =0.026 and 0.019, respectively). CONCLUSIONS: In this cohort of SWS children diagnosed with unilateral glaucoma, the risk of fellow-eye involvement was higher in girls, within the first 4 years, and in cases with choroidal hemangioma. The fellow-eye-involved children underwent surgery on the first eye earlier than those without fellow-eye involvement.


Assuntos
Glaucoma , Hemangioma , Mancha Vinho do Porto , Síndrome de Sturge-Weber , Criança , Feminino , Humanos , Recém-Nascido , Pré-Escolar , Masculino , Síndrome de Sturge-Weber/complicações , Síndrome de Sturge-Weber/diagnóstico , Síndrome de Sturge-Weber/epidemiologia , Incidência , Mancha Vinho do Porto/diagnóstico , Pressão Intraocular , Glaucoma/complicações , Glaucoma/diagnóstico , Glaucoma/epidemiologia , Hemangioma/complicações , Fatores de Risco
20.
Stroke ; 54(12): 3002-3011, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37942640

RESUMO

BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Adulto Jovem , Adulto , AVC Isquêmico/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , Isquemia Encefálica/complicações , Estudos Prospectivos , Anticoagulantes/uso terapêutico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/complicações , Resultado do Tratamento
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