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BACKGROUND: Despite the availability of effective therapies for patients with chronic kidney disease, type 2 diabetes, and hypertension (the kidney-dysfunction triad), the results of large-scale trials examining the implementation of guideline-directed therapy to reduce the risk of death and complications in this population are lacking. METHODS: In this open-label, cluster-randomized trial, we assigned 11,182 patients with the kidney-dysfunction triad who were being treated at 141 primary care clinics either to receive an intervention that used a personalized algorithm (based on the patient's electronic health record [EHR]) to identify patients and practice facilitators to assist providers in delivering guideline-based interventions or to receive usual care. The primary outcome was hospitalization for any cause at 1 year. Secondary outcomes included emergency department visits, readmissions, cardiovascular events, dialysis, and death. RESULTS: We assigned 71 practices (enrolling 5690 patients) to the intervention group and 70 practices (enrolling 5492 patients) to the usual-care group. The hospitalization rate at 1 year was 20.7% (95% confidence interval [CI], 19.7 to 21.8) in the intervention group and 21.1% (95% CI, 20.1 to 22.2) in the usual-care group (between-group difference, 0.4 percentage points; P = 0.58). The risks of emergency department visits, readmissions, cardiovascular events, dialysis, or death from any cause were similar in the two groups. The risk of adverse events was also similar in the trial groups, except for acute kidney injury, which was observed in more patients in the intervention group (12.7% vs. 11.3%). CONCLUSIONS: In this pragmatic trial involving patients with the triad of chronic kidney disease, type 2 diabetes, and hypertension, the use of an EHR-based algorithm and practice facilitators embedded in primary care clinics did not translate into reduced hospitalization at 1 year. (Funded by the National Institutes of Health and others; ICD-Pieces ClinicalTrials.gov number, NCT02587936.).
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Diabetes Mellitus Tipo 2 , Hospitalização , Hipertensão , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Hospitalização/estatística & dados numéricos , Hipertensão/epidemiologia , Hipertensão/terapia , Diálise Renal , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Medicina de Precisão , Registros Eletrônicos de Saúde , Algoritmos , Atenção Primária à Saúde/estatística & dados numéricosRESUMO
SIGNIFICANCE STATEMENT: ESKD incidence has changed substantially in the past four decades, but differences by age and race have been unexplored. Using data from the United States Renal Data System, we found that ESKD incidence rose for Black and White teenagers, adults, and older adults for two decades beginning in 1980. Growth in incidence slowed for most groups by 1993, and by 2006, the annual percent change (APC) in ESKD incidence had declined for all groups, except White adults, for whom rates continued to rise. By 2019, ESKD incidence among Black and White adolescents nearly returned to 1980 levels, but no other group achieved that degree of improvement. Nonetheless, the ESKD incidence rate among Black American patients exceeds that of White patients in every age group. Distinct patterns in ESKD incidence among patients of different age, sex, and racial groups are shown. These findings could reflect changes in dialysis acceptance rates, access to preventive health care, incidence of diabetes mellitus, implementation of evidence-based guidelines for treatment of CKD, or other unrecognized factors. There may be population-specific opportunities to change the growth of the US ESKD population and address current racial disparities. BACKGROUND: Substantial changes in ESKD incidence over four decades among Black and White Americans of different ages have been incompletely explored. METHODS: We analyzed United States Renal Data System data from 1980 to 2019 to determine ESKD incidence trends among Black and White adolescent (13-17 years), adult (18-64 years), and older adult (≥65) populations. We used the National Cancer Institute Joinpoint Regression Program to estimate annual percent change (APC) in ESKD incidence and to define points in time where a statistically significant change in APC slope occurred for each group. RESULTS: ESKD incidence rose after 1980 for all groups, although the trends differed ( P < 0.001). Growth in incidence slowed for most by 1993, and by 2006, the APC in ESKD incidence had declined for all groups, except White adults, for whom rates continued to rise ( P < 0.05). By 2019, ESKD incidence among Black and White adolescents nearly returned to 1980 levels, but no other group achieved that degree of improvement. Nonetheless, the ESKD incidence among Black American patients exceeds that of White patients in every age group. CONCLUSIONS: Distinct patterns in ESKD incidence among patients of different age, sex, and racial groups are shown. These findings could reflect changes in dialysis acceptance rates, access to preventive health care, incidence of diabetes mellitus, implementation of evidence-based guidelines for treatment of CKD, or other unrecognized factors. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_03_13_ASN0000000000000310.mp3.
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Diabetes Mellitus , Insuficiência Renal Crônica , Adolescente , Idoso , Humanos , Negro ou Afro-Americano , Incidência , Grupos Raciais , Estados Unidos/epidemiologia , Brancos , Adulto Jovem , Adulto , Pessoa de Meia-IdadeRESUMO
PURPOSE: Diabetes and obesity, components of the metabolic syndrome (MetS), are risk factors for urinary incontinence (UI) and chronic kidney disease (CKD). We interrogated US population-based data to explore independent, sex-specific associations between nondiabetic MetS, with and without obesity, and UI and/or CKD. MATERIALS AND METHODS: We analyzed data from 8586 males and 8420 females ≥20 years from the National Health and Nutrition Examination Survey. Multivariable logistic regression models were used to examine associations of UI or CKD with diabetes and 4 nondiabetic obesity/metabolic phenotypes: non-MetS/nonobese, MetS/nonobese, non-MetS/obese, and MetS/obese. Multinominal logistic regression models were used to assess associations of co-occurring UI/CKD with obesity/metabolic phenotypes. RESULTS: Male MetS/obese participants had increased odds of any UI (1.25; 95% CI 1.00-1.57) and urgency UI (1.36; 1.03-1.80), compared with non-MetS/nonobese participants. Female MetS/obese participants had increased odds of any UI (2.16; 95% CI 1.76-2.66), stress UI (1.51; 1.21-1.87), and mixed UI (1.66; 1.31-2.11) compared with non-MetS/nonobese participants. The odds of co-occurring UI/CKD were increased relative to either condition alone in persons with diabetes, and in males with MetS/obese phenotypes and females with MetS phenotypes as compared to same sex participants with neither obesity nor MetS. CONCLUSIONS: We found novel associations between MetS/obese and urgency UI in males without diabetes, and between SUI and both MetS and obesity in females without diabetes. Odds estimates for UI/CKD were increased by existing obesity or MetS as compared to those for UI or CKD alone. Improved understanding of modifiable factors associated with UI will inform prevention and treatment opportunities.
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Diabetes Mellitus , Síndrome Metabólica , Insuficiência Renal Crônica , Incontinência Urinária por Estresse , Incontinência Urinária , Masculino , Humanos , Feminino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Inquéritos Nutricionais , Obesidade/complicações , Obesidade/epidemiologia , Diabetes Mellitus/epidemiologia , Incontinência Urinária/etiologia , Incontinência Urinária/complicações , Fatores de Risco , Incontinência Urinária por Estresse/complicações , Insuficiência Renal Crônica/diagnósticoRESUMO
Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.
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Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Masculino , Estadiamento de Neoplasias , Vacina BCG/uso terapêuticoRESUMO
Pediatric fibromyxoid soft tissue tumors may be associated with gene fusions such as YHWAZ::PLAG1, with only three reported cases in the literature. We present the fourth case, a 13-year-old male with a pediatric fibromyxoid brachial plexus tumor with YWHAZ::PLAG1 gene fusion. This is also the first case to be reported in an adolescent, in the brachial plexus, and in the Philippines. The patient presented with a 10-year history of a slowly growing left supraclavicular mass and a 1-year history of intermittent dysesthesia in the left upper extremity. Neurologic examination was unremarkable. Imaging revealed a large left supraclavicular lesion with intrathoracic extension. Surgical excision was performed, and histopathology revealed a fibromyxoid tumor with YWHAZ::PLAG1 gene fusion. Although previous examples of this gene fusion pointed toward lipoblastoma as their primary pathology, our tumor does not completely fulfill the current diagnostic criteria for a lipoblastoma and may represent an intermediate form of the disease. Our case is unique not only because it is the first reported adolescent patient harboring such a lesion but also because of the relatively lengthy natural history exhibited by the tumor prior to its resection. This provided us with valuable information about its behavior, which suggests a more indolent growth pattern. This case also highlights the clinical importance of molecular testing of tumors, where recognition of disease entities can assist clinicians in deciding and advocating for the proper management.
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Plexo Braquial , Humanos , Masculino , Adolescente , Plexo Braquial/cirurgia , Fusão Gênica/genética , Proteínas 14-3-3/genética , Fibroma/genética , Fibroma/cirurgia , Neoplasias do Sistema Nervoso Periférico/genética , Neoplasias do Sistema Nervoso Periférico/cirurgia , Neoplasias do Sistema Nervoso Periférico/patologia , Proteínas de Ligação a DNA/genética , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/cirurgia , Neoplasias de Tecidos Moles/patologiaRESUMO
Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive lesioning technique used to treat movement disorders such as essential tremor (ET), Parkinson's disease (PD), and X-linked dystonia-parkinsonism (XDP). We would like to report our experience in establishing and developing our MRgFUS program and preliminary results. Adult patients with tremor-dominant PD (TDPD), ET, and XDP were considered for initial screening (neurologic evaluation, skull density ratio [SDR] determination). Eligible patients underwent secondary screening (neurosurgical and neuropsychological evaluation, psychiatric and medical clearance). During the procedure, a neuro-anesthesiologist and neurologist were also present to monitor the patient and perform neurologic evaluation, respectively. Clinical follow-up was scheduled at 2 weeks post-treatment, then at every 3 months. A total of 30 patients underwent MRgFUS treatment: 22 TDPD, 6 XDP, and 2 ET. The mean age was 55.7 years, and majority were male (86.7%). Mean disease duration was 8.6 years. Mean SDR was 0.46. The targets for TDPD and ET were the contralateral ventral intermediate nucleus of the thalamus; for XDP, it was the pallidothalamic tract. The mean maximum temperature was 59.8oC; number of sonocations, 7.3; and treatment time, 64.6 min. Majority of patients improved after the procedure. Transient intraprocedural adverse events (headache, dizziness) were reported in 20% of patients while post-procedural events (mild weakness, numbness) were seen in 16.7%. Only 26.7% of patients had follow-up data. Despite the unique challenges encountered, MRgFUS treatment is feasible in resource-limited settings. Additional steps would have to be made to develop and improve the program.
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Tremor Essencial , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Tremor Essencial/terapia , Idoso , Adulto , Filipinas , Doença de Parkinson/terapia , Resultado do Tratamento , Região de Recursos LimitadosRESUMO
Thumb carpometacarpal (CMC) osteoarthritis (OA) has been one of the most common locations of hand OA. CMC OA disproportionately occurs in females over males. In severe cases, surgical intervention may be needed. However, to determine the effects of surgical treatment, normative, pre-, and postsurgery function must be understood. The goals of this work were to compare the thumb motion and force abilities of older healthy (OH) females without CMC OA to those of females with CMC OA and who received ligament reconstruction with tendon interposition (LRTI) surgery at time points presurgery, 3- and 6-months postsurgery. On average, CMC OA participants 3- and 6-months postsurgery showed 35.6% and 32.9% less overall metacarpal motion compared to presurgery, 31.9% and 29.1% less than OH, and exhibited altered motion. Metacarpal flexion/extension and abduction/adduction ranges were 51.9 deg and 43.4 deg for OH, 52.9 deg and 40.3 deg presurgery, 39.9 deg and 33.5 deg at 3-months, and 42.6 deg and 32.7 deg at 6-months postsurgery. On average, participants had increased force generation at 6-months postsurgery compared to presurgery, and 20% of participants returned to the level of OH females. These data sets highlight changes in thumb metacarpal movement and thumb force generation due to disease and surgical intervention. This work has the ability to support both surgeons and patients through improved outcome assessments as well as additional data to inform the decision process on intervention.
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Articulações Carpometacarpais , Osteoartrite , Masculino , Humanos , Feminino , Articulações Carpometacarpais/cirurgia , Polegar/cirurgia , Osteoartrite/cirurgia , Tendões , Movimento (Física)RESUMO
The thumb carpometacarpal (CMC) joint is one of the most likely joints to develop osteoarthritis (OA). If conservative treatments fail to alleviate symptoms, surgery may be pursued. Kinematic outcomes of CMC surgery techniques have been described, but current tools have limitations in capturing motion abilities. The goals of this study were (1) develop a new and robust set of kinematic outcome measures, and apply them to (2) a cohort of younger and older control individuals without CMC OA to determine age and sex-related changes, and (3) a cohort of participants with CMC OA before, 3 months, and 6 months after undergoing thumb ligament reconstruction with tendon interposition surgery to detect the impacts of surgery. 52 (26 males, 26 females) control and 18 (3 males, 15 females) surgical participants were tested. Kinematics were investigated using motion capture by mapping the three-dimensional motion space of the whole thumb, and two-dimensional motion boundaries of the metacarpal (MC) and proximal phalange (PP). Visual analog pain score was recorded. Older control participants had shifted regions of motion compared to younger participants (p ≤ 0.027), suggesting asymptomatic CMC wear. Control females had 31% more metacarpophalangeal (MCP) motion than control males (p = 0.013), which could alter loading paths through the CMC joint and increase OA risk. Pain at 6 months postsurgery was 72% less than presurgery (p < 0.001), but motion abilities were 20-28% less than presurgery (p ≤ 0.074) and 24-40% less than control participants (p ≤ 0.066). These techniques have the possibility of identifying presymptomatic motion changes, including those at the metacarpophalangeal joint in CMC OA progression.
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Articulações Carpometacarpais , Osteoartrite , Masculino , Feminino , Humanos , Polegar/cirurgia , Fenômenos Biomecânicos , Osteoartrite/cirurgia , Articulação Metacarpofalângica/cirurgia , Articulações Carpometacarpais/cirurgia , Ligamentos Articulares , DorRESUMO
On constate des pratiques très variées en matière d'évaluation et de prise en charge des jeunes nourrissons fiévreux. Bien que la plupart des jeunes nourrissons fiévreux mais dans un bon état général soient atteints d'une maladie virale, il est essentiel de détecter ceux qui sont à risque de présenter des infections bactériennes invasives, notamment une bactériémie et une méningite bactérienne. Le présent document de principes porte sur les nourrissons de 90 jours ou moins dont la température rectale est de 38,0 °C ou plus, mais qui semblent être dans un bon état général. Il est conseillé d'appliquer les récents critères de stratification du risque pour orienter la prise en charge, ainsi que d'intégrer la procalcitonine à l'évaluation diagnostique. Les décisions sur la prise en charge des nourrissons qui satisfont aux critères de faible risque devraient refléter la probabilité d'une maladie, tenir compte de l'équilibre entre les risques et les préjudices potentiels et faire participer les parents ou les proches aux décisions lorsque diverses options sont possibles. La prise en charge optimale peut également dépendre de considérations pragmatiques, telles que l'accès à des examens diagnostiques, à des unités d'observation, à des soins tertiaires et à un suivi. Des éléments particuliers, tels que la mesure de la température, le risque d'infection invasive à Herpes simplex et la fièvre postvaccinale, sont également abordés.
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The evaluation and management of young infants presenting with fever remains an area of significant practice variation. While most well-appearing febrile young infants have a viral illness, identifying those at risk for invasive bacterial infections, specifically bacteremia and bacterial meningitis, is critical. This statement considers infants aged ≤90 days who present with a rectal temperature ≥38.0°C but appear well otherwise. Applying recent risk-stratification criteria to guide management and incorporating diagnostic testing with procalcitonin are advised. Management decisions for infants meeting low-risk criteria should reflect the probability of disease, consider the balance of risks and potential harm, and include parents/caregivers in shared decision-making when options exist. Optimal management may also be influenced by pragmatic considerations, such as access to diagnostic investigations, observation units, tertiary care, and follow-up. Special considerations such as temperature measurement, risk for invasive herpes simplex infection, and post-immunization fever are also discussed.
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Síndrome Metabólica , Inquéritos Nutricionais , Obesidade , Insuficiência Renal Crônica , Incontinência Urinária , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Obesidade/epidemiologia , Obesidade/complicações , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Estados Unidos/epidemiologia , Diabetes Mellitus/epidemiologiaRESUMO
Cancer cell-killing by CD8+ T cells demands effective tumor antigen presentation by human leukocyte antigen class I (HLA-I) molecules. Screening and designing highly immunogenic neoantigens require quantitative computations to reliably predict HLA-peptide binding affinities. Here, with all-atom molecular dynamics (MD) simulations and free energy perturbation (FEP) methods, we design a collection of antigenic peptide candidates through in silico mutagenesis studies on immunogenic neoantigens, yielding enhanced binding affinities to HLA-B*44:02. In-depth structural dissection shows that introducing positively charged residues such as arginine to position 6 or lysine to position 7 of the candidates triggers conformational shifts in both peptides and the antigen-binding groove of the HLA, following the "induced-fit" mechanism. Enhancement in binding affinities compared to the wild-type was found in three out of five mutated candidates. The HLA pocket, capable of accommodating positively charged residues in positions from 5 to 7, is designated as the "dynamic pocket". Taken together, we showcase an effective structure-based binding affinity optimization framework for antigenic peptides of HLA-B*44:02 and underscore the importance of dynamic nature of the antigen-binding groove in concert with the anchoring motifs. This work provides structural insights for rational design of favorable HLA-peptide bindings and future developments in neoantigen-based therapeutics.
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Simulação de Dinâmica Molecular , Peptídeos , Ligação Proteica , Humanos , Peptídeos/química , Peptídeos/imunologia , Antígeno HLA-B44/química , Antígeno HLA-B44/imunologia , Antígeno HLA-B44/genética , Simulação por Computador , Sítios de Ligação , Conformação ProteicaRESUMO
Background: External ventricular drain (EVD) insertion is a common neurosurgical procedure used to treat acute hydrocephalus. In this report, we present a rare case of an EVD that was initially correctly placed within the frontal horn but subsequently migrated to the cisterna magna, the first to be reported in the literature. Case Description: A 46-year-old man with postoperative meningitis and hydrocephalus underwent EVD insertion using an improvised EVD system. The EVD was also used as a route for the administration of intraventricular antibiotics. The patient was restless and agitated during his treatment, causing him to move his head frequently. Serial computed tomography scans showed that the EVD was initially correctly placed within the frontal horn and then migrated to the cisterna magna. Conclusion: Inward catheter migration is a rare complication of EVD insertion and is an important concern since it may cause neurologic deficits and potentially harmful sequelae. We have also highlighted measures that can be taken to prevent a similar event in the future.
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BACKGROUND: Better living conditions and health care advancements have improved life expectancy worldwide, increasing the number of older patients who require neurosurgery. We would like to report our experience with geriatric neurosurgical patients at our institution. METHODS: This is a retrospective study on geriatric patients (aged ≥ 65 years) who underwent neurosurgery at our center between 2015 and 2022. Data on age, sex, comorbidities, pre-morbid status, type of admission, diagnosis, operation, complications, short-term outcome, hospital length of stay (LOS), and 30-day readmission were collected. Descriptive statistics and multiple regression analysis were used. RESULTS: A total of 327 patients were included. The mean age was 70.4 years and 51.3 % were female. Majority (70.6 %) had at least one comorbid condition, most commonly hypertension. Most patients were admitted through emergency systems (80.1 %), with 40.4 % consulting for traumatic brain injury. The top diagnoses were chronic subdural hematoma (35.2 %), ruptured intracerebral aneurysm (15.6 %), and meningioma (10.1 %). The most common procedures were burrhole drainage of hematoma (34.8 %), brain tumor excision (16.7 %), and aneurysm clipping (14.6 %). The post-operative complication rate was 15.2 %, and mean LOS was 16.7 days. Majority of patients (86.9 %) were discharged home, and 2.8 % were readmitted within 30 days. The 30-day mortality rate was 13.1 %. Lower pre-operative GCS, certain comorbidities, and intra- and post-operative complications were significantly associated with mortality and LOS. CONCLUSION: Advanced age alone should not be a contraindication to surgery; other factors such as frailty and comorbid conditions should also be considered. Proper patient selection and preoperative preparation are key to achieving good outcomes.
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Goal: Distance information is highly requested in assistive smartphone Apps by people who are blind or low vision (PBLV). However, current techniques have not been evaluated systematically for accuracy and usability. Methods: We tested five smartphone-based distance-estimation approaches in the image center and periphery at 1-3 meters, including machine learning (CoreML), infrared grid distortion (IR_self), light detection and ranging (LiDAR_back), and augmented reality room-tracking on the front (ARKit_self) and back-facing cameras (ARKit_back). Results: For accuracy in the image center, all approaches had <±2.5 cm average error, except CoreML which had ±5.2-6.2 cm average error at 2-3 meters. In the periphery, all approaches were more inaccurate, with CoreML and IR_self having the highest average errors at ±41 cm and ±32 cm respectively. For usability, CoreML fared favorably with the lowest central processing unit usage, second lowest battery usage, highest field-of-view, and no specialized sensor requirements. Conclusions: We provide key information that helps design reliable smartphone-based visual assistive technologies to enhance the functionality of PBLV.
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Biological control uses naturally occurring antagonists such as bacteria or fungi for environmentally friendly control of plant pathogens. Bacillus spp. have been used for biocontrol of numerous plant and insect pests and are well-known to synthesize a variety of bioactive secondary metabolites. We hypothesized that bacteria isolated from agricultural soil would be effective antagonists of soilborne fungal pathogens. Here, we show that the Delaware soil isolate Bacillus velezensis strain S4 has in vitro activity against soilborne and foliar plant pathogenic fungi, including two with a large host range, and one oomycete. Further, this strain shows putative protease and cellulase activity, consistent with our prior finding that the genome of this organism is highly enriched in antifungal and antimicrobial biosynthetic gene clusters. We demonstrate that this bacterium causes changes to the fungal and oomycete hyphae at the inhibition zone, with some of the hyphae forming bubble-like structures and irregular branching. We tested strain S4 against Magnaporthe oryzae spores, which typically form germ tubes and penetration structures called appressoria, on the surface of the leaf. Our results suggest that after 12 hours of incubation with the bacterium, fungal spores form germ tubes, but instead of producing appressoria, they appear to form rounded, bubble-like structures. Future work will investigate whether a single antifungal molecule induces all these effects, or if they are the result of a combination of bacterially produced antimicrobials.
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Purpose: To investigate the contributions of the microstructural and metabolic brain environment to glaucoma and their association with visual field (VF) loss patterns by using advanced diffusion magnetic resonance imaging (dMRI), proton magnetic resonance spectroscopy (MRS), and clinical ophthalmic measures. Methods: Sixty-nine glaucoma and healthy subjects underwent dMRI and/or MRS at 3 Tesla. Ophthalmic data were collected from VF perimetry and optical coherence tomography. dMRI parameters of microstructural integrity in the optic radiation and MRS-derived neurochemical levels in the visual cortex were compared among early glaucoma, advanced glaucoma, and healthy controls. Multivariate regression was used to correlate neuroimaging metrics with 16 archetypal VF loss patterns. We also ranked neuroimaging, ophthalmic, and demographic attributes in terms of their information gain to determine their importance to glaucoma. Results: In dMRI, decreasing fractional anisotropy, radial kurtosis, and tortuosity and increasing radial diffusivity correlated with greater overall VF loss bilaterally. Regionally, decreasing intra-axonal space and extra-axonal space diffusivities correlated with greater VF loss in the superior-altitudinal area of the right eye and the inferior-altitudinal area of the left eye. In MRS, both early and advanced glaucoma patients had lower gamma-aminobutyric acid (GABA), glutamate, and choline levels than healthy controls. GABA appeared to associate more with superonasal VF loss, and glutamate and choline more with inferior VF loss. Choline ranked third for importance to early glaucoma, whereas radial kurtosis and GABA ranked fourth and fifth for advanced glaucoma. Conclusions: Our findings highlight the importance of non-invasive neuroimaging biomarkers and analytical modeling for unveiling glaucomatous neurodegeneration and how they reflect complementary VF loss patterns.
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Tomografia de Coerência Óptica , Testes de Campo Visual , Campos Visuais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Campos Visuais/fisiologia , Tomografia de Coerência Óptica/métodos , Idoso , Transtornos da Visão/fisiopatologia , Transtornos da Visão/metabolismo , Imagem de Difusão por Ressonância Magnética , Glaucoma/fisiopatologia , Glaucoma/metabolismo , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Glaucoma de Ângulo Aberto/metabolismo , Glaucoma de Ângulo Aberto/fisiopatologia , Córtex Visual/metabolismo , Córtex Visual/diagnóstico por imagem , Espectroscopia de Prótons por Ressonância Magnética , Adulto , Pressão Intraocular/fisiologiaRESUMO
Excitotoxicity from the impairment of glutamate uptake constitutes an important mechanism in neurodegenerative diseases such as Alzheimer's, multiple sclerosis, and Parkinson's disease. Within the eye, excitotoxicity is thought to play a critical role in retinal ganglion cell death in glaucoma, diabetic retinopathy, retinal ischemia, and optic nerve injury, yet how excitotoxic injury impacts different retinal layers is not well understood. Here, we investigated the longitudinal effects of N-methyl-D-aspartate (NMDA)-induced excitotoxic retinal injury in a rat model using deep learning-assisted retinal layer thickness estimation. Before and after unilateral intravitreal NMDA injection in nine adult Long Evans rats, spectral-domain optical coherence tomography (OCT) was used to acquire volumetric retinal images in both eyes over 4 weeks. Ten retinal layers were automatically segmented from the OCT data using our deep learning-based algorithm. Retinal degeneration was evaluated using layer-specific retinal thickness changes at each time point (before, and at 3, 7, and 28 days after NMDA injection). Within the inner retina, our OCT results showed that retinal thinning occurred first in the inner plexiform layer at 3 days after NMDA injection, followed by the inner nuclear layer at 7 days post-injury. In contrast, the retinal nerve fiber layer exhibited an initial thickening 3 days after NMDA injection, followed by normalization and thinning up to 4 weeks post-injury. Our results demonstrated the pathological cascades of NMDA-induced neurotoxicity across different layers of the retina. The early inner plexiform layer thinning suggests early dendritic shrinkage, whereas the initial retinal nerve fiber layer thickening before subsequent normalization and thinning indicates early inflammation before axonal loss and cell death. These findings implicate the inner plexiform layer as an early imaging biomarker of excitotoxic retinal degeneration, whereas caution is warranted when interpreting the ganglion cell complex combining retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses in conventional OCT measures. Deep learning-assisted retinal layer segmentation and longitudinal OCT monitoring can help evaluate the different phases of retinal layer damage upon excitotoxicity.