RESUMEN
This research focused on distinguishing distinct matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) spectral signatures of three Enterococcus species. We evaluated and compared the predictive performance of four supervised machine learning algorithms, K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF), to accurately classify Enterococcus species. This study involved a comprehensive dataset of 410 strains, generating 1640 individual spectra through on-plate and off-plate protein extraction methods. Although the commercial database correctly identified 76.9% of the strains, machine learning classifiers demonstrated superior performance (accuracy 0.991). In the RF model, top informative peaks played a significant role in the classification. Whole-genome sequencing showed that the most informative peaks are biomarkers connected to proteins, which are essential for understanding bacterial classification and evolution. The integration of MALDI-TOF MS and machine learning provides a rapid and accurate method for identifying Enterococcus species, improving healthcare and food safety.
Asunto(s)
Enterococcus , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Aprendizaje Automático Supervisado , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Enterococcus/clasificación , Enterococcus/química , Enterococcus/aislamiento & purificación , Enterococcus/genética , Algoritmos , Máquina de Vectores de Soporte , Técnicas de Tipificación Bacteriana/métodos , Aprendizaje AutomáticoRESUMEN
Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals. The comorbidity of the two neurological disorders represents a grave health threat to older populations. This review presents a brief background of the development of novel concepts and their clinical potentials. The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca 2+ influx is critical for neuronal function. An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca 2+ mainly via N-methyl-D-aspartate receptors, particularly of those at the extrasynaptic site. This Ca 2+ -evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity. Furthermore, mild but sustained Ca 2+ increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic, but gradually set off deteriorating Ca 2+ -dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways. Based on the Ca 2+ hypothesis of Alzheimer's disease and recent advances, this Ca 2+ -activated "silent" degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis. The N-methyl-D-aspartate receptor subunit GluN3A, primarily at the extrasynaptic site, serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity. Ischemic stroke and Alzheimer's disease, therefore, share an N-methyl-D-aspartate receptor- and Ca 2+ -mediated mechanism, although with much different time courses. It is thus proposed that early interventions to control Ca 2+ homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia. This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.
RESUMEN
With complex topography and geomorphology, mountainous cities possess abundant natural resources. They are constrained by ecological environment and topographic conditions, leading to a prominent contradiction between urbanization development and ecological protection. As a result, ecosystem services (ESs) are under greater regulatory pressure. The identification of ecosystem services bundles (ESBs) can be the foundation for developing zonal ecological protection planning policies. We took Chongqing as a case study, investigated the impact mechanisms of socio-ecological factors on the level of ES supply in each ESB. The findings reveal that: (1) The quantitative assessment of ESs for 2000, 2010, and 2020 showed that ESs were temporally stable and spatially heterogeneous. Areas with high supplies of food production (FP) and water yield (WY) were predominantly found in the northwestern cropland and urban built-up regions, whereas high supply areas for the other four ESs were primarily located in the northeastern Dabashan Mountains and the southern Wuling Mountains. (2) The quantification of trade-offs and synergies between ESs showed that FP had a trade-off effect with all five other ESs, while most other ES pairs exhibited synergistic effects. It was found that the interrelationships produced changes over time. (3) Then, three types of ESBs were identified. After examining the influence mechanisms of socio-ecological factors across the three ESBs, individual ESs were found to have essentially the same types of main impact factors in three ESBs, but varies in impact. (4) Finally, with reference to changes in ES levels and interrelationships and the driving mechanisms of socio-ecological factors in each zone, this study proposed zonal strategies for managing ecosystem services and optimizing territorial space based on the geographic characteristics and socio-economic development in different ESBs, with the goal of attaining sustainable urban development and improve human welfare.
RESUMEN
In this paper, a novel numerical model capable of high-resolution, accurate simulation of the accumulation, wash-off, and migration of nonpoint source (NPS) pollutants on roads is proposed, effectively addressing the challenge of limited pipe network data for high-density urban building communities. This approach is based on a 1D-2D hydrodynamic and water quality dynamic bidirectional coupling model: GAST-SWMM. The calculation accuracy of the GAST two-dimensional road NPS wash-off model is validated via comparison with experimental data. The obtained Nash-Sutcliffe efficiency (NSE) is greater than 0.8. Moreover, the model was used to simulate the NPSs in a densely populated urban region of Xi'an, China, lacking building community pipeline data. The NPS pollutant transport and fate under the influence of both road runoff and the building community hydrodynamic water quality during rainfall events with a specific return period were examined. The proposed model can effectively and accurately replicate the accumulation and removal of NPS pollutants on a two-dimensional road and their dynamic interaction with the drainage network. With increasing rainfall return period, the peak time of the surface contaminant total load is postponed. The maximum surface pollutant load durations during rainfall events with 2-, 10-, and 50-year return periods are 60, 75, and 80 minutes, respectively. During the peak surface pollutant load time, the overflow pollutant fraction can exceed 85% for a 50-year rainfall return period. The simulation method presented in this paper accurately captures the spatial and temporal variations in NPS pollutants in densely populated urban areas, even when pipe network data for building communities are lacking. This method offers valuable technical assistance for urban environmental management and water quality protection.
RESUMEN
Coal mining endangers the environment by contaminating of soil, surface, and ground water with coal mine drainage water (CMW) polluted by heavy metals. Microalgal cultures, hyper-accumulators of heavy metals, represent a promising solution for CMW biotreatment. A bottleneck of this approach is the availability of microalgal strains that combine a large capacity for heavy metal biocapture with a high resilience to their toxic effects. Biotopes contaminated with heavy metals are frequently inhabited by microalgae evolved to be resilient to heavy metal toxicity. Therefore, the autochthonous (locally isolated) microalgal strains are a priori considered to be superior for biotreatment of heavy metal-polluted waste streams. Still, strains from biocollections combine a high pollutant resilience with other biotechnologically important traits such as high productivity, high CO2 sequestration rate etc. Moreover, the strains available "off-the-shelf" would enable rapid development of bioprocesses. Here, we compared the efficiency of CMW biotreatment with autochthonous (isolated from the coal mine drainage sump) and allochthonous microalgae (from a geographically distant phosphate-polluted site). Both autochthonous strains and allochthonous strains turned to be interchangeable under our experimental conditions. Still, the autochthonous strains showed a higher capacity for sequestration of iron, zinc, and manganese, the specific pollutants of the studied CMW. It can be important when the duration of unattended exploitation of the CMW treatment facility is a priority or spikes of the heavy metal concentration in CMW are expected. Therefore, the "off-the-shelf" strains can be a plausible solution for rapid development of CMW treatment technologies from scratch (although screening for acute toxicity of CMW is imperative). On the other hand, locally isolated strains can offer distinct advantages and should be always considered if sufficient time and other resources are available for the development of microalgae-based process for CMW treatment.
RESUMEN
Polyethylene terephthalate (PET) is one of the most widely produced man-made polymers and is a significant contributor to microplastics pollution. The environmental and human health impacts of microplastics pollution have motivated a concerted effort to develop microbe- and enzyme-based strategies to degrade PET and similar plastics. A PETase derived from the bacteria Ideonella sakaiensis was previously shown to enzymatically degrade PET, triggering multidisciplinary efforts to improve the robustness and activity of this and other PETases. However, because these enzymes only erode the surface of the insoluble PET substrate, it is difficult to measure standard kinetic parameters, such as kon, koff and kcat, complicating interpretation of the activity of mutants using traditional enzyme kinetics frameworks. To address this challenge, we developed a single-molecule microscopy assay that quantifies the landing rate and binding duration of quantum dot-labeled PETase enzymes interacting with a surface-immobilized PET film. Wild-type PETase binding durations were well fit by a biexponential with a fast population having a 2.7 s time constant, interpreted as active binding events, and a slow population interpreted as non-specific binding interactions that last tens of seconds. A previously described hyperactive mutant, S238F/W159H had both a faster apparent on-rate and a slower off-rate than wild-type PETase, potentially explaining its enhanced activity. Because this single-molecule approach provides a more detailed mechanistic picture of PETase enzymatic activity than standard bulk assays, it should aid future efforts to engineer more robust and active PETases to combat global microplastics pollution.
RESUMEN
Recent progress in the study of Parkinson's disease (PD) has highlighted the pivotal role of beta oscillations within the basal ganglia-thalamo-cortical network in modulating motor symptoms. Predominantly manifesting as transient bursts, these beta oscillations are central to the pathophysiology of PD motor symptoms, especially bradykinesia. Our central hypothesis is that increased bursting duration in cortex, coupled with kinematics of movement, disrupts the typical flow of neural information, leading to observable changes in motor behavior in PD. To explore this hypothesis, we employed an integrative approach, analyzing the interplay between moment-to-moment brain dynamics and movement kinematics, and the modulation of these relationships by therapeutic deep brain stimulation (DBS). Local field potentials were recorded from the hand motor (M1) and premotor cortical (PM) areas, and internal Globus Pallidus (GPi) in 26 PD patients undergoing DBS implantation surgery. Participants executed rapid alternating hand movements in 30-second blocks, both with and without therapeutic pallidal stimulation. Behaviorally, the analysis revealed bradykinesia, with hand movement cycle width increasing linearly over time during DBS-OFF blocks. Crucially, there was a moment-to-moment correlation between M1 low beta burst duration and movement cycle width, a relationship that dissipated with therapeutic DBS. Further analyses suggest that high gamma activity correlates with enhanced motor performance with DBS-ON. Regardless of the nature of coupling, DBS's modulation of cortical bursting activity appeared to amplify the brain signals' informational content regarding instantaneous movement changes. Our findings underscore that DBS significantly reshapes the interaction between motor behavior and neural signals in PD, not only modulating specific bands but also expanding the system's capability to process and relay information for motor control. These insights shed light on the possible network mechanisms underlying DBS therapeutic effects, suggesting a profound impact on both neural and motor domains. Mirpour and Pouratian investigate the interplay between movement, brain oscillations and deep brain stimulation (DBS) in Parkinson's disease. They show that beta oscillations interfere with the moment-to-moment control of movement, and that DBS can enhance communication within brain networks, mitigating these effects.
RESUMEN
BACKGROUND: The optimal duration of preoperative imatinib (IM) remains controversial. This study aimed to evaluate the safety, therapeutic effectiveness, and optimal duration of preoperative IM in patients with locally advanced gastric gastrointestinal stromal tumors (GIST). METHODS: The clinicopathologic data of 41 patients with locally advanced gastric GIST who received preoperative IM and underwent surgical resection from January 2014 and December 2021 were retrospectively analyzed. RESULTS: After a median of 7.0 (IQR: 4.5-10) months of preoperative IM treatment, 30 patients experienced adverse events (AEs), 80% of which were grade 1/2 AEs. The mean tumor size decreased from 12.71 ± 5.34 cm to 8.26 ± 4.00 cm, with a reduction rate of 35%. Setting 8 months as the cut-off value according to the results of ROC analysis. The proportion of laparoscopic surgery was higher in patients with short-term (≤8 months) versus long-term (>8 months) preoperative IM. Compared with the subtotal/total gastrectomy group, patients in the local gastrectomy group exhibited less intraoperative blood loss, shorter length of postoperative hospital stay, and fewer postoperative complications. The 3-year recurrence-free survival (RFS) and overall survival (OS) rates were 82.9% and 97.6%, and the expected 5-year RFS and OS rates were 75.6% and 90.2% respectively. RFS was better in the short-term than in the long-term preoperative IM treatment group, and it was also better in pre- plus postoperative IM treatment group than that in the preoperative IM alone group. Both univariate and multivariate COX analysis showed that a higher mitotic index and long-term preoperative IM treatment were associated with worse RFS, while postoperative IM treatment could significantly improve RFS. CONCLUSIONS: The study suggests that in patients with locally advanced gastric GIST, preoperative short-term (≤8 months) use of IM is associated with higher RFS than long-term use.
Asunto(s)
Gastrectomía , Tumores del Estroma Gastrointestinal , Mesilato de Imatinib , Neoplasias Gástricas , Humanos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/mortalidad , Masculino , Femenino , Mesilato de Imatinib/uso terapéutico , Mesilato de Imatinib/administración & dosificación , Mesilato de Imatinib/efectos adversos , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Gastrectomía/efectos adversos , Gastrectomía/métodos , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Resultado del Tratamiento , Adulto , Factores de TiempoRESUMEN
Introduction: Tropical climates in remote Aboriginal and Torres Strait Islander communities in northern Australia are conducive to the transmission of canine helminths such as hookworms, as well as ectoparasites such as fleas and ticks. In addition to their veterinary importance, these parasites may present a zoonotic risk either directly, or as potential vectors for bacterial pathogens. These factors necessitate efficacious and effective antiparasitic treatment programs for community dogs. Methods: A cluster-randomised trial was performed on three islands in the Torres Strait to examine the short-term efficacy and medium-term effectiveness of three treatment programs. Treatments administered included oral oxibendazole/praziquantel (Paragard®) and oral afoxolaner (Nexgard®); topical moxidectin/imidacloprid (Advocate®) and imidacloprid/flumethrin collars (Seresto®); and off-label oral ivermectin (Bomectin®). Canine faecal samples were collected and examined for endoparasites by faecal flotation and real-time PCR at baseline, 7-11 days after treatment and 6 months later. Results: The proportion of dogs positive for Ancylostoma caninum at baseline and negative at day 7-11 was 9% (95% CI 4.4-17.4) for dogs treated with oxibendazole, 56.4% (95% CI 41-70.7) for moxidectin, and 89.7% (95% CI 73.6-96.4) for ivermectin. Faecal flotation results showed a greater than 90% egg reduction in 29.2% (95% CI 19.9-40.5) of dogs treated with oxibendazole, 79.4% (95% CI 63.2-89.7) for moxidectin, and 95% (95% CI 76.4-99.1) for off-label ivermectin. Elimination of ectoparasite infestation was observed at day 7-11 in 69.9% (95% CI 56.7-80.1) of dogs treated with afoxolaner, 80% (95% CI 60.9-91.1) with imidacloprid/flumethrin collars, and 0% (95% CI 0-11.7) for off-label ivermectin. Mixed effects modelling revealed only treatment group to be significantly associated with outcome measures. Discussion: Based on these study results, the poor efficacy of oxibendazole against A. caninum renders it inept for treatment, while ivermectin and moxidectin were suitable. Ivermectin was unsuitable for ectoparasite treatment due to its poor efficacy, while afoxolaner and imidacloprid/flumethrin collars appear suitable.
RESUMEN
BACKGROUND: Out-of-hours primary care (OOH-PC) has emerged as a promising solution to improve efficiency, accessibility, and quality of care and to reduce the strain on emergency departments. As this modality gains traction in diverse healthcare settings, it is increasingly important to fully assess its societal value-for-money and conduct thorough process evaluations. However, current economic evaluations mostly emphasise direct- and short-term effect measures, thus lacking a broader societal perspective. AIM: This study offers a comprehensive overview of current effect measures in OOH-PC evaluations and proposes additional measures from the evaluation of integrated care programmes. APPROACH AND DEVELOPMENT: First, we systematically identified the effect measures from published cost-effectiveness studies and classified them as process, outcome, and resource use measures. Second, we elaborate on the incorporation of 'productivity gains', 'health promotion and early intervention', and 'continuity of care' as additional effects into economic evaluations of OOH-PC. Seeking care affects personal and employee time, potentially resulting in decreased productivity. Challenges in taking time off work and limited access to convenient care are often cited as barriers to accessing primary care. As such, OOH-PC can potentially reduce opportunity costs for patients. Furthermore, improving access to healthcare is important in determining whether people receive promotional and preventive services. Health promotion involves empowering people to take control of their health and its determinants. Given the unscheduled nature and the fragmented or rotational care in OOH-PC, the degree to which interventions and modalities provide continuity should be monitored, assessed, and included in economic evaluations. Continuity of care in primary care improves patient satisfaction, promotes adherence to medical advice, reduces reliance on hospitals, and reduces mortality. CONCLUSION: Although it is essential to also address local settings and needs, the integration of broader scope measures into OOH-PC economic evaluations improves the comprehensive evaluation that aligns with welfare gains.
Asunto(s)
Atención Posterior , Análisis Costo-Beneficio , Atención Primaria de Salud , Humanos , Accesibilidad a los Servicios de SaludRESUMEN
Bacteria are the primary cause of infectious diseases, making rapid and accurate identification crucial for timely pathogen diagnosis and disease control. However, traditional identification techniques such as polymerase chain reaction and loop-mediated isothermal amplification are complex, time-consuming, and pose infection risks. This study explores remote (~3 m) bacterial identification using laser-induced breakdown spectroscopy (LIBS) with a Cassegrain reflective telescope. Principal component analysis (PCA) was employed to reduce the dimensionality of the LIBS spectral data, and the accuracy of support vector machine (SVM) and Random Forest (RF) algorithms was compared. Multiple repeated experiments showed that the RF model achieved a classification accuracy, recall, precision, and F1-score of 99.81%, 99.80%, 99.79%, and 0.9979, respectively, outperforming the SVM model and providing more accurate remote bacterial identification. The method based on laser-induced plasma spectroscopy and machine learning has broad application prospects, supporting noncontact disease diagnosis, improving public health, and advancing medical research and technological development.
RESUMEN
OBJECTIVE: To explore the survival effect of thoracic gross tumor volume (GTV) in three-dimensional (3D) radiotherapy for stage IV non-small cell lung cancer (NSCLC). METHODS: The data cases were obtained from a single-center retrospective analysis. From May. From 2008 to August 2018, 377 treatment criteria were enrolled. GTV was defined as the volume of the primary lesion and the hilus as well as the mediastinal metastatic lymph node. Chemotherapy was a platinum-based combined regimen of two drugs. The number of median chemotherapy cycles was 4 (2-6), and the cut-off value of the planning target volume (PTV) dose of the primary tumor was 63 Gy (30-76.5 Gy). The cut-off value of GTV volume was 150 cm3 (5.83-3535.20 cm3). RESULTS: The survival rate of patients with GTV <150 cm3 is better than patients with GTV ≥150 cm3. Multivariate Cox regression analyses suggested that peripheral lung cancer, radiation dose ≥63 Gy, GTV <150 cm3, 4-6 cycles of chemotherapy, and CR + PR are good prognostic factors for patients with stage IV non-small cell lung cancer. The survival rate of patients with GTV <150 cm3 was longer than patients with ≥150 cm3 when they underwent 2 to 3 cycles of chemotherapy concurrent 3D radiotherapy (p < 0.05). When performing 4 to 6 cycles of chemotherapy concurrent 3D radiotherapy, there was no significant difference between <150 cm3 and ≥150 cm3. CONCLUSIONS: The volume of stage IV NSCLC primary tumor can affect the survival of patients. Appropriate treatment methods can be opted by considering the volume of tumors to extend patients' lifetime to the utmost.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Quimioradioterapia , Neoplasias Pulmonares , Estadificación de Neoplasias , Carga Tumoral , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Femenino , Quimioradioterapia/métodos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano de 80 o más Años , Pronóstico , Tasa de SupervivenciaRESUMEN
Introduction Acute coronary syndrome (ACS) and acute pulmonary embolism (PE) are life-threatening conditions with similar clinical presentations. As current diagnostic tools, such as computed tomography pulmonary angiography, for distinguishing between these two conditions are time-consuming and may not be available in all settings, we tried in this study to devise a diagnostic tool based on electrocardiography to distinguish between ACS and acute PE based on T wave features. Methods Medical records of patients with diagnoses of ACS and acute PE, who were referred to three hospitals affiliated with Shiraz University of Medical Sciences, Shiraz, Iran, from March 2019 to March 2021, were evaluated. One expert cardiologist read patients' electrocardiograms (ECGs). All ECGs were recorded at the standard 25 mm/s and 10 mm/mV. The sum of T wave inversion or TWI (mV) in consecutive leads, including anterior leads (V1, V2, V3, and V4), inferior leads (II, III, aVF), and lateral leads (I, aVL, V5, and V6) were calculated to estimate the cut-off points used to differentiate ACS versus acute PE. The receiver operating characteristic (ROC) curve was used to estimate the diagnostic accuracy of T wave changes. The Youden index was used to calculate the optimum cut-offs for sensitivity and specificity. Results Of 151 patients with a mean age of 55.44±12.88 years, 74 were in the acute PE and 77 were in the ACS groups. The results showed that the TWI sum in anterior leads >1.2 mV (P<0.001), in lateral leads >0.9 mV (P<0.001), in anterior-to-inferior leads ratio >12 (P<0.001), and V4/V1 leads ratio >4 (P<0.001) rules out acute PE. Anterior-to-lateral TWI ratio (AUC=0.807, sensitivity=70.3%, specificity=10%) was significantly distinctive among ACS and acute PE patients. Conclusion TWI sum in anterior leads >1.2 mV, in lateral leads >0.9 mV, in anterior-to-inferior leads ratio >12, and in V4/V1 leads ratio >4 rules out acute PE. The anterior-to-lateral TWI ratio obtained from patients' ECG was significantly distinctive among the patients and can be used as a screening tool.
RESUMEN
Online adaptive radiotherapy (ART) enables accommodation for variations in patient setup and anatomical changes, allowing for fractional replanning for target coverage, organ at risk (OAR) sparing, and application of CT simulation-free (SF) workflows. SF workflows bypass the conventional simulation CT scan at the potential trade-off in dosimetric uncertainty. ART can alleviate many of these uncertainties, and this work extends previous experience with an Ethos adaptive cone-beam computed tomography (CBCT)-based SF process to treating a unique bony and soft tissue case with stereotactic body radiation therapy (SBRT). The patient is an 83-year-old male with metastatic prostate cancer, presenting with metastases near the right posterior ischium and a right perirectal lymph node. The patient's history includes multiple radiation treatments and androgen deprivation therapy (ADT). Rising prostate-specific antigen(PSA) levels and new metastases identified via positron emission tomography (PET)/CT prostate-specific membrane antigen (PSMA) led to SBRT re-irradiation, considered safe due to the time lapse since previous treatments. Using a HyperSight-equipped Ethos ART system, an SF SBRT workflow utilized the patient's recent PET/CT images for target and OAR delineation. A nine-field adaptive intensity-modulated radiotherapy(IMRT) treatment plan was generated to deliver 3600 Gy in three fractions with a primary focus to limit the dose to proximal OARs and the previously treated region. At the adaptive treatment, the patient is positioned based on anatomical marks, and axial images from HyperSight CBCT are used to contour the OARs and targets. These modified contours accommodate daily variations and are used to recalculate the reference plan and generate a new adapted plan. The adapted plan is selected if coverage improvement and OAR sparing are achieved. For each newly adapted plan, Ethos-generated synthetic CT is reviewed prior to treatment to verify no errors occurred in the deformable propagation between the reference image and the fractional CBCT. For this patient, the adapted plan was selected for all fractions due to improved target coverage, particularly of the soft tissue target, and OAR sparing. The patient tolerated the treatment well and demonstrated a good response on three-month follow-up PSMA PET/CT imaging. This case highlights the efficacy of CBCT-driven SF ART in complex re-irradiation scenario. Future enhancements in the Ethos treatment planning system, including direct dose computation on HyperSight CBCT images, will streamline SF workflows and expand their applicability. Careful consideration of potential on-unit OAR changes and target motion remains crucial for successful SF ART applications.
RESUMEN
Researchers are often interested in estimating the effect of sustained use of a treatment on a health outcome. However, adherence to strict treatment protocols can be challenging for individuals in practice and, when non-adherence is expected, estimates of the effect of sustained use may not be useful for decision making. As an alternative, more relaxed treatment protocols which allow for periods of time off treatment (i.e. grace periods) have been considered in pragmatic randomized trials and observational studies. In this article, we consider the interpretation, identification, and estimation of treatment strategies which include grace periods. We contrast natural grace period strategies which allow individuals the flexibility to take treatment as they would naturally do, with stochastic grace period strategies in which the investigator specifies the distribution of treatment utilization. We estimate the effect of initiation of a thiazide diuretic or an angiotensin-converting enzyme inhibitor in hypertensive individuals under various strategies which include grace periods.
RESUMEN
Background: The rates of return to play (RTP) after anterior cruciate ligament (ACL) reconstruction among professional and National Collegiate Athletic Association (NCAA) Division I athletes are well described in the orthopaedic literature. Less is known about these rates and risk factors for failure to RTP in Division II and III collegiate athletes. Purpose: To determine the RTP rate after ACL reconstruction among Division II and III collegiate athletes and to explore the factors associated with RTP. Study Design: Case series; Level of evidence, 4. Methods: Demographic and RTP data were retrospectively reviewed for collegiate athletes who underwent ACL reconstructions across high-risk sports over 6 years (2015/16 to 2021/22 seasons) at 5 northeastern NCAA Division II and III institutions. Clinical data collected included Patient Acceptable Symptom State (PASS) on the Knee injury and Osteoarthritis Outcome Score (KOOS) Sport and Recreation questionnaire, graft type, concomitant reparative surgery, reinjury, need for reoperation, and time to RTP and return to preinjury level. Participants completed the survey using a secure web-based questionnaire sent via email or over the telephone at a minimum 6-month follow-up. Descriptive frequencies were calculated for all documented variables, with chi-square and analysis of variance statistics used to assess for associations and significant differences between variables. Results: A total of 61 eligible student-athletes with primary ACL reconstructions were identified in this study period, and 40 knees were enrolled for analysis with a mean time from surgery to survey completion of 45.0 months. The overall RTP rate was 77.5% (31/40) at a mean of 10.1 months. However, only 50.0% (20/40) returned to their preinjury level of competitive play. There was a graft failure rate of 20% (8/40). Of the 32 athletes who did not reinjure their ACL, 81.25% (26/32) demonstrated a PASS on KOOS Sports and Recreation. Graft rerupture (P < .001) and reoperation (P = .007) had significant effects on rates of RTP. Concomitant procedures (P = .010) influenced return to preinjury level of sports. Injury during the active season versus the off-season significantly influenced KOOS PASS status (P = .038). Conclusion: This study demonstrated that the rate of RTP after ACL reconstruction in this patient population of Division II and III collegiate athletes was 77.5%, with only 50% returning to their preinjury level of competitive play. The graft failure rate in this population was 20%. Surgical factors, such as concomitant surgeries and reinjury of ACL graft, as well as athlete-specific data, such as injury in the off-season, were statistically significant negative influences on patient outcomes. Further research is needed to evaluate other potential factors that may play a role in RTP after ACL reconstruction.
RESUMEN
The sensing of and response to ambient chemical gradients by microorganisms via chemotaxis regulates many microbial processes fundamental to ecosystem function, human health, and disease. Microfluidics has emerged as an indispensable tool for the study of microbial chemotaxis, enabling precise, robust, and reproducible control of spatiotemporal chemical conditions. Previous techniques include combining laminar flow patterning and stop-flow diffusion to produce quasi-steady chemical gradients to directly probe single-cell responses or loading micro-wells to entice and ensnare chemotactic bacteria in quasi-steady chemical conditions. Such microfluidic approaches exemplify a trade-off between high spatiotemporal resolution of cell behavior and high-throughput screening of concentration-specific chemotactic responses. However, both aspects are necessary to disentangle how a diverse range of chemical compounds and concentrations mediate microbial processes such as nutrient uptake, reproduction, and chemorepulsion from toxins. Here, we present a protocol for the multiplexed chemotaxis device (MCD), a parallelized microfluidic platform for efficient, high-throughput, and high-resolution chemotaxis screening of swimming microbes across a range of chemical concentrations. The first layer of the two-layer polydimethylsiloxane (PDMS) device comprises a serial dilution network designed to produce five logarithmically diluted chemostimulus concentrations plus a control from a single chemical solution input. Laminar flow in the second device layer brings a cell suspension and buffer solution into contact with the chemostimuli solutions in each of six separate chemotaxis assays, in which microbial responses are imaged simultaneously over time. The MCD is produced via standard photography and soft lithography techniques and provides robust, repeatable chemostimulus concentrations across each assay in the device. This microfluidic platform provides a chemotaxis assay that blends high-throughput screening approaches with single-cell resolution to achieve a more comprehensive understanding of chemotaxis-mediated microbial processes. Key features ⢠Microchannel master molds are fabricated using photolithography techniques in a clean room with a mask aligner to fabricate multilevel feature heights. ⢠The microfluidic device is fabricated from PDMS using standard soft lithography replica molding from the master molds. ⢠The resulting microchannel requires a one-time calibration of the driving inlet pressures, after which devices from the same master molds have robust performance. ⢠The microfluidic platform is optimized and tested for measuring chemotaxis of swimming prokaryotes.
RESUMEN
Background and Objectives: Deep brain stimulation (DBS) is a well-established treatment for Parkinson disease (PD), with programming methods continually evolving. This study aimed to compare the efficacy and patient burden between conventional ring-mode programming (CP-RM) and image-guided volume of tissue activated (IG-VTA) programming for subthalamic nucleus (STN) DBS in PD. Methods: In this retrospective study, patients with PD who underwent STN-DBS between 2011 and 2014 (CP-RM group) and 2019 and 2021 (IG-VTA group) were evaluated. The primary outcome was the improvement in the UPDRS III score from preoperative OFF to postoperative ON state without medication at one-year follow-up. Secondary outcomes included hospital stay duration and programming sessions. Results: A total of 26 patients were analyzed (IG-VTA: n = 12, CP-RM: n = 14). Both groups showed similar improvements in UPDRS III scores (IG-VTA: 43.62, CP-RM: 41.29). However, the IG-VTA group experienced shorter immediate postoperative hospital stays and fewer hospitalizations after discharge. Discussion: IG-VTA programming preserved the clinical efficacy of STN-DBS over 1 year and reduced the patient and clinician burden of hospital stay and programming sessions. However, conclusions drawn must consider the limitations of retrospective design, differing time epochs, and evolving clinical practices. Further multicentric and prospective studies are warranted to validate these findings in the evolving field of neurostimulation. Trial Registration Information: The trial is registered on clinicaltrials.gov (NCT05103072).
RESUMEN
Pasteurization (PS) causes the abnormal changes in volatiles and off-flavors in juices and limit the commercial production of juices. Herein, the first study on the biochemical reaction of volatile and nonvolatile compounds in response to PS factors during the process of sea buckthorn pulp (SBP) was evaluated. Processing conditions (mainly 80 °C for 20 min) had significant effects on the volatile and nonvolatile compounds. The restricted unsaturated fatty acid metabolism led to the greatest decrease of 20.25% in esters with fruity odor, and furans, smelling like caramel and toast, exhibited the highest increase of 136.40% because of the enhancement of the Maillard reaction. Dimethyl sulfide and dimethyl trisulfide elicited a cooked onion-like off-flavor, generated mainly from Strecker degradation of sulfur-containing amino acids, strengthened by the high pH and sufficient substrates due to the highest consumption rates of 4.66% and 12.01% for organic acids and sugars. Reasonable temperature and time control are crucial to the improvement of the process for PS for the SBP industry. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05943-z.
RESUMEN
Aim: The current review aims to explore postoperative neurological complications in third molar extractive surgery. Materials and Methods: The PRISMA protocols were followed when conducting this review. We found a total of 2,250 articles that matched our topic using the Boolean keywords, mandibular nerve complications AND oral surgery, from PubMed (1,083), Scopus (435), and Web of Science (732), with the filters of English language articles, time range January 1, 2003, to September 30, 2023, and human studies. After 762 duplicates were eliminated, there remained 1,488 articles. Eleven final articles were deemed of the highest relevance to our topic by eliminating articles in animals, non-English language, reviews, meta-analysis, and off-topic. A potential risk in the third molar extraction was temporary loss of sensibility often caused by mild compression or irritation of the mandibular nerve. This typically resolves within weeks or months, but in severe cases, recovery might take longer. Permanent loss of sensation can occur, indicating significant nerve damage and lasting effects on touch, temperature, or pain perception. Conclusions: Various treatments exist for nerve damage, including low-level laser therapy, pain management medications, or physical therapy. While these therapies may improve neurosensory impairment, patients often report a decline in their quality of life.