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Journal of Nanobiotechnology Jun 2024Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized... (Review)
Review
Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized more frequently in periodontal therapy due to their designability and unique drug delivery system. However, local and systemic immune response reactions driven by the implantation of biomaterials could result in inflammation, tissue damage, and fibrosis, which could end up with the failure of the implantation. Therefore, immunological adjustment of biomaterials through precise design can reduce the host reaction while eliminating the periodontal tissue's long-term chronic inflammation response. It is important to note that macrophages are an active immune system component that can participate in the progression of periodontal disease through intricate polarization mechanisms. And modulating macrophage polarization by designing biomaterials has emerged as a new periodontal therapy technique. In this review, we discuss the role of macrophages in periodontitis and typical strategies for polarizing macrophages with biomaterials. Subsequently, we discuss the challenges and potential opportunities of using biomaterials to manipulate periodontal macrophages to facilitate periodontal regeneration.
Topics: Humans; Periodontitis; Biocompatible Materials; Macrophages; Animals; Immunotherapy; Drug Delivery Systems
PubMed: 38907216
DOI: 10.1186/s12951-024-02592-4 -
Medicine Jun 2024Acute epiglottitis is not uncommon and it can cause high mortality due to airway obstruction. Acute epiglottitis complicated with cervical necrotizing fasciitis has...
INTRODUCTION
Acute epiglottitis is not uncommon and it can cause high mortality due to airway obstruction. Acute epiglottitis complicated with cervical necrotizing fasciitis has rarely been reported, and it is also a life-threatening disease with a fatality rate of 7% to 50%.
PATIENT CONCERNS
A 64-year-old woman presented to our hospital with chief complaints of sore throat and cervical swelling, long with foreign body sensation and hoarseness. Endoscopic laryngoscopy showed erythematous and swollen epiglottis with purulent secretions on the surface. Computed tomography (CT) scan showed swollen epiglottis and swelling of the neck with air- and fluid-containing necrotizing tissue.
DIAGNOSES
The diagnosis was acute epiglottitis and abscess complicated with cervical necrotizing fasciitis.
INTERVENTIONS
With the patient in awake condition, airway access was established by performing intubation with adjunctive use of gum elastic bougie, followed by surgical debridement under general anesthesia; a flap was used for skin coverage and intravenous piperacillin-tazobactam was administered.
OUTCOMES
The patient was discharged without complications.
CONCLUSION
Gum elastic bougie is a usable tool in difficult intubation. Adequate pre-anesthesia evaluation, patient sedation, and gentle manipulation assured the intubation success in this case.
Topics: Humans; Female; Fasciitis, Necrotizing; Middle Aged; Epiglottitis; Intubation, Intratracheal; Abscess; Acute Disease; Neck; Debridement; Laryngoscopy; Anti-Bacterial Agents; Tomography, X-Ray Computed
PubMed: 38905392
DOI: 10.1097/MD.0000000000038658 -
JMIR Human Factors Jun 2024Strokes pose a substantial health burden, impacting 1 in 6 people globally. One-tenth of patients will endure a second, often more severe, stroke within a year....
BACKGROUND
Strokes pose a substantial health burden, impacting 1 in 6 people globally. One-tenth of patients will endure a second, often more severe, stroke within a year. Alarmingly, a younger demographic is being affected due to recent lifestyle changes. As fine motor and cognitive issues arise, patient disability as well as the strain on caregivers and health care resources is exacerbated. Contemporary occupational therapy assesses manual dexterity and cognitive functions through object manipulation and pen-and-paper recordings. However, these assessments are typically isolated, which makes it challenging for therapists to comprehensively evaluate specific patient conditions. Furthermore, the reliance on one-on-one training and assessment approaches on manual documentation is inefficient and prone to transcription errors.
OBJECTIVE
This study examines the feasibility of using an interactive electronic pegboard for stroke rehabilitation in clinical settings.
METHODS
A total of 10 patients with a history of stroke and 10 healthy older individuals were recruited. With a limit of 10 minutes, both groups of participants underwent a series of challenges involving tasks related to manual operation, shape recognition, and color discrimination. All participants underwent the Box and Block Test and the Purdue Pegboard Test to assess manual dexterity, as well as an array of cognitive assessments, including the Trail Making Test and the Mini-Mental Status Examination, which served as a basis to quantify participants' attention, executive functioning, and cognitive abilities.
RESULTS
The findings validate the potential application of an interactive electronic pegboard for stroke rehabilitation in clinical contexts. Significant statistical differences (P<.01) were observed across all assessed variables, including age, Box and Block Test results, Purdue Pegboard Test outcomes, Trail Making Test-A scores, and Mini-Mental Status Examination performance, between patients with a history of stroke and their healthy older counterparts. Functional and task testing, along with questionnaire interviews, revealed that patients with a history of stroke demonstrated prolonged completion times and slightly inferior performance. Nonetheless, most patients perceived the prototype as user-friendly and engaging. Thus, in the context of patient rehabilitation interventions or the evaluation of patient cognition, physical functioning, or manual dexterity assessments, the developed pegboard could potentially serve as a valuable tool for hand function, attention, and cognitive rehabilitation, thereby mitigating the burden on health care professionals.
CONCLUSIONS
Health care professionals can use digital electronic pegboards not only as a precise one-on-one training tool but also as a flexible system that can be configured for online or offline, single-player or multiplayer use. Through data analysis, a more informed examination of patients' cognitive and functional issues can be conducted. Importantly, patient records will be fully retained throughout practices, exercises, or tests, and by leveraging the characteristics of big data, patients can receive the most accurate rehabilitation prescriptions, thereby assisting them in obtaining optimal care.
Topics: Humans; Male; Female; Aged; Middle Aged; Stroke Rehabilitation; Cognition; Motor Skills; User-Computer Interface; Occupational Therapy; Feasibility Studies
PubMed: 38904991
DOI: 10.2196/56357 -
Journal of Vision Jun 2024Accurately estimating time to contact (TTC) is crucial for successful interactions with moving objects, yet it is challenging under conditions of sensory and contextual...
Accurately estimating time to contact (TTC) is crucial for successful interactions with moving objects, yet it is challenging under conditions of sensory and contextual uncertainty, such as occlusion. In this study, participants engaged in a prediction motion task, monitoring a target that moved rightward and an occluder. The participants' task was to press a key when they predicted the target would be aligned with the occluder's right edge. We manipulated sensory uncertainty by varying the visible and occluded periods of the target, thereby modulating the time available to integrate sensory information and the duration over which motion must be extrapolated. Additionally, contextual uncertainty was manipulated by having a predictable and unpredictable condition, meaning the occluder either reliably indicated where the moving target would disappear or provided no such indication. Results showed differences in accuracy between the predictable and unpredictable occluder conditions, with different eye movement patterns in each case. Importantly, the ratio of the time the target was visible, which allows for the integration of sensory information, to the occlusion time, which determines perceptual uncertainty, was a key factor in determining performance. This ratio is central to our proposed model, which provides a robust framework for understanding and predicting human performance in dynamic environments with varying degrees of uncertainty.
Topics: Humans; Motion Perception; Uncertainty; Male; Female; Adult; Young Adult; Photic Stimulation; Eye Movements; Reaction Time; Time Perception; Psychomotor Performance
PubMed: 38904641
DOI: 10.1167/jov.24.6.14 -
ArXiv May 2024Optogenetics is widely used to study the effects of neural circuit manipulation on behavior. However, the paucity of causal inference methodological work on this topic...
Optogenetics is widely used to study the effects of neural circuit manipulation on behavior. However, the paucity of causal inference methodological work on this topic has resulted in analysis conventions that discard information, and constrain the scientific questions that can be posed. To fill this gap, we introduce a nonparametric causal inference framework for analyzing "closed-loop" designs, which use dynamic policies that assign treatment based on covariates. In this setting, standard methods can introduce bias and occlude causal effects. Building on the sequentially randomized experiments literature in causal inference, our approach extends history-restricted marginal structural models for dynamic regimes. In practice, our framework can identify a wide range of causal effects of optogenetics on trial-by-trial behavior, such as, fast/slow-acting, dose-response, additive/antagonistic, and floor/ceiling. Importantly, it does so without requiring negative controls, and can estimate how causal effect magnitudes evolve across time points. From another view, our work extends "excursion effect" methods--popular in the mobile health literature--to enable estimation of causal contrasts for treatment sequences greater than length one, in the presence of positivity violations. We derive rigorous statistical guarantees, enabling hypothesis testing of these causal effects. We demonstrate our approach on data from a recent study of dopaminergic activity on learning, and show how our method reveals relevant effects obscured in standard analyses.
PubMed: 38903744
DOI: No ID Found -
Global Advances in Integrative Medicine... 2024Authoritative research demonstrating efficacy of traditional dysphagia therapy for Head & Neck Cancer (HNC) patients is limited. A 2019 survey reported...
BACKGROUND
Authoritative research demonstrating efficacy of traditional dysphagia therapy for Head & Neck Cancer (HNC) patients is limited. A 2019 survey reported speech-language-pathologists (SLPs) have started using Manual Therapy (MT) to prevent or rehabilitate dysphagia in HNC patients. This application of MT is supported theoretically but no research has established efficacy. Further, specific contents of MT protocols employed in this setting remain unknown.
OBJECTIVES
In the absence of HNC dysphagia specific MT protocols, this study aimed to better understand MT protocols employed by SLPs to prevent and treat dysphagia in HNC patients during and after Radiation Therapy (RT).
METHODS
An internet-based questionnaire for SLPs who use MT with HNC patients was developed and tested for face/content validity. It was sent to SLPs practicing in the USA, twice, through three national listservs (ASHA-SIG13, ASHA-SIG3, University of Iowa Voiceserv).
RESULTS
Of 64 respondents, 44 completed the survey. Of the 44, 15(34%) provided proactive MT during RT, 37(84%) provided proactive MT after RT (to prevent dysphagia), and 44(100%) provided reactive MT after RT (to treat dysphagia). 40(91%) were trained in MT through a CE course and 25(57%) had HNC-specific MT training. The most common MT techniques were laryngeal manipulation (LM) and myofascial release (MFR). During RT, MT protocols are gentler and highly tailored, with simple home programs of mild intensity. After RT, protocols are more regimented and aggressive, but still highly customized, with more diverse home programs of at least moderate intensity.
CONCLUSION
MT for HNC patients lacks a standard protocol or approach, but MFR and LM, or components of those techniques, are used most frequently. Given the frequency with which MFR and LM are employed to treat dysphagia during and post-RT, and the lack of empirical evidence supporting or refuting their use, a collaboratively designed RCT is warranted to establish the safety and efficacy of MT for HNC patients.
PubMed: 38903482
DOI: 10.1177/27536130241263349 -
Frontiers in Plant Science 2024Crop breeding entails developing and selecting plant varieties with improved agronomic traits. Modern molecular techniques, such as genome editing, enable more efficient... (Review)
Review
Crop breeding entails developing and selecting plant varieties with improved agronomic traits. Modern molecular techniques, such as genome editing, enable more efficient manipulation of plant phenotype by altering the expression of particular regulatory or functional genes. Hence, it is essential to thoroughly comprehend the transcriptional regulatory mechanisms that underpin these traits. In the multi-omics era, a large amount of omics data has been generated for diverse crop species, including genomics, epigenomics, transcriptomics, proteomics, and single-cell omics. The abundant data resources and the emergence of advanced computational tools offer unprecedented opportunities for obtaining a holistic view and profound understanding of the regulatory processes linked to desirable traits. This review focuses on integrated network approaches that utilize multi-omics data to investigate gene expression regulation. Various types of regulatory networks and their inference methods are discussed, focusing on recent advancements in crop plants. The integration of multi-omics data has been proven to be crucial for the construction of high-confidence regulatory networks. With the refinement of these methodologies, they will significantly enhance crop breeding efforts and contribute to global food security.
PubMed: 38903438
DOI: 10.3389/fpls.2024.1421503 -
BioRxiv : the Preprint Server For... May 2024Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles made of hyperphosphorylated tau and senile plaques composed of beta-amyloid. These...
BACKGROUND
Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles made of hyperphosphorylated tau and senile plaques composed of beta-amyloid. These pathognomonic deposits have been implicated in the pathogenesis, although the molecular mechanisms and consequences remain undetermined. UFM1 is an important, but understudied ubiquitin-like protein that is covalently attached to substrates. This UFMylation has recently been identified as major modifier of tau aggregation upon seeding in experimental models. However, potential alterations of the UFM1 pathway in human AD brain have not been investigated yet.
METHODS
Here we used frontal and temporal cortex samples from individuals with or without AD to measure the protein levels of the UFMylation pathway in human brain. We used multivariable regression analyses followed by Bonferroni correction for multiple testing to analyze associations of the UFMylation pathway with neuropathological characteristics, primary biochemical measurements of tau and additional biochemical markers from the same cases. We further studied associations of the UFMylation cascade with cellular stress pathways using Spearman correlations with bulk RNAseq expression data and functionally validated these interactions using gene-edited neurons that were generated by CRISPR-Cas9.
RESULTS
Compared to controls, human AD brain had increased protein levels of UFM1. Our data further indicates that this increase mainly reflects conjugated UFM1 indicating hyperUFMylation in AD. UFMylation was strongly correlated with pathological tau in both AD-affected brain regions. In addition, we found that the levels of conjugated UFM1 were negatively correlated with soluble levels of the deUFMylation enzyme UFSP2. Functional analysis of UFM1 and/or UFSP2 knockout neurons revealed that the DNA damage response as well as the unfolded protein response are perturbed by changes in neuronal UFM1 signaling.
CONCLUSIONS
There are marked changes in the UFMylation pathway in human AD brain. These changes are significantly associated with pathological tau, supporting the idea that the UFMylation cascade might indeed act as a modifier of tau pathology in human brain. Our study further nominates UFSP2 as an attractive target to reduce the hyperUFMylation observed in AD brain but also underscores the critical need to identify risks and benefits of manipulating the UFMylation pathway as potential therapeutic avenue for AD.
PubMed: 38903110
DOI: 10.1101/2024.05.24.595755 -
Oncotarget Jun 2024Prostate cancer (PCa) poses significant challenges in treatment, particularly when it progresses to a metastatic, castrate-resistant state. Conventional therapies,... (Review)
Review
Prostate cancer (PCa) poses significant challenges in treatment, particularly when it progresses to a metastatic, castrate-resistant state. Conventional therapies, including chemotherapy, radiotherapy, and hormonal treatments, often fail due to toxicities, off-target effects, and acquired resistance. This research perspective defines an alternative therapeutic strategy focusing on the metabolic vulnerabilities of PCa cells, specifically their reliance on non-essential amino acids such as cysteine. Using an engineered enzyme cyst(e)inase to deplete the cysteine/cystine can induce oxidative stress and DNA damage in cancer cells. This depletion elevates reactive oxygen species (ROS) levels, disrupts glutathione synthesis, and enhances DNA damage, leading to cancer cell death. The combinatorial use of cyst(e)inase with agents targeting antioxidant defenses, such as thioredoxins, further amplifies ROS accumulation and cytotoxicity in PCa cells. Overall, in this perspective provides a compressive overview of the previous work on manipulating amino acid metabolism and redox balance modulate the efficacy of DNA repair-targeted and immune checkpoint blockade therapies in prostate cancer.
Topics: Humans; DNA Damage; Immunotherapy; Prostatic Neoplasms; Reactive Oxygen Species; Male; Oxidative Stress; DNA Repair; Animals; Cysteine
PubMed: 38900609
DOI: 10.18632/oncotarget.28595 -
RSC Pharmaceutics Jun 2024Mitonafide-loaded liposomes are a promising strategy to overcome the neurotoxicity observed in clinical trials for this drug. This study investigates the influence of...
Mitonafide-loaded liposomes are a promising strategy to overcome the neurotoxicity observed in clinical trials for this drug. This study investigates the influence of loaded mitonafide or a dimer analogue on different liposomal formulations and their therapeutic efficacy . Physicochemical properties of the liposomes were manipulated using different loading methods (namely bilayer or core loading) and varying the rigidity of the bilayer using distinct phospholipid compositions. Our results demonstrated that the mitonafide dimer analogue had a comparable encapsulation efficiency (EE%) into the liposomes when loaded into rigid or flexible bilayers in contrast to the low mitonafide monomer EE%. A pH gradient core loading method resulted in a more efficient mechanism to load the monomer into the liposomes. DOSY NMR and spectrofluorometric studies revealed key differences in the structure of the vesicles and the arrangement of the monomer or the dimer in the bilayer or the core of the liposomes. The assessment of the formulations using MDA-MB-231 and RT-112 cells revealed that a flexible lipid bilayer allows a faster drug release, which correlated well with the spectroscopy studies. This study investigated for the first time that the characteristics of the lipid bilayer and the loading method influence the encapsulation efficacy, colloidal properties, photoactivity and stability of mono and bis-naphthalimides loaded in a liposomal carrier, essential factors that will impact the performance of the formulation in a biological scenario.
PubMed: 38899150
DOI: 10.1039/d3pm00060e