Bioorthogonal targeted cell membrane vesicles/cell-sheet composites reduce postoperative tumor recurrence and scar formation of melanoma.

While surgical resection is the predominant clinical strategy in the treatment of melanoma, postoperative recurrence and undetectable metastasis are both pernicious drawbacks to this otherwise highly successful approach. Furthermore, the deep cavities result from tumor excision can leave long lasting wounds which are slow to heal and often leave visible scars. These unmet needs are addressed in the present work through the use of a multidimensional strategy, and also promotes wound healing and scar reduction. In the first phase, cell membrane-derived nanovesicles (NVs) are engineered to show PD-1 and dibenzocyclooctyne (DBCO). These are capable of reactivating T cells by blocking the PD-1/PD-L1 pathway. In the second phase, azido (N3) labeled mesenchymal stem cells (MSCs) are cultured into cell sheets using tissue engineering, then apply directly to surgical wounds to enhance tissue repair. Owing to the complementary association between DBCO and N3 groups, PD-1 NVs were accumulated at the site of excision. This strategy can inhibit postoperative tumor recurrence and metastasis, whilst also promoting wound healing and reducing scar formation. The results of this study set a precedent for a new and innovative multidimensional therapeutic strategy in the postoperative treatment of melanoma.

IoT-based external attacks aware secure healthcare framework using blockchain and SB-RNN-NVS-FU techniques.

BACKGROUND: In recent times, there has been widespread deployment of Internet of Things (IoT) applications, particularly in the healthcare sector, where computations involving user-specific data are carried out on cloud servers. However, the network nodes in IoT healthcare are vulnerable to an increased level of security threats. OBJECTIVE: This paper introduces a secure Electronic Health Record (EHR) framework with a focus on IoT. METHODS: Initially, the IoT sensor nodes are designated as registered patients and undergo initialization. Subsequently, a trust evaluation is conducted, and the clustering of trusted nodes is achieved through the application of Tasmanian Devil Optimization (STD-TDO) utilizing the Student's T-Distribution. Utilizing the Transposition Cipher-Squared random number generator-based-Elliptic Curve Cryptography (TCS-ECC), the clustered nodes encrypt four types of sensed patient data. The resulting encrypted data undergoes hashing and is subsequently added to the blockchain. This configuration functions as a network, actively monitored to detect any external attacks. To accomplish this, a feature reputation score is calculated for the network's features. This score is then input into the Swish Beta activated-Recurrent Neural Network (SB-RNN) model to classify potential attacks. The latest transactions on the blockchain are scrutinized using the Neutrosophic Vague Set Fuzzy (NVS-Fu) algorithm to identify any double-spending attacks on non-compromised nodes. Finally, genuine nodes are granted permission to decrypt medical records. RESULTS: In the experimental analysis, the performance of the proposed methods was compared to existing models. The results demonstrated that the suggested approach significantly increased the security level to 98%, reduced attack detection time to 1300 ms, and maximized accuracy to 98%. Furthermore, a comprehensive comparative analysis affirmed the reliability of the proposed model across all metrics. CONCLUSION: The proposed healthcare framework's efficiency is proved by the experimental evaluation.

Lossless Encoding of Time-Aggregated Neuromorphic Vision Sensor Data Based on Point-Cloud Compression.

Neuromorphic Vision Sensors (NVSs) are emerging sensors that acquire visual information asynchronously when changes occur in the scene. Their advantages versus synchronous capturing (frame-based video) include a low power consumption, a high dynamic range, an extremely high temporal resolution, and lower data rates. Although the acquisition strategy already results in much lower data rates than conventional video, NVS data can be further compressed. For this purpose, we recently proposed Time Aggregation-based Lossless Video Encoding for Neuromorphic Vision Sensor Data (TALVEN), consisting in the time aggregation of NVS events in the form of pixel-based event histograms, arrangement of the data in a specific format, and lossless compression inspired by video encoding. In this paper, we still leverage time aggregation but, rather than performing encoding inspired by frame-based video coding, we encode an appropriate representation of the time-aggregated data via point-cloud compression (similar to another one of our previous works, where time aggregation was not used). The proposed strategy, Time-Aggregated Lossless Encoding of Events based on Point-Cloud Compression (TALEN-PCC), outperforms the originally proposed TALVEN encoding strategy for the content in the considered dataset. The gain in terms of the compression ratio is the highest for low-event rate and low-complexity scenes, whereas the improvement is minimal for high-complexity and high-event rate scenes. According to experiments on outdoor and indoor spike event data, TALEN-PCC achieves higher compression gains for time aggregation intervals of more than 5 ms. However, the compression gains are lower when compared to state-of-the-art approaches for time aggregation intervals of less than 5 ms.

Utilizing the Newest Vital Sign (NVS) to Assess Health Literacy at a Regional Academic Medical Center's Family Medicine Clinic.

Researchers examined the correlation between the physician's subjective assessment of health literacy rates and actual health literacy rates among patients as determined by the Newest Vital Sign (NVS). A sample of n = 150 patients, 18 years of age or older, were verbally interviewed using NVS tool before seeing their physician. After the physician met with the patient, the physician was asked to measure that patient's level of health literacy on a Likert-type scale and a "yes/no" scale. Frequency and percentage statistics were performed in SPSS to describe the distributions of patient and physician responses. Between-subjects statistics were used. Analysis of the patient surveys revealed one in 4 patients has a high likelihood of low health literacy. Analysis revealed there were significant positive correlations between physician response to perception of a patient's low health literacy risk and NVS survey responses. Despite the risk of limited literacy, 97.3% of physicians perceived the patient to understand what the physician was saying. Physicians should use teach-back and other health literacy principles with each patient, regardless of perceived risk.

Mood and anxiety disorders within the Research Domain Criteria framework of Positive and Negative Valence Systems: a scoping review.

Introduction: While a growing body of research is adopting Research Domain Criteria (RDoC)-related methods and constructs, there is still a lack of comprehensive reviews on the state of published research on Positive Valence Systems (PVS) and Negative Valence Systems (NVS) in mood and anxiety disorders consistent with the RDoC framework. Methods: Five electronic databases were searched to identify peer-reviewed publications covering research on "positive valence" and "negative valence" as well as "valence," "affect," and "emotion" for individuals with symptoms of mood and anxiety disorders. Data was extracted with a focus on disorder, domain, (sub-) constructs, units of analysis, key results, and study design. Findings are presented along four sections, distinguishing between primary articles and reviews each for PVS, NVS, and cross-domain PVS and NVS. Results: A total of 231 abstracts were identified, and 43 met the inclusion criteria for this scoping review. Seventeen publications addressed research on PVS, seventeen on NVS, and nine covered cross-domain research on PVS and NVS. Psychological constructs were typically examined across different units of analysis, with the majority of publications incorporating two or more measures. Molecular, genetic, and physiological aspects were mainly investigated via review articles, primary articles focused on self-report, behavioral, and, to a lesser extent, physiological measures. Conclusions: This present scoping review shows that mood and anxiety disorders were actively studied using a range of genetic, molecular, neuronal, physiological, behavioral, and self-report measures within the RDoC PVS and NVS. Results highlight the essential role of specific cortical frontal brain structures and of subcortical limbic structures in impaired emotional processing in mood and anxiety disorders. Findings also indicate overall limited research on NVS in bipolar disorders and PVS in anxiety disorders, a majority of self-report studies, and predominantly observational studies. Future research is needed to develop more RDoC-consistent advancements and intervention studies targeting neuroscience-driven PVS and NVS constructs.

Comparison of extruded cell nanovesicles and exosomes in their molecular cargos and regenerative potentials.

Extracellular vesicles (EVs) generated from mesenchymal stem cells (MSCs) play an essential role in modulating cell-cell communication and tissue regeneration. The clinical translation of EVs is constrained by the poor yield of EVs. Extrusion has recently become an effective technique for producing a large scale of nanovesicles (NVs). In this study, we systematically compared MSC NVs (from extrusion) and EVs (from natural secretion). Proteomics and RNA sequencing data revealed that NVs resemble MSCs more closely than EVs. Additionally, microRNAs in NVs are related to cardiac repair, fibrosis repression, and angiogenesis. Lastly, intravenous delivery of MSC NVs improved heart repair and cardiac function in a mouse model of myocardial infarction. Electronic Supplementary Material: Supplementary material (Figs. S1-S4) is available in the online version of this article at 10.1007/s12274-023-5374-3.

QTL Pyramiding Provides Marginal Improvement in 2NvS-Based Wheat Blast Resistance.

Wheat blast, caused by the fungus Magnaporthe oryzae Triticum pathotype (MoT), is a devastating disease affecting South America, Bangladesh, and Zambia. Resistance to wheat blast has strongly relied on the 2NvS translocation; however, newer MoT isolates have increased aggressiveness, threatening the 2NvS translocation's effectiveness and durability. To identify genomic regions associated with wheat blast resistance, we performed a quantitative trait loci (QTL) mapping study using 187 double-haploid (DH) lines from a cross between the Brazilian wheat cultivars 'TBIO Alvorada' and 'TBIO Sossego', which are moderately resistant and susceptible to blast, respectively. The DH population was evaluated in a greenhouse in Brazil and Bolivia, and field conditions in Bolivia. Contrasting models best explained the relationship between traits evaluated according to differences in disease levels and the presence of the 2NvS. A large effect-locus, derived from 'TBIO Sossego', was identified on chromosome 2AS, which was confirmed to be 2NvS translocation and explained 33.5 to 82.4% of the phenotypic variance. Additional significant loci were identified on 5AL, 1DS, 4DS, 5DL, and 6DL chromosome arms with phenotypic variance <6%, but they were not consistent across trait-environment combinations. QTL pyramiding analyses showed that some specific loci had an additive effect when combined with the 2NvS, suggesting that stacking multiple loci may be an effective strategy to help manage wheat blast. The markers associated with the 2NvS can be used as dominant diagnostic markers for this alien translocation. Additional characterization of these loci using a broader set of MoT isolates is critical to validate their effectiveness against current MoT populations.

High performance carbon dots based prodrug Platform: Image-Guided photodynamic and chemotherapy with On-Demand drug release upon laser irradiation.

The design of therapeutic nanoplatforms based on fluorescent carbon dots (CDs) has become a viable strategy because of their aqueous solubility, biocompatibility, and ease of further functionalization. By doping various heteroatoms into pristine CDs structures, we synthesized N-, Cl-, and S-doped CDs (NClS/CDs), as well as Se-, N-, and Cl-doped CDs (NClSe/CDs) with superior optoelectronic properties using rapid and straightforward microwave heating. The quantum efficiencies of these NClS/CDs and NClSe/CDs were enhanced to 30.7 % and 42.9 %, respectively, compared to those of undoped CDs (0.66 %). Owing to their better light absorption properties, NClS/CDs efficiently produced reactive oxygen species (ROS) under 532 nm laser irradiation for photodynamic therapy (PDT). Considering the ROS generation and surface carrier abilities of NClS/CDs, we designed the loading of camptothecin (CPT) drug via a thioketal linker (TL), resulting in h/CDs@CPT nanovesicles (NVs) with a drug-loading efficiency of 46.5 %. Under laser irradiation in an acidic environment, ROS-triggered CPT release was observed, with 50.2 % of CPT released following the breakdown of the ROS-sensitive TL. In vitro cellular studies revealed that h/CDs@CPT NVs possessed minimal cytotoxicity toward HeLa and 4 T1 cancer cells, despite the high clinical efficacy of PDT and ROS-induced chemotherapeutic response under laser treatment. Confocal microscopy of HeLa and 4 T1 cells revealed that h/CDs@CPT NVs produced red-emissive photographs for potential cancer cell detection. Therefore, our study presents an image-guided PDT and chemotherapeutic platform based on h/CDs@CPT NVs, which will be an attractive candidate for future cancer treatment.

Results of the BfR MEAL Study: Highest levels of retinol found in animal livers and of ß-carotene in yellow-orange and green leafy vegetables.

This Total Diet Study (TDS) provides representative data on substance levels in foods, prepared as typically consumed by the population in Germany for future dietary exposure assessment. Vitamin A is essential and must be obtained from the diet, either as preformed vitamin A or as provitamin A carotenoids. Levels of retinol and ß-carotene were analysed in 333 and 271 foods, respectively. Highest mean retinol levels were found in cod liver (25,000 µg∙100 g-1), followed by other animal livers, liver-based products, butter, eel and fortified margarine. In contrast, highest mean ß-carotene levels were found in carrots (4,650 µg∙100 g-1), followed by other yellow-orange fruits and vegetables, green leafy vegetables and fortified fruit nectars. Sampling by production type and seasonality revealed differences in retinol and ß-carotene levels in individual foods. This TDS expands the existing data for ß-carotene and vitamin A extensively by providing representative data on most consumed foods.

Is the unrealistic expectation of getting cured related to poor treatment adherence among Indian Asthma patients? A hospital based mixed methods study from central India.

Background: Prevention of premature deaths due to asthma requires continued disease control through efforts of both patients and healthcare providers. The expectations of patients have been shown to influence treatment adherence and disease control. Methodology: We conducted a hospital-based sequential exploratory mixed methods study and used definitions of the Global Initiative for Prevention of Asthma (GINA). We recruited 80 asthma patients in a tertiary public health facility of central India. We assessed treatment expectations, health literacy, awareness, behavioural risk factors, self-care, treatment adherence, and disease control. We conducted a thematic analysis of qualitative data through manual inductive coding and used statistical software R version-3.6.1 for quantitative analysis. Results: Sixty-seven (83.75%) patients expected that the current doctor would help them achieve 'cure', while 28 (35%) expected to obtain information about asthma. 81.2% and 77.5% of participants had inadequate health literacy and inadequate awareness, respectively. 73.8% were using inhalers and 21.2% were not using any treatment. Forced expiratory volume in 1 (FEV1) and Forced vital capacity (FVC) values were available for only 46.25%, while a meagre 6.25% were using peak-flow meter for self-monitoring. Though 21.2% reported optimal treatment adherence, 27.5% had good control. We found the expectation of cure and poor health literacy being significantly related to sub-optimal treatment adherence. We didn't find any association between the expectations of patients and their disease control. Conclusion: Asthma patients in our setting mostly expected to get cured. The unrealistic expectation of 'cure' is related to poor treatment adherence and possibly poor disease control.

Understanding Health Literacy among University Health Science Students of Different Nationalities.

An adequate level of health literacy is essential for clear communication between patients and health care workers. The internationalization of universities is increasing in the field of health care. The aims of our research were to measure (1) the level of health literacy and its correlation among university students and (2) the relationship between the different instruments measuring health literacy. A cross-sectional study was conducted in the 2020/2021 academic year. The questionnaire included questions on sociodemographic status, study data, health status, and health literacy level. According to the HLS-EU-Q16 health literacy questionnaire, more than half of the students had a limited HL level in disease prevention (52.4%) and health promotion (58.4%) subindexes. Nationality was found to be an influencing factor (p < 0.001). According to the NVS, 80.1% of the students had an adequate HL level. A significant correlation was found between the results and nationality (p = 0.005). None of the Chew questions demonstrated a correlation with nationality (q1 p = 0.269, q2 p = 0.368, q3 p = 0.528). Nationality is a key factor in the level of subjective and functional health literacy. We need to measure both types of levels to see the real results.

Results of the BfR MEAL Study: The food type has a stronger impact on calcium, potassium and phosphorus levels than factors such as seasonality, regionality and type of production.

The BfR MEAL Study aims to provide representative levels of chemical substances in foods consumed by the population in Germany for dietary exposure assessment. Calcium, potassium and phosphorus (Ca, K, P) are essential to obtain physiological functions in humans. Levels were investigated in 356 foods. Foods were purchased representatively, prepared as typically consumed and pooled before analysis. High mean levels were found in milk, dairy products, legumes, nuts, oilseeds and spices as well as chia seeds (Ca, K, P), chewing gum (Ca) and cocoa powder (K). Different levels comparing organically and conventionally produced foods were determined among others in cereal cracker (puffed), olives and tofu. Higher K levels were found in fried compared to boiled potatoes. Similar P levels were mainly found in regionally and seasonally sampled foods. These data provide a substantially improved basis to address dietary exposure assessment of the population in Germany for Ca, K and P.

Successful identification of Granulicatella adiacens in postoperative acute infectious endophthalmitis using a bacterial 16S ribosomal RNA gene-sequencing platform with MinION™: A case report.

Purpose: To evaluate the efficacy of identifying the bacteria by aqueous sampling and vitreous sampling in postoperative infectious endophthalmitis using 16S ribosomal RNA (rRNA) gene analysis with a nanopore sequencer (MinION™). Observation: A 55-year-old woman who underwent cataract surgery at an ophthalmology clinic 18 days ago was referred to our hospital for suspected endophthalmitis. She had light perception visual acuity in her right eye; however, the eye was severely inflamed, with a hypopyon and a fibrinous membrane in the anterior chamber. The fundus was not visible because of vitreous opacity on a B-scan image. Based on the diagnosis of postoperative acute infectious endophthalmitis, we performed a vitrectomy, intraocular lens extraction, and silicone oil tamponade. On postoperative day 14, the inflammation resolved. An aqueous sample was collected before surgical treatment, and the vitreous sample was collected during the operation. Both samples underwent 16S rRNA gene analysis with a nanopore sequencer MinION™ to identify the causative organism. Conclusions and Importance: In the aqueous humor, Granulicatella adiacens and Cutibacterium acnes were identified before the operation, while only Granulicatella adiacens was detected in the vitreous sample after the operation. Although the aqueous humor sample might contain commensal bacteria, it could provide a predictable result before the operation. It can also provide a substitute for a vitreous sample to allow earlier identification of the causative organism.

The First Case of Granulicatella adiacens Identified from a Resected Heart Valve by Next Generation Sequencing (NGS) in Poland.

In this report, we describe the course and successful treatment of a case of complicated infective endocarditis (IE). A patient presented with a high-grade, irregular fever with chills lasting at least 2 months along with dyspnoea, chest pain, fatigue, weight loss, and night sweats during the previous 3 months. As well as cardiac congenital disorders, he was found to have Granulicatella adiacens infective aortic valve endocarditis, presumably transmitted from the oral cavity niche. Validated metagenomic 16S rDNA next generation sequencing was used to perform taxonomic identification, allowing for specific adequate antibiotic therapy instead of empiric therapy. This paper highlights the critical role of rapid taxonomic identification of nutritionally variant streptococci and the benefit of proper IE treatment in avoiding relapses or fatal complications.

Cellular membrane-based vesicles displaying a reconstructed B cell maturation antigen for multiple myeloma therapy by dual targeting APRIL and BAFF.

Excessive secretion of cytokines (such as APRIL and BAFF) in the bone marrow microenvironment (BMM) plays an essential role in the formation of relapsed or refractory multiple myeloma (MM). Blocking the binding of excessive cytokines to their receptors is becoming a promising approach for MM therapy. Here, we proposed a strategy of engineering cell membrane-based nanovesicles (NVs) to reconstruct B cell maturation antigen (BCMA), a receptor of APRIL and BAFF, to capture excess APRIL/BAFF in BMM as a bait protein. Our results showed that reconstructed BCMA expressed on the membrane of NVs (Re-BCMA-NVs) retained the ability of binding to soluble and surface-bound APRIL/BAFF in BMM. Consequently, Re-BCMA-NVs blocked the activation of the NF-κB pathway, downregulating the expression of anti-apoptosis genes and cell cycle-related genes, and hence inhibiting MM cell survival. Importantly, Re-BCMA-NVs showed a synergistic anti-MM effect when administrated together with bortezomib (BTZ) in vitro and in vivo. Our NVs targeting multiple cytokines in cancer microenvironment provides a solution to enhance sensitivity of MM cells to BTZ-based therapy. STATEMENT OF SIGNIFICANCE: Excessive APRIL and BAFF is reported to promote the survival of MM cell and facilitate the formation of resistance to bortezomib therapy. In this study, we bioengineered cell membrane derived reconstructed BCMA nanovesicles (Re-BCMA-NVs) to capture both soluble and cell-surface APRIL and BAFF. These NVs inhibited the activation of NF-κB pathway and thus inhibit the survival of MM cells in 2D, 3D and subcutaneous mouse tumor models. Importantly, Re-BCMA-NVs showed a synergistic anti-MM effect when administrated together with bortezomib in vitro and in vivo. Taken together, our NVs targeting multiple cytokines in cancer microenvironment provides a solution to enhance sensitivity of MM cells to bortezomib-based therapy.

The right pick: Does a self-assessment measurement tool correctly identify health care consumers with inadequate health literacy?

OBJECTIVES: The aim of this study was to investigate whether a self-report measurement instrument (the Brief Health Literacy Screen, BHLS) correctly identifies healthcare consumers with inadequate health literacy. The yardstick for assessing the tool was the Newest Vital Sign (NVS). METHODS: The study used baseline data from the Västerbotten Intervention Programme - VIsualiZation of Asymptomatic Atherosclerotic disease for Optimum Cardiovascular Prevention (VIPVIZA), a randomized controlled trial that is nested within the Västerbotten Intervention Program (VIP) in Sweden. Our analyses were computed on a subsample of 460 persons who underwent the measure of both health literacy scales. ROC analysis was used for the crucial computations. RESULTS: The potential of the BHLS to identify healthcare consumers with inadequate health literacy remained unsatisfying for the complete sample, but reached an acceptable level for women and persons with only basic education. CONCLUSIONS: The relationship is somewhat weaker than in comparable research in various other European countries. The differences might partly have been caused by the use of self-perception questions. Self-delusions, invariably a part of self-perception, may have affected the respective measure. PRACTICE IMPLICATIONS: Caution is advised when patients' health literacy is assessed by only a few questions for self-report.

Synthesis of NVS-BPTF-1 and evaluation of its biological activity.

BPTF (bromodomain and PHD finger containing transcription factor) is a multidomain protein that plays essential roles in transcriptional regulation, T-cell homeostasis and stem cell pluripotency. As part of the chromatin remodeling complex hNURF (nucleosome remodeling factor), BPTF epigenetic reader subunits are particularly important for BPTF cellular function. Here we report the synthesis of NVS-BPTF-1, a previously reported highly potent and selective BPTF-bromodomain inhibitor. Evaluation of the impact of the inhibition of BPTF-bromodomain using NVS-BPTF-1 on selected proteins involved in the antigen processing pathway revealed that exclusively targeting BPTF-bromodomain is insufficient to observe an increase of PSMB8, PSMB9, TAP1 and TAP2 proteins.

Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways.

It has been reported that monoamine neurotransmitters can be produced by gut microbiota, and that several related metabolites of amino acids in these pathways are associated with nervous system (NVS) diseases. Herein, we focused on three pathways, namely, phenylalanine (Phe), tryptophan (Trp), and glutamic acid (Glu), and established an underivatized liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of nineteen monoamine neurotransmitters and related metabolites in the gut microbiota. The neurotransmitters and related metabolites included Phe, tyrosine (Tyr), l-dopa (Dopa), dopamine (DA), 3-methoxytyramine, Trp, hydroxytryptophan, 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), kynurenine (KN), kynurenic acid (KYNA), melatonin, tryptamine (TA), indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), indolyl-3-propionic acid (IPA), Glu, gamma-aminobutyric acid (GABA), and acetylcholine (Ach). A fluoro-phenyl bonded column was used for separation, and the mobile phase consisted of methanol:acetonitrile (1:1) and water, with 0.2% formic acid in both phases. The compounds exhibited symmetric peak shapes and sufficient sensitivity under a total analysis time of 8.5 min. The method was fully validated with acceptable linearity, accuracy, precision, matrix effect, extraction recovery, and stability. The results showed that neurotransmitters, such as Dopa, DA, 5-HT, GABA, and Ach, were present in the gut microbiota. The metabolic pathway of Trp was disordered under depression, with lower levels of 5-HT, 5-HIAA, KN, KYNA, TA, ILA, IAA, IPA, and Glu, and a higher ratio of KYNA/KN. In addition, some first-line NVS drugs, such as sertraline, imipramine, and chlorpromazine, showed regulatory potential on these pathways in the gut microbiota.

Skipped vertebral spontaneous spondylodiscitis caused by Granulicatella adiacens: Case report and a systematic literature review.

BACKGROUND: Granulicatella adiacens is a nutritional variant of streptococcus (NVS), which has been rarely reported as an etiologic agent in spondylodiscitis (SD). MATERIAL AND METHODS: We report a case of a 51-year-old male with from chronic low-back pain associated with right sciatica and ipsilateral monoparesis. Spinal MRI showed radiological signs on L1-L2 and L5-S1 discs consistent with SD. We also performed a systematic review of the pertinent literature in order to retrieve all the key information regarding microbiological and clinical features. RESULTS: Including our patients, seven cases with a mean age 56 ±â€¯10.2 years were reported in English literature. Six patients were conservatively managed with antibiotic therapy (66%), whereas three with surgery in combination with antibiotics (33%). An endocarditis was associated in three cases, and a pacemaker infection in one. All patients received targeted antibiotic therapy resulting in a quick improvement of clinical symptoms with favorable outcome. Our case is the only with a skip spontaneous SD, which needed a surgical decompression due to the associated neurological symptoms. CONCLUSIONS: This incidence of SD sustained by Granulicatella adiances could be underestimated due to their particular microbiological conditions requested for their cultures. However, this infection should be suspected in cases of culture-negative SD, especially when associated with endocarditis.

Attenuation of Tumor Necrosis Factor-α Induced Inflammation by Umbilical Cord-Mesenchymal Stem Cell Derived Exosome-Mimetic Nanovesicles in Endothelial Cells.

BACKGROUND: Inflammation induces dysfunction of endothelial cells via inflammatory cell adhesion, and this phenomenon and reactive oxygen species accumulation are pivotal triggers for atherosclerosis-related vascular disease. Although exosomes are excellent candidate as an inhibitor in the inflammation pathway, it is necessary to develop exosome-mimetic nanovesicles (NVs) due to limitations of extremely low release rate and difficult isolation of natural exosomes. NVs are produced in much larger quantities than natural exosomes, but due to the low flexibility of the cell membranes, the high loss caused by hanging on the filter membranes during extrusion remains a challenge to overcome. Therefore, by making cell membranes more flexible, more efficient production of NVs can be expected. METHODS: To increase the flexibility of the cell membranes, the suspension of umbilical cord-mesenchymal stem cells (UC-MSCs) was subjected to 5 freeze and thaw cycles (FT) before serial extrusion. After serial extrusion through membranes with three different pore sizes, FT/NVs were isolated using a tangential flow filtration (TFF) system. NVs or FT/NVs were pretreated to the human coronary artery endothelial cells (HCAECs), and then inflammation was induced using tumor necrosis factor-α (TNF-α). RESULTS: With the freeze and thaw process, the production yield of exosome-mimetic nanovesicles (FT/NVs) was about 3 times higher than the conventional production method. The FT/NVs have similar biological properties as NVs for attenuating TNF-α induced inflammation. CONCLUSION: We proposed the efficient protocol for the production of NVs with UC-MSCs using the combination of freeze and thaw process with a TFF system. The FT/NVs successfully attenuated the TNF-α induced inflammation in HCAECs.