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Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.
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Bexiga Urinária , Infecções Urinárias , Animais , Humanos , Bexiga Urinária/cirurgia , Urodinâmica/fisiologia , Próteses e Implantes , CistectomiaRESUMO
Vocal fatigue is a measurable form of performance fatigue resulting from overuse of the voice and is characterized by negative vocal adaptation. Vocal dose refers to cumulative exposure of the vocal fold tissue to vibration. Professionals with high vocal demands, such as singers and teachers, are especially prone to vocal fatigue. Failure to adjust habits can lead to compensatory lapses in vocal technique and an increased risk of vocal fold injury. Quantifying and recording vocal dose to inform individuals about potential overuse is an important step toward mitigating vocal fatigue. Previous work establishes vocal dosimetry methods, that is, processes to quantify vocal fold vibration dose but with bulky, wired devices that are not amenable to continuous use during natural daily activities; these previously reported systems also provide limited mechanisms for real-time user feedback. This study introduces a soft, wireless, skin-conformal technology that gently mounts on the upper chest to capture vibratory responses associated with vocalization in a manner that is immune to ambient noises. Pairing with a separate, wirelessly linked device supports haptic feedback to the user based on quantitative thresholds in vocal usage. A machine learning-based approach enables precise vocal dosimetry from the recorded data, to support personalized, real-time quantitation and feedback. These systems have strong potential to guide healthy behaviors in vocal use.
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Canto , Distúrbios da Voz , Voz , Humanos , Retroalimentação , Distúrbios da Voz/etiologia , Voz/fisiologia , Prega Vocal/fisiologiaRESUMO
SLURP1 and SLURP2 are both small secreted members of the Ly6/u-PAR family of proteins and are highly expressed in keratinocytes. Loss-of-function mutations in SLURP1 lead to a rare autosomal recessive palmoplantar keratoderma (PPK), Mal de Meleda (MdM), which is characterized by diffuse, yellowish palmoplantar hyperkeratosis. Some individuals with MdM experience pain in conjunction with the hyperkeratosis that has been attributed to fissures or microbial superinfection within the affected skin. By comparison, other hereditary PPKs such as pachyonychia congenita and Olmsted syndrome show prevalent pain in PPK lesions. Two mouse models of MdM, Slurp1 knock-out and Slurp2X knock-out, exhibit robust PPK in all four paws. However, whether the sensory experience of these animals includes augmented pain sensitivity remains unexplored. In this study, we demonstrate that both models exhibit hypersensitivity to mechanical and thermal stimuli as well as spontaneous pain behaviors in males and females. Anatomical analysis revealed slightly reduced glabrous skin epidermal innervation and substantial alterations in palmoplantar skin immune composition in Slurp2X knock-out mice. Primary sensory neurons innervating hindpaw glabrous skin from Slurp2X knock-out mice exhibit increased incidence of spontaneous activity and mechanical hypersensitivity both in vitro and in vivo. Thus, Slurp knock-out mice exhibit polymodal PPK-associated pain that is associated with both immune alterations and neuronal hyperexcitability and might therefore be useful for the identification of therapeutic targets to treat PPK-associated pain.
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Antígenos Ly , Ceratodermia Palmar e Plantar , Camundongos Knockout , Ativador de Plasminogênio Tipo Uroquinase , Animais , Feminino , Masculino , Camundongos , Antígenos Ly/genética , Antígenos Ly/metabolismo , Modelos Animais de Doenças , Hiperalgesia/genética , Hiperalgesia/fisiopatologia , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/patologia , Camundongos Endogâmicos C57BL , Limiar da Dor/fisiologia , Ativador de Plasminogênio Tipo Uroquinase/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
A human lectin array has been developed to probe the interactions of innate immune receptors with pathogenic and commensal micro-organisms. Following the successful introduction of a lectin array containing all of the cow C-type carbohydrate-recognition domains (CRDs), a human array described here contains the C-type CRDs as well as CRDs from other classes of sugar-binding receptors, including galectins, siglecs, R-type CRDs, ficolins, intelectins and chitinase-like lectins. The array is constructed with CRDs modified with single-site biotin tags, ensuring that the sugar-binding sites in CRDs are displayed on a streptavidin-coated surface in a defined orientation and are accessible to the surfaces of microbes. A common approach used for expression and display of CRDs from all of the different structural categories of glycan-binding receptors allows comparisons across lectin families. In addition to previously documented protocols for binding of fluorescently-labeled bacteria, methods have been developed for detecting unlabeled bacteria bound to the array by counter-staining with DNA-binding dye. Screening has also been undertaken with viral glycoproteins and bacterial and fungal polysaccharides. The array provides an unbiased screen for sugar ligands that interact with receptors and many show binding not anticipated from earlier studies. For example, some of the galectins bind with high affinity to bacterial glycans that lack lactose or N-acetyllactosamine. The results demonstrate the utility of the human lectin array for providing a unique overview of the interactions of multiple classes of glycan-binding proteins in the innate immune system with different types of micro-organisms.
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We recently established a long-term SARS-CoV-2 infection model using lung-cancer xenograft mice and identified mutations that arose in the SARS-CoV-2 genome during long-term propagation. Here, we applied our model to the SARS-CoV-2 Delta variant, which has increased transmissibility and immune escape compared with ancestral SARS-CoV-2. We observed limited mutations in SARS-CoV-2 Delta during long-term propagation, including two predominant mutations: R682W in the spike protein and L330W in the nucleocapsid protein. We analyzed two representative isolates, Delta-10 and Delta-12, with both predominant mutations and some additional mutations. Delta-10 and Delta-12 showed lower replication capacity compared with SARS-CoV-2 Delta in cultured cells; however, Delta-12 was more lethal in K18-hACE2 mice compared with SARS-CoV-2 Delta and Delta-10. Mice infected with Delta-12 had higher viral titers, more severe histopathology in the lungs, higher chemokine expression, increased astrocyte and microglia activation, and extensive neutrophil infiltration in the brain. Brain tissue hemorrhage and mild vacuolation were also observed, suggesting that the high lethality of Delta-12 was associated with lung and brain pathology. Our long-term infection model can provide mutant viruses derived from SARS-CoV-2 Delta and knowledge about the possible contributions of emergent mutations to the properties of new variants.
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COVID-19 , SARS-CoV-2 , Humanos , Animais , Camundongos , Xenoenxertos , SARS-CoV-2/genética , EncéfaloRESUMO
SARS-CoV-2 Omicron has the largest number of mutations among all the known SARS-CoV-2 variants. The presence of these mutations might explain why Omicron is more infectious and vaccines have lower efficacy to Omicron than other variants, despite lower virulence of Omicron. We recently established a long-term in vivo replication model by infecting Calu-3 xenograft tumors in immunodeficient mice with parental SARS-CoV-2 and found that various mutations occurred majorly in the spike protein during extended replication. To investigate whether there are differences in the spectrum and frequency of mutations between parental SARS-CoV-2 and Omicron, we here applied this model to Omicron. At 30 days after infection, we found that the virus was present at high titers in the tumor tissues and had developed several rare sporadic mutations, mainly in ORF1ab with additional minor spike protein mutations. Many of the mutant isolates had higher replicative activity in Calu-3 cells compared with the original SARS-CoV-2 Omicron virus, suggesting that the novel mutations contributed to increased viral replication. Serial propagation of SARS-CoV-2 Omicron in cultured Calu-3 cells resulted in several rare sporadic mutations in various viral proteins with no mutations in the spike protein. Therefore, the genome of SARS-CoV-2 Omicron seems largely stable compared with that of the parental SARS-CoV-2 during extended replication in Calu-3 cells and xenograft model. The sporadic mutations and modified growth properties observed in Omicron might explain the emergence of Omicron sublineages. However, we cannot exclude the possibility of some differences in natural infection.
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COVID-19 , Neoplasias Pulmonares , Mutação , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Replicação Viral , Animais , Replicação Viral/genética , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Camundongos , Humanos , COVID-19/virologia , Neoplasias Pulmonares/virologia , Neoplasias Pulmonares/genética , Glicoproteína da Espícula de Coronavírus/genética , Modelos Animais de Doenças , Linhagem Celular TumoralRESUMO
BACKGROUND: With the rapidly aging population in China, there is an urgent need to understand and address the community care needs of older adults. This study sought to examine these unmet community care needs of older adults in China and the factors influencing them, with the goal of providing essential groundwork for the development of community care health policies. METHODS: This study used data from the 2018 China Longitudinal Healthy Longevity Survey of 8,870 adults aged 65 years and older. Logistic regression analysis was performed to identify factors related to unmet community care needs. RESULTS: The results showed that lower number of children, increased years of schooling, poorer self-perceived economic and health status, residing in an institution rather than living with household members, not having public old-age pensions, and not having activity due to daily living impairments were associated with a higher likelihood of unmet community care needs among older adults. CONCLUSIONS: These findings indicate the necessity for crafting policies that consider the factors affecting unmet community care needs of older adults, including their health vulnerabilities and individual needs. Implementing national initiatives aimed at enhancing the quality of services delivered to older adults is crucial, along with establishing programmes to proactively address their vulnerabilities and individual needs. This study can contribute to the formulation of policy measures aimed at enhancing community care services of older adults in China.
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Necessidades e Demandas de Serviços de Saúde , Humanos , Idoso , China/epidemiologia , Masculino , Feminino , Idoso de 80 Anos ou mais , Serviços de Saúde Comunitária/tendências , Serviços de Saúde Comunitária/métodos , Estudos Longitudinais , Atividades CotidianasRESUMO
In the context of LiDAR sensor-based autonomous vehicles, segmentation networks play a crucial role in accurately identifying and classifying objects. However, discrepancies between the types of LiDAR sensors used for training the network and those deployed in real-world driving environments can lead to performance degradation due to differences in the input tensor attributes, such as x, y, and z coordinates, and intensity. To address this issue, we propose novel intensity rendering and data interpolation techniques. Our study evaluates the effectiveness of these methods by applying them to object tracking in real-world scenarios. The proposed solutions aim to harmonize the differences between sensor data, thereby enhancing the performance and reliability of deep learning networks for autonomous vehicle perception systems. Additionally, our algorithms prevent performance degradation, even when different types of sensors are used for the training data and real-world applications. This approach allows for the use of publicly available open datasets without the need to spend extensive time on dataset construction and annotation using the actual sensors deployed, thus significantly saving time and resources. When applying the proposed methods, we observed an approximate 20% improvement in mIoU performance compared to scenarios without these enhancements.
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Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by genetic predisposition, environmental factors, immune dysregulation, and skin barrier dysfunction. The skin microbiome and metabolome play crucial roles in modulating the skin's immune environment and integrity. However, their specific contributions to AD remain unclear. We aimed to investigate the distinct skin microbial communities and skin metabolic compounds in AD patients compared to healthy controls (HCs). Seven patients with AD patients and seven HCs were enrolled, from whom skin samples were obtained for examination. The study involved 16S rRNA metagenomic sequencing and bioinformatics analysis as well as the use of gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) to detect metabolites associated with AD in the skin. We observed significant differences in microbial diversity between lesional and non-lesional skin of AD patients and HCs. Staphylococcus overgrowth was prominent in AD lesions, while Cutibacterium levels were decreased. Metabolomic analysis revealed elevated levels of several metabolites, including hypoxanthine and glycerol-3-phosphate in AD lesions, indicating perturbations in purine metabolism and energy production pathways. Moreover, we found a positive correlation between hypoxanthine and glycerol-3-phosphate and clinical severity of AD and Staphylococcus overgrowth. These findings suggest potential biomarkers for monitoring AD severity. Further research is needed to elucidate the causal relationships between microbial dysbiosis, metabolic alterations, and AD progression, paving the way for targeted therapeutic interventions.
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Dermatite Atópica , Metaboloma , Microbiota , Pele , Dermatite Atópica/microbiologia , Dermatite Atópica/metabolismo , Humanos , Pele/microbiologia , Pele/metabolismo , Feminino , Masculino , Adulto , RNA Ribossômico 16S/genética , Metabolômica/métodos , Adulto Jovem , Pessoa de Meia-Idade , Estudos de Casos e ControlesRESUMO
Zika virus (ZIKV), transmitted by Aedes mosquitoes, has been a global health concern since 2007. It primarily causes fetal microcephaly and neuronal defects through maternal transmission and induces neurological complications in adults. Recent studies report elevated proinflammatory cytokines and persistent neurological alterations post recovery, but the in vivo mechanisms remain unclear. In our study, viral RNA loads in the brains of mice infected with ZIKV peaked at 7 days post infection and returned to baseline by day 21, indicating recovery. RNA sequencing of the cerebral cortex at 7 and 21 days revealed upregulated genes related to neuroinflammation and microglial activation. Histological analyses indicated neuronal cell death and altered neurite morphology owing to severe neuroinflammation. Additionally, sustained microglial activation was associated with increased phospho-Tau levels, constituting a marker of neurodegeneration. These findings highlight how persistent microglial activation leads to neuronal dysfunction post ZIKV recovery, providing insights into the molecular pathogenesis of ZIKV-induced brain abnormalities.
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Microglia , Neurônios , Infecção por Zika virus , Zika virus , Animais , Infecção por Zika virus/virologia , Infecção por Zika virus/patologia , Infecção por Zika virus/metabolismo , Microglia/virologia , Microglia/metabolismo , Microglia/patologia , Camundongos , Zika virus/fisiologia , Zika virus/patogenicidade , Neurônios/virologia , Neurônios/metabolismo , Neurônios/patologia , Sinapses/patologia , Sinapses/metabolismo , Encéfalo/virologia , Encéfalo/patologia , Encéfalo/metabolismo , Modelos Animais de Doenças , Feminino , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/virologia , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/metabolismo , Carga ViralRESUMO
Background and Objectives: This study aimed to evaluate the mid-term effectiveness and safety of a combined ultrasound (US) and fluoroscopy (FL)-guided approach in comparison to US-guided and FL-guided caudal epidural steroid injections (CESI) for treating unilateral lower lumbar radicular pain. Materials and Methods: A total of 154 patients who underwent CESI between 2018 and 2022 were included. Patients were categorized into three groups based on the guidance method: combined US and FL (n = 51), US-guided (n = 51), and FL-guided (n = 52). The study design was retrospective case-controlled, utilizing patient charts and standardized forms to assess clinical outcomes, adverse events, complications during the procedures. Results: In all groups, Oswestry Disability Index and Verbal Numeric Scale scores improved at 1, 3, and 6 months after the last injection, with no significant differences between groups (p < 0.05). The treatment success rate at all time points was also similar among the groups. Logistic regression analysis showed that injection method, cause, sex, age, number of injections, and pain duration did not independently predict treatment success. Blood was aspirated before injection in 2% (n = 1), 13.5% (n = 7), and 4% (n = 2) of patients in the combined US and FL groups, FL-guided groups, and US-guided groups, respectively. Intravascular contrast spread was detected in one patient in the combined method groups and seven in the FL-guided groups. Conclusions: When comparing pain reduction and functional improvement, there was no significant difference between the three methods. The combined method took less time compared to using FL alone. The combined approach also showed a lower occurrence of intravascular injection compared to using FL alone. Moreover, blood vessels at the injection site can be identified with an ultrasound using the combined method. Given these advantages, it might be advisable to prioritize the combined US- and FL-guided therapy when administering CESI for patients with unilateral lumbar radicular pain.
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Dor Lombar , Esteroides , Humanos , Estudos Retrospectivos , Fluoroscopia/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Injeções Epidurais/métodos , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Dor Lombar/tratamento farmacológico , Adulto , Idoso , Ultrassonografia de Intervenção/métodos , Resultado do Tratamento , Radiculopatia/tratamento farmacológico , Radiculopatia/complicações , Estudos de Casos e Controles , Vértebras Lombares , Ultrassonografia/métodos , Região LombossacralRESUMO
Nitric oxide (NO) is a gaseous molecule intricately implicated in oncologic processes, encompassing the modulation of angiogenesis and instigating apoptosis. Investigation of the antitumor effects of NO is currently underway, necessitating a detailed understanding of its cellular-level reactions. Regulating the behavior of radical NO species has been a significant challenge, primarily due to its instability in aqueous environments by rapid O2-induced degradation. In this study, we devised an electrochemical platform to investigate the cellular responses to reactive gaseous molecules. Our designed platform precisely controlled the NO flux and diffusion rates of NO to tumor cells. COMSOL Multiphysics calculations based on diffusion and reaction kinetics were conducted to simulate the behavior of electrochemically generated NO. We discerned that the effective radius, NO flux, and electrolysis duration are pivotal factors governing cellular response by NO.
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Peptides are promising therapeutic agents for COVID-19 because of their specificity, easy synthesis, and ability to be fine-tuned. We previously demonstrated that a cell-permeable peptide corresponding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike C-terminal domain (CD) inhibits the interaction between viral spike and nucleocapsid proteins that results in SARS-CoV-2 replication in vitro. Here, we used docking studies to design R-t-Spike CD(D), a more potent short cell-penetrating peptide composed of all D-form amino acids and evaluated its inhibitory effect against the replication of SARS-CoV-2 S clade and other variants. R-t-Spike CD(D) was internalized into Vero cells and Calu-3 cells and suppressed the replication of SARS-CoV-2 S clade, delta variant, and omicron variant with higher potency than the original peptide. In hemizygous K18-hACE2 mice, intratracheal administration of R-t-Spike CD(D) effectively delivered the peptide to the trachea and lungs, whereas intranasal administration delivered the peptide mostly to the upper respiratory system and stomach, and a small amount to the lungs. Administration by either route reduced viral loads in mouse lungs and turbinates. Furthermore, intranasally administered R-t-Spike CD(D) mitigated pathological change in the lungs and increased the survival of mice after infection with the SARS-CoV-2 S clade or delta variant. Our data suggest that R-t-Spike CD(D) has potential as a therapeutic agent against SARS-CoV-2 infection.
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COVID-19 , Peptídeos Penetradores de Células , Chlorocebus aethiops , Animais , Camundongos , Peptídeos Penetradores de Células/farmacologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Células VeroRESUMO
BACKGROUND: The generation of immortalized erythroid progenitor cell lines capable of producing enough red blood cells (RBCs) for blood transfusion typically requires the overexpression of oncogenes in stem cells or progenitor cells to permanently proliferate immature cells. It is essential that any live oncogene-expressing cells are eliminated from the final RBC products for clinical use. STUDY DESIGN AND METHODS: It is believed that safety issues may be resolved by using a leukoreduction filter or by irradiating the final products, as is conventionally done in blood banks; however, this has never been proven to be effective. Therefore, to investigate whether immortalized erythroblasts can be completely removed using γ-ray irradiation, we irradiated the erythroblast cell line, HiDEP, and the erythroleukemic cell line, K562 that overexpress HPV16 E6/E7. We then analyzed the extent of cell death using flow cytometry and polymerase chain reaction (PCR). The cells were also subjected to leukoreduction filters. RESULTS: Using γ-ray irradiation at 25 Gy, 90.4% of HiDEP cells, 91.6% of K562-HPV16 E6/E7 cells, and 93.5% of non-transduced K562 cells were dead. In addition, 5.58 × 107 HiDEP cells were passed through a leukoreduction filter, and 38 intact cells were harvested, revealing a filter removal efficiency of 99.9999%. However, both intact cells and oncogene DNA were still detected. DISCUSSION: Irradiation cannot induce total cell death of oncogene-expressing erythroblasts and leukocyte filter efficiency is not 100%. Therefore, our findings imply that for clinical applications, safer methods should be developed to completely remove residual nucleated cells from cell line-derived RBC products.
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Eritrócitos , Células Eritroides , Humanos , Eritrócitos/metabolismo , Células Precursoras Eritroides , Células K562 , Citometria de FluxoRESUMO
AIMS: The objectives of this study were to evaluate the effect of combination treatment with cold plasma (CP), vacuum packaging (VP), and hot water (HW) on the inactivation of foodborne pathogens on buckwheat seeds, and determined the germination rates of seeds and the quality of sprouts following combination treatment. METHODS AND RESULTS: Buckwheat seeds inoculated with Salmonella Typhimurium and Listeria monocytogenes were treated with CP, HW, CP + HW, VP + HW, or CP + VP + HW. The germination rates of the HW-, CP + HW-, VP + HW-, and CP + VP + HW-treated seeds and the antioxidant activities and rutin contents of the CP + HW- and CP + VP + HW-treated sprouts were determined. HW, CP + HW, and CP + VP + HW were found to reduce the levels of the two pathogens to below the detection limit (1.0 log CFU g-1) at 70°C. However, HW and CP + HW significantly reduced the germination rate of buckwheat seeds. CP + VP + HW did not affect the germination rate of seeds nor the antioxidant activities and rutin content of buckwheat sprouts. CONCLUSIONS: These results indicate that CP + VP + HW can be used as a novel control method to reduce foodborne pathogens in seeds without causing quality deterioration.
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Fagopyrum , Listeria monocytogenes , Salmonella typhimurium , Vácuo , Antioxidantes , Microbiologia de Alimentos , Contagem de Colônia Microbiana , Água , Sementes , Rutina/farmacologia , GerminaçãoRESUMO
BACKGROUND: Pseudoclavibacter alba isolated from human urine in culture collection was introduced as a new species, but since then, no other reports on P. alba isolated from the environment or organisms have been published. We thus present the first case report of P. alba bacteremia. METHODS: An 85-year-old female patient was admitted with intermittent abdominal pain and chills that had persisted for one week. She was diagnosed cholangitis with common bile duct stones. RESULTS: Gram-positive bacteria were detected in her peripheral blood culture and identified Pseudoclavibacter species by matrix-assisted laser desorption-ionization-time of flight mass spectrometry. Pseudoclavibacter alba was identified by performing the 16S ribosomal RNA gene sequence. CONCLUSIONS: This is the first case report of P. alba bacteremia in a patient with cholangitis.
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Actinobacteria , Bacteriemia , Colangite , Humanos , Feminino , Idoso de 80 Anos ou mais , Dor AbdominalRESUMO
To resolve the problem of target specificity and light transmission to deep-seated tissues in photodynamic therapy (PDT), we report a cancer cell-targeted photosensitizer using photoprotein-conjugated upconversion nanoparticles (UCNPs) with high target specificity and efficient light transmission to deep tissues. Core-shell UCNPs with low internal energy back transfer were conjugated with recombinant proteins that consists of a photosensitizer (KillerRed; KR) and a cancer cell-targeted lead peptide (LP). Under near infrared (NIR)-irradiating condition, the UCNP-KR-LP generated superoxide anion radicals as reactive oxygen species via NIR-to-green light conversion and exhibited excellent specificity to target cancer cells through receptor-mediated cell adhesion. Consequently, this photosensitizing process facilitated rapid cell death in cancer cell lines (MCF-7, MDA-MB-231, and U-87MG) overexpressing integrin beta 1 (ITGB1) receptors but not in a cell line (SK-BR-3) with reduced ITGB1 expression and a non-invasive normal breast cell line (MCF-10A). In contrast to green light irradiation, NIR light irradiation exhibited significant PDT efficacy in cancer cells located beneath porcine skin tissues up to a depth of 10 mm, as well as in vivo tumor xenograft mouse models. This finding suggests that the designed nanocomposite is useful for sensing and targeting various deep-seated tumors.
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Nanopartículas , Neoplasias , Humanos , Animais , Camundongos , Suínos , Fármacos Fotossensibilizantes/farmacologia , Luz , Mama , Proteínas Luminescentes , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: With a rapidly ageing population and a decline in the availability of family caregivers, the number of older adults with disabilities who have unmet long-term care needs is gradually increasing worldwide. However, whether there are gender differences in the association between primary caregivers or their attitudes and unmet needs for activities of daily living (ADL) assistance remains largely unknown. METHODS: This study used the latest 2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), containing the data of 1187 older adults with disabilities aged 65 and older, to identify gender differences in the attitudes of primary caregivers toward the unmet needs for ADL assistance among with disabilities adults in China. Binary logistic regression analysis was conducted to determine the effects of primary caregivers and their caregiving attitudes on the unmet care experiences of older adults with ADLs. In addition, a gender-stratified analysis was conducted to compare the differences based on older adults' gender. RESULTS: The results revealed that the lack of positive attitudes from primary caregivers might create a situation of unmet needs for ADL assistance among older adults. When family members carry the main burden of care, older adults with disabilities, especially older women, have a lower level of unmet needs for ADL assistance. Therefore, it is important to consider gender-specific interventions to improve ADL assistance among older adults. CONCLUSIONS: The findings suggest that the presence of a family member as a caregiver has a significant effect on unmet needs for ADL assistance in women, highlighting the importance of developing an emotional bond with the caregiver. Given that the availability of informal caregivers, such as family members, is declining, it is crucial to provide financial assistance and formal services, such as paid home services and community-based care services, and reduce the burden on family caregivers to address the unmet needs for ADL assistance among older adults with disabilities in China.
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Cuidadores , Pessoas com Deficiência , Humanos , Feminino , Idoso , Cuidadores/psicologia , Atividades Cotidianas , Fatores Sexuais , Nível de SaúdeRESUMO
Ornithine decarboxylase (ODC), the first rate-limiting enzyme in polyamine synthesis, has emerged as a therapeutic target for cancer and Alzheimer's disease (AD). To inhibit ODC, α-difluoromethylornithine (DFMO), an irreversible ODC inhibitor, has been widely used. However, due to its poor pharmacokinetics, the need for discovery of better ODC inhibitors is inevitable. For high-throughput screening (HTS) of ODC inhibitors, an ODC enzyme assay using supramolecular tandem assay has been introduced. Nevertheless, there has been no study utilising the ODC tandem assay for HTS, possibly due to its intolerability to dimethyl sulfoxide (DMSO), a common amphipathic solvent used for drug libraries. Here we report a DMSO-tolerant ODC tandem assay in which DMSO-dependent fluorescence quenching becomes negligible by separating enzyme reaction and putrescine detection. Furthermore, we optimised human cell-line-based mass production of ODC for HTS. Our newly developed assay can be a crucial first step in discovering more effective ODC modulators than DFMO.
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Ensaios de Triagem em Larga Escala , Ornitina Descarboxilase , Humanos , Dimetil Sulfóxido , Bioensaio , PutrescinaRESUMO
Cold atmospheric plasma (CAP) may have applications in treating various types of malignant tumors. This study assessed the anticancer effects of CAP using melanoma and colon cancer cell lines. CAP treatment significantly reduced the in vitro viability of melanoma and colon cancer cell lines and had a negligible effect on the viability of normal human melanocytes. Additionally, CAP and epidermal growth factor receptor (EGFR) inhibitor had an additive anticancer effect in a CAP-resistant melanoma cell line. Reactive oxygen and nitrogen species known to be generated by CAP enhanced the anticancer effects of CAP and EGFR inhibitors. The in vivo anticancer activities of CAP were evaluated by testing its effects against syngeneic tumors induced in mice by melanoma and colon cancer cells. CAP treatment reduced tumor volume and weight in both cancer models, with the extent of tumor reduction dependent on the duration and number of CAP treatments. Histologic examination also revealed the tumoricidal effects of CAP in both tumor models. In conclusion, CAP inhibits the growth of mouse melanoma and colon cancer cell lines in vitro and shows tumoricidal effects against mouse models of melanoma and colon cancer in vivo.