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Aside from centrally induced trained immunity in the bone marrow (BM) and peripheral blood by parenteral vaccination or infection, evidence indicates that mucosal-resident innate immune memory can develop via a local inflammatory pathway following mucosal exposure. However, whether mucosal-resident innate memory results from integrating distally generated immunological signals following parenteral vaccination/infection is unclear. Here we show that subcutaneous Bacillus Calmette-Guérin (BCG) vaccination can induce memory alveolar macrophages (AMs) and trained immunity in the lung. Although parenteral BCG vaccination trains BM progenitors and circulating monocytes, induction of memory AMs is independent of circulating monocytes. Rather, parenteral BCG vaccination, via mycobacterial dissemination, causes a time-dependent alteration in the intestinal microbiome, barrier function and microbial metabolites, and subsequent changes in circulating and lung metabolites, leading to the induction of memory macrophages and trained immunity in the lung. These data identify an intestinal microbiota-mediated pathway for innate immune memory development at distal mucosal tissues and have implications for the development of next-generation vaccine strategies against respiratory pathogens.
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Vacina BCG , Macrófagos Alveolares , Imunidade Treinada , Pulmão , Vacinação , Imunidade InataRESUMO
Recently, photodynamic therapy (PDT) has found wide application as a noninvasive treatment modality for several cancers. However, the suboptimal delivery of photosensitizers (PSs) to the tumor site is a drawback, which inhibits the effectiveness of PDT. Hydrophobicity, strong oxygen and light dependence, and limited tissue penetrability of photosensitizers represent the major barriers to the clinical application of PDT. In order to improve biopharmaceutical properties of a clinically approved photosensitizer chlorin e6 (Ce6), we developed a nanoformulation encapsulating Ce6 in methoxy-poly(ethylene glycol)-poly(d,l-lactide) (mPEG-PLA) copolymeric micelles. The physicochemical properties, including particle size, zeta potential, encapsulation efficiency, drug loading, generation of reactive oxygen species following near-infrared light illumination (633 nm), and in vitro drug release, were determined. The therapeutic efficacy of Ce6-mPEG-PLA micelles following illumination were evaluated in vitro in both two- and three-dimensional cell culture systems by using human uterine cervix carcinoma (HeLa) and human alveolar adenocarcinoma (A549) cells in monolayers and in A549 spheroids, respectively. The mPEG-PLA micelles were stable with a particle size of 189.6 ± 14.32 nm and loaded Ce6 efficiently (encapsulation efficiency â¼75%). The Ce6-loaded micelles generated singlet oxygen at a higher concentration compared to free Ce6 in aqueous media. Ce6-mPEG-PLA micelle mediated PDT showed improved cellular internalization in both of the cell lines, resulting in enhanced cytotoxicity compared to free Ce6. In contrast, the Ce6-loaded micelles did not show any cytotoxicity in the absence of irradiation. The Ce6-loaded micelles exhibited deep penetration in the spheroids leading to phototoxicity and cellular apoptosis in the A549 spheroidal model. Results from this study indicated that the newly developed nanoformulation of Ce6 could be utilized in PDT as an effective treatment modality for solid tumors.
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Poliésteres/química , Polímeros/química , Linhagem Celular Tumoral , Células HeLa , Humanos , Micelas , Neoplasias/metabolismo , Fotoquimioterapia , Polietilenoglicóis/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
Neuromotor impairments resulting from natural aging and aging-related diseases are often accompanied by a heightened prevalence of falls and fall-related injuries. Conventionally, the study of factors contributing to falls focuses on intrinsic characteristics, such as sensorimotor processing delays and weakness, and extrinsic factors, such as environmental obstacles. However, the impact of these factors only becomes evident in response to people's decisions about how and where they will move in their environment. This decision-making process can be considered a behavioral risk factor, and it influences the extent to which a person engages in activities that place them near the limits of their capacity. While there are readily available tools for assessing intrinsic and extrinsic fall risk, our understanding of how to assess behavioral risk is limited. Measuring behavioral risk requires a systematic assessment of how people make decisions when walking in complex environments and how these decisions relate to their functional capacity. We propose that experimental methods and computational models derived from behavioral economics can stimulate the development of such assessments. Behavioral economics relies on theoretical models and empirical studies to characterize the factors that influence how people make decisions under risky conditions where a given decision can have variable outcomes. Applying a behavioral economic approach to walking can provide insight into how internal assessment of one's fall risk influences the tasks that one is willing to perform. Ultimately, these assessments will allow us to identify people who make choices that increase their likelihood of fall-related injuries.
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INTRODUCTION: Patients who recovered from the acute phase of COVID-19 experience several post-COVID-19 health and social problems. This study was therefore done to explore the living experiences and the various health problems experienced by people and their determinants during the post-recovery phase of COVID-19. METHODOLOGY: This cross-sectional study was conducted in Mangalore in March 2022. Data were collected using a semi-structured questionnaire designed as a Google Doc. Post-COVID-19 conditions were defined as adverse health consequences returning, new, or persistent beyond 1 month after SARS-CoV-2 infection. The experiences in the post-recovery phase of COVID-19 were assessed based on a scoring system for the related items in the questionnaire. RESULTS: Out of 235 participants, 204 (86.8%) reported post-COVID-19 health problems between 1 and 6 months following SARS-CoV-2 infection. The majority of them reported fatigue [114 (55.9%)]. Self-perceived health status and social relationships were significantly poorer among participants in the post-COVID-19 phase than before infection. In the multivariable analysis, unmarried/divorced/widow status, staying within city limits, and history of being admitted to the hospital due to various COVID-19-related emergencies were independently associated with the presence of post-COVID-19 conditions among the participants. The living experience in the post-recovery phase was positive only among 22 (9.4%) participants and was found to be significantly associated with the severe status of COVID-19 at the time of disease presentation. CONCLUSIONS: Post-COVID-19 health problems were present among several participants. Those identified to be at risk of developing these conditions need to be periodically screened and managed with a multi-disciplinary care and rehabilitation program. There is also a need to address social problems and encourage positive living experiences among COVID-19 patients during the post-recovery phase of the disease.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Índia/epidemiologia , Estudos Transversais , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem , Nível de Saúde , Idoso , AdolescenteRESUMO
Amidst the economic, political, and social turmoil caused by the COVID-19 pandemic, contrasting responses to government mandated and recommended mitigation strategies have posed many challenges for governments as they seek to persuade individuals to adhere to prevention guidelines. Much research has subsequently examined the tendency of individuals to either follow (or not) such guidelines, and yet a 'grey area' also exists wherein many rules are subject to individual interpretation. In a large study of Canadians (N = 1032, Mage = 34.39, 52% female; collected April 6, 2020), we examine how social dominance orientation (SDO) as an individual difference predicts individual propensity to 'bend the rules' (i.e., engaging in behaviors that push the boundaries of adherence), finding that SDO is significantly and positively associated with greater intentions toward rule-bending behaviors. We further find that highlighting a self-oriented or in-group identity enhances the relationship between SDO and rule-bending, whereas making salient a superordinate-level identity (e.g., Canada) attenuates this effect. Implications for theory and practice are discussed.
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COVID-19 , Adulto , Canadá , Feminino , Humanos , Masculino , Pandemias , SARS-CoV-2 , Predomínio SocialRESUMO
Purpose: The coronavirus disease 19 (COVID-19) pandemic has resulted in a huge impact on the health care system. Diversion of health care workforce toward management of a high number of COVID-19 cases and lockdown restrictions have affected the follow-up of patients. The objective of this study was to analyze the impact of this situation on the control of diabetes, eventually resulting in related neuro-ophthalmological complications. Methods: This retrospective case series included diabetic patients visiting the neuro-ophthalmology clinic at a tertiary care eye center in India from 25 March 2020 to 25 September 2020 during the lockdown. The incidence of diabetes-related neuro-ophthalmological complications, including third, fourth, sixth nerve palsies and non-arteritic anterior ischemic optic neuropathy (NAION) was evaluated and compared with that of the same period during 2019. Results: Overall disease incidence rate was significantly higher in the year 2020 (60.2%) compared to the previous year of 2019 (29.8%). The proportion of third nerve palsy (4.8% vs 16.3%, P < 0.001) and NAION (0.3% vs 14.3%, P < 0.001) had increased. Even though the percentage of sixth nerve palsy was 25% in 2020, this was not significantly different from 2019. There was a reduction in the percentage of fourth nerve palsy cases from the year 2019 to 2020. Conclusion: There was a significant increase in diabetes-related neuro-ophthalmic complications during the COVID-19 lockdown. This can possibly be attributed to worsening of glycemic control in diabetic patients.
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Doenças do Nervo Abducente , COVID-19 , Complicações do Diabetes , Diabetes Mellitus , Neuropatia Óptica Isquêmica , Controle de Doenças Transmissíveis , Humanos , Índia , Estudos RetrospectivosRESUMO
BACKGROUND: The Elixhauser Comorbidity Index (ECI) is a stratification tool to predict adverse surgical outcomes. No studies have explored the relationship between ECI and outcomes following primary 1- to 2-level lumbar fusion (1-2LF). The purpose was to determine whether an ECI score greater than 1 correlated with (1) longer in-hospital length of stay (LOS) and (2) greater odds of developing 90-day medical complications. METHODS: A retrospective review from 2004 to 2015 was performed using the Medicare Standard Analytical Files for patients undergoing primary LF. Patients with ECI scores from 2 to 5 served as the study cohorts (1 for each ECI score), and patients with an ECI score of 1 served as the control cohort. In-hospital LOS and 90-day medical complications were compared between cohorts. A P value of <0.001 was statistically significant. RESULTS: A total of 105,120 patients were equally distributed between the 5 cohorts. Patients with an ECI score of 2 (6.00 ± 4.51), ECI 3 (6.22 ± 4.67), ECI 4 (7.35 ± 5.05), or ECI 5 (8.99 ± 5.67) had longer in-hospital LOS compared with patients with an ECI score of 1 (4.28 ± 4.36) (all P < 0.001). Patients with an ECI score of 2 (OR: 1.17, 95% CI: 1.05-1.30, P = 0.003; 2.85% vs 2.45%), ECI 3 (OR: 1.22, 95% CI: 1.10-1.36, P < 0.001; 2.98% vs 2.45%), ECI 4 (OR: 1.26, 95% CI: 1.13-1.40, P < 0.001; 3.10% vs 2.45%), or ECI 5 (OR: 1.18, 95% CI: 1.06-1.31, P = 0.001; 2.89% vs 2.45%) had greater incidence and odds of 90-day medical complications such as pneumonia, deep vein thrombosis, cerebrovascular accidents, and myocardial infarctions than patients in the control group (all P < 0.0001). CONCLUSIONS: Increasing ECI score was associated with longer in-hospital LOS and increased 90-day medical complication rates following 1-2LF. This study is the first to establish a correlation between ECI score, in-hospital LOS, and complication rates following lumbar fusion. CLINICAL RELEVANCE: ECI score may assist physicians in adjusting pre- and postoperative care for complex patients undergoing 1-2LF.
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People with Parkinson's disease (PD) commonly have gait impairments that reduce their ability to walk safely in the community. These impairments are characterized, in part, by a compromised ability to turn and negotiate both predictable and unpredictable environments. Here, we describe the development and usability assessment of a virtual reality training application, Wordplay VR, that allows people with PD to practice skills such as turning, obstacle avoidance, and problem-solving during over-ground walking in a game-based setting. Nine people with PD completed three sessions with Wordplay VR, and each session was directed by their personal physical therapist. Our outcome measures included perceived sense of presence measured using the International Test Commission-Sense of Presence Inventory (ITC-SOPI), levels of motivation using the Intrinsic Motivation Inventory (IMI), overall system usability using the System Usability Scale (SUS), and setup time by the physical therapists. Both the people with PD and the physical therapists rated their sense of presence in the training system positively. The system received high ratings on the interest and value subscales of the IMI, and the system was also rated highly on usability, from the perspective of both the patient during gameplay and the therapist while controlling the experience. These preliminary results suggest that the application and task design yielded an experience that was motivating and user-friendly for both groups. Lastly, with repeated practice over multiple sessions, therapists were able to reduce the time required to help their patients don the headset and sensors and begin the training experience.
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We report the retinal and choroidal manifestations using multimodal imaging in a patient with Neurofibromatosis type 1 (NF-1). In this report, we describe the occurrence of a new retinal finding which we label as retinal café-au-lait macules. Also, we describe the superiority of multicolour imaging in comparison to colour fundus photography for identifying the retinal manifestations in NF-1.