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1.
Lancet ; 404(10461): 1419-1429, 2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39396349

RESUMO

BACKGROUND: WHO currently recommends a single dose of typhoid conjugate vaccine (TCV) in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials. Given the decay of immunogenicity, the protection beyond 2 years is unknown. We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination. METHODS: We conducted a cluster randomised controlled trial (TyVAC; ISRCTN11643110) in Dhaka, Bangladesh, between 2018 and 2021. Children aged 9 months to 15 years were invited to receive a single dose of TCV or Japanese encephalitis vaccine between April 15, 2018, and November 16, 2019, based on the randomisation of their clusters of residence. Children who received the Japanese encephalitis vaccine were invited to receive TCV at the final visit between Jan 6, and Aug 31, 2021, according to the protocol. This follow-on study extended the follow-up of the original trial until Aug 14, 2023. The primary endpoint of this study was to compare the incidence of blood culture-confirmed typhoid between children who received TCV in 2018-19 (the previous-TCV group) and those who received the vaccine in 2021 (the recent-TCV group), to evaluate the relative decline in vaccine protection. We also did a nested study using the test-negative design comparing the recent-TCV and previous-TCV groups with unvaccinated individuals, as well as an immunogenicity study in a subset of 1500 children. FINDINGS: Compared with the recent-TCV group, the previous-TCV group had an increased risk of typhoid fever between 2021-23, with an adjusted incidence rate ratio of 3·10 (95% CI 1·53 to 6·29; p<0·0001), indicating a decline in the protection of a single-dose of TCV 3-5 years after vaccination. The extrapolated vaccine effectiveness in years 3-5 was 50% (95% CI -13 to 78), and was validated using the test-negative design analysis, with a vaccine effectiveness of 84% (74 to 90) in the recent-TCV group and 55% (36 to 68) in the previous-TCV group, compared with unvaccinated individuals. Anti-Vi-IgG responses declined over the study period. The highest rate of decay was seen in children vaccinated at younger than 2 years in the original trial. The inverse correlation between age and the decay of antibodies was also seen in the subgroup analysis of vaccine effectiveness, where the youngest age group (<7 years at fever visits) exhibited the fastest waning, with vaccine effectiveness dropping to 24% (95% CI -29 to 55) at 3-5 years after vaccination. INTERPRETATION: A decline in the protection conferred by a single-dose TCV was observed 3-5 years after vaccination, with the greatest decline in protection and immune responses observed in children vaccinated at younger ages. A booster dose of TCV around school entry age might be needed for children vaccinated while younger than 2 years to sustain protection against typhoid fever during the school years when the risk is the highest. FUNDING: The Bill & Melinda Gates Foundation.


Assuntos
Toxoide Tetânico , Febre Tifoide , Vacinas Tíficas-Paratíficas , Vacinas Conjugadas , Humanos , Bangladesh/epidemiologia , Pré-Escolar , Criança , Feminino , Masculino , Vacinas Tíficas-Paratíficas/imunologia , Vacinas Tíficas-Paratíficas/administração & dosagem , Lactente , Vacinas Conjugadas/imunologia , Vacinas Conjugadas/administração & dosagem , Toxoide Tetânico/imunologia , Toxoide Tetânico/administração & dosagem , Febre Tifoide/prevenção & controle , Febre Tifoide/imunologia , Adolescente , Eficácia de Vacinas , Vacinas contra Encefalite Japonesa/imunologia , Vacinas contra Encefalite Japonesa/administração & dosagem , Seguimentos
2.
ERJ Open Res ; 10(5)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39351387

RESUMO

Background: Disease control in chronic diseases is an overarching concept that reflects the degree to which the goals of therapy are met. However, to date, there is no consensus on the definition of disease control in chronic cough. This study aimed to provide a conceptual exploration of patient-reported cough control in chronic cough. Methods: This research is comprised of two subanalyses. First, patients with chronic cough receiving care at referral clinics were evaluated. Correlation analyses were performed between patient-reported cough control (a 5-point Likert scale), cough-specific patient-reported outcomes (PROs) and generic health PRO scores. Second, a survey was conducted among patients with refractory chronic cough and physicians to identify factors pertinent to cough control. Results: The analysis of 341 patients (mean age: 55.5±15.1 years; female: 66.6%) revealed that cough control rating was moderately correlated with cough severity visual analogue scale and Leicester Cough Questionnaire scores, while demonstrating weaker correlations with cough-associated throat symptoms, cough-related complications or general health-related quality of life (QoL). In the survey of patients and physicians, both groups considered certain factors, such as cough frequency, severity and impact on QoL, to be relevant to the concept of cough control. However, patients rated "need for cough rescue drug" notably higher than physicians. Conclusion: Patient-reported cough control was associated with cough severity or impact on QoL; however, cough control may not be fully captured by conventional cough PRO measurement tools. Further studies are warranted to define the consensus and tools to measure disease control in chronic cough.

3.
Front Immunol ; 15: 1457785, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39257585

RESUMO

Controlled human infection model (CHIM) studies, which involve deliberate exposure of healthy human volunteers to an infectious agent, are recognised as important tools to advance vaccine development. These studies not only facilitate estimates of vaccine efficacy, but also offer an experimental approach to study disease pathogenesis and profile vaccine immunogenicity in a controlled environment, allowing correlation with clinical outcomes. Consequently, the data from CHIMs can be used to identify immunological correlates of protection (CoP), which can help accelerate vaccine development. In the case of invasive Salmonella infections, vaccination offers a potential instrument to prevent disease. Invasive Salmonella disease, caused by the enteric fever pathogens Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi A, B and C, and nontyphoidal Salmonella (iNTS), remains a significant cause of mortality and morbidity in low- and middle-income countries, resulting in over 200,000 deaths and the loss of 15 million DALYs annually. CHIM studies have contributed to the understanding of S. Typhi infection and provided invaluable insight into the development of vaccines and CoP following vaccination against S. Typhi. However, CoP are less well understood for S. Paratyphi A and iNTS. This brief review focuses on the contribution of vaccine-CHIM trials to our understanding of the immune mechanisms associated with protection following vaccines against invasive Salmonella pathogens, particularly in relation to CoP.


Assuntos
Infecções por Salmonella , Vacinas contra Salmonella , Humanos , Vacinas contra Salmonella/imunologia , Infecções por Salmonella/imunologia , Infecções por Salmonella/prevenção & controle , Salmonella typhi/imunologia , Vacinação , Eficácia de Vacinas , Febre Tifoide/prevenção & controle , Febre Tifoide/imunologia , Salmonella/imunologia
4.
Korean J Intern Med ; 39(5): 746-758, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39252487

RESUMO

The emerging field of gut-lung axis research has revealed a complex interplay between the gut microbiota and respiratory health, particularly in asthma. This review comprehensively explored the intricate relationship between these two systems, focusing on their influence on immune responses, inflammation, and the pathogenesis of respiratory diseases. Recent studies have demonstrated that gut microbiota dysbiosis can contribute to asthma onset and exacerbation, prompting investigations into therapeutic strategies to correct this imbalance. Probiotics and prebiotics, known for their ability to modulate gut microbial compositions, were discussed as potential interventions to restore immune homeostasis. The impact of antibiotics and metabolites, including short-chain fatty acids produced by the gut microbiota, on immune regulation was examined. Fecal microbiota transplantation has shown promise in various diseases, but its role in respiratory disorders is not established. Innovative approaches, including mucus transplants, inhaled probiotics, and microencapsulation strategies, have been proposed as novel therapeutic avenues. Despite challenges, including the sophisticated adaptability of microbial communities and the need for mechanistic clarity, the potential for microbiota-based interventions is considerable. Collaboration between researchers, clinicians, and other experts is essential to unravel the complexities of the gut-lung axis, paving a way for innovative strategies that could transform the management of respiratory diseases.


Assuntos
Asma , Disbiose , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Prebióticos , Probióticos , Humanos , Probióticos/uso terapêutico , Asma/microbiologia , Asma/imunologia , Asma/terapia , Animais , Pulmão/microbiologia , Pulmão/imunologia , Pulmão/metabolismo , Pneumopatias/microbiologia , Pneumopatias/terapia , Pneumopatias/imunologia
5.
Viruses ; 16(8)2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39205271

RESUMO

Mayaro virus (MAYV) is an arbovirus first isolated in Trinidad and Tobago in 1954. MAYV is the causative agent of Mayaro fever, which is characterised by high fever, maculopapular rash, myalgia and arthralgia. The potential for chronic arthralgia is of particular clinical concern. Currently, MAYV outbreaks are restricted to South and Central America, with some cases reported in Africa as well as several imported cases in Europe. However, in recent years, MAYV has become a growing global concern due to its potential to emerge into urban transmission cycles. Challenges faced with diagnostics, as well as a lack of specific antivirals or licensed vaccines further exacerbate the potential global health threat posed by MAYV. In this review, we discuss this emerging arboviral threat with a particular focus on the current treatment and vaccine development efforts. Overall, MAYV remains a neglected arbovirus due to its limited area of transmission. However, with the potential of its urbanisation and expanding circulation, the threat MAYV poses to global health cannot be overlooked. Further research into the improvement of current diagnostics, as well as the development of efficacious antivirals and vaccines will be crucial to help prevent and manage potential MAYV outbreaks.


Assuntos
Infecções por Alphavirus , Alphavirus , Humanos , Alphavirus/isolamento & purificação , Infecções por Alphavirus/epidemiologia , Infecções por Alphavirus/virologia , Infecções por Alphavirus/transmissão , Animais , América/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Surtos de Doenças , Vacinas Virais/imunologia , Antivirais/uso terapêutico , Saúde Global
6.
Psychiatry Investig ; 21(9): 987-993, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39155554

RESUMO

OBJECTIVE: Obstructive sleep apnea (OSA) is a breathing disorder characterized by recurrent airway obstruction during sleep. Previous western studies have investigated the link between medical disorders and the pathophysiology of OSA. The prevalence and comorbidity rates of OSA; however, vary across different countries and racial groups. This study aimed to delve into medical comorbidities in patients with OSA using a large nationwide healthcare database in Korea. METHODS: This nationwide study used the Korean National Health Insurance claims database (2010-2019). The effect of OSA on the incidence of medical disorders was estimated using the Cox proportional hazard ratio (HR) model. The results were reported as crude and adjusted HRs with 95% confidence intervals (CI). Subgroup analysis was conducted by sex and age. RESULTS: In total, 103,785 patients with OSA and 207,570 patients without OSA were included. OSA group had significantly higher HRs for ischemic heart disease and stroke even after adjusting for hypertension, dyslipidemia, and diabetes. The OSA group also showed an increased risk of metabolic syndrome-related diseases, chronic kidney disease, and gastroesophageal reflux disease. Female patients with OSA exhibited notably higher rates of comorbid liver cirrhosis, chronic obstructive pulmonary disease, and asthma. The cardiovascular burden of patients increased in accordance with the patients' age. CONCLUSION: Korean patients with OSA have a significantly increased risk of cardio-cerebrovascular diseases, which aligns with the previous studies conducted in the western countries. This result holds particular significance as it represents the first nationwide, population-based study conducted in Asia.

7.
Viruses ; 16(6)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38932175
8.
Psychiatry Investig ; 21(5): 457-463, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38810994

RESUMO

OBJECTIVE: This narrative review aims to provide a comprehensive assessment of the existing literature on the relationship between hypnotics and dementia, considering both potential link and inconclusive or lack of association. METHODS: Data from studies that investigate the association between hypnotic medications and dementia were reviewed. Studies included both cohort studies and systematic reviews, participants with various type of dementia and hypnotics including benzodiazepines (BZDs) and Z-drugs (ZDs). RESULTS: The existing literatures presents conflicting evidence regarding the association between hypnotics, including BZDs and ZDs, and the risk of dementia. Some studies suggest a potential link between prolonged use of hypnotics and an increased risk of dementia. However, other studies indicate inconclusive or lacking evidence regarding this association. Factors such as study design, sample characteristics, and control of confounding variables contribute to the variability in findings. CONCLUSION: The relationship between hypnotics and dementia remains complex and controversial. While some studies suggest a potential association, others find inconclusive or conflicting evidence. Future research should focus on addressing methodological limitations, considering classifying dementia subtypes, and try to adjust medication lag time.

9.
Clin Psychopharmacol Neurosci ; 22(2): 211-221, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38627069

RESUMO

Sleep disturbance and abnormal circadian rhythm might be closely related to bipolar disorder. Several studies involving disturbed sleep/wake cycle, changes in rhythms such as melatonin and cortisol, clock genes, and circadian preference have shown the relationship between bipolar disorder and circadian rhythm. The results differed across different studies. In some studies, a delay in the circadian rhythm was observed in the depressive episode and advanced circadian rhythm was observed during the manic episode. In other studies, a delay in circadian rhythm was observed independent of mood episodes. Accordingly, circadian rhythm disorder was proposed as a trait marker for bipolar disorder. The altered circadian rhythm may represent a pathological mechanism that contributes to the mood episodes. However, a prospective cohort study is needed for further clarification.

10.
Lancet ; 403(10436): 1554-1562, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38555928

RESUMO

BACKGROUND: Enteric fever caused by Salmonella enterica Typhi and Salmonella Paratyphi A is an important public health problem, especially in low-income and middle-income countries with limited access to safe water and sanitation. We present results from, to our knowledge, the first ever human study of a bivalent paratyphoid A-typhoid conjugate vaccine (Sii-PTCV). METHODS: In this double-blind phase 1 study, 60 healthy Indian adults were randomly assigned (1:1) to receive a single intramuscular dose of either Sii-PTCV or typhoid conjugate vaccine (Typbar-TCV). Safety was assessed by observing solicited adverse events for 1 week, unsolicited events for 1 month, and serious adverse events (SAEs) over 6 months. Immunogenicity at 1 month and 6 months was assessed by measuring anti-capsular polysaccharide antigen Vi (anti-Vi) IgG and IgA against Salmonella Typhi and anti-lipopolysaccharide (LPS) IgG against Salmonella Paratyphi A by ELISA, and functional antibodies using serum bactericidal assay (SBA) against Salmonella Paratyphi A. This study is registered with Clinical Trial Registry-India (CTRI/2022/06/043608) and is completed. FINDINGS: 60 participants were enrolled. Of these 60 participants, 57 (95%) participants were male and three (5%) participants were female. Solicited adverse events were observed in 27 (90%) of 30 participants who received Sii-PTCV and 26 (87%) of 30 participants who received Typbar-TCV. The most common local solicited event was pain in 27 (90%) participants who received Sii-PTCV and in 23 (77%) participants who received Typbar-TCV. The most common solicited systemic event was myalgia in five (17%) participants who received Sii-PTCV, whereas four (13%) participants who received Typbar-TCV had myalgia and four (13%) had headache. No vaccine-related unsolicited adverse events or SAEs were reported. The seroconversion rates on day 29 were 96·7% (95% CI 82·8-99·9) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgG; 93·3% (77·9-99·2) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgA; 100·0% (88·4-100·0) with Sii-PTCV and 3·3% (0·1-17·2) with Typbar-TCV for anti-LPS (paratyphoid); and 93·3% (77·9-99·2) with Sii-PTCV and 0% (0·0-11·6) with Typbar-TCV for SBA titres (paratyphoid). Paratyphoid anti-LPS immune responses were sustained at day 181. INTERPRETATION: Sii-PTCV was safe and immunogenic for both typhoid and paratyphoid antigens indicating its potential for providing comprehensive protection against enteric fever. FUNDING: Serum Institute of India.


Assuntos
Salmonella enterica , Febre Tifoide , Vacinas Tíficas-Paratíficas , Adulto , Feminino , Humanos , Masculino , Antibacterianos , Imunoglobulina A , Imunoglobulina G , Mialgia , Salmonella typhi , Febre Tifoide/prevenção & controle , Vacinas Combinadas , Vacinas Conjugadas , Método Duplo-Cego
11.
Vaccine ; 42(8): 2018-2025, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38395723

RESUMO

BACKGROUND: Previously, the Vi-typhoid conjugate vaccine (Vi-TT) was found to be highly efficacious in Nepalese children under 16 years of age. We assessed the immunogenicity of Vi-TT at 9 and 12 months of age and response to a booster dose at 15 months of age. METHODS: Infants were recruited at Patan Hospital, Kathmandu and received an initial dose of Vi-TT at 9 or 12 months of age with a booster dose at 15 months of age. Blood was taken at four timepoints, and antibody titres were measured using a commercial ELISA kit. The primary study outcome was seroconversion (4-fold rise in antibody titre) of IgG one month after both the doses. FINDINGS: Fifty children were recruited to each study group.Some visits were disrupted by the COVID19 pandemic and occurred out of protocol windows.Both the study groups attained 100 % IgG seroconversion after the initial dose. IgG seroconversion in the 9-month group was significantly higher than in the 12-month group (68.42 % vs 25.8 %, p < 0.001). Among individuals who attended visits per protocol, IgG seroconversion after the first dose occurred in 100 % of individuals (n = 27/27 in 9-month and n = 32/32 in 12-month group). However, seroconversion rates after the second dose were 80 % in the 9-month and 0 % in the shorter dose-interval 12-month group (p < 0.001) (n = 16/20 and n = 0/8, respectively). INTERPRETATION: Vi-TT is highly immunogenic at both 9 and 12 months of age. Stronger response to a booster in the 9-month group is likely due to the longer interval between doses.


Assuntos
Febre Tifoide , Vacinas Tíficas-Paratíficas , Criança , Lactente , Humanos , Febre Tifoide/prevenção & controle , Vacinas Conjugadas , Nepal/epidemiologia , Imunidade , Imunoglobulina G , Anticorpos Antibacterianos , Imunogenicidade da Vacina
12.
Clin Exp Dermatol ; 49(8): 848-858, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38365318

RESUMO

BACKGROUND: The relationship between human papillomavirus (HPV) and Bowen disease (BD) is not fully understood. OBJECTIVES: To investigate the differences in HPV detection rates in BD samples across various body regions and analyse the expression patterns of p53, p16 and Ki-67 in relation to HPV presence. METHODS: Tissue samples from patients diagnosed with BD, confirmed through histopathology, were retrospectively collected. Next-generation sequencing was used for HPV DNA detection. Immunohistochemistry (IHC) for p16, p53 and Ki-67 was performed. RESULTS: Out of 109 patients with BD, 21 (19.3%) were HPV-positive. All identified types were α-HPVs, with HPV-16 being the most common. The HPV detection rate was significantly higher in the pelvic (9/13, 69%, P < 0.001) and digital (5/10, 50%, P = 0.02) areas compared with those in the other regions. HPV presence was significantly correlated with p53 negativity (P = 0.002), the p53 'non-overexpression' IHC pattern (P < 0.001) and p16-p53 immunostain pattern discordance (P < 0.001). Conversely, there was no notable association between HPV presence and p16 positivity, the p16 IHC pattern or Ki-67 expression. CONCLUSIONS: Our findings suggest the oncogenic role of sexually transmitted and genito-digitally transmitted α-HPVs in the pathogenesis of BD in pelvic and digital regions.


Assuntos
Doença de Bowen , Infecções por Papillomavirus , Proteína Supressora de Tumor p53 , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Bowen/diagnóstico , Doença de Bowen/virologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA Viral/análise , Papillomavirus Humano , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/diagnóstico , Pelve/virologia , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/virologia , Proteína Supressora de Tumor p53/metabolismo
13.
J Psychosom Res ; 179: 111618, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38412653

RESUMO

BACKGROUND: The objectives of this cross-sectional study were to explore the relationship between weekend catch-up sleep (WCUS) and the risk of prediabetes/diabetes and to assess how this risk varies based on WCUS duration, using a large population sample in South Korea. METHODS: Data were sourced from the 2021 Korea National Health and Nutrition Examination Survey, involving 2472 subjects aged 30 years and above, employed, and not using blood glucose-lowering medications. Prediabetes/diabetes risk was examined based on the presence of WCUS. Participants were categorized into four groups by WCUS duration (< 1, ≥ 1 and < 2, ≥ 2 and < 3, and ≥ 3 h) to evaluate the prediabetes/diabetes risk across varying WCUS durations. RESULTS: No significant difference in prediabetes/diabetes risk was observed between the WCUS and non-WCUS groups. In subgroup analysis, a WCUS duration of 1 to 2 h was related to a lower odds ratio of prediabetes (aOR = 0.618, 95% CI = 0.382-0.999), while 3 h or more was associated with a higher odds ratio of diabetes (aOR = 3.098, 95% CI = 1.561-6.149). CONCLUSIONS: In individuals who experience insufficient sleep during weekdays and manage to achieve the optimal average sleep duration of 1 to 2 h of WCUS, WCUS was associated with improved blood glucose regulation. However, compensating for excessive weekday sleep deprivation with WCUS of 3 h or more was associated with impaired blood glucose regulation.


Assuntos
Estado Pré-Diabético , Humanos , Estado Pré-Diabético/epidemiologia , Estudos Transversais , Glicemia , Inquéritos Nutricionais , Sono/fisiologia , Privação do Sono/complicações
14.
Lung ; 202(2): 97-106, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38411774

RESUMO

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.


Assuntos
Antitussígenos , Codeína , Humanos , Codeína/uso terapêutico , Antitussígenos/uso terapêutico , Estudos Prospectivos , Tosse Crônica , Estudos de Coortes , Tosse/tratamento farmacológico , Tosse/etiologia
15.
Nature ; 625(7996): 768-777, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38200313

RESUMO

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes1-17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.


Assuntos
Líquido Cefalorraquidiano , Vértebras Cervicais , Drenagem , Vasos Linfáticos , Animais , Camundongos , Envelhecimento/metabolismo , Líquido Cefalorraquidiano/metabolismo , Vértebras Cervicais/metabolismo , Células Endoteliais/metabolismo , Fluorescência , Genes Reporter , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Vasos Linfáticos/fisiologia , Miócitos de Músculo Liso/metabolismo , Óxido Nítrico/metabolismo , Nariz/fisiologia , Faringe/metabolismo , Receptores Adrenérgicos alfa/metabolismo , Análise de Célula Única , Transdução de Sinais
16.
Sci Immunol ; 8(88): eadg6155, 2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37801517

RESUMO

High neonatal susceptibility to meningitis has been attributed to the anatomical barriers that act to protect the central nervous system (CNS) from infection being immature and not fully developed. However, the mechanisms by which pathogens breach CNS barriers are poorly understood. Using the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) to study virus propagation into the CNS during systemic infection, we demonstrate that mortality in neonatal, but not adult, mice is high after infection. Virus propagated extensively from the perivenous sinus region of the dura mater to the leptomeninges, choroid plexus, and cerebral cortex. Although the structural barrier of CNS border tissues is comparable between neonates and adults, immunofluorescence staining and single-cell RNA sequencing analyses revealed that the neonatal dural immune cells are immature and predominantly composed of CD206hi macrophages, with major histocompatibility complex class II (MHCII)hi macrophages being rare. In adults, however, perivenous sinus immune cells were enriched in MHCIIhi macrophages that are specialized for producing antiviral molecules and chemokines compared with CD206hi macrophages and protected the CNS against systemic virus invasion. Our findings clarify how systemic pathogens enter the CNS through its border tissues and how the immune barrier at the perivenous sinus region of the dura blocks pathogen access to the CNS.


Assuntos
Encefalite Viral , Coriomeningite Linfocítica , Meningite Viral , Meningoencefalite , Camundongos , Animais , Sistema Nervoso Central , Meninges , Vírus da Coriomeningite Linfocítica
17.
Nutrients ; 15(17)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37686886

RESUMO

Sarcopenic obesity, low muscle mass, and high body fat are growing health concerns in the aging population. This review highlights the need for standardized criteria and explores nutraceuticals as potential therapeutic agents. Sarcopenic obesity is associated with insulin resistance, inflammation, hormonal changes, and reduced physical activity. These factors lead to impaired muscle activity, intramuscular fat accumulation, and reduced protein synthesis, resulting in muscle catabolism and increased fat mass. Myostatin and irisin are myokines that regulate muscle synthesis and energy expenditure, respectively. Nutritional supplementation with vitamin D and calcium is recommended for increasing muscle mass and reducing body fat content. Testosterone therapy decreases fat mass and improves muscle strength. Vitamin K, specifically menaquinone-4 (MK-4), improves mitochondrial function and reduces muscle damage. Irisin is a hormone secreted during exercise that enhances oxidative metabolism, prevents insulin resistance and obesity, and improves bone quality. Low-glycemic-index diets and green cardamom are potential methods for managing sarcopenic obesity. In conclusion, along with exercise and dietary support, nutraceuticals, such as vitamin D, calcium, vitamin K, and natural agonists of irisin or testosterone, can serve as promising future therapeutic alternatives.


Assuntos
Resistência à Insulina , Sarcopenia , Humanos , Idoso , Sarcopenia/terapia , Cálcio , Fibronectinas , Suplementos Nutricionais , Obesidade/complicações , Obesidade/terapia , Vitaminas , Cálcio da Dieta , Vitamina K , Vitamina D/uso terapêutico
18.
Materials (Basel) ; 16(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37687622

RESUMO

We studied the behavioral characteristics of a newly developed dual-layer ablator, which uses carbon-phenolic as a recession layer and silica-phenolic as an insulating layer. The ablator specimens were tested in a 0.4 MW supersonic arc-jet plasma wind tunnel, employing two different shapes (flat-faced and hemispherical-faced) and varying thicknesses of the carbon-phenolic recession layer. The specimens underwent two test conditions, namely, stationary tests (7.5 MW/m2, ~40 s) and transient tests simulating an interplanetary spacecraft re-entry heat flux trajectory (6.25↔9.4 MW/m2, ~108 s). During the stationary tests, stagnation point temperatures of the specimens were measured. Additionally, internal temperatures of the specimens were measured at three locations for both stationary and transient tests: inside the carbon-phenolic recession layer, inside the silica-phenolic insulating layer, and at the recession layer-insulating layer intersection. The hemispherical-faced specimen surface temperatures were about 3000 K, which is about 350 K higher than those of flat-faced specimens, resulting in higher internal temperatures. The recession layer internal temperatures rose more exponentially when moved closer to the specimen stagnation point. Layer interaction and insulating layer internal temperatures were found to be dependent on both the recession layer thickness and the exposed surface shape. The change in exposed surface shape increased mass loss and recession, with hemispherical-faced specimens showing ~1.4-fold higher values than the flat-faced specimens.

19.
Skin Res Technol ; 29(8): e13426, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37632182

RESUMO

BACKGROUND: Numerous nonsurgical but invasive cosmetic procedures are performed blindly in the dermis or subcutaneous fat layer of the facial skin. OBJECTIVES: To measure the numerical skin thickness of the facial areas where dermatological procedures are performed by applying ultrasound techniques, and to make it possible to estimate the skin thickness by investigating the influence of several individual constitutional factors such as age, sex, and body mass index (BMI), so that these variables can be applied to estimate skin thickness. MATERIALS AND METHODS: Skin thickness was measured at eight different facial points using an ultrasound machine (Affiniti 50; Philips Inc.). Demographic data were gathered using questionnaires. Manual BMI was calculated from the weight and height of each participant, and individual BMI measurements were performed using a body composition analyzer. RESULTS: In terms of whole skin thickness, the thickest point was the mouth corner, and the thinnest point was the lateral forehead. The thickest point in the epidermis was the chin, and the thinnest point was the nasolabial fold. The thickest point in the dermis was the corner of the mouth, and the thinnest was the lateral forehead. Full skin thickness and dermal thickness were mostly lower in females. Skin thickness was not significantly correlated with BMI. CONCLUSION: The skin thickness at different points on the face was variable, and realistic data about skin thickness can be obtained by in vivo ultrasonographic analysis of the skin.


Assuntos
Testa , Pele , Feminino , Humanos , Índice de Massa Corporal , Pele/diagnóstico por imagem , Epiderme , Sulco Nasogeniano
20.
Materials (Basel) ; 16(10)2023 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-37241344

RESUMO

We developed and tested two carbon-phenolic-based ablators for future Korean spacecraft heat shield applications. The ablators are developed with two layers: an outer recession layer, fabricated from carbon-phenolic material, and an inner insulating layer, fabricated either from cork or silica-phenolic material. The ablator specimens were tested in a 0.4 MW supersonic arc-jet plasma wind tunnel at heat flux conditions ranging from 6.25 MW/m2 to 9.4 MW/m2, with either specimen being stationary or transient. Stationary tests were conducted for 50 s each as a preliminary investigation, and the transient tests were conducted for ~110 s each to stimulate a spacecraft's atmospheric re-entry heat flux trajectory. During the tests, each specimen's internal temperatures were measured at three locations: 25 mm, 35 mm, and 45 mm from the specimen stagnation point. During the stationary tests, a two-color pyrometer was used to measure specimen stagnation-point temperatures. During the preliminary stationary tests, the silica-phenolic-insulated specimen's reaction was normal compared to the cork-insulated specimen; hence, only the silica-phenolic-insulated specimens were further subjected to the transient tests. During the transient tests, the silica-phenolic-insulated specimens were stable, and the internal temperatures were lower than 450 K (~180 °C), achieving the main objective of this study.

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