Background: Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related. This observational study assessed the prevalence, ...severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes. Methods: The study enrolled patients with stable COPD in clinical practice. Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded. Results: The full analysis set included 727 patients: 65.8% male, mean +/- standard deviation age 67.2 +/- 8.8 years, % predicted FEV1 52.8 +/- 20.5%. In each part of the 24-hour day, > 60% of patients reported experiencing >= 1 symptom in the week before baseline. Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively). Symptom severity was comparable for each period assessed. Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in >= 2 parts of the 24-hour day. Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001). Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both). Nighttime, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period). In each part of the 24-hour day, there was also an association between symptoms and a patient's physical activity level (p < 0.05 for each period). Conclusions: More than half of patients experienced COPD symptoms throughout the whole 24-hour day. There was a significant relationship between night-time, early morning and daytime symptoms. In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.
The centrosome is essential for cytotoxic T lymphocyte (CTL) function, contacting the plasma membrane and directing cytotoxic granules for secretion at the immunological synapse. Centrosome docking ...at the plasma membrane also occurs during cilia formation. The primary cilium, formed in nonhematopoietic cells, is essential for vertebrate Hedgehog (Hh) signaling. Lymphocytes do not form primary cilia, but we found and describe here that Hh signaling played an important role in CTL killing. T cell receptor activation, which "prearms" CTLs with cytotoxic granules, also initiated Hh signaling. Hh pathway activation occurred intracellularly and triggered Rac1 synthesis. These events "prearmed" CTLs for action by promoting the actin remodeling required for centrosome polarization and granule release. Thus, Hh signaling plays a role in CTL function, and the immunological synapse may represent a modified cilium.
This study was conducted to provide information regarding the chemistry-including structure, synthesis, formulation, and mechanical properties-of two types of chemically modified anti-adhesion gels ...made of hyaluronic acid. Gel A (Hyalobarrier
) and gels B and C (HyaRegen
and MetaRegen
) that are used in postsurgical adhesion prevention. To date, little information is available on their physicochemical attributes. This information is necessary in order to understand the differences in their in vivo behavior.
Comparative analyses were conducted under laboratory-controlled conditions, including measuring the shear viscosity, storage modulus G', peel strength, and extrusion forces.
All polymers exhibited viscoelastic behavior. Polymer A showed a shear viscosity approximately three times larger than both polymers B and C (114 Pa.s
vs. 36-38 Pa.s
) over the shear-rate range measured, indicating a possible better ability to resist flows and potentially remain in place at the site of application in vivo. The results of storage modulus (G') measurements showed 100 Pa for polymer A and 16 Pa and 20 Pa for polymers B and C, respectively. This translated into a weaker elastic behavior for gels B and C, and a lower ability to resist sudden deformation. The peel test results showed a rupture strength of 72 mN (0.016 lbf) for polymer A, 39.6 mN (0.0089 lbf) for polymer B, and 38.3 mN (0.0086 lbf) for polymers C, indicating possible higher adhesive properties for polymer A. Tests measuring the extrudability of the hyaluronic acid gels in their commercial syringes showed an average extrusion force of 20 N (4.5 lbf) for polymer A, 28 N (6.33 lbf) for polymer B, and 17 N (3.79 lbf) for polymer C.
Modified anti-adhesion gels made of hyaluronic acid differed in mechanical properties and concentration. Further clinical studies are needed to confirm whether these differences make one polymer easier to apply during surgery and more likely to stay in place longer after in vivo application, and to determine which is potentially superior in terms of preventing adhesions.
Scope
Application of metabolomics to nutrition and health research is increasing and while much effort has been invested in understanding factors that influence the metabolomic profile there is ...relatively little known about the impact of fitness level. This study aimed to examine the relationship between fitness level, substrate oxidation rates, and the metabolic profile.
Methods and results
Two hundred and fourteen healthy adults (18–60 years) were recruited and 65 subjects were selected based on their estimated maximal oxygen consumption levels. Metabolomic analysis was performed. The subjects were split into fitness groups according to their maximal oxygen consumption levels (mL/kg/min) and analysis revealed significant differences in normalized fat and carbohydrate oxidation levels between the groups. Urinary metabolomic analysis revealed significantly different profiles in the groups with 15 amino acids significantly higher in the low fitness groups. Effects of fitness level in the plasma metabolic profiles were also demonstrated.
Conclusion
This study demonstrates a relationship between fitness level and the amino acid profile. Moreover, the metabolite changes show that a reduced excretion of amino acids in adults is associated with increased fitness levels and an increased fat oxidation rate during exercise. Interestingly, higher levels of branched chain amino acids were associated with lower fitness levels and higher insulin resistance.
ABSTRACT Ladle furnace slag is a waste composed essentially of quicklime or hydrated lime, whose contents depend on the raw material and the cooling process that led to the slag batch. With this ...chemical composition, it is used by civil construction as a hydraulic binder in cement matrices. The chemical compounds mentioned are also present in Portland cement, which are part of the chemical reactions of hydration and hardening. However, the quality of LFS batches calls for attention to volume expansion caused by chemical compounds whose presence and content can be controlled by the cooling method adopted in the production. Considering the use of this material as a partial replacement for Portland cement, the objective of this study was the physicochemical characterization of LFS samples to evaluate the influence of the cooling method on its potential as a complementary binder in cementitious matrices. In this sense, 3 samples from different batches were analyzed and the effects of each cooling process. The results include analysis of specific mass, laser diffraction for particle size analysis, X-ray fluorescence and X-Ray Diffraction tests. It was verified that the sample obtained by slow cooling is the most suitable as binder, as it features less possibility of expansive chemical reactions and presents greater fineness.
RESUMO A escória de forno panela é um resíduo composto essencialmente por cal virgem ou cal hidratada, cujos teores dependem da matéria-prima e do processo de resfriamento que deu origem ao lote de escória. Com essa composição química, ela é utilizada pela construção civil como aglomerante hidráulico em matrizes cimentícias. Os compostos químicos citados também estão presentes no cimento Portland, que fazem parte das reações químicas de hidratação e endurecimento. No entanto, a qualidade dos lotes EFP requer atenção à expansão de volume, causada por compostos químicos cuja presença e teor pode ser controlada pelo método de resfriamento adotado na produção. Considerando o uso deste material em substituição parcial ao cimento Portland, o objetivo deste estudo foi a caracterização físico-química de amostras de EFP para avaliar a influência do método de resfriamento em seu potencial como aglomerante complementar em matrizes cimentícias. Neste sentido foram analisadas 3 amostras de diferentes lotes e os efeitos de cada processo de resfriamento. Os resultados incluem análise de massa específica, difração de laser para análise de tamanho de partícula, fluorescência de raios X e testes de difração de raios X. Verificou-se que a amostra obtida por resfriamento lento é a mais indicada como aglomerante, pois apresenta menor possibilidade de reações químicas expansivas e apresenta maior finura.
Haemodynamic variables are prognostic factors in pulmonary arterial hypertension (PAH). However, right heart catheterization (RHC) is not systematically recommended to assess the risk-status during ...follow-up. This study aimed to assess the added value of haemodynamic variables in prevalent patients to predict the risk of death or lung transplantation according to their risk status assessed by the non-invasive 4 strata model as recommended by the European guidelines.
We evaluated incident patients with PAH enrolled in the French PAH Registry between 2009 and 2020 who had a first follow-up RHC. Cox regression identified, in each follow-up risk status, haemodynamic variables significantly associated with transplant-free survival (TFS). Optimal thresholds were determined by time-dependent Receiver-Operating Characteristics. Several multivariable Cox regression models were performed to identify the haemodynamic variables improving the non-invasive risk stratification model.
We analysed 1240 incident patients reassessed within a year by RHC. None of haemodynamic variable were significantly associated with TFS among low-risk (n=386) or high-risk (n=71) patients. Among patients at intermediate (-low, n=483, -high, n=300) risk at first follow-up, multivariable models including either stroke volume index (SVi) or mixed venous oxygen saturation (SvO
) were the best. The prognostic performance of refined 6 strata risk stratification model including the non-invasive 4 strata model and SVi>37 mL·m
and/or SvO
>65% for patients at intermediate-risk (Area Under the Curve 0.81, c-index 0.74), was better than that of 4 strata model (0.79, p=0.009; c-index 0.72).
Cardiopulmonary haemodynamics may improve risk stratification at follow-up in patients at intermediate-risk.
To examine how adolescent-parent dyads describe decision-making regarding initiation of the human papillomavirus (HPV) vaccine series, specifically who they viewed as making the final decision.
...Semistructured interviews with adolescent-parent dyads were audio-recorded and transcribed. Responses to the question: “How did you make a decision about whether or not to receive the HPV vaccine series?” were content-coded for each individual member of the dyad.
Adolescent medicine clinics of 2 large urban medical centers and through snowball sampling.
Adolescents 14-17 years of age and a parent (N = 262). Qualitative analyses were conducted for those who agreed that they were offered and started the HPV vaccine series (n = 109).
None.
Descriptions of the decision-making included 1 person (adolescent or parent) making the decision or joint decision-making by the adolescent and parent together.
More than half of the dyads did not agree on who made the decision to start the vaccine. Most adolescents and parents described a similar account about when they were offered the HPV vaccine, although the interpretation of the event in terms of the decision-maker might have differed. More than half of adolescents and parents individually mentioned the health care provider in their description of the HPV vaccine decision-making process even though they were not queried about the role of the provider.
Understanding the range of descriptions of these dyads is helpful to guide interventions to promote vaccine uptake in a manner that balances provider expertise, adolescent autonomy, and parental involvement.
The human nasopharynx contains a stable microbial ecosystem of commensal and potentially pathogenic bacteria, which can elicit protective primary and secondary immune responses. Experimental ...intranasal infection of human adults with the commensal
produced safe, sustained pharyngeal colonization. This has potential utility as a vehicle for sustained release of antigen to the human mucosa, but commensals in general are thought to be immunologically tolerated. Here, we show that engineered
, chromosomally transformed to express a heterologous vaccine antigen, safely induces systemic, antigen-specific immune responses during carriage in humans. When the
expressing the meningococcal antigen Neisseria Adhesin A (NadA) was inoculated intranasally into human volunteers, all colonized participants carried the bacteria asymptomatically for at least 28 days, with most (86%) still carrying the bacteria at 90 days. Compared to an otherwise isogenic but phenotypically wild-type strain, colonization with NadA-expressing
generated NadA-specific immunoglobulin G (IgG)- and IgA-secreting plasma cells within 14 days of colonization and NadA-specific IgG memory B cells within 28 days of colonization. NadA-specific IgG memory B cells were detected in peripheral blood of colonized participants for at least 90 days. Over the same period, there was seroconversion against NadA and generation of serum bactericidal antibody activity against a NadA-expressing meningococcus. The controlled infection was safe, and there was no transmission to adult bedroom sharers during the 90-day period. Genetically modified
could therefore be used to generate beneficial immune responses to heterologous antigens during sustained pharyngeal carriage.
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