Cell-Based Therapy for Fibrosing Interstitial Lung Diseases, Current Status, and Potential Applications of iPSC-Derived Cells.

Fibrosing interstitial lung diseases (FILDs), e.g., due to idiopathic pulmonary fibrosis (IPF), are chronic progressive diseases with a poor prognosis. The management of these diseases is challenging and focuses mainly on the suppression of progression with anti-fibrotic drugs. Therefore, novel FILD treatments are needed. In recent years, cell-based therapy with various stem cells has been investigated for FILD, and the use of mesenchymal stem cells (MSCs) has been widely reported and clinical studies are also ongoing. Induced pluripotent stem cells (iPSCs) have also been reported to have an anti-fibrotic effect in FILD; however, these have not been as well studied as MSCs in terms of the mechanisms and side effects. While MSCs show a potent anti-fibrotic effect, the possibility of quality differences between donors and a stable supply in the case of donor shortage or reduced proliferative capacity after cell passaging needs to be considered. The application of iPSC-derived cells has the potential to overcome these problems and may lead to consistent quality of the cell product and stable product supply. This review provides an overview of iPSCs and FILD, followed by the current status of cell-based therapy for FILD, and then discusses the possibilities and perspectives of FILD therapy with iPSC-derived cells.

Serum C-reactive protein is associated with earlier mortality across different interstitial lung diseases.

BACKGROUND AND OBJECTIVE: The acute-phase protein C-reactive protein (CRP) is known to be associated with poor outcomes in cancer and cardiovascular disease, but there is limited evidence of its prognostic implications in interstitial lung diseases (ILDs). We therefore set out to test whether baseline serum CRP levels are associated with mortality in four different ILDs. METHODS: In this retrospective study, clinically measured CRP levels, as well as baseline demographics and lung function measures, were collected for ILD patients first presenting to the Royal Brompton Hospital between January 2010 and December 2019. Cox regression analysis was used to determine the relationship with 5-year mortality. RESULTS: Patients included in the study were: idiopathic pulmonary fibrosis (IPF) n = 422, fibrotic hypersensitivity pneumonitis (fHP) n = 233, rheumatoid arthritis associated ILD (RA-ILD) n = 111 and Systemic Sclerosis associated ILD (SSc-ILD) n = 86. Patients with a recent history of infection were excluded. Higher CRP levels were associated with shorter 5-year survival in all four disease groups on both univariable analyses, and after adjusting for age, gender, smoking history, immunosuppressive therapy and baseline disease severity (IPF: HR (95% CI): 1.3 (1.1-1.5), p = 0.003, fHP: 1.5 (1.2-1.9), p = 0.001, RA-ILD: 1.4 (1.1-1.84), p = 0.01 and SSc-ILD: 2.7 (1.6-4.5), p < 0.001). CONCLUSION: Higher CRP levels are independently associated with reduced 5-year survival in IPF, fHP, RA-ILD and SSc-ILD.

The effect of suboccipital muscle inhibition and posture correction exercises on chronic tension-type headaches.

BACKGROUND: Compared with healthy people, patients with chronic tension-type headache (CTTH) are likely to have forward head postures (FHP) and a higher number of active trigger points (aTrP) on the suboccipital muscle. OBJECTIVE: This study aims to verify how the suboccipital muscle inhibition (SMI) on aTrPs and the FHP correction exercise can effectively reduce symptoms of the CTTH patients. METHOD: The subjects of this study were 45 individuals with CTTH, divided into three groups of 15 patients each: a) the SMI group using the myofascial release technique; b) the SMIEx group subject to both the SMI therapy and FHP correction exercises; and c) the control group. Group A and B were given the relevant interventions twice a week for four consecutive weeks, and went through the headache impact test (HIT-6) and examinations on the pressure pain threshold (PPT) of the headache areas, the type and number of myofascial trigger points (TrP), the soft tissue PPT, and the posture before and after the intervention. RESULTS: There was a significant improvement in the HIT-6, the headache PPT, the soft tissue PPT, the TrP, and the posture in Group A and B patients to whom the SMI technique and SMIEx interventions were applied. The biggest reduction and increase in the HIT-6 and the headache PPT respectively were seen in the SMIEx group. CONCLUSION: According to this study, the SMIEx can be an effective intervention for patients with CTTH.

Effects of Cervical Spine Mobilization on Respiratory Function and Cervical Angles of Stroke Patients: A Pilot Study.

The forward head posture (FHP) of stroke patients has a negative impact on respiratory function. Cervical spine mobilization is a manual therapy technique that used to prevent and treat FHP and respiratory function. This pilot study investigated whether cervical spine mobilization can effectively improve outcomes following FHP and respiratory function of stroke patients. Twenty-four patients participated in our assessor-blinded randomized controlled trial. All the participants received neurodevelopmental treatments (gait training and trunk rehabilitation). The experimental group additionally received 15-min sessions of cervical spine mobilization three times per week for 4 weeks. The control group received cervical spine sham mobilization during the same period. For the cervical angles, the cranial vertebral angle (CVA) and cranial rotation angle (CRA) were measured. A respiratory function test was performed to measure the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and chest circumferences (upper and lower chest sizes). Except for MIP, there was no significant difference between the experimental group and the control group. The CVA and CRA were significantly increased in the experimental group only. Cervical spine mobilization improved cervical angles and inspiratory function of the stroke patients in this study. However, a comparative study with a larger number of patients is needed to confirm this finding from our pilot study, which had a small sample size.

Pseudomonas aeruginosa prioritizes detoxification of hydrogen peroxide over nitric oxide.

OBJECTIVE: Bacteria are exposed to multiple concurrent antimicrobial stressors within phagosomes. Among the antimicrobials produced, hydrogen peroxide and nitric oxide are two of the most deleterious products. In a previous study, we discovered that when faced with both stressors simultaneously, Escherichia coli prioritized detoxification of hydrogen peroxide over nitric oxide. In this study, we investigated whether such a process was conserved in another bacterium, Pseudomonas aeruginosa. RESULTS: P. aeruginosa prioritized hydrogen peroxide detoxification in a dose-dependent manner. Specifically, hydrogen peroxide detoxification was unperturbed by the presence of nitric oxide, whereas larger doses of hydrogen peroxide produced longer delays in nitric oxide detoxification. Computational modelling revealed that the rate of nitric oxide consumption in co-treated cultures was biphasic, with cells entering the second phase of detoxification only after hydrogen peroxide was eliminated from the culture.

Immediate Effect of Cervico-thoracic Mobilization on Deep Neck Flexors Strength in Individuals with Forward Head Posture: A Randomized Controlled Trial.

INTRODUCTION: Forward head posture is the most frequently observed postural deviations and is said to be associated with shortening of posterior cervical extensors and weakening of the anterior deep cervical flexors. Manual therapy has the potential to achieve reflexogenic changes in muscle and enhance the motor activity and strength. PURPOSE OF THE STUDY: To evaluate the immediate effect of grade IV cervicothoracic Maitland mobilization on deep neck flexors strength in individuals with forward head posture. STUDY DESIGN: A Single-blinded randomized placebo-controlled trial. METHOD: Sixty individuals were randomly divided into two groups. Placebo-controlled (PBO) group (n = 30) received the grade I and experimental (EXP) group (n = 30) received grade IV posteroanterior central and unilateral Maitland mobilization from the upper cervical to the upper thoracic spine. Outcome measure: Clinical Cranio-cervical flexion test (CCFT) was used to measure the motor activity and the strength of deep neck flexors. RESULTS: The strength of deep neck flexors effectively increased (p = <0.0001) after advocating grade IV mobilization. CONCLUSION: This study concluded that grade IV central and unilateral posteroanterior Maitland mobilization demonstrated significant increase in the deep neck flexors strength in individuals with forward head posture.

A Comparison Study of Posture and Fatigue of Neck According to Monitor Types (Moving and Fixed Monitor) by Using Flexion Relaxation Phenomenon (FRP) and Craniovertebral Angle (CVA).

This study quantified the neck posture and fatigue using the flexion relaxation phenomenon (FRP) and craniovertebral angle (CVA); further, it compared the difference between the level of fatigue and neck posture induced by two types of monitors (regular fixed monitor and moving monitor). Twenty-three male participants were classified into two groups-the low-flexion relaxation ratio (FRR) group and the normal-FRR group, depending on the FRR value. All participants performed a document task for 50 min using both types of monitors. It was found that the FRR values significantly decreased after the documentation task. The CVA analysis showed that the moving monitor's frequency of forward head posture (FHP) was lower than that for the fixed monitor. Overall, the moving monitor worked better than the fixed monitor; this can be interpreted as proof that such monitors can reduce neck fatigue.

An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by Pseudomonas aeruginosa.

Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2-) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3-) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3-→NO2-→NO). Deeper understanding of NO metabolism in P. aeruginosa will increase knowledge of its pathogenesis, and computational models have proven to be useful tools for the quantitative dissection of NO biochemical networks. Here we developed such a model for P. aeruginosa and confirmed its predictive accuracy with measurements of NO, O2, NO2-, and NO3- in mutant cultures devoid of Fhp or NorCB (NO reductase) activity. Using the model, we assessed whether NO was metabolically cycled in aerobic P. aeruginosa cultures. Calculated fluxes indicated a bottleneck at NO3-, which was relieved upon O2 depletion. As cell growth depleted dissolved O2 levels, NO3- was converted to NO2- at near-stoichiometric levels, whereas NO2- consumption did not coincide with NO or NO3- accumulation. Assimilatory NO2- reductase (NirBD) or NorCB activity could have prevented NO cycling, and experiments with ΔnirB, ΔnirS, and ΔnorC showed that NorCB was responsible for loss of flux from the cycle. Collectively, this work provides a computational tool to analyze NO metabolism in P. aeruginosa, and establishes that P. aeruginosa use NorCB to prevent metabolic cycling of NO.

Circunstâncias da ocorrência da gravidez não planejada em mulheres adultas / Circumstances of occurrence of non-planned pregnancy in women user of the Family Health Program ­ Bahia

A gravidez é marcada por mudanças físicas e psicossociais que define novos papéis para a mulher, podendo ser fruto de livre escolha reprodutiva ou ser referida como não planejada. Ações buscando garantir o direito das mulheres a decidir livremente sobre os padrões de reprodução estão implantadas na rede pública de saúde, entretanto um número significativo de mulheres refere vivenciar gravidez não planejada. O PSF se apresenta como possibilidade de dar respostas mais efetivas às demandas das mulheres, pois foi erguido sob princípios que valorizam as especificidades de cada grupo populacional no âmbito da atenção básica. O estudo teve como objetivo conhecer o contexto de vida de mulheres, usuárias do PSF, por ocasião da ocorrência de gravidez não planejada e analisar as circunstâncias de sua ocorrência. A pesquisa foi desenvolvida sob abordagem qualitativa e enfoque teórico de gênero. O universo empírico do estudo foi constituído por dez mulheres, cadastradas em duas Unidades de Saúde da Família localizadas no Distrito Sanitário do Subúrbio Ferroviário de Salvador-Ba, sendo o material empírico produzido por meio de entrevistas estruturadas e semi-estruturadas. Os depoimentos das participantes do estudo foram analisados pela técnica de análise de discurso. O discurso expressa uma posição social, cujas representações ideológicas são materializadas na linguagem e sua análise revela a visão de mundo dos sujeitos, sendo essa determinada socialmente. Os resultados mostraram que a maternidade é concebida como importante elemento identitário por todas as mulheres do estudo. Nas que estavam vivenciando a primeira gravidez, em relações estáveis, houve desejo do casal e descuidos que resultaram em gravidez, confirmando-se ambivalência, com aceitação imediata e sentimento de realização feminina. Para mulheres com gravidez subsequente, com desejo de ser mãe concretizado, as circunstâncias da ocorrência fizeram emergir sentimentos contraditórios e se estabeleceu o conflito entre aceitação e rejeição, havendo situações de desejo ou tentativas de abortamento. Quanto ao parceiro, foi constatada a não assunção de responsabilidade com a contracepção, tendo seu apoio importante papel no desfecho da gravidez. As dificuldades das mulheres em compartilhar a responsabilidade com seus parceiros, na gestão cotidiana da contracepção, somaram-se à informações fragmentadas e dificuldades de acesso aos métodos com descontinuidade e/ou limitação na oferta; incompatibilidade entre horários do trabalho com o do serviço de saúde; desejo do parceiro e da própria mulher ancorado nas construções identitárias. Desse modo, a gravidez ocorreu com inexistência da decisão consciente da mulher ou do casal, sendo a ambivalência um forte componente do processo. Uma vez tais situações ocorrendo em área de cobertura do PSF, afirmamos que este se encontra comprometido em seus fundamentos e urge rever a organização das práticas e a vontade política em todos os níveis da gestão para abrir caminhos à autonomia e à liberdade feminina, negadas pelos resultados deste estudo. (AU)

Programa de saúde da família: uma análise a partir das crenças dos seus prestadores de serviço / Family health program: an analysis from the beliefs of their service providers

O estudo pretendeu avaliar qualitativamente o Programa Saúde da Família (PSF) a partir das crenças dos profissionais da Equipe de Saúde da Família (ESF). Foi selecionada uma amostra de cinco Unidades de Saúde da Família (USF), nas quais foram entrevistados 30 profissionais. A análise de conteúdo das entrevistas demonstrou que os profissionais da ESF avaliam negativamente o PSF no tocante às condições de trabalho fornecidas pelos gestores, ao deficitário sistema de referência e contra-referência, a falta e/ou insuficiência de capacitações, a sobrecarga de trabalho e a falta de compreensão da população sobre o PSF. A avaliação das USF corroborou o discurso dos profissionais das ESF quanto às precárias condições de trabalho das unidades do PSF. Não obstante, os profissionais da ESF avaliam positivamente o vínculo estabelecido com a população e expressam satisfação em um trabalho educativo, de prevenção e promoção de saúde, pautado em ideais de justiça social.

This study intended to qualitatively evaluate the Family Health Program (FHP) from the beliefs of Family Health Team (FHT) professionals. It was selected a sample of five Family Health Units (FHU), in which 30 professionals were interviewed. The analysis of the interviews' content showed that the professionals of FHT negatively evaluate the FHP in relation to working conditions provided by managers, the deficient reference and cross-reference systems, the absence and/or lack of training, the overload of work and a lack of understanding about the project. The evaluation of the FHU corroborated the speech of the FHT professionals about the precarious working conditions of the FHP sites. Despite all the criticism, the professionals positively evaluate the link established with the population and they express satisfaction with an educative, of prevention and promotion of health work which is ruled by ideals of social justice.