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Journal of Translational Medicine Jun 2024Interstitial lung disease (ILD) is the primary cause of mortality in systemic sclerosis (SSc), an autoimmune disease characterized by tissue fibrosis. SSc-related ILD...
BACKGROUND
Interstitial lung disease (ILD) is the primary cause of mortality in systemic sclerosis (SSc), an autoimmune disease characterized by tissue fibrosis. SSc-related ILD (SSc-ILD) occurs more frequently in females aged 30-55 years, whereas idiopathic pulmonary fibrosis (IPF) is more prevalent in males aged 60-75 years. SSc-ILD occurs earlier than IPF and progresses rapidly. FCN1, FABP4, and SPP1 macrophages are involved in the pathogenesis of lung fibrosis; SPP1 macrophages demonstrate upregulated expression in both SSc-ILD and IPF. To identify the differences between SSc-ILD and IPF using single-cell analysis, clarify their distinct pathogeneses, and propose directions for prevention and treatment.
METHODS
We performed single-cell RNA sequencing on NCBI Gene Expression Omnibus (GEO) databases GSE159354 and GSE212109, and analyzed lung tissue samples across healthy controls, IPF, and SSc-ILD. The primary measures were the filtered genes integrated with batch correction and annotated cell types for distinguishing patients with SSc-ILD from healthy controls. We proposed an SSc-ILD pathogenesis using cell-cell interaction inferences, and predicted transcription factors regulating target genes using SCENIC. Drug target prediction of the TF gene was performed using Drug Bank Online.
RESULTS
A subset of macrophages activates the MAPK signaling pathway under oxidative stress. Owing to the lack of inhibitory feedback from ANNEXIN and the autoimmune characteristics, this leads to an earlier onset of lung fibrosis compared to IPF. During initial lung injury, fibroblasts begin to activate the IL6 pathway under the influence of SPP1 alveolar macrophages, but IL6 appears unrelated to other inflammatory and immune cells. This may explain why tocilizumab (an anti-IL6-receptor antibody) only preserves lung function in patients with early SSc-ILD. Finally, we identified BCLAF1 and NFE2L2 as influencers of MAPK activation in macrophages. Metformin downregulates NFE2L2 and could serve as a repurposed drug candidate.
CONCLUSIONS
SPP1 alveolar macrophages play a role in the profibrotic activity of IPF and SSc-ILD. However, SSc-ILD is influenced by autoimmunity and oxidative stress, leading to the continuous activation of MAPK in macrophages. This may result in an earlier onset of lung fibrosis than in IPF. Such differences could serve as potential research directions for early prevention and treatment.
Topics: Humans; Scleroderma, Systemic; Macrophages; Lung Diseases, Interstitial; Female; Male; Middle Aged; Adult; Idiopathic Pulmonary Fibrosis; Aged; Gene Expression Regulation; Single-Cell Analysis; Lung
PubMed: 38937794
DOI: 10.1186/s12967-024-05403-4 -
BMC Oral Health Jun 2024To examine the patterns of pretreatment facial soft tissue shape in orthodontic cases with premolar extraction using artificial intelligence (AI) and to investigate the... (Comparative Study)
Comparative Study
OBJECTIVE
To examine the patterns of pretreatment facial soft tissue shape in orthodontic cases with premolar extraction using artificial intelligence (AI) and to investigate the corresponding changes.
METHODS
One hundred and fifty-two patients who underwent orthodontic treatment with premolar extraction were enrolled. Lateral cephalograms were obtained before and after the treatment. For each record, the outlines of the nose-lip-chin profile and corresponding 21 cephalometric variables were extracted. The AI method classified pretreatment records into three subject groups based on the feature variables extracted from the outline. Dentoskeletal and soft tissue facial form changes observed after treatment were compared statistically (P < 0.05) between the groups using ANOVA. Multivariate regression models were used for each group.
RESULTS
Group 1 (n = 59) was characterized by Class II high-angle retrognathic mandible with an incompetent lip, group 2 (n = 55) by Class I malocclusion with retruded and thin lips, and group 3 (n = 38) by Class I malocclusion with an everted superior lip before treatment. The ratios of anteroposterior soft tissue to hard tissue movements in Group 1 were 56% (r = 0.64) and 83% (r = 0.75) for the superior and inferior lips, respectively, whereas those in Group 2 were 49% (r = 0.78) and 91% (r = 0.80), and 40% (r = 0.54) and 79% (r = 0.70), respectively, in Group 3.
CONCLUSIONS
The modes of facial form changes differed depending on the pre-treatment profile patterns classified by the AI. This indicates that the determination of the pre-treatment profile pattern can help in the selection of soft tissue to hard tissue movement ratios, which helps estimate the post-treatment facial profile with a moderate to high correlation.
Topics: Humans; Cephalometry; Face; Bicuspid; Tooth Extraction; Female; Male; Lip; Adolescent; Nose; Malocclusion, Angle Class I; Artificial Intelligence; Chin; Malocclusion, Angle Class II; Mandible; Tooth Movement Techniques; Child; Young Adult; Malocclusion
PubMed: 38937790
DOI: 10.1186/s12903-024-04512-2 -
NPJ Primary Care Respiratory Medicine Jun 2024The British Thoracic Society (BTS) and Scottish Intercollege Guidelines Network (SIGN), as well as National Institute for Health and Care Excellence (NICE), have... (Review)
Review
The British Thoracic Society (BTS) and Scottish Intercollege Guidelines Network (SIGN), as well as National Institute for Health and Care Excellence (NICE), have previously produced separate asthma guidance differing in some key aspects in diagnosis and management leading to confusion, potentially hampering guideline dissemination and uptake. While there are inherent challenges, the upcoming release of new joint BTS/SIGN/NICE asthma guidance presents an opportunity to assess guideline adoption and its impact on clinical practice. The use of prescription data via databases such as OpenPrescribing can be used as a surrogate for guideline adoption and potentially linked to clinical outcomes such as hospital episode statistics (HES). The potential recommendation for anti-inflammatory reliever therapy (AIR) and maintenance and reliever therapy (MART) with inhaled corticosteroid/formoterol combination therapy in the next iteration of UK asthma guidance will require the accurate coding for the respective therapeutic approaches on prescribing platforms in order to assess their impact in real-life clinical practice. This could then direct targeted measures to improve wider guidance adoption leading to better clinical care in asthma based on up to date evidence.
Topics: Humans; Asthma; Practice Guidelines as Topic; United Kingdom; Anti-Asthmatic Agents; Guideline Adherence; Adrenal Cortex Hormones
PubMed: 38937520
DOI: 10.1038/s41533-024-00379-6 -
Scientific Reports Jun 2024Exploring a novel approach to mental health technology, this study illuminates the intricate interplay between exteroception (the perception of the external world), and...
Exploring a novel approach to mental health technology, this study illuminates the intricate interplay between exteroception (the perception of the external world), and interoception (the perception of the internal world). Drawing on principles of sensory substitution, we investigated how interoceptive signals, particularly respiration, could be conveyed through exteroceptive modalities, namely vision and hearing. To this end, we developed a unique, immersive multisensory environment that translates respiratory signals in real-time into dynamic visual and auditory stimuli. The system was evaluated by employing a battery of various psychological assessments, with the findings indicating a significant increase in participants' interoceptive sensibility and an enhancement of the state of flow, signifying immersive and positive engagement with the experience. Furthermore, a correlation between these two variables emerged, revealing a bidirectional enhancement between the state of flow and interoceptive sensibility. Our research is the first to present a sensory substitution approach for substituting between interoceptive and exteroceptive senses, and specifically as a transformative method for mental health interventions, paving the way for future research.
Topics: Humans; Interoception; Female; Male; Adult; Young Adult; Acoustic Stimulation; Respiration; Photic Stimulation
PubMed: 38937475
DOI: 10.1038/s41598-024-63231-4 -
Nature Communications Jun 2024The genome of Mycobacterium tuberculosis encodes for a large repertoire of toxin-antitoxin systems. In the present study, MenT3 and MenT4 toxins belonging to MenAT...
The genome of Mycobacterium tuberculosis encodes for a large repertoire of toxin-antitoxin systems. In the present study, MenT3 and MenT4 toxins belonging to MenAT subfamily of TA systems have been functionally characterized. We demonstrate that ectopic expression of these toxins inhibits bacterial growth and this is rescued upon co-expression of their cognate antitoxins. Here, we show that simultaneous deletion of menT3 and menT4 results in enhanced susceptibility of M. tuberculosis upon exposure to oxidative stress and attenuated growth in guinea pigs and mice. We observed reduced expression of transcripts encoding for proteins that are essential or required for intracellular growth in mid-log phase cultures of ΔmenT4ΔT3 compared to parental strain. Further, the transcript levels of proteins involved in efficient bacterial clearance were increased in lung tissues of ΔmenT4ΔT3 infected mice relative to parental strain infected mice. We show that immunization of mice and guinea pigs with ΔmenT4ΔT3 confers significant protection against M. tuberculosis infection. Remarkably, immunization of mice with ΔmenT4ΔT3 results in increased antigen-specific T1 bias and activated memory T cell response. We conclude that MenT3 and MenT4 are important for M. tuberculosis pathogenicity and strains lacking menT3 and menT4 have the potential to be explored further as vaccine candidates.
Topics: Animals; Guinea Pigs; Mycobacterium tuberculosis; Mice; Bacterial Proteins; Tuberculosis; Female; Lung; Gene Deletion; Bacterial Toxins; Mice, Inbred C57BL; Tuberculosis Vaccines; Oxidative Stress; Virulence
PubMed: 38937463
DOI: 10.1038/s41467-024-49246-5 -
Nature Communications Jun 2024Progressive lung fibrosis is associated with poorly understood aging-related endothelial cell dysfunction. To gain insight into endothelial cell alterations in lung...
Progressive lung fibrosis is associated with poorly understood aging-related endothelial cell dysfunction. To gain insight into endothelial cell alterations in lung fibrosis we performed single cell RNA-sequencing of bleomycin-injured lungs from young and aged mice. Analysis reveals activated cell states enriched for hypoxia, glycolysis and YAP/TAZ activity in ACKR1+ venous and TrkB+ capillary endothelial cells. Endothelial cell activation is prevalent in lungs of aged mice and can also be detected in human fibrotic lungs. Longitudinal single cell RNA-sequencing combined with lineage tracing demonstrate that endothelial activation resolves in young mouse lungs but persists in aged ones, indicating a failure of the aged vasculature to return to quiescence. Genes associated with activated lung endothelial cells states in vivo can be induced in vitro by activating YAP/TAZ. YAP/TAZ also cooperate with BDNF, a TrkB ligand that is reduced in fibrotic lungs, to promote capillary morphogenesis. These findings offer insights into aging-related lung endothelial cell dysfunction that may contribute to defective lung injury repair and persistent fibrosis.
Topics: Animals; Endothelial Cells; Aging; Bleomycin; Humans; Mice; Pulmonary Fibrosis; Lung; Lung Injury; Receptor, trkB; Mice, Inbred C57BL; Brain-Derived Neurotrophic Factor; YAP-Signaling Proteins; Male; Single-Cell Analysis; Adaptor Proteins, Signal Transducing; Female; Disease Models, Animal
PubMed: 38937456
DOI: 10.1038/s41467-024-49545-x -
Farmacia Hospitalaria : Organo Oficial... Jun 2024Respiratory diseases present a challenge for the healthcare system due to their prevalence and clinical impact. The aim of this study was to explore the current...
OBJECTIVE
Respiratory diseases present a challenge for the healthcare system due to their prevalence and clinical impact. The aim of this study was to explore the current situation of hospital pharmacy in the field of respiratory diseases.
METHOD
Observational, cross-sectional study, with a national scope, divided into 2 parts. In an initial phase, the activity and level of pharmaceutical care in respiratory diseases was evaluated through an online questionnaire using REDCap. The survey was addressed to department chiefs and consisted of 17 items, divided into 2 modules: general data and general activity. The second phase was open to hospital pharmacists, with the aim of exploring their opinion on care, training, and improvement needs. The number of items in this phase was 19, divided into 5 modules: general data, pharmaceutical care, competencies, training, and degree of satisfaction.
RESULTS
In the first phase, 23 hospitals were included. Most of them (n=20) had a pharmacist in charge of respiratory diseases. However, a large proportion of them dedicated less than 40% of their working day to this activity. The pharmacist's activity occurred at the level of external patients (n=21), hospitalised patients (n=16), and secondarily in management (n=8). Integration is greater in pathologies such as asthma, IPF, pulmonary hypertension, and bronchiectasis. Participation in committees was present in 15 hospitals, with variability in pathologies and degree of involvement. In the second phase, 164 pharmacists participated, who considered pharmaceutical care in cystic fibrosis, asthma, and lung transplant as a priority. 51% considered integration to be adequate and 91% considered it necessary to implement prioritisation criteria. Professional competencies ranged from 6.5 to 6.9 out of 10 points. Only 45% of participants had received specific training in the last 4 years, indicating greater priority for asthma, pulmonary hypertension, and IPF.
CONCLUSIONS
Most centers have pharmacists specialised in respiratory diseases. However, there is room for improvement in terms of subspecialisation, participation in multidisciplinary committees, implementation of prioritisation criteria, diversification in pathologies treated, as well as greater specific training in this area.
PubMed: 38937161
DOI: 10.1016/j.farma.2024.05.010 -
The Journal of Maternal-fetal &... Dec 2024
Topics: Humans; Infant, Newborn; Ultrasonography; Lung; Intensive Care Units, Neonatal; Respiratory Distress Syndrome, Newborn
PubMed: 38937118
DOI: 10.1080/14767058.2024.2371541 -
Global Health, Science and Practice Jun 2024Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy...
Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy uses chest radiography (CXR) and GeneXpert (Xpert) rapid diagnostic testing to improve early detection of TB disease. Household contacts and vulnerable populations (e.g., individuals aged 60 years and older, smokers, diabetics, those with alcohol use disorders, and those previously treated for TB) with and without TB symptoms were screened in community campaigns using CXRs, followed by Xpert for those with a positive screen. In public non-TB district facilities, diabetics, respiratory outpatients, inpatients with lung disease, and other vulnerable populations underwent 2X evaluation. During COVID-19 restrictions in Vietnam, the 2X strategy improved access to TB services by decentralization to commune health stations, the lowest level of the health system, and enabling self-screening using a quick response mobile application. The number needed to screen (NNS) with CXRs to diagnose 1 person with TB disease was calculated for all 2X models and showed the highest yield among self-screeners (11 NNS with CXR), high yield for vulnerable populations in communities (60 NNS) and facilities (19 NNS), and moderately high yield for household contacts in community campaigns (154 NNS). Computer-aided diagnosis for CXRs was incorporated into community and facility implementation and improved physicians' CXR interpretations and Xpert referral decisions. Integration of TB infection and TB disease evaluation increased eligibility for TB preventive treatment among household contacts, a major challenge during implementation. The 2X strategy increased the rational use of Xpert, employing a health system-wide approach that reached vulnerable populations with and without TB symptoms in communities and facilities for early detection of TB disease. This strategy was effectively adapted to different levels of the health system during COVID-19 restrictions and contributed to post-pandemic TB recovery in Vietnam.
Topics: Humans; Vietnam; COVID-19; Tuberculosis, Pulmonary; Mass Screening; SARS-CoV-2; Middle Aged; Radiography, Thoracic; Tuberculosis; Female; Pandemics; Male; Vulnerable Populations
PubMed: 38936961
DOI: 10.9745/GHSP-D-24-00024 -
The Kobe Journal of Medical Sciences Jun 2024Olfactory neuroblastoma (ONB) is an uncommon malignant tumor and is usually treated by a multidisciplinary approach includes surgery, radiotherapy, and chemotherapy. A...
Olfactory neuroblastoma (ONB) is an uncommon malignant tumor and is usually treated by a multidisciplinary approach includes surgery, radiotherapy, and chemotherapy. A 62 years-old male had a tumor in the nasal cavity and diagnosed as ONB with Kadish A stage. Anterior skull base surgery was performed as radical treatment. Since the surgical margin was negative, no postoperative radiotherapy was administered. 14 years after the surgery, bilateral otitis media with effusion (OME) was occurred, we found the recurrence tumor at bilateral retropharyngeal lymph node (RPLN) which surrounded the internal carotid arteries. Since these were unresectable, we planned chemoradiotherapy which was 70Gy of intensity modulated radiotherapy combined with two courses of carboplatin and etoposide. The tumor volume was reduced and bilateral OME were improved. He has been alive for 3 years after salvage treatment. Although ONB has a relatively good prognosis, it is known to often cause cervical lymph node metastasis. Grades III and IV of Hyams classification are considered high risk. This case, initial tumor was limited in the nasal cavity and its clinical classification was early stage, but Hyams classification was grade III. In reference to this case, considering that RPLN metastasis are difficult to radically resect at the salvage surgery, including this area in postoperative radiotherapy was considered an option.
Topics: Humans; Male; Esthesioneuroblastoma, Olfactory; Middle Aged; Lymphatic Metastasis; Nose Neoplasms; Nasal Cavity; Skull Base; Neoplasm Recurrence, Local; Chemoradiotherapy
PubMed: 38936878
DOI: 10.24546/0100489917