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American Journal of Respiratory and... Nov 2014Myeloid cells encompass distinct populations with unique functions during homeostasis and disease. Recently, a novel subset of innate cells, myeloid-derived suppressor...
RATIONALE
Myeloid cells encompass distinct populations with unique functions during homeostasis and disease. Recently, a novel subset of innate cells, myeloid-derived suppressor cells (MDSCs), has been described in cancer, which suppresses T-cell responses and fosters disease progression. The role of MDSCs in infection is insufficiently addressed.
OBJECTIVES
To examine the presence and function of MDSCs during experimental pulmonary tuberculosis (TB) and further understand the immunologic consequences of direct interactions between MDSCs and lung bacterial pathogens.
METHODS
Using cell-based approaches and experimental mouse models for pulmonary TB we characterized MDSCs as novel myeloid populations directly interacting with Mycobacterium tuberculosis (Mtb).
MEASUREMENTS AND MAIN RESULTS
MDSCs readily phagocytosed Mtb, and released proinflammatory (IL-6, IL-1α) and immunomodulatory (IL-10) cytokines while retaining their suppressive capacity. MDSCs were identified at the site of infection in the lung in disease-resistant and -susceptible mice during pulmonary TB. Excessive MDSC accumulation in lungs correlated with elevated surface expression of IL-4Rα and heightened TB lethality, whereas targeted depletion of MDSCs ameliorated disease.
CONCLUSIONS
Our data reveal that MDSCs provide a niche for pathogen survival and tailor immunity in TB. These findings suggest MDSCs as amenable targets for host-directed therapies and emphasize them as cellular-immune regulators during chronic inflammatory conditions, including chronic infections and microbial complications of neoplastic disorders.
Topics: Animals; Mice; Mice, Inbred C57BL; Myeloid Cells; Tuberculosis, Pulmonary
PubMed: 25275852
DOI: 10.1164/rccm.201405-0828OC -
BMC Medical Genomics Jun 2024Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death....
BACKGROUND
Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death. Studies have shown a statistical association between RSV subtype or phylogenic lineage and RSV disease severity, although these results have been inconsistent. Associations between variation within RSV gene coding regions or residues and RSV disease severity has been largely unexplored.
METHODS
Nasal swabs from children (< 8 months-old) infected with RSV in Rochester, NY between 1977-1998 clinically presenting with either mild or severe disease during their first cold-season were used. Whole-genome RSV sequences were obtained using overlapping PCR and next-generation sequencing. Both whole-genome phylogenetic and non-phylogenetic statistical approaches were performed to associate RSV genotype with disease severity.
RESULTS
The RSVB subtype was statistically associated with disease severity. A significant association between phylogenetic clustering of mild/severe traits and disease severity was also found. GA1 clade sequences were associated with severe disease while GB1 was significantly associated with mild disease. Both G and M2-2 gene variation was significantly associated with disease severity. We identified 16 residues in the G gene and 3 in the M2-2 RSV gene associated with disease severity.
CONCLUSION
These results suggest that phylogenetic lineage and the genetic variability in G or M2-2 genes of RSV may contribute to disease severity in young children undergoing their first infection.
Topics: Humans; Respiratory Syncytial Virus Infections; Phylogeny; Genetic Variation; Severity of Illness Index; Infant; Respiratory Syncytial Virus, Human; Male; Genotype; Female; Genome, Viral
PubMed: 38898440
DOI: 10.1186/s12920-024-01930-7 -
Nature Immunology Oct 2023
PubMed: 37723351
DOI: 10.1038/s41590-023-01646-3 -
Frequent Benign, Nontraumatic, Noninflammatory Causes of Low Back Pain in Adolescents: MRI Findings.Radiology Research and Practice 2018Low back pain (LBP) is common in children and adolescents. There are many factors that cause LBP, including structural disorders, degenerative changes, Scheuermann's...
INTRODUCTION
Low back pain (LBP) is common in children and adolescents. There are many factors that cause LBP, including structural disorders, degenerative changes, Scheuermann's disease, fractures, inflammation, and tumors. Magnetic Resonance Imaging is the gold standard for diagnosing spinal abnormalities and is mandatory when neurological symptoms exist. The study focuses on common MRI findings in adolescents with persistent LBP, without history of acute trauma or evidence of either inflammatory or rheumatic disease.
MATERIALS AND METHODS
Eleven adolescents were submitted to thoracic and/or lumbar spine MRI due to persistent LBP. The protocol consisted of T1 WI, T2 WI, and T2 WI with FS, in the axial, sagittal, and coronal plane.
RESULTS
MRI revealed structural abnormalities (scoliosis and kyphosis) in 4/11 (36.36%); disc abnormalities and endplate changes were found on 11/11 (100%). Typical Scheuermann's disease was found in 3/11 (27.27%). Endplate changes were severe in Scheuermann's patients and mild to moderate in the remaining 8/11 (72.72%). Kyphosis was in all cases secondary to Scheuermann's disease. Disk bulges and hernias were found in 8/11 (72.72%), all located in the lumbar spine.
CONCLUSION
In adolescents with LBP, structural spinal disorders, degenerative changes, and Scheuermann's disease are commonly found on MRI; however, degenerative changes prevail.
PubMed: 29593901
DOI: 10.1155/2018/7638505 -
Science Translational Medicine Aug 2022Despite the remarkable efficacy of COVID-19 vaccines, waning immunity and the emergence of SARS-CoV-2 variants such as Omicron represents a global health challenge....
Despite the remarkable efficacy of COVID-19 vaccines, waning immunity and the emergence of SARS-CoV-2 variants such as Omicron represents a global health challenge. Here, we present data from a study in nonhuman primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine comprising the receptor binding domain of the ancestral strain (RBD-Wu) on the I53-50 nanoparticle adjuvanted with AS03, which was recently authorized for use in individuals 18 years or older. Vaccination induced neutralizing antibody (nAb) titers that were maintained at high concentrations for at least 1 year after two doses, with a pseudovirus nAb geometric mean titer (GMT) of 1978 and a live virus nAb GMT of 1331 against the ancestral strain but not against the Omicron BA.1 variant. However, a booster dose at 6 to 12 months with RBD-Wu or RBD-β (RBD from the Beta variant) displayed on I53-50 elicited high neutralizing titers against the ancestral and Omicron variants. In addition, we observed persistent neutralization titers against a panel of sarbecoviruses, including SARS-CoV. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Vaccination resulted in protection against Omicron infection in the lung and suppression of viral burden in the nares at 6 weeks after the final booster immunization. Even at 6 months after vaccination, we observed protection in the lung and rapid control of virus in the nares. These results highlight the durable and cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine.
Topics: Adjuvants, Immunologic; Animals; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2; Vaccines, Subunit; Viral Vaccines
PubMed: 35976993
DOI: 10.1126/scitranslmed.abq4130 -
European Journal of Physical and... Aug 2023In the literature, there are several papers on Scheuermann's kyphosis. It is a structural deformity of the spine that is characterized by anterior wedging of 5° or more... (Observational Study)
Observational Study
BACKGROUND
In the literature, there are several papers on Scheuermann's kyphosis. It is a structural deformity of the spine that is characterized by anterior wedging of 5° or more of 3 adjacent thoracic vertebral bodies with kyphosis measuring greater than 45° between T5 and T12. Bracing treatment is able to obtain, during skeletal growth, remodeling of the deformed vertebrae.
AIM
The aim of this study was to evaluate the effectiveness of conservative treatment in Scheuermann's kyphosis at a minimum follow-up of 10 years.
DESIGN
This is an observational controlled cohort study nested in a prospective clinical on-going database in patients with Scheuermann kyphosis.
SETTING
Inpatients and outpatients in Rome.
METHODS
From a consecutive series of patients included in a prospective database, we selected 158 patients with thoracic Scheuermann's kyphosis who were treated using an anti-gravity brace: 93 males and 65 females. The mean age at the beginning of the treatment was 14 years. The time bracing prescribed was a max of 20 hours daily and a min of 16 hours daily. Weaning was started when a full recovery of vertebral geometry was seen on a lateral radiograph view or when growing was ended. Radiographical measurements were performed on radiographs from a lateral projection at baseline (t1), at the end of the treatment (t2) and at 10 years of minimum follow-up (t3). To avoid the great variance in the range of curve angles in thoracic kyphosis (TK) that rely on the radiological position, X-rays were performed observing the following position: standing with head straight, arms bent at 45° and hands lightly placed on a support. The anterior wedging angle (Alpha) of the apex vertebra and the degrees of the curve (Cobb methods) were analyzed using statistical analysis.
RESULTS
The results from our study showed that in 158 patients with TK curves, the mean Cobb angle was 57.6±6.3 SD at baseline, 43.3±7.8 SD at the end of treatment and 44.49±7.4 SD at ten years of follow-up. The alpha angle was 14.43±2.535 SD at baseline and 8.571±3.589 SD at the end of treatment, and after ten years of follow-up, it was 8.654±3.57 SD. The mean duration of treatment was 28.42±12.07 months, and the mean follow-up was 128.3±11.07 months. The difference between baseline and end of treatment, tested with the one-way ANOVA comparisons test, was significant (P<0.0001) for both Cobb angle and alpha; instead, the difference between the end of treatment and follow-up was not significant (P=0.3277).
CONCLUSIONS
The results confirm that conservative treatment in Scheuermann's kyphosis during skeletal growth is effective. Bracing treatment can remodel the deformed vertebrae.
CLINICAL REHABILITATION IMPACT
At the 10-year follow-up after bracing, kyphosis curve correction was stable over time.
Topics: Female; Male; Humans; Adolescent; Scheuermann Disease; Cohort Studies; Research Design; Conservative Treatment; Thoracic Vertebrae
PubMed: 37746785
DOI: 10.23736/S1973-9087.23.08070-X -
PloS One 2024The COVID-19 pandemic prompted immense work on the investigation of the SARS-CoV-2 virus. Rapid, accurate, and consistent interpretation of generated data is thereby of...
The COVID-19 pandemic prompted immense work on the investigation of the SARS-CoV-2 virus. Rapid, accurate, and consistent interpretation of generated data is thereby of fundamental concern. Ontologies-structured, controlled, vocabularies-are designed to support consistency of interpretation, and thereby to prevent the development of data silos. This paper describes how ontologies are serving this purpose in the COVID-19 research domain, by following principles of the Open Biological and Biomedical Ontology (OBO) Foundry and by reusing existing ontologies such as the Infectious Disease Ontology (IDO) Core, which provides terminological content common to investigations of all infectious diseases. We report here on the development of an IDO extension, the Virus Infectious Disease Ontology (VIDO), a reference ontology covering viral infectious diseases. We motivate term and definition choices, showcase reuse of terms from existing OBO ontologies, illustrate how ontological decisions were motivated by relevant life science research, and connect VIDO to the Coronavirus Infectious Disease Ontology (CIDO). We next use terms from these ontologies to annotate selections from life science research on SARS-CoV-2, highlighting how ontologies employing a common upper-level vocabulary may be seamlessly interwoven. Finally, we outline future work, including bacteria and fungus infectious disease reference ontologies currently under development, then cite uses of VIDO and CIDO in host-pathogen data analytics, electronic health record annotation, and ontology conflict-resolution projects.
Topics: Humans; Pandemics; Biological Ontologies; Vocabulary, Controlled; Virus Diseases; Communicable Diseases; COVID-19
PubMed: 38236918
DOI: 10.1371/journal.pone.0285093 -
The Journal of Investigative Dermatology Feb 2024Tissue transcriptomics is used to uncover molecular dysregulations underlying diseases. However, the majority of transcriptomics studies focus on single diseases with... (Comparative Study)
Comparative Study
Tissue transcriptomics is used to uncover molecular dysregulations underlying diseases. However, the majority of transcriptomics studies focus on single diseases with limited relevance for understanding the molecular relationship between diseases or for identifying disease-specific markers. In this study, we used a normalization approach to compare gene expression across nine inflammatory skin diseases. The normalized datasets were found to retain differential expression signals that allowed unsupervised disease clustering and identification of disease-specific gene signatures. Using the NS-Forest algorithm, we identified a minimal set of biomarkers and validated their use as diagnostic disease classifier. Among them, PTEN was identified as being a specific marker for cutaneous lupus erythematosus and found to be strongly expressed by lesional keratinocytes in association with pathogenic type I IFNs. In fact, PTEN facilitated the expression of IFN-β and IFN-κ in keratinocytes by promoting activation and nuclear translocation of IRF3. Thus, cross-comparison of tissue transcriptomics is a valid strategy to establish a molecular disease classification and to identify pathogenic disease biomarkers.
Topics: Humans; Biomarkers; Dermatitis; Gene Expression Profiling; Keratinocytes; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; PTEN Phosphohydrolase; Skin
PubMed: 37598867
DOI: 10.1016/j.jid.2023.06.211 -
Orthopaedic Surgery Apr 2024Degenerative thoracolumbar hyperkyphosis (DTH) is a disease that negatively affects individual health and requires surgical intervention, yet the ideal surgical approach...
OBJECTIVE
Degenerative thoracolumbar hyperkyphosis (DTH) is a disease that negatively affects individual health and requires surgical intervention, yet the ideal surgical approach and complications, especially distal junctional failures (DJF), remain poorly understood. This study aims to investigate DJF in DTH and to identify the risk factors for DJF so that we can improve surgical decision-making, and advance our knowledge in the field of spinal surgery to enhance patient outcomes.
METHODS
This study retrospectively reviewed 78 cases (late osteoporotic vertebral compression fracture [OVCF], 51; Scheuermann's kyphosis [SK], 17; and degenerative disc diseases [DDD], 10) who underwent corrective surgery in our institute from 2008 to 2019. Clinical outcomes were assessed using health-related quality of life (HRQOL) measures, including the visual analogue scale (VAS) scores for back and leg pain, the Oswestry disability index (ODI), and the Japanese Orthopaedic Association (JOA) scoring system. Multiple radiographic parameters, such as global kyphosis (GK) and thoracolumbar kyphosis (TLK), were assessed to determine radiographic outcomes. Multivariate logistic regression analysis was employed to identify the risk factors associated with DJF.
RESULTS
HRQOL improved, and GK, TLK decreased at the final follow-up, with a correction rate of 67.7% and 68.5%, respectively. DJF was found in 13 of 78 cases (16.7%), two cases had wedging in the disc (L3-4) below the instrumentation, one case had a fracture of the lowest instrumented vertebrae (LIV), one case had osteoporotic fracture below the fixation, nine cases had pull-out or loosening of the screws at the LIV and three cases (23.1%) required revision surgery. The DJF group had older age, lower computed tomography Hounsfield unit (CT HU), longer follow-up, more blood loss, greater preoperative sagittal vertical axis (SVA), and poorer postoperative JOA and VAS scores (back). The change in TLK level was larger in the non-DJF group. Post-sagittal stable vertebrae (SSV) moved cranially compared with pre-SSV.
CONCLUSION
Age, CT HU, length of follow-up, estimated blood loss, and preoperative SVA were independent risk factors for DJF. We recommend fixation of the two vertebrae below the apex vertebrae for DTH to minimize surgical trauma.
Topics: Humans; Quality of Life; Retrospective Studies; Fractures, Compression; Treatment Outcome; Thoracic Vertebrae; Spinal Fractures; Kyphosis; Osteoporotic Fractures; Lumbar Vertebrae; Spinal Fusion
PubMed: 38384146
DOI: 10.1111/os.13973 -
Veterinary Surgery : VS Jan 2021To evaluate the evidence for the conservative and surgical management of pericardial effusions for neoplastic and idiopathic etiologies in dogs.
OBJECTIVE
To evaluate the evidence for the conservative and surgical management of pericardial effusions for neoplastic and idiopathic etiologies in dogs.
STUDY DESIGN
Systematic review.
SAMPLE POPULATION
Peer-reviewed English-language articles describing the treatment and outcome of naturally occurring pericardial effusion in domestic dogs.
METHODS
A literature search was performed with PubMed, Cab Abstracts, Scopus, and Agricola in August 2019 for articles describing pericardial effusion treatment in dogs. Inclusion criteria were applied, and articles were evaluated for reported outcome and level of evidence by using The Oxford 2011 Levels of Evidence, a previously described hierarchical system, and GRADE (Grading of Recommendations, Assessment, Development and Evaluation).
RESULTS
One hundred eight of the 641 unique articles that were identified and evaluated met inclusion criteria. Most articles included were case studies (68.2%) or retrospective case series (25.2%), with all articles providing a low level of evidence. The articles had inconsistent inclusion criteria, outcome measures, and follow-up, making comparison of outcomes difficult.
CONCLUSION
Because of the low quality of evidence of the studies included in this systematic review and the variability of the outcomes, there is not sufficient evidence to recommend one treatment option rather than another.
CLINICAL SIGNIFICANCE
There is a requirement for higher quality evidence such as randomized controlled trials and prospective comparative cohort studies. Standardization of outcome measures reported for each treatment option and disease process studied will allow for better comparison of outcomes between studies.
Topics: Animals; Dog Diseases; Dogs; Pericardial Effusion
PubMed: 32678497
DOI: 10.1111/vsu.13475