bluuebunny/crossref_metadata_2025 huggingface dataset:
Pericyte derived chemokines amplify neutrophil recruitment across the cerebrovascular endothelial barrier
Authors: Gil Eliza , Venturini Cristina , Stirling David , Turner Carolin , Tezera Liku B. , Ercoli Giuseppe , Baker Tina , Best Katharine , Brown Jeremy S. , Noursadeghi Mahdad
Published: July 2022

Excessive neutrophil extravasation can drive immunopathology, exemplified in pyogenic meningitis caused byStreptococcus pneumoniaeinfection. Insufficient knowledge of the mechanisms that amplify neutrophil extravasation has limited innovation in therapeutic targeting of neutrophil mediated pathology. Attention has focussed on neutrophil interactions with endothelia, but data from mouse models also point to a role for the underlying pericyte layer, as well as perivascular macrophages, the only other cell type found within the perivascular space in the cerebral microvasculature. We tested the hypothesis that human brain vascular pericytes (HBVP) contribute to neutrophil extravasation in a transwell model of the cerebral post-capillary venule. We show that pericytes augment endothelial barrier formation. In response to inflammatory cues, they significantly enhance neutrophil transmigration across the endothelial barrier, without increasing the permeability to small molecules. In our model, neither pericytes nor endothelia responded directly to bacterial stimulation. Instead, we show that paracrine signalling by multiple cytokines from monocyte derived macrophages drives transcriptional upregulation of multiple neutrophil chemokines by pericytes. Pericyte mediated amplification of neutrophil transmigration was independent of transcriptional responses by endothelia, but could be mediated by direct chemokine translocation across the endothelial barrier. Our data support a model in which microbial sensing by perivascular macrophages generates an inflammatory cascade where pericytes serve to amplify production of neutrophil chemokines that are translocated across the endothelial barrier to act directly on circulating neutrophils. In view of the striking redundancy in inflammatory cytokines that stimulate pericytes and in the neutrophil chemokines they produce, we propose that the mechanism of chemokine translocation may offer the most effective therapeutic target to reduce neutrophil mediated pathology in pyogenic meningitis.
Real-life data on monoclonal antibodies and antiviral drugs in Italian inborn errors of immunity patients during COVID-19 pandemic
Authors: Garzi Giulia , Cinetto Francesco , Firinu Davide , Di Napoli Giulia , Lagnese Gianluca , Punziano Alessandra , Bez Patrick , Cinicola Bianca Laura , Costanzo Giulia , Scarpa Riccardo , Pulvirenti Federica , Rattazzi Marcello , Spadaro Giuseppe , Quinti Isabella , Milito Cinzia
Published: July 2022

Background

Since the beginning of the COVID-19 pandemic, patients with Inborn Errors of Immunity have been infected by SARS-CoV-2 virus showing a spectrum of disease ranging from asymptomatic to severe COVID-19. A fair number of patients did not respond adequately to SARS-CoV-2 vaccinations, thus early therapeutic or prophylactic measures were needed to prevent severe or fatal course or COVID-19 and to reduce the burden of hospitalizations.

Methods

Longitudinal, multicentric study on patients with Inborn Errors of Immunity immunized with mRNA vaccines treated with monoclonal antibodies and/or antiviral agents at the first infection and at reinfection by SARS-CoV-2. Analyses of efficacy were performed according to the different circulating SARS-CoV-2 strains.

Results

The analysis of the cohort of 192 SARS-CoV-2 infected patients, across 26 months, showed the efficacy of antivirals on the risk of hospitalization, while mabs offered a positive effect on hospitalization, and COVID-19 severity. This protection was consistent across the alpha, delta and early omicron waves, although the emergence of BA.2 reduced the effect of available mabs. Hospitalized patients treated with mabs and antivirals had a lower risk of ICU admission. We reported 16 re-infections with a length of SARS-CoV-2 positivity at second infection shorter among patients treated with mabs. Treatment with antivirals and mabs was safe.

Conclusions

The widespread use of specific therapy, vaccination and better access to care might have contributed to mitigate risk of mortality, hospital admission, and severe disease. However, the rapid spread of new viral strains underlines that mabs and antiviral beneficial effects should be re- evaluated over time.
Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infection
Authors: Zhang Leidan , Wei Yuqing , Wang Di , Du Juan , Wang Xinyue , Li Bei , Jiang Meiqing , Zhang Mengyuan , Chen Na , Deng Meiju , Song Chuan , Chen Danying , Wu Liang , Xiao Jiang , Liang Hongyuan , Zhao Hongxin , Kong Yaxian
Published: July 2022

Persistent immune activation, which occurs during the whole course of HIV infection, plays a pivotal role in CD4+T cells depletion and AIDS progression. Furthermore, immune activation is a key factor that leads to impaired immune reconstitution after long-term effective antiretroviral therapy (ART), and is even responsible for the increased risk of developing non-AIDS co-morbidities. Therefore, it’s imperative to identify an effective intervention targeting HIV-associated immune activation to improve disease management. Double negative T cells (DNT) were reported to provide immunosuppression during HIV infection, but the related mechanisms remained puzzled. Foxp3 endows Tregs with potent suppressive function to maintain immune homeostasis. However, whether DNT cells expressed Foxp3 and the accurate function of these cells urgently needed to be investigated. Here, we found that Foxp3+DNT cells accumulated in untreated people living with HIV (PLWH) with CD4+T cell count less than 200 cells/µl. Moreover, the frequency of Foxp3+DNT cells was negatively correlated with CD4+T cell count and CD4/CD8 ratio, and positively correlated with immune activation and systemic inflammation in PLWH. Of note, Foxp3+DNT cells might exert suppressive regulation by increased expression of CD39, CD25, or vigorous proliferation (high levels of GITR and ki67) in ART-naive PLWH. Our study underlined the importance of Foxp3+DNT cells in the HIV disease progression, and suggest that Foxp3+DNT may be a potential target for clinical intervention for the control of immune activation during HIV infection.
Potential correlation of allograft infiltrating group 2 innate lymphoid cells with acute rejection after liver transplantation
Authors: Sun Jie , Zhou Guang-Peng , Li Shi-Peng , Chen Xiao-Jie , Zhang Jin-Ming , Jiang Yi-Zhou , Cui Bin , Zhang Hai-Ming , Sun Li-Ying , Zhu Zhi-Jun
Published: July 2022

Accumulating evidence indicates the critical roles of group 2 innate lymphoid cells (ILC2s) in immunoregulation. However, the role of ILC2s in acute rejection after liver transplantation (LT) remains elusive. In this study, we analyzed the frequency, counts, and signature cytokines of ILC2s in liver transplant recipients by flow cytometric analysis and multiplex immunofluorescence assay. We also assessed the spatial distribution and correlation between hepatic ILC2s and Treg cells. The changes of ILC2s were dynamically monitored in the mouse LT model. We found that the frequencies of circulating ILC2s were comparable in liver transplant recipients with either rejection or non-rejection compared with the control group. The hepatic ILC2s counts were significantly increased in the rejection group than in the non-rejection and control groups, and a similar trend was observed for Treg cells. In the mouse LT model, allograft infiltrating ILC2s dramatically increased within 14 days post-transplant. The frequency of ILC2s in bone marrow significantly increased at 7 days post-transplant and rapidly decreased at 14 days after LT. Similarly, there was a significant increase in the frequency of splenic ILC2s within two weeks post-transplant. Multiplex immunofluorescence assay showed a close correlation between hepatic ILC2s and Treg cells by analyzing their spatial distribution and distance. In conclusion, the number of allograft infiltrating ILC2s was closely related to rejection after LT. Allograft infiltrating ILC2s may play inhibitory roles in posttransplant immune homeostasis, favoring resolution of liver allograft rejection by interacting with Treg cells or promoting the migration of Tregs cells into the liver allograft.
Coexistence of anti-SOX1 and anti-GABAB receptor antibodies with paraneoplastic limbic encephalitis presenting with seizures and memory impairment in small cell lung cancer: A case report
Authors: Gong Sizhu , Han Yue , He Enling , Liu Min , Fu Xiyao , Deng Fang
Published: July 2022

Purpose

Paraneoplastic neurological syndromes associated with autoantibodies are rare diseases that cause abnormal manifestations of the nervous system. Early diagnosis of paraneoplastic neurological syndromes paves the way for prompt and efficient therapy.

Case report

we reported a 56-year-old man presenting with seizures and rapidly progressive cognitive impairment diagnosed as paraneoplastic limbic encephalitis (PLE) with anti-SRY-like high-mobility group box-1 (SOX-1) and anti-γ-aminobutyric acid B (GABAB) receptor antibodies and finally confirmed by biopsy as small cell lung cancer (SCLC). At the first admission, brain magnetic resonance imaging (MRI) showed no abnormal signal in bilateral hippocampal regions and no abnormal enhancement of enhanced scan. The serum anti-GABAB receptor antibody was 1:100 and was diagnosed as autoimmune encephalitis (AE). The computed tomography (CT) scans of the chest showed no obvious tumor signs for the first time. Although positron emission tomography-computed tomography (PET-CT) revealed hypermetabolism in the para mid-esophageal, the patient and his family declined to undertake a biopsy. The patient improved after receiving immunoglobulin, antiepileptic therapy, and intravenous methylprednisolone (IVMP) pulse treatment. However, after 4 months, the symptoms reappeared. Brain MRI revealed abnormal signals in the hippocampal regions. Reexamination of the cerebral fluid revealed anti-GABAB receptor and anti-SOX-1 antibodies, which contributed to the diagnosis of PLE. SCLC was found in a para mid-esophageal pathological biopsy. Antiepileptic medications and immunoglobulin were used to treat the patient, and the symptoms were under control.

Conclusion

Our findings increase the awareness that patients with limbic encephalitis with cognitive dysfunction and epileptic seizures should be enhanced to detect latent malignancy. Our case also highlights the importance of anti-SOX1 antibodies in the detection of underlying neoplasm, particularly SCLC. Our findings raise awareness of the cognitive impairment seen by patients with limbic encephalitis.
The EGFR/ErbB inhibitor neratinib modifies the neutrophil phosphoproteome and promotes apoptosis and clearance by airway macrophages
Authors: Herman Kimberly D. , Wright Carl G. , Marriott Helen M. , McCaughran Sam C. , Bowden Kieran A. , Collins Mark O. , Renshaw Stephen A. , Prince Lynne R.
Published: July 2022

Dysregulated neutrophilic inflammation can be highly destructive in chronic inflammatory diseases due to prolonged neutrophil lifespan and continual release of histotoxic mediators in inflamed tissues. Therapeutic induction of neutrophil apoptosis, an immunologically silent form of cell death, may be beneficial in these diseases, provided that the apoptotic neutrophils are efficiently cleared from the tissue. Previous research in our group identified ErbB inhibitors as able to induce neutrophil apoptosis and reduce neutrophilic inflammation bothin vitroandin vivo. Here, we extend that work using a clinical ErbB inhibitor, neratinib, which has the potential to be repurposed in inflammatory diseases. We show that neratinib reduces neutrophilic migration o an inflammatory site in zebrafish larvae. Neratinib upregulates efferocytosis and reduces the number of persisting neutrophil corpses in mouse models of acute, but not chronic, lung injury, suggesting that the drug may have therapeutic benefits in acute inflammatory settings. Phosphoproteomic analysis of human neutrophils shows that neratinib modifies the phosphorylation of proteins regulating apoptosis, migration, and efferocytosis. This work identifies a potential mechanism for neratinib in treating acute lung inflammation by upregulating the clearance of dead neutrophils and, through examination of the neutrophil phosphoproteome, provides important insights into the mechanisms by which this may be occurring.
Innate immunity and microbial dysbiosis in hidradenitis suppurativa – vicious cycle of chronic inflammation
Authors: Chopra Divya , Arens Rachel A. , Amornpairoj Watcharee , Lowes Michelle A. , Tomic-Canic Marjana , Strbo Natasa , Lev-Tov Hadar , Pastar Irena
Published: July 2022

Hidradenitis Suppurativa (HS) is a chronic multifactorial inflammatory skin disease with incompletely understood mechanisms of disease pathology. HS is characterized by aberrant activation of the innate immune system, resulting in activation of pathways that aim to protect against pathogenic microorganisms, and also contribute to failure to resolve inflammation. Imbalance in innate immunity is evident in deregulation of host antimicrobial peptides (AMPs) and the complement system associated with the microbiome dysbiosis. The pathology is further complicated by ability of pathogens associated with HS to overcome host immune response. Potential roles of major AMPs, cathelicidin, defensins, dermcidin, S100 proteins, RNAse 7 and complement proteins are discussed. Dysregulated expression pattern of innate immunity components in conjunction with bacterial component of the disease warrants consideration of novel treatment approaches targeting both host immunity and pathogenic microbiome in HS.
Identification of key interferon-stimulated genes for indicating the condition of patients with systemic lupus erythematosus
Authors: Shen Mengjia , Duan Congcong , Xie Changhao , Wang Hongtao , Li Zhijun , Li Baiqing , Wang Tao
Published: July 2022

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with highly heterogeneous clinical symptoms and severity. There is complex pathogenesis of SLE, one of which is IFNs overproduction and downstream IFN-stimulated genes (ISGs) upregulation. Identifying the key ISGs differentially expressed in peripheral blood mononuclear cells (PBMCs) of patients with SLE and healthy people could help to further understand the role of the IFN pathway in SLE and discover potential diagnostic biomarkers.

The differentially expressed ISGs (DEISG) in PBMCs of SLE patients and healthy persons were screened from two datasets of the Gene Expression Omnibus (GEO) database. A total of 67 DEISGs, including 6 long noncoding RNAs (lncRNAs) and 61 messenger RNAs (mRNAs) were identified by the “DESeq2” R package. According to Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, those DEISGs were mainly concentrated in the response to virus and immune system processes. Protein-protein interaction (PPI) network showed that most of these DEISGs could interact strongly with each other. Then, IFIT1, RSAD2, IFIT3, USP18, ISG15, OASL, MX1, OAS2, OAS3, and IFI44 were considered to be hub ISGs in SLE by “MCODE” and “Cytohubba” plugins of Cytoscape, Moreover, the results of expression correlation suggested that 3 lncRNAs (NRIR, FAM225A, and LY6E-DT) were closely related to the IFN pathway.

The lncRNA NRIR and mRNAs (RSAD2, USP18, IFI44, and ISG15) were selected as candidate ISGs for verification. RT-qPCR results showed that PBMCs from SLE patients had substantially higher expression levels of 5 ISGs compared to healthy controls (HCs). Additionally, statistical analyses revealed that the expression levels of these ISGs were strongly associated to various clinical symptoms, including thrombocytopenia and facial erythema, as well as laboratory indications, including the white blood cell (WBC) count and levels of autoantibodies. The Receiver Operating Characteristic (ROC) curve demonstrated that the IFI44, USP18, RSAD2, and IFN score had good diagnostic capabilities of SLE.

According to our study, SLE was associated with ISGs including NRIR, RSAD2, USP18, IFI44, and ISG15, which may contribute to the future diagnosis and new personalized targeted therapies.
Contribution of the seagrass Syringodium isoetifolium to the metabolic functioning of a tropical reef lagoon
Authors: Olivé Irene , García-Robledo Emilio , Silva João , Pintado-Herrera Marina G. , Santos Rui , Kamenos Nicholas A. , Cuet Pascale , Frouin Patrick
Published: July 2022

Seagrasses are gaining attention thanks to their metabolism and potential major role as carbon sinks, with further implications as nature-based solutions against climate change. Despite their recognized importance and the growing number of studies published, there is still a striking paucity of information on seagrass metabolism and contribution to biogeochemical cycles for some seagrass species and ocean areas. In this study we assessed the metabolic balance and nutrient cycling contribution of seagrasses to the benthic compartment of a tropical reef lagoon in Reunion Island, providing original information on a barely studied seagrass species (Syringodium isoetifolium) and a poorly studied ocean region (West Indian Ocean). We measured the net productivity, respiration and the metabolic balance in different components of the lagoon benthic compartment (i.e. seagrass, sediment, and benthic community) and the water-sediment nutrient benthic fluxes at differently impacted sites within the lagoon. The biogeochemical environmental variability, including inorganic and organic indicators of anthropogenic contamination, was also assessed at each site.

Large spatial variability was detected in the metabolic balance of each benthic component assessed, also associated with the natural and/or anthropic-driven environmental variability found in the lagoon. The seagrass S. isoetifolium was net autotrophic across the lagoon and contributed to the lagoon benthic metabolism with net plant productivity exceeding by one order of magnitude the plant respiration. The lowest seagrass metabolism was detected at the impacted site. The metabolic balance of the sediment was heterotrophic but the high productivity of S. isoetifolium contributed to reducing the heterotrophy of the whole benthic community. The lagoon-wide benthic metabolic balance was slightly heterotrophic, but the associated uncertainty ranged from autotrophy to heterotrophy. Nutrient concentrations in the lagoon were low and the benthic community capacity for nutrient retention (uptake) and removal (denitrification and anammox) indicated potential for buffering moderate nutrient inputs into the lagoon. Organic contaminants of emerging concern (CECs) were low but detectable in the lagoon, especially in highly frequented beach areas, arising as an environmental quality indicator of interest.
Genetic Variation in Heat Tolerance of the Coral Platygyra Daedalea Indicates Potential for Adaptation to Ocean Warming
Authors: Elder Holland , Weis Virginia M. , Montalvo-Proano Jose , Mocellin Veronique J. L. , Baird Andrew H. , Meyer Eli , Bay Line K.
Published: July 2022

Ocean warming represents the greatest threat to the persistence of reef ecosystems. Most coral populations are projected to experience temperatures above their current bleaching thresholds annually by 2050. Adaptation to higher temperatures is necessary if corals are to persist in a warming future. While many aspects of heat stress have been well studied, few data are available for predicting the capacity for adaptive cross-generational responses in corals. Consistent sets of heat tolerant genomic markers that reliably predict thermal tolerance have yet to be identified. To address this knowledge gap, we quantified the heritability and genetic variation associated with heat tolerance in Platygyra daedalea from the Great Barrier Reef. We tracked the survival of ten quantitative genetic crosses of larvae produced form six parental colonies in a heat tolerance selection experiment. We also identified allelic shifts in heat-selected (35°C) survivors compared with paired, non-selected controls (27°C). The narrow-sense heritability of survival under heat stress was 0.66 and a total of 1,069 single nucleotide polymorphisms (SNPs) were associated with different survival probabilities. While 148 SNPs were shared between several experimental crosses, no common SNPs were identified for all crosses, which suggests that specific combinations of many markers are responsible for heat tolerance. However, we found two regions that overlap with previously identified loci associated with heat tolerance in Persian Gulf populations of P. daedalea, which reinforces the importance of these markers for heat tolerance. These results illustrate the importance of high heritability and the complexity of the genomic architecture underpinning host heat tolerance. These findings suggest that this P. daedalea population has the genetic prerequisites for adaptation to increasing temperatures. This study also provides knowledge for the development of high throughput genomic tools which may screen for variation within and across populations to enhance adaptation through assisted gene flow and assisted migration.
Multi-utility of therapeutic drug monitoring in inflammatory bowel diseases
Authors: Martins Camilla de Almeida , Garcia Karoline Soares , Queiroz Natália Sousa Freita
Published: July 2022

Inflammatory bowel disease (IBD) treatment targets have progressed over time from clinical response to clinical and endoscopic remission. Several data have shown a positive correlation between serum biologic drug concentrations and favorable therapeutic outcomes. Therapeutic drug monitoring (TDM) has evolved as an important approach for optimizing the use of immunobiologics, especially antitumor necrosis factor therapy, in patients with IBD. The use of TDM is supported by medical societies and IBD experts in different contexts; however, challenges remain due to knowledge gaps that limit the widespread use of it. The aim of this review is to assess the role of TDM in IBD, focusing on the implementation of this strategy in different scenarios and demonstrating the multi-utility aspects of this approach in clinical practice.
Evolution of red blood cell membrane complement regulatory proteins and rheology in septic patients: An exploratory study
Authors: Vanderelst Julie , Rousseau Alexandre , Selvais Nicolas , Biston Patrick , Zouaoui Boudjeltia Karim , Piagnerelli Michaël
Published: July 2022

Background

During sepsis, red blood cell (RBC) deformability is altered. Persistence of these alterations is associated with poor outcome. Activation of the complement system is enhanced during sepsis and RBCs are protected by membrane surface proteins like CD35, CD55 and CD59. In malaria characterized by severe anemia, a study reported links between the modifications of the expression of these RBCs membrane proteins and erythrophagocytosis. We studied the evolution of RBCs deformability and the expression of RBC membrane surface IgG and regulatory proteins in septic patients.

Methods

By flow cytometry technics, we measured at ICU admission and at day 3–5, the RBC membrane expression of IgG and complement proteins (CD35, 55, 59) in septic patients compared to RBCs from healthy volunteers. Results were expressed in percentage of RBCs positive for the protein. RBC shape was assessed using Pearson's second coefficient of dissymmetry (PCD) on the histogram obtained with a flow cytometer technique. A null value represents a perfect spherical shape. RBC deformability was determined using ektacytometry by the elongation index in relation to the shear stress (0.3–50 Pa) applied to the RBC membrane. A higher elongation index indicates greater RBC deformability.

Results

RBCs from 11 septic patients were compared to RBCs from 21 volunteers. At ICU admission, RBCs from septic patients were significantly more spherical and RBC deformability was significantly lower in septic patients for all shear stress ≥1.93 Pa. These alterations of shape and deformability persists at day 3–5. We observed a significant decrease at ICU admission only in CD35 expression on RBCs from septic patients. This low expression remained at day 3–5.

Conclusions

We observed in RBCs from septic patients a rapid decrease expression of CD35 membrane protein protecting against complement activation. These modifications associated with altered RBC deformability and shape could facilitate erythrophagocytosis, contributing to anemia observed in sepsis. Other studies with a large number of patients and assessment of erythrophagocytosis were needed to confirm these preliminary data.
Hematological indices in the adult saudi population: Reference intervals by gender, age, and region
Authors: Shaheen Naila A. , Rehan Hina , Moghairi Areej , Gmati Giamal , Damlaj Moussab , Salama Hind , Rather Mushtaq , Mendoza May Anne , Alanazi Abeer , Al Ahmari Bader , Al Zahrani Mohsen , Al-Hejazi Ayman , Alaskar Ahmed S.
Published: July 2022

Introduction

Hematological parameters are critical in disease diagnosis, management, and monitoring; however, complete blood count (CBC) reference intervals vary across populations. The aim of the current study was to provide the reference ranges of hematological parameters/indices in the healthy adult Saudi population.

Methods

A multicenter retrospective cross-sectional study was conducted with a sample of employees who were screened pre-employment from January 2015 to December 2019, at tertiary care hospitals in three regions. Demographic and CBC data were extracted from the electronic health system. The 2.5th and 97.5th percentiles were used to determine the reference intervals.

Results

Of a total of 1,388 participants, 53.82% were male. The majority 96% was less than 40 years old, and 85% were from the Central region. Gender-related differences were observed for the RBC count, Hb, HCT, MCV, MCH, MCHC, and the platelet count. Age-related differences were observed for the RBC, Hb, HCT, and eosinophils. The WBC parameters did not differ by gender or age categories. Region-related differences were observed for the RBC, hemoglobin, HCT, MCV, WBC, and basophils. The platelet count was higher in the female group, the age group 40 years and above, and in the Western region. The prevalence of anemia was high in the female group and the Eastern region. The overall neutropenia rate was 12.8%.

Conclusion

The data from this study provide hematological parameter reference ranges for the adult Saudi population by gender, age, and region. Gender and age-related differences were observed for the hematological parameters. Anemia was more frequent in the female group and the Eastern region. Caution must be taken when comparing or interpreting results from different age groups, gender, region of origin, and ethnicity.
Case report: Clinical and histopathological characteristics of psoriasiform erythema and de novo IL-17A cytokines expression on lesioned skin in atopic dermatitis children treated with dupilumab
Authors: Ali Kamran , Wu Liming , Qiu YunMi , Li Menghua
Published: July 2022

Background

Atopic dermatitis (AD) is a chronic recurrent inflammatory disease, and dupilumab, a human monoclonal antibody, is the firstly approved biological drug for AD. Psoriasiform erythema (PE) during dupilumab treatment in adults has been reported. This study describes the risk of PE in children after initiation of dupilumab treatment.

Objectives

To evaluate the de novo cytokines gene expression in the transition of atopic dermatitis symptoms to psoriasiform erythema during dupilumab treatment in children.

Methods

Two 17-year-old teenage twin patients with AD were included in this study who developed psoriasiform erythema after initiation of dupilumab. The lesional skin biopsy specimens were obtained for the histopathological investigation and RNA Fluorescence In Situ Hybridization (RNA-FISH). Dermoscopy, cytometry (cytokine detection in the blood), and blood investigations were completed for the pedigree and the lesioned descriptions.

Results

Two twin patients with AD presented with erythematic scaly plaques on the back, scalp, abdomen, and extensor extremities after 20 weeks of dupilumab treatment. The transitional change of AD to psoriasiform erythema treated with dupilumab was observed. Our subjects' dermoscopy showed pinpoint bleeding and white scales on pink background. Histopathology features showed psoriasiform hyperplasia, epidermal hyperplasia (acanthosis), ectatic capillaries, perivascular lymphocytes infiltration, and parakeratosis, with the absence of the granular cell layer. mRNA (RNA-FISH) cytokines gene expression showed a significantly high concentration of IL-17A. Blood investigation results showed a high concentration of (Immunoglobulin E) IgE and Eosinophils, and cytokines detection in blood showed IL-5,6 and IL-17 in one patient; however, only IL-5 in another patient. The dupilumab was discontinued and initiated with Baricitinib. Baricitinib showed a significant reduction in skin lesions.

Conclusion

Psoriasiform erythema can appear during dupilumab treatment in atopic dermatitis children. Potently, by suppressing skewed Th2 activation in patients with AD, the balance might shift toward Th1/Th17 predominance, and psoriasis develops. Baricitinib is a potential drug for psoriasiform erythema with significant therapeutic effects.
Endoscopic dacryocystorhinostomy with short-term, pushed-type bicanalicular intubation vs. pulled-type monocanalicular intubation for primary acquired nasolacrimal duct obstruction
Authors: Chi Yi-Chun , Lai Chun-Chieh
Published: July 2022

Dacryocystorhinostomy (DCR) has been a primary treatment for adults with nasolacrimal duct obstruction, while the optimal approach and technique remain controversial. With the advancement of endoscopic DCR and the silicone stents, an update of the surgical outcomes and preferable approaches is required. This study aims at comparing the surgical outcomes of endoscopic DCR using pushed bicanalicular intubation (BCI) to pulled monocanalicular intubation (MCI) in adults with primary acquired nasolacrimal duct obstruction (PANDO). Forty five eyes of 45 patients were enrolled, including 22 eyes of 22 patients treated with endoscopic DCR with pulled MCI and 23 eyes of 23 patients with pushed BCI from January 2014 to June 2021. The success rates at stent removal, 1 month and 3 months after removal were 95, 91, and 82%, respectively, in the MCI group, and 100, 87, and 87% in the BCI group. The BCI group had better success rates but failed to reach a significant difference (p = 0.49, p = 0.67, p = 0.24, respectively). After analyzing with binary logistic regression, the implant material was demonstrated as the predictive of surgical success (p = 0.045). There was no significant difference in success rates between patients with dacryocystitis and those without dacryocystitis. We conclude that endoscopic DCR with pushed BCI is easily manipulated and has a promising surgical outcome over pulled MCI. Stent indwelling duration as well as history of dacryocystitis have less influence on the success rates.
Review of investigational medical devices' clinical trials and regulations in Africa as a benchmark for new innovations
Authors: Matovu Brian , Takuwa Mercy , Mpaata Charles Norman , Denison Fiona , Kiwanuka Noah , Lewis Steff , Norrie John , Ononge Sam , Muhimbise Owen , Tuck Sharon , Etuket Maureen Dimitri , Ssekitoleko Robert T.
Published: July 2022

Medical technologies present a huge potential in improving global health playing a key role toward achieving Sustainable Development Goal 3 by 2030. A number of clinicians, innovators, business entities and biomedical engineers among others have developed a number of innovative medical devices and technologies to address the healthcare challenges especially in Africa. Globally, medical devices clinical trials present the most acceptable method for determining the risks and benefits of medical device innovations with the aim of ascertaining their effectiveness and safety as compared with established medical practice. However, there are very few medical device clinical trials reported in Africa compared to other regions like USA, UK and Europe. Most of the medical device clinical trials reported in Africa are addressing challenges around HIV/AIDS, maternal health and NCDs. In this mini review, we report about some of the published medical device clinical trials in Africa PubMed and Google Scholar and their associated challenges.
Bacillus velezensis SYL-3 suppresses Alternaria alternata and tobacco mosaic virus infecting Nicotiana tabacum by regulating the phyllosphere microbial community
Authors: Liu He , Jiang Jun , An Mengnan , Li Bin , Xie Yunbo , Xu Chuantao , Jiang Lianqiang , Yan Fangfang , Wang Zhiping , Wu Yuanhua
Published: July 2022

The occurrence of plant diseases is closely associated with the imbalance of plant tissue microecological environment. The regulation of the phyllosphere microbial communities has become a new and alternative approach to the biological control of foliar diseases. In this study, Bacillus velezensis SYL-3 isolated from Luzhou exhibited an effective inhibitory effect against Alternaria alternata and tobacco mosaic virus (TMV). The analysis of phyllosphere microbiome by PacBio sequencing indicated that SYL-3 treatment significantly altered fungal and bacterial communities on the leaves of Nicotiana tabacum plants and reduced the disease index caused by A. alternata and TMV. Specifically, the abundance of P. seudomo, Sphingomonas, Massilia, and Cladosporium in the SYL-3 treatment group increased by 19.00, 9.49, 3.34, and 12.29%, respectively, while the abundances of Pantoea, Enterobacter, Sampaiozyma, and Rachicladosporium were reduced. Moreover, the abundance of beneficial bacteria, such as Pseudomonas and Sphingomonas, was negatively correlated with the disease indexes of A. alternata and TMV. The PICRUSt data also predicted the composition of functional genes, with significant differences being apparent between SYL-3 and the control treatment group. Further functional analysis of the microbiome also showed that SYL-3 may induce host disease resistance by motivating host defense-related pathways. These results collectively indicate that SYL-3 may suppress disease progression caused by A. alternata or TMV by improving the microbial community composition on tobacco leaves.
A Lactobacilli diet that confers MRSA resistance causes amino acid depletion and increased antioxidant levels in the C. elegans host
Authors: Møller Katrine Vogt , Nguyen Hien Thi Thu , Mørch Maria Grymer Metz , Hesselager Marianne Overgaard , Mulder Frans A. A. , Fuursted Kurt , Olsen Anders
Published: July 2022

Probiotic bacteria are increasingly popular as dietary supplements and have the potential as alternatives to traditional antibiotics. We have recently shown that pretreatment with Lactobacillus spp. Lb21 increases the life span of C. elegans and results in resistance toward pathogenic methicillin-resistant Staphylococcus aureus (MRSA). The Lb21-mediated MRSA resistance is dependent on the DBL-1 ligand of the TGF-β signaling pathway. However, the underlying changes at the metabolite level are not understood which limits the application of probiotic bacteria as timely alternatives to traditional antibiotics. In this study, we have performed untargeted nuclear magnetic resonance-based metabolic profiling. We report the metabolomes of Lactobacillus spp. Lb21 and control E. coli OP50 bacteria as well as the nematode-host metabolomes after feeding with these diets. We identify 48 metabolites in the bacteria samples and 51 metabolites in the nematode samples and 63 across all samples. Compared to the control diet, the Lactobacilli pretreatment significantly alters the metabolic profile of the worms. Through sparse Partial Least Squares discriminant analyses, we identify the 20 most important metabolites distinguishing probiotics from the regular OP50 food and worms fed the two different bacterial diets, respectively. Among the changed metabolites, we find lower levels of essential amino acids as well as increased levels of the antioxidants, ascorbate, and glutathione. Since the probiotic diet offers significant protection against MRSA, these metabolites could provide novel ways of combatting MRSA infections.
Traits along the leaf economics spectrum are associated with communities of foliar endophytic symbionts
Authors: Tellez Peter H. , Arnold A. Elizabeth , Leo Ashton B. , Kitajima Kaoru , Van Bael Sunshine A.
Published: July 2022

Leaf traits of plants worldwide are classified according to the Leaf Economics Spectrum (LES), which links leaf functional traits to evolutionary life history strategies. As a continuum ranging from thicker, tough leaves that are low in nitrogen (N) to thinner, softer, leaves that are high in N, the LES brings together physical, chemical, and ecological traits. Fungal endophytes are common foliar symbionts that occur in healthy, living leaves, especially in tropical forests. Their community composition often differs among co-occurring host species in ways that cannot be explained by environmental conditions or host phylogenetic relationships. Here, we tested the over-arching hypothesis that LES traits act as habitat filters that shape communities of endophytes both in terms of composition, and in terms of selecting for endophytes with particular suites of functional traits. We used culture-based and culture-free surveys to characterize foliar endophytes in mature leaves of 30 phylogenetically diverse plant species with divergent LES traits in lowland Panama, and then measured functional traits of dominant endophyte taxa in vitro. Endophytes were less abundant and less diverse in thick, tough, leaves compared to thin, softer, leaves in the same forest, even in closely related plants. Endophyte communities differed according to leaf traits, including leaf punch strength and carbon and nitrogen content. The most common endophyte taxa in leaves at different ends of the LES differ in their cellulase, protease, chitinase, and antipathogen activity. Our results extend the LES framework for the first time to diverse and ecologically important endophytes, opening new hypotheses regarding the degree to which foliar symbionts respond to, and extend, the functional traits of leaves they inhabit.
The effect of environment on intestinal microbial diversity of Panthera animals may exceed genetic relationship
Authors: Chen Lei , Xu Di , Sun Mengyao , Li Ying , Wang Shen , Gao Ying , Gao Zenghao , Shi Yuying
Published: July 2022

Intestinal microbes are important symbiotes in the gastrointestinal tract of mammals, which are affected by food, environment, climate, genetics, and other factors. The gut microbiota of felines has been partially studied, but a comprehensive comparison of the gut microbiota of Panthera species was less reported. In this study, we compared the gut microbial composition and diversity of five species of Panthera (Panthera tigris, Panthera leo, Panthera onca, Panthera pardus, and Panthera uncia) by 16S ribosomal RNA (rRNA) amplicon sequencing. The results showed that Firmicutes was the most abundant phylum among all the Panthera species, followed by Actinobacteria, Fusobacteria, Bacteroidetes, Proteobacteria, Acidobacteria, Verrucomicrobia, Gemmatimonadetes, and Euryarchaeota. There were significant differences in observed species of fecal microbiota among different Panthera animals (P < 0.05), indicating that there is species specificity among Panthera fecal microbiota. When the samples were further grouped according to sampling locations, the comparison of the alpha diversity index between groups and beta diversity analysis showed that there were significant differences in the fecal microflora of animals from different sampling locations. Cluster analysis showed that fecal microbes of animals from the same sampling location were clustered, while gut microbes of animals of the same species, but from different sampling locations, were separated. These results indicate that environment may have more influence on mammals’ fecal microbial diversity than genetic relationships.
Clinical determinants and neural correlates of presbyphagia in community-dwelling older adults
Authors: Labeit Bendix , Muhle Paul , von Itter Jonas , Slavik Janna , Wollbrink Andreas , Sporns Peter , Rusche Thilo , Ruck Tobias , Hüsing-Kabar Anna , Gellner Reinhold , Gross Joachim , Wirth Rainer , Claus Inga , Warnecke Tobias , Dziewas Rainer , Suntrup-Krueger Sonja
Published: July 2022

Background

“Presbyphagia” refers to characteristic age-related changes in the complex neuromuscular swallowing mechanism. It has been hypothesized that cumulative impairments in multiple domains affect functional reserve of swallowing with age, but the multifactorial etiology and postulated compensatory strategies of the brain are incompletely understood. This study investigates presbyphagia and its neural correlates, focusing on the clinical determinants associated with adaptive neuroplasticity.

Materials and methods

64 subjects over 70 years of age free of typical diseases explaining dysphagia received comprehensive workup including flexible endoscopic evaluation of swallowing (FEES), magnetoencephalography (MEG) during swallowing and pharyngeal stimulation, volumetry of swallowing muscles, laboratory analyzes, and assessment of hand-grip-strength, nutritional status, frailty, olfaction, cognition and mental health. Neural MEG activation was compared between participants with and without presbyphagia in FEES, and associated clinical influencing factors were analyzed. Presbyphagia was defined as the presence of oropharyngeal swallowing alterations e.g., penetration, aspiration, pharyngeal residue pooling or premature bolus spillage into the piriform sinus and/or laryngeal vestibule.

Results

32 of 64 participants showed swallowing alterations, mainly characterized by pharyngeal residue, whereas the airway was rarely compromised. In the MEG analysis, participants with presbyphagia activated an increased cortical sensorimotor network during swallowing. As major clinical determinant, participants with swallowing alterations exhibited reduced pharyngeal sensation. Presbyphagia was an independent predictor of a reduced nutritional status in a linear regression model.

Conclusions

Swallowing alterations frequently occur in otherwise healthy older adults and are associated with decreased nutritional status. Increased sensorimotor cortical activation may constitute a compensation attempt to uphold swallowing function due to sensory decline. Further studies are needed to clarify whether the swallowing alterations observed can be considered physiological per se or whether the concept of presbyphagia may need to be extended to a theory with a continuous transition between presbyphagia and dysphagia.
Predicting the rupture status of small middle cerebral artery aneurysms using random forest modeling
Authors: Zhou Jiafeng , Xia Nengzhi , Li Qiong , Zheng Kuikui , Jia Xiufen , Wang Hao , Zhao Bing , Liu Jinjin , Yang Yunjun , Chen Yongchun
Published: July 2022

Objective

Small intracranial aneurysms are increasingly being detected; however, a prediction model for their rupture is rare. Random forest modeling was used to predict the rupture status of small middle cerebral artery (MCA) aneurysms with morphological features.

Methods

From January 2009 to June 2020, we retrospectively reviewed patients with small MCA aneurysms (<7 mm). The aneurysms were randomly split into training (70%) and internal validation (30%) cohorts. Additional independent datasets were used for the external validation of 78 small MCA aneurysms from another four hospitals. Aneurysm morphology was determined using computed tomography angiography (CTA). Prediction models were developed using the random forest and multivariate logistic regression.

Results

A total of 426 consecutive patients with 454 small MCA aneurysms (<7 mm) were included. A multivariate logistic regression analysis showed that size ratio (SR), aspect ratio (AR), and daughter dome were associated with aneurysm rupture, whereas aneurysm angle and multiplicity were inversely associated with aneurysm rupture. The areas under the receiver operating characteristic (ROC) curves (AUCs) of random forest models using the five independent risk factors in the training, internal validation, and external validation cohorts were 0.922, 0.889, and 0.92, respectively. The random forest model outperformed the logistic regression model (p = 0.048). A nomogram was developed to assess the rupture of small MCA aneurysms.

Conclusion

Random forest modeling is a good tool for evaluating the rupture status of small MCA aneurysms and may be considered for the management of small aneurysms.
The Polish Version of the Alberta Infant Motor Scale: Cultural Adaptation and Validation
Authors: Eliks Małgorzata , Sowińska Anna , Gajewska Ewa
Published: July 2022

The Alberta Infant Motor Scale (AIMS) is a diagnostic tool for the assessment of the motor performance of infants from the time of birth, to the period of independent walking (0–18 months). This study aims to derive a Polish version of the AIMS through its cultural adaptation and validation. The study included 145 infants aged 0–18 months, who were divided into four further age groups: 0–3 months, 4–7 months, 8–11 months, and older than 12 months. The validation was based on an analysis of intrarater and interrater reliability values, as well as concurrent validity, using the gross motor scale of Peabody Developmental Motor Scales-2 (PDMS-2). The total Intraclass Correlation Coefficient (ICC) for intrarater reliability was 0.99 (ICC range in positions was 0.87–0.99, in subgroups was 0.91–0.99), while in particular positions, the ICC ranges were as follows: prone 0.97–0.99, supine 0.94–0.99, sitting 0.95–0.99, and standing: 0.63–0.99. The total ICC for interrater reliability was 0.99 (ICC range in positions was 0.98–0.99, in subgroups was 0.91–0.99), while in particular positions, the ICC ranges were as follows: prone 0.95–0.99, supine 0.93–0.96, sitting 0.93–0.98, standing 0.91–0.98. Only the standing position was analyzed for the subgroup of participants over 12 months old. The Spearman correlation between the Polish version of the AIMS and the gross motor scale of PDMS-2 was significant in the total population (r = 0.97, p < 0.0001) and in subgroups (r = 0.79–0.85, p < 0.0001). The results of our study confirm that the Polish version of the AIMS is reliable for infants aged 0–18 months and can be applied to this population for clinical and scientific purposes.

Trial Registry

ClinicalTrials.gov ID NCT05264064, URL https://clinicaltrials.gov/ ct2/show/NCT05264064.