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Introduction: Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections. However, their role during recall responses is unclear. Here, we used hepatitis C virus (HCV) reinfection in humans as a model to study the recall collaborative interaction between circulating CD4 T follicular helper cells (cTfh) and memory B cells (MBCs) leading to the generation of NAbs., Methods: We evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR/SR, n = 14) or chronic infection (SR/CI, n = 8)., Results: Both groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4 + CXCR5 + PD-1 + ICOS + FoxP3 - ) occurred in SR/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19 + CD27 + IgM - E2-Tet + ) peaked during the early acute phase in SR/SR but not in SR/CI. Finally, the frequency of the activated cTfh1 (CXCR3 + CCR6 - ) subset correlated with the neutralization breadth and potency of NAbs., Conclusion: These results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Eisa, Gomez-Escobar, Bédard, Abdeltawab, Flores, Mazouz, Fieffé-Bédard, Sakayan, Gridley, Abdel-Hakeem, Bruneau, Grakoui and Shoukry.)

Successive episodes of hepatitis C virus (HCV) infection represent a unique natural rechallenge experiment to define correlates of long-term protective immunity and inform vaccine development. We applied a systems immunology approach to characterize longitudinal changes in the peripheral blood transcriptomic signatures in eight subjects who spontaneously resolved two successive HCV infections. Furthermore, we compared these signatures with those induced by an HCV T cell-based vaccine regimen. We identified a plasma cell transcriptomic signature during early acute HCV reinfection. This signature was absent in primary infection and following HCV vaccine boost. Spontaneous resolution of HCV reinfection was associated with rapid expansion of glycoprotein E2-specifc memory B cells in three subjects and transient increase in E2-specific neutralizing antibodies in six subjects. Concurrently, there was an increase in the breadth and magnitude of HCV-specific T cells in 7 out of 8 subjects. These results suggest a cooperative role for both antibodies and T cells in clearance of HCV reinfection and support the development of next generation HCV vaccines targeting these two arms of the immune system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Mazouz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl 4 -induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F + Kupffer cells (KCs) and infiltrating IBA1 + CLEC4F - monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Flores Molina, Abdelnabi, Mazouz, Villafranca-Baughman, Trinh, Muhammad, Bédard, Osorio Laverde, Hassan, Di Polo and Shoukry.)

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is a major health problem with complex pathogenesis. Although sex differences in NAFLD pathogenesis have been reported, the mechanisms underlying such differences remain understudied. Interleukin (IL)22 is a pleiotropic cytokine with both protective and/or pathogenic effects during liver injury. IL22 was shown to be hepatoprotective in NAFLD-related liver injury. However, these studies relied primarily on exogenous administration of IL22 and did not examine the sex-dependent effect of IL22. Here, we sought to characterize the role of endogenous IL22-receptor signaling during NAFLD-induced liver injury in males and females., Methods: We used immunofluorescence, flow cytometry, histopathologic assessment, and gene expression analysis to examine IL22 production and characterize the intrahepatic immune landscape in human subjects with NAFLD (n = 20; 11 men and 9 women) and in an in vivo Western high-fat diet-induced NAFLD model in IL22RA knock out mice and their wild-type littermates., Results: Examination of publicly available data sets from 2 cohorts with NAFLD showed increased hepatic IL22 gene expression in females compared with males. Furthermore, our immunofluorescence analysis of liver sections from NAFLD subjects (n = 20) showed increased infiltration of IL22-producing cells in females. Similarly, IL22-producing cells were increased in wild-type female mice with NAFLD and the hepatic IL22/IL22 binding protein messenger RNA ratio correlated with expression of anti-apoptosis genes. The lack of endogenous IL22-receptor signaling (IL22RA knockout) led to exacerbated liver damage, inflammation, apoptosis, and liver fibrosis in female, but not male, mice with NAFLD., Conclusions: Our data suggest a sex-dependent hepatoprotective antiapoptotic effect of IL22-receptor signaling during NAFLD-related liver injury in females., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent years, walkability is increasingly integrated into sustainability strategies, considering its many health and environmental benefits. Besides, thermal comfort also has been progressively promoted as a critical measure for pedestrian comfort and wellbeing. Despite the relevance of the two concepts, few studies combined them in a comprehensive model. This study considers thermal comfort in assessing walkability by developing a new measurement tool, the Street Walkability and Thermal Comfort Index (SWTCI), which focuses on comfort facilities and Physiological Equivalent Temperature (PET), at the street scale. The applied point system method requires combining a questionnaire survey, observations, and in situ measurements (air temperature, wind velocity, and relative humidity). The questionnaire survey (330 responders) measured 21 street design indicators' importance, using a five-point Likert scale ranging from 1 (least important) to 5 (very important). The observation technique seeks to evaluate every pedestrian comfort indicator score (Si s ). The in situ measurements permit Envi-met's calibrated data validation and getting the mean radian temperature (T mrt ). Those were considered in the PET's calculation using Rayman software. Three distinct streets have been chosen in Annaba city, Algeria, within the Mediterranean climate (Csa). The results show that the SWTCI achieves its highest score on the three streets when the thermal perception is neutral (20 < PET <26), and its lowest score, with a warm thermal sensation (28 < PET < 31). Despite the divergence in PET values, the highest score of SWTCI was 33%, reflecting a low comfort quality and minimal pedestrian facilities. Applying the SWTCI method can transform uncomfortable streets into an ideal walkable and pleasant path by finding the problems and proposing improvements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hepatitis C virus (HCV) infection resolves spontaneously in ∼25% of acutely infected humans where viral clearance is mediated primarily by virus-specific CD8 + T cells. Previous cross-sectional analysis of the CD8 + TCR repertoire targeting two immunodominant HCV epitopes reported widespread use of public TCRs shared by different subjects, irrespective of infection outcome. However, little is known about the evolution of the public TCR repertoire during acute HCV and whether cross-reactivity to other Ags can influence infectious outcome. In this article, we analyzed the CD8 + TCR repertoire specific to the immunodominant and cross-reactive HLA-A2-restricted nonstructural 3-1073 epitope during acute HCV in humans progressing to either spontaneous resolution or chronic infection and at ∼1 y after viral clearance. TCR repertoire diversity was comparable among all groups with preferential usage of the TCR-β V04 and V06 gene families. We identified a set of 13 public clonotypes in HCV-infected humans independent of infection outcome. Six public clonotypes used the V04 gene family. Several public clonotypes were long-lived in resolvers and expanded on reinfection. By mining publicly available data, we identified several low-frequency CDR3 sequences in the HCV-specific repertoire matching human TCRs specific for other HLA-A2-restricted epitopes from melanoma, CMV, influenza A, EBV, and yellow fever viruses, but they were of low frequency and limited cross-reactivity. In conclusion, we identified 13 new public human CD8 + TCR clonotypes unique to HCV that expanded during acute infection and reinfection. The low frequency of cross-reactive TCRs suggests that they are not major determinants of infectious outcome., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Competing Interests: The authors have no conflict of interest to disclose.

Psychiatric disorders in burn victims are well known and studied, but few articles treat the impact of pre-existing psychiatric pathologies on the evolution of burns. The aim of our study is to compare the evolution in terms of complications, length of stay and survival between patients with and without pre-existing mental disorders. This is a bi-centric case-control study (N = 92), conducted at the Plastic Surgery Department of Rabat University Hospital, and the Plastic Surgery Department of the Tangier-Morocco Regional Hospital, between January 2012 and February 2018. Characteristics of the patients were collected and two groups of patients were identified and compared (n = 67): a preexisting mental disorder group (n = 22) and a control group (n = 45). TBSA (total body surface area) burned and 2nd and 3rd degree burned TBSA were significantly greater in the group with a history of mental disorders compared to the control group (p = 0.012, p <0.001, p = 0.014). Mean length of stay before discharge was greater (p = 0.005). Finally, mortality in the group with pre-existing mental illness was 31.8% versus 6.7% in the control group (p = 0.011). Patients with pre-existing mental disorders seem to present worse burns and need more time to recover from them, resulting in higher morbidity and mortality and a higher cost of care. The systematic screening of burned patients in search of a psychiatric diagnosis and early management of these disorders could improve the prognosis and quality of life of these patients., (Copyright © 2019 Euro-Mediterranean Council for Burns and Fire Disasters.)

The discoidin domain receptor 1 (DDR1) is a member of the receptor tyrosine kinase family that signals in response to collagen and that has been implicated in cancer progression. In the present study, we investigated the expression and role of DDR1 in human melanoma progression. Immunohistochemical staining of human melanoma specimens (n = 52) shows high DDR1 expression in melanoma lesions that correlates with poor prognosis. DDR1 expression was associated with the clinical characteristics of Clark level and ulceration and with BRAF mutations. Downregulation of DDR1 by small interfering RNA (siRNA) in vitro inhibited melanoma cells malignant properties, migration, invasion, and survival in several human melanoma cell lines. A DDR tyrosine kinase inhibitor (DDR1-IN-1) significantly inhibited melanoma cell proliferation in vitro, and ex vivo and in tumor xenografts, underlining the promising potential of DDR1 inhibition in melanoma., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Most individuals exposed to hepatitis C virus (HCV) become persistently infected while a minority spontaneously eliminate the virus. Although early immune events influence infection outcome, the cellular composition, molecular effectors, and timeframe of the host response active shortly after viral exposure remain incompletely understood. Employing specimens collected from people who inject drugs (PWID) with high risk of HCV exposure, we utilized RNA-Seq and blood transcriptome module (BTM) analysis to characterize immune function in peripheral blood mononuclear cells (PBMC) before, during, and after acute HCV infection resulting in spontaneous resolution. Our results provide a detailed description of innate immune programs active in peripheral blood during acute HCV infection, which include prominent type I interferon and inflammatory signatures. Innate immune gene expression rapidly returns to pre-infection levels upon viral clearance. Comparative analyses using peripheral blood gene expression profiles from other viral and vaccine studies demonstrate similarities in the immune responses to acute HCV and flaviviruses. Of note, both acute dengue virus (DENV) infection and acute HCV infection elicit similar innate antiviral signatures. However, while transient in DENV infection, this signature was sustained for many weeks in the response to HCV. These results represent the first longitudinal transcriptomic characterization of human immune function in PBMC during acute HCV infection and identify several dynamically regulated features of the complex response to natural HCV exposure., Competing Interests: The authors have declared that no competing interests exist.

The introduction of small molecules targeting viral functions has caused a paradigm shift in hepatitis C virus (HCV) treatment. Administration of these direct-acting antivirals (DAAs) achieves a complete cure in almost all treated patients with short-duration therapy and minimal side effects. Although this is a major improvement over the previous pegylated interferon plus ribavirin (PEG-IFNα/RBV) standard-of-care treatment for HCV, remaining questions address several aspects of the long-term benefits of DAA therapy. Interferon (IFN)-based treatment with successful outcome was associated with substantial reduction in liver disease-related mortality. However, emerging data suggest a complex picture and several confounding factors that influence the effect of both IFN-based and DAA therapies on immune restoration and limiting liver disease progression. We review current knowledge of restoration of innate and HCV-specific immune responses in DAA-mediated viral elimination in chronic HCV infection, and we identify future research directions to achieve long-term benefits in all cured patients and reduce HCV-related liver disease morbidity and mortality., Competing Interests: The authors have nothing to disclose., (Copyright © 2018 Canadian Association for the Study of the Liver.)

Chronic viral infections remain a global health concern. The early events that facilitate viral persistence have been linked to the activity of the immunoregulatory cytokine IL-10. However, the mechanisms by which IL-10 facilitates the establishment of chronic infection are not fully understood. Herein, we demonstrated that the antigen sensitivity of CD8 + T cells was decreased during chronic infection and that this was directly mediated by IL-10. Mechanistically, we showed that IL-10 induced the expression of Mgat5, a glycosyltransferase that enhances N-glycan branching on surface glycoproteins. Increased N-glycan branching on CD8 + T cells promoted the formation of a galectin 3-mediated membrane lattice, which restricted the interaction of key glycoproteins, ultimately increasing the antigenic threshold required for T cell activation. Our study identified a regulatory loop in which IL-10 directly restricts CD8 + T cell activation and function through modification of cell surface glycosylation allowing the establishment of chronic infection., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The traditional brazier remains a means of cooking and warming for thousands of families in isolated rural areas in Morocco. From simple burns due to accidental contact to limb carbonizations, these burns are all the more serious when they are secondary to epileptic seizures or carbon monoxide poisoning. The sequelae are important in the associated forms, mainly because of delay in management and non-adherence to therapeutic protocols by patients of low socioeconomic status.

PKR is a cellular kinase involved in the regulation of the integrative stress response (ISR) and pro-inflammatory pathways. Two N-terminal dsRNA Binding Domains (DRBD) are required for activation of PKR, by interaction with either dsRNA or PACT, another cellular DRBD-containing protein. A role for PKR and PACT in inflammatory processes linked to neurodegenerative diseases has been proposed and raised interest for pharmacological PKR inhibitors. However, the role of PKR in inflammation is subject to controversy. We identified the flavonoid luteolin as an inhibitor of the PKR/PACT interaction at the level of their DRBDs using high-throughput screening of chemical libraries by homogeneous time-resolved fluorescence. This was further validated using NanoLuc-Based Protein Complementation Assay. Luteolin inhibits PKR phosphorylation, the ISR and the induction of pro-inflammatory cytokines in human THP1 macrophages submitted to oxidative stress and toll-like receptor (TLR) agonist. Similarly, luteolin inhibits induction of pro-inflammatory cytokines in murine microglial macrophages. In contrast, luteolin increased activation of the inflammasome, in a PKR-independent manner. Collectively, these data delineate the importance of PKR in the inflammation process to the ISR and induction of pro-inflammatory cytokines. Pharmacological inhibitors of PKR should be used in combination with drugs targeting directly the inflammasome.

Aims: So far, a total of five patients with eclipsed mitral regurgitation (MR) have been reported in the literature by three different teams. The aim of this article was to detail clinical and echocardiographic characteristics, and outcome of patients presenting eclipsed MR., Methods and Results: We defined eclipsed MR as spontaneous appearance, at rest, from 1 min to the next of an acute restriction in the motion of mitral leaflets preventing coaptation and leading to massive MR in patients with normal left ventricular end-diastolic diameter, left ventricular ejection fraction >45%, and baseline MR ≤2. Spontaneous regression occurred within 30 min, and no obvious trigger such as acute hypertension, new-onset arrhythmia, or myocardial ischaemia is present. Clinical data, ECG, echocardiographic data, surgery report, and follow-up status of six patients with eclipsed MR are reported: all were post-menopausal women with median age of 74 [57-80] years presenting hypertension (4/6), chronic kidney disease (5/6), or chronic anaemia (4/6). Five out of six patients experienced acute pulmonary oedema requiring hospitalization and underwent mitral valve replacement because of heart failure recurrence. Two patients died in the first days after surgery while the three others are free of symptoms at, respectively, 56, 18, and 10 months follow-up., Conclusion: Eclipsed MR is a clinical and echocardiographic syndrome responsible for heart failure with preserved EF. It is presently underdiagnosed and should be evoked in cases of recurrent acute pulmonary oedema without obvious trigger, in particular in patients presenting discordant evaluation of MR severity over time., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

We report the case of a 65-year old patient presenting with well-defined nodular basal cell carcinom measuring 5mm in diameter in the right paramedian nasal tip and the superior margin of the nasal wing, near the free edge. The tumor was removed, with resection margin of 1mm. It was associated with multiple hyperkeratotic lesions spread across his face. The patient was a farmer with a past history of massive sun exposure. He lived in rural, mountainous and remote regions. The nasal tumor had evolved very slowly and very gradually in volume. The patient underwent surgical excision of BCC with resection margin of 1mm. We reconstructed the loss-of-substance with a very simple small local flap (Zitelli bilobed flap) which allowed to cover the loss of substance and to close it. The recipient healed well after one month-follow-up of local treatment and dressings. The patient underwent the removal of the sutures on day 10, then he underwent fat dressings with cortisone cream every other day over a period of 15 days.

The umbilicus is our first scar. It is the last remain of our life in utero. Besides the umbilical hernia, a common pathology during the first three years of life that rarely requires surgery, there are some rare congenital abnormalities such as gastroschisis and omphalocele, which occur in about 1-5/10,000 births. Gastroschisis is a birth defect of the anterior abdominal wall, through which the fetal intestines freely protrude and are not covered by any membranes. During the 13th week prenatal ultrasound, the umbilical cord can be seen to be properly attached while the intestines float freely in the amniotic fluid. This defect is most common in young women who smoke and/or use cocaine and is not typically associated with genetic disorders. Omphalocele is an average coelosomy, in which a visceral hernia protrudes into the base of the umbilical cord. Omphalocele is typically diagnosed during the prenatal phase, and occurs most commonly in older mothers. It is frequently associated with genetic and morphologic abnormalities, therefore a karyotype should automatically be performed. For these two pathologies, the surgical problem lies in managing, during the reintegration, the conflict container/content responsible to lower vena cava syndrome and disorders ventilatory. Deciding on the technique will depend on the clinical form, and on the tolerance to reinsertion. The success of the surgery is directly linked to the postoperative emergence care for the pre-, per- and postnatal phases. The umbilical cord is preserved in the case of a gastroschisis. A primary or secondary umbilicoplasty will be performed for an omphalocele closure. The umbilicoplasty aims to create an umbilicus in a good position by giving it a shape, ideally oval, but also and especially an umbilication. The primary or secondary umbilicoplasty remains a challenge in a growing abdomen (change in position, deformation, loss of intussusception with growth). Many techniques are described: cutaneous flaps randomly placed, excision and skin plasty, resection and controlled wound healing. The choice of technique is a matter of practice but must be done in a rational way, depending on the scar condition when secondary reconstruction, and with minimal scarring, for primary reconstruction. To avoid morphological changes associated with growth, secondary umbilicoplasty should be proposed after the age of five., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

CD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in-transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P < 0.05 for both) in primary melanoma patients. CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P < 10(-8) ). Multivariate analysis retained CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P < 0.05 for both). CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Due to the increasing number of fat grafting procedures, several laboratories have developed their own fat processing system (Puregraft(®), LipiVage(®), Viafill(®), etc.), such as closed harvesting systems, centrifugation or washing and filtration devices, or even simple decantation techniques. However, all these tissue-engineering systems are expensive. Our team has developed a simple and fast autologous fat grafting system, useable even for a large volume of lipofilling, and based on low-pressure suction and a sterile closed-system for processing the harvested fat tissue. It is a cost-effective system, as it only costs 9.28Eur (10.52USD) for a 500milliliters autologous fat graft procedure., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: After implant-based breast reconstruction, the nipple reconstruction technique must be carefully chosen, especially in patients with a history of radiotherapy. When the contralateral nipple is not available, using a classical dermal-fat local flap may lead to the implant exposure, and consequently, removal. We describe here a simple nipple reconstruction technique, using a strictly dermal local flap and evaluate its complication rate., Patients and Methods: All patients who underwent our technique for nipple reconstruction between January 2012 and April 2015 were included in this retrospective study. We described our surgical technique and noted the occurrence of postoperative complications., Results: Forty-nine nipples, in 47 patients with a history of radiotherapy, were reconstructed with our technique. The mean age was 53 years old (range 27-78 years old). The average time between radiotherapy and nipple reconstruction was 42.5 months (range from 4.6 to 274.8 months). The mean follow-up was 30.9 months (range from 6 to 47 months). No implant exposure occurred. Regarding the nipple flap, two partial flap loss and one infection occurred, the whole complication rate was 6.1%. Regarding nipple projection, it was quite low (between 2 and 5 mm) after 6 months, but remained stable., Conclusion: Our strictly dermal local flap technique for nipple reconstruction is a safe procedure and represents a good alternative to composite contralateral nipple graft in irradiated patients with an implant-based reconstructed breast., (Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)