Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy.

We study a patient with the human papilloma virus (HPV)-2-driven "tree-man" phenotype and two relatives with unusually severe HPV4-driven warts. The giant horns form an HPV-2-driven multifocal benign epithelial tumor overexpressing viral oncogenes in the epidermis basal layer. The patients are unexpectedly homozygous for a private CD28 variant. They have no detectable CD28 on their T cells, with the exception of a small contingent of revertant memory CD4+ T cells. T cell development is barely affected, and T cells respond to CD3 and CD2, but not CD28, costimulation. Although the patients do not display HPV-2- and HPV-4-reactive CD4+ T cells in vitro, they make antibodies specific for both viruses in vivo. CD28-deficient mice are susceptible to cutaneous infections with the mouse papillomavirus MmuPV1. The control of HPV-2 and HPV-4 in keratinocytes is dependent on the T cell CD28 co-activation pathway. Surprisingly, human CD28-dependent T cell responses are largely redundant for protective immunity.

Prognosis and long-term outcomes in type I cryoglobulinemia: A multicenter study of 168 patients.

Type I cryoglobulinemia (CG) accounts for 10%-15% of all cryoglobulinemias and are exclusively seen in clonal proliferative hematologic conditions. In this multicenter nationwide cohort study, we analyzed the prognosis and long-term outcomes of 168 patients with type I CG (93 (55.4%) IgM and 75 [44.6%] IgG). Five- and 10-year event-free survivals (EFS) were 26.5% (95% CI 18.2%-38.4%) and 20.8% (95% CI 13.1%-33.1%), respectively. In multivariable analysis, factors associated with poorer EFS were renal involvement (HR: 2.42, 95% CI 1.41-4.17, p = .001) and IgG type I CG (HR: 1.96, 95% CI 1.13-3.33, p = 0.016), regardless of underlying hematological disorders. IgG type I CG patients had higher cumulative incidence of relapse (94.6% [95% CI 57.8%-99.4%] vs. 56.6% [95% CI 36.6%-72.4%], p = .0002) and death at 10 years (35.8% [19.8%-64.6%] vs. 71.3% [54.0%-94.2%], p = .01) as compared to IgM CG, respectively. Overall, complete response of type I CG at 6 months was 38.7%, with no significant difference between Igs isotypes. In conclusion, renal involvement and IgG CG were identified as independent poor prognostic factors of type I CG.

Flurona: The First Autopsied Case.

COVID-19-associated coinfections increase the patient's risk of developing a severe form of the disease and, consequently, the risk of death. The term "flurona" was proposed to describe the coinfection of the influenza virus and SARS-CoV-2. This report is about a case of a 7-month-old female infant who died due to flurona coinfection. A histopathological exam showed activation of microglia (becoming CD45 positive), bronchial inflammation, diffuse alveolar damage in proliferative phase with vasculitis, a peribronchial infiltrate that was predominantly CD20-positive, and a vascular wall infiltrate that was predominantly CD3-positive. The aggressiveness of the two respiratory viruses added up and they caused extensive lung inflammation, which led to respiratory failure, multiple organ failure, and death. Tissues injuries caused by both the influenza virus and SARS-CoV-2 could be observed, without the ability to certify the dominance of the aggression of one of the two viruses.

[Student tutoring, an essential part of nursing practice]. / Le tutorat des étudiants, un acte essentiel de la pratique infirmière.

Tutoring nursing students in the field requires a strong involvement from the staff, tutors and supervisors. Tutoring is a real educational follow-up by peers, in collaboration with the training managers, and is also a sharing of experience with the students. Story of nurses highly committed to this function in an orthopaedic surgery department.

Self-Confined Nucleation of Iron Oxide Nanoparticles in a Nanostructured Amorphous Precursor.

Crystallization from solution is commonly described by classical nucleation theory, although this ignores that crystals often form via disordered nanostructures. As an alternative, the classical theory remains widely used in a "multistep" variant, where the intermediate nanostructures merely introduce additional thermodynamic parameters. However, this variant still requires validation by experiments addressing indeed proper time and spatial scales (millisecond, nanometer). Here, we used in situ X-ray scattering to determine the mechanism of magnetite crystallization and, in particular, how nucleation propagates at the nanometer scale within amorphous precursors. We find that the self-confinement by an amorphous precursor slows down crystal growth by 2 orders of magnitude once the crystal size reaches the amorphous particle size (∼3 nm). Thus, not only the thermodynamic properties of transient amorphous nanostructures but also their spatial distribution determine crystal nucleation.

Toward a Chemical Control of Colloidal YVO4 Nanoparticles Microstructure.

Rare-earth-doped oxides are a class of compounds that have been largely studied in the context of the development of luminescent nanocrystals for various applications including fluorescent labels for bioimaging, MRI contrast agents, luminescent nanocomposite coatings, etc. Elaboration of colloidal suspensions is usually achieved through coprecipitation. Particles exhibit emission properties that are similar to the bulk counterparts, although altered by crystalline defects or surface quenching species. Focusing on YVO4:Eu, one of the first reported systems, the aim of this work is to revisit the elaboration of nanoparticles obtained through a simple aqueous coprecipitation route. The objective is more precisely to get a better understanding of the parameters affecting the particles' internal microstructure, a feature that is poorly controlled and characterized. We show that the hydroxyl concentration in the precursor solution has a drastic effect on the particles' microstructure. Moreover, discrepancies in the reported particle structure are shown to possibly arise from the carbonation of the strongly basic orthovanadate precursor. For this study, SAXS/WAXS is shown to be a powerful tool to characterize the multiscale structure of the particles. It could be shown that playing on the precursor composition, it may be varied between almost monocrystalline nanocrystals to particles exhibiting a hierarchical microstructure well described by a surface fractal model. This work provides a new methodology for the characterization of nanoparticles microstructure and opens new directions for its optimization in view of applications.

Understanding virtual urology clinics: a systematic review.

OBJECTIVES: To perform a systematic review to identify the clinical, fiscal and environmental evidence on the use of urological telehealth and/or virtual clinic (VC) strategies, and to highlight research gaps in this rapidly evolving field. METHODS: Our PROSPERO-registered (CRD42019151946) systematic search of Embase, Medline and the Cochrane Review Database was performed to identify original research articles pertaining to adult urology telehealth or VC strategies. Risk-of-bias (RoB) assessment was performed according to the Cochrane 2.0 RoB tool or the Joanna Briggs Institute Checklist for non-randomized studies. RESULTS: A total of 5813 participants were included from 18 original articles (two randomized controlled trials [RCTs], 10 prospective studies, six retrospective studies). Urology sub-specialities comprised: uro-oncology (n = 6); general urology (n = 8); endo-urology (n = 2); and lower urinary tract symptoms and/or incontinence (n = 2). Across all sub-specialties, prospective studies using VCs reported a primary median (interquartile range [IQR]) VC discharge rate of 16.6 (14.7-29.8)% and a primary median (IQR) face-to-face (FTF) clinic referral rate of 32.4 (15.5-53.3)%. Direct cost analysis demonstrated median (IQR) annual cost savings of £56 232 (£46 260-£61 116). Grade II and IIIb complications were reported in two acute ureteric colic studies, with rates of 0.20% (3/1534) and 0.13% (2/1534), respectively. The annual carbon footprint avoided ranged from 0.7 to 4.35 metric tonnes of CO2 emissions, depending on the mode of transport used. Patient satisfaction was inconsistently reported, and assessments lacked prospective evaluation using validated questionnaires. CONCLUSION: Urology VCs are a promising new platform which can offer clinical, financial and environmental benefits to support an increasing urological referral burden. Further prospective evidence is required across urological sub-specialties to confirm equivalency and safety against traditional FTF assessment.

Aerogels from Cellulose Phosphates of Low Degree of Substitution: A TBAF·H2O/DMSO Based Approach.

Biopolymer aerogels of appropriate open-porous morphology, nanotopology, surface chemistry, and mechanical properties can be promising cell scaffolding materials. Here, we report a facile approach towards the preparation of cellulose phosphate aerogels from two types of cellulosic source materials. Since high degrees of phosphorylation would afford water-soluble products inappropriate for cell scaffolding, products of low DSP (ca. 0.2) were prepared by a heterogeneous approach. Aiming at both i) full preservation of chemical integrity of cellulose during dissolution and ii) utilization of specific phase separation mechanisms upon coagulation of cellulose, TBAF·H2O/DMSO was employed as a non-derivatizing solvent. Sequential dissolution of cellulose phosphates, casting, coagulation, solvent exchange, and scCO2 drying afforded lightweight, nano-porous aerogels. Compared to their non-derivatized counterparts, cellulose phosphate aerogels are less sensitive towards shrinking during solvent exchange. This is presumably due to electrostatic repulsion and translates into faster scCO2 drying. The low DSP values have no negative impact on pore size distribution, specific surface (SBET ≤ 310 m2 g-1), porosity (Π 95.5-97 vol.%), or stiffness (Eρ ≤ 211 MPa cm3 g-1). Considering the sterilization capabilities of scCO2, existing templating opportunities to afford dual-porous scaffolds and the good hemocompatibility of phosphorylated cellulose, TBAF·H2O/DMSO can be regarded a promising solvent system for the manufacture of cell scaffolding materials.

Clinical, fiscal and environmental benefits of a specialist-led virtual ureteric colic clinic: a prospective study.

OBJECTIVES: To evaluate the clinical, fiscal and environmental impact of a specialist-led acute ureteric colic virtual clinic (VC) pathway. PATIENTS AND METHODS: All patients with uncomplicated acute ureteric colic, referred to a single tertiary centre, were prospectively entered into the study over a 4-year period (January 2015-December 2018). Inclusion criteria were: low-dose non-contrast computed tomography of kidneys, ureters and bladder; white blood cell count <16 × 109/L; pain controlled; normal renal function; and no clinical concern. Primary outcomes were: time (days) from referral to VC outcome; VC outcome (discharge, further VC, face-to-face [FTF] clinic, extracorporeal shockwave lithotripsy [ESWL], ureterorenoscopy [URS], percutaneous nephrolithotomy [PCNL]); and adverse events (sepsis or obstruction). Secondary outcomes were patient and stone demographics, cost and environmental analysis. The minimum follow-up was 3 months. RESULTS: A total of 1008 patients entered the study, of whom 91.5% (n = 922) were of working age. The median (interquartile range) time from presentation to VC outcome was 2 (4) days. VC outcomes were as follows: 16.3% of patients (n = 164) were discharged; 18.2% (n = 183) were discharged after further VC; 17.2% (n = 173) underwent an intervention; and 48.4% (n = 488) were referred to an FTF clinic. Interventions comprised: PCNL 0.5% (n = 5); ESWL 7.7% (n = 78); and URS 8.9% (n = 90). Stone demographics were as follows: 570 patients (56.5%) had lower, 157 (15.6%) had upper, 96 (9.5%) had mid-ureteric and 163 (16.2%) had renal calculi, and in 22 patients (2.2%) the stones had recently passed. The mean (sd) stone size was 3.5  (2.3) mm. Two adverse events (0.2%) were reported. Introducing a VC saved £145,152 for Clinical Commissioning Groups, the equivalent NHS tariff payment of performing 106 URS procedures or 211 ureteric stent insertions. Overall, 15,085 patient journey kilometres were avoided, equal to 0.70-2.93 metric tonnes of carbon dioxide equivalent production and the need to plant 14.7 trees to achieve carbon balance. CONCLUSION: A specialist-led acute ureteric colic VC reduced time to treatment decision to a median of 2 days. This creates additional clinic capacity and reduces the fiscal burden of traditional clinics and their associated carbon footprint.

Array-CGH predicts prognosis in plasma cell post-transplantation lymphoproliferative disorders.

Plasma-cell post-transplantation lymphoproliferative disorder (PC-PTLD) is a rare monomorphic PTLD entity divided into plasma cell myeloma (PCM) and plasmacytoma-like lesion (PLL) PTLD. To date, there are no exhaustive published cytogenetic data on PC-PTLD. We report array-based comparative genomic hybridization (aCGH) of 10 cases of PCM and PLL-PTLD. Patients had received kidney (n = 6), heart (n = 2), lung (n = 1) or bone marrow (n = 1) transplantation. There were six men and median age at time of PTLD was 56.5 years (3-74). We identified two different cytological features, plasmacytic and plasmablastic, among six PLL and three PCM PTLD. Eight cases were associated with EBV. First line treatment was heterogeneous: rituximab alone (n = 5), CHOP-like (n = 3) and multiple myeloma-like (n = 1). One patient died before any treatment. After a median follow-up of 19.5 months (0-150), five patients died (four from PTLD) and five were alive without evidence of disease. By aCGH, 5/10 demonstrated a complex profile. The most frequent abnormalities were +7q (5/10), +16q (5/10), +17q (5/10), +17p (4/10), +5q (4/10), t7 (4/10), t9 (3/10), del1p (3/10). No del17p13 (TP53) were observed. Del1p32.3 (CDKN2C) was observed in 2 cases. On univariate prognostic analysis, a complex aCGH was associated with a shorter OS. Thus, cytogenetic abnormalities seem to be closely related to those reported in multiple myeloma or diffuse large B cell lymphoma. Complex aCGH constitutes an unfavorable prognostic marker and aCGH should be integrated in the evaluation of patients with PLL/PCM-PTLD. © 2016 Wiley Periodicals, Inc.

Midgut microbiota of the malaria mosquito vector Anopheles gambiae and interactions with Plasmodium falciparum infection.

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.

Tailoring photoluminescence properties in ionic nanoparticle networks.

To investigate the original and promising luminescence properties of ionic nanoparticle networks (INN), various material compositions were investigated. In this work, the linker used to network the silica nanoparticles was varied; numerous substituted or non-substituted imidazolium, pyrazolium and pyridinium linkers are presented. Photoluminescence experiments on the INN hybrid materials revealed strong emission bands over a broad range in the visible region of the light spectrum. Varying the aromatic linker between the imidazolium units induced clear shifts of the emission maxima up to 100 nm, as a consequence of π-π stacking interactions. Steric hindrance and inductive effects of the substituents, introduced on the aromatic units, also strongly influenced the luminescence properties of the materials by modifying the π-π stacking between the imidazolium rings. Small and wide-angle X-ray scattering (SAXS, WAXS) experiments revealed a clear trend between the obtained structural parameters (short-range order parameter and distance of the aromatic units within the hybrid material) and the luminescence quantum yields of the INN materials.

Exploring the molecular structure of imidazolium-silica-based nanoparticle networks by combining solid-state NMR spectroscopy and first-principles calculations.

A DFT-based molecular model for imidazolium-silica-based nanoparticle networks (INNs) is presented. The INNs were synthesized and characterized by using small-angle X-ray scattering (SAXS), NMR spectroscopy, and theoretical ab initio calculations. (11)B and (31)P HETCOR CP MAS experiments were recorded. Calculated (19)F NMR spectroscopy results, combined with the calculated anion-imidazolium (IM) distances, predicted the IM chain density in the INN, which was also confirmed from thermogravimetric analysis/mass spectrometry results. The presence of water molecules trapped between the nanoparticles is also suggested. First considerations on possible π-π stacking between the IM rings are presented. The predicted electronic properties confirm the photoluminescence emissions in the correct spectral domain.

Determination of rare earth elements in saline matrices using dispersed particle extraction and inductively coupled plasma mass spectrometry.

RATIONALE: Rare earth elements play an important role in identifying and indexing the origin of historical and geological samples. In this work, a new approach for the characterization of rare earth elements (REEs) in aqueous sample solutions with high salinity is presented. METHODS: Prior to analysis by inductively coupled plasma mass spectrometry (ICP-MS) the target analytes were separated from interfering matrix constituents by the use of surface-functionalized nanoparticles. Compared with common matrix separation techniques, such as solid-phase extraction (SPE), the strength of the method lies in the combination of an advanced extraction procedure with internal standard correction. Thus, known limitations of SPE such as column clogging or incomplete analyte elution could be completely circumvented. Furthermore, time-consuming approaches for signal quantification such as matrix-matched calibration could be avoided since the applied internal standard allows the correction of matrix-induced deviations in sample extraction and ICP-MS analysis. RESULTS: With the developed procedure detection limits <1 ng L(-1) could be achieved for all the investigated elements, with satisfactory relative standard deviations (RSDs) of 3-26% for unspiked samples and <1-2% for spiked samples. Results derived from recovery experiments with spiked oil accumulation water samples confirmed the applicability of the proposed procedure for the determination of REEs in highly saline sample solutions. The procedure was successfully applied to the study of oil accumulation water samples from different oil fields in Lower Austria. CONCLUSIONS: A sample pretreatment procedure with subsequent ICP-MS analysis for the accurate determination of REEs in aqueous sample solutions with high salinity has been developed.

Human MSH6 deficiency is associated with impaired antibody maturation.

Ig class-switch recombination (Ig-CSR) deficiencies are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect, defective Ig-CSR may also be associated with impaired somatic hypermutation (SHM) of the Ig V regions. Although the mechanisms underlying Ig-CSR and SHM in humans have been revealed (at least in part) by studying natural mutants, the role of mismatch repair in this process has not been fully elucidated. We studied in vivo and in vitro Ab maturation in eight MSH6-deficient patients. The skewed SHM pattern strongly suggests that MSH6 is involved in the human SHM process. Ig-CSR was found to be partially defective in vivo and markedly impaired in vitro. The resolution of γH2AX foci following irradiation of MSH6-deficient B cell lines was also found to be impaired. These data suggest that in human CSR, MSH6 is involved in both the induction and repair of DNA double-strand breaks in switch regions.

A rare case of lysozyme-induced anaphylaxis in a child with egg allergy.

We report an unusual case of anaphylaxis induced by the lysozyme-containing over-the-counter-drug Lysopaine®, which contains 20 mg lysozyme hydrochloride and 1.5 mg cetylpyridinium chloride, in a 9-year-old child with allergy to hen's egg as well as multiple IgE-mediated food allergies. The involvement of lysozyme was confirmed by positive skin prick tests for Lysopaine® and the presence of specific IgE against lysozyme. Our case highlights the importance of properly educating allergic patients to recognize allergens, even minor ones. Despite the presence of lysozyme in various food and drug products, it is not necessarily perceived as an allergenic protein by patients with egg allergy, and the labeling may be misleading, thereby exposing patients to potentially severe reactions.

An mHealth Intervention for Gay and Bisexual Men's Mental, Behavioral, and Sexual Health in a High-Stigma, Low-Resource Context (Project Comunica): Protocol for a Randomized Controlled Trial.

BACKGROUND: The World Health Organization reported that 80% of new HIV diagnoses in Europe in 2014 occurred in Central and Eastern Europe. Romania has a particularly high HIV incidence, AIDS prevalence, and number of related deaths. HIV incidence in Romania is largely attributed to sexual contact among gay and bisexual men. However, homophobic stigma in Romania serves as a risk factor for HIV infection for gay and bisexual men. The Comunica intervention aims to provide a much-needed HIV risk reduction strategy, and it entails the delivery of motivational interviewing and cognitive behavioral therapy skills across 8 live text-based counseling sessions on a mobile platform to gay and bisexual men at risk of HIV. The intervention is based on the information-motivation-behavior and minority stress models. There is preliminary evidence suggesting that Comunica holds promise for reducing gay and bisexual men's co-occurring sexual (eg, HIV transmission risk behavior), behavioral (eg, heavy alcohol use), and mental (eg, depression) health risks in Romania. OBJECTIVE: This paper describes the protocol for a randomized controlled trial designed to test the efficacy of Comunica in a national trial. METHODS: To test Comunica's efficacy, 305 gay and bisexual men were randomized to receive Comunica or a content-matched education attention control condition. The control condition consisted of 8 time-matched educational modules that present information regarding gay and bisexual men's identity development, information about HIV transmission and prevention, the importance of HIV and sexually transmitted infection testing and treatment, heavy alcohol use and its associations with HIV transmission risk behavior, sexual health communication, finding social support, and creating sexual health goals. Participants undergo rapid HIV and syphilis testing and 3-site chlamydia and gonorrhea testing at baseline and the 12-month follow-up. Outcomes are measured before the intervention (baseline) and at the 4-, 8-, and 12-month follow-ups. RESULTS: The study was funded in September 2018, and data collection began in May 2019. The last participant follow-up was in January 2024. Currently, the data analyst is cleaning data sets in preparation for data analyses, which are scheduled to begin in April 2024. Data analysis meetings are scheduled regularly to establish timelines and examine the results as analyses are gradually being conducted. Upon completion, a list of manuscripts will be reviewed and prioritized, and the team will begin preparing them for publication. CONCLUSIONS: This study is the first to test the efficacy of an intervention with the potential to simultaneously support the sexual, behavioral, and mental health of gay and bisexual men in Central and Eastern Europe using motivational interviewing support and sensitivity to the high-stigma context of the region. If efficacious, Comunica presents a scalable platform to provide support to gay and bisexual men living in Romania and similar high-stigma, low-resource countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT03912753; https://clinicaltrials.gov/study/NCT03912753. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52853.

Immune checkpoint inhibitor therapy associated with IgA nephropathy: a case report and literature review.

Immune checkpoint inhibitors (ICIs) dramatically improve the prognosis of many malignancies but at the cost of numerous side effects, which may limit their benefits. Acute kidney injury associated with immune checkpoint inhibitors most frequently are acute tubulointerstitial nephritis (ATIN), but various cases of glomerulonephritis have also been reported. Herein, we report a case of severe IgA nephropathy (IgAN) associated with ICIs and carry out a literature review. IgAN was diagnosed in a median time of 5 months (range 1-12 months) after the initiation of ICIs, with heterogeneous severity, and usually treated by corticosteroid and discontinuation of ICIs. In contrast to our case, renal outcomes in literature were often favorable, with recovery of renal function and a reduction in proteinuria on treatment. Although IgAN related to ICIs is a much rarer complication than ATIN, it may still be underdiagnosed. Careful questioning and screening for asymptomatic hematuria should be performed before using ICIs.

Spatial sequestration of activated-caspase 3 in aggresomes mediates resistance of neuroblastoma cell to bortezomib treatment.

Neuroblastoma (NB) is the most common pediatric tumor and is currently treated by several types of therapies including chemotherapies, such as bortezomib treatment. However, resistance to bortezomib is frequently observed by mechanisms that remain to be deciphered. Bortezomib treatment leads to caspase activation and aggresome formation. Using models of patients-derived NB cell lines with different levels of sensitivity to bortezomib, we show that the activated form of caspase 3 accumulates within aggresomes of NB resistant cells leading to an impairment of bortezomib-induced apoptosis and increased cell survival. Our findings unveil a new mechanism of resistance to chemotherapy based on an altered subcellular distribution of the executioner caspase 3. This mechanism could explain the resistance developed in NB patients treated with bortezomib, emphasizing the potential of drugs targeting aggresomes.