Evaluation of the Cytokine Response Induced by Specific Allergen Immunotherapy in Patients with Vespa velutina Anaphylaxis.

INTRODUCTION: Changes in the cytokine profile from type 2 to type 1 together with the induction of regulatory cells are expected during hymenoptera venom immunotherapy (VIT). The present study was aimed to investigate the changes in type 1, type 2, and regulatory cytokines induced by a Vespula spp. VIT in patients with anaphylaxis to Vespa velutina. METHODS: Twenty consecutive patients with anaphylaxis due to Vespa velutina were treated with Vespula spp. VIT. Serum cytokines (IL-4, IL-5, IL-10, IL-13, and IFN-É£) were measured at baseline, 6, and 12 months after starting VIT. RESULTS: A significant increase in serum IFN-y was detected after 6 and 12 months of VIT. An increase in serum IL-10 and a decrease in IL-5 were observed after 12 months. IL-4 was undetectable all along the study, and an unexpected increase of IL-13 was present at 12 months of treatment. CONCLUSION: Vespula spp. VIT seems to be able to induce a shift to type 1 cytokine production measured through IFN-y levels and IL-10 production after, at least, 6 and 12 months of VIT, respectively.

Impact of an interventional bundle on complications associated with peripheral venous catheters in elderly patients.

PURPOSE: Elderly patients admitted to geriatrics departments often require peripheral venous catheters (PVC), which should be inserted and maintained following a series of preventive recommendations. Our objective was to evaluate the impact of a training bundle comprising measures aimed at reducing complications associated with the use of PVC in elderly patients admitted to a tertiary teaching hospital. METHODS: We performed a prospective study of patients who received a PVC within 24 h of admission to a geriatrics department. After a 10-month pre-interventional period, we implemented an educational and interventional bundle over a 9-month period. Follow-up was until catheter withdrawal. We analyzed and compared clinical and microbiological data between both study periods. RESULTS: A total of 344 patients (475 PVC) were included (pre-intervention period, 204 patients (285 PVC); post-intervention period, 140 patients (190 PVC)). No statistically significant differences in demographic characteristics were observed between the study periods. The colonization and phlebitis rates per 1000 admissions in both periods were, respectively, 36.7 vs. 24.3 (p = 0.198) and 81.5 vs. 65.1 (p = 0.457). The main reason for catheter withdrawal was obstruction/malfunctioning (33.3%). Obstruction rate was higher for those inserted in the hand than for those inserted at other sites (55.7% vs. 44.3%, p = 0.045). CONCLUSIONS: We found no statistically significant differences regarding phlebitis and catheter tip colonization rates. It is necessary to carry out randomized studies assessing the most cost-effective measure to reduce complications associated with PVC.

Fish acute toxicity of nine nanomaterials: Need of pre-tests to ensure comparability and reuse of data.

Fish acute toxicity tests are commonly used in aquatic environmental risk assessments, being required in different international substances regulations. A general trend in the toxicity testing of nanomaterials (NMs) has been to use standardized aquatic toxicity tests. However, as these tests were primarily developed for soluble chemical, issues regarding particle dissolution, agglomeration or sedimentation during the time of exposure are not considered when reporting the toxicity of NMs. The aim of this study was to characterize the NM behaviour throughout the fish acute test and to provide criteria to assay the toxicity of nine NMs based on TiO2, ZnO, SiO2, BaSO4, bentonite, and carbon nanotubes, on rainbow trout following OECD Test Guideline (TG) nº203. Our results showed the importance of conducting a preliminary test (without fish) when working with NMs. They provide valuable information on, sample monitoring, agglomeration, sedimentation, dissolution, actual concentrations of NMs, needed to design the test. Among the NMs tested, only bentonite nanoparticles were stable during the 96-h pre-test and test in aquarium water. In contrast, the remaining NMs exhibited considerable loss and sedimentation within the first 24 h. The high sedimentation observed for almost all NMs highlights the need of consistently measuring the concentrations throughout the entire duration of the fish acute toxicity test to make reliable concentration-response relationships. Notable differences emerged in LC50 values when using actual concentrations as nominal concentrations overestimated concentrations by up to 85.6%. Among all NMs tested, only ZnO NMs were toxic to rainbow trout. A flow chart was specifically developed for OECD TG 203, aiding users in making informed decisions regarding the selection of test systems and necessary modifications to ensure accurate, reliable, and reusable toxicity data. Our findings might contribute to the harmonization of TG 203 improving result reproducibility and interpretability and supporting the development of read-across and QSAR models.

Position statement on infection screening, prophylaxis, and vaccination of pediatric patients with rheumatic diseases and immunosuppressive therapies, part 3: precautions in situations of surgery, fever, and opportunistic infections.

The objective of this study is to provide practical recommendations on the management of pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapies. The recommendations specifically address the cases of surgery, fever, and opportunistic infections (varicella, herpes-zoster, tuberculosis, invasive fungal disease). A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify publications on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapies. The results were presented and discussed in a nominal group meeting, comprising a committee of 12 pediatric rheumatologists from the Infection Prevention and Treatment Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process; this was extended to members of the Spanish Society of Pediatric Rheumatology and Spanish Society of Pediatric Infectious Disease of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (totally disagree) to 10 (totally agree). Agreement was defined as a vote ≥ 7 by at least 70% of participants. The literature review included more than 400 articles. Overall, 63 recommendations (19 on surgery, fever, and opportunistic infections) were generated and voted by 59 pediatric rheumatologists and other pediatric specialists. Agreement was reached for all 63 recommendations. The recommendations on special situations cover management in cases of surgery, fever, and opportunistic infections (varicella, herpes-zoster, tuberculosis, and invasive fungal disease).  Conclusions: Hereby, we provided consensus and updated of recommendations about the management of special situations such as surgery, fever, and opportunistic in children with immune-mediated rheumatic diseases receiving immunosuppressive therapies. Several of the recommendations depend largely on clinical judgement and specific balance between risk and benefit for each individual and situation. To assess this risk, the clinician should have knowledge of the drugs, the patient's previous situation as well as the current infectious disease, in addition to experience. What is Known: • Infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. • Information on how to manage the treatment in situations of fever, opportunistic infections, and surgery in children is limited, and guidelines for action are often extrapolated from adults. What is New: • In the absence of strong evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that could support the clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists.

Trauma-informed systems change training has transcultural, transcontinental transformative healing power: An analysis of leaders in the United States and Angola, Africa.

The Institute for Trauma-Informed Systems Change (ITISC) facilitated a 2-day, 12-hr trauma-informed workshop, delivered virtually, using the Training for Change curriculum. The workshop took place in Portuguese in September 2021 with a group of Angolan leaders (N = 51) and in May 2022, in English, with neonatal intensive care unit (NICU) workers from the United States (N = 73). Surveys were administered before (Time [T] 0) and after the workshop (T1) and consisted of demographic questions and the Survey for Trauma-Informed Systems Change (STISC), which assesses system-wide knowledge and attitudes about trauma-informed systems change and the intersection of culture, safety, and acceptance in the workplace. At T1, 18 (35.3%) participants in the Angolan leaders' group and 46 (63.0%) in the NICU group completed the surveys. Mean scores on the STISC Self-Assessed Knowledge and Attitudes subscale and STISC System-Wide Knowledge and Attitudes subscale increased significantly in both groups after the training. Effect sizes were large for self-assessed knowledge and attitudes, Angolan leaders: d = 1.11, NICU: d = 1.97, and small-to-medium for system-wide knowledge and attitudes, Angolan leaders: d = 0.52, NICU: d = 0.38. Limitations include the relatively small sample size and low participation rates for survey responses. Future research should examine the efficacy of the curriculum in larger samples that include individuals from diverse professions and additional countries. Together, the findings provide initial support that this training can be directly translated and implemented on a global scale.

The role of cognitive reserve in traumatic brain injury: a systematic review of observational studies.

OBJECTIVE: Evaluate the role of cognitive reserve (CR) on cognitive and physical sequelae in traumatic brain injury (TBI). METHODS: A comprehensive search strategy was conducted in four databases in English and Spanish in the last 12 years (2011-2023). Inclusion criteria: original cross-sectional and longitudinal studies whose main or secondary objective was to evaluate the effect of CR in adult patients with TBI. PRISMA guidelines were used to report the search and selection method and STROBE checklist was used to evaluate the quality of studies. RESULTS: Eighteen observational studies were included in this review. Multiple sources of variability were observed: number of patients, time of evolution, severity of the TBI, type of CR proxy, cognitive assessment instrument, etc. However, the most commonly used indicators of CR were premorbid IQ and educational attainment. A positive and consistent association between CR and performance on cognitive tests after injury was found. CONCLUSIONS: CR has a consistent positive effect on cognition and on some other aspects of recovery in traumatic brain injury. In future studies, it will be necessary to promote the use of CR indices based on various indicators and explore the effects of CR on other aspects related to the recovery of brain trauma.

Infants Receiving Very Early Antiretroviral Therapy Have High CD4 Counts in the First Year of Life.

We followed 54 infants with in utero HIV after initiating very early antiretroviral treatment. At weeks 24 and 48, ≥80% had CD4 ≥1500 cells/mm3 and CD4% ≥25%. Routine Pneumocystis jirovecii pneumonia prophylaxis in the first year of life may not be necessary for all very early treated infants. CLINICAL TRIALS REGISTRATION: NCT02140255.

Biomarker Profiles Associated with COVID-19 Severity and Mortality.

INTRODUCTION: The aim of this study was to analyze biomarkers that might predict the severity and progression of the SARS-CoV-2 infection, both in the acute phase and after recovery. METHODS: Unvaccinated patients infected with the original strain of COVID-19 requiring ward (Group 1, n = 48) or ICU (Group 2, n = 41) admission were included. At the time of admission (visit 1), a clinical history was acquired, and blood samples were obtained. One and six months after discharge from the hospital (visits 2 and 3, respectively), a clinical history, lung function tests, and blood samples were carried out. At visit 2, patients also underwent a chest CT scan. Different cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, G-CSF, GM-CSF, IFN-É£, MCP-1, MIP-1ß, and TNF-α) and lung fibrosis biomarkers (YKL-40 and KL-6) were measured in blood samples obtained at visits 1, 2, and 3. RESULTS: At visit 1, IL-4, IL-5, and IL-6 levels were higher in Group 2 (p = 0.039, 0.011, and 0.045, respectively), and IL-17 and IL-8 levels were higher in Group 1 (p = 0.026 and 0.001, respectively). The number of patients in Groups 1 and 2 who died during hospitalization was 8 and 11, respectively. YKL-40 and KL-6 levels were higher in patients who died. Serum YKL-40 and KL-6 levels determined at visit 2 correlated negatively with FVC (p = 0.022 and p = 0.024, respectively) and FEV1 (p = 0.012 and p = 0.032, respectively) measured at visit 3. KL-6 levels also correlated negatively with the diffusing capacity of the lungs for carbon monoxide (DLCO, p = 0.001). CONCLUSIONS: Patients who required ICU admission had higher levels of Th2 cytokines, while patients admitted to the ward showed an innate immune response activation, with IL-8 release and Th1/Th17 lymphocyte contribution. Increased levels of YKL-40 and KL-6 were associated with mortality in COVID-19 patients.

Artificial Dendritic Cells: A New Era of Promising Antitumor Immunotherapy.

The accelerated development of antitumor immunotherapies in recent years has brought immunomodulation into the spotlight. These include immunotherapeutic treatments with dendritic cell (DC)-based vaccines which can elicit tumor-specific immune responses and prolong survival. However, this personalized treatment has several drawbacks, including being costly, labor-intensive, and time consuming. This has sparked interest in producing artificial dendritic cells (aDCs) to open up the possibility of standardized "off-the-shelf" protocols and circumvent the cumbersome and expensive personalized medicine. aDCs take advantage of materials that can be designed and tailored for specific clinical applications. Here, an overview of the immunobiology underlying antigen presentation by DCs is provided in an attempt to select the key features to be mimicked and/or improved through the development of aDCs. The inherent properties of aDCs that greatly impact their performance in vivo and, consequently, the fate of the triggered immune response are also outlined.

Resistance rates among antiretroviral regimens in pregnant people living with HIV.

OBJECTIVES: To update nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) resistance rates and describe the frequency of HIV subtypes in a cohort of pregnant people living with HIV (PPLH) at a national Prevention of Mother-To-Child HIV Transmission (PMTCT) centre. METHODS: We evaluated genotypic resistance among PPLH during prenatal care who were antiretroviral therapy-naïve or experienced. We determined mutations by the Surveillance of Drug Resistance Mutations (SDRM) dataset and also focused on studying participants with intermediate or high resistance defined through the Stanford score. RESULTS: From 2018 to 2021, 1170 PPLH received prenatal care at the centre and 550 were genotyped. Among the 295 SDRMs, with respect to NRTI resistance mutations, there were 27/295 (9.2%) M184V/I, 14/295 (4.7%) T215Y/C/D/E/F/V/I/S and 12/295 (4.1%) M41L. For NNRTI, there were 75/295 (25.4%) K103N, 18/295 (6.1%) M230L and 14/295 (4.7%) G190A/E/S mutations. For PI, the most frequent mutations were 13/295 (4.4%) V82A/S/F/T, 12/295 (4.1%) M46I/L and 10/295 (3.4%) D30N. Based on the Stanford score, 36/224 (16%) naïve participants had one or more antiretroviral resistance mutations, 81% of whom had NNRTI resistance. In the treatment-experience group, 108/326 (33%) had one or more mutations, 91% of whom had NNRTI resistance. The most frequent HIV subtype was B (82.5%). CONCLUSIONS: Our findings suggest that continuous surveys of HIV genotype appear to be important tools to map the distribution and evolution of HIV subtypes and resistance to provide information to support treatment policies. Furthermore, concerns about the use of rilpivirine-containing regimens underscore the importance of resistance surveillance.

Compliance and clinical benefit of deferasirox granule and dispersible tablet formulation in pediatric patients with transfusional iron overload: in a randomized, open-label, multicenter, phase II study.

CALYPSO (NCT02435212), a randomized, open-label, multicenter, phase 2 study evaluated the compliance, clinical benefits, and safety of deferasirox granules and dispersible tablets in pediatric patients with iron overload. Iron chelation therapy-naive and iron chelation therapy-pre-treated patients aged 2 to 0.5 mg/mg; 24.5% and 34.2%), upper respiratory tract infection (28.2% and 29.7%), and pyrexia (26.4% and 23.4%). In iron chelation therapy-naive patients, mean compliance and change from baseline in serum ferritin with both deferasirox formulations were not significantly different. The safety profile was comparable between granule and dispersible tablets formulations, and was consistent with the general safety profile of deferasirox.

Medroxyprogesterone acetate: an alternative to GnRH-antagonist in oocyte vitrification for social fertility preservation and preimplantation genetic testing for aneuploidy.

RESEARCH QUESTION: Can medroxyprogesterone acetate (MPA) be used as a pituitary suppressor instead of a gonadotrophin releasing hormone (GnRH) antagonist during ovarian stimulation in elective fertility preservation and preimplantation genetic testing for aneuploidy (PGT-A) cycles? DESIGN: A multicentre, retrospective, observational, cohort study conducted in 11 IVIRMA centres affiliated to private universities. Of a total of 1652 cycles of social fertility preservation, 267 patients were stimulated using a progestin-primed ovarian stimulation protocol (PPOS), and 1385 patients received a GnRH antagonist. In the PGT-A cycles, 5661 treatments were analysed: 635 patients received MPA and 5026 patients received GnRH antagonist. A further 66 fertility preservation and 1299 PGT-A cycles were cancelled. All cycles took place between June 2019 and December 2021. RESULTS: In the social fertility preservation cycles, the number of mature oocytes vitrified in MPA was similar to the number of those treated with an antagonist, a trend that was seen regardless of age (≤35 or >35 years). In the PGT-A cycles, no differences were found in number of metaphase II, two pronuclei, number of biopsied embryos (4.4 ± 3.1 versus 4.5 ± 3.1), rate of euploidy (57.9% versus 56.4%) or ongoing pregnancy rate (50.4% versus 47.1%, P = 0.119) between the group receiving MPA versus a GnRH antagonist, whereas the clinical miscarriage rate was higher in the antagonist group (10.4% versus 14.8%, P = 0.019). CONCLUSIONS: Administration of PPOS yields similar results to GnRH antagonists in oocytes retrieved, rate of euploid embryos and clinical outcome. Hence, PPOS can be recommended for ovarian stimulation in social fertility preservation and PGT-A cycles, as it allows greater patient comfort.

The prognostic value of neutrophile/lymphocyte ratio and serum chemerin to predict maternal-fetal complications in pregnant systemic lupus erythematosus patients.

BACKGROUND: Pregnancy in SLE continues to be a challenge. The neutrophil-to-lymphocyte ratio (NLR) and chemerin are predictors of preeclampsia in the general population; however, their role as predictors of maternal-fetal complications in pregnant SLE patients has not been analyzed. OBJECTIVE: To investigate the prognostic value of NLR and serum chemerin, to predict maternal-fetal complications in pregnant SLE patients, and compare both biomarkers among three study groups. METHODS: Design: Analytical cross-sectional study of cases and controls with the following study groups: systemic lupus erythematosus (SLE), preeclampsia, and healthy. NLR and chemerin serum were determined between 20 and 25 weeks of gestation. Patients were evaluated every 4-6 weeks until pregnancy resolution. Maternal and fetal outcomes were registered. We employed Receiver Operating Characteristic (ROC) curves to validate prognostic values. RESULTS: Seventy pregnant patients were included: 20 with SLE, 20 with preeclampsia, and 30 healthy pregnant women; NLR values were 4 (2.3-5.6) in SLE, 6 (4.6-9.2) in preeclampsia, and 2.8 (2.1-2.9) in the group of healthy women (p = .0001). Chemerin levels were: 26 (15.3-56.2) in SLE, 96 (37.3-146.2) in preeclampsia, and 24.6 ng/mL (15.3-47.4) in the healthy group (p = .007) Maternal complications were observed in 11 (55%), 20 (100%), and 8 (26%) per group, respectively. Thrombocytopenia was the most frequent complication in all pregnant women, followed by hypertensive disorders. Fetal complications were registered in 12 (60%), 16 (80%), and 2 (6.7%), respectively. Congenital malformations and prematurity were the most frequent fetal complications. NLR had good diagnostic accuracy in predicting maternal-fetal complications (AUROC 0.715) p = .015, CI 95% 0.56-0.86, cut-off point level: 2.9, sensitivity 61%, specificity 78%, positive predictive value (PPV) 65%, negative predictive value (NPV) 75%. Regarding chemerin, a cut-off point level >43 ng/mL had a sensitivity of 75%, specificity of 72% AUROC 0.75, p = .001, CI 95% 0.61-0.89, PPV 51.7% NPV 87.8%, meaning that 51.7% of patients with chemerin levels >43 ng/mL have or will have preeclampsia. CONCLUSION: The NLR may help predict maternal-fetal complications in SLE pregnancy, constituting a marker of subclinical inflammation. Chemerin levels may be associated with preeclampsia. These biomarkers could improve the care of SLE patients with timely intervention of potential complications during pregnancy.

A fatal respiratory complication of malaria caused by Plasmodium vivax.

BACKGROUND: Malaria is endemic and represents an important public health issue in Brazil. Knowledge of risk factors for disease progression represents an important step in preventing and controlling malaria-related complications. Reports of severe forms of Plasmodium vivax malaria are now becoming a common place, but respiratory complications are described in less than 3% of global literature on severe vivax malaria. CASE PRESENTATION: A severe respiratory case of imported vivax malaria in a previously healthy 40-year-old woman has been reported. The patient died after the fifth day of treatment with chloroquine and primaquine due to acute respiratory distress syndrome. CONCLUSIONS: Respiratory symptoms started 48 h after the initiation of anti-malarial drugs, raising the hypothesis that the drugs may have been involved in the genesis of the complication. The concept that vivax malaria is a benign disease that can sometimes result in the development of serious complications must be disseminated. This report highlights, once more, the crucial importance of malaria early diagnosis, a true challenge in non-endemic areas, where health personnel are not familiar with the disease and do not consider its diagnosis promptly.

Crosstalk between estrogen, dendritic cells, and SARS-CoV-2 infection.

The novel coronavirus disease 2019 (Covid-19) first appeared in Wuhan and has so far killed more than four million people worldwide. Men are more affected than women by Covid-19, but the cellular and molecular mechanisms behind these differences are largely unknown. One plausible explanation is that differences in sex hormones could partially account for this distinct prevalence in both sexes. Accordingly, several papers have reported a protective role of 17ß-estradiol during Covid-19, which might help explain why women appear less likely to die from Covid-19 than men. 17ß-estradiol is the predominant and most biologically active endogenous estrogen, which signals through estrogen receptor α, estrogen receptor ß, and G protein-coupled estrogen receptor 1. These receptors are expressed in mature cells from the innate and the adaptive immune system, particularly on dendritic cells (DCs), suggesting that estrogens could modulate their effector functions. DCs are the most specialized and proficient antigen-presenting cells, acting at the interface of innate and adaptive immunity with a powerful capacity to prime antigen-specific naive CD8+ T cells. DCs are richly abundant in the lung where they respond to viral infection. A relative increase of mature DCs in broncho-alveolar lavage fluids from Covid-19 patients has already been reported. Here we will describe how SARS-CoV-2 acts on DCs, the role of estrogen on DC immunobiology, summarise the impact of sex hormones on the immune response against Covid-19, and explore clinical trials regarding Covid-19.

Technology-enabled virtual ward for COVID management of the elderly and immunocompromised in Singapore: a descriptive cohort.

BACKGROUND: To address the hospital bed demand for Delta and Omicron surges in Singapore, the National University Health System (NUHS) developed a COVID Virtual Ward to relieve bed pressures on its three acute hospitals-National University Hospital, Ng Teng Fong General Hospital, Alexandra Hospital. To serve a multilingual population, the COVID Virtual Ward featuring protocolized teleconsultation of high-risk patients, use of a vital signs chatbot, supplemented by home visits where necessary. This study aims to evaluate the safety, outcomes and utilisation of the Virtual Ward as a scalable response to COVID-19 surges. METHODS: This is a retrospective cohort study of all patients admitted to the COVID Virtual Ward between 23 September to 9 November 2021. Patients were defined as "early discharge" if they were referred from inpatient COVID-19 wards and "admission avoidance" if they were referred directly from primary care or emergency services. Patient demographics, utilisation measures and clinical outcomes were extracted from the electronic health record system. The primary outcomes were escalation to hospital and mortality. Use of the vital signs chatbot was evaluated by examining compliance levels, need for automated reminders and alerts triggered. Patient experience was evaluated using data extracted from a quality improvement feedback form. RESULTS: 238 patients were admitted to the COVID Virtual Ward from 23 September to 9 November, of whom 42% were male, 67.6% of Chinese ethnicity. 43.7% were over the age of 70, 20.5% were immunocompromised, and 36.6% were not fully vaccinated. 17.2% of patients were escalated to hospital and 2.1% of patients died. Patients who were escalated to hospital were more likely to be immunocompromised or to have a higher ISARIC 4C-Mortality Score. There were no missed deteriorations. All patients received teleconsults (median of 5 teleconsults per patient, IQR 3-7). 21.4% of patients received home visits. 77.7% of patients engaged with the vital signs chatbot, with a compliance rate of 84%. All patients would recommend the programme to others in their situation. CONCLUSIONS: Virtual Wards are a scalable, safe and patient-centered strategy to care for high risk COVID-19 patients at home. TRIAL REGISTRATION: NA.

Transition metal (Ti, Cu, Zn, Pt) single-atom modified graphene/AS2 (A = Mo, W) van der Waals heterostructures for removing airborne pollutants.

Air pollution is a worldwide issue that affects human health and the environment. The scientific community tries to control it through different approaches, from experimental to theoretical assessments. Here, we perform DFT calculations to describe CO2, NO2, and SO2 detection on a single-atom (Ti, Cu, Zn, Pt) graphene supported on 2D molybdenum disulfide (MoS2) and tungsten disulfide (WS2). Transition metal single atoms on graphene improve the monolayer reactivity by generating an effective way to remove airborne pollutants. Results indicate that SO2 and NO2 chemically adsorb on all tested transition metals, whereas CO2 stands on top of the incorporated atoms through van der Waals interactions. Since strong Ti-O interactions appear, the Ti single-atom graphene/MoS2(WS2) systems efficiently remove CO2 from the environment. Compared to pristine graphene, our proposed heterostructures improve the SO2, NO2, and CO2 adsorption energies. The heterostructures' electronic properties change once the molecules interact with the transition metals, generating sensible and selective pollutant molecule detection and removal.

Position statement on infection screening, prophylaxis, and vaccination in pediatric patients with rheumatic diseases and immunosuppressive therapies, part 2: infection prophylaxis.

This study aims to provide practical recommendations on prophylaxis for infection in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy. A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify articles that analyzed data on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapy. The results were presented and discussed in a nominal group meeting comprising a committee of 12 pediatric rheumatologists from the Prevention and Treatment of Infections Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process that was extended to members of the Spanish Society of Pediatric Rheumatology and the Vaccine Advisory Committee of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (completely disagree) to 10 (completely agree). Agreement was considered to have been reached if at least 70% of participants voted ≥ 7. The literature review included more than 400 articles. Overall, 63 recommendations were generated (23 on infection prophylaxis) and voted by 59 pediatric rheumatologists and other pediatric specialists, all of whom achieved the pre-established level of agreement. The recommendations on prophylaxis of infection cover vaccination and prophylaxis against varicella zoster virus, tuberculosis, Pneumocystis jiroveccii, and invasive fungal infections in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy.  Conclusion: Based on current evidence and a Delphi process, we provided consensus and updated recommendations on prophylaxis and treatment of infections to guide those caring for pediatric rheumatology patients. What is Known: •Data largely derived from adults find that infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. •It is crucial to be aware of the preventive measures that should be implemented to prevent these infections in children, although most guidelines are often extrapolated from adult cases. What is New: •In the absence of evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that could prove useful in clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists. •The recommendations focus on tuberculosis, herpes zoster virus, fungal infections, and Pneumocystis jirovecii.

ER-mitochondria communication is involved in NLRP3 inflammasome activation under stress conditions in the innate immune system.

Endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which are key events in the initiation and/or progression of several diseases, are correlated with alterations at ER-mitochondria contact sites, the so-called "Mitochondria-Associated Membranes" (MAMs). These intracellular structures are also implicated in NLRP3 inflammasome activation which is an important driver of sterile inflammation, however, the underlying molecular basis remains unclear. This work aimed to investigate the role of ER-mitochondria communication during ER stress-induced NLRP3 inflammasome activation in both peripheral and central innate immune systems, by using THP-1 human monocytes and BV2 microglia cells, respectively, as in vitro models. Markers of ER stress, mitochondrial dynamics and mass, as well as NLRP3 inflammasome activation were evaluated by Western Blot, IL-1ß secretion was measured by ELISA, and ER-mitochondria contacts were quantified by transmission electron microscopy. Mitochondrial Ca2+ uptake and polarization were analyzed with fluorescent probes, and measurement of aconitase and SOD2 activities monitored mitochondrial ROS accumulation. ER stress was demonstrated to activate the NLRP3 inflammasome in both peripheral and central immune cells. Studies in monocytes indicate that ER stress-induced NLRP3 inflammasome activation occurs by a Ca2+-dependent and ROS-independent mechanism, which is coupled with upregulation of MAMs-resident chaperones, closer ER-mitochondria contacts, as well as mitochondrial depolarization and impaired dynamics. Moreover, enhanced ER stress-induced NLRP3 inflammasome activation in the immune system was found associated with pathological conditions since it was observed in monocytes derived from bipolar disorder (BD) patients, supporting a pro-inflammatory status in BD. In conclusion, by demonstrating that ER-mitochondria communication plays a key role in the response of the innate immune cells to ER stress, this work contributes to elucidate the molecular mechanisms underlying NLRP3 inflammasome activation under stress conditions, and to disclose novel potential therapeutic targets for diseases associated with sterile inflammation.