Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy.

BACKGROUND: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres. METHODS: We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution. RESULTS: We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens. CONCLUSIONS: The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.

Fractional Radiofrequency and Oral Isotretinoin-A Prospective Randomized Controlled Split-Face Trial Comparing Concurrent Versus Delayed Fractional Radiofrequency Treatment for Acne Scars.

BACKGROUND: Therapeutic dogma has been to treat acne scars no less than 6 months after isotretinoin (ITN) cessation. OBJECTIVE: To evaluate the safety and efficacy of fractional radiofrequency (FRF) in patients treated concurrently with ITN. METHODS: We conducted a prospective randomized control 3-arm comparative trial to evaluate the treatment of acne scars. Patients received one of three treatment options: (A) ITN and FRF concurrent treatment, (B) ITN monotherapy, and (C) FRF 6 months post-ITN treatment. Patients in the FRF cohorts received three monthly sessions. Patients were followed for adverse effects up to 6-9 months post-FRF treatment. Final cosmesis was scored by three independent dermatologists using two scales: the Echelle d'Evaluation Clinique des Cicatrices d'Acne (ECCA) and an internal 5-point investigator's scale, indicating the percentage of improvement. Subjective analyses by patients were also assessed. RESULTS: Objective and subjective analyses revealed improvement in the ITN-FRF cohort, which was superior to the delayed FRF cohort and the ITN monotherapy cohort. Specifically, the concurrently treated cohort (ITN-FRF) had a significant reduction in acne scar volume from baseline mean (151.1 ± 44.7 to 97.0 ± 31.2, p < 0.005), outperforming both the delayed FRF and monotherapy ITN treatment cohorts, respectively (155.4 ± 37.8 to 122.0 ± 46.2, 144.6 ± 82.8 to 132.4 ± 62.7). Additionally, the concurrently treated cohort demonstrated improved ECCA scores (36.8 ± 15.5), significantly better than the ITN monotherapy cohort (101.5 ± 20.1, p < 0.01). LIMITATIONS: Limited patient sample size: 38 patients completed the study; mostly Fitzpatrick Type II-III skin; photographic assessments utilized. CONCLUSION: Per our prospective trial, concurrent treatment of ITN-FRF is superior to delayed FRF treatment 6 months post-ITN cessation.

Fractional ablative CO2 laser and oral isotretinoin-A prospective randomized controlled split-face trial comparing concurrent versus delayed laser treatment for acne scars.

BACKGROUND: Therapeutic dogma has been to treat acne scars with ablative fractional laser no less than 6 months after isotretinoin (ITN) cessation. OBJECTIVE: To evaluate the safety and efficacy of fractional ablative CO2 laser (FACL) in patients treated concurrently with ITN. METHODS: We conducted a prospective split-face randomized control trial in patients treated with FACL concurrently with ITN versus patients treated with FACL 6 months post-ITN treatment. Patients received 3 monthly sessions of FACL with concurrent ITN treatment on half of the face; the other side of the face received the same FACL treatment regimen 6 months post-ITN cessation. Patients were followed for adverse effects up to 6 months post-FACL treatment. Final cosmesis was scored using the Quantitative Global Acne Scarring Grading System (GASGS) by three independent dermatologists. RESULTS: The GASGS of the concurrent ITN-FACL treated side of the face was significantly lower than the side treated with delayed laser therapy (4.7 ± 2.5 vs. 7.7 ± 2.9, respectively, p < 0.001). LIMITATIONS: The laser's settings were standardized, and not adjusted per patient skin type. CONCLUSION: Per our prospective trial, concurrent treatment of FACL -ITN is superior to delayed FACL treatment 6 months post-ITN cessation. Fractional ablative laser treatment is effective in improving acne scars, which persist despite isotretinoin therapy.

Aluminium 8-Hydroxyquinolinate N-Oxide as a Precursor to Heterometallic Aluminium-Lanthanide Complexes.

A reaction in anhydrous toluene between the formally unsaturated fragment [Ln(hfac)3] (Ln3+ = Eu3+, Gd3+ and Er3+; Hhfac = hexafluoroacetylacetone) and [Al(qNO)3] (HqNO = 8-hydroxyquinoline N-oxide), here prepared for the first time from [Al(OtBu)3] and HqNO, affords the dinuclear heterometallic compounds [Ln(hfac)3Al(qNO)3] (Ln3+ = Eu3+, Gd3+ and Er3+) in high yields. The molecular structures of these new compounds revealed a dinuclear species with three phenolic oxygen atoms bridging the two metal atoms. While the europium and gadolinium complexes show the coordination number (CN) 9 for the lanthanide centre, in the complex featuring the smaller erbium ion, only two oxygens bridge the two metal atoms for a resulting CN of 8. The reaction of [Eu(hfac)3] with [Alq3] (Hq = 8-hydroxyquinoline) in the same conditions yields a heterometallic product of composition [Eu(hfac)3Alq3]. A recrystallization attempt from hot heptane in air produced single crystals of two different morphologies and compositions: [Eu2(hfac)6Al2q4(OH)2] and [Eu2(hfac)6(µ-Hq)2]. The latter compound can be directly prepared from [Eu(hfac)3] and Hq at room temperature. Quantum mechanical calculations confirm (i) the higher stability of [Eu(hfac)3Al(qNO)3] vs. the corresponding [Eu(hfac)3Alq3] and (ii) the preference of the Er complexes for the CN 8, justifying the different behaviour in terms of the Lewis acidity of the metal centre.

Comparison of 2 Hyaluronic Acid-based Fillers for the Treatment of Acne Scars: Structural Lifting Versus Biostimulatory Effect.

BACKGROUND: Hyaluronic acid (HA)-based fillers are effective at mitigating acne scars due to their filling effect. Complexes of high and low molecular weight HA demonstrated a delayed biostimulatory effect. OBJECTIVE: The authors sought to compare the results of acne scar treatment using a filler composed of complexes of high and low molecular weight HA versus a traditional cross-linking HA filler. METHODS: Thirty patients with moderate-to-severe atrophic acne scarring were included in this prospective, split-face, double-blinded, randomized controlled study. Each underwent 3 monthly injections of a novel formula of combined high and low molecular weight HA (P) to the base of acne scars on 1 side of the face and traditional cross-linking HA (JV) filler on the other. Patients were evaluated 6 months after their last treatment for objective and subjective improvements. RESULTS: For JV, statistically significant reductions were observed in the acne scar volume but nearly no change in elasticity and stretch during early treatments. For P, no significant differences were observed in early treatments; however, statistically significant improvements were observed in later visits. CONCLUSION: Although the traditional JV filler demonstrated an earlier impact than P, the latter produced delayed positive changes that were more pronounced than the traditional filler.

Increased risk of emergency department presentations for bronchiolitis in infants exposed to air pollution.

Air pollution has been linked to an increased risk of several respiratory diseases in children, especially respiratory tract infections. The present study aims to evaluate the association between pediatric emergency department (PED) presentations for bronchiolitis and air pollution. PED presentations due to bronchiolitis in children aged less than 1 year were retrospectively collected from 2007 to 2018 in Padova, Italy, together with daily environmental data. A conditional logistic regression based on a time-stratified case-crossover design was performed to evaluate the association between PED presentations and exposure to NO2 , PM2.5, and PM10. Models were adjusted for temperature, relative humidity, atmospheric pressure, and public holidays. Delayed effects in time were evaluated using distributed lag non-linear models. Odds ratio for lagged exposure from 0 to 14 days were obtained. Overall, 2251 children presented to the PED for bronchiolitis. Infants' exposure to higher concentrations of PM10 and PM2.5 in the 5 days before the presentation to the PED increased the risk of accessing the PED by more than 10%, whereas high concentrations of NO2 between 2 and 12 days before the PED presentation were associated with an increased risk of up to 30%. The association between pollutants and infants who required hospitalization was even greater. A cumulative effect of NO2 among the 2 weeks preceding the presentation was also observed. In summary, PM and NO2 concentrations are associated with PED presentations and hospitalizations for bronchiolitis. Exposure of infants to air pollution could damage the respiratory tract mucosa, facilitating viral infections and exacerbating symptoms.

How to investigate human health effects related to exposure to mixtures of per- and polyfluoroalkyl substances: A systematic review of statistical methods.

BACKGROUND: Humans are exposed to several per- and polyfluoroalkyl substances (PFAS) daily; however, most previous studies have focused on individual PFAS. Although attention to effects of exposure to mixtures of PFAS has grown in recent years, there is no consensus on the appropriate statistical methods that can be used to assess their combined effect on human health. OBJECTIVES: We aim to perform a comprehensive review of the statistical methods used in the existing studies which evaluate the association between exposure to mixtures of PFAS and any adverse human health effect. METHODS: The online databases PubMed, Embase and Scopus were searched for eligible studies, published during the last ten years (last search performed on April 08, 2021). Covidence software was used by two different reviewers to perform a title/abstract screening, followed by a full text revision of the selected papers. RESULTS: A total of 3640 papers were identified, and after the screening process, 53 papers were included in the current review. Most of the studies were published between 2019 and 2021 and were conducted mainly in North America and Europe; more than half of the studies (28 out of 53) were conducted on mother and child pairs. WQS (Weighted Quantile Sum) Regression and BKMR (Bayesian Kernel Machine Regression) were used in 36 out of 53 papers to model mixtures' effects. Health outcomes included in the studies are immunotoxicity (n = 8), fetal development (n = 7), neurodevelopment (n = 9), reproductive hormones (n = 6), thyroid hormones (n = 7), outcomes related to metabolic pathways (n = 16). CONCLUSION: Studies on human exposure to PFAS as complex mixtures and health consequences have substantially increased in the last few years. Based on our findings, we propose that addressing risk from PFAS mixtures will likely require combinations of approaches and implementation of constantly evolving statistical methods. Specific guidelines and tools for quality assessment and publication of mixture observational studies are warranted.

Perfluoroalkyl substances and thyroid stimulating hormone levels in a highly exposed population in the Veneto Region.

BACKGROUND: Per- and poly-fluoroalkyl substances (PFAS) are persistent and widespread environmental pollutants. People living in Veneto Region (Italy) have been exposed from the late 1970s to 2013 to elevated concentrations of PFAS through drinking water. The effect of PFAS on thyroid function is still controversial and studies focusing on thyroid stimulating hormone (TSH) have shown inconsistent results. The aim of this study was to evaluate the association between serum PFAS and TSH levels and its dose-response relationship in a large population of highly exposed individuals. METHODS: A cross-sectional study was conducted on 21,424 individuals aged 14-39 living in the contaminated area. In the main analysis, participants with prevalent thyroid disease and pregnant women were excluded. Serum levels of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) were measured. Generalized Additive Models were used to evaluate the association between TSH levels and serum PFAS, using thin plate spline smooth terms to model the potential non-linear relationship. Models were stratified by sex and age group and adjusted for potential confounders. A secondary analysis was conducted to evaluate the association between PFAS with prevalent self-reported thyroid disorders. RESULTS: We found no association between TSH and any type of PFAS among adolescents or women. A decrease in TSH concentration was observed in association with an IQR increase in PFHxS and a mild decrease in TSH at low levels of PFOA, PFOS and PFHxS among male adults. Self-reported thyroid disease was more common among women with higher levels of PFNA concentrations, whereas all other PFAS were not associated with thyroid diseases regardless of sex or age. CONCLUSIONS: Overall there is no evidence of an association between TSH and PFAS. However, some results are suggestive of a possible inverse association of TSH with PFOA, PFOS and PFHxS among adult males.

Epstein-Barr Virus (EBV) Epithelial Associated Malignancies: Exploring Pathologies and Current Treatments.

Epstein-Barr virus (EBV) is one of eight known herpesviruses with the potential to infect humans. Globally, it is estimated that between 90-95% of the population has been infected with EBV. EBV is an oncogenic virus that has been strongly linked to various epithelial malignancies such as nasopharyngeal and gastric cancer. Recent evidence suggests a link between EBV and breast cancer. Additionally, there are other, rarer cancers with weaker evidence linking them to EBV. In this review, we discuss the currently known epithelial malignancies associated with EBV. Additionally, we discuss and establish which treatments and therapies are most recommended for each cancer associated with EBV.

Hepatitis B and Hepatitis D Viruses: A Comprehensive Update with an Immunological Focus.

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) are highly prevalent viruses estimated to infect approximately 300 million people and 12-72 million people worldwide, respectively. HDV requires the HBV envelope to establish a successful infection. Concurrent infection with HBV and HDV can result in more severe disease outcomes than infection with HBV alone. These viruses can cause significant hepatic disease, including cirrhosis, fulminant hepatitis, and hepatocellular carcinoma, and represent a significant cause of global mortality. Therefore, a thorough understanding of these viruses and the immune response they generate is essential to enhance disease management. This review includes an overview of the HBV and HDV viruses, including life cycle, structure, natural course of infection, and histopathology. A discussion of the interplay between HDV RNA and HBV DNA during chronic infection is also included. It then discusses characteristics of the immune response with a focus on reactions to the antigenic hepatitis B surface antigen, including small, middle, and large surface antigens. This paper also reviews characteristics of the immune response to the hepatitis D antigen (including small and large antigens), the only protein expressed by hepatitis D. Lastly, we conclude with a discussion of recent therapeutic advances pertaining to these viruses.

Perioperative management of children with neuromuscular disorders based on a common protocol: A prospective, national study in Italy.

BACKGROUND: Children with neuromuscular diseases (NMDs) often display respiratory muscle weakness which increases the risk of postoperative pulmonary complications (PPCs) after general anaesthesia. Non-invasive ventilation (NIV) associated with mechanical insufflation-exsufflation (MI-E) can reduce the incidence and severity of PPCs. The aim of this study was to report our experience with a shared perioperative protocol that consists in using NIV combined with MI-E to improve the postoperative outcome of NMD children (IT-NEUMA-Ped). METHOD: We conducted a multicentre, observational study on 167 consecutive paediatric patients with NMDs undergoing anaesthesia from December 2015 to December 2018 in a network of 13 Italian hospitals. RESULTS: We found that 89% of the 167 children (mean age 8 years old) were at high risk of PPCs, due to the presence of at least one respiratory risk factor. In particular, 51% of them had preoperative ventilatory support dependence. Only 14 (8%) patients developed PPCs, and only two patients needed tracheostomy. Average hospital length of stay (LOS) was 6 (2-14) days. The study population was stratified according to preoperative respiratory devices dependency and invasiveness of the procedure. Patients with preoperative ventilatory support dependence showed significantly higher intensive care unit (ICU) admission rate and longer hospital LOS. CONCLUSION: Disease severity seems to be more related to the outcome of this population than invasiveness of procedures. NIV combined with MI-E can help in preventing and resolve PPCs.

Excess of all-cause mortality is only partially explained by COVID-19 in Veneto (Italy) during spring outbreak.

BACKGROUND: Italy has been the first European country to be affected by the COVID-19 epidemic which started out at the end of February. In this report, we focus our attention on the Veneto Region, in the North-East of Italy, which is one of the areas that were first affected by the rapid spread of SARS-CoV-2. We aim to evaluate the trend of all-cause mortality and to give a description of the characteristics of the studied population. METHODS: Data used in the analyses were released by the majority of municipalities and cover the 93% of the total population living in the Veneto Region. We evaluated the trend of overall mortality from Jan.01 to Jun.30. 2020. Moreover we compared the COVID-19-related deaths to the overall deaths. RESULTS: From March 2020, the overall mortality rate increased exponentially, affecting males and people aged > 76 the most. The confirmed COVID-19-related death rate in the Veneto region between Mar.01 and Apr.302020 is 30 per 100,000 inhabitants. In contrast, the all-cause mortality increase registered in the same months in the municipalities included in the study is 219 per 100,000 inhabitants. CONCLUSIONS: COVID-19 has a primary role in the increase in mortality but does not entirely explain such a high number of deaths. Strategies need to be developed to reduce this gap in case of future waves of the pandemic.

Evasion of the Host Immune Response by Betaherpesviruses.

The human immune system boasts a diverse array of strategies for recognizing and eradicating invading pathogens. Human betaherpesviruses, a highly prevalent subfamily of viruses, include human cytomegalovirus (HCMV), human herpesvirus (HHV) 6A, HHV-6B, and HHV-7. These viruses have evolved numerous mechanisms for evading the host response. In this review, we will highlight the complex interplay between betaherpesviruses and the human immune response, focusing on protein function. We will explore methods by which the immune system first responds to betaherpesvirus infection as well as mechanisms by which viruses subvert normal cellular functions to evade the immune system and facilitate viral latency, persistence, and reactivation. Lastly, we will briefly discuss recent advances in vaccine technology targeting betaherpesviruses. This review aims to further elucidate the dynamic interactions between betaherpesviruses and the human immune system.

[Gender and age factors affecting the mortality during the COVID-19 epidemic in Italy]. / Effetti del genere e dell'età sugli eccessi di mortalità durante l'epidemia di COVID-19 in Italia.

BACKGROUND: the COVID-19 epidemic severely affected Italy among European countries causing a considerable number of deaths across the country, especially in Northern Italy, leading also to serious problems to the Italian healthcare system, in particular the overcrowding of Intensive Care Units (ICU). In literature, the debate on the overall mortality during the COVID-19 epidemic, directly and indirectly, associated with the disease, is still open. OBJECTIVES: to describe the time trend of the mortality in Italy during the COVID-19 pandemic accounting for age, gender, and geographical areas. DESIGN: analysis of mortality trend, by region, age, and gender. SETTING AND PARTICIPANTS: the Italian mortality data, released by the Italian National Institute of Statistics (Istat), have been considered for the analyses. The data refer to the first four months of 2015-2019 and 2020, involving 7,270 municipalities, corresponding to 93% of the Italian population. MAIN OUTCOME MEASURES: the mortality rates in the first four months of 2015-2019 and 2020, age-adjusted, have been calculated together with the percent variation. The data were analysed by gender, age class (<65; >=65 years), Region, and geographical areas (Northern versus Central-Southern Italy). The overall daily mortality series have been represented as rates over 100,000 resident population. RESULTS: in addition to the geographical location, the age component was a major determinant of the mortality pattern. The greater increase in the overall mortality was evidenced among elderly subjects in the Northern Italian Regions most affected by the epidemic. In these areas, also gender component played an important role in determining the mortality excess: higher mortality rates in the first four months of 2020 are observed for males in comparison to female populations. CONCLUSIONS: this research reveals that the population components are an important issue in determining the COVID-19 mortality excess. For this reason, it is of primary importance to monitor mortality (overall and by COVID-19) by age and gender and to consider these components and the related factors (comorbidity, exposures affecting the lung) in the public prevention policies towards the protection of the most fragile population groups.

Herpes Simplex Virus, Human Papillomavirus, and Cervical Cancer: Overview, Relationship, and Treatment Implications.

There is a significant body of research examining the role of human papillomavirus (HPV) in the pathogenesis of cervical cancer, with a particular emphasis on the oncogenic proteins E5, E6, and E7. What is less well explored, however, is the relationship between cervical cancer and herpes simplex virus (HSV). To date, studies examining the role of HSV in cervical cancer pathogenesis have yielded mixed results. While several experiments have determined that HPV/HSV-2 coinfection results in a higher risk of developing cervical cancer, others have questioned the validity of this association. However, clarifying the potential role of HSV in the pathogenesis of cervical cancer may have significant implications for both the prevention and treatment of this disease. Should this relationship be clarified, treating and preventing HSV could open another avenue with which to prevent cervical cancer. The importance of this is highlighted by the fact that, despite the creation of an effective vaccine against HPV, cervical cancer still impacts 604,000 women and is responsible for 342,000 deaths annually. This review provides an overview of HSV and HPV infections and then delves into the possible links between HPV, HSV, and cervical cancer. It concludes with a summary of preventive measures against and recent treatment advances in cervical cancer.

Competing excitation paths in luminescent heterobimetallic Ln-Al complexes: Unraveling interactions via experimental and theoretical investigations.

The interest for heterometallic lanthanide-d or-p metal (Ln-M) complexes is growing because of a potential cooperative or synergistic effect related to the proximity of two different metals in the same molecular architecture affording special tunable physical properties. To exploit the potentiality of Ln-M complexes, suitable synthetic approaches, and the in-depth understanding of the effect of each building block on their properties are mandatory. Here, we report the study on a family of heterometallic luminescent complexes [Ln(hfac)3Al(L)3], Ln= Eu3+ and Tb3+. Using different L ligands, we investigated the effect of the steric and electronic properties of the Al(L)3 fragment, highlighting the general validity of the employed synthetic route. A marked difference in the light emission of [Eu(hfac)3Al(L)3] and [Tb(hfac)3Al(L)3] complexes has been observed. Thanks to photoluminescence experiments and Density Functional Theory calculations, Ln3+ emissions are explained with a model involving two non-interacting excitation paths through hfac or Al(L)3 ligands.

A role for the centrosome in regulating the rate of neuronal efferocytosis by microglia in vivo.

During brain development, many newborn neurons undergo apoptosis and are engulfed by microglia, the tissue-resident phagocytes of the brain, in a process known as efferocytosis. A hallmark of microglia is their highly branched morphology characterized by the presence of numerous dynamic extensions that these cells use for scanning the brain parenchyma and engulfing unwanted material. The mechanisms driving branch formation and apoptotic cell engulfment in microglia are unclear. By taking a live-imaging approach in zebrafish, we show that while microglia generate multiple microtubule-based branches, they only successfully engulf one apoptotic neuron at a time. Further investigation into the mechanism underlying this sequential engulfment revealed that targeted migration of the centrosome into one branch is predictive of phagosome formation and polarized vesicular trafficking. Moreover, experimentally doubling centrosomal numbers in microglia increases the rate of engulfment and even allows microglia to remove two neurons simultaneously, providing direct supporting evidence for a model where centrosomal migration is a rate-limiting step in branch-mediated efferocytosis. Conversely, light-mediated depolymerization of microtubules causes microglia to lose their typical branched morphology and switch to an alternative mode of engulfment, characterized by directed migration towards target neurons, revealing unexpected plasticity in their phagocytic ability. Finally, building on work focusing on the establishment of the immunological synapse, we identified a conserved signalling pathway underlying centrosomal movement in engulfing microglia.

Multifaceted Role of AMPK in Viral Infections.

Viral pathogens often exploit host cell regulatory and signaling pathways to ensure an optimal environment for growth and survival. Several studies have suggested that 5'-adenosine monophosphate-activated protein kinase (AMPK), an intracellular serine/threonine kinase, plays a significant role in the modulation of infection. Traditionally, AMPK is a key energy regulator of cell growth and proliferation, host autophagy, stress responses, metabolic reprogramming, mitochondrial homeostasis, fatty acid ß-oxidation and host immune function. In this review, we highlight the modulation of host AMPK by various viruses under physiological conditions. These intracellular pathogens trigger metabolic changes altering AMPK signaling activity that then facilitates or inhibits viral replication. Considering the COVID-19 pandemic, understanding the regulation of AMPK signaling following infection can shed light on the development of more effective therapeutic strategies against viral infectious diseases.

Stress-Induced Epstein-Barr Virus Reactivation.

Epstein-Barr virus (EBV) is typically found in a latent, asymptomatic state in immunocompetent individuals. Perturbations of the host immune system can stimulate viral reactivation. Furthermore, there are a myriad of EBV-associated illnesses including various cancers, post-transplant lymphoproliferative disease, and autoimmune conditions. A thorough understanding of this virus, and the interplay between stress and the immune system, is essential to establish effective treatment. This review will provide a summary of the interaction between both psychological and cellular stressors resulting in EBV reactivation. It will examine mechanisms by which EBV establishes and maintains latency and will conclude with a brief overview of treatments targeting EBV.

Air Pollution Relates to Airway Pathology in Children with Wheezing.

Rationale: Outdoor air pollution contributes to asthma development and exacerbations, yet its effects on airway pathology have not been defined in children. Objectives: To explore the possible link between air pollution and airway pathology, we retrospectively examined the relationship between environmental pollutants and pathological changes in bronchial biopsy specimens from children undergoing a clinically indicated bronchoscopy. Methods: Structural and inflammatory changes (basement membrane [BM] thickness, epithelial loss, eosinophils, neutrophils, macrophages, mast cells, and lymphocytes) were quantified in biopsy specimens by using immunohistochemistry. The association between exposure to particulate matter less than 10 µm in aerodynamic diameter (PM10), SO2 and NO2 and biopsy findings was evaluated by using a generalized additive model with Gamma family to allow for overdispersion, adjusted for atmospheric pressure, temperature, humidity, and wheezing. Results: Overall, 98 children were included (age 5.3 ± 2.9 yr; 53 with wheezing/45 without wheezing). BM thickness increased with prolonged exposure to PM10 (rate ratio [RR], 1.29; 95% confidence interval [CI], 1.09-1.52), particularly in children with wheezing. Prolonged exposure to PM10 was also associated with eosinophilic inflammation in children with wheezing (RR, 3.16; 95% CI, 1.35-7.39). Conversely, in children without wheezing, increased PM10 exposure was associated with a reduction of eosinophilic inflammation (RR, 0.12; 95% CI, 0.02-0.6) and neutrophilic inflammation (RR, 0.36; 95% CI, 0.14-0.89). Moreover, NO2 exposure was also linked to reductions in neutrophil infiltration (RR, 0.57; 95% CI, 0.34-0.93) and eosinophil infiltration (RR, 0.33; 95% CI, 0.14-0.77). Conclusions: Different patterns of association were observed in children with wheezing and in children without wheezing. In children without wheezing, exposure to PM10 and NO2 was linked to reduced eosinophilic and neutrophilic inflammation. Conversely, in children with wheezing, prolonged exposure to PM10 was associated with increased BM thickness and eosinophilic inflammation, suggesting that it might contribute to asthma development by promoting airway remodeling and inflammation.