The inflammation of allergic diseases is characterized by a complex interaction between type 2 and type 3 immune responses, explaining clinical symptoms and histopathological patterns. Airborne ...stimuli activate the mucosal epithelium to release a number of molecules impacting the activity of resident immune and environmental cells. Signals from the mucosal barrier, regulatory cells, and the inflamed tissue are crucial conditions able to modify innate and adaptive effector cells providing the selective homing of eosinophils or neutrophils. The high plasticity of resident T‐ and innate lymphoid cells responding to external signals is the prerequisite to explain the multiplicity of endotypes of allergic diseases. This notion paved the way for the huge use of specific biologic drugs interfering with pathogenic mechanisms of inflammation. Based on the response of the epithelial barrier, the activity of resident regulatory cells, and functions of structural non‐lymphoid environmental cells, this review proposes some immunopathogenic scenarios characterizing the principal endotypes which can be associated with a precise phenotype of asthma. Recent literature indicates that similar concepts can also be applied to the inflammation of other non‐respiratory allergic disorders. The next challenges will consist in defining specific biomarker(s) of each endotype allowing for a quick diagnosis and the most effective personalized therapy.
The issue of subjects with mild cognitive impairment (MCI) reverting to normal cognition (NC) has to date been taken in limited consideration, and no conclusive data are available on the rate of ...reversion. We aimed at systematically reviewing available longitudinal studies on MCI and meta-analyzing data with the purpose of estimating the proportion of subjects reverting to NC.
We performed a systematic bibliographic search on PubMed, the Cochrane Library, and the ISI Web of Science databases. We included in the review all longitudinal studies on MCI published from 1999 up to November 2015. Only studies with a longitudinal design, a follow-up ≥2 years, enrolling subjects with MCI, and reporting the number or the percentage of subjects reverting to NC were included. Data extraction was performed independently by 2 authors. The methodological quality of studies was also assessed by 2 independent authors using the QUIPS tool.
Twenty-five studies were included. The quality of evidence was found to be moderate. We observed an overall 18% (95% CI 14-22) reversion rate from MCI to NC. Results from the metaregression showed a significant association between effect size and study setting. In particular, estimates significantly varied according to study setting, with an 8% (95% CI 4-11) reversion rate in clinical-based studies and a 25% (95% CI 19-30) rate in population-based studies. The frequency of reversion from MCI to NC further increased to 26% when considering only studies of better quality. Only a few studies were designed to specifically investigate the reversion from MCI to NC, thus relevant information on this topic was frequently missing.
Our data confirm that reversion to normality is a common outcome in subjects with MCI, thus leading to recommend a more balanced view when approaching the construct of MCI both in a clinical and in a research setting.
The coronavirus disease 2019 (COVID‐19) pandemic started in March 2020 and caused over 5 million confirmed deaths worldwide as far August 2021. We have been recently overwhelmed by a wide literature ...on how the immune system recognizes severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and contributes to COVID‐19 pathogenesis. Although originally considered a respiratory viral disease, COVID‐19 is now recognized as a far more complex, multi‐organ‐, immuno‐mediated‐, and mostly heterogeneous disorder. Though efficient innate and adaptive immunity may control infection, when the patient fails to mount an adequate immune response at the start, or in advanced disease, a high innate‐induced inflammation can lead to different clinical outcomes through heterogeneous compensatory mechanisms. The variability of viral load and persistence, the genetic alterations of virus‐driven receptors/signaling pathways and the plasticity of innate and adaptive responses may all account for the extreme heterogeneity of pathogenesis and clinical patterns. As recently applied to some inflammatory disorders as asthma, rhinosinusitis with polyposis, and atopic dermatitis, herein we suggest defining different endo‐types and the related phenotypes along COVID‐19. Patients should be stratified for evolving symptoms and tightly monitored for surrogate biomarkers of innate and adaptive immunity. This would allow to preventively identify each endo‐type (and its related phenotype) and to treat patients precisely with agents targeting pathogenic mechanisms.
The pathogenesis of Alzheimer’s disease (AD) is somewhat complex and has yet to be fully understood. As the effectiveness of the therapy currently available for AD has proved to be limited, the need ...for new drugs has become increasingly urgent. The modulation of the endogenous cannabinoid system (ECBS) is one of the potential therapeutic approaches that is attracting a growing amount of interest. The ECBS consists of endogenous compounds and receptors. The receptors CB1 and CB2 have already been well characterized: CB1 receptors, which are abundant in the brain, particularly in the hippocampus, basal ganglia and cerebellum, regulate memory function and cognition. It has been suggested that the activation of CB1 receptors reduces intracellular Ca concentrations, inhibits glutamate release and enhances neurotrophin expression and neurogenesis. CB2 receptors are expressed, though to a lesser extent, in the central nervous system, particularly in the microglia and immune system cells involved in the release of cytokines. CB2 receptors have been shown to be upregulated in neuritic plaque-associated microglia in the hippocampus and entorhinal cortex of patients, which suggests that these receptors play a role in the inflammatory pathology of AD. The role of the ECBS in AD is supported by cellular and animal models. By contrast, few clinical studies designed to investigate therapies aimed at reducing behaviour disturbances, especially night-time agitation, eating behaviour and aggressiveness, have yielded positive results. In this review, we will describe how the manipulation of the ECBS offers a potential approach to the treatment of AD.
As of 29 August 2023, a total of 89,596 confirmed cases of Mpox (monkeypox) have been documented across 114 countries worldwide, with 157 reported fatalities. The Mpox outbreak that transpired in ...2022 predominantly affected young men who have sex with men (MSM). While most cases exhibited a mild clinical course, individuals with compromised immune systems, particularly those living with HIV infection and possessing a CD4 count below 200 cells/mm3, experienced a more severe clinical trajectory marked by heightened morbidity and mortality. The approach to managing Mpox is primarily symptomatic and supportive. However, in instances characterized by severe or complicated manifestations, the utilization of antiviral medications becomes necessary. Despite tecovirimat’s lack of official approval by the FDA for treating Mpox in humans, a wealth of positive clinical experiences exists, pending the outcomes of ongoing clinical trials. Brincidofovir and cidofovir have also been administered in select cases due to the unavailability of tecovirimat. Within the scope of this narrative review, our objective was to delve into the clinical attributes of Mpox and explore observational studies that shed light on the utilization of these antiviral agents.
This paper introduces the electronic interface for a capacitive airborne particle matter detector. The proposed circuit relies on two matched ring oscillators and a mixer to detect the frequency ...difference induced by the deposition of a particle onto an interdigitated capacitor, which constitutes the load of one of the oscillators. The output of the mixer is digitized through a simple counter. In order to compensate the oscillation frequency offset of the two ring oscillators due to process and mismatch variations, a capacitive trimming circuit has been implemented. The sensor is connected to host through an I2C interface for communication and configuration. The sensor has been implemented using a standard 130-nm CMOS technology by STMicroelectronics and occupies 0.12-mm
die area. Experimental measurements using talcum powder show a sensitivity of 60 kHz/fF and a 3σ resolution equal to 165 aF.
Investigating the driving forces leading to the formation of a specific supramolecular architecture among a wide spectrum of all the possibly obtainable structures is not an easy task. The ...contemporary literature provides several models for correctly predicting the thermodynamically accessible structures that can originate from a library of building blocks. Definitions are rigid by their very nature, so their application may sometimes require a shift in perspective. In the study presented herein, we describe the crystal structures of three metallo-supramolecular architectures assembled from deprotonated derivatives of 3,6,9-trioxaundecanedioic acid and Mn(II), Co(II) and Zn(II). In the Mn(II) case, the complexation resulted in a complex of a discrete/heptacoordinated nature, whereas the other two structures appeared as helical polymers. To explain such an anomaly, in this work, we describe how the interplay between the flexibility of the ligand spacer and the number of coordinating atoms involved determines the divergent or convergent organisation of the final coordination architecture.
Interest in co-crystals formation has been constantly growing since their discovery, almost a century ago. Such success is due to the ability to tune the physical-chemical properties of the ...components in solid state by avoiding a change in their molecular structure. The properties influenced by the co-crystals formation range from an improvement of mechanical features and chemical stability to different solubility. In the scientific research area, the pharmacological field is undoubtedly one of those in which an expansion of the co-crystal knowledge can offer wide benefits. In this work, we described the crystalline structure of hexamethylenetetramine co-crystallized with the isophthalic acid, and we compared it with another co-crystal, showing the same components but different stoichiometry. To give a wider overview on the nature of the interactions behind the observed crystal packing and to rationalize the reasons of its formation, a computational analysis on such structures was carried out.
In recent years, the possibility of favorably influencing the cognitive trajectory through promotion of lifestyle modifications has been increasingly investigated. In particular, the relationship ...between nutritional habits and cognitive health has attracted special attention. The present review is designed to retrieve and discuss recent evidence (published over the last 3 years) coming from randomized controlled trials (RCTs) investigating the efficacy of nutritional interventions aimed at improving cognitive functioning and/or preventing cognitive decline in non-demented older individuals. A systematic review of literature was conducted, leading to the identification of 11 studies of interest. Overall, most of the nutritional interventions tested by the selected RCTs were found to produce statistically significant cognitive benefits (defined as improved neuropsychological test scores). Nevertheless, the clinical meaningfulness of such findings was not adequately discussed and appears controversial. In parallel, only 2 studies investigated between-group differences concerning incident dementia and mild cognitive impairment cases, reporting conflicting results. Results of the present review suggest that several dietary patterns and nutritional components may constitute promising strategies in postponing, slowing, and preventing cognitive decline. However, supporting evidence is overall weak and further studies are needed.
Molnupiravir and Nirmatrelvir/r (NMV-r) have been proven to reduce severe Coronavirus Disease 2019 (COVID-19) in unvaccinated high-risk individuals. Data regarding their impact in fully vaccinated ...vulnerable subjects with mild-to-moderate COVID-19 are still limited, particularly in the era of Omicron and sub-variants.
Our retrospective study aimed to compare the safety profile and effectiveness of the two antivirals in all consecutive high-risk outpatients between 11 January and 10 July 2022. A logistic regression model was carried out to assess factors associated with the composite outcome defined as all-cause hospitalization and/or death at 30 days.
A total of 719 individuals were included: 554 (77%) received Molnupiravir, whereas 165 (23%) were NMV-r users. Overall, 43 all-cause hospitalizations (5.9%) and 13 (1.8%) deaths were observed at 30 days. A composite outcome occurred in 47 (6.5%) individuals. At multivariate analysis, male sex OR 3.785;
= 0.0021, age ≥ 75 OR 2.647;
= 0.0124, moderate illness OR 16.75;
< 0.001, and treatment discontinuation after medical decision OR 8.148;
= 0.0123 remained independently associated with the composite outcome.
No differences between the two antivirals were observed. In this real-life setting, the early use of both of the oral antivirals helped limit composite outcome at 30 days among subjects who were at high risk of disease progression.
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