Biocompatibility of micro- and nano-particles in the colon. Part II.

Pathological colonic tissues were investigated with an Environmental Scanning Electron Microscope technique to verify the presence of inorganic, non-biodegradable pollutants, i.e. micro- and nano-debris of exogenous origin, after debris in liver and kidney had been discovered. In all, 18 samples of colon tissues affected by cancer and Crohn's disease were evaluated and found in all the cases to contain micro- and nano-particles. Their chemistry, detected with an X-ray microprobe, indicated a heterogeneous nature, whereas the size of the particles was homogeneous. Three control samples of healthy, young, cadavers were analysed and showed the absence of debris within the normal, healthy colon mucosa. The study reveals the presence of particulate debris, generally considered as biocompatible, in pathological specimens of human colon. The findings suggest a possible link between the presence of such particles and the underlying pathology in the cases analysed

Particles in the Eluate from Double Filtration Plasmapheresis—A Case Study Using Field Emission Scanning Electron Microscopy/Energy-Dispersive X-ray Spectroscopy (FE-SEM/EDX)

Unwanted substances can be effectively removed from the blood using double-filtration plasmapheresis (DFPP). In our case study, we used field emission scanning electron microscopy/energy-dispersive X-ray analysis (FE-SEM-EDX) to examine if the eluate obtained by a specific type of DFPP (INUSpheresis with a TKM58 filter) contains nano- and microparticles and what chemical composition these particles have. We identified micro- and nanoparticles of various sizes and chemical composition, including microparticles high in the concentration of calcium, iron, silicon, aluminium and titanium. Furthermore, thread-like objects were identified. We discuss the possible origin of the particles and objects, their pathophysiological relevance and the potential of FE-SEM-EDX analysis of the eluate in terms of diagnostics and therapy for environmental medicine applications on patients. Keywords: double-filtration plasmapheresis; INUSpheresis; scanning electron microscopy/energy-dispersive X-ray analysis; FE-SEM-EDX; microparticle

In vivo diffuse correlation spectroscopy investigation of the ocular fundus

Diffuse correlation spectroscopy (DCS) measurements in vivo recorded from rabbits' ocular fundus are presented. Despite the complexity of these ocular tissues, we provide a clear and simple demonstration of the DCS abilities to analyze variations in physiological quantities of clinical interest. Indeed, the reported experimental activities demonstrate that DCS can reveal both choroidal-flow and temperature variations and detect nano- and microaggregates in ocular fundus circulation. Such abilities can be of great interest both in fundamental research and practical clinical applications. The proposed measuring system can be useful in: (a) monitoring choroidal blood flow variations, (b) determining the end-point for photo-dynamic therapy and transpupillary thermo therapy and, (c) managing the dye injection and determining an end-point for dye-enhanced photothrombosis. Moreover, it could allow both diagnoses when the presence of nano- and micro-aggregates is related to specific diseases and verifying the effects of nanoparticle injection in nanomedicine. Even though the reported results demonstrate the applicability of DCS to investigate ocular fundus, a detailed and accurate investigation of the limits of detection is beyond the scope of this article. \uc2\ua9 2013 Society of Photo-Optical Instrumentation Engineers

Intracellular heavy metal nanoparticle storage: progressive accumulation within lymph nodes with transformation from chronic inflammation to malignancy

A 25-year-old man had complained of sudden fever spikes for two years and his blood tests were within the normal range. In 1993, a surgical biopsy of swollen left inguinal lymph nodes was negative for malignancy, but showed reactive lymphadenitis and widespread sinus histiocytosis. A concomitant needle biopsy of the periaortic lymph nodes and a bone marrow aspirate were also negative. In 1994, after an emergency hospital admission because of a sport-related thoracic trauma, a right inguinal lymph node biopsy demonstrated Hodgkin’s lymphoma Stage IVB (scleronodular mixed cell subtype). Although it was improved by chemotherapy, the disease suddenly relapsed, and a further lymph node biopsy was performed in 1998 confirming the same diagnosis. Despite further treatment, the patient died of septic shock in 2004, at the age of 38 years. Retrospective analysis of the various specimens showed intracellular heavy metal nanoparticles within lymph node, bone marrow, and liver samples by field emission gun environmental scanning electron microscopy and energy dispersive spectroscopy. Heavy metals from environmental pollution may accumulate in sites far from the entry route and, in genetically conditioned individuals with tissue specificity, may act as cofactors for chronic inflammation or even malignant transformation. The present anecdotal report highlights the need for further pathologic ultrastructural investigations using serial samples and the possible role of intracellular nanoparticles in human disease

Sarcoidosis in a dental surgeon: a case report

<p>Abstract</p> <p>Introduction</p> <p>Although the causes of sarcoidosis are still unknown, past and current studies have provided evidence that this disease may be associated with occupational exposure to specific environmental agents. We describe a case of sarcoidosis in a dental surgeon with long exposure to inorganic dusts. To the best of our knowledge, this is the first report of this kind in the literature.</p> <p>Case presentation</p> <p>At the beginning of 2000, a 52-year-old Caucasian man, who worked as a dental surgeon, presented with shortness of breath during exercise, cough and retrosternal pain. After diagnosis of sarcoidosis, a scanning electronic microscopy with X-ray microanalysis of biopsy specimens was used in order to determine whether the disease could be traced to an occupational environmental agent. Results showed the presence of inorganic dust particles within sarcoidotic granulomas, and demonstrated that the material detected was identical to that found in a powder used by our patient for several years.</p> <p>Conclusions</p> <p>Although these results cannot be considered as definitive proof, they do however provide strong evidence that this disease may be associated with material used by dental surgeons.</p

Interfacial Morphology Addresses Performance of Perovskite Solar Cells Based on Composite Hole Transporting Materials of Functionalized Reduced Graphene Oxide and P3HT

The development of novel hole transporting materials (HTMs) for perovskite solar cells (PSCs) that can enhance device's reproducibility is a largely pursued goal, even to the detriment of a very high efficiency, since it paves the way to an effective industrialization of this technology. In this work, we study the covalent functionalization of reduced graphene oxide (RGO) flakes with different organic functional groups with the aim of increasing the stability and homogeneity of their dispersion within a poly(3-hexylthiophene) (P3HT) HTM. The selected functional groups are indeed those recalling the two characteristic moieties present in P3HT, i.e., the thienyl and alkyl residues. After preparation and characterization of a number of functionalized RGO@P3HT blends, we test the two containing the highest percentage of dispersed RGO as HTMs in PSCs and compare their performance with that of pristine P3HT and of the standard Spiro-OMeTAD HTM. Results reveal the big influence of the morphology adopted by the single RGO flakes contained in the composite HTM in driving the final device performance and allow to distinguish one of these blends as a promising material for the fabrication of highly reproducible PSCs

Ultrastructural detection of environmental nanoparticles in circulating blood

The increase in the incidence of acute myeloid leukemia (AML) may suggest a possible environmental etiology. PM2.5 was declared by the International Agency for Research on Cancer (WHO organ) a Class I carcinogen. To date, no reports have focused on particulate environmental pollution together with AML. The study investigated the presence and composition of particulate matter in circulating blood with a Environmental Scanning Electron Microscope coupled with an Energy Dispersive Spectroscope for the elemental analysis of the samples. 38 peripheral blood samples, 19 AML cases and 19 healthy controls, were analysed. A significant overload of particulate matter-derived nanoparticles linked or aggregated to blood components was found in AML patients, while almost absent in matched healthy controls. Two tailed Student’s t-test, MANOVA and Principal Component Analysis indicated that the total numbers of aggregates and particles were statistically different between cases and controls (MANOVA,

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage