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In this study, the instantaneous collection efficiency and pressure drop of an N95 facemask is numerically simulated in a setting similar (but not identical) to that used by NIOSH to certify N95 respirators. More specifically, a CPU-friendly macroscale model is developed, for the first time, to simulate the performance of an electrostatically-charged facemask when the mask is clean and when it is loaded with neutral or neutralized nanoparticles. The simulations were performed using ANSYS software enhanced with in-house subroutines, and they were calibrated using the experimental data reported in the literature for the initial efficiency of N95 masks. In addition, a correction factor was developed for the Kozeny-Carman permeability equation to expand its application to the case of nanoparticle-deposits, where the dendrites porosity is very high and the aerodynamic slip is expected to occur. Copyright © 2023 American Association for Aerosol Research [ABSTRACT FROM AUTHOR]

This paper reports on a computational study about the impact of fiber dipole orientation on particle collection efficiency of a bipolarly charged filter. The simulations were carried out using ANSYS software in a series of 2-D geometries comprised of randomly distributed fibers. The simulations were enhanced with in-house subroutines to incorporate Coulomb and dielectrophoretic forces in calculating particle trajectories and thereby simulating filter efficiency. The highest and lowest efficiencies were observed for dipole orientations that were perpendicular and parallel to the airflow direction, respectively. The simulation results were also compared with the predictions of the popular semi-empirical correlations from the literature and good general agreement was observed, without the need for any empirical correction factors. In addition, it was observed that the predictions of the semi-empirical correlations better agreed with the simulation results obtained for media comprised of fibers with random dipole orientations when challenged with neutralized particles. [Display omitted] • Electrostatic particle filtration was modeled from the first principles. • Filter media was modeled as disordered arrangement of fibers in 2-D. • Simulation results compared very well with experimental correlations. • Importance of fiber dipole orientation was highlighted. • Best experimental agreement was for media with random dipole orientation. [ABSTRACT FROM AUTHOR]

This study presents a microscale simulation method that allows one to study the impact of particle loading on the aerosol capture efficiency of an electrostatically charged filter. This was done by considering a bipolarly charged fiber loaded with different amounts of neutral and charged particles with a diameter of 300 nm. The simulations predicted the deposition pattern of the aerosol particles as well as their impact on the electrostatic field of the bipolar fiber. The particle-loaded fiber was then challenged with aerosol particles in the range of 50 nm to 1 μm and with different charge polarities to study how the electrostatic field of the deposited particles interacts with that of the fiber to attract or repel the incoming airborne particles. More specifically, our simulations revealed that particle deposition can enhance the capture efficiency of a bipolar fiber when it is challenged with small particles (smaller than about 400 nm) regardless of the charge polarity of the airborne or deposited particles. The numerical simulations reported in this paper were conducted using the ANSYS CFD code enhanced with in-house subroutines to superimpose the electrostatic field of the deposited particles to that of the bipolar fiber and to include Brownian, polarization, and Coulomb forces in particle trajectory calculations. [Display omitted] • Simulated the electrostatic field around a particle-loaded corona-charged fiber. • Demonstrated the impact of particles' electrostatic field on fiber's capture efficiency. • Discussed the effects of fiber polarity on particle loading. • Demonstrated agreement between simulation results and experimental observations. [ABSTRACT FROM AUTHOR]

The human T cell leukemia/lymphoma virus (HTLV-I) is the etiologic agent of adult T cell leukemia (ATL). CD4+ lymphocytes are the preferential targets of infection, even though other cell types can be infected in vitro by the virus. Although ATL cells show CD3 and CD4 surface markers, some ATL-derived cell lines were reported to express also myeloid antigens. In order to analyze possible phenotypic changes induced by HTLV-I after infection of human lymphocytes, CD4+ cells were isolated from peripheral blood of three healthy donors, by separation through immunomagnetic beads. CD4+ lymphocytes were then infected by coculture with irradiated HTLV-I producing MT-2 cells. The phenotypic profile of infected cells was studied by flow cytometric analysis using monoclonal antibodies against lymphoid (CD3, CD4, TCR alpha/beta) and myelomonocitic markers (CD13, CD14, CD15, CD33, CD34). The results show that HTLV-I immortalized cell lines coexpressed CD13, CD33 and lymphoid markers. No expression of CD14, CD15 and CD34 was observed. These data suggest that the presence of both myeloid and lymphoid phenotype in HTLV-I infected T cells is the results of an induction rather than a selection mechanism. [ABSTRACT FROM AUTHOR]

Nemaline rod myopathy (NM) is a rare form of congenital myopathy characterized by slowly progressive or nonprogressive muscle weakness and pathognomonic rod-like structures within the muscle fibers. To the best of our knowledge, this is first documentation of the clinicopathological features of this rare entity from India. All cases of NM diagnosed in our laboratory were retrieved. Clinical and pathological features were reviewed. During a period of 1.5 years (Jan 2004 to June 2005), we received 750 muscle biopsies for various reasons. Of which, 15 were diagnosed as congenital myopathies and four as nemaline rod myopathies. Thus, NM comprises 0.53% of all muscle diseases and 22.6% of all congenital myopathies. All of them presented in childhood (first five years of life) with generalized hypotonia, feeding problems, repeated respiratory infections and muscle weakness. Both males and females were equally affected. The CPK levels were normal and EMG was myopathic. Microscopic examination revealed minimal changes but characteristic red-colored material was seen on modified Gomori trichrome staining which was immunopositive to alpha actinin. Ultrastructural examination confirmed this material to be nemaline rods. NM, although a rare form of congenital myopathies, should be suspected in children who present with generalized hypotonia, repeated chest infections and slowly progressive muscle weakness. This report highlights the importance of histochemistry and ultrastructural examination in the diagnosis of this entity, in the absence of the availability of methodology for genetic studies. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF)-A, placenta growth factor (PlGF) and their corresponding membrane receptors are involved in autocrine and paracrine regulation of melanoma growth and metastasis. Besides the membrane receptors, a soluble form of the VEGF receptor (VEGFR)-1 (sVEGFR-1) has been identified, that behaves both as a decoy receptor, sequestering VEGF-A and PlGF, and as an extracellular matrix (ECM) molecule, promoting endothelial cell adhesion and migration through the interaction with α5β1 integrin. To analyse whether sVEGFR-1 plays a role during melanoma progression. sVEGFR-1 expression was evaluated in a panel of 36 melanoma cell lines and 11 primary human melanocyte cultures by quantitative real-time polymerase chain reaction analysis and in specimens of primary or metastatic melanoma lesions from 23 patients by immunohistochemical analysis. sVEGFR-1 expression was highly upregulated in melanoma cell lines with respect to human melanocytes. Interestingly, cell lines obtained from cutaneous metastases showed a significant reduction of sVEGFR-1 expression, as compared with cell lines derived from primary tumours. These results were confirmed by immunohistochemical analysis of sections from primary skin melanomas and the corresponding cutaneous metastases, suggesting that modulation of sVEGFR-1 expression influences ECM invasion by melanoma cells and metastasis localization. Moreover, we provide evidence that adhesion of melanoma cells to sVEGFR-1 is favoured by the activation of a VEGF-A/VEGFR-2 autocrine loop. Our data strongly suggest that sVEGFR-1 plays a role in melanoma progression and that low sVEGFR-1/VEGF-A and sVEGFR-1/transmembrane VEGFR-1 ratios might predict a poor outcome in patients with melanoma. [ABSTRACT FROM AUTHOR]

A significant proportion of human cancers overexpress DNA polymerase beta (Pol β), the major DNA polymerase involved in base excision repair. The underlying mechanism and biological consequences of overexpression of this protein are unknown. We examined whether Pol β, expressed at levels found in tumor cells, is involved in the repair of DNA damage induced by oxaliplatin treatment and whether the expression status of this protein alters the sensitivity of cells to oxaliplatin. DNA damage induced by oxaliplatin treatment of HCT116 and HT29 colon cancer cells was observed to be associated with the stabilization of Pol β protein on chromatin. In comparison with HCT116 colon cancer cells, isogenic oxaliplatin-resistant (HCT-OR) cells were found to have higher constitutive levels of Pol β protein, faster in vitro repair of a DNA substrate containing a single nucleotide gap and faster repair of 1,2-GG oxaliplatin adduct levels in cells. In HCT-OR cells, small interfering RNA knockdown of Pol β delayed the repair of oxaliplatin-induced DNA damage. In a different model system, Pol β-deficient fibroblasts were less able to repair 1,2-GG oxaliplatin adducts and were hypersensitive to oxaliplatin treatment compared with isogenic Pol β-expressing cells. Consistent with previous studies, Pol β-deficient mouse fibroblasts were not hypersensitive to cisplatin treatment. These data provide the first link between oxaliplatin sensitivity and DNA repair involving Pol β. They demonstrate that Pol β modulates the sensitivity of cells to oxaliplatin treatment. [ABSTRACT FROM AUTHOR]

Background The chromosome 9p21 and its CDKN locus, with the p16 tumour suppressor gene ( CDKN2A), are recognized as the genomic regions involved in the pathogenesis of melanoma. Objectives To elucidate further the role of such regions during the different phases of melanocytic tumorigenesis. Methods Tissue sections from naevi, primary and metastatic melanomas were investigated by fluorescence in situ hybridization for allelic loss at the 9p21 chromosome and by immunochemistry for p16CDKN2A expression. Results Dysplastic naevi and primary or secondary melanomas were found to carry hemizygous deletions within the entire 9p21 region at similar frequencies (varying from 55% to 62%). Allelic deletion spanning the CDKN locus was observed at significantly increased rates moving from early (7%) to advanced (28%) primary melanomas and to secondary melanoma lesions (37%) ( P = 0·018). Also, inactivation of the p16 gene ( CDKN2A) was absent in naevi and present at steadily increasing rates moving from primary melanomas (7% early lesions to 17% advanced lesions) to melanoma metastases (62%) ( P = 0·004). Conclusions Our findings indicate that, in a model of sequential accumulation of genetic alterations, 9p21 deletions may play a role in melanocytic transformation and tumour initiation whereas rearrangements at the CDKN locus, and p16 gene ( CDKN2A) inactivation may contribute to tumour progression. [ABSTRACT FROM AUTHOR]

Abstract: Anti-tumour activity of triazene compounds of clinical interest [i.e. dacarbazine and temozolomide (TMZ)] relies mainly on the generation of methyl adducts to purine bases of DNA. Two DNA repair enzyme systems, i.e. the O6-guanine-alkyl-transferase (MGMT) and mismatch repair (MMR), play a predominant role in conditioning the cytotoxic effects of triazenes. In particular, high levels of MGMT associated with target cells are responsible of resistance to triazenes. On the contrary, the presence of MMR is required for the cytotoxic effects of these compounds. Previous studies performed by our group and a more recent clinical investigation reported by Karen Seiter, pointed out that triazene compounds could play an important role in the treatment of refractory acute leukaemia. Leukaemia blasts, especially of lymphoblastic leukaemia, show frequently high levels of MGMT activity. Therefore, it reasonable to hypothesize that combined treatment of leukaemia patients with triazene compounds along with MGMT inhibitors could lead to a better control of the disease. PaTrin-2 (O6-(4-bromothenyl)guanine, PAT) is a potent and scarcely toxic MGMT inhibitor recently introduced in clinical trials. This drug is used in combination with triazene compounds in order to augment their anti-tumour efficacy against neoplastic cells endowed with high MGMT activity. The present report describes, for the first time, pre-clinical in vitro studies on the cytotoxic activity of combined treatment with PAT+TMZ against long-term cultured leukaemia cells and primary leukaemia blasts obtained from patients with acute lymphoblastic leukaemia or acute myeloblastic leukaemia. The results point out that, both in long-term cultured leukaemia cell lines and in primary blast samples, PAT could improve dramatically the sensitivity of malignant cells to the cytotoxic effects of TMZ. This sensitizing effect is detectable when leukaemia cells show resistance mechanisms based on a MGMT-proficient phenotype. On the contrary, when resistance to TMZ is dependent on MMR deficiency, no influence of PAT can be detected in various experimental conditions. In conclusion, these results appear to provide disease-oriented rational basis to design novel clinical protocols for the treatment of acute leukaemia with combined administration of PAT and triazene compounds. [Copyright &y& Elsevier]

The article presents the clinical diagnosis of a seventy-year old man with an itchy plaque over the chest. The detailed medical history of the patient is being given. He had taken arsenic carcinogens for therapy and medical personnel believe it had a negative effect since these carcinogens can lead to cancers of the skin and internal organs.