ASSESSMENT OF HUMAN EXPOSURE TO TOLUENE DIISOCYANATE

Assessment of human exposure to toluene diisocyanate. Toluene diisocyanate (TDI), an aromatic compound, may be dangerous for human health. Diisocyanates have wide industrial use in the fabrication of flexible and rigid foams, fibers, elastomers, and coatings such as paints and varnishes. Isocyanates are known skin and respiratory sensitizers, and proper engineering controls should be in place to prevent exposure to isocyanate liquid and vapor; exposure to TDI vapors is well documented to increase asthma risk. The study focused on the exposure of workers and nearby populations to toluene diisocyanate in a Polyurethane Foam Factory located in Baia Mare, Romania. Workplace air measurements were performed in different departments of the plant, after sampling either in fixed points or as personal monitoring. Sampling in four different locations of Baia Mare town was carried out, - during and after the foaming process. TDI sampling was performed on silica cartridge followed by GC-MS analysis. TDI concentration at workplace was lower than 0,035 mg/m³, which represents the permissible exposure limit, while in the city the TDI concentration had shown values below 0,20 μg/m³. Health assessment of a group of 49 workers was based on questionnaire interview, determination of TDI antibodies and lung function tests. Data collected until this stage do not show any negative effects of TDI on the employees health. Since this plant had only recently begun operating, continuous workplace and ambient air TDI monitoring, along with workers health surveillance, is deemed necessary

SARS-CoV-2 Variant Surveillance in Genomic Medicine Era

In the genomic medicine era, the emergence of SARS-CoV-2 was immediately followed by viral genome sequencing and world-wide sequences sharing. Almost in real-time, based on these sequences, resources were developed and applied around the world, such as molecular diagnostic tests, informed public health decisions, and vaccines. Molecular SARS-CoV-2 variant surveillance was a normal approach in this context yet, considering that the viral genome modification occurs commonly in viral replication process, the challenge is to identify the modifications that significantly affect virulence, transmissibility, reduced effectiveness of vaccines and therapeutics or failure of diagnostic tests. However, assessing the importance of the emergence of new mutations and linking them to epidemiological trend, is still a laborious process and faster phenotypic evaluation approaches, in conjunction with genomic data, are required in order to release timely and efficient control measures

Chromophobe renal cell carcinoma with massive sarcomatoid differentiation

Chromophobe renal cell carcinoma (CRCC) is a distinct subtype of renal cell carcinoma with unique histological, immunohistochemical, cytogenetic, and ultrastructural features, which usually has a favorable clinical course, with only a small percentage of patients developing recurrence, metastasis, or death due to its complications. Sarcomatoid differentiation can occur in any subtype of renal cell carcinoma and currently represents the transformation into a higher degree of malignancy, its presence being associated with a reserved prognosis, with a reported incidence of average survival of less than 1 year after diagnosis. In this study, we present an unusual case of CRCC with massive sarcomatoid differentiation, which infiltrated the left adrenal gland and was surgically resected. The histological features of this tumor as well as a brief review of literature are presented

Radiotherapy and Immunotherapy, Combined Treatment for Unresectable Mucosal Melanoma with Vaginal Origin

Gynecologic melanomas are uncommon and malignant mucosal melanomas with vaginal origin are extremely rare, treatment strategies are limited and extrapolated from those of cutaneous melanoma. A better understanding of the vulvovaginal melanoma’s biology and its risk factors is needed. Therapeutic strategies include surgery, systemic therapy and radiotherapy. For vulvovaginal melanoma, surgery is selected as the primary treatment. Immunotherapy and target treatment have recently enhanced the systemic therapy for cutaneous melanoma (CM). Immunotherapy and new target agents demonstrated a better survival of melanoma and might be considered as treatment of vulvovaginal melanoma. Radiotherapy is included in the therapeutic arsenal for mucosal melanoma and may be performed on selected patients who may receive concurrent checkpoints and inhibition neoadjuvant radiotherapy with the purpose of reducing morbidity and mortality

Radiotherapy and Immunotherapy, Combined Treatment for Unresectable Mucosal Melanoma with Vaginal Origin

Gynecologic melanomas are uncommon and malignant mucosal melanomas with vaginal origin are extremely rare, treatment strategies are limited and extrapolated from those of cutaneous melanoma. A better understanding of the vulvovaginal melanoma’s biology and its risk factors is needed. Therapeutic strategies include surgery, systemic therapy and radiotherapy. For vulvovaginal melanoma, surgery is selected as the primary treatment. Immunotherapy and target treatment have recently enhanced the systemic therapy for cutaneous melanoma (CM). Immunotherapy and new target agents demonstrated a better survival of melanoma and might be considered as treatment of vulvovaginal melanoma. Radiotherapy is included in the therapeutic arsenal for mucosal melanoma and may be performed on selected patients who may receive concurrent checkpoints and inhibition neoadjuvant radiotherapy with the purpose of reducing morbidity and mortality

Evaluation of Oxidative Stress Biomarkers, Pro-Inflammatory Cytokines, and Histological Changes in Experimental Hypertension, Dyslipidemia, and Type 1 Diabetes Mellitus

The present study aims to compare the oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes induced by three cardiovascular risk factors, namely, hypertension, dyslipidemia, and type 1 diabetes mellitus. Hypertension was induced with 40 mg/kg body weight (b.w.) of N omega-nitro-L-arginine-methyl (L-NAME) administered orally. Dyslipidemia was induced by the administration of a diet with a high cholesterol (2%) content. Diabetes mellitus was induced by intraperitoneal administration of a single dose of streptozocin (65 mg/kg). Malondialdehyde (MDA) and total oxidative status (TOS) are increased by all three cardiovascular risk factors (up to 207%). The indirect assessment of NO synthesis (NOx) is observed to be reduced after L-NAME administration (43%), and dyslipidemia induction (16%), while type 1 diabetes mellitus is associated with the highest levels of NOx (increased 112%). Hypertension, dyslipidemia, and type 1 diabetes reduced the total antioxidative capacity (TAC) and total thiol (SH) levels (up to 57%). The values of evaluated pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), assessed from the ascending aorta were elevated by all three cardiovascular risk factors, with the highest levels induced by type 1 diabetes mellitus (up to 259%). The histopathological examination of the ascending and descending aorta revealed reversible pro-atherogenic changes consisting of the accumulation of lipid droplets in the subendothelial connective tissue on rats with hypertension and dyslipidemia. Irreversible pro-atherogenic changes consisting of a reduction of the specific elasticity of the arteries were observed in rats with type 1 diabetes mellitus. Type 1 diabetes mellitus demonstrates an alteration of the oxidative stress parameters, the elevation of tissue levels of the pro-inflammatory cytokines and causing irreversible pro-atherogenic changes on the aortic wall

Assessment of Total Antioxidant Capacity, 8-Hydroxy-2′-deoxy-guanosine, the Genetic Landscape, and Their Associations in <i>BCR::ABL-1</i>-Negative Chronic and Blast Phase Myeloproliferative Neoplasms

Myeloproliferative neoplasms (MPNs), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal stem cell disorders defined by an excessive production of functionally mature and terminally differentiated myeloid cells. MPNs can transform into secondary acute myeloid leukemia (sAML/blast phase MPN) and are linked to alterations in the redox balance, i.e., elevated concentrations of reactive oxygen species and markers of oxidative stress (OS), and changes in antioxidant systems. We evaluated OS in 117 chronic phase MPNs and 21 sAML cases versus controls by measuring total antioxidant capacity (TAC) and 8-hydroxy-2′-deoxy-guanosine (8-OHdG) concentrations. TAC was higher in MPNs than controls (p = 0.03), particularly in ET (p = 0.04) and PMF (p = 0.01). MPL W515L-positive MPNs had higher TAC than controls (p = 0.002) and triple-negative MPNs (p = 0.01). PMF patients who had treatment expressed lower TAC than therapy-free subjects (p = 0.03). 8-OHdG concentrations were similar between controls and MPNs, controls and sAML, and MPNs and sAML. We noted associations between TAC and MPNs (OR = 1.82; p = 0.05), i.e., ET (OR = 2.36; p = 0.03) and PMF (OR = 2.11; p = 0.03), but not sAML. 8-OHdG concentrations were not associated with MPNs (OR = 1.73; p = 0.62) or sAML (OR = 1.89; p = 0.49). In conclusion, we detected redox imbalances in MPNs based on disease subtype, driver mutations, and treatment history

Kinetics and persistence of cellular and humoral immune responses to SARS-CoV-2 vaccine in healthcare workers with or without prior COVID-19

SARS-CoV-2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS-CoV-2 infection. No new infections were diagnosed during follow-up. At 6 months, post-vaccination or post-infection, despite a downward trend in the level of anti-S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live-virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow-up in persons vaccinated after prior infection. Anti-S IgA levels showed a significant descending trend in vaccinated subjects (p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1-3) or low neutralizing activity (30%-40%) at 6 months, although with lower T-cell stimulation index (p = 0.046) and IFN-γ secretion (p = 0.0007) compared to those with preserved humoral responses.1293130513EU Horizon 202