Spectroscopic diagnosis and metabolite characterization of cisplatin resistance regulated by FDFT1 in bladder cancer tissue.

As is the case for most solid tumours, chemotherapy remains the backbone in the management of metastatic disease. However, the occurrence of chemotherapy resistance is a cause to worry, especially in bladder cancer. Extensive evidence indicates molecular changes in bladder cancer cells to be the underlying cause of chemotherapy resistance, including the reduced expression of farnesyl-diphosphate farnesyltransferase 1 (FDFT1) - a gene involved in cholesterol biosynthesis. This can likely be a hallmark in examining the resistance and sensitivity of chemotherapy drugs. This work performs spectroscopic analysis and metabolite characterization on resistant, sensitive, stable-disease and healthy bladder tissues. Raman spectroscopy has detected peaks at around 1003 cm-1 (squalene), 1178 cm-1 (cholesterol), 1258 cm-1 (cholesteryl ester), 1343 cm-1 (collagen), 1525 cm-1 (carotenoid), 1575 cm-1 (DNA bases) and 1608 cm-1 (cytosine). The peak parameters were examined, and statistical analysis was performed on the peak features, attaining significant differences between the sample groups. Small-angle x-ray scattering (SAXS) measurements observed the triglyceride peak together with 6th, 7th and 8th - order collagen peaks; peak parameters were also determined. Neutron activation analysis (NAA) detected seven trace elements. Carbon (Ca), magnesium (Mg), chlorine (Cl) and sodium (Na) have been found to have the greatest concentration in the sample groups, suggestive of a role as a biomarker for cisplatin resistance studies. Results from the present research are suggested to provide an important insight into understanding the development of drug resistance in bladder cancer, opening up the possibility of novel avenues for treatment through personalised interventions.

Exploring measurement tools to optimise hospital physician distribution.

INTRODUCTION: Equitable healthcare delivery is essential and requires resources to be distributed, which include assets and healthcare workers. To date, there is no gold standard for measuring the correct number of physicians to meet healthcare needs. This rapid review aims to explore measurement tools employed to optimise the distribution of hospital physicians, with a focus on ensuring fair resource allocation for equitable healthcare delivery. MATERIALS AND METHODS: A literature search was performed across PubMed, EMBASE, Emerald Insight and grey literature sources. The key terms used in the search include 'distribution', 'method', and 'physician', focusing on research articles published in English from 2002 to 2022 that described methods or tools to measure hospital-based physicians' distribution. Relevant articles were selected through a two-level screening process and critically appraised. The primary outcome is the measurement tools used to assess the distribution of hospital-based physicians. Study characteristics, tool advantages and limitations were also extracted. The extracted data were synthesised narratively. RESULTS: Out of 7,199 identified articles, 13 met the inclusion criteria. Among the selected articles, 12 were from Asia and one from Africa. The review identified eight measurement tools: Gini coefficients and Lorenz curve, Robin Hood index, Theil index, concentration index, Workload Indicator of Staffing Need method, spatial autocorrelation analysis, mixed integer linear programming model and cohortcomponent model. These tools rely on fundamental data concerning population and physician numbers to generate outputs. Additionally, five studies employed a combination of these tools to gain a comprehensive understanding of physician distribution dynamics. CONCLUSION: Measurement tools can be used to assess physician distribution according to population needs. Nevertheless, each tool has its own merits and limitations, underscoring the importance of employing a combination of tools. The choice of measuring tool should be tailored to the specific context and research objectives.

EDXRF and the relative presence of K, Ca, Fe and as in amyloidogenic tissues.

Trace and minor elements play crucial roles in a variety of biological processes, including amyloid fibrils formation. Mechanisms include activation or inhibition of enzymatic reactions, competition between elements and metal proteins for binding positions, also changes to the permeability of cellular membranes. These may influence carcinogenic processes, with trace and minor element concentrations in normal and amyloid tissues potentially aiding in cancer diagnosis and etiology. With the analytical capability of the spectroscopic technique X-ray fluorescence (XRF), this can be used to detect and quantify the presence of elements in amyloid characterization, two of the trace elements known to be associated with amyloid fibrils. In present work, involving samples from a total of 22 subjects, samples of normal and amyloid-containing tissues of heart, kidney, thyroid, and other tissue organs were obtained, analyzed via energy-dispersive X-ray fluorescence (EDXRF). The elemental distribution of potassium (K), calcium (Ca), arsenic (As), and iron (Fe) was examined in both normal and amyloidogenic tissues using perpetual thin slices. In amyloidogenic tissues the levels of K, Ca, and Fe were found to be less than in corresponding normal tissues. Moreover, the presence of As was only observed in amyloidogenic samples; in a few cases in which there was an absence of As, amyloid samples were found to contain Fe. Analysis of arsenic in amyloid plaques has previously been difficult, often producing contradictory results. Using the present EDXRF facility we could distinguish between amyloidogenic and normal samples, with potential correlations in respect of the presence or concentration of specific elements.

Epithelial-mesenchymal transition profiles in triple negative breast carcinoma may explain its aggressive nature.

Epithelial-mesenchymal transition (EMT) is increasingly explored in cancer progression. Considering that triple negative (TN) breast cancer has the poorest survival among molecular subtypes, we investigated 49 TN, 45 luminal and 25 HER2-enriched female breast carcinomas for EMT expression (using E-cadherin and vimentin immunohistochemistry) against lymphovascular and/or lymph node invasion. E-cadherin and vimentin expressions were semi-quantitated for positive- cancer cells (0=0-<1%, 1=1-10%, 2 =11-50%, 3=>50%) and staining intensity (0=negative, 1=weak, 2=moderate, 3=strong), with final score (low=0-4 and high=6-9) derived by multiplying percentage and intensity scores for each marker. Low E-cadherin and/or high vimentin scores defined EMT positivity. Low E-cadherin co-existing with high vimentin defined "complete" (EMT-CV), while low E-cadherin (EMT-C) or high vimentin (EMT-V) occurring independently defined "partial" subsets. 38 (31.9%) cancers expressed EMT, while 59.2 % TN, 13.3% luminal and 12% HER2-enriched cancers expressed EMT (p<0.05). Among the cancers with lymphovascular and/or lymph node invasion, EMT positivity by molecular types were 66.7% TN, 7.4% luminal and 11.8% HER2-enriched (p<0.05). Although EMT-V, associated with stem-cell properties was the dominant TN EMT profile, EMT-CV, a profile linked to vascular metastases, was encountered only in TN. EMT appears important in TN cancer and different EMT profiles may be associated with its aggressive nature.

Carbon rich media for luminescence-based surface dosimetry and study of associated surface defects.

The present study continues research into the utilisation of carbonaceous media for medical radiation dosimetry, focusing on the effects of surface area-to-volume ratio and carbon content on structural interaction alterations and dosimetric properties in sheet- and bead-type graphitic materials (with the respective carbon content of ∼98 wt% and ∼90 wt%). Using 60Co gamma-rays and doses from 0.5 Gy to 20 Gy, the study has been made of the response of commercially available graphite in the form of 0.1 mm, 0.2 mm, 0.3 mm and 0.5 mm thick sheets, also of activated carbon beads. Confocal Raman and photoluminescence spectroscopy have been employed, examining radiation-induced structural interaction alterations. Dose-dependent variation in the Raman intensity ratio ID/IG relates to the varying dominance of defect generation and dose-driven defect annealing. Of the various thickness graphite sheets, the 0.1 mm thick medium possesses the greatest surface area-to-volume ratio. Perhaps unsurprisingly, it also exhibits the greatest thermoluminescence (TL) yield compared to that of the other carbonaceous sheet foils used herein. Moreover, the second greatest mass-normalised TL yield has been observed to be that of the porous beads, reflected in the greater defect density (ID/IG > 2) when compared to the other media, due in part to their inherent feature of large internal surface area. Considering the challenge posed in matching skin thickness with skin dose, the near tissue equivalent graphite sheets show particular promise as a skin dosimeter, sensitive as a function of depth.

Distinct Lipid Phenotype of Cancer-Associated Fibroblasts (CAFs) Isolated From Overweight/Obese Endometrial Cancer Patients as Assessed Using Raman Spectroscopy.

Obesity is strongly linked with increased risk and poorer prognosis of endometrial cancer (EC). Cancer-associated fibroblasts (CAFs) are activated fibroblasts that form a large component of the tumor microenvironment and undergo metabolic reprogramming to provide critical metabolites for tumor growth. However, it is still unknown how obesity, characterized by a surplus of free fatty acids drives the modifications of CAFs lipid metabolism which may provide the mechanistic link between obesity and EC progression. The present study aims to evaluate the utility of Raman spectroscopy, an emerging nondestructive analytical tool to detect signature changes in lipid metabolites of CAFs from EC patients with varying body mass index. We established primary cultures of fibroblasts from human EC tissues, and CAFs of overweight/obese and nonobese women using antibody-conjugated magnetic beads isolation. These homogeneous fibroblast cultures expressed fibroblast markers, including α-smooth muscle actin and vimentin. Analysis was made in the Raman spectra region best associated with cancer progression biochemical changes in lipids (600-1800 cm-1 and 2800-3200 cm-1). Direct band analysis and ratiometric analysis were conducted to extract information from the Raman spectrum. Present results demonstrated minor shifts in the CH2 symmetric stretch of lipids at 2879 cm-1 and CH3 asymmetric stretching from protein at 2932 cm-1 in the overweight/obese CAFS compared to nonobese CAFs, indicating increased lipid content and a higher degree of lipid saturation. Principal component analysis showed that CAFs from overweight/obese and nonobese EC patients can be clearly distinguished indicating the capability of Raman spectroscopy to detect changes in biochemical components. Our results suggest Raman spectroscopy supported by chemometric analysis is a reliable technique for characterizing metabolic changes in clinical samples, providing an insight into obesity-driven alteration in CAFs, a critical stromal component during EC tumorigenesis.

A review: Exploring the metabolic and structural characterisation of beta pleated amyloid fibril in human tissue using Raman spectrometry and SAXS.

Amyloidosis is a deleterious condition caused by abnormal amyloid fibril build-up in living tissues. To date, 42 proteins that are linked to amyloid fibrils have been discovered. Amyloid fibril structure variation can affect the severity, progression rate, or clinical symptoms of amyloidosis. Since amyloid fibril build-up is the primary pathological basis for various neurodegenerative illnesses, characterization of these deadly proteins, particularly utilising optical techniques have been a focus. Spectroscopy techniques provide significant non-invasive platforms for the investigation of the structure and conformation of amyloid fibrils, offering a wide spectrum of analyses ranging from nanometric to micrometric size scales. Even though this area of study has been intensively explored, there still remain aspects of amyloid fibrillization that are not fully known, a matter hindering progress in treating and curing amyloidosis. This review aims to provide recent updates and comprehensive information on optical techniques for metabolic and proteomic characterization of ß-pleated amyloid fibrils found in human tissue with thorough literature analysis of publications. Raman spectroscopy and SAXS are well established experimental methods for study of structural properties of biomaterials. With suitable models, they offer extended information for valid proteomic analysis under physiologically relevant conditions. This review points to evidence that despite limitations, these techniques are able to provide for the necessary output and proteomics indication in order to extrapolate the aetiology of amyloid fibrils for reliable diagnostic purposes. Our metabolic database may also contribute to elucidating the nature and function of the amyloid proteome in development and clearance of amyloid diseases.

Thermoluminescent characterization and defect studies of graphite-rich media under high dose neutron exposure.

Thermoluminescence (TL) materials have a broad variety of uses in various fields, such as clinical research, individual dosimetry, and environmental dosimetry, amongst others. However, the use of individual neutron dosimetry has been developing more aggressively lately. In this regard, present study establishes a relationship between the neutron dosage and the optical property changes of graphite-rich materials caused by high doses of neutron radiation. This has been done with the intention of developing a novel, graphite-based radiation dosimeter. Herein, the TL yield of commercially graphite-rich materials (i.e. graphite sheet, 2B and HB grade pencils) irradiated by neutron radiation with doses ranging from 250 Gy to 1500 Gy has been investigated. The samples were bombarded with thermal neutrons as well as a negligible amount of gamma rays, from the nuclear reactor TRIGA-II installed at the Bangladesh Atomic Energy Commission. The shape of the glow curves was observed to be independent of the given dosage, with the predominant TL dosimetric peak maintained within the region of 163 °C-168 °C for each sample. By studying the glow curves of the irradiated samples, some of the most well theoretical models and techniques were used to compute the kinetic parameters such as the order of kinetics (b), activation energy (E) or trap depth, frequency factor (s) or escape probability, and trap lifetime (τ). All of the samples were found to have a good linear response over the whole dosage range, with 2B grade of polymer pencil lead graphite (PPLGs) demonstrating a higher level of sensitivity than both HB grade and graphite sheet (GS) samples. Additionally, the level of sensitivity shown by each of them is highest at the lowest dosage that was given, and it decreases as the dose increases. Importantly, the phenomenon of dose-dependent structural modifications and internal annealing of defects has been observed by assessing the area of deconvoluted micro-Raman spectra of graphite-rich materials in high-frequency areas. This trend is consistent with the cyclical pattern reported in the intensity ratio of defect and graphite modes in previously investigated carbon-rich media. Such recurrent occurrences suggest the idea of employing Raman microspectroscopy as a radiation damage study tool for carbonaceous materials. The excellent responses of the key TL properties of the 2B grade pencil demonstrate its usefulness as a passive radiation dosimeter. As a consequence, the findings suggest that graphite-rich materials have the potential to be useful as a low-cost passive radiation dosimeter, with applications in radiotherapy and manufacturing.

Exploring NFκB pathway as a potent strategy to mitigate COVID-19 severe morbidity and mortality.

The pandemic of coronavirus disease 2019 (COVID-19), for which there does not appear to be an approved cure, the primary treatment options consist of non-pharmacological preventive measures and supportive treatment that are aimed at halting the progression of the disease. Nuclear factor kappa B (NFkB) presents a promising therapeutic opportunity to mitigate COVID-19-induced cytokine storm and reduce the risk of severe morbidity and mortality resulting from the disease. However, the effective clinical application of NFkB modulators in COVID-19 is hampered by a number of factors that must be taken into consideration. This paper therefore explored the modulation of the NFB pathway as a potential strategy to mitigate the severe morbidity and mortality caused by COVID-19. The paper also discusses the factors that form the barrier, and it offers potential solutions to the various limitations that may impede the clinical use of NFkB modulators against COVID-19. This paper revealed and identified three key potential solutions for the future clinical use of NFkB modulators against COVID-19. These solutions are pulmonary tissue-specific NFkB blockade, agents that target common regulatory proteins of both canonical and non-canonical NFkB pathways, and monitoring clinical indicators of hyperinflammation and cytokine storm in COVID-19 prior to using NFkB modulators.

Dosimetric characteristics of Gd-doped silica glass subjected to neutron and gamma irradiations.

The dosimetric characteristics of newly developed gadolinium (Gd) glass dosimeter produced via sol-gel method are reported. Irradiation were made using a 750 kW neutron flux thermal power and 1.25 MeV 60Co gamma rays with entrance doses from 2 to 10 Gy. Investigation has been done on various Gd dopant concentrations, ranging from 1 to 10 mol%. The Gd-doped silica glass have been characterised for thermoluminescence (TL) dose response, sensitivity, linearity index, glow curve and kinetic parameter analysis. For particular dopant concentration obtained in 6 mol% Gd, the least squares fit shows the change in TL yield, correlation coefficient (r2) of better than 0.980 (at 95% confidence level), with neutron and gamma exposure to be 8 and 4 times greater than that of 1 mol% Gd, respectively. Broad peaks in the absence of any sharp peak observed in the glow curve confirms the amorphous nature of the prepared glass. A glow curve of Gd-doped SiO2 sample is observed with a single prominent peak (Tm) within 200-250 °C (peak shifting appears with respect to the increment of dopant concentration) and 350 °C (for all respective Gd dopants) for neutron and gamma irradiations, respectively. Deconvolution shows the glow curves of the Gd-doped SiO2 glass to be formed of seven and five overlapping peaks, with figures of merit below 2% (FOM) of between 1.38-1.79 and 1.30-1.97 for the particular neutron and gamma irradiations, respectively. Through use of Glowfit deconvolution software, the key trapping parameters of activation energy, E and frequency factor, s-1 were calculated for the Gd-doped SiO2 glass. The mechanism of TL yield with the gradual increase in Gd concentrations and doses is explained upon the incorporation of Gd and radiation damage that change the structure of the electron traps in the glass matrix. These early results indicate that selectively screened Gd-SiO2 glass can be developed into a promising TL system towards dosimetric applications.

Low-cost commercial graphite-rich pencils subjected to electron irradiation for passive radiation dosimetry.

Various thicknesses of 2B grade polymer pencil lead graphite (PPLG) were used in the present study, which focussed on the alteration in crystalline lattice and the structural defect caused by the electron irradiation dosage ranging from 0.5 to 20 Gy delivered by an Elekta HD Linac. The fundamental trap parameters i.e. kinetics order (b), activation energy (E), and frequency factor (s) of the PPLG samples have been estimated using the initial rise and peak shape approaches by fitting the thermoluminescence (TL) glow peaks of the PPLG samples exposed to 20 Gy. The lifetime of the TL glow peak is also presented, which provides information on the stability of the TL signal at maximum temperatures. Raman, Photoluminescence (PL), and X-ray diffraction (XRD) spectra are being used to observe the structural changes that have occurred as a result of the radiation doses. These spectroscopies offer an understanding of the physical parameters that are related to the defects and taking part in the luminescence process. When all of the data are taken into account, it is anticipated that 0.3 mm PPLG is an effective material for dosimetry. The results of these lines of research are intended to educate the innovation of versatile graphite radiation dosimeters as a low-cost efficient system for radiation detection. The studied PPLG offers tissue equivalence as well as high spatial resolution, both are desirable criteria for a material to be used in the monitoring of ionising radiation or a variety of medical applications.

Studies of defect states and kinetic parameters of car windscreen for thermoluminescence retrospective dosimetry.

In case of any natural disasters or technical failures of nuclear facilities, the surrounding media including human beings may receive unexpected radiation exposures. In such a situation, there is no viable way to know how much radiation dose is received by human beings. Realizing that motorized vehicles are parked at fixed but increasing distances within the nuclear installation and industrial environment, this study investigates the kinetic parameters of readily available car windscreens which form the basis to be employed in post-accident dose reconstruction or for retrospective dosimetry. To understand the luminescence features of this crystalline media, a convenient thermoluminescence (TL) technique has been employed. Several well-defined theoretical models and methods were employed to calculate the kinetic parameters including the order of kinetics (b), activation energy (E) or trap depth, frequency factor (s) or escape probability and trap lifetime (τ), by analyzing the glow curves of the irradiated samples. The analysed trapping parameters indicate that the Toyota (E = 0.75-1.31 eV, s = 3.0E+6 - 3.7E+9 (s-1), τ = 6.9E+5 - 1.3E+14 s) and Honda (E = 0.95-1.68 eV, s = 2.1E+10 - 4.1E+13 (s-1), τ = 2.2E+9 - 3.1E+20 s) windscreen offer promising features for conventional TL dosimetry applications, while the obtained longer lifetime (τ = 6.8E+10 - 8.6E+29 s) or higher activation energy (E = 1.23-2.15 eV) for Proton brand windscreen indicates better stability or slow fading of the material, thus suitable for retrospective TL dosimetry. In addition, by assessing the area of deconvoluted micro-Raman spectra of windshield glasses in high-frequency regions, it has been observed the phenomenon of dose-dependent structural alterations and internal annealing of defects. This pattern is also consistent with those cyclical pattern observed in the intensity ratio of defect and graphite modes in the studies of carbon-rich media. Such common phenomena indicate the possibility of using the Raman microspectroscopy as a probe of radiation damage in silica-based media.

Spinal 5-HT2A receptor is involved in electroacupuncture inhibition of chronic pain.

Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, and it is a typical disease which can develop chronic pain. Our previous study has proved that endocannabinoid (2-AG)-CB1R-GABA-5-HT pathway is involved in electroacupuncture (EA) mediated inhibition of chronic pain. However, it is still unclear which among the 5-HT receptor subtype is involved in EA evoked 5-HT mediated inhibition of chronic pain in the dorsal spinal cord. 5-HT2A is a G protein-coupled receptor and it is involved in 5-HT descending pain modulation system. We found that EA treatment at frequency of 2 Hz +1 mA significantly increased the expression of 5-HT2A receptor in the dorsal spinal cord and intrathecal injection of 5-HT2A receptor antagonist or agonist reversed or mimicked the analgesic effect of EA in each case respectively. Intrathecal injection of a selective GABAA receptor antagonist Bicuculline also reversed the EA effect on pain hypersensitivity. Additionally, EA treatment reversed the reduced expression of GABAA receptor and KCC2 in the dorsal spinal cord of KOA mice. Furthermore, we demonstrated that intrathecal 5-HT2A receptor antagonist/agonist reversed or mimicked the effect of EA up-regulate of KCC2 expression, respectively. Similarly, intrathecal injection of PLC and PKC inhibitors prevented both anti-allodynic effect and up-regulation of KCC2 expression by EA treatment. Our data suggest that EA treatment up-regulated KCC2 expression through activating 5-HT2A-Gq-PLC-PKC pathway and enhanced the inhibitory function of GABAA receptor, thereby inhibiting chronic pain in a mouse model of KOA.

Correction: Tailored Ge-doped fibres for passive electron radiotherapy dosimetry.

[This corrects the article DOI: 10.1371/journal.pone.0235053.].

The potential of decorative building materials (marble) for retrospective thermoluminescence dosimetry.

Among the various types of decorative materials used in Bangladeshi dwellings, the marble/marble stone is one of the most common ones that used largely for enhancing the beauty and/or aristocracy of the dwelling environment. In this study, the most commonly used, six types of marble stones, have been analyzed for retrospective accident dosimetry. With the interest of characterizing several key thermoluminescence properties to examine their potentiality for dosimetry, annealing - irradiation - readout steps have been done chronologically which comprises the analysis of glow curves, relative sensitivity, dose dependence, repeatability and fading. Considering the various TL parameters, marble 'Carrara' imported from Italy present relatively better capability for reconstruction of radiation dose in the dose range of 10-50 Gy. From fading result, it is clear that for reconstruction of absorbed dose up to four weeks of post exposure, the marble 'Carrara' is found to be the most reliable media among the studied marble types. The Zeff values for the various marble samples are found to be in the range of 13.65-19.12, comparing favorably in replace of TLD-200 (Zeff = 16.3) which can be used for low-level environmental radiation dosimetry. Present work constitutes the first study to investigate the potentials of marble stone for reconstruction of absorbed dose in the range of 10-50 Gy dose.

Borosilicate glass 60Co high dose rate brachytherapy thermoluminescence dosimetry.

Brachytherapy is commonly used in treatment of cervical, prostate, breast and skin cancers, also for oral cancers, typically via the application of sealed radioactive sources that are inserted within or alongside the area to be treated. A particular aim of the various brachytherapy techniques is to accurately transfer to the targeted tumour the largest possible dose, at the same time minimizing dose to the surrounding normal tissue, including organs at risk. The dose fall-off with distance from the sources is steep, the dose gradient representing a prime factor in determining the dose distribution, also representing a challenge to the conduct of measurements around sources. Amorphous borosilicate glass (B2O3) in the form of microscope cover slips is recognized to offer a practicable system for such thermoluminescence dosimetry (TLD), providing for high-spatial resolution (down to < 1 mm), wide dynamic dose range, good reproducibility and reusability, minimal fading, resistance to water and low cost. Herein, investigation is made of the proposed dosimeter using a 1.25 MeV High Dose Rate (HDR) 60Co brachytherapy source, characterizing dose response, sensitivity, linearity index and fading. Analysis of the TL glow curves were obtained using the Tmax-Tstop method and first-order kinetics using GlowFit software, detailing the frequency factors and activation energy.

Indication of high lipid content in epithelial-mesenchymal transitions of breast tissues.

The epithelial-mesenchymal transition (EMT) is a crucial process in cancer progression and metastasis. Study of metabolic changes during the EMT process is important in seeking to understand the biochemical changes associated with cancer progression, not least in scoping for therapeutic strategies aimed at targeting EMT. Due to the potential for high sensitivity and specificity, Raman spectroscopy was used here to study the metabolic changes associated with EMT in human breast cancer tissue. For Raman spectroscopy measurements, tissue from 23 patients were collected, comprising non-lesional, EMT and non-EMT formalin-fixed and paraffin embedded breast cancer samples. Analysis was made in the fingerprint Raman spectra region (600-1800 cm-1) best associated with cancer progression biochemical changes in lipid, protein and nucleic acids. The ANOVA test followed by the Tukey's multiple comparisons test were conducted to see if there existed differences between non-lesional, EMT and non-EMT breast tissue for Raman spectroscopy measurements. Results revealed that significant differences were evident in terms of intensity between the non-lesional and EMT samples, as well as the EMT and non-EMT samples. Multivariate analysis involving independent component analysis, Principal component analysis and non-negative least square were used to analyse the Raman spectra data. The results show significant differences between EMT and non-EMT cancers in lipid, protein, and nucleic acids. This study demonstrated the capability of Raman spectroscopy supported by multivariate analysis in analysing metabolic changes in EMT breast cancer tissue.

Mycoremediation of acetaminophen: Culture parameter optimization to improve efficacy.

Untreated pharmaceutical pollution and their possibly toxic metabolites, resulting from overloaded wastewater treatment processes, end up in aquatic environments and are hazardous to the ecosystem homeostasis. Biological wastewater remediation could supplement traditional methods and overcome the release of these biologically active compounds in the environment. Mycoremediation is especially promising due to the unspecific nature of fungi to decompose compounds through exoenzymes and the uptake of compounds as nutrients. In the present study, we improved on the previous advances made using the fungus Mucor hiemalis to remediate one of the most commonly occurring pharmaceuticals, acetaminophen (APAP), at higher concentrations. The limitation of nitrogen, adjustment of pH, and comparison to, as well as co-cultivation with the white-rot fungus Phanerochaete chrysosporium, were tested. Nitrogen limitation did not significantly improve the APAP remediation efficiency of M. hiemalis. Maintaining the pH of the media improved the remediation restraint of 24 h previously observed. The APAP remediation efficiency of P. chrysosporium was far superior to that of M. hiemalis, and co-cultivation of the two resulted in a decreased remediation efficiency compared to P. chrysosporium in single.

Low-cost commercial borosilicate glass slides for passive radiation dosimetry.

For x- and gamma- irradiations delivering entrance doses from 2- up to 1000 Gy to commercial 1.0 mm thick borosilicate glass microscope slides, study has been made of their thermoluminescence yield. With an effective atomic number of 10.6 (approximating bone equivalence), photon energy dependency is apparent in the low x-ray energy range, with interplay between the photoelectric effect and attenuation. As an example, over the examined dose range, at 120 kVp the photon sensitivity has been found to be some 5× that of 60Co gamma irradiations, also with repeatability to within ~1%. The glow-curves, taking the form of a single prominent broad peak, have been deconvolved yielding at best fit a total of five peaks, the associated activation energies and frequency factors also being obtained. The results indicate borosilicate glass slides to offer promising performance as a low-cost passive radiation dosimeter, with utility for both radiotherapy and industrial applications.

Two clusters of Toscana virus meningo-encephalitis in Livorno Province and Elba Island, July-September 2018.

BACKGROUND: Toscana virus (TOSV) is an arbovirus transmitted to humans by Phlebotomus spp sandflies. It causes aseptic meningitis and meningoencephalitis with marked seasonality. Here we describe the clinical, microbiological and epidemiological features of two clusters of cases occurred in Tuscany in 2018. METHODS: A confirmed case was defined as the detection of anti-TOSV IgM and IgG in serum sample, in presence of typical clinical manifestations. We consulted hospital records of hospitalized patients to collect clinical information and obtained epidemiological information from the local health authority investigation report. We telephonically interviewed patients using a standard questionnaire for a 6 months follow-up. RESULTS: A total of 12 cases of TOSV meningo-encephalitis with onset between 4th of July and 12th of September accessed health care services in the province of Livorno. Eight cases were males with median age 41,5 and four were not resident in the area. Serological investigations confirmed a recent TOSV infection. Eight cases reported visiting Elba Island and four had a possible occupational-related exposure. CONCLUSIONS: This surge of infection emphasizes the need of information campaigns coupled with adequate surveillance and control interventions against TOSV that, among other arboviruses, is a growing issue of concern in Italy.