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1.
Int J Mol Sci ; 24(7)2023 Mar 30.
Article in English | MEDLINE | ID: mdl-37047465

ABSTRACT

The aim of this in vitro study was to analyze, both experimentally and theoretically, the mechanical behavior of two types of composite materials used in restoring dental integrity. The samples of each composite resin, namely Filtek Supreme XT (3M ESPE, St. Paul, MN, USA) and Filtek Z250 (3M ESPE, St. Paul, MN, USA), were experimentally analyzed by determining their compressive strength and fracture behavior. The fractured fragments of the samples were subjected to surface evaluation by scanning electron microscopy. The compressive stress-compressive strain dependencies revealed stronger cracking of the Filtek Supreme XT composite than Filtek Z250 prior to fracture. Theoretically, the evaluation was made by means of holographic implementations of such types of composite materials. A Hooke-type equation in a differential form is presented, which links the proposed theoretical model with the experimentally obtained data.


Subject(s)
Composite Resins , Fractures, Bone , Humans , Microscopy, Electron, Scanning , Materials Testing , Dental Materials , Surface Properties
2.
Molecules ; 28(19)2023 Oct 02.
Article in English | MEDLINE | ID: mdl-37836751

ABSTRACT

Among the many commonly encountered hazards, improvised explosive devices (IEDs) remain the primary threat to military and civilian personnel due to the ease of their production and the widespread availability of their raw materials and precursors. Identifying traces of potential precursors is the first step in developing appropriate control measures. An interesting approach is to identify the precursors that are released around the site as they are handled and transformed into the final IEDs. CO2 laser photoacoustic spectroscopy can offer the spectral characterization of a number of explosives-related compounds without sample preparation. Benzene, toluene, acetone, and ethylene glycol absorption spectra were determined in the IR region between 9.2 and 10.8 µm. Each substance emitted a unique photoacoustic response corresponding to its chemical composition that could be further used to identify the explosive material.

3.
Clin Lab ; 68(9)2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36125134

ABSTRACT

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice in patients with Fanconi anemia (FA). The aim of our study is to evaluate the impact and benefits of allogenic matched donor HSCT in a case of a 12 year-old girl with FA, who displayed good clinical evolution following 2 months post-transplantation. METHODS: In the pre-transplant phase, reference blood samples from the donor and recipient were collected on EDTA. The DNA from blood samples was extracted using an automated Maxwell® 48 RSC instrument (Promega, USA) with the Maxwell® RSC Whole blood DNA kit (Promega, USA). For DNA quantification, the PowerQuant System kit (Promega, USA) was used with the ABI 7500 Real-time PCR system (Applied Biosystems, USA). The amplification of the short tandem repeat markers was performed using the 24plex Investigator QS kit (Qiagen, Germany) on a ProFlex PCR System. Furthermore, the PCR products were separated and detected on an ABI 3500 Genetic Analyzer (Applied Biosytems, USA). RESULTS: Thirty days post transplantation, a complete chimerism (CC) was achieved with a full replacement by do-nor derived hematopoietic cells. Sixty days post transplantation, the CC status was maintained with improvement of hematological findings. CONCLUSIONS: In FA, chimerism monitoring after HSCT provides useful information regarding engraftment or possibility of post-transplantation complications such as graft versus host disease.


Subject(s)
Fanconi Anemia , Hematopoietic Stem Cell Transplantation , Child , Edetic Acid , Fanconi Anemia/genetics , Fanconi Anemia/therapy , Female , Humans , Real-Time Polymerase Chain Reaction , Transplantation Chimera/genetics
4.
J Med Genet ; 58(9): 648-652, 2021 09.
Article in English | MEDLINE | ID: mdl-32843487

ABSTRACT

Pathogenic variants in BRCA1 gene in heterozygous state are known to be associated with breast-ovarian cancer susceptibility; however, biallelic variants cause a phenotype recognised as Fanconi anaemia complementation group S. Due to its rarity, medical management and preventive screening measures are insufficiently understood. Here, we present nine individuals (one new and eight previously presented) with biallelic variants in BRCA1 gene, to delineate clinical features in comparison with other chromosome instability syndromes and understand the patients' health risk. Features seen in these 9 individuals (7 females/2 males) include prenatal and postnatal growth failure (9/9), microcephaly (9/9), hypo/hyperpigmented lesions (9/9), facial dysmorphism (9/9), mild developmental delay (8/9) and early-onset solid tumours (5/9). None presented bone marrow failure or immunodeficiency. Individuals with biallelic variants in BRCA1 also showed chromosomal instability by mitomycin and diepoxybutane test. The phenotype caused by biallelic BRCA1 variants is best framed between Fanconi anaemia and Nijmegen syndrome, yet distinct due to lack of bone marrow failure and immunodeficiency. We hypothesise that disease class should be reframed and medical management in people with biallelic variants in BRCA1 should emphasise on detection of solid tumour development and avoiding exposure to ionising radiation.


Subject(s)
BRCA1 Protein/genetics , DNA Repair-Deficiency Disorders/diagnosis , DNA Repair-Deficiency Disorders/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Mutation , Phenotype , Alleles , Biomarkers , Genetic Association Studies/methods , Humans , Male , Pedigree , Symptom Assessment
5.
Molecules ; 27(6)2022 Mar 15.
Article in English | MEDLINE | ID: mdl-35335255

ABSTRACT

Cadmium (Cd) is not considered a fundamental element for plants inducing general growth disturbances and inhibition in many species of plants. The purpose of our research was to examine the ethylene (C2H4) and ammonia (NH3), emissions in alfalfa sprouts with or without Cd, using infrared laser photoacoustic spectroscopy (IR LPAS), in order to suggest new markers that may add a better knowledge of Cd effect. The responses of alfalfa sprouts to C2H4 and NH3 may fluctuate, depending on tissue sensitivity and the phase of plant development. From the determinations of this study, the C2H4 was established to be inhibited, while NH3 was established to be in a higher concentration with the amount of Cd added to the alfalfa seeds for growth when the values were correlated to the control and BIOalfalfa sprouts (Sonnentor).


Subject(s)
Cadmium , Medicago sativa , Cadmium/toxicity , Plants , Spectrum Analysis
6.
Molecules ; 27(11)2022 Jun 04.
Article in English | MEDLINE | ID: mdl-35684554

ABSTRACT

Wearing surgical face masks is among the measures taken to mitigate coronavirus disease (COVID-19) transmission and deaths. Lately, concern was expressed about the possibility that gases from respiration could build up in the mask over time, causing medical issues related to the respiratory system. In this research study, the carbon dioxide concentration and ethylene in the breathing zone were measured before and immediately after wearing surgical face masks using the photoacoustic spectroscopy method. From the determinations of this study, the C2H4 was established to be increased by 1.5% after one hour of wearing the surgical face mask, while CO2 was established to be at a higher concentration of 1.2% after one hour of wearing the surgical face mask, when the values were correlated with the baseline (control).


Subject(s)
COVID-19 , Masks , COVID-19/prevention & control , Gases , Humans , Respiration , SARS-CoV-2 , Spectrum Analysis
7.
Eur Respir J ; 58(3)2021 09.
Article in English | MEDLINE | ID: mdl-33574078

ABSTRACT

BACKGROUND: The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB. METHODS: Adult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points. RESULTS: 50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9-0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001). CONCLUSION: Biomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.


Subject(s)
Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary , Adult , Antitubercular Agents/therapeutic use , Duration of Therapy , Humans , Transcriptome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy
8.
Molecules ; 25(21)2020 Nov 04.
Article in English | MEDLINE | ID: mdl-33158021

ABSTRACT

Photoacoustic spectroscopy is one of the most exciting areas of research in physics and chemistry, covering a broad range of applications from agricultural to biological, including atmospheric monitoring, space science, and air-quality measurements to security and workplace surveillance, in addition to its great potential in preclinical and clinical biomedical applications [...].


Subject(s)
Air Pollution , Biomedical Research , Environmental Monitoring , Spectrum Analysis
9.
Molecules ; 25(7)2020 Apr 09.
Article in English | MEDLINE | ID: mdl-32283766

ABSTRACT

In this review, applications of near-infrared photoacoustic spectroscopy are presented as an opportunity to evaluate human respiration because the measurement of breath is fast, intact and simple to implement. Recently, analytical methods for measuring biomarkers in exhaled air have been extensively developed. With laser-based photoacoustic spectroscopy, volatile organic compounds can be identified with high sensitivity, at a high rate, and with very good selectivity. The literature review has shown the applicability of near-infrared photoacoustic spectroscopy to one of the problems of the real world, i.e., human health. In addition, the review will consider and explore different breath sampling methods for human respiration analysis.


Subject(s)
Biomarkers , Breath Tests/methods , Photoacoustic Techniques , Respiration , Spectroscopy, Near-Infrared/methods , Algorithms , Biomarkers/analysis , Humans , Lasers , Models, Theoretical
10.
Molecules ; 25(7)2020 Apr 02.
Article in English | MEDLINE | ID: mdl-32252370

ABSTRACT

Lead (Pb) is the most prevalent heavy metal pollutant in the natural environment. Pb is not a fundamental element for plants, but they absorb it when it is present in their environment, having no known physiological activity. The aim of our research was to evaluate the efficacy of laser photoacoustic spectroscopy as a tool to monitor changes induced by Pb in plant respiration by highlighting two molecular markers (C2H4 and CO2). To better understand Pb phytotoxicity, we monitored the plantlets evolution as well as the morphology of the root cells. Firstly, we showed that the treatment hinders the plantlet's development. Furthermore, using laser photoacoustic spectroscopy, we found a decrease in the concentration of C2H4 and CO2 vapors measured in the respiration of treated plants. Finally, fluorescence microscopy results showed that in Pb treated plantlets, the cell roots morphology is clearly altered as compared with the untreated ones. All the results are well correlated and can help further in understanding Pb phytotoxicity.


Subject(s)
Carbon Dioxide/chemistry , Lead/toxicity , Seeds/growth & development , Cell Respiration/drug effects , Ethylenes/chemistry , Lasers , Lead/analysis , Photoacoustic Techniques , Plant Roots/chemistry , Plant Roots/drug effects , Plant Roots/growth & development , Seeds/chemistry , Seeds/drug effects
11.
Molecules ; 25(7)2020 Mar 28.
Article in English | MEDLINE | ID: mdl-32231145

ABSTRACT

This paper focuses on the dissociation of carbon dioxide (CO2) following the absorption processes of microwave radiation by noncontact metal wire (tungsten). Using a microwave plasma generator (MPG) with a single-mode cavity, we conducted an interaction of microwaves with a noncontact electrode in a CO2 atmosphere. High energy levels of electromagnetic radiation are generated in the focal point of the MPG's cylindrical cavity. The metal wires are vaporized and ionized from this area, subsequently affecting the dissociation of CO2. The CO2 dissociation is highlighted through plasma characterization and carbon monoxide (CO) quantity determination. For plasma characterization, we used an optical emission spectroscopy method (OES), and for CO quantity determination, we used a gas analyzer instrument. Using an MPG in the CO2 atmosphere, we obtained a high electron temperature of the plasma and a strong dissociation of CO2. After 20 s of the interaction between microwaves and noncontact electrodes, the quantity of CO increased from 3 ppm to 1377 ppm (0.13% CO). This method can be used in space applications to dissociate CO2 and refresh the atmosphere of closed spaces.


Subject(s)
Carbon Dioxide/chemistry , Microwaves , Plasma Gases , Algorithms , Carbon Monoxide/chemistry , Gases/chemistry , Models, Chemical , Spectrum Analysis
12.
J Environ Sci Health B ; 55(4): 329-341, 2020.
Article in English | MEDLINE | ID: mdl-31793375

ABSTRACT

Closed lakes located in urban parks act as sinks of organochlorine pesticides (OCPs), which have been used, for decades, as insecticides, herbicides and fungicides. The closed lakes from Bucharest, Romania, are periodically managed to prevent eutrophication and accumulation of pollutants. However, it is not known if these practices reduce or enhance the legacy pollution with OCPs. The aim of this study was to explore the spatial variation of OCPs in closed lakes. The total concentration of OCPs in water and sediments ranged between 0.0176 and 37.1 µg/L, and between 122 to 1,890 ng/g, respectively. The concentrations of OCPs were compared with the consensus-based sediment quality guidelines (SQGs) in order to evaluate the ecological risks of sediments. The highest potential adverse effects were associated with γ-HCH exposure. Periodical draining and dredging of lakes lead to the resuspension of contaminants, increasing pesticide bioavailability and accumulation in sediments. In addition, we observed that fluorescent dissolved organic matter (DOM) might influence the OCPs cycle. The quantity and character of fluorescent DOM can provide further insight into OCPs degradation. Also, this study may help urban planners to determine the state of urban waters and to find the best solution for water management.


Subject(s)
Hydrocarbons, Chlorinated/analysis , Lakes/analysis , Pesticides/analysis , Water Pollutants, Chemical/analysis , Cities , Environmental Monitoring , Geologic Sediments/analysis , Hexachlorocyclohexane/analysis , Hydrogen-Ion Concentration , Romania
13.
Am J Respir Crit Care Med ; 198(3): 379-386, 2018 08 01.
Article in English | MEDLINE | ID: mdl-29509468

ABSTRACT

RATIONALE: Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in Europe. Reported treatment success rates are around 50% or less, and cure rates are even lower. OBJECTIVES: To document the management and treatment outcome in patients with MDR-TB in Europe. METHODS: We performed a prospective cohort study, analyzing management and treatment outcomes stratified by incidence of patients with MDR-TB in Europe. Treatment outcomes were compared by World Health Organization and alternative simplified definitions by the Tuberculosis Network European Trialsgroup (TBNET). MEASUREMENTS AND MAIN RESULTS: A total of 380 patients with MDR-TB were recruited and followed up between 2010 and 2014 in 16 European countries. Patients in high-incidence countries compared with low-incidence countries were treated more frequently with standardized regimen (83.2% vs. 9.9%), had delayed treatment initiation (median, 111 vs. 28 d), developed more additional drug resistance (23% vs. 5.8%), and had increased mortality (9.4% vs. 1.9%). Only 20.1% of patients using pyrazinamide had proven susceptibility to the drug. Applying World Health Organization outcome definitions, frequency of cure (38.7% vs. 9.7%) was higher in high-incidence countries. Simplified outcome definitions that include 1 year of follow-up after the end of treatment showed similar frequency of relapse-free cure in low- (58.3%), intermediate- (55.8%), and high-incidence (57.1%) countries, but highest frequency of failure in high-incidence countries (24.1% vs. 14.6%). CONCLUSIONS: Conventional standard MDR-TB treatment regimens resulted in a higher frequency of failure compared with individualized treatments. Overall, cure from MDR-TB is substantially more frequent than previously anticipated, and poorly reflected by World Health Organization outcome definitions.


Subject(s)
Antitubercular Agents/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Cohort Studies , Europe/epidemiology , Humans , Incidence , Prospective Studies , Treatment Outcome
14.
Molecules ; 24(6)2019 Mar 22.
Article in English | MEDLINE | ID: mdl-30909457

ABSTRACT

Ethylene is a classical plant hormone and has appeared as a strong molecule managing many physiological and morphological reactions during the life of a plant. With laser-based photoacoustic spectroscopy, ethylene can be identified with high sensitivity, at a high rate and with very good selectivity. This research presents the dynamics of trace gases molecules for ethylene released by cherry flowers, apple flowers and strawberry flowers. The responses of distinctive organs to ethylene may fluctuate, depending on tissue sensitivity and the phase of plant development. From the determinations of this study, the ethylene molecules at the flowers in the nitrogen flow were established in lower concentrations when the value is correlated to the ethylene molecules at the flowers in synthetic air flow.


Subject(s)
Ethylenes/chemistry , Flowers/chemistry , Fruit/chemistry , Cell Respiration , Ethylenes/analysis , Flowers/metabolism , Fruit/metabolism , Plant Growth Regulators/analysis , Plant Growth Regulators/chemistry , Spectrum Analysis
15.
Environ Monit Assess ; 192(1): 59, 2019 Dec 20.
Article in English | MEDLINE | ID: mdl-31863207

ABSTRACT

Urban lakes represent the most extensive water bodies in cities and provide blue ecosystem services, by retaining pollutants, offering cultural services, and mitigating climate change. Human activities threaten to decrease the supply of ecosystem services associated with urban lakes. Exorheic lakes play an essential role in reducing and changing the characteristics of pollutants and organic matter along the environmental continuum. This study aims to gain further understanding on the distribution and fate of organochlorine pesticides (OCPs) in relation to fluorescent dissolved organic matter (DOM) within an exorheic lake system, located along Colentina river, Bucharest. Results indicated a historical usage of HCHs, which were present in lake water and sediment samples, in concentrations exceeding the regulatory limits, with potential eco-toxicity on aquatic biota. Decades of intense applications along the river, before OCPs ban, led to their accumulation in sediments and their re-mobilization, each year, after the lakes were drained, dredged, and refilled. Fluorescence measurements revealed that DOM accumulated in certain lakes due to wastewater discharges, and surface runoff, but decreased towards the end of the exorheic lakes through dilution, sedimentation, and biodegradation. The results also showed that fluorescent DOM may have a substantial impact on OCPs cycle in urban lakes and may help to determine the conditions and effectiveness of removing OCPs from water and sediments. These issues contribute to the decrease of ecosystem services supply associated with urban lakes, having multiple hidden consequences on the urban environment.


Subject(s)
Environmental Monitoring/methods , Geologic Sediments/chemistry , Hydrocarbons, Chlorinated/analysis , Lakes/chemistry , Pesticides/analysis , Water Pollutants, Chemical/analysis , Biodegradation, Environmental , China , Cities , Ecosystem , Humans , Rivers/chemistry
16.
Gen Physiol Biophys ; 35(3): 299-310, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27045672

ABSTRACT

Superparamagnetic iron oxide nanoparticles (SPION) have attracted a lot of interest due to their widespread biomedical and diagnostic applications. Coating the SPIONs with various surface layers can provide an interface between the core and the surrounding environment. The aim of this study was to examine the in vivo behaviour of dextran-coated iron oxide nanoparticles (D-IONPs) in aqueous suspensions. The SPIONs stabilized with dextran (D-IONPs) were synthesized in aqueous solutions by co-precipitation method. The average grain size deduced from transmission electron microscopy is 7.5 nm. The hematological parameters registered for the rats exposed to D-IONPs at 1 ml/kg have had values approximately equal to those examined for the control specimen. The architecture of liver and kidneys was not affected after one day of intraperitoneal injection of D-IONPs compared to the reference group. After 21 and 28 days respectively from the administration of the D-IONPs solution, the liver and kidneys from the injected rats showed a normal aspect without abnormalities compared to the rats uninjected. Our findings suggest that the administration of 1 ml/kg D-IONPs did not cause any toxicological effect since the parameters of renal and liver function were in the normal range as reported to the control group.


Subject(s)
Blood Cells/drug effects , Coated Materials, Biocompatible/toxicity , Dextrans/toxicity , Kidney/drug effects , Liver/drug effects , Magnetite Nanoparticles/toxicity , Nanocapsules/toxicity , Animals , Blood Cells/pathology , Cells, Cultured , Coated Materials, Biocompatible/administration & dosage , Dextrans/administration & dosage , Dose-Response Relationship, Drug , Drug Tolerance , Injections, Intraperitoneal , Kidney/pathology , Liver/pathology , Magnetite Nanoparticles/administration & dosage , Male , Materials Testing , Nanocapsules/administration & dosage , Particle Size , Rats
17.
Phys Chem Chem Phys ; 17(3): 2268-73, 2015 Jan 21.
Article in English | MEDLINE | ID: mdl-25486336

ABSTRACT

Using density functional theory (DFT) and thermodynamic considerations we study the shape and stability of Pd nanoparticles in oxygen-lean and oxygen-rich atmospheres. We find that at very high oxygen coverage cubes exposing (100) faces will form, which are stabilized due to the formation of a O/(√5 × âˆš5)R27° overlayer. The shape of oxygen-covered Pd and Pt nanoparticles is compared in this study.

18.
J Biophotonics ; 17(6): e202400074, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38566476

ABSTRACT

Helicobacter pylori (H. pylori) is a type of bacteria that infects the stomach. The detection of H. pylori is an essential part of current clinical practices because this disease can cause peptic ulcers, chronic inflammation of the stomach lining but also stomach cancer. Helicobacter pylori has a naturally occurring enzyme that hydrolyzes urea into ammonium carbonate called urease. Many methods exist for the detection of H. pylori infection, but an innovative approach is to detect the ammonia in the breath (ABT, Ammonia Breath Test). In this research study, using photoacoustic spectroscopy method, the ammonia concentration in the breathing zone of people with H. pylori were measured and were compared with ammonia concentration from the respiration of healthy people. From the ABT determinations of this study, the ammonia was established to be increased with 498 ppb at people with H. pylori when we compare with ABT of healthy people.


Subject(s)
Ammonia , Breath Tests , Helicobacter Infections , Helicobacter pylori , Photoacoustic Techniques , Humans , Helicobacter pylori/metabolism , Breath Tests/methods , Ammonia/metabolism , Helicobacter Infections/microbiology , Male , Adult , Female
19.
J Nephrol ; 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39271638

ABSTRACT

Contraception, pregnancy and fertility are seldom discussed with women receiving dialysis and the medical staff of dialysis centres. Since the majority of women on dialysis are past childbearing age, these themes are not always given proper consideration and this category of patients may be missing important information. Young women of childbearing age who are on dialysis frequently experience sexual dysfunction and hormonal disorders of the hypothalamic-pituitary-gonadal axis. In addition, dialysis often has a relevant psychological impact and affects the person's social role. Physical changes may accompany kidney failure, including the presence of a vascular or peritoneal access. The dialysis ward is not a place that facilitates privacy, and discussing contraception is not always easy, particularly in some cultural contexts, or between a male doctor and a young woman. While pregnancy and contraception are routinely addressed with women waiting for a kidney transplant, they are less frequently discussed with women on dialysis. Numerous studies have found that over half of the pregnancies in women on dialysis are unplanned. How frequently patients are seen (at each dialysis session, or during periodic visits) does not necessarily make things better, as often some issues are taken for granted or discussing them is postponed. In our centre, over 160 patients are on chronic hemodialysis (HD) and 20 are on peritoneal or home HD. Only nine women were of childbearing age in our center, all on HD. We discussed with them on counselling about pregnancy, and to ensure that all women of childbearing age would be offered counselling on contraception and pregnancy, we designed simple leaflets and an infographic, in collaboration with our nursing team and residents, as a guide and a reminder for our staff to discuss these topics with the patients.

20.
Pathog Immun ; 9(2): 25-42, 2024.
Article in English | MEDLINE | ID: mdl-38939039

ABSTRACT

Background: Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation. Objective: We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy. Methods: Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was validated in an additional fourth cohort of patients with MDR/RR-TB from Romania. Results: A total of 52 patients from the 3 identification cohorts received linezolid treatment. Of those, 24 (46.2%) developed peripheral and/or optic neuropathies during linezolid treatment. The majority (59.3%) of the episodes were of moderate (grade 2) severity. In total, the expression of 1,479 genes differed significantly at baseline of treatment. Suprabasin (SBSN) was identified as a potential biomarker to predict linezolid-associated neuropathy. In the validation cohort, 10 of 42 (23.8%) patients developed grade ≥3 neuropathies. The area under the curve for the biomarker algorithm prediction of grade ≥3 neuropathies was 0.63 (poor; 95% confidence interval: 0.42 - 0.84). Conclusions: We identified and preliminarily validated a potential clinical biomarker to predict linezolid-associated neuropathies before the initiation of MDR/RR-TB therapy. Larger studies of the SBSN biomarker in more diverse populations are warranted.

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