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1.
Environ Microbiol Rep ; 16(5): e70008, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39267332

ABSTRACT

This scoping review aimed to investigate the potential association between climate change and the rise of antibiotic resistance while also exploring the elements of climate change that may be involved. A scoping review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews, comprehensively searching scientific literature up to 31 January 2024. Multiple databases were utilized, including MEDLINE, Web of Science and SCOPUS. Various search strategies were employed, and selection criteria were established to include articles relevant to antibiotic resistance and climate change. The review included 30 selected articles published predominantly after 2019. Findings from these studies collectively suggest that rising temperatures associated with climate change can contribute to the proliferation of antibiotic resistance, affecting diverse ecosystems. This phenomenon is observed in soil, glaciers, rivers and clinical settings. Rising temperatures are associated with a rise in the prevalence of antibiotic resistance across various environments, raising concerns for global health. However, these studies provide valuable insights but do not establish a definitive causal link between environmental temperature and antibiotic resistance. The selective pressure exerted by antibiotics and their residues in ecosystems further complicates the issue.


Subject(s)
Anti-Bacterial Agents , Climate Change , Anti-Bacterial Agents/pharmacology , Ecosystem , Drug Resistance, Microbial/genetics , Humans , Bacteria/drug effects , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Drug Resistance, Bacterial , Temperature
2.
Public Health Nurs ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39256191

ABSTRACT

BACKGROUND: Technological disasters in Asia have significant public health and environmental implications, but there is limited epidemiological analysis of these events. This study aims to characterize the epidemiological profile of technological disasters in Asia from 2000 to 2021, focusing on morbidity and mortality trends. METHODS: A retrospective descriptive observational analysis was conducted using data from emergency events database (EM-DAT), DesInventar, NatCAt, and Sigma. The study categorized disasters into transport, industrial, and miscellaneous accidents. Statistical analyses were used to examine frequencies, trends, and correlations among the different disaster types. RESULTS: From 2000 to 2021, Asia experienced 2333 technological disasters, with transport accidents being the most frequent (55.77%), followed by industrial (26.10%) and miscellaneous accidents (18.13%). The overall trend showed a statistically significant decrease in the frequency of these disasters and in average mortality and injury rates. The study highlighted the varying impact of different disaster types, with industrial accidents causing the highest fatality and affected rates despite being less frequent than transport accidents. CONCLUSIONS: The study indicates a declining trend in the frequency and severity of technological disasters in Asia, reflecting improved safety measures and disaster management. However, the high impact of industrial accidents underscores the need for targeted prevention strategies.

3.
Int J Mol Sci ; 25(15)2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39125709

ABSTRACT

The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06-30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24-14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04-1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94-6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71-76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10-19-NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19-269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05-16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22-20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58-91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7-75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9-112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16-73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.


Subject(s)
Anti-Asthmatic Agents , Antibodies, Monoclonal, Humanized , Asthma , Polymorphism, Single Nucleotide , Humans , Asthma/drug therapy , Asthma/genetics , Female , Male , Antibodies, Monoclonal, Humanized/therapeutic use , Middle Aged , Anti-Asthmatic Agents/therapeutic use , Adult , Retrospective Studies , Biomarkers , Treatment Outcome , Aged
4.
Emerg Microbes Infect ; 13(1): 2392659, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39137261

ABSTRACT

Early detection of disseminating vancomycin-resistant Enterococcus faecium (VREfm) in ICU wards is crucial for outbreak identification and the implementation of prompt infection control measures. Genotypic methods like pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) are costly and time-consuming, hindering rapid response due to batch dependency. Fourier-transform infrared spectroscopy (FT-IR) offers the potential for real-time outbreak detection and reliable strain typing. We utilized FT-IR to identify clonal VREfm dissemination and compared its performance to PFGE and WGS. Between February through October 2023, an unusually high number of VREfm were recovered at a tertiary hospital in Barcelona. Isolates were examined for antimicrobial susceptibility, carriage of vanA/vanB genes and clonality was also studied using FT-IR, PFGE, and WGS. Routine FT-IR inspections revealed recurring VREfm clustering during the outbreak's initial weeks. In total, 104 isolates were recovered from 75 patients and from multiple wards. However, only one isolate was recovered from an environmental sample, suggesting the absence of environmental reservoirs. An ST80 vancomycin-resistant (vanA) E. faecium strain was the main strain responsible for the outbreak, although a few additional VREfm strains were also identified, all belonging to CC17. PFGE and cgMLST (WGS) yielded identical clustering results to FT-IR, and WGS confirmed vanA/vanB gene carriage in all VREfm isolates. Infection control measures led to a rapid decline in VREfm isolates, with no isolates detected in November. FT-IR spectroscopy offers rapid turnaround times, sensitivity, and reproducibility, comparable to standard typing methods. It proved as an effective tool for monitoring VREfm dissemination and early outbreak detection.


Subject(s)
Cross Infection , Electrophoresis, Gel, Pulsed-Field , Enterococcus faecium , Gram-Positive Bacterial Infections , Vancomycin-Resistant Enterococci , Whole Genome Sequencing , Humans , Enterococcus faecium/genetics , Enterococcus faecium/drug effects , Enterococcus faecium/isolation & purification , Enterococcus faecium/classification , Vancomycin-Resistant Enterococci/genetics , Vancomycin-Resistant Enterococci/isolation & purification , Vancomycin-Resistant Enterococci/drug effects , Vancomycin-Resistant Enterococci/classification , Spectroscopy, Fourier Transform Infrared/methods , Cross Infection/microbiology , Cross Infection/epidemiology , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/epidemiology , Whole Genome Sequencing/methods , Disease Outbreaks , Bacterial Proteins/genetics , Microbial Sensitivity Tests , Spain/epidemiology , Carbon-Oxygen Ligases/genetics , Anti-Bacterial Agents/pharmacology
5.
Microbiol Spectr ; : e0296123, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39194256

ABSTRACT

The study aimed to describe the epidemiology of multidrug-resistant (MDR) bacteria among solid cancer (SC) patients with bloodstream infections (BSIs), evaluating inappropriate empiric antibiotic treatment (IEAT) use and mortality trends over a 25-year period. All BSI occurrences in adult SC patients at a university hospital were analyzed across five distinct five-year intervals. MDR bacteria were classified as extended-spectrum beta-lactamases (ESBL)-producing and/or Carbapenem-resistant Enterobacterales, non-fermenting Gram-negative bacilli (GNB) resistant to at least three antibiotic classes, methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococci. A multivariate regression model identified the risk factors for MDR BSI. Of 6,117 BSI episodes, Gram-negative bacilli (GNB) constituted 60.4% (3,695/6,117), being the most common are Escherichia coli with 26.8% (1,637/6,117), Klebsiella spp. with 12.4% (760/6,117), and Pseudomonas aeruginosa with 8.6% (525/6,117). MDR-GNB accounted for 644 episodes (84.8% of MDR or 644/759), predominantly ESBL-producing strains (71.1% or 540/759), which escalated significantly over time. IEAT was administered in 24.8% of episodes, mainly in MDR BSI, and was associated with higher mortality (22.9% vs. 14%, P < 0.001). Independent factors for MDR BSI were prior antibiotic use [odds ratio (OR) 2.93, confidence interval (CI) 2.34-3.67], BSI during antibiotic treatment (OR 1.46, CI 1.18-1.81), biliary (OR 1.84, CI 1.34-2.52) or urinary source (OR 1.86, CI 1.43-2.43), admission period (OR) 1.28, CI 1.18-1.38, and community-acquired infection (OR 0.57, CI 0.39-0.82). The study showed an increase in MDR-GNB among SC patients with BSI. A quarter received IEAT, which was linked to increased mortality. Improving risk assessment for MDR infections and the judicious prescription of empiric antibiotics are crucial for better outcomes. IMPORTANCE: Multidrug-resistant (MDR) bacteria pose a global public health threat as they are more challenging to treat, and they are on the rise. Solid cancer patients are often immunocompromised due to their disease and cancer treatments, making them more susceptible to infections. Understanding the changes and trends in bloodstream infections in solid cancer patients is crucial, to help physicians make informed decisions about appropriate antibiotic therapies, manage infections in this vulnerable population, and prevent infection. Solid cancer patients often require intensive and prolonged treatments, including surgery, chemotherapy, and radiation therapy. Infections can complicate these treatments, leading to treatment delays, increased healthcare costs, and poorer patient outcomes. Investigating new strategies to combat MDR infections and researching novel antibiotics in these patients is of paramount importance to avoid these negative impacts.

6.
Trop Med Int Health ; 29(8): 731-738, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38962808

ABSTRACT

OBJECTIVE: The objective of this study is to analyse the epidemiological profile of global climate-related disasters in terms of morbidity and mortality, as well as to examine their temporal trends. METHOD: This cross-sectional study analysed climate-related global disasters from 2000 to 2021, utilising definitions and criteria from the United Nations Strategy for Disaster Reduction and the Centre for Research on the Epidemiology of Disasters. Data were sourced from the EM-DAT database. The study assessed trends over the entire period and compared them with previous years (1978-2000). RESULTS: A total of 7398 climate-related disasters were recorded, with hydrological disasters being the most frequent, followed by meteorological and climatological disasters. Statistically significant differences were noted in the average rates of affected individuals and injuries per million inhabitants. No significant trends were found in mortality rates, but the frequency trends for the entire period (1978-2021) and the subperiod (1978-2000) were increasing and statistically significant. However, the trend from 2000 onwards showed a non-significant decrease, potentially reflecting better disaster preparedness and response strategies under the Hyogo and Sendai Framework. CONCLUSION: The study highlights hydrological disasters as the most frequent and deadliest climate-related events, with climatological disasters affecting and injuring the most people. The lack of standardised criteria for disaster inclusion in databases presents a significant challenge in comparing results and analysing trends. Establishing uniform inclusion criteria is crucial for effective data analysis and disaster management.


Subject(s)
Disasters , Humans , Cross-Sectional Studies , Climate , Global Health , Climate Change
7.
Heliyon ; 10(13): e33512, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39040399

ABSTRACT

Primary Processed Foods are a class of food items that are ready for consumption after minimal processing in the supply chain. These products are ubiquitous in our daily diet, but so far a limited number of studies dealt with the optimization of quality control methods to check their content of contaminants. Among primary processed foods, bee pollen is a nutritionally acclaimed food supplement, whose contamination with pesticides and mycotoxins has been largely proven. For this reason, the present study aimed at optimizing for the first time a comprehensive LC-MS/MS method capable of analyzing 282 pesticides and 8 mycotoxins in bee pollen. To obtain a suitable method, two extraction procedures (QuEChERS and Accelerated Solvent Extraction), as well as different chromatographic gradients and columns, were tested. The optimized methodology, comprehending an extraction based on semi-automated QuEChERS, and an analytical method including inert LC column technology, was validated and applied to a sample set of 34 bee pollens. The analyzed samples collectively showed the presence of 41 pesticides and 1 mycotoxin.

8.
Talanta ; 278: 126448, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38905962

ABSTRACT

The analysis of pesticide residues and mycotoxins in baby food demands exceptionally low limits of quantitation, necessitating the use of highly sensitive instruments capable of conducting trace analyses. High-resolution instruments typically fail to detect such low levels. However, the latest advancements in liquid time-of-flight technology, when coupled with ion trapping, enable ion enrichment, thereby improving detection levels. This allows for the analysis of these substances at low concentration levels, benefiting from enhanced mass accuracy. Additionally, the use of mass accuracy data helped eliminate matrix interferences, thereby enabling high-confidence identification. We developed a multi-residue method to analyse 219 pesticide residues and 9 mycotoxin residues in baby food matrices. Utilizing a QuEChERS-based extraction method, the samples were then analysed using an LC-ZenoTOF 7600 system with mass window screening acquisition. For pesticides, the limit of quantitation was 0.001-0.003 mg/kg for 81 % of the evaluated compounds, 0.005 mg/kg for 13 %, 0.010 mg/kg for 4 % and 0.020-0.030 for 2 %; good linearities were obtained at these levels. Apparent recoveries were evaluated at 0.003, 0.005, and 0.010 mg/kg. At the lowest recovery level, 93 % of compounds showed recoveries between 70 and 120 %. The rest of the compounds were in the range of 63-129 %, with relative standard deviation values below 20 %. For mycotoxins, the limits of quantitation ranged from 0.0001 to 0.100 mg/kg, with matrix-matched concentrations assessed within this range. Recoveries were evaluated at low concentration range (0.001-0.003 mg/kg) and high range (0.020-0.050) with apparent recoveries values between 92 and 140 %. Finally, a total of 31 commercial baby food samples were analysed using this method. The results indicated that 16 samples contained pesticide residues, while two samples were found to have mycotoxins.


Subject(s)
Food Contamination , Infant Food , Mycotoxins , Pesticide Residues , Mycotoxins/analysis , Pesticide Residues/analysis , Infant Food/analysis , Food Contamination/analysis , Mass Spectrometry/methods , Humans , Limit of Detection , Infant
9.
Microbiol Spectr ; 12(6): e0061424, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38727230

ABSTRACT

We describe four cases of a novel carbapenem-resistant Pseudomonas aeruginosa ST179 clone carrying the blaKPC-2 or blaKPC-35 gene together with blaIMP-16, imported from Peru to Spain and isolated from leukemia patients. All isolates were multidrug-resistant but remained susceptible to fosfomycin, cefiderocol, and colistin. Whole-genome sequencing revealed that blaKPC-2 and blaKPC-35 were located in an IncP6 plasmid, whereas blaIMP-16 was in a chromosomal type 1 integron. This study highlights the global threat of multidrug-resistant P. aeruginosa clones and underscores the importance of monitoring and early detection of emerging resistance mechanisms to guide appropriate treatment strategies. The importation and spread of such clones emphasize the urgent need to implement strict infection control measures to prevent the dissemination of carbapenem-resistant bacteria. IMPORTANCE: This is the first documented case of a Pseudomonas aeruginosa ST179 strain carrying the blaKPC-35 gene, and it represents the first report of a P. aeruginosa co-harboring blaIMP-16 and either blaKPC-2 or blaKPC-35, which wre imported from Peru to Spain, highlighting a threat due to the capacity of spreading carbapenem-resistance via plasmid conjugation.


Subject(s)
Anti-Bacterial Agents , Carbapenems , Drug Resistance, Multiple, Bacterial , Pseudomonas Infections , Pseudomonas aeruginosa , beta-Lactamases , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification , Pseudomonas aeruginosa/enzymology , Humans , Spain , Peru , Pseudomonas Infections/microbiology , Carbapenems/pharmacology , beta-Lactamases/genetics , beta-Lactamases/metabolism , Anti-Bacterial Agents/pharmacology , Male , Drug Resistance, Multiple, Bacterial/genetics , Plasmids/genetics , Microbial Sensitivity Tests , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Whole Genome Sequencing , Female , Middle Aged , Adult
10.
Trop Med Int Health ; 29(5): 343-353, 2024 May.
Article in English | MEDLINE | ID: mdl-38481292

ABSTRACT

AIM: This study aimed to investigate the impact of communicable diseases with epidemic potential in complex emergency (CE) situations, focusing on the epidemiological profile of incidence and mortality and exploring underlying factors contributing to increased epidemic risks. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review (PRISMA-ScR) guidelines, we conducted a scoping review of articles published between 1990 and 2022. The search included terms related to complex emergencies, communicable diseases, outbreaks, and epidemics. We identified 92 epidemics related to CE occurring in 32 different countries. RESULTS: Communicable diseases like Shigellosis, Cholera, Measles, Meningococcal meningitis, Yellow Fever, and Malaria caused significant morbidity and mortality. Diarrhoeal diseases, particularly Cholera and Shigellosis, had the highest incidence rates. Shigella specifically had an incidence of 241.0 per 1000 (people at risk), with a mortality rate of 11.7 per 1000, while Cholera's incidence was 13.0 per 1000, with a mortality rate of 0.22 per 1000. Measles followed, with an incidence of 25.0 per 1000 and a mortality rate of 0.76 per 1000. Meningococcal Meningitis had an incidence rate of 1.3 per 1000 and a mortality rate of 0.13 per 1000. Despite their lower incidences, yellow fever at 0.8 per 1000 and malaria at 0.4 per 1000, their high case fatality rates of 20.1% and 0.4% remained concerning in CE. The qualitative synthesis reveals that factors such as water, sanitation, and hygiene, shelter and settlements, food and nutrition, and public health and healthcare in complex emergencies affect the risk of epidemics. CONCLUSION: Epidemics during complex emergencies could potentially lead to a public health crisis. Between 1990 and 2022, there have been no statistically significant changes in the trend of incidence, mortality, or fatality rates of epidemic diseases in CE. It is crucial to understand that all epidemics identified in CE are fundamentally preventable.


Subject(s)
Emergencies , Epidemics , Humans , Incidence , Emergencies/epidemiology , Communicable Diseases/epidemiology , Communicable Diseases/mortality , Altruism
11.
Int J Infect Dis ; 143: 107020, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38548167

ABSTRACT

OBJECTIVES: De-escalation (DES) from echinocandins to azoles is recommended by several medical societies in Candida infections. We summarise the evidence of DES on clinical and microbiological cure and 30-day survival and compare it with continuing the treatment with echinocandins (non-DES). METHODS: We searched MEDLINE, Embase, Web of Science and Scopus. Studies describing DES in inpatients and reporting any of the outcomes evaluated were included. Pooled estimates of the tree outcomes were calculated with a fixed or random-effects model. Heterogeneity was explored stratifying by subgroups and via meta-regression. This systematic review is registered with PROSPERO (CRD42023475486). RESULTS: Of 1853 records identified, 9 studies were included, totalling 1575 patients. Five studies stepped-down to fluconazole; one to voriconazole and three to any of azoles. The mean day of DES was 5.2 (4.6-6.5) days. The clinical cure OR was 1.29 (95% CI: 0.88-1.88); the microbiological cure 1.62 (95% CI: 0.71-3.71); and 30-day survival 2.17 (95% CI: 1.09-4.32). The 30-day survival data into subgroups showed higher effect on critically ill patients and serious-risk bias studies. Meta-regression did not identify significant effect modifiers. CONCLUSIONS: DES is a safe strategy; it showed no higher 30-day mortality and a trend towards greater clinical and microbiological cure.


Subject(s)
Antifungal Agents , Candidiasis , Humans , Antifungal Agents/therapeutic use , Candidiasis/drug therapy , Candidiasis/mortality , Candidiasis/microbiology , Fluconazole/therapeutic use , Candida/drug effects , Voriconazole/therapeutic use , Echinocandins/therapeutic use , Treatment Outcome , Azoles/therapeutic use , Azoles/pharmacology
12.
Int Emerg Nurs ; 74: 101442, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38537317

ABSTRACT

BACKGROUND: The competence of a Primary Health Care nurse to handle emergency situations depends largely on prior acquisition of theoretical knowledge to make appropriate decisions, combined with the corresponding practical skills to carry out swift and effective interventions. METHODS: Cross-sectional study conducted in through a survey auto-administered to a simple random sample of 269 nurses (n) with replacement of Asturias, Spain from the total nursing staff of 730 members (N) in Asturias. RESULTS: In rural areas, the most frequently mentioned reasons were the lack of practical skills (18.9%) and the absence of adequate material (14.4 %). In the semi-urban area, the most common reasons were the lack of practical skills (13.2 %) and the lack of theoretical knowledge (10.3 %). Finally, in the urban area, the main reasons were the lack of practical skills (14.4 %) and the absence of adequate material (7.2 %). The differences were significant (p = 0.025). CONCLUSIONS: Despite the requirement that they acquire the necessary theoretical and practical skills, not all PHC nurses perceive themselves to be sufficiently prepared. The degree of self-perceived acquisition of this knowledge and skills, which is so important and necessary, is heterogeneous, with clear differences according to the respective field of work.


Subject(s)
Clinical Competence , Primary Health Care , Humans , Cross-Sectional Studies , Spain , Female , Male , Adult , Clinical Competence/standards , Middle Aged , Surveys and Questionnaires , Primary Care Nursing , Emergency Nursing
13.
Eur J Med Chem ; 265: 116114, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38194775

ABSTRACT

The BRCA2-RAD51 interaction remains an intriguing target for cancer drug discovery due to its vital role in DNA damage repair mechanisms, which cancer cells become particularly reliant on. Moreover, RAD51 has many synthetically lethal partners, including PARP1-2, which can be exploited to induce synthetic lethality in cancer. In this study, we established a 19F-NMR-fragment based approach to identify RAD51 binders, leading to two initial hits. A subsequent SAR program identified 46 as a low micromolar inhibitor of the BRCA2-RAD51 interaction. 46 was tested in different pancreatic cancer cell lines, to evaluate its ability to inhibit the homologous recombination DNA repair pathway, mediated by BRCA2-RAD51 and trigger synthetic lethality in combination with the PARP inhibitor talazoparib, through the induction of apoptosis. Moreover, we further analyzed the 46/talazoparib combination in 3D pancreatic cancer models. Overall, 46 showed its potential as a tool to evaluate the RAD51/PARP1-2 synthetic lethality mechanism, along with providing a prospect for further inhibitors development.


Subject(s)
Antineoplastic Agents , Pancreatic Neoplasms , Humans , Antineoplastic Agents/chemistry , BRCA2 Protein/antagonists & inhibitors , BRCA2 Protein/metabolism , Cell Line, Tumor , DNA Repair , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Poly(ADP-ribose) Polymerase Inhibitors/chemistry , Rad51 Recombinase/antagonists & inhibitors , Rad51 Recombinase/metabolism , Synthetic Lethal Mutations
14.
Infection ; 52(1): 165-172, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37515691

ABSTRACT

PURPOSE: We aimed to evaluate the performance of the FilmArray (FA) meningitis/encephalitis (ME) panel. Secondarily, we analyzed the false positive (FP) and false negative (FN) results, as well as the predictive values of the technique, regarding the cerebrospinal fluid (CSF) characteristics. METHODS: FA is a multiplex real-time PCR detecting 14 of the most common ME pathogens in CSF. All FA performed at our hospital (2018-2022) were retrospectively reviewed. FA was compared to conventional techniques and its performance was assessed based on the final diagnosis of the episode. RESULTS: FA was performed in 313 patients with suspicion of ME. Most patients had altered mental status (65.2%) and fever (61%). Regarding CSF characteristics, 49.8% and 53.7% presented high CSF proteins and pleocytosis, respectively. There were 84 (26.8%) positive FA results, mainly for HSV-1 (10.9%), VZV (5.1%), Enterovirus (2.6%), and S. pneumoniae (1.9%). In the 136 cases where both FA and routine methods were performed, there was a 25.7% lack of agreement. We identified 6.6% FN results, but 28.6% FP, mainly due to HSV-1. This resulted in a high negative predictive value (NPV) of 93.4%, but a positive predictive value (PPV) of 73%. Remarkably, PPV as low as 36.9%, and 70.2%, were found in cases without pleocytosis, or lack of high CSF protein levels, respectively. CONCLUSION: FA was associated with high NPV, but frequent FP results and low PPV, particularly for HSV-1, and especially in patients without high CSF protein levels or pleocytosis.


Subject(s)
Encephalitis , Meningitis , Meningoencephalitis , Humans , Meningitis/diagnosis , Encephalitis/diagnosis , Real-Time Polymerase Chain Reaction , Retrospective Studies , Leukocytosis , Meningoencephalitis/diagnosis , Multiplex Polymerase Chain Reaction/methods
15.
Glob Health Promot ; 31(1): 111-119, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37933817

ABSTRACT

OBJETIVO: identificar el nivel de conocimientos sobre la COVID-19 que tiene la población adulta residente en Gijón (España) después de dos años de pandemia. MÉTODOS: se realizó un estudio descriptivo transversal entre marzo del 2021 y marzo del 2022. Los datos se obtuvieron mediante un cuestionario telefónico sobre una muestra estratificada de tres zonas básicas de salud de Gijón, España (Calzada, Zarracina y Parque-Somió). El tamaño muestral se compuso de 305 personas. Se empleó el análisis ji-cuadrado para estudiar la relación entre variables categóricas y ANOVA para comparar las medias de la puntuación total por zona básica. Se realizaron regresiones logísticas para calcular las odds ratio entre la variable dependiente (poseer conocimientos avanzados) y las independientes (variables sociodemográficas). Se construyó un modelo predictivo entre la existencia o no de conocimiento avanzado y las variables independientes mediante regresión logística. RESULTADOS: se encontraron diferencias en la puntuación media del nivel de conocimientos entre Parque-Somió y Calzada (p = 0.000) y Parque-Somió y Zarracina (p = 0.045), obteniendo mayor puntuación media la de Parque-Somió. Se observó una asociación entre el nivel de conocimientos y las variables medio de información utilizado (p = 0.018), edad (p = 0.036), zona básica de salud (p = 0.000), nivel educativo (p = 0.000) e historia previa de contacto estrecho (p = 0.004). CONCLUSIONES: el nivel de conocimientos avanzado se presenta sobre todo en las zonas básicas de salud con mayor nivel socioeconómico, población con nivel educativo alto, de 25 a 45 años, que se ha informado por su entorno y con historia previa de seguimiento por ser contacto estrecho.


Subject(s)
Alkalies , COVID-19 , Lactose/analogs & derivatives , Humans , COVID-19/epidemiology , Retrospective Studies
16.
Article in English | MEDLINE | ID: mdl-38127203

ABSTRACT

Few studies have reported long-term follow-up data on selective preventive interventions for adolescents. No follow-up selective preventive transdiagnostic studies for adolescents at-risk for emotional disorders, such as anxiety and depression, have been reported. To fill this gap, this study aims to provide the first follow-up assessment of a randomized controlled trial (RCT) studying selective transdiagnostic prevention in at-risk adolescents. A 12-month follow-up assessment was conducted with subjects who originally received either PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), PROCARE+, which includes the PROCARE protocol along with personalized add-on modules or an active control condition (ACC) based on emotional psychoeducation, and their respective booster session for each experimental condition. 80 subjects (47.5% girls) aged between 12 and 18 years (M = 14.62; SD 1.43) who completed these treatment conditions were available for the 12-month follow-up. The results demonstrate the superior long-term efficacy of the PROCARE+ intervention in mitigating emotional symptoms and obsessive-compulsive symptomatology compared to the PROCARE and ACC conditions, with effect sizes notably exceeding those commonly observed in preventive programs. While the three treatments demonstrated beneficial impacts, the pronounced results associated with PROCARE+ at the 12-month follow-up emphasized the importance of personalized treatment modules and the sustained benefits of booster sessions in the realm of preventive psychological interventions. The findings also highlight the potential role of add-on modules in enhancing the effects of the PROCARE+ condition.

17.
Anal Bioanal Chem ; 415(26): 6551-6560, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37698599

ABSTRACT

Spices such as paprika, curry, turmeric, dry chilli, and black pepper are grown in various geographic locations and widely used by consumers across the world. Pesticides applied during crop production practices could contaminate the produce, affecting the quality and posing a health risk for consumers. The complexity of the spice matrix and the wide range of target pesticides potentially present require special sample extraction and clean-up treatments to overcome matrix interference and ion suppression. In this study, sample extracts from spice matrices (paprika/curry/turmeric/dry chilli/black pepper) were cleaned up by an automated µSPE clean-up method for multi-residue analysis of pesticides using LC-MS/MS. The automated µSPE clean-up method involves pre-filled cartridges containing various sorbent materials suitable for numerous co-extractives and the automated clean-up process was carried out using an autosampler. The regulatory limit for pesticides in spices varies with type, with a low MRL of 0.05 mg kg-1 or higher for 99% of the analytes. At spiking concentrations of 0.05 and 0.1 mg kg-1, good recoveries between 70 and 120% with RSD values below 20% were achieved for more than 98% of the compounds. With automatic clean-up of samples that takes 5 min/sample, 20% increased output per day shows an important advantage achieved compared to manual clean-up.

18.
Prehosp Disaster Med ; 38(5): 601-605, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37559200

ABSTRACT

INTRODUCTION: Peru's health infrastructures, particularly hospitals, are exposed to disaster threats of different natures. Traditionally, earthquakes have been the main disaster in terms of physical and structural vulnerability, but the coronavirus disease 2019 (COVID-19) pandemic has also shown their functional vulnerability. Public hospitals in Lima are very different in terms of year constructed, type of construction, and number of floors, making them highly vulnerable to earthquakes. In addition, they are subject to a high demand for care daily. Therefore, if a major earthquake were to occur in Lima, the hospitals would not have the capacity to respond to the high demand. OBJECTIVE: The aim of this study was to analyze the Hospital Safety Index (HSI) in hospitals in Lima (Peru). MATERIALS AND METHODS: This was a cross-sectional observational study of 18 state-run hospitals that met the inclusion criteria; open access data were collected for the indicators proposed by the Pan American Health Organization (PAHO) Version 1. Associations between variables were calculated using the chi-square test, considering a confidence level of 95%. A P value less than .05 was considered to determine statistical significance. RESULTS: The average bed occupancy rate was 90%, the average age was 70 years, on average had one bed per 25,126 inhabitants, and HSI average score was 0.36 with a vulnerability of 0.63. No association was found between HSI and hospital characteristics. CONCLUSION: Most of the hospitals were considered Category C in earthquake and disaster safety, and only one hospital was Category A. The hospital situation needs to be clarified, and the specific deficiencies of each institution need to be identified and addressed according to their own characteristics and context.


Subject(s)
COVID-19 , Disaster Planning , Disasters , Humans , Aged , Peru/epidemiology , Hospitals, State , Cross-Sectional Studies , COVID-19/epidemiology , Hospitals
19.
J Antimicrob Chemother ; 78(9): 2291-2296, 2023 09 05.
Article in English | MEDLINE | ID: mdl-37533351

ABSTRACT

OBJECTIVES: To assess the microbiological characteristics of Escherichia coli causing healthcare-associated bacteraemia of urinary origin (HCA-BUO) in Spain (ITUBRAS-2 project), with particular focus on ESBL producers and isolates belonging to ST131 high-risk clone (HiRC). Clinical characteristics and outcomes associated with ST131 infection were investigated. METHODS: A total of 222 E. coli blood isolates were prospectively collected from patients with HCA-BUO from 12 tertiary-care hospitals in Spain (2017-19). Antimicrobial susceptibility and ESBL/carbapenemase production were determined. ST131 subtyping was performed. A subset of 115 isolates were selected for WGS to determine population structure, resistome and virulome. Clinical charts were reviewed. RESULTS: ESBL-producing E. coli prevalence was 30.6% (68/222). ST131 represented 29.7% (66/222) of E. coli isolates and accounted for the majority of ESBL producers (46/68, 67.6%). The C2/H30-Rx subclone accounted for most ST131 isolates (44/66) and was associated with CTX-M-15 (37/44) and OXA-1 enzymes (27/44). Cluster C1-M27 was identified in 4/10 isolates belonging to subclade C1/H30-R1 and associated with CTX-M-27. Additionally, ST131 isolates showed a high content of other acquired resistance genes, and clade C/ST131 isolates carried characteristic QRDR mutations. They were categorized as uropathogenic E. coli and had higher aggregate virulence scores. ST131 infection was associated with more complex patients, prior use of cephalosporins and inadequate empirical treatment but was not associated with worse clinical outcomes. CONCLUSIONS: ST131 HiRC is the main driver of ESBL-producing E. coli causing HCA-BUO in Spain, mainly associated with the expansion of subclade CTX-M-15-C2/H30-Rx and the emergence of CTX-M-27-C1/H30-R1 (Cluster C1-M27).


Subject(s)
Bacteremia , Escherichia coli Infections , Humans , Escherichia coli , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Spain/epidemiology , Molecular Epidemiology , Genotype , Bacteremia/epidemiology , beta-Lactamases/genetics , Delivery of Health Care
20.
J Vasc Access ; : 11297298231189963, 2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37503714

ABSTRACT

BACKGROUND: The peripheral venous catheter is one of the most frequently used devices in inpatient units worldwide. The risk of complications arising from use of peripheral venous catheters is low, but phlebitis frequently develops. METHODS: A multicentre, prospective cohort study was conducted in 65 Spanish hospitals on 10,247 inpatients who had had a total of 38,430 peripheral venous catheters inserted. Data were collected for 15 consecutive days in 2017, 2018, 2019, 2020 and 2021. Central tendency and dispersion were measured, cumulative incidence and incidence density were determined and odds ratios (OR) were also calculated using binary logistic regression. RESULTS: The incidence density of phlebitis, during the period from 2017 to 2021, was 1.82 cases of phlebitis per 100 venous catheter-days. The difference between average cumulative incidence of phlebitis per year was statistically significant as determined by ANOVA test results (F = 10.51; df = 4; p < 0.000). Unequivocal risk factors for phlebitis were revealed to be hospitals with more than 500 beds (OR = 1.507; p < 0.001), patients suffering from neoplastic disease (OR = 1.234; p < 0.001) and the first 3-4 days after insertion (OR = 1.159; p < 0.001). CONCLUSIONS: A correct knowledge of insertion technique and venous catheter maintenance is likely to reduce the incidence of phlebitis and other complications, and hence continuing education of nurses is essential.

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