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by Catarina Simões, Diana S. Vasconcelos, Raquel Xavier, Xavier Santos, Catarina Rato, D. James Harris
Fire has long been recognized as an important ecological and evolutionary force in plant communities, but its influence on vertebrate community ecology, particularly regarding predator-prey interactions, remains understudied. This study reveals the impact of wildfires on the diet of Podarcis lusitanicus, a lizard species inhabiting a fire-prone region in the Iberian Peninsula. In order to explore diet variability associated with different local burn histories, we evaluated P. lusitanicus diet across three types of sites in Northern Portugal: those had not burned since 2016, those burned in 2016, and those more recently burned in 2022. Podarcis lusitanicus is a generalist arthropod predator with dietary flexibility. Given the turnover of arthropod species after fire, it is expected to find variations in diet caused by different fire histories, especially between unburned and recently burned sites. From DNA metabarcoding of faecal samples, our study revealed that while prey richness remained unaffected by wildfire regime, significant shifts occurred in diet composition between more recently burned and unburned areas. Specifically, we found that differences in diet composition between these two fire regimes were due to the presence of Tapinoma ants and jumping spiders (Salticus scenicus). These prey were present in the diets of lizards occupying unburned areas, while these were absent in areas burned in 2022. Interestingly, diets in unburned areas and areas burned in 2016 showed no significant differences, highlighting the lizards’ ecological flexibility and the habitat’s resilience over time. The ant species T. topitotum was found in dominance in both burned areas, suggesting that this species may be fire tolerant. In addition, families such as Cicadellidae and Noctuidae were found to be more associated with more recently burned areas. The use of DNA metabarcoding in this study was essential to provide a more detailed and accurate view of predator-prey interactions in ecosystems susceptible to fire, and therefore a better understanding of changes in prey consumption in this fire-adapted ecosystem.To measure the perceived autonomy level in managing lower respiratory tract infections (LRTIs) among paediatric residents and to compare perceived autonomy with the assessments by tutors who directly supervise and evaluate residents
A survey on managing LRTIs was distributed among all Italian paediatric residents and tutors via Google Forms between January 1 and 31, 2024.
Participants, residents and tutors were classified according to their training year and clinical setting: primary care paediatrics (PCP), emergency department (ED) and hospital ward (HW).
Perceived autonomy of paediatric residents in managing LRTI in different settings; overall perceived autonomy and interest in employment.
A total of 391 questionnaires were returned, with 273 completed by residents and 118 by tutors. Among residents, 3% in their first year felt fully capable of managing LRTIs without supervision in both ED and HW settings. This percentage remained below 25% until the third year and increased to 72% in ED and 83% in HW by the fifth year. In PCP settings, autonomy ranged from 15% in the first year to 96% in the final year. No differences were found between residents’ self-evaluations and tutors’ assessments. Confidence in skills showed no regional differences across Italy.
Most residents did not feel ready to manage winter respiratory infections in children without supervision, especially in the ED compared with the HW; however, self-confidence was higher in the PCP setting. Tutors shared similar perceptions. The location did not affect the response pattern. These findings caution against employing residents to work autonomously, particularly in emergency settings.
In Indonesia, antibiotics are often purchased without a prescription at community pharmacies, contrary to current regulations. This practice may increase the risk of out-of-specification (OOS) medicines being dispensed, potentially contributing to treatment failure and antibiotic resistance. To address this concern, we assessed the quality of antibiotics purchased without a prescription at private drug retail outlets (PDROs) in Indonesia.
We conducted a cross-sectional study in Tabalong and Bekasi, Indonesia, using standardised patients (SPs) who purchased antibiotics without a prescription for three clinical scenarios: upper respiratory tract infection (URTI), tuberculosis (TB) and child diarrhoea. The pharmacies and drug stores were randomly selected from each subdistrict based on the probability proportional method. We measured the active pharmaceutical ingredient (API) content of the antibiotic samples using high-performance liquid chromatography (HPLC).
The quality of 183 antibiotics including amoxicillin tablets (148/183, 80.9%, 95% CI 74.7% to 86.1%), amoxicillin dry syrup (12/183, 6.6%, 95% CI 3.6% to 10.8%), ampicillin tablets (5/183, 2.7%, 95% CI 1.1% to 5.9%) and ciprofloxacin tablets (18/183, 9.8%, 95% CI 6.2% to 14.8%) obtained from 117/166 (70.5%, 95% CI 62.8 to 77.2) PDROs were tested. Descriptive statistics were used to describe the characteristics of the purchased antibiotics, and the API content of each antibiotic was compared against the United States Pharmacopeia 43-National Formulary 38 (USP 43-NF 38) standards in absolute values and percentages.
Almost all samples produced in Indonesia (182/183, 99.5%, 95% CI 97.5% to 99.9%) were unbranded (123/183, 67.2%, 95% CI 60.2% to 73.7%) or branded generic (60/183, 32.8%, 95% CI 26.3% to 39.8%) and packaged in strips (165/183, 90.2%, 95% CI 85.2% to 93.8%). Around 12/183 (6.6%, 95% CI 3.6% to 10.8%) antibiotics were found to be OOS; these were mostly amoxicillin 125 mg dry syrup (6/12, 50%, 95% CI 24.3% to 75.7%) and ciprofloxacin 500 mg tablet (5/18, 27.8%, 95% CI 11.5% to 50.6%). Around 33% (4/12, 95% CI 12.5% to 61.2%) of amoxicillin 125 mg dry syrup samples had an API content above the label claim, the highest being 187%, whereas 16.7% (2/12, 95% CI 3.6% to 43.6%) were below the label claim, the lowest being 64%. About 27.8% (5/18, 95% CI 11.5% to 50.6%) of ciprofloxacin samples tested had an API content above the label claim; the highest was 120%.
While the proportion of OOS antibiotics identified was relatively small, at a population level, it represents a significant proportion of sub-optimally treated infections.
by Ian C. Lock, Nathan H. Leisenring, Warren Floyd, Eric S. Xu, Lixia Luo, Yan Ma, Erin C. Mansell, Diana M. Cardona, Chang-Lung Lee, David G. Kirsch
BackgroundThe tumor suppressor p53 (Trp53), also known as p53, is the most commonly mutated gene in cancer. Canonical p53 DNA damage response pathways are well characterized and classically thought to underlie the tumor suppressive effect of p53. Challenging this dogma, mouse models have revealed that p53-driven apoptosis and cell cycle arrest are dispensable for tumor suppression. Here, we investigated the inverse context of a p53 mutation predicted to drive the expression of canonical targets but is detected in human cancer.
MethodsWe established a novel mouse model with a single base pair mutation (GAG>GAT, p53E221D) in the DNA-Binding domain that has wild-type function in screening assays, but is paradoxically found in human cancer in Li-Fraumeni syndrome. Using mouse p53E221D and the analogous human p53E224D mutants, we evaluated expression, transcriptional activation, and tumor suppression in vitro and in vivo.
ResultsExpression of human p53E224D from cDNA translated to a fully functional p53 protein. However, p53E221D/E221D RNA transcribed from the endogenous locus is mis-spliced resulting in nonsense-mediated decay. Moreover, fibroblasts derived from p53E221D/E221D mice do not express a detectable protein product. Mice homozygous for p53E221D exhibited increased tumor penetrance and decreased life expectancy compared to p53WT/WT animals.
ConclusionsMouse p53E221D and human p53E224D mutations lead to splice variation and a biologically relevant p53 loss of function in vitro and in vivo.
by Irazú Contreras-Yáñez, Guillermo A. Guaracha-Basáñez, Diana Padilla-Ortiz, Laura L. Franco-Mejía, Laura V. Vargas-Sánchez, Julia G. Jiménez-Decle, Virginia Pascual-Ramos
IntroductionMany factors influence how doctors make treatment decisions. The study compares the outcomes of patients with rheumatic diseases and adequate control (AC) whose treating rheumatologists prescribed their first choice of treatment (FCHO) versus the second choice (SCHO) and the motivations behind them. It also investigates the motivations associated with FCHO.
Patients and methodsThe study was conducted at an outpatient clinic from February 2023 to February 2024. Patients with an RMD diagnosis were identified using systematic sampling (P-1). After their consultation, their rheumatologists detailed their treatment choice (FCHO vs. SCHO), the motivations behind it, and the outcomes. In a subsample of patients from P-1 and AC (SubP-1), treating rheumatologists repeated the assessment of outcomes at the next scheduled consultation. Descriptive statistics and multivariate regression analysis were used.
ResultsThere were 703 patients enrolled (P-1), 543 (77.2%) had AC, and 292 (Subp-1) underwent a follow-up evaluation. In P-1 and subP-1, FCHO was prescribed to 644 (91.5%) and 269 (92.1%) patients.Motivations related to evidence-based medicine and personal experience were more frequently referred to in FCHO. Concerns related to current or future drug shortages and a history of adverse events/intolerance were more frequent in SCHO.In SubP-1, a higher proportion of patients remained in AC and experienced remission/ improved disease activity with FCHO. Patients who received FCHO experienced a greater risk for favorable outcomes.The following motivations were associated with FCHO: “It aligns with guidelines”; “solid scientific evidence supporting the treatment effectiveness”; “I am concerned that the shortage of the drug may hinder the continuation of the treatment” and “history of adverse events or intolerance”.
ConclusionsPatients with AC of their underlying RMD, whose rheumatologists prescribed their FCHO, had better outcomes than those who were prescribed SCHO. Evidence-based motivations, rheumatologists´ concern of medication shortage, and patient-related motivations were associated with FCHO.
To investigate the effectiveness of antimicrobial agents against wound infections, experiments using either 2D cultures with planktonic microorganisms or animal infection models are frequently carried out. However, the transferability of the results to human skin is limited by the lack of complexity of the 2D models or by the poor translation of the results from animal models. Hence, there is a need for wound infection models capable of assessing antimicrobial agents. In this study, an easily standardized wound infection model was established. This model consists of a mechanically wounded human skin model on a collagen matrix infected with various clinically relevant bacteria. Infection of the model led to recognition of the pathogens and induction of an inflammatory response. The untreated infection spread over time, causing significant tissue damage. By applying an antimicrobial-releasing wound dressing, the bacterial load could be reduced and the success of the treatment could be further measured by a decrease in the inflammatory reaction. In conclusion, this wound infection model can be used to evaluate new antimicrobial therapeutics as well as to study host-pathogen interactions.
FreshRSS 