Re-evaluation of shellac (E 904) as a food additive and a new application on the extension of use of shellac (E 904) in dietary foods for special medical purposes.

The present opinion deals with the re-evaluation of shellac (E 904) when used as a food additive and with the new application on the extension of use of shellac (E 904) in dietary foods for special medical purposes. The Panel derived an acceptable daily intake (ADI) of 4 mg/kg body weight (bw) per day for wax-free shellac (E 904) produced by physical decolouring, based on a NOAEL of 400 mg/kg bw per day and applying an uncertainty factor of 100. The Panel concluded that the ADI of 4 mg/kg bw per day should be considered temporary for wax-free shellac (E 904) produced by chemical bleaching, while new data are generated on the identity and levels of the organochlorine impurities in E 904. This ADI is not applicable for wax-containing shellac as a food additive. For several age groups, the ADI was exceeded at the 95th percentile in the non-brand-loyal exposure assessment scenario and maximum level exposure assessment scenario. Considering the low exceedance and the fact that both the exposure estimation and the toxicological evaluation of shellac were conservative, the panel concluded that the calculated exceedance of the ADI does not indicate a safety concern. The Panel recommended to the European Commission separating specifications for E 904 depending on the manufacturing process, chemical bleaching and physical decolouring, because they result in different impurities; revising the definition of the food additive to include a description of each manufacturing process; deleting information on wax-containing shellac from the EU specifications; revising the acid value for wax-free shellac produced by chemical bleaching; lowering the maximum limit for lead; to consider introducing limits for other toxic elements potentially present in shellac; including a maximum limit for chloroform and total inorganic chloride in the EU specification for shellac produced by chemical bleaching.

Flavouring Group Evaluation 80, Revision 2 (FGE.80Rev2): Consideration of alicyclic, alicyclic-fused and aromatic-fused ring lactones evaluated by the JECFA (61st and 82nd meetings) structurally related to an aromatic lactone evaluated in FGE.27.

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 14 flavouring substances assigned to the Flavouring Group Evaluation 80 (FGE.80), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Thirteen substances have already been considered in FGE.80 and its revision and in FGE.96 [FL-no: 10.005, 10.024, 10.025, 10.050, 10.061, 10.069, 10.070, 10.072, 10.169, 13.009, 13.012, 13.161 and 16.055]. The remaining flavouring substance 3a,4,5,7a-tetrahydro-3,6-dimethylbenzofuran-2(3H)-one [FL-no: 10.057] has been cleared with respect to genotoxicity in FGE.217Rev3 and it is considered in this revision 2 of FGE.80. The substance [FL-no: 10.057] was evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, threshold of toxicological concern (TTC) and available data on metabolism and toxicity. The Panel concluded that [FL-no: 10.057] does not give rise to safety concerns at its levels of dietary intake, when estimated on the basis of the 'Maximised Survey-derived Daily Intake' (MSDI) approach. Besides the safety assessment of the flavouring substance, the specifications for the material of commerce have also been considered and the information provided was complete for [FL-no: 10.057]. However, for the flavouring substance [FL-no: 10.057] in the present revision and for eight substances evaluated in previous revisions, the 'modified Theoretical Added Maximum Daily Intakes' (mTAMDIs) values are above the TTC for their structural class (III). For four substances previously evaluated in FGE.80Rev1 and in FGE.96, use levels are still needed to calculate the mTAMDI estimates. Therefore, in total for 13 flavouring substances, data on uses and use levels should be provided to finalise their safety evaluations. For [FL-no: 10.050, 10.069 and 13.161], information on the composition of stereoisomeric mixtures is needed.

Glycaemia and ischaemia-reperfusion brain injury in patients with ischaemic stroke treated with mechanical thrombectomy (GLIAS-MT): an observational, unicentric, prospective study protocol.

INTRODUCTION: Poststroke hyperglycaemia is an independent risk factor for poorer outcomes in patients treated with mechanical thrombectomy (MT) and is associated with a lower probability of functional recovery and higher mortality at 3 months. This study aims to evaluate the association between glucose levels during cerebral reperfusion with MT and functional recovery at 3 months, measured by subcutaneous continuous glucose monitoring (CGM) devices. METHODS: This prospective observational study aims to recruit 100 patients with ischaemic stroke and large anterior circulation vessel occlusion, in whom MT is indicated. CGM will be performed using a Freestyle Libre ProIQ device (FSL-CGM, Abbott Diabetes Care, Alameda, California, USA), which will be implanted on admission to the emergency department, to monitor glucose levels before, during and after reperfusion. The study's primary endpoint will be the functional status at 3 months, as measured by the dichotomised modified Rankin Scale (0-2 indicating good recovery and 3-6 indicating dependency or death). We will analyse expression profiles of microRNA (miRNA) at the time of reperfusion and 24 hours later, as potential biomarkers of ischaemic-reperfusion injury. The most promising miRNAs include miR-100, miR-29b, miR-339, miR-15a and miR-424. All patients will undergo treatment according to current international recommendations and local protocols for the treatment of stroke, including intravenous thrombolysis if indicated. ETHICS AND DISSEMINATION: This study (protocol V.1.1, dated 29 October 2021, code 6017) has been approved by the Clinical Research Ethics Committee of La Paz University Hospital (Madrid, Spain) and has been registered in ClinicalTrials.gov (NCT05871502). Study results will be disseminated through peer-reviewed publications in Open Access format and at conference presentations. TRIAL REGISTRATION NUMBER: NCT05871502.

Distance-dependent neuromodulation effect during thermal ablation for atrial fibrillation.

INTRODUCTION: Thermal atrial fibrillation (AF) ablation exerts an additive treatment effect on the cardiac autonomic nervous system (CANS). This effect is mainly reported during ablation of the right superior pulmonary vein (RSPV), modulating the right anterior ganglionated plexus (RAGP), which contains parasympathetic innervation to the sinoatrial node in the epicardial fat pad between RSPV and superior vena cava (SVC). However, a variable response to neuromodulation after ablation is observed, with little to no effect in some patients. Our objective was to assess clinical and anatomic predictors of thermal ablation-induced CANS changes, as assessed via variations in heart rate (HR) postablation. METHODS: Consecutive paroxysmal AF patients undergoing first-time PV isolation by the cryoballoon (CB) or radiofrequency balloon (RFB) within a 12-month time frame and with preprocedural cardiac computed tomography (CT), were evaluated. Preablation and 24-h postablation electrocardiograms in sinus rhythm were collected and analyzed to assess HR. Anatomic evaluation by CT included the measurement of the shortest distance between the SVC and RSPV ostium (RSPV-SVC distance). RESULTS: A total of 97 patients (CB, n = 50 vs. RFB, n = 47) were included, with similar baseline characteristics between both groups. A significant HR increase postablation (ΔHR ≥ 15 bpm) occurred in a total of 37 patients (38.1%), without difference in number of patients between both thermal ablation technologies (CB, 19 [51%]), RFB, 18 [49%]). Independent predictors for increased HR were RSPV-SVC distance (odds ratio [OR]: 0.49, CI: 0.34-0.71, p value < .001), and age (OR: 0.94, CI: 0.89-0.98, p value = .003). CONCLUSIONS: Thermal balloon-based PV isolation influences the CANS through its effect on the RAGP, especially in younger patients and patients with shorter RSPV-SVC distance.

Dynamin-2 mutations linked to neonatal-onset centronuclear myopathy impair exocytosis and endocytosis in adrenal chromaffin cells.

Dynamins are large GTPases whose primary function is not only to catalyze membrane scission during endocytosis but also to modulate other cellular processes, such as actin polymerization and vesicle trafficking. Recently, we reported that centronuclear myopathy associated dynamin-2 mutations, p.A618T, and p.S619L, impair Ca2+-induced exocytosis of the glucose transporter GLUT4 containing vesicles in immortalized human myoblasts. As exocytosis and endocytosis occur within rapid timescales, here we applied high-temporal resolution techniques, such as patch-clamp capacitance measurements and carbon-fiber amperometry to assess the effects of these mutations on these two cellular processes, using bovine chromaffin cells as a study model. We found that the expression of any of these dynamin-2 mutants inhibits a dynamin and F-actin-dependent form of fast endocytosis triggered by single action potential stimulus, as well as inhibits a slow compensatory endocytosis induced by 500 ms square depolarization. Both dynamin-2 mutants further reduced the exocytosis induced by 500 ms depolarizations, and the frequency of release events and the recruitment of neuropeptide Y (NPY)-labeled vesicles to the cell cortex after stimulation of nicotinic acetylcholine receptors with 1,1-dimethyl-4-phenyl piperazine iodide (DMPP). They also provoked a significant decrease in the Ca2+-induced formation of new actin filaments in permeabilized chromaffin cells. In summary, our results indicate that the centronuclear myopathy (CNM)-linked p.A618T and p.S619L mutations in dynamin-2 affect exocytosis and endocytosis, being the disruption of F-actin dynamics a possible explanation for these results. These impaired cellular processes might underlie the pathogenic mechanisms associated with these mutations.

Increased Levels of Phosphorylated-P38α Induce WNT/ß-Catenin and NGF/P75NTR/TrkA Pathways Disruption and SN56 Cell Death following Single and Repeated Chlorpyrifos Treatment.

Chlorpyrifos (CPF) biocide, exposure to which is mainly produced in the human population through diet, induces several neurotoxic effects. CPF single and repeated exposure induces memory and learning disorders, although the mechanisms that produce these outcomes are complex and not well understood. CPF treatment (single and repeated) of cholinergic septal SN56 cells induced an increase in phosphorylated-P38α levels that led to WNT/ß-Catenin and NGF/P75NTR/TrkA pathways disruption and cell death. These results provide new knowledge on the mechanisms that mediate CPF basal forebrain cholinergic neuronal loss induced by CPF single and repeated exposure and can help unravel the way through which this compound produces cognitive decline and develop efficient treatments against these effects.

Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response.

BACKGROUND: Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. METHODS: We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. RESULTS: Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. CONCLUSION: These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.

Unraveling diabetes complexity through natural products, miRNAs modulation, and future paradigms in precision medicine and global health.

BACKGROUND AND AIMS: The challenge posed by diabetes necessitates a paradigm shift from conventional diagnostic approaches focusing on glucose and lipid levels to the transformative realm of precision medicine. This approach, leveraging advancements in genomics and proteomics, acknowledges the individualistic genetic variations, dietary preferences, and environmental exposures in diabetes management. The study comprehensively analyzes the evolving diabetes landscape, emphasizing the pivotal role of genomics, proteomics, microRNAs (miRNAs), metabolomics, and bioinformatics. RESULTS: Precision medicine revolutionizes diabetes research and treatment by diverging from traditional diagnostic methods, recognizing the heterogeneous nature of the condition. MiRNAs, crucial post-transcriptional gene regulators, emerge as promising therapeutic targets, influencing key facets such as insulin signaling and glucose homeostasis. Metabolomics, an integral component of omics sciences, contributes significantly to diabetes research, elucidating metabolic disruptions, and offering potential biomarkers for early diagnosis and personalized therapies. Bioinformatics unveils dynamic connections between natural substances, miRNAs, and cellular pathways, aiding in the exploration of the intricate molecular terrain in diabetes. The study underscores the imperative for experimental validation in natural product-based diabetes therapy, emphasizing the need for in vitro and in vivo studies leading to clinical trials for assessing effectiveness, safety, and tolerability in real-world applications. Global cooperation and ethical considerations play a pivotal role in addressing diabetes challenges worldwide, necessitating a multifaceted approach that integrates traditional knowledge, cultural competence, and environmental awareness. CONCLUSIONS: The key components of diabetes treatment, including precision medicine, metabolomics, bioinformatics, and experimental validation, converge in future strategies, embodying a holistic paradigm for diabetes care anchored in cutting-edge research and global healthcare accessibility.

Performance of risk scores in predicting mortality at 3, 6, and 12 months in patients diagnosed with community-acquired pneumonia.

BACKGROUND: Risk scores (RS) evaluate the likelihood of short-term mortality in patients diagnosed with community-acquired pneumonia (CAP). However, there is a scarcity of evidence to determine the risk of long-term mortality. This article aims to compare the effectiveness of 16 scores in predicting mortality at three, six, and twelve months in adult patients with CAP. METHODS: A retrospective cohort study on individuals diagnosed with CAP was conducted across two hospitals in Colombia. Receiver Operating Characteristic (ROC) curves were constructed at 3, 6, and 12 months to assess the predictive ability of death for the following scoring systems: CURB-65, CRB-65, SCAP, CORB, ADROP, NEWS, Pneumonia Shock, REA-ICU, PSI, SMART-COP, SMRT-CO, SOAR, qSOFA, SIRS, CAPSI, and Charlson Comorbidity Index (CCI). RESULTS: A total of 3688 patients were included in the final analysis. Mortality at 3, 6, and 12 months was 5.2%, 8.3%, and 16.3% respectively. At 3 months, PSI, CCI, and CRB-65 scores showed ROC curves of 0.74 (95% CI: 0.71-0.77), 0.71 (95% CI: 0.67-0.74), and 0.70 (95% CI: 0.66-0.74). At 6 months, PSI and CCI scores showed performances of 0.74 (95% CI: 0.72-0.77) and 0.72 (95% CI: 0.69-0.74), respectively. Finally at 12 months, all evaluated scores showed poor discriminatory capacity, including PSI, which decreased from acceptable to poor with an ROC curve of 0.64 (95% CI: 0.61-0.66). CONCLUSION: When predicting mortality in patients with CAP, at 3 months, PSI, CCI, and CRB-65 showed acceptable predictive performances. At 6 months, only PSI and CCI maintained acceptable levels of accuracy. For the 12-month period, all evaluated scores exhibited very limited discriminatory ability, ranging from poor to almost negligible.

Barriers to and facilitators of implementing colorectal cancer screening evidence-based interventions in federally qualified health centers: a qualitative study.

BACKGROUND: There is an urgent need to increase colorectal cancer screening (CRCS) uptake in Texas federally qualified health centers (FQHCs), which serve a predominantly vulnerable population with high demands. Empirical support exists for evidence-based interventions (EBIs) that are proven to increase CRCS; however, as with screening, their use remains low in FQHCs. This study aimed to identify barriers to and facilitators of implementing colorectal cancer screening (CRCS) evidence-based interventions (EBIs) in federally qualified health centers (FQHCs), guided by the Consolidated Framework for Implementation Research (CFIR). METHODS: We recruited employees involved in implementing CRCS EBIs (e.g., physicians) using data from a CDC-funded program to increase the CRCS in Texas FQHCs. Through 23 group interviews, we explored experiences with practice change, CRCS promotion and quality improvement initiatives, organizational readiness, the impact of COVID-19, and the use of CRCS EBIs (e.g., provider reminders). We used directed content analysis with CFIR constructs to identify the critical facilitators and barriers. RESULTS: The analysis revealed six primary CFIR constructs that influence implementation: information technology infrastructure, innovation design, work infrastructure, performance measurement pressure, assessing needs, and available resources. Based on experiences with four recommended EBIs, participants described barriers, including data limitations of electronic health records and the design of reminder alerts targeted at deliverers and recipients of patient or provider reminders. Implementation facilitators include incentivized processes to increase provider assessment and feedback, existing clinic processes (e.g., screening referrals), and available resources to address patient needs (e.g., transportation). Staff buy-in emerged as an implementation facilitator, fostering a conducive environment for change within clinics. CONCLUSIONS: Using CFIR, we identified barriers, such as the burden of technology infrastructure, and facilitators, such as staff buy-in. The results, which enhance our understanding of CRCS EBI implementation in FQHCs, provide insights into designing nuanced, practical implementation strategies to improve cancer control in a critical setting.

Sex and aging signatures of proteomics in human cerebrospinal fluid identify distinct clusters linked to neurodegeneration.

Sex and age are major risk factors for chronic diseases. Recent studies examining age-related molecular changes in plasma provided insights into age-related disease biology. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and neurodegeneration. By comprehensively examining 7,006 aptamers targeting 6,139 proteins in CSF obtained from 660 healthy individuals aged from 43 to 91 years old, we subsequently identified significant sex and aging effects on 5,097 aptamers in CSF. Many of these effects on CSF proteins had different magnitude or even opposite direction as those on plasma proteins, indicating distinctive CSF-specific signatures. Network analysis of these CSF proteins revealed not only modules associated with healthy aging but also modules showing sex differences. Through subsequent analyses, several modules were highlighted for their proteins implicated in specific diseases. Module 2 and 6 were enriched for many aging diseases including those in the circulatory systems, immune mechanisms, and neurodegeneration. Together, our findings fill a gap of current aging research and provide mechanistic understanding of proteomic changes in CSF during a healthy lifespan and insights for brain aging and diseases.

Encountering the health and social environment after a pregnancy loss: A grounded theory study from male perspective.

AIM: To develop an empirical model that explores and explains the social process of the encounters of men who suffered pregnancy loss with health and social environments. METHODS: A constructivist grounded theory method was performed, whereby 23 couples were interviewed using a semi-structured interview. Men that suffered pregnancy loss were analysed iteratively, with line-by-line and incident-to-incident coding, focused coding and axial coding, until data saturation and the emergence of theory. RESULTS: The theory Behind bars that hide and mask them illustrates the social process of the encounters of men who suffered pregnancy loss with the health and social environment. Social taboo and gender stereotypes could repress, marginalize, and hide men's feelings. This transposed into the healthcare setting, which focused on the physical aspects of the woman, and lacked an emotional approach, follow-up, and sensitivity. Men reported a lack of recognition or family and social support. CONCLUSION: Many men report not feeling involved in the care process after pregnancy loss, in addition to the prioritisation of medicalised care, which can be explained by a medical paternalism approach. These results provide a basis to reflect and plan the inclusion of men for the provision of comprehensive and couple-centred care. IMPLICATIONS FOR PRACTICE: Communication strategies and emotional management, self-reflection of health professionals, theoretical-practical content with a gender perspective in the training of nurses and midwives, involvement of the organisation and leadership, and further research is required.

Impact of SARS-CoV-2 infection on the cognitive functioning of patients institutionalized in nursing homes.

BACKGROUND: COVID-19 disease affected the cognitive level of institutionalized patients in nursing homes, especially in the older subjects regardless of gender. This study aims to assess cognitive impairment using the Mini-Mental State Examination (MMSE) before and after COVID-19 infection, and to determine whether these changes varied based on gender. METHODS: A pre- and post-COVID-19 study was conducted, involving 68 geriatric patients (34 men and 34 women) from two nursing homes. Cognitive impairment was assessed using the MMSE. RESULTS: COVID-19 infection had a notable impact on the cognitive health of older adults residing in nursing homes, primarily attributed to the social isolation they experienced. This effect was more pronounced in older individuals. A comparison of the MMSE results by gender before and after contracting COVID-19 revealed significant differences in attention and calculation, with women obtaining the worst score before the virus. However, following their recovery from the virus, men demonstrated significantly lower scores in time and space orientation and evocation. CONCLUSION: COVID-19 has led to a decline in cognitive functioning, significantly worsening the mental state of older individuals, even after recovery from the virus. Consequently, it is crucial to implement proactive measures to prevent isolation and safeguard the cognitive well-being of this vulnerable population.

Equine Corneal Wound Healing Using Mesenchymal Stem Cell Secretome: Case Report.

Corneal ulcers are a common and potentially vision-threatening condition in horses that can be challenging to treat with conventional therapies alone. This case report describes the successful treatment of a non-healing corneal ulcer in a 28-year-old Hispano-Bretón mare using the secretome derived from adipose tissue-derived mesenchymal stem cells (ASCs). Despite initial treatment with antibiotics, anti-inflammatory drugs, and surgical debridement, the corneal ulcer failed to heal properly, exhibiting persistent epithelial defects and stromal complications. As an alternative regenerative approach, the ASC secretome, a rich source of trophic factors, cytokines, and extracellular vesicles, was topically administered to the affected eye. Remarkably, within one week of secretome treatment, the clinical signs of blepharospasm and epiphora resolved, and the corneal ulcer exhibited complete re-epithelialization, regained transparency, and reduced neovascularization. No recurrence was observed during the 1.5-year follow-up period. This case highlights the potential therapeutic benefits of the ASC secretome in promoting corneal wound healing and suggests its promise as a novel cell-free therapy for treating refractory corneal ulcers in horses.

Influence of the pressure wire on the fractional flow reserve calculation: CFD analysis of an ideal vessel and clinical patients with stenosis.

BACKGROUND AND OBJECTIVE: Fractional Flow Reserve (FFR) is generally considered the gold standard in hemodynamics to assess the impact of a stenosis on the blood flow. The standard procedure to measure involves the displacement of a pressure guide along the circulatory system until it is placed next to the lesion to be analyzed. The main objective of the present study is to analyze the influence of the pressure guide on the invasive FFR measurements and its implications in clinical practice. METHODS: We studied the influence of pressure wires on the measurement of Fractional Flow Reserve (FFR) through a combination of Computational Fluid Dynamics (CFD) simulations using 45 clinical patient data with 58 lesions and ideal geometries. The analysis is conducted considering patients that were subjected to a computer tomography and also have direct measurements using a pressure guide. Influence of the stenosis severity, degree of occlusion and blood viscosity has also been studied. RESULTS: The influence of pressure wires specifically affects severe stenosis with a lumen diameter reduction of 50 % or greater. This type of stenosis leads to reduced hyperemic flow and increased coronary pressure drop. Thus, we identified that the placement of wires during FFR measurements results in partial obstruction of the coronary artery lumen, leading to increased pressure drop and subsequent reduction in blood flow. The severity of low FFR values associated with severe stenosis may be prone to overestimation when compared to stenosis without severe narrowing. These results have practical implications, particularly in the interpretation of lesions falling within the "gray zone" (0,75-0,80). CONCLUSIONS: The pressure wire's presence significantly alters the flow on severe lesions, which has an impact on the FFR calculation. In contrast, the impact of the pressure wire appears to be reduced when the FFR is larger than 0.8. The findings provide critical information for physicians, emphasizing the need for cautious interpretation of FFR values, particularly in severe stenosis. It also offers insights into improving the correlation between FFRct models and invasive measurements by incorporating the influence of pressure wires.

Rapid and Simple Morphological Assay for Determination of Susceptibility/Resistance to Combined Ciprofloxacin and Ampicillin, Independently, in Escherichia coli.

Current antibiograms cannot discern the particular effect of a specific antibiotic when the bacteria are incubated with a mixture of antibiotics. To prove that this task is achievable, Escherichia coli strains were treated with ciprofloxacin for 45 min, immobilized on a slide and stained with SYBR Gold. In susceptible strains, the nucleoid relative surface started to decrease near the MIC, being progressively condensed as the dose increased. The shrinkage level correlated with the DNA fragmentation degree. Ciprofloxacin-resistant bacilli showed no change. Additionally, E. coli strains were incubated with ampicillin for 45 min and processed similarly. The ampicillin-susceptible strain revealed intercellular DNA fragments that increased with dose, unlike the resistant strain. Co-incubation with both antibiotics revealed that ampicillin did not modify the nucleoid condensation effect of ciprofloxacin, whereas the quinolone partially decreased the background of DNA fragments induced by ampicillin. Sixty clinical isolates, with different combinations of susceptibility-resistance to each antibiotic, were co-incubated with the EUCAST breakpoints of susceptibility of ciprofloxacin and ampicillin. The morphological assay correctly categorized all the strains for each antibiotic in 60 min, demonstrating the feasible independent evaluation of a mixture of quinolone and beta-lactam. The rapid phenotypic assay may shorten the incubation times and necessary microbial mass currently required for evaluation.

Not all severe malaria cases are severe: Is it time to redefine severity criteria for malaria in non-endemic regions?

BACKGROUND: The current definition of severe malaria in non-endemic areas follows WHO criteria, which mainly target children in malaria-endemic areas, potentially misclassifying cases in non-endemic regions. We assessed the performance of a modified severe malaria classification criteria within our patient cohort. METHODS: A cohort study of patients managed for malaria in a non-endemic setting (2005-2023) was analyzed. We classified patients into severe malaria (SM) using WHO 2013 criteria except for hyperparasitemia, where 2 % threshold was applied. Patients with SM were distinguished as very severe malaria (VSM) when presenting at least one of the following conditions: parasitemia >10 %, pulmonary edema, impaired consciousness, seizures, renal failure, metabolic acidosis or hyperlactatemia, shock or hypoglycemia. In patients with SM and no criteria for VSM, less severe malaria (LSM) was defined by: 2-10 % parasitemia, hyperbilirubinemia, prostration, anemia or minor bleeding. The primary composite outcome was death or the need for a life-saving intervention, as analyzed in the three comparative groups. Secondary outcome was the prevalence of co-infections. RESULTS: Among 506 patients with malaria, 176 (34.8 %) presented with SM. A total of 37 (7.3 %) patients developed a life-threatening condition, namely death (n = 4) and/or the need for life-saving interventions (n = 34). All fatalities and 33 out of the 34 life-saving interventions occurred in the VSM group. Patients in LSM group did not develop any life-threatening conditions. As to co-infections, 28 (5.5 %) patients had a community-acquired co-infection, with no differences between groups (p = 0.763). CONCLUSIONS: Severity criteria definitions would benefit from a review when assessing patients with malaria in non-endemic areas. Within the spectrum of SM, patients reclassified as LSM have a low risk of developing a life-threatening condition and present low co-infection incidence and could benefit from management out of intensive care units and a restrictive use of empirical antibiotics.

Pereskia sacharosa Griseb. (Cactaceae) Prevents Lipopolysaccharide-Induced Neuroinflammation in Rodents via Down-Regulating TLR4/CD14 Pathway and GABAA γ2 Activity.

Pereskia sacharosa Griseb. is a plant used in traditional herbal medicine to treat inflammation. We analyzed the phenolic content of P. sacharosa leaves (EEPs) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and investigated the anti-inflammatory properties of EEPs and its flavonoid fraction (F10) in animal models subjected to acute neuroinflammation induced by bacterial lipopolysaccharide (LPS). Coronal brain sections of C57BL/6JN male mice or Wistar male rats administered with EEPs or F10 before LPS were subjected to in situ hybridization to determine c-fos and CD14 mRNA levels in the hypothalamus or GABAA γ2 mRNA levels in the hippocampus. Theta oscillations were recorded every 6 h in the hippocampus of Wistar rats. In total, five flavonoids and eight phenolic acids were identified and quantified in P. sacharosa leaves. Either EEPs or F10 crossed the blood-brain barrier (BBB) into the brain and reduced the mRNA expression of c-fos, CD14, and GABAA γ2. A decrease in theta oscillation was observed in the hippocampus of the LPS group, while the F10 + LPS group overrode the LPS effect on theta activity. We conclude that the bioactive compounds of P. sacharosa reduce the central response to inflammation, allowing the early return of ambulatory activity and well-being of the animal.

Conception, pregnancy, and childbirth from the perspective of transgender men: A meta-ethnography.

BACKGROUND: Transgender men who decide to gestate biologically often face a health system that is highly feminized and discriminatory. In addition, the lack of preparation and knowledge among healthcare professionals leads to the provision of care that fails to meet their specific needs. AIM: To synthesise the experiences of transgender men with regard to conception, pregnancy, and childbirth. METHOD: Ten studies were included in a synthesis of qualitative studies, following the interpretive meta-ethnography method developed by Noblit and Hare and summarized in accordance with the eMERGe meta-ethnography reporting guidelines. RESULTS: The metaphor of a divergent matryoshka dealing with a constricted reality helps us to understand the experiences of conception, pregnancy, and childbirth of transgender men, who often face stigma, discrimination, and marginalization in society and healthcare. The metaphor also highlights the gender dysphoria that arises from the physical changes associated with these processes. Four key themes emerge from this metaphor: (1) The decision to conceive being a trans man; (2) The challenge of adjusting to a new body reality; (3) The significance of navigating in an environment of non-representation; and (4) The marked absence of transsexuality in mainstream healthcare. CONCLUSIONS: Actions should prioritize strengthening ethical sensitivities and improve the training of health professionals to address issues such as gender perspectives, equality, and communication skills. Additionally, social visibility policies need to be implemented.

Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: a plain language summary of the monarchE study.

WHAT IS THIS SUMMARY ABOUT?: This article summarizes the most recent results of the monarchE study. This study was completed in participants with a type of breast cancer called HR+, HER2-, node-positive, high-risk early breast cancer. In this study, abemaciclib, a non-chemotherapy treatment, was administered with standard of care endocrine therapy after curative surgery. Most participants had received prior chemotherapy and/or radiotherapy. The study investigated if abemaciclib helped participants live longer without their cancer returning compared with participants who only received standard of care endocrine therapy. The study participants were assigned to 1 of 2 treatment groups. Participants in Group A were assigned to receive standard of care endocrine therapy with abemaciclib for 2 years, followed by endocrine therapy for a total of at least 5 years. Participants in Group B were assigned to receive standard of care endocrine therapy only for at least 5 years. The effect of treatment was compared between these 2 groups. WHAT WERE THE RESULTS?: Overall, the results showed that the cancer was 34% less likely to come back after surgery in the participants in Group A (abemaciclib plus endocrine therapy) compared with those in Group B (endocrine therapy only). At 4 years since the start of the study treatment, more participants who received the combination of abemaciclib plus endocrine therapy remained free of cancer compared with participants who received endocrine therapy alone (86% versus 79%). Participants who received abemaciclib plus endocrine therapy had more side effects than those who received endocrine therapy alone, but most of these effects were mild to moderate and reversible upon the end of therapy. The most common side effects in the abemaciclib group were diarrhea, infections, low number of white blood cells, and tiredness. WHAT DO THE RESULTS MEAN?: This study found that administering abemaciclib in combination with standard endocrine therapy after curative breast surgery helped lower the risk of cancer returning in people with HR+, HER2-, node-positive, high-risk early breast cancer. Abemaciclib is a new treatment option for people with this diagnosis. People with high-risk early breast cancer should always talk to their doctors and nurses before making any decisions about their treatment.Clinical Trial Registration: NCT03155997 (monarchE study).