Antibody-mediated rejection diagnosed in early protocol biopsies in high immunological risk kidney transplant recipients.

BACKGROUND: Renal transplant recipients with donor-specific anti-HLA antibodies are at an increased risk of antibody-mediated rejection (AMR). Early protocolized renal biopsies may serve as a strategy to improve diagnosis in this patient population. METHODS: We evaluated 155 highly sensitized renal transplant recipients with cPRA class I + II > 90% pre-transplant from 2015 to 2022. Patients with protocol biopsies within the first two weeks post-transplant were included. RESULTS: A total of 122 patients were included in the study. Of these, 13 (10.6%) were diagnosed with very early antibody-mediated rejection (veABMR) within the first two weeks post-transplant. This corresponds to 52% (13/25 patients) of all ABMR cases reported during the follow-up of this population. The graft survival rates at one and three years were significantly lower in patients with veABMR (p < 0.001) compared to patients without rejection in the early protocol biopsy. In terms of severity, the veABMR cohort exhibited a hazard ratio (HR) of 10.33 (95% CI 3.23-33.06; p < 0.001) for graft failure. The presence of donor-specific antibodies (DSA) class II on the day of transplantation and a higher percentage of eplet mismatch (EpMM), particularly EpMM DQA1, correlated with the development of veABMR. CONCLUSION: Early protocol biopsies play a pivotal role in the early detection of veABMR in high-risk immunological patients. Patients with veABMR face significant risks of graft loss, despite early treatment of rejection.

Innovative External Cranial Devices for Protecting a Craniectomy Site: A Scoping Review on Noninvasive Approaches for Patients Awaiting Cranioplasty.

BACKGROUND AND OBJECTIVES: Decompressive craniectomy (DC) is a commonly performed procedure to alleviate high intracranial pressure. To enhance patient quality of life and minimize complications after DC in patients awaiting cranioplasty (CP), multidisciplinary teams have designed and implemented external protective prototypes, including 3-dimensional printing and plaster models, whenever feasible. The aim of this scoping review was to assess the evidence available on innovative external cranial devices that protect the craniectomy site for patients who have undergone DC while awaiting CP in high-income countries and low- and middle-income countries. METHODS: This scoping review was conducted following the methodology outlined by the Joanna Briggs Institute. Searches were performed in databases such as MEDLINE, Embase, Web of Science, Scielo, Scopus, and World Health Organization Global Health Index Medicus. Patent documents were also searched in Espacenet, Google Patents, and World Intellectual Property Organization. This scoping review included external protective devices for adult patients who underwent DC and CP, while invasive devices were excluded. RESULTS: A total of 9 documents described external cranial devices, with 7 of them led by researchers from high-income countries, including the United States (n = 4), Singapore (n = 1), the United Kingdom (n = 1), and Hong Kong SAR, China (n = 1). Among these devices, 77.7% (n = 7) were created using 3-dimensional printing, while 22.3% (n = 2) were developed through plaster hand modeling. The individual study results were summarized. CONCLUSION: Sustainable Development Goal (SDG) 3, SDG 9, and SDG 10 play a crucial role in the advancement of innovative strategies to ensure access to essential neurosurgical care, reduce global disparities in treatment outcomes, mitigate postoperative complications, and provide life-saving interventions. This scoping review provides fundamental evidence for multidisciplinary teams involved in designing noninvasive innovations to minimize the risks associated with post-DC complications. It is anticipated that more cost-effective models, particularly in low- and middle-income countries, can be implemented based on the findings of this review.

Air quality in a small city: criteria pollutants, volatile organic compounds, metals, and microbes.

This work presents a year-long integral study of air quality parameters in Ciudad Real, a small city in the center of Spain, and its influence on the nearby national park, Las Tablas de Daimiel. The study covers meteorological parameters and criteria pollutants such as O3, NO, NO2, SO2, and PM10. Additionally, for each month, a 1-week campaign was performed sampling air in sorbent tubes with 8-h time resolution to analyze anthropogenic volatile organic compounds and the effects of seasons, daytime, and working-weekend days. During these campaigns, 24-h PM2.5 samples were also collected to measure the load of bacteria and fungi, as well as the trace concentrations of elements.The city and the national park NOx profiles showed that emissions from the town had a non-perceivable effect on the protected area. PM10 levels in Ciudad Real were influenced by Saharan intrusions, as was the national park; however, Ciudad Real had a higher contribution from anthropogenic sources. Ozone levels were lower in the city during the cold season due to the higher concentration of NOx and have not changed significantly in the last decade.The VOCs with higher average concentrations were toluene, m,p-xylene, benzene, methylene chloride, and o-xylene, with traffic being the main source of these pollutants in the city. For benzene and carbon tetrachloride levels, weak carcinogenic risks were estimated. In PM2.5, the most abundant metals were Na, Zn, Mg, Ca, Al, Fe, and K. The carcinogenic and non-carcinogenic risks estimated from the levels of the studied metals were negligible. Bacterial and fungal counts positively correlated with the concentration of PM2.5. Microbial community composition showed seasonal variability, with the dominance of human pathogenic bacteria which correlated with certain pollutants such as SO2. Bacillus and Cutibacterium were the most abundant genera.

Molecular characterization of gliomas and glioneuronal tumors amid Noonan syndrome: cancer predisposition examined.

Introduction: In the setting of pediatric and adolescent young adult cancer, increased access to genomic profiling has enhanced the detection of genetic variation associated with cancer predisposition, including germline syndromic conditions. Noonan syndrome (NS) is associated with the germline RAS pathway activating alterations and increased risk of cancer. Herein, we describe our comprehensive molecular profiling approach, the association of NS with glioma and glioneuronal tumors, and the clinical and histopathologic characteristics associated with the disease. Methods: Within an institutional pediatric cancer cohort (n = 314), molecular profiling comprised of paired somatic disease-germline comparator exome analysis, RNA sequencing, and tumor classification by DNA methylation analysis was performed. Results: Through the implementation of paired analysis, this study identified 4 of 314 (1.3%) individuals who harbored a germline PTPN11 variant associated with NS, of which 3 individuals were diagnosed with a glioma or glioneuronal tumor. Furthermore, we extend this study through collaboration with a peer institution to identify two additional individuals with NS and a glioma or glioneuronal tumor. Notably, in three of five (60%) individuals, paired genomic profiling led to a previously unrecognized diagnosis of Noonan syndrome despite an average age of cancer diagnosis of 16.8 years. The study of the disease-involved tissue identified signaling pathway dysregulation through somatic alteration of genes involved in cellular proliferation, survival, and differentiation. Discussion: Comparative pathologic findings are presented to enable an in-depth examination of disease characteristics. This comprehensive analysis highlights the association of gliomas and glioneuronal tumors with RASopathies and the potential therapeutic challenges and importantly demonstrates the utility of genomic profiling for the identification of germline cancer predisposition.

Radiomic detection of abnormal brain regions in tuberous sclerosis complex.

BACKGROUND: Radiomics refers to the extraction of quantitative information from medical images and is most commonly utilized in oncology to provide ancillary information for solid tumor diagnosis, prognosis, and treatment response. The traditional radiomic pipeline involves segmentation of volumes of interest with comparison to normal brain. In other neurologic disorders, such as epilepsy, lesion delineation may be difficult or impossible due to poor anatomic definition, small size, and multifocal or diffuse distribution. Tuberous sclerosis complex (TSC) is a rare genetic disease in which brain magnetic resonance imaging (MRI) demonstrates multifocal abnormalities with variable imaging and epileptogenic features. PURPOSE: The purpose of this study was to develop a radiomic workflow for identification of abnormal brain regions in TSC, using a whole-brain atlas-based approach with generation of heatmaps based on signal deviation from normal controls. METHODS: This was a retrospective pilot study utilizing high-resolution whole-brain 3D FLAIR MRI datasets from retrospective enrollment of tuberous sclerosis complex (TSC) patients and normal controls. Subjects underwent MRI including high-resolution 3D FLAIR sequences. Preprocessing included skull stripping, coregistration, and intensity normalization. Using the Brainnetome and Harvard-Oxford atlases, brain regions were parcellated into 318 discrete regions. Expert neuroradiologists spatially labeled all tubers in TSC patients using ITK-SNAP. The pyradiomics toolbox was used to extract 88 radiomic features based on IBSI guidelines, comparing tuber-affected and non-tuber-affected parenchyma in TSC patients, as well as normal brain tissue in control patients. For model training and validation, regions with tubers from 20 TSC patients and 30 normal control subjects were randomly divided into two training sets (80%) and two validation sets (20%). Additional model testing was performed on a separate group of 20 healthy controls. LASSO (least absolute shrinkage and selection operator) was used to perform variable selection and regularization to identify regions containing tubers. Relevant radiomic features selected by LASSO were combined to produce a radiomic score ω, defined as the sum of squared differences from average control group values. Region-specific ω scores were converted to heat maps and spatially coregistered with brain MRI to reflect overall radiomic deviation from normal. RESULTS: The proposed radiomic workflow allows for quantification of deviation from normal in 318 regions of the brain with the use of a summative radiomic score ω. This score can be used to generate spatially registered heatmaps to identify brain regions with radiomic abnormalities. The pilot study of TSC showed radiomic scores ω that were statistically different in regions containing tubers from regions without tubers/normal brain (p < 0.0001). Our model exhibits an AUC of 0.81 (95% confidence interval: 0.78-0.84) on the testing set, and the best threshold obtained on the training set, when applied to the testing set, allows us to identify regions with tubers with a specificity of 0.91 and a sensitivity of 0.60. CONCLUSION: We describe a whole-brain atlas-based radiomic approach to identify abnormal brain regions in TSC patients. This approach may be helpful for identifying specific regions of interest based on relatively greater signal deviation, particularly in clinical scenarios with numerous or poorly defined anatomic lesions.

An approach to analyze spatiotemporal patterns of gene expression at single-cell resolution in Candida albicans-infected mouse tongues.

Microbial gene expression measurements derived from infected organs are invaluable to understand pathogenesis. However, current methods are limited to "bulk" analyses that neglect microbial cell heterogeneity and the lesion's spatial architecture. Here, we report the use of hybridization chain reaction RNA fluorescence in situ hybridization (HCR RNA-FISH) to visualize and quantify Candida albicans transcripts at single-cell resolution in tongues of infected mice. The method is compatible with fixed-frozen and formalin-fixed paraffin-embedded tissues. We document cell-to-cell variation and intriguing spatiotemporal expression patterns for C. albicans mRNAs that encode products implicated in oral candidiasis. The approach provides a spatial dimension to gene expression analyses of host-Candida interactions. IMPORTANCE: Candida albicans is a fungal pathobiont inhabiting multiple mucosal surfaces of the human body. Immunosuppression, antibiotic-induced microbial dysbiosis, or implanted medical devices can impair mucosal integrity enabling C. albicans to overgrow and disseminate, causing either mucosal diseases such as oropharyngeal candidiasis or life-threatening systemic infections. Profiling fungal genes that are expressed in the infected mucosa or in any other infected organ is paramount to understand pathogenesis. Ideally, these transcript profiling measurements should reveal the expression of any gene at the single-cell level. The resolution typically achieved with current approaches, however, limits most gene expression measurements to cell population averages. The approach described in this report provides a means to dissect fungal gene expression in infected tissues at single-cell resolution.

Crystal structure, spectroscopy, DFT, and thermal studies of 3-cyano-2(1H)-pyridones as potential anticancer agents.

A series of 3-cyano-2(1H)-pyridones 4a-c were efficiently synthesized using an expeditious microwave-assisted multicomponent approach. Single-crystal XRD analysis revealed the presence of six independent molecules in the asymmetric unit cell for all compounds, with the crystal packing stabilized by a network of cyclic dimers formed by N-H⋯O[double bond, length as m-dash]C and C-H⋯O[double bond, length as m-dash]C intermolecular interactions. Additional supramolecular interactions, including C-H⋯π, C-N⋯π, and π⋯π, and C-H⋯X (for halogenated derivatives, i.e., 4b and 4c), appear crucial for crystal stabilization. Density Functional Theory (DFT) calculations were employed to understand the electronic structures and potential binding affinities. Comprehensive spectroscopic characterization by FT-IR, UV-Vis, NMR, and HMRS techniques confirmed the structures of all synthesized compounds. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were employed to evaluate the thermal stability of these compounds. The in vitro anticancer activity was evaluated against a panel of 60 human cancer cell lines, demonstrating promising activity against non-small-cell lung and breast cancer cell lines. Notably, compounds 4a and 4c exhibited the highest anticancer activity against the HOP-92 and MCF7 cell lines, with growth inhibition percentages (GI%) of 54.35 and 40.25, respectively.

Characterizing Neurobehavioral Dysregulation Among Former American Football Players: Findings From the DIAGNOSE CTE Research Project.

OBJECTIVE: Neurobehavioral dysregulation (NBD), a core clinical feature of traumatic encephalopathy syndrome, encompasses neuropsychiatric symptoms reported among individuals with a history of repetitive head impact exposure, including contact sport athletes. The objective of this study was to examine the construct and subconstructs of NBD through a series of factor and cluster analyses. METHODS: Six clinician-scientists selected self-report questionnaire items relevant to NBD from seven available neuropsychiatric scales through a blinded voting process. These items were subjected to confirmatory factor analyses in a sample of 178 former college and professional American football players and 60 asymptomatic individuals without a history of repetitive head impact exposure. All participants were enrolled in the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Factor scores were generated on the basis of the optimal expert-informed model for NBD. Construct validity was assessed with neuropsychiatric scales not included in generation of the factor scores. Cluster analyses with NBD factor scores were used to examine symptom profiles. RESULTS: Factor analyses confirmed that NBD was composed of four subconstructs: explosivity, emotional dyscontrol, impulsivity, and affective lability. Cluster analyses indicated four distinct symptom profiles of NBD in this group of former football players: asymptomatic (N=80, 45%), short fuse (N=33, 19%), high affective lability (N=34, 19%), and high NBD (N=31, 17%). CONCLUSIONS: These findings characterize NBD as a multifaceted clinical construct with a heterogeneous presentation, providing a foundation for empirical work on the diagnostic criteria for traumatic encephalopathy syndrome and research on the neurobiological underpinnings of NBD.

In Vivo Intra-Articular Antibiotic Concentrations at 24 Hours After TKA Fall Below the Minimum Inhibitory Concentration for Most Bacteria: A Randomized Study of Commercially Available Bone Cement.

BACKGROUND: The use of antibiotic-loaded bone cement (ALBC) to help reduce the risk of infection after primary total knee arthroplasty (TKA) is controversial. There is a paucity of in vivo data on the elution characteristics of ALBC. We aimed to determine whether the antibiotic concentrations of 2 commercially available ALBCs met the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) for common infecting organisms. METHODS: Forty-five patients undergoing TKA were randomized to receive 1 of the following: bone cement without antibiotic (the negative control; n = 5), a commercially available formulation containing 1 g of tobramycin (n = 20), or a commercially available formulation containing 0.5 g of gentamicin (n = 20). Intra-articular drains were placed, and fluid was collected at 4 and 24 hours postoperatively. An automated immunoassay measuring antibiotic concentration was performed, and the results were compared against published MIC and MBEC thresholds. RESULTS: The ALBC treatment groups were predominantly of White (65%) or Black (32.5%) race and were 57.5% female and 42.4% male. The mean age (and standard deviation) was 72.6 ± 7.2 years in the gentamicin group and 67.6 ± 7.4 years in the tobramycin group. The mean antibiotic concentration in the tobramycin group was 55.1 ± 37.7 µg/mL at 4 hours and 19.5 ± 13.0 µg/mL at 24 hours, and the mean concentration in the gentamicin group was 38.4 ± 25.4 µg/mL at 4 hours and 17.7 ± 15.4 µg/mL at 24 hours. Time and antibiotic concentration had a negative linear correlation coefficient (r = -0.501). Most of the reference MIC levels were reached at 4 hours. However, at 24 hours, a considerable percentage of patients had concentrations below the MIC for many common pathogens, including Staphylococcus epidermidis (gentamicin: 65% to 100% of patients; tobramycin: 50% to 85%), methicillin-sensitive Staphylococcus aureus (gentamicin: 5% to 90%; tobramycin: 5% to 50%), methicillin-resistant S . aureus (gentamicin: 5% to 65%; tobramycin: 50%), Streptococcus species (gentamicin: 10% to 100%), and Cutibacterium acnes (gentamicin: 10% to 65%; tobramycin: 100%). The aforementioned ranges reflect variation in the MIC among different strains of each organism. Gentamicin concentrations reached MBEC threshold values at 4 hours only for the least virulent strains of S . aureus and Escherichia coli. Tobramycin concentrations did not reach the MBEC threshold for any of the bacteria at either time point. CONCLUSIONS: The elution of antibiotics from commercially available ALBC decreased rapidly following TKA, and only at 4 hours postoperatively did the mean antibiotic concentrations exceed the MIC for most of the pathogens. Use of commercially available ALBC may not provide substantial antimicrobial coverage following TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Effect of Light Quality on the seed Germination and Development of Coffee Seedlings (Coffea arabica).

Coffee (Coffea arabica) cultivation is vital to the global economic, social and cultural life of farmers. However, senescent and disease-susceptible plantations affect coffee productivity. Therefore, it is crucial to improve biotechnological strategies such as micropropagation to increase the number of plants for replanting. In this study, the dark condition (T1) and different light qualities (T0-white light 400-700 nm; T2-red light 660 nm and T3-blue light 460 nm) were evaluated to optimize the in vitro propagation of 4 and 9 month-old coffee seeds. The results showed that red light had the highest percentage, an outstanding germination rate index, which may suggest that in the case of coffee seeds could be involved phytochromes that promote germination in a red light quality. In summary, the ideal conditions for in vitro micropropagation of coffee are under white and red light condition.

[Post liver transplantation complications in pediatric patients in a third level hospital, Lima-Peru, 2016-2020]. / Complicaciones post trasplante hepático en pacientes pediátricos en un hospital de tercer nivel, Lima-Perú, 2016-2020.

OBJECTIVE: determine the complications during the first year after liver transplantation in pediatric patients of the INSN-SB during the period 2016-2020. MATERIALS AND METHODS: Descriptive, cross-sectional study. The medical records of liver transplant patients seen during post-transplant follow-up at the INSN-SB were reviewed, collecting epidemiological characteristics, transplant indication; PELD score, CHILD score and complications prior to the transplant, as well as the frequency of the main complications presented during the first year after the transplant. RESULTS: Of the 16 patients evaluated, 62.5% were under 1 year of age, with a median weight of 7.4kg, 50% presented a CHILD C score, with a median PELD of 23, the main reason for transplantation was atresia of bile ducts (62.5%), the main complications prior to transplantation were portal hypertension (75%) and malnutrition (68.8%). All post-transplant patients presented at least one infectious complication: bacterial (53%), CMV infection (75%) and EBV infection (31%); Regarding vascular complications, 25% presented portal vein thrombosis and one patient (6%) presented hepatic artery stenosis; Regarding biliary complications, 12.5% presented biliary fistula, also 12.5% presented bile duct dilation, while 6.25% presented bilioma. CONCLUSIONS: Among the main complications of the post-liver transplant patient, we can highlight that all patients presented at least one infectious complication (100%), vascular complications in 31% and biliary complications in 31.25% of patients.

Inside-out, antimicrobial resistance mediated by efflux pumps in clinical strains of Acinetobacter baumannii isolated from burn wound infections.

Acinetobacter baumannii belongs to the ESKAPE group. It is classified as a critical priority group by the World Health Organization and a global concern on account of its capacity to acquire and develop resistance mechanisms to multiple antibiotics. Data from the United States indicates 500 deaths annually. Resistance mechanisms of this bacterium include enzymatic pathways such as ß-lactamases, carbapenemases, and aminoglycoside-modifying enzymes, decreased permeability, and overexpression of efflux pumps. A. baumannii has been demonstrated to possess efflux pumps, which are classified as members of the MATE family, RND and MFS superfamilies, and SMR transporters. The aim of our work was to assess the distribution of efflux pumps and their regulatory gene expression in clinical strains of A. baumannii isolated from burned patients. METHODS: From the Clinical Microbiology Laboratory at the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra collection in Mexico, 199 strains were selected. Antibiotics susceptibilities were performed by broth microdilutions to determine minimal inhibitory concentrations. Phenotypic assays with efflux pump inhibitors were conducted using carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and phenylalanine-arginine ß-naphthylamide (PAßN) in conjunction with amikacin, ceftazidime, imipenem, meropenem and levofloxacin. A search was conducted for structural genes that are linked to efflux pumps, and the relative expression of the adeR, adeS, and adeL genes was analyzed. RESULTS: Among a total of 199 strains, 186 exhibited multidrug resistance (MDR). Fluoroquinolones demonstrated the highest resistance rates, while minocycline and amikacin displayed comparatively reduced resistance rates (1.5 and 28.1, respectively). The efflux activity of fluorquinolones exhibited the highest phenotypic detection (from 85 to 100%), while IMP demonstrated the lowest activity of 27% with PAßN and 43.3% with CCCP. Overexpression was observed in adeS and adeL, with adeR exhibiting overexpression. Concluding that clinical strains of A. baumannii from our institution exhibited efflux pumps as one of the resistance mechanisms.

Relationship of Genetic Polymorphisms and Microbial Composition with Binge Eating Disorder: A Systematic Review.

Humans are the result of an evolutionary process, and because of this, many biological processes are interconnected with each other. The intestine-brain axis consists of an intricately connected neuronal-neuroendocrine circuit that regulates the sensation of hunger and satiety. Genetic variations and the consumption of unnatural diets (ultra-processed foods, high contents of sugars, etc.) can override this circuit and cause addiction to certain foods and/or the inability to feel satiety in certain situations. The patients who come to consultations (mainly psychology or nutrition) in an attempt to resolve this problem sometimes fail, which leads to them looking for new strategies based on biological predisposition. This investigation aims to evaluate the genetic studies regarding the microbiota carried out in the last 12 years in humans to try to determine which genes and microbes that have been recently studied are related to patients diagnosed with binge eating disorder or compulsive eating (presenting obesity or not). The protocol followed the PRISMA statement, and the following databases were searched from 2012 until the present day: PubMed, PsycINFO, SCOPUS, and Web of Science. Twenty-four international articles were analyzed, including cross-sectional or exploratory studies; five of them referred to the microbial composition, and in nineteen, the existence of genetic polymorphisms present in binge eating disorder or in compulsive eating could be observed: DRD2, OPRM1, COMT, MC4R, BNDF, FTO, SLC6A3, GHRL, CARTPT, MCHR2, and LRP11. Even though there is still much to investigate on the subject, it must be highlighted that, in the last 4 years, a two-fold increase has been observed in potential markers and in studies related to the matter, also highlighting the importance of different analyses in relation to psychosocial factors and their interaction with the genetic and microbial factors, for which research on the matter must be continued.

Nasal microbiome and the effect of nasal decolonization with a novel povidone-iodine antiseptic solution: a prospective and randomized clinical trial.

The aim of this study was to assess the profile of nasal microbiome and evaluate the effect of a specific nasal decolonization solution on the microbiome. We conducted a randomized, placebo-controlled, and parallel-group clinical study of 50 volunteers aged 18 years and older. The subjects were randomly assigned to receive a nasal antiseptic solution, containing povidone-iodine as the main ingredient, (n = 25) or a control solution (n = 25). Nasal swabs were obtained before application (baseline) and at 3 timepoints after application (5 min, 2 h, 24 h). Nasal swabs were subjected to next generation sequencing analysis and cultured in agar plates. At baseline, there were substantial associations between anaerobic species, Corynebacterium spp., Staphylococcus spp., and Dolosigranulum spp. Then, a high bioburden reduction was observed after the application of povidone-iodine (log10 3.68 ± 0.69 at 5 min; log10 3.57 ± 0.94 at 2 h; log10 1.17 ± 1.40 at 24 h), compared to the control. The top species affected by the treatment were Cutibacterium acnes, Staphylococcus, and Corynebacterium species. None of the subjects experienced any adverse effects, nor increases in mucociliary clearance time. Antiseptic solutions applied to the anterior nares can transiently and markedly reduce the bioburden of the nose. The registration number for this clinical trial is NCT05617729.

Effects of massive desiccation of olive waste residues on air quality.

New industries are proliferating in the recovery of agri-food wastes, such as those involved in the revaluation of alperujo, generated in the production of olive oil. Despite the potential environmental benefits, their activity is not exempt from new forms of emissions, aggravated by the massification of waste treatments. This work reports a six-month field campaign carried out in an alperujo desiccation plant which can serve as a proxy for these emerging industries in the Mediterranean countries. The study focused on air quality parameters, covering criteria pollutants, metals and microbiological load of particulate matter and the characterization of volatile organic compounds (VOCs). The results show a slight contribution of the factory to the NOx levels in the surroundings (3.0-12.5 µg/m3). Statistically significant effects were not observed for ozone, CO, SO2, or PM10. Concerning the levels of metals, concentrations were low and calculated health risk indexes indicated safe conditions in the area. The most abundant elements were Na (6.5 × 102 ng/m3), K (4.0 × 102 ng/m3), Al (2.7 × 102 ng/m3), Zn (2.1 × 102 ng/m3), Ca (2.16 × 102 ng/m3), Fe (3.6 × 101 ng/m3) and Mg (3.2 × 101 ng/m3). Bacterial counts, with a mean value of 15.9 CFU/m3, showed a seasonal shift, mainly explained by weather (air moisture and temperature) and PM2.5 concentration. The genomic analysis showed Cutibacterium as the dominant genus during the cold months while Bacillus predominated in the warm season. The VOCs with higher average concentrations were acetic acid (130 µg/m3), nonanoic acid (124 µg/m3), benzoic acid (29.7 µg/m3), octanoic acid (19.9 µg/m3) and nonanal (4.70 µg/m3), with the rest of compounds in concentrations below 4 µg/m3. Odorant pollutants with the greatest contribution to olfactory nuisance were aldehydes (from pentanaldehyde to decanaldehyde), acetic acid and phenol. Although the observable effects of the waste treatments were low, several parameters showed an influence on the environment which should be assessed to foresee and prevent long-term consequences.

Antimicrobial and Antibiofilm Potential of Flourensia retinophylla against Staphylococcus aureus.

Staphylococcus aureus is a Gram-positive bacteria with the greatest impact in the clinical area, due to the high rate of infections and deaths reaching every year. A previous scenario is associated with the bacteria's ability to develop resistance against conventional antibiotic therapies as well as biofilm formation. The above situation exhibits the necessity to reach new effective strategies against this pathogen. Flourensia retinophylla is a medicinal plant commonly used for bacterial infections treatments and has demonstrated antimicrobial effect, although its effect against S. aureus and bacterial biofilms has not been investigated. The purpose of this work was to analyze the antimicrobial and antibiofilm potential of F. retinophylla against S. aureus. The antimicrobial effect was determined using an ethanolic extract of F. retinophylla. The surface charge of the bacterial membrane, the K+ leakage and the effect on motility were determined. The ability to prevent and remove bacterial biofilms was analyzed in terms of bacterial biomass, metabolic activity and viability. The results showed that F. retinophylla presents inhibitory (MIC: 250 µg/mL) and bactericidal (MBC: 500 µg/mL) activity against S. aureus. The MIC extract increased the bacterial surface charge by 1.4 times and the K+ concentration in the extracellular medium by 60%. The MIC extract inhibited the motility process by 100%, 61% and 40% after 24, 48 and 72 h, respectively. The MIC extract prevented the formation of biofilms by more than 80% in terms of biomass production and metabolic activity. An extract at 10 × MIC reduced the metabolic activity by 82% and the viability by ≈50% in preformed biofilms. The results suggest that F. retinophylla affects S. areus membrane and the process of biofilm formation and removal. This effect could set a precedent to use this plant as alternative for antimicrobial and disinfectant therapies to control infections caused by this pathogen. In addition, this shrub could be considered for carrying out a purification process in order to identify the compounds responsible for the antimicrobial and antibiofilm effect.

Novel Penicillin-Based Sulfone-Siderophore Conjugates for Restoring ß-Lactam Antibiotic Efficacy.

Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate delivery of the antibacterial agent to the target has become a growing research area in the infectious diseases field as a means of improving drug efficacy. Although the efficient transport of siderophore-antibiotic conjugates into the cytosol still remains challenging, great success has been achieved in the delivery of ß-lactam antibiotics into the periplasmic space via bacterial iron uptake pathways. Cefiderocol, the first siderophore-cephalosporin conjugate approved by the US Food and Drug Administration, is a good example. These conjugation strategies have also been applied to the precise delivery of ß-lactamase inhibitors, such as penicillin-based sulfone 1, to restore ß-lactam antibiotic efficacy in multidrug-resistant bacteria. Herein, we have explored the impact on the bacterial activity of 1 by modifying its iron chelator moiety. A set of derivatives functionalized with diverse iron chelator groups and linkages to the scaffold (compounds 2-8) were synthesized and assayed in vitro. The results on the ability of derivatives 2-8 to recover ß-lactam antibiotic efficacy in difficult-to-treat pathogens that produce various ß-lactamase enzymes, along with kinetic studies with the isolated enzymes, allowed us to identify compound 2, a novel ß-lactamase inhibitor with an expanded spectrum of activity. Molecular dynamics simulation studies provided us with further information regarding the molecular basis of the relative inhibitory properties of the most relevant compound described herein.

Operating Room Air May Harbor Pathogens: The Role of an Ultraviolet Air Filtration Unit.

BACKGROUND: One important factor for the prevention of surgical site infections is ultraclean air in the operating room (OR). Still, the direct sterilization potential of most technologies, especially in a dynamic clinical setting, is not well understood. We aimed to determine and compare the microbial presence from the inlet and outlet flow of a filtration unit with crystalline ultraviolet-C (C-UVC) light. METHODS: A prospective study was conducted at a single institution, where primary total joint arthroplasty and spine surgeries were performed. The OR was fitted with a positive ventilation system. In addition, a filtration unit with a C-UVC sterilizing light was placed in the OR. The inlet and outlet air flows were swabbed simultaneously and compared. Swabs were processed for culture and next-generation sequencing. RESULTS: The mean length of the surgical procedures sampled was 68 ± 13 minutes. Overall, 19 out of 200 (9.5%) swabs isolated microorganisms. Inlet air swabs were positive at a higher rate (16 versus 3%; P < .01) compared to the outlet air swabs. A wide variety of Gram-positive, Gram-negative, and anaerobic bacteria were isolated, but fungi were only recovered from inlet air swabs. The detection of microorganisms was also higher when more door openings were performed (32.5 ± 7.1 versus 27.9 ± 5.6; P < .01). CONCLUSIONS: Air swabs mainly isolated microorganisms from the inlet flow to the filtration unit with a C-UVC light. The sterilizing unit counteracted factors affecting the air quality in the OR, namely door openings, surgical personnel, and tissue combustion.

Cs2CO3-Promoted Alkylation of 3-Cyano-2(1H)-Pyridones: Anticancer Evaluation and Molecular Docking.

Herein, a Cs2CO3-promoted N-alkylation of 3-cyano-2(1H)-pyridones containing alkyl groups with diverse alkyl halides to synthesize N-alkyl-2-pyridones over O-alkylpyridines is reported. The use of alkyl dihalides resulted in complex mixtures of N- and O-alkylated products. The primary factor influencing regioselectivity in these reactions is the electronic effects of substituents on the 2(1H)-pyridone ring, as evidenced by the preferential formation of O-alkylpyridines upon the introduction of aryl groups. Remarkably, we efficiently employed CuAAC and Ti(Oi-Pr)4-catalyzed amidation reactions to functionalize N-alkyl-2-pyridones containing propargyl and ester groups, leading to the synthesis of 1,2,3-triazoles and amides, respectively. Moreover, O-alkylpyridines 10 b and 10 d displayed remarkable selectivity toward the A-498 renal cancer cell line with growth inhibition percentages (%GI) of 54.75 and 67.64, respectively. The binding modes of compounds 10 b and 10 d to the PIM-1 kinase enzyme were determined through molecular docking studies.