Antimicrobial Stewardship in the Emergency Department Observation Unit: Definition of a New Indicator and Evaluation of Antimicrobial Use and Clinical Outcomes.

We aimed to define a novel indicator for monitoring antimicrobial use specifically in the Emergency Department Observation Unit (EDOU) and to assess the long-term impact of an institutional education-based antimicrobial stewardship program (ASP) on the antimicrobial prescribing pattern and clinical outcomes in this setting. A quasi-experimental interrupted time-series study was performed from 2011 to 2022. An educational ASP was implemented at the EDOU in 2015. To estimate changes in antimicrobial use, we designed an indicator adjusted for patients at risk of antimicrobial prescribing: defined daily doses (DDDs) per 100 patients transferred from the Emergency Department to the Observation Unit (TOs) per quarter. The number of bloodstream infections (BSIs) and the crude all-cause 14-day mortality were assessed as clinical outcomes. Antimicrobial use showed a sustained reduction with a trend change of -1.17 DDD per 100 TO and a relative effect of -45.6% (CI95% -64.5 to -26.7), particularly relevant for meropenem and piperacillin-tazobactam, with relative effects of -80.4% (-115.0 to -45.7) and -67.9% (-93.9 to -41.9), respectively. The incidence density of all BSIs increased significantly during the ASP period, with a relative effect of 123.2% (41.3 to 284.7). The mortality rate remained low and stable throughout the study period, with an absolute effect of -0.7% (-16.0 to 14.7). The regular monitoring of antimicrobial use in the EDOU by using this new quantitative indicator was useful to demonstrate that an institutional education-based ASP successfully achieved a long-term reduction in overall antimicrobial use, with a low and steady BSI mortality rate.

Impact of a daily legume-based meal on blood and anthropometric parameters in a group of omnivorous adults: A pilot study.

This pilot study aimed to assess the impact of substituting a traditional lunch for a vegetarian legume-based meal on blood and anthropometric parameters in a group of omnivorous adults. A one-group comparison, quasi-experimental dietary intervention was designed. A vegetarian legume-based meal was offered for 8 consecutive weeks (weekdays) to non-vegetarian individuals (n = 26), (28 years [P25 = 20.0, P75 = 35.5]; 21.9 kg/m2 [P25 = 21.3, P75 = 24.8]). Sociodemographic data, health status and lifestyle-related information were recorded. Three-day food records were used to collect food intake at baseline and at the end of the intervention. Anthropometric parameters were recorded and fasting blood analyses were performed following standard procedures. Wilcoxon signed-rank test was used for statistical comparisons. A p-value <0.05 was considered statistically significant. Participants showed a median intake of 79.8 g of cooked legumes per meal, meaning 13 (50.0%) subjects met the Portuguese daily legume intake recommendations during the intervention days. There were no statistically significant differences in anthropometric parameters. Transferrin concentration increased after 8 weeks (+12.5 mg/dL; p = 0.001). Total cholesterol concentration reduced after 8 weeks (-6 mg/dL; p = 0.041), as well as low-density lipoprotein (LDL) cholesterol (-7 mg/dL; p = 0.003). Triglycerides (+9 mg/dL; p = 0.046), fasting glucose (+2 mg/dL; p = 0.037) and HbA1c (+0.1 mg/dL; p = 0.010) concentration increased after the 2-month legume-based trial. Results suggest a cholesterol-lowering potential of legume-rich diets. However, unfavourable results regarding the impact on glucose metabolism-related biomarkers and triglyceride levels were observed. The study's limitations in design and sample size emphasise the importance of conducting further research with larger cohorts to attain more conclusive findings.

Pd2Spermine as an Alternative Therapeutics for Cisplatin-Resistant Triple-Negative Breast Cancer.

Cisplatin (cDDP) resistance is a matter of concern in triple-negative breast cancer therapeutics. We measured the metabolic response of cDDP-sensitive (S) and -resistant (R) MDA-MB-231 cells to Pd2Spermine(Spm) (a possible alternative to cDDP) compared to cDDP to investigate (i) intrinsic response/resistance mechanisms and (ii) the potential cytotoxic role of Pd2Spm. Cell extracts were analyzed by untargeted nuclear magnetic resonance metabolomics, and cell media were analyzed for particular metabolites. CDDP-exposed S cells experienced enhanced antioxidant protection and small deviations in the tricarboxylic acid cycle (TCA), pyrimidine metabolism, and lipid oxidation (proposed cytotoxicity signature). R cells responded more strongly to cDDP, suggesting a resistance signature of activated TCA cycle, altered AMP/ADP/ATP and adenine/uracil fingerprints, and phospholipid biosynthesis (without significant antioxidant protection). Pd2Spm impacted more markedly on R/S cell metabolisms, inducing similarities to cDDP/S cells (probably reflecting high cytotoxicity) and strong additional effects indicative of amino acid depletion, membrane degradation, energy/nucleotide adaptations, and a possible beneficial intracellular γ-aminobutyrate/glutathione-mediated antioxidant mechanism.

Transcriptomic signature of luteinized cumulus cells of oocytes developing to live birth after women received intracytoplasmic sperm injection.

OBJECTIVE: To compare the transcriptome of human cumulus cells (CCs) from oocytes with different outcomes (pregnancy yes/no, live birth [LB] yes/no), to identify noninvasive biomarkers for oocyte selection as well as new therapeutic targets to increase LB rates from assisted reproductive technologies (ART). DESIGN: Retrospective observational study. SETTINGS: This study was conducted at a University Hospital in Switzerland. PATIENTS: Subfertile couples undergoing controlled ovarian superstimulation and intracytoplasmic sperm injection with subsequent unbiopsied embryo transfer below the female age of 43 years. INTERVENTION(S): RNA sequencing of CCs from oocytes results in a pregnancy, no pregnancy, LB, or no LB. MAIN OUTCOME MEASURES: Differential gene expression (DEG) between CCs of oocytes results in "no pregnancy" vs. "pregnancy" and "pregnancy only" vs. "live birth." RESULTS: Although RNA sequencing did not reveal DEGs when comparing the transcriptomic profiles of the groups "no pregnancy" with "pregnancy," we identified 139 DEGs by comparing "pregnancy only" with "live birth," of which 28 belonged to clusters relevant to successful ART outcomes (i.e., CTGF, SERPINE2, PCK1, HHIP, HS3ST, and BIRC5). A functional enrichment analysis revealed that the transcriptome of CCs associated with LB depicts pathways of extracellular matrix, inflammatory cascades leading to ovulation, cell patterning, proliferation, and differentiation, and silencing pathways leading to apoptosis. CONCLUSION: We identified a CCs transcriptomic profile associated with LB after embryo transfer that, after further validation, could serve to predict successful ART outcomes. The definition of relevant pathways of CCs related to oocyte competency contributes to a broader understanding of the cumulus oocyte complex and helps identify further therapeutic targets for improving ART success.

Metabolic Evaluation of Lupin-Enriched Yogurt by Nuclear Magnetic Resonance Metabolomics.

Untargeted nuclear magnetic resonance (NMR) metabolomics was used to evaluate compositional changes during yogurt fermentation upon lupin enrichment compared to traditional conditions. Lupin significantly changed the sample metabolic profile and its time course dynamics, seemingly delaying microbial action. The levels of organic and amino acids were significantly altered, along with those of some sugars, nucleotides, and choline compounds. Lupin seemed to favor acetate and formate synthesis, compared to that of citrate and fumarate; a higher formate levels may suggest increased levels of Streptococcus thermophilus action, compared toLactobacillus bulgaricus. Lupin-yogurt was poorer in hippurate, lactose (and hence lactate), galactose, glucose-1-phosphate, and galactose-1-phosphate, containing higher orotate levels (possibly related to increased uridine derivatives), among other differences. Trigonelline was confirmed as a lupin marker, possibly together with glutamate and histidine. Other metabolite trajectories remained unchanged upon lupin addition, unveiling unaffected underlying processes. These results demonstrate the usefulness of untargeted NMR metabolomics to understand/develop new foodstuffs and their production processes, highlighting the identity of a variety of bioactive metabolites with importance for human health.

Electronic Medication Reconciliation Tools Aimed at Healthcare Professionals to Support Medication Reconciliation: a Systematic Review.

The development of health information technology available and accessible to professionals is increasing in the last few years. However, a low number of electronic health tools included some kind of information about medication reconciliation. To identify all the electronic medication reconciliation tools aimed at healthcare professionals and summarize their main features, availability, and clinical impact on patient safety. A systematic review of studies that included a description of an electronic medication reconciliation tool (web-based or mobile app) aimed at healthcare professionals was conducted. The review protocol was registered with PROSPERO: registration number CRD42022366662, and followed PRISMA guidelines. The literature search was performed using four healthcare databases: PubMed, EMBASE, Cochrane Library, and Scopus with no language or publication date restrictions. We identified a total of 1227 articles, of which only 12 met the inclusion criteria.Through these articles,12 electronic tools were detected. Viewing and comparing different medication lists and grouping medications into multiple categories were some of the more recurring features of the tools. With respect to the clinical impact on patient safety, a reduction in adverse drug events or medication discrepancies was detected in up to four tools, but no significant differences in emergency room visits or hospital readmissions were found. 12 e-MedRec tools aimed at health professionals have been developed to date but none was designed as a mobile app. The main features that healthcare professionals requested to be included in e-MedRec tools were interoperability, "user-friendly" information, and integration with the ordering process.

Disclosing a metabolic signature of cisplatin resistance in MDA-MB-231 triple-negative breast cancer cells by NMR metabolomics.

This work compared the metabolic profile of a parental MDA-MB-231 cisplatin-sensitive triple negative breast cancer (TNBC) cell line with that of a derived cisplatin-resistant line, to characterize inherent metabolic adaptations to resistance, as a means for marker and new TNBC therapies discovery. Supported by cytotoxic, microscopic and biochemical characterization of both lines, Nuclear Magnetic Resonance (NMR) metabolomics was employed to characterize cell polar extracts for the two cell lines, as a function of time (0, 24 and 48 h), and identify statistically relevant differences both between sensitive and resistant cells and their time course behavior. Biochemical results revealed a slight increase in activation of the NF-κB pathway and a marked decrease of the ERK signaling pathway in resistant cells. This was accompanied by lower glycolytic and glutaminolytic activities, possibly linked to glutamine being required to increase stemness capacity and, hence, higher survival to cisplatin. The TCA cycle dynamics seemed to be time-dependent, with an apparent activation at 48 h preferentially supported by anaplerotic aromatic amino acids, leucine and lysine. A distinct behavior of leucine, compared to the other branched-chain-amino-acids, suggested the importance of the recognized relationship between leucine and in mTOR-mediated autophagy to increase resistance. Suggested markers of MDA-MB-231 TNBC cisplatin-resistance included higher phosphocreatine/creatine ratios, hypotaurine/taurine-mediated antioxidant protective mechanisms, a generalized marked depletion in nucleotides/nucleosides, and a distinctive pattern of choline compounds. Although the putative hypotheses generated here require biological demonstration, they pave the way to the use of metabolites as markers of cisplatin-resistance in TNBC and as guidance to develop therapies.

Impact of Conventional and Potential New Metal-Based Drugs on Lipid Metabolism in Osteosarcoma MG-63 Cells.

This work investigated the mechanisms of action of conventional drugs, cisplatin and oxaliplatin, and the potentially less deleterious drug Pd2Spermine (Spm) and its Pt(II) analog, against osteosarcoma MG-63 cells, using nuclear-magnetic-resonance metabolomics of the cellular lipidome. The Pt(II) chelates induced different responses, namely regarding polyunsaturated-fatty-acids (increased upon cisplatin), suggesting that cisplatin-treated cells have higher membrane fluidity/permeability, thus facilitating cell entry and justifying higher cytotoxicity. Both conventional drugs significantly increased triglyceride levels, while Pt2Spm maintained control levels; this may reflect enhanced apoptotic behavior for conventional drugs, but not for Pt2Spm. Compared to Pt2Spm, the more cytotoxic Pd2Spm (IC50 comparable to cisplatin) induced a distinct phospholipids profile, possibly reflecting enhanced de novo biosynthesis to modulate membrane fluidity and drug-accessibility to cells, similarly to cisplatin. However, Pd2Spm differed from cisplatin in that cells had equivalent (low) levels of triglycerides as Pt2Spm, suggesting the absence/low extent of apoptosis. Our results suggest that Pd2Spm acts on MG-63 cells mainly through adaptation of cell membrane fluidity, whereas cisplatin seems to couple a similar effect with typical signs of apoptosis. These results were discussed in articulation with reported polar metabolome adaptations, building on the insight of these drugs' mechanisms, and particularly of Pd2Spm as a possible cisplatin substitute.

Enhancing breadth and durability of humoral immune responses in non-human primates with an adjuvanted group 1 influenza hemagglutinin stem antigen.

Seasonal influenza vaccines must be updated annually and suboptimally protect against strains mismatched to the selected vaccine strains. We previously developed a subunit vaccine antigen consisting of a stabilized trimeric influenza A group 1 hemagglutinin (H1) stem protein that elicits broadly neutralizing antibodies. Here, we further optimized the stability and manufacturability of the H1 stem antigen (H1 stem v2, also known as INFLUENZA G1 mHA) and characterized its formulation and potency with different adjuvants in vitro and in animal models. The recombinant H1 stem antigen (50 µg) was administered to influenza-naïve non-human primates either with aluminum hydroxide [Al(OH)3] + NaCl, AS01B, or SLA-LSQ formulations at week 0, 8 and 34. These SLA-LSQ formulations comprised of varying ratios of the synthetic TLR4 agonist 'second generation synthetic lipid adjuvant' (SLA) with liposomal QS-21 (LSQ). A vaccine formulation with aluminum hydroxide or SLA-LSQ (starting at a 10:25 µg ratio) induced HA-specific antibodies and breadth of neutralization against a panel of influenza A group 1 pseudoviruses, comparable with vaccine formulated with AS01B, four weeks after the second immunization. A formulation with SLA-LSQ in a 5:2 µg ratio contained larger fused or aggregated liposomes and induced significantly lower humoral responses. Broadly HA stem-binding antibodies were detectable for the entire period after the second vaccine dose up to week 34, after which they were boosted by a third vaccine dose. These findings inform about potential adjuvant formulations in clinical trials with an H1 stem-based vaccine candidate.

Comparison of heart, grace and TIMI scores to predict major adverse cardiac events from chest pain in a Spanish health care region.

Acute non-traumatic chest pain (ANTCP) is the second cause of consultation in the Emergency department (ED). About 70% of all Acute Myocardial Infarctions present as non persistent ST-elevation acute coronary syndrome (NSTE-ACS) in the electrocardiogram. Our aim was to compare whether the HEART risk score is more effective than the GRACE and TIMI scores for the diagnosis and prognosis of Major Adverse Cardiac Events (MACE) at six weeks in patients with ANTCP and NSTE-ACS. A prospective cohort study was conducted with patients with ANTCP that attended an ED and a Primary Care Emergency Center (PCEC) from April 2018 to December 2020. The primary outcome was MACE at six weeks. Diagnostic performance was calculated for each scale as the Area under the Receiver Operating Characteristic (ROC) curve (AUC), sensitivity (SE), specificity (SP), and predictive values (PV). Qualitative variables were compared using the Chi-square test, and continuous variables were compared using the nonparametric Kruskal-Wallis test. We adjusted a logistic regression for risk groups, age, and gender to determine the effect of the HEART, GRACE, and TIMI scores on MACE. The degree of agreement (kappa index) was calculated in the categorical classification of patients according to the three risk scales. Cox proportional hazards regressions were performed for each scale and were compared using partial likelihood ratio tests for non-nested models. From a sample of 317 patients with ANTCP, 14.82% had MACE at six weeks. The AUC was 0.743 (95% CI 0.67-0.81) for the HEART score, 0.717 (95% CI 0.64-0.79) for the TIMI score, and 0.649 (95% CI 0.561-0.738) for the GRACE score. The HEART scale identified low-risk patients with a higher SE and negative PV than the GRACE and TIMI scores. The HEART scale was better than the GRACE and TIMI scores at diagnosing and predicting MACE at six weeks in patients with ANTCP and probable NSTE-ACS. It was also a reliable tool for risk stratification in low-risk patients. Its application is feasible in EDs and PCECs, avoiding the need for complementary tests and their associated costs without compromising patient health.

Erosive balanitis caused by Staphylococcus haemolyticus in a healthy, circumcised adult male.

Introduction: Balanitis is an inflammation of the glans penis. Balanoposthitis involves both the glans penis and prepuce and occurs only in uncircumcised males. Recurrent balanoposthitis represents a strong indication for circumcision. After Candida infections, aerobic bacteria are the second most common aetiological cause of acute infectious balanoposthitis, mainly streptococci groups B and D, and staphylococci, usually S. aureus . Their clinical manifestations are variable inflammatory changes, including diffuse erythema and oedema. Severe balanopreputial oedema with purulent exudate occurs in painful, erosive streptococcal balanoposthitis.Coagulase-negative staphylococci (CoNS) are commensal skin bacteria, but are also recognized pathogens of the genitourinary system, mainly related to urinary tract infections. Staphylococcus haemolyticus is one of the main species of CoNS that is part of the cutaneous microflora but is also associated with nosocomial infections. In addition, S. haemolyticus also causes other infections of the male urogenital tract, such as chronic prostatitis and epididymo-orchitis, but it has not been associated with balanitis. Case presentation: A 45-year-old man reports having suffered several episodes of balanoposthitis in the last 3 years, which were treated with topical antifungal treatments alone or associated with corticosteroids. For this reason, he underwent a postectomy by his urologist 8 months ago to avoid further recurrences.The patient consulted for an episode of painful, erosive and exudative lesions on the glans penis and over the post-operative scars lasting 5 days. He had no urinary discomfort or inguinal lymphadenopathy. A complete blood count, biochemical analysis, C-reactive protein (CRP), prostate-specific antigen (PSA) and urinalysis were normal. Abundant growth of S. haemolyticus was obtained in the culture on tryptone soya agar with sheep blood and chocolate agar with Vitox media. The MicroScan panel CIM 37 (PM37) was used to study the antimicrobial susceptibilities of the isolated bacteria. The fungal culture on Sabouraud dextrose agar was negative. Based on the antimicrobial susceptibility study, treatment with oral ciprofloxacin and topical mupirocin was started, and the genital infection was completely cured. Conclusion: We present a healthy, non-diabetic, circumcised male patient with severe, erosive and painful balanitis probably due to S. haemolyticus .

[Translated article] Analysis of the appropriateness of antibiotic prophylaxis in surgical procedures in Spain. Protocol for the "ProA-Q" study.

Surgical antibiotic prophylaxis is one of the most useful measures to prevent surgical wound infection. OBJECTIVE: The aim of this project is to evaluate the appropriateness of the use of antibiotic prophylaxis in surgical procedures performed in Spanish hospitals, both globally and according to the type of surgery performed. METHOD: For this purpose, an observational, retrospective, cross-sectional, and multicentre study has been designed to collect all the variables that allow the evaluation of the appropriateness of surgical antibiotic prophylaxis by comparing the prescribed treatment, the recommendations included in the local guidelines, and the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology and the Spanish Association of Surgeons. Indication, choice of antimicrobial, dose, route and duration of administration, timing, re-dosing, and duration of the prophylaxis will be taken into account. The sample will consist of patients who underwent scheduled or emergency surgery, either as inpatients or outpatients, in hospitals in Spain. A sample size of 2335 patients has been established to estimate, with 95% confidence and 80% power, a percentage of appropriateness that is expected to be around 70%. Differences between variables will be analysed using Student's t-test, Mann-Whitney U test, Chi-square test, or Fisher's test, as appropriate. The degree of agreement between the antibiotic prophylaxis recommended by the guidelines of the different hospitals and that recommended in the literature will be analysed by calculating the Cohen's kappa indicator. Binary logistic regression analysis using generalised linear mixed models will be performed to identify possible factors associated with differences in the appropriateness of antibiotic prophylaxis. DISCUSSION: The results of this clinical study will allow us to focus on specific surgical areas with higher rates of inappropriateness, identify key points of action and guide future strategies for antimicrobial stewardship programs in the area of antibiotic prophylaxis.

Análisis de la adecuación de la profilaxis antibiótica en procedimientos quirúrgicos en España. Protocolo del estudio ProA-Q / Analysis of the appropriateness of antibiotic prophylaxis in surgical procedures in Spain. Protocol for the "ProA-Q" study

La profilaxis antibiótica quirúrgica es una de las medidas más útiles para la prevención de la infección de la herida quirúrgica.Objetivoel objetivo de este proyecto es evaluar la adecuación del uso de profilaxis antibiótica en procedimientos quirúrgicos realizados en centros hospitalarios españoles, tanto de forma global como en función del tipo de cirugía realizada. Metodología para ello, se ha diseñado un estudio observacional, retrospectivo, transversal y multicéntrico, donde se recopilarán todas aquellas variables que permitan evaluar la adecuación de la profilaxis antibiótica quirúrgica mediante la comparación del tratamiento prescrito, las recomendaciones recogidas en las guías locales y el documento de consenso de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica y la Asociación Española de Cirujanos. Se tendrán en cuenta la indicación, elección del antimicrobiano, dosis, vía de administración y tiempo de infusión, momento de la administración de la primera dosis, redosificación y la duración de la profilaxis. La muestra estará constituida por pacientes que hayan sido intervenidos de forma programada o urgente, en régimen de hospitalización o ambulatorio, en centros hospitalarios de España. Se ha establecido un tamaño muestral de 2.335 pacientes para estimar con una confianza del 95% y una potencia del 80%, un porcentaje de adecuación que se espera esté en torno al 70%. Las diferencias entre las variables se analizarán mediante la prueba t-Student, U de Mann-Whitney, el test Chi2 o test de Fisher, según proceda. El grado de concordancia entre la profilaxis antibiótica recomendada por las guías de los distintos hospitales y la recomendada en la literatura se analizará mediante el cálculo del indicador Kappa de Cohen... (AU)

Surgical antibiotic prophylaxis is one of the most useful measures to prevent surgical wound infection. Objective The aim of this project is to evaluate the appropriateness of the use of antibiotic prophylaxis in surgical procedures performed in Spanish hospitals, both globally and according to the type of surgery performed. Method For this purpose, an observational, retrospective, cross-sectional and multicenter study has been designed to collect all the variables that allow the evaluation of the appropriateness of surgical antibiotic prophylaxis by comparing the prescribed treatment, the recommendations included in the local guidelines and the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology and the Spanish Association of Surgeons. Indication, choice of antimicrobial, dose, route and duration of administration, timing, re-dosing and duration of the prophylaxis will be taken into account. The sample will consist of patients who underwent scheduled or emergency surgery, either as inpatients or outpatients, in hospitals in Spain. A sample size of 2,335 patients has been established to estimate, with 95% confidence and 80% power, a percentage of appropriateness that is expected to be around 70%. Differences between variables will be analyzed using Student's t-test, Mann-Whitney U test, Chi-square test, or Fisher's test, as appropriate. The degree of agreement between the antibiotic prophylaxis recommended by the guidelines of the different hospitals and that recommended in the literature will be analyzed by calculating the Cohen's kappa indicator. Binary logistic regression analysis using generalized linear mixed models will be performed to identify possible factors associated with differences in the appropriateness of antibiotic prophylaxis... (AU)

Pooling of six respiratory samples for the detection of SARS-CoV-2: A validation and cost study in a cohort in Lima, Peru.

Background: The continuous evolution of the SARS-CoV-2 pandemic has led to a high demand for diagnostic testing and major shortages in testing materials, especially in low- and middle-income countries. As an alternative to testing individual samples, pooling of respiratory samples has been suggested. Previous studies have assessed performance of pooling, mainly using nasopharyngeal samples for the detection of SARS-CoV-2, but few studies have examined the performance of pooling the more practical nasal swabs or saliva samples. Objective: To evaluate the sensitivity, specificity, and potential cost reduction of pooling of nasal swab (NS) and saliva (SL) samples for detection of SARS-CoV-2 in a community-based cohort study in Lima, Peru. Study design: A prospective cohort study was conducted in a community setting in San Juan de Lurigancho, Lima-Peru. NS and SL samples were collected from 132 participants twice-a-week for a 2-month period. Pools of 2 to 12 samples of the same type, from participants of the same household, were tested by RT-PCR. After pooled testing, all individual samples from positive pools and all individual samples from randomly chosen negative pools were evaluated. For assessment of diagnostic performance, pool testing results were compared with results from individual testing, which served as reference, and concordance in pooled and individual test detections was evaluated. Laboratory costs for both types of samples and testing were compared. Results: A total of 2008 NS and 2002 SL samples were collected from 132 study participants. We tested 329 NS and 333 SL pools. The mean pool size for NS and SL pools was 6.22 (SD = 0.92) and 6.39 (SD = 1.71), respectively. Using individual testing as reference, NS pooling of 6 had a sensitivity and specificity of 94% and 100%, respectively, with kappa of 0.97 (CI 95%: 0.93-1.00). The corresponding values for SL pooling of 6 were 83%, 100%, and 0.90 (CI 95%: 0.83-0.97). Compared with individual testing, pooling resulted in a cost reduction of 74.8% for NS and 72.4% for SL samples. Conclusions: Pooling easy-to-collect respiratory samples, especially NS, demonstrated very high diagnostic performance for detection of SARS-CoV-2 with substantial cost savings. This approach could be considered in large population screening programs, especially in LMIC.

In Vivo Genotoxicity and Toxicity Assessment of Sterigmatocystin Individually and in Mixture with Aflatoxin B1.

Mycotoxins are natural food and feed contaminants produced by several molds. The primary mode of exposure in humans and animals is through mixtures. Aflatoxin B1 (AFB1) and sterigmatocystin (STER) are structurally related mycotoxins that share the same biosynthetic route. Few in vivo genotoxicity assays have been performed with STER. In the present genotoxicity study, Wistar rats were dosed orally with STER (20 mg/kg b.w.), AFB1 (0.25 mg/kg b.w.) or a mixture of both in an integrated micronucleus (bone marrow) and comet study (liver and kidney). STER was dosed at the highest feasible dose in corn oil. No increase in the percentage of micronuclei in bone marrow was observed at any condition. Slight DNA damage was detected in the livers of animals treated with AFB1 or the mixture (DNA strand breaks and Fpg (Formamidopyrimidine DNA glycosylase)-sensitive sites, respectively). Plasma, liver, and kidney samples were analyzed with LC-MS/MS demonstrating exposure to both mycotoxins. General toxicity parameters (organs absolute weight, biochemistry, and histopathology) were not altered either individually or in the mixture. The overall absence of individual genotoxicity did not allow us to set any type of interaction in the mixture. However, a possible toxicokinetic interaction was observed.

Association between nasopharyngeal colonization with multiple pneumococcal serotypes and total pneumococcal colonization density in young Peruvian children.

OBJECTIVES: We examined the association of nasopharyngeal (NP) pneumococcal co-colonization (>1 pneumococcal serotype) and pneumococcal density in young Peruvian children enrolled in a prospective cohort study. METHODS: NP swabs collected monthly from children aged <3 years during both asymptomatic and acute respiratory illness (ARI) periods underwent culture-enriched microarray for pneumococcal detection and serotyping and lytA polymerase chain reaction for density assessment. We examined the serotypes commonly associated with co-colonization and the distribution of densities by co-colonization, age, current ARI, and other covariates. The association of co-colonization and pneumococcal density was assessed using a multivariable mixed-effects linear regression model, accounting for repeated measures and relevant covariates. RESULTS: A total of 27 children contributed 575 monthly NP samples. Pneumococcus was detected in 302 of 575 (53%) samples, and co-colonization was detected in 61 of these 302 (20%). The total densities were higher during ARI than non-ARI periods and lowest among the youngest children, increasing with age. In the multivariable analysis, there was no significant association between pneumococcal density and co-colonization (coefficient estimate 0.22, 95% confidence interval 0.11-0.55; reference: single-serotype detections). Serotypes 23B and 19F were detected significantly more frequently as single isolates. CONCLUSION: Pneumococcal co-colonization was common and not associated with increased pneumococcal density. Differential propensity for co-colonization was observed among individual serotypes.

Tumor Lipid Signatures Are Descriptive of Acquisition of Therapy Resistance in an Endocrine-Related Breast Cancer Mouse Model.

The lipid metabolism adaptations of estrogen and progesterone receptor-positive breast cancer tumors from a mouse syngeneic model are investigated in relation to differences across the transition from hormone-dependent (HD) to hormone-independent (HI) tumor growth and the acquisition of endocrine therapy (ET) resistance (HIR tumors). Results are articulated with reported polar metabolome results to complete a metabolic picture of the above transitions and suggest markers of tumor progression and aggressiveness. Untargeted nuclear magnetic resonance metabolomics was used to analyze tumor and mammary tissue lipid extracts. Tumor progression (HD-HI-HIR) was accompanied by increased nonesterified cholesterol forms and phospholipids (phosphatidylcholine, phosphatidylethanolamine, sphingomyelins, and plasmalogens) and decreased relative contents of triglycerides and fatty acids. Predominating fatty acids became shorter and more saturated on average. These results were consistent with gradually more activated cholesterol synthesis, ß-oxidation, and phospholipid biosynthesis to sustain tumor growth, as well as an increase in cholesterol (possibly oxysterol) forms. Particular compound levels and ratios were identified as potential endocrine tumor HD-HI-HIR progression markers, supporting new hypotheses to explain acquired ET resistance.

Model-Informed Precision Dosing Software Tools for Dosage Regimen Individualization: A Scoping Review.

BACKGROUND: Pharmacokinetic nomograms, equations, and software are considered the main tools available for Therapeutic Drug Monitoring (TDM). Model-informed precision dosing (MIPD) is an advanced discipline of TDM that allows dose individualization, and requires a software for knowledge integration and statistical calculations. Due to its precision and extensive applicability, the use of these software is widespread in clinical practice. However, the currently available evidence on these tools remains scarce. OBJECTIVES: To review and summarize the available evidence on MIPD software tools to facilitate its identification, evaluation, and selection by users. METHODS: An electronic literature search was conducted in MEDLINE, EMBASE, OpenAIRE, and BASE before July 2022. The PRISMA-ScR was applied. The main inclusion criteria were studies focused on developing software for use in clinical practice, research, or modelling. RESULTS: Twenty-eight software were classified as MIPD software. Ten are currently unavailable. The remaining 18 software were described in depth. It is noteworthy that all MIPD software used Bayesian statistical methods to estimate drug exposure and all provided a population model by default, except NONMEN. CONCLUSIONS: Pharmacokinetic software have become relevant tools for TDM. MIPD software have been compared, facilitating its selection for use in clinical practice. However, it would be interesting to standardize the quality and validate the software tools.

In vitro evaluation of membranes for regenerative procedures against oral bacteria.

The current literature on guided bone regeneration (GBR) and guided tissue regeneration (GTR) membrane contamination reports that the physicochemical characteristics of these biomaterials might influence affinity to bacteria, which appears to be a major drawback for the clinical outcome of the regenerative procedures. Thus, this study aimed to evaluate, in vitro, a multispecies biofilm adherence and passage of bacteria through different types of commercially available membranes for GTR/GBR. Four types of membranes were tested (n=12): LC) Lumina Coat®; JS) Jason®; BG) Biogide®; and LP) Lumina PTFE®. Aluminum foil (AL) simulated an impermeable barrier and was used as the control. The membranes were adapted to specific apparatus and challenged with a mixed bacterial culture composed of A. actinomycetemcomitans b, S. mutans, S. mitis, and A. israelii. After 2 h or 7 days, bacterial adhesion and passage of bacteria were evaluated through CFU counting, which was analyzed by two-way ANOVA e post hoc Tukey, at a 5% significance level. Representative areas of two membranes of each group were analyzed through scanning electron microscopy (SEM) to assess the morphology and organization of the biofilm over the membrane fibers. LC and LP presented similar values of adhered bacterial cells (p > 0.05), significantly inferior when compared to the other groups, in both time points (p < 0.05). All the tested groups were permeable to bacterial cells, with no significant difference between the trial period of 2 h and 7 days (p > 0.05). SEM analyses demonstrated that adhered bacteria number increased throughout the time points (2 h < 7 days). Commercially available biological membranes demonstrated intense bacterial adherence and passage of bacteria, which increased throughout the trial period.