Plasma sodium during the recovery of renal function in critically ill adult patients: Multicenter prospective cohort study.

BACKGROUND: Sodium increases during acute kidney injury (AKI) recovery. Both hypernatremia and positive fluid balances are associated with increased mortality. We aimed to evaluate the association between daily fluid balance and daily plasma sodium during the recovery from AKI among critical patients. METHODS: Adult patients with AKI were enrolled in four ICUs and followed up for four days or until ICU discharge or hemodialysis initiation. Day zero was the peak day of creatinine. The primary outcome was daily plasma sodium; the main exposure was daily fluid balance. RESULTS: 93 patients were included. The median age was 66 years; 68% were male. Plasma sodium increased in 79 patients (85%), and 52% presented hypernatremia. We found no effect of daily fluid balance on plasma sodium (ß -0.26, IC95%: -0.63-0.13; p = 0.19). A higher total sodium variation was observed in patients with lower initial plasma sodium (ß -0.40, IC95%: -0.53 to -0.27; p < 0.01), higher initial urea (ß 0.07, IC95%: 0.04-0.01; p < 0.01), and higher net sodium balance (ß 0.002, IC95%: 0.0001-0.01; p = 0.05). CONCLUSIONS: The increase in plasma sodium is common during AKI recovery and can only partially be attributed to the water and electrolyte balances. The incidence of hypernatremia in this population of patients is higher than in the general critically ill patient population.

Eribulin in metastatic breast cancer: Real world data.

BACKGROUND: Metastatic breast cancer (MBC) is incurable. Systemic therapy is the standard treatment; however, an optimal sequence of chemotherapy has not been established. OBJECTIVE: Evaluating effectiveness and safety of eribulin in MBC treatment and comparing the results obtained with published literature. METHODS: Observational, descriptive and retrospective study of patients with MBC treated with eribulin from 01/12/2015 to 30/10/2021. Effectiveness was analysed using Kaplan-Meier-survival-curves, for the overall number of patients treated and stratified by treatment line. Safety was measured according to adverse events (AE) based on CTCAE v5.0. Data analysis was performed using R v4.0.1. RESULTS: They were included in this study 53 women who received eribulin (median age 58 years). Comparison of median survival from this study versus published data were: progression-free-survival (PFS) 3 (IC95%: 3-4) versus 3.7 months and overall-survival (OS) 8 (IC95%: 3-4) versus 13.2 months for the overall number of patients. For the 1-3 line treatment group, PFS was 6 (IC95%: 3-NA) and OS was 15 (IC95%: 6-NA). There were 322 AEs, the most frequent being blood disorders 16% (52), general disorders 12% (38), and gastrointestinal disorders 12% (38). CONCLUSIONS: The median PFS was similar to that reported previously, with lower OS. There was a tendency to achieve better results when eribulin was used earlier. Eribulin is a less well-tolerated drug than published literature.

Dose reduction and toxicity of lenalidomide-dexamethasone in multiple myeloma: A machine-learning prediction model.

PURPOSE: Lenalidomide remains an effective drug for multiple myeloma, but it is often associated with adverse events and requires dose adjustments. The objective of this study was to propose a model for predicting whether a patient would require dose adjustment. METHODS: This retrospective observational study included patients treated with lenalidomide and dexamethasone from June 2014 to September 2018 at a tertiary hospital. Demographic variables, patient functional status, disease, analytical data specific to myeloma, and treatment-related variables were collected. Univariate and machine learning (logistic regression and classification and regression trees model) analyses were also performed. Kaplan-Meier analysis was used to determine the time of toxicity onset. Only lenalidomide (and not dexamethasone) related dose reductions are included. RESULTS: A total of 64 patients received lenalidomide-dexamethasone. 69% (44) required dose reduction or discontinuation of treatment due to lenalidomide-related adverse events. The median time between treatment beginning and lenalidomide dose reduction or discontinuation was 8.0 months (95% CI: 6.0-17.0). Age, platelet count, and neutrophil count were related to dose reduction in the univariate model. In the multivariate models, age and neutrophil count were significant in the logistic regression model, renal clearance, and neutrophil count in the classification and regression trees model. CONCLUSION: Elderly patients and those with low bone marrow reserves are prone to dose-limiting adverse events. This study can aid in making follow-up, prophylaxis, and dosing decisions to achieve better pharmacotherapeutic results.

Utility of the Serum Protein Electrophoresis in the Opportunistic Screening for the Deficiency of Alpha-1 Antitrypsin.

BACKGROUND: A deficiency in alpha-1 antitrypsin (AAT1) is a rare disorder that represents a significant health threat and early diagnostic priority issue. We investigated the usefulness of the serum protein electrophoresis (SPE) as an opportunistic screening tool for AAT1 deficiency. METHODS: For 6 months, all SPE carried out for any reasons were evaluated in our center. In those with less than 3% of alpha-1 globulins, AAT1 concentrations were studied. The SERPINA1 gene was subsequently sequenced in those patients displaying concentrations below 100 mg/dL. RESULTS: Out of the total, 14 patients (0.3%) were identified with low AAT1 concentrations, with 11 of them agreeing to enter the study. Of those, mutations in the SERPINA1 gene were discovered in 10 patients (91%). Heterozygous mutations were detected in seven patients; three had the c.1096G>A mutation (p.Glu366Lys; Pi*Z), two had the c.863A>T mutation (p.Glu288Val; Pi*S), one had the c.221_223delTCT mutation (p.Phe76del; Pi*Malton), and the last one had the c.1066G>A (p.Ala356Thr) mutation, which was not previously described. Finally, one patient had the c.863A>T mutation in homozygosis, whereas two double heterozygous patients c.863A>T/c.1096G>A were detected. CONCLUSIONS: An altered result in the concentration of AAT1 anticipates a mutation in the SERPINA1 gene in a manner close to 91%. The relationship between a decrease in the alpha-1 globulin band of the SPE and an alteration in the AAT1 concentration is direct in basal states of health. The SPE is presented as a highly sensitive test for opportunistic screening of AAT1 deficiency.

[Positivity of antigen test in healthcare workers in the first week after diagnosis of SARS-CoV-2 infection.] / Positividad de test de antígenos en trabajadores sanitarios en la primera semana tras el diagnóstico de infección por SARS-CoV-2.

OBJECTIVE: The Surveillance and Control Strategy against COVID-19 of the spanish Ministry of Health focuses, since December 2021, on actions aimed at vulnerable people and areas, including healthcare professionals. According to these protocols, a diagnostic test for acute infection (PDIA), with a negative result, is required prior to returning to work (at least five days after the start of clinical practice). The aim of the study was to analyze the proportion of positive antigen (Ag) test results in the first week of diagnosis among healthcare professionals in a university hospital belonging to the province of A Coruña (Spain). METHODS: We calculated the proportion of healthcare professionals who had symptoms on the 5th day after diagnosis of COVID-19 between January and March 2022, and the proportion of Ag tests performed after returning to work with positive results. These results were compared according to the month and 95% confidence intervals were calculated. RESULTS: 1,085 cases of COVID-19 were diagnosed among healthcare professionals. 18.62% (95%CI 16.34-21.63; n=202/1,085) were still symptomatic on the 5th day. 55.27% (95% CI 51.92-58.58; n=488/833) of the Ag tests performed after return to work were positive. The mean number of days to perform the Ag test after diagnosis was 6.76 days (SD 0.76). CONCLUSIONS: Our results show a high proportion of positive results one week after diagnosis of COVID-19 in asymptomatic patients. Taking into account that in the general population, discharge is based on clinical and temporal criteria, and assuming that not every positive test indicates infectivity, adopting a strategy similar to the rest of the population in healthcare workers would be considered plausible.

OBJETIVO: La Estrategia de Vigilancia y Control frente a la COVID-19 del Ministerio de Sanidad se centra, desde diciembre de 2021, en actuaciones dirigidas a personas y ámbitos vulnerables, entre los que se encuentran los profesionales sanitarios. Atendiendo a dichos protocolos, se requiere una prueba diagnóstica de infección aguda (PDIA), con resultado negativo, previa a su reincorporación laboral (transcurridos al menos cinco días desde inicio de clínica). El objetivo del estudio fue analizar la proporción de resultados positivos de test de antígenos (Ag) en la primera semana del diagnóstico entre los profesionales sanitarios en un hospital universitario perteneciente a la provincia de A Coruña. METODOS: Se calculó la proporción de sanitarios que, tras diagnóstico de COVID-19 entre enero y marzo de 2022, tenían síntomas al 5º día y la proporción de test de Ag realizados previa reincorporación laboral con resultado positivo. Se compararon estos resultados en función del mes y se calcularon los intervalos de confianza al 95%. RESULTADOS: Se diagnosticaron 1.085 casos de COVID-19 entre los profesionales sanitarios. Un 18,62% (IC95% 16,34-21,63; n=202/1.085) continuaba con síntomas al 5º día. El 55,27% (IC95% 51,92-58,58; n=488/833) de los test de Ag realizados previa reincorporación laboral fueron positivos. La media de días para realizar el test de Ag tras el diagnóstico fue de 6,76 días (DE 0,76). CONCLUSIONES: Nuestros resultados muestran una alta proporción de resultados positivos tras una semana del diagnóstico de COVID-19 en asintomáticos. Teniendo en cuenta que en la población general el alta se basa en criterios clínicos y temporales, asumiendo que no todo test positivo indica infectividad, consideraríamos plausible adoptar una estrategia similar a la del resto de la población en estos profesionales.

Real-world Data Study of the Efficacy and Toxicity of Nivolumab vs. Cetuximab and Predictors of Response to Nivolumab in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck in a European Population.

BACKGROUND/AIM: This study aimed to assess the effectiveness and safety of nivolumab versus cetuximab in patients with Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M HNSCC), as well as to analyze possible prognostic factors for response to treatment with nivolumab. PATIENTS AND METHODS: We conducted an observational, retrospective, descriptive study of patients with R/M HNSCC who initiated treatment with nivolumab or cetuximab monotherapy in two periods of equivalent duration. Overall efficacy was measured in terms of progression-free survival (PFS) and overall survival (OS). Safety was evaluated using the Common Terminology Criteria for Adverse Events classification version 5.0 of the National Cancer Institute. RESULTS: Median OS was 9.1 months with nivolumab (n=34) and 6.3 months with cetuximab (n=12). PFS was 4.3 months for nivolumab and 4.65 months for cetuximab. Any grade adverse events (AEs) were reported in 97% and 100% of the patients treated with nivolumab and cetuximab. Serious AEs were observed in 26% and 58% of the patients, respectively. Elevated albumin values, lymphocytosis, neutropenia, and elevated neutrophil/lymphocyte ratio values were found to have positive prognostic value on the response to nivolumab in R/M HNSCC. CONCLUSION: Effectiveness of nivolumab in terms of OS remains superior to cetuximab. OS, PFS and severe or any grade AEs were superior in both arms of our study compared to those in clinical trials. The AEs profile of nivolumab differed in our study from that in the clinical trials' observations. We have identified four statistically significant prognostic variables on the response to nivolumab in R/M HNSCC.

Positividad de test de antígenos en trabajadores sanitarios en la primera semana tras el diagnóstico de infección por SARS-CoV-2 / Positivity of antigen test in healthcare workers in the first week after diagnosis of SARS-CoV-2 infection

Fundamentos: LaEstrategia de Vigilancia y Control frente a la COVID-19 del Ministerio de Sanidad se centra, desde diciembre de 2021, en actuaciones dirigidas a personas y ámbitos vulnerables, entre los que se encuentran los profesionales sanitarios. Atendiendo a dichos protocolos, se requiere una prueba diagnóstica de infección aguda (PDIA), con resultado negativo, previa a sureincorporación laboral (transcurridos al menos cinco días desde inicio de clínica). El objetivo del estudio fue analizar la proporción deresultados positivos de test de antígenos (Ag) en la primera semana del diagnóstico entre los profesionales sanitarios en un hospitaluniversitario perteneciente a la provincia de A Coruña. Métodos: Se calculó la proporción de sanitarios que, tras diagnóstico de COVID-19 entre enero y marzo de 2022, tenían síntomasal 5º día y la proporción de test de Ag realizados previa reincorporación laboral con resultado positivo. Se compararon estos resulta-dos en función del mes y se calcularon los intervalos de confianza al 95%. Resultados: Se diagnosticaron 1.085 casos de COVID-19 entre los profesionales sanitarios. Un 18,62% (IC95% 16,34-21,63;n=202/1.085) continuaba con síntomas al 5º día. El 55,27% (IC95% 51,92-58,58; n=488/833) de los test de Ag realizados previa reincorporación laboral fueron positivos. La media de días para realizar el test de Ag tras el diagnóstico fue de 6,76 días (DE 0,76). Conclusiones: Nuestros resultados muestran una alta proporción de resultados positivos tras una semana del diagnósticode COVID-19 en asintomáticos. Teniendo en cuenta que en la población general el alta se basa en criterios clínicos y temporales,asumiendo que no todo test positivo indica infectividad, consideraríamos plausible adoptar una estrategia similar a la del resto de lapoblación en estos profesionales.(AU)

Background: TheSurveillance and Control Strategy against COVID-19 of the spanish Ministry of Health focuses, since December2021, on actions aimed at vulnerable people and areas, including healthcare professionals. According to these protocols, a diagnostictest for acute infection (PDIA), with a negative result, is required prior to returning to work (at least five days after the start of clinicalpractice). The aim of the study was to analyze the proportion of positive antigen (Ag) test results in the first week of diagnosis amonghealthcare professionals in a university hospital belonging to the province of A Coruña (Spain). Methods: We calculated the proportion of healthcare professionals who had symptoms on the 5th day after diagnosis of COVID-19between January and March 2022, and the proportion of Ag tests performed after returning to work with positive results. These resultswere compared according to the month and 95% confidence intervals were calculated. Results: 1,085 cases of COVID-19 were diagnosed among healthcare professionals. 18.62% (95%CI 16.34-21.63; n=202/1,085) werestill symptomatic on the 5th day. 55.27% (95% CI 51.92-58.58; n=488/833) of the Ag tests performed after return to work were positive. The mean number of days to perform the Ag test after diagnosis was 6.76 days (SD 0.76).Conclusions: Our results show a high proportion of positive results one week after diagnosis of COVID-19 in asymptomaticpatients. Taking into account that in the general population, discharge is based on clinical and temporal criteria, and assuming thatnot every positive test indicates infectivity, adopting a strategy similar to the rest of the population in healthcare workers would beconsidered plausible.(AU)

Microplastic levels on sandy beaches: Are the effects of tourism and coastal recreation really important?

This study assessed the effect of tourism and other recreational activities on microplastic (MP) levels and their characteristics in the sand and surf zone of the seawater. Six sites were chosen belonging to three sandy beaches with similar geomorphologic and morphodynamic characteristics but with different tourism activities. On average, a concentration of 1133.3 ± 811.3 items/kg dry weight (d.w.) and 12.7 ± 14.9 items/m3 were found in the sand and seawater samples, respectively. Fibers and films predominated and were less than 1 mm in length. In the sand, the films mainly matched the PE polymer spectra and the fibers matched PET polymer, cotton, and indigo blue dye; in the seawater samples, PP films and PET fibers prevailed. At the Pehuén-Co - Monte Hermoso Coastal Marine MPA where the flow of tourists is low, the MP levels were the lowest and the largest particles were found, mainly blue or black fibers, with less polymer diversity, cotton and PET being the most prevalent suggesting a recent input of textile fibers to this site. Moreover, the highest concentration of MPs was found on the southern site of a beach considered to be more pristine due to negligible human activity, including the smallest size pattern, mostly composed of white films or fibers with a greater diversity of polymers, predominantly PE > PET > PP. A great occurrence of PVC white films was also found in the surf zone at this site. Proximity to the mouth of a river, littoral drift, and other point sources were identified as the main sources, indicating that, apart from the local tourism and recreational activities, other sources might play a major role in the input of MPs to sandy beaches, such as extensive/intensive agricultural land use and irrigation areas.

Beached microplastics at the Bahia Blanca Estuary (Argentina): Plastic pellets as potential vectors of environmental pollution by POPs.

Microplastics (MPs) from the coastal areas of a highly anthropised estuary were sampled to assess their distribution in coastal sediments and their role as potential vectors of pollution. The average MP density was 1693 ± 2315 MPs/kg, which mainly accumulated in the high tide and storm berm areas of the beach. The Microplastic Pollution Index (MPPI), Microplastic Impact Coefficient (CMPI), Hierarchical Cluster Analysis and Principal Component Analysis revealed spatial variation in MPs pollution. High-density polyethylene plastic pellets were abundant at two beaches (192 ± 218 MPs/kg sediment). Furthermore, the presence of sorbed chemicals on pellets was assessed through GC-MS, showing 0.95 ± 0.09 ng/g of ∑7OCPs, 4.03 ± 0.89 ng/g of ∑7PCBs, 108.76 ± 12.88 ng/g of ∑16 PAHs and 122.79 ± 11.13 g/g of ∑29 PAHs. The sorption capacity of plastics, combined with their abundance, poses an environmental concern and also highlights their suitability as indicators of chemical exposure.

Effect of Fish Oil Parenteral Emulsion Supplementation on Inflammatory Parameters after Esophagectomy.

(Background) Esophagectomy (EPG) presents high morbidity and mortality. Omega-3 fatty acids (ω-3FA) are a pharmaconutrient with benefits for postoperative morbidity. Studies of ω-3FA administered parenterally after esophagectomy are scarce. This study proposes to investigate the effect of combining fish oil lipid emulsions (LE) administered parenterally with enteral nutrition support. (Methods) Randomization was 1:1:1 in three groups: Group A received a LE mixture of 0.4 g/kg/day of fish oil and 0.4 g/kg/day of LCT/MCT 50:50, Group B received 0.8 g/kg/day of fish oil LE, and Group C received 0.8 g/kg/day of LCT/MCT 50:50. Variables were measured at recruitment time and day +1, +3, and +5. Inflammatory variables studied were Interlukin-6, C-reactive protein (CRP), tumoral necrosis factor-α (TNF-α), IL-10, IL-8 and CD25s. Safety, nutritional parameters and complications were analyzed. (Results) Administration of ω-3LE in the immediate postoperative period did not modulate the earlier inflammatory response. Statistically significant differences were found in IL-6 and CRP overall temporal evolution but were not found when studying the type of LE administered or in patients needing critical care. Administration of ω-3 resulted in safe and improved hypertriglyceridemia, depending on the dose. (Conclusions) ω-3FA has no impact on the early inflammatory postoperative response assessed for a short period but was safe. More studies for longer periods are needed.

Treatment of melasma with platelet-rich plasma: A self-controlled clinical trial.

Melasma is a common circumscribed hypermelanosis of sun-exposed areas of the skin. Platelet-Rich Plasma therapy has been evidenced to inhibit melanin synthesis in animals and humans. To determine the effectiveness of platelet-rich plasma as a treatment for melasma. Twenty female patient with melasma were involved in this study. The intervention included three Platelet-Rich Plasma application sessions at 15-day intervals. Patients were evaluated before and after treatment. Variables measured included the facial melanin concentration using the melasma area and severity index score, melasma quality of life scale satisfaction grade, and histologic changes. Mean age was 41 ± 7 years. An initial MELASQOL score of 42 ± 14.8 and final score of 16.6 ± 7.2 (p = 0.008) were reported; the initial and final MASI score were 15.5 ± 8.4 and 9.5 ± 7.2 (p = 0.001), respectively. The dermatoscopy examination revealed a decrease in pigmentation after intervention (p = 0.001). Histopathologic improvement was detected in reductions in cutaneous atrophy (14 [70%] vs. 11 [55%]), solar elastosis (15 [75%] vs.11 [55%]), and inflammatory infiltrate (9 [45%] vs. 6 [30%]), before and after treatment, respectively. The intervention was associated with decreased intensity of the melasma patch and improved skin quality, shown by the MELASQOL and MASI scores.

Occurrence and Genomic Characterization of Clone ST1193 Clonotype 14-64 in Uncomplicated Urinary Tract Infections Caused by Escherichia coli in Spain.

We conducted a prospective, multicenter, specific pilot study on uncomplicated urinary tract infections (uUTI). One-hundred non-duplicated uropathogenic Escherichia coli (UPEC) from uUTI occurred in 2020 in women attending 15 primary care centers of a single health region of northern Spain were characterized using a clonal diagnosis approach. Among the high genetic diversity showed by 59 different phylogroup-clonotype combinations, 11 clones accounted for 46% of the isolates: B2-ST73 (CH24-30); B2-ST73 (CH24-103); B2-ST131 (CH40-30); B2-ST141 (CH52-5); B2-ST372 (CH103-9); B2-ST404 (CH14-27); B2-ST404 (CH14-807); B2-ST1193 (CH14-64); D-ST69 (CH35-27); D-ST349 (CH36-54), and F-ST59 (CH32-41). The screening of the UPEC status found that 69% of isolates carried ≥ 3 of chuA, fyuA, vat, and yfcV genes. Multidrug resistance to at least one antibiotic of ≥ 3 antimicrobial categories were exhibited by 30% of the isolates, with the highest rates of resistance against ampicillin/amoxicillin (48%), trimethoprim (35%), norfloxacin (28%), amoxicillin-clavulanic acid (26%), and trimethoprim-sulfamethoxazole (24%). None extended-spectrum beta-lactamase/carbapenemase producer was recovered. According to our results, fosfomycin and nitrofurantoin should be considered as empirical treatment of choice for uUTI by E. coli (resistance rates 4% and 2%, respectively). We uncover the high prevalence of the pandemic fluoroquinolone-resistant ST1193 clone (6%) in uUTI, which represents the first report in Spain in this pathology. The genomic analysis showed similar key traits than those ST1193 clones disseminated worldwide. Through the SNP comparison based on the core genome, the Spanish ST1193 clustered with isolates retrieved from the Enterobase, showing high genomic similarity than the global ST1193 described in the United States, Canada and Australia. IMPORTANCE Analyzing the clonal structure and antimicrobial resistance of E. coli isolates implicated in uncomplicated urinary tract infections, one of the most frequent visits managed in primary health care, is of interest for clinicians to detect changes in the dynamics of emerging uropathogenic clones associated with the spread of fluoroquinolone resistance. It can also provide consensus concerning optimal control and antibiotic prescribing.

Bilateral vocal fold paralysis after COVID-19 infection. Another neuro-invasive manifestation? Case series / Parálisis bilateral de cuerdas vocales tras infección por COVID-19. ¿Una manifestación neuroinvasiva? Serie de casos

Abstract The agent that causes the coronavirus disease (COVID-19), associated with the severe acute respiratory syndrome (SARS-CoV-2), produces a spectrum of symptoms that mainly affect the respiratory system, the central nervous system (CNS), the regulation of hemostasis and the immune system. Bilateral vocal fold paralysis (BVFP) is a condition of unknown incidence among infected patients, either because it is short-lived or because of the difficulty in establishing a direct cause to the virus. Viral infection has been described in the literature as a cause of BVFP and there is the suspicion that a proportion of the idiopathic cases are due to undiagnosed viral infections. Although the neurotropic mechanisms for SARS-CoV-2 remain unclear, there is strong evidence to ensure its neuroinvasive potential. The most frequent etiologies of BVFP are trauma, neoplasm, and neurological, but a viral origin should not be ruled out. Causality between COVID-19 and BVFP is plausible and will require further study in the short and long term. We present a case series that support and discuss the hypothesis under consideration.

Resumen El agente causal de la enfermedad por coronavirus (COVID-19), asociado a síndrome respiratorio agudo grave (SARS-CoV-2), genera un espectro de síntomas que afectan fundamentalmente el sistema respiratorio, el sistema nervioso central (SNC), la regulación hemostásica y el sistema inmune. La parálisis bilateral de cuerdas vocales (PBCV) es una entidad cuya incidencia en infectados se desconoce, bien porque no se presentan durante el tiempo suficiente o por la dificultad de establecer una causalidad directa con el virus. La infección vírica, como causa de PBCV, está descrita en la literatura y se sospecha que una parte de los casos idiopáticos corresponden a infecciones víricas no diagnosticadas. Aunque los mecanismos neurotrópicos no están completamente aclarados para el SARS-CoV-2, existen indicios sólidos para asegurar su potencial neuroinvasivo. Las causas traumáticas, neoplásicas y neurológicas son las etiologías más comunes de PBCV, sin que se pueda descartar el origen vírico. Es plausible una causalidad entre el COVID-19 y la PBCV, que requerirá mayores estudios a corto y largo plazo. Presentamos una serie de casos que sostienen y discuten la hipótesis en consideración.

Atmospheric PAHs in rural, urban, industrial and beach locations in Buenos Aires Province, Argentina: sources and health risk assessment.

The first atmospheric PAHs levels and associated inhalation cancer risk were assessed over southwest Buenos Aires region by deploying PUF disk PAS samplers. Eight sampling location included coastal zones, touristic beaches, and rural inland areas were considered. PUF disks were fortified with surrogate standards and extracted by automated Soxhlet prior to GC-MS analysis. Σ16 PAHs ranged from 1.13 to 44.5 ng m-3 (10.3 ± 9.8), while urban locations showed up to 10 times higher PAH levels than rural or beach locations. Direct sources of PAHs, such as intensive vehicle traffic, heating, and general combustion activities, were identified. PAHs with four to six rings (46.62%) were predominantly Flt, Pyr, BbF, and BkF, and carcinogenic risk was expressed by BaP (0.10 ± 0.07 ng m-3) and BaPTEQs (0.26 ± 0.22 ng m-3). Inhalation ECR (2.23E-5, WHO) presented the lowest risk at beach locations. Molecular ratios and PCA showed a strong dominance in pyrolytic sources, such as biomass and coal combustion, with a particular signature in fires at inland locations. Overall, this study demonstrated that PUF disk passive air sampling provided a sound and simple approach for tracking air PAHs, their sources and public health risks, bringing a cost-effective tool for pollution control measures, even at small and remote towns. This is particularly relevant in extensive countries with medium or low income, such as Argentina.

HI-NESS: a family of genetically encoded DNA labels based on a bacterial nucleoid-associated protein.

The interplay between three-dimensional chromosome organisation and genomic processes such as replication and transcription necessitates in vivo studies of chromosome dynamics. Fluorescent organic dyes are often used for chromosome labelling in vivo. The mode of binding of these dyes to DNA cause its distortion, elongation, and partial unwinding. The structural changes induce DNA damage and interfere with the binding dynamics of chromatin-associated proteins, consequently perturbing gene expression, genome replication, and cell cycle progression. We have developed a minimally-perturbing, genetically encoded fluorescent DNA label consisting of a (photo-switchable) fluorescent protein fused to the DNA-binding domain of H-NS - a bacterial nucleoid-associated protein. We show that this DNA label, abbreviated as HI-NESS (H-NS-based indicator for nucleic acid stainings), is minimally-perturbing to genomic processes and labels chromosomes in eukaryotic cells in culture, and in zebrafish embryos with preferential binding to AT-rich chromatin.

Detection of archived lamivudine-associated resistance mutations in virologically suppressed, lamivudine-experienced HIV-infected adults by different genotyping techniques (GEN-PRO study).

BACKGROUND: Previously selected lamivudine resistance-associated mutations (RAMs) may remain archived within the proviral HIV-DNA. OBJECTIVES: To evaluate the ability of proviral DNA genotyping to detect lamivudine RAMs in HIV-1 virologically suppressed participants; the correlation between Sanger and next generation sequencing (NGS); and predictive factors for detection of lamivudine RAMs in proviral DNA. METHODS: Cross-sectional study of participants on stable antiretroviral therapy and suppressed for ≥1 year. Analysis of proviral DNA was performed by Sanger sequencing in whole blood and by NGS in PBMCs. RESULTS: We analysed samples from 102 subjects (52 with and 50 without lamivudine RAMs in historical plasma RNA-genotypes). Among participants with previous lamivudine resistance, Sanger sequencing detected RAMs in 26.9%. Detection rates significantly increased using NGS: 47.9%, 64.6%, 75% and 87.5% with the 20%, 10%, 5% and 1% thresholds, respectively. As for participants without historical lamivudine resistance, Sanger detected the RAMs in 1/49 (2%), and NGS (5% threshold) in 8/45 (17.8%). Multivariate models fitted to the whole population revealed that having a history of lamivudine resistance was a risk factor for detection of lamivudine RAMs by NGS. Among participants with historical lamivudine resistance, multivariate analysis showed that a longer time since HIV diagnosis was associated with persistence of archived mutations by NGS at thresholds of >10% [OR 1.10 (95% CI: 1.00-1.24)] and >5% [OR 1.16 (95% CI: 1.02-1.32)]. CONCLUSIONS: Proviral DNA Sanger sequencing does not detect the majority of historical lamivudine RAMs. NGS increases the sensitivity of detection at lower thresholds, although the relevance of these minority populations with lamivudine RAMs needs further evaluation.