Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A

Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N= 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel

Influence of inflammation on parasitism and area of experimental amoebic liver abscess: an immunohistochemical and morphometric study

The influence of inflammation on the number of trophozoites and on the murine amoebic liver abscess area following infection with Entamoeba histolytica and E. dispar was evaluated. Immunohistochemistry and digital morphometry were used to identify and quantify the trophozoites, neutrophils, macrophages, and lesions. Positive correlation was observed between the number of trophozoites and inflammatory cells. A significant decrease in parasitism and inflammation in groups treated with dexamethasone was observed. The scarceness or absence of trophozoites in the treated groups suggest the importance of the inflammatory response in the production of amoebic hepatic abscesses in spite of the inherent virulence of the parasite being decisive in the establishment of the lesion

Combinations of Plant Water-Stress and Neonicotinoids Can Lead to Secondary Outbreaks of Banks Grass Mite (Oligonychus Pratensis Banks)

Spider mites, a cosmopolitan pest of agricultural and landscape plants, thrive under hot and dry conditions, which could become more frequent and extreme due to climate change. Recent work has shown that neonicotinoids, a widely used class of systemic insecticides that have come under scrutiny for non-target effects, can elevate spider mite populations. Both water-stress and neonicotinoids independently alter plant resistance against herbivores. Yet, the interaction between these two factors on spider mites is unclear, particularly for Banks grass mite (Oligonychus pratensis; BGM). We conducted a field study to examine the effects of water-stress (optimal irrigation = 100% estimated evapotranspiration (ET) replacement, water stress = 25% of the water provided to optimally irrigated plants) and neonicotinoid seed treatments (control, clothianidin, thiamethoxam) on resident mite populations in corn (Zea mays, hybrid KSC7112). Our field study was followed by a manipulative field cage study and a parallel greenhouse study, where we tested the effects of water-stress and neonicotinoids on BGM and plant responses. We found that water-stress and clothianidin consistently increased BGM densities, while thiamethoxam-treated plants only had this effect when plants were mature. Water-stress and BGM herbivory had a greater effect on plant defenses than neonicotinoids alone, and the combination of BGM herbivory with the two abiotic factors increased the concentration of total soluble proteins. These results suggest that spider mite outbreaks by combinations of changes in plant defenses and protein concentration are triggered by water-stress and neonicotinoids, but the severity of the infestations varies depending on the insecticide active ingredient

Impact of the COVID-19 pandemic on the organisation of stroke care. Madrid Stroke Care Plan

La sobrecarga asistencial y los cambios organizativos frente a la pandemia de COVID-19 podrían estar repercutiendo en la atención al ictus agudo en la Comunidad de Madrid. Métodos: Encuesta estructurada en bloques: características del hospital, cambios en infraestructura y recursos, circuitos de código ictus, pruebas diagnósticas, rehabilitación y atención ambulatoria. Análisis descriptivo según el nivel de complejidad en la atención del ictus (disponibilidad o no de unidad de ictus y de trombectomía mecánica). Resultados: De los 26 hospitales del SERMAS que atienden urgencias en adultos, 22 cumplimentaron la encuesta entre el 16 y 27 de abril. El 95% han cedido neurólogos para atender a pacientes afectados por la COVID-19. Se han reducido camas de neurología en el 89,4%, modificado los circuitos en urgencias para ictus en el 81%, con circuitos específicos para sospecha de infección por SARS-CoV2 en el 50%, y en el 42% de los hospitales los pacientes con ictus agudo positivos para SARS-CoV2 no ingresan en camas de neurología. Ha mejorado el acceso altratamiento, con trombectomía mecánica las 24 h en el propio hospital en 10 hospitales, y sehan reducido los traslados interhospitalarios secundarios. Se ha evitado el ingreso de pacientescon ataque isquémico transitorio o ictus leve (45%) y se han incorporado consultas telefónicaspara seguimiento en el 100%.Conclusiones: Los cambios organizativos de los hospitales de la Comunidad de Madrid frente ala pandemia por SARS-Co2 han modificado la dedicación de recursos humanos e infraestructurasde las unidades de neurología y los circuitos de atención del ictus, realización de pruebasdiagnósticas, ingreso de los pacientes y seguimientoThe overload of the healthcare system and the organisational changes made inresponse to the COVID-19 pandemic may be having an impact on acute stroke care in the Regionof Madrid.Methods: We conducted a survey with sections addressing hospital characteristics, changes ininfrastructure and resources, code stroke clinical pathways, diagnostic testing, rehabilitation,and outpatient care. We performed a descriptive analysis of results according to the level ofcomplexity of stroke care (availability of stroke units and mechanical thrombectomy).Results: The survey was completed by 22 of the 26 hospitals in the Madrid Regional HealthSystem that attend adult emergencies, between 16 and 27 April 2020. Ninety-five percent ofhospitals had reallocated neurologists to care for patients with COVID-19. The numbers of neuro-logy ward beds were reduced in 89.4% of hospitals; emergency department stroke care pathwayswere modified in 81%, with specific pathways for suspected SARS-CoV2 infection established in50% of hospitals; and SARS-CoV2-positive patients with acute stroke were not admitted to neu-rology wards in 42%. Twenty-four hour on-site availability of mechanical thrombectomy wasimproved in 10 hospitals, which resulted in a reduction in the number of secondary hospitaltransfers. The admission of patients with transient ischaemic attack or minor stroke was avoi-ded in 45% of hospitals, and follow-up through telephone consultations was implemented in100%.Conclusions: The organisational changes made in response to the SARS-Co2 pandemic in hos-pitals in the Region of Madrid have modified the allocation of neurology department staff andinfrastructure, stroke units and stroke care pathways, diagnostic testing, hospital admissions,and outpatient follow-u

Bioaccessibility of selenium after human ingestion in relation to its chemical species and compartmentalization in maize

International audienceSelenium is a micronutrient needed by all living organisms including humans, but often present in low concentration in food with possible deficiency. From another side, at higher concentrations in soils as observed in seleniferous regions of the world, and in function of its chemical species, Se can also induce (eco)toxicity. Root Se uptake was therefore studied in function of its initial form for maize (Zea mays L.), a plant widely cultivated for human and animal food over the world. Se phytotoxicity and compartmentalization were studied in different aerial plant tissues. For the first time, Se oral human bioaccessibility after ingestion was assessed for the main Se species (SeIV and SeVI) with the BARGE ex vivo test in maize seeds (consumed by humans), and in stems and leaves consumed by animals. Corn seedlings were cultivated in hydroponic conditions supplemented with 1 mg L−1 of selenium (SeIV, SeVI, Control) for 4 months. Biomass, Se concentration, and bioaccessibility were measured on harvested plants. A reduction in plant biomass was observed under Se treatments compared to control, suggesting its phytotoxicity. This plant biomass reduction was higher for selenite species than selenate, and seed was the main affected compartment compared to control. Selenium compartmentalization study showed that for selenate species, a preferential accumulation was observed in leaves, whereas selenite translocation was very limited toward maize aerial parts, except in the seeds where selenite concentrations are generally high. Selenium oral bioaccessibility after ingestion fluctuated from 49 to 89 % according to the considered plant tissue and Se species. Whatever the tissue, selenate appeared as the most human bioaccessible form. A potential Se toxicity was highlighted for people living in seleniferous regions, this risk being enhanced by the high Se bioaccessibility

Genome Sequence of Fusobacterium nucleatum Subspecies Polymorphum — a Genetically Tractable Fusobacterium

Fusobacterium nucleatum is a prominent member of the oral microbiota and is a common cause of human infection. F. nucleatum includes five subspecies: polymorphum, nucleatum, vincentii, fusiforme, and animalis. F. nucleatum subsp. polymorphum ATCC 10953 has been well characterized phenotypically and, in contrast to previously sequenced strains, is amenable to gene transfer. We sequenced and annotated the 2,429,698 bp genome of F. nucleatum subsp. polymorphum ATCC 10953. Plasmid pFN3 from the strain was also sequenced and analyzed. When compared to the other two available fusobacterial genomes (F. nucleatum subsp. nucleatum, and F. nucleatum subsp. vincentii) 627 open reading frames unique to F. nucleatum subsp. polymorphum ATCC 10953 were identified. A large percentage of these mapped within one of 28 regions or islands containing five or more genes. Seventeen percent of the clustered proteins that demonstrated similarity were most similar to proteins from the clostridia, with others being most similar to proteins from other gram-positive organisms such as Bacillus and Streptococcus. A ten kilobase region homologous to the Salmonella typhimurium propanediol utilization locus was identified, as was a prophage and integrated conjugal plasmid. The genome contains five composite ribozyme/transposons, similar to the CdISt IStrons described in Clostridium difficile. IStrons are not present in the other fusobacterial genomes. These findings indicate that F. nucleatum subsp. polymorphum is proficient at horizontal gene transfer and that exchange with the Firmicutes, particularly the Clostridia, is common

Detection of selected bacterial species in intraoral sites of patients with chronic periodontitis using multiplex polymerase chain reaction

OBJECTIVE: The aim of this study was to detect the prevalence of selected bacterial species in intraoral sites of patients with chronic periodontitis (CP) using multiplex polymerase chain reaction (PCR). METHODOLOGY: Samples were collected from the tongue dorsum, buccal mucosa, supragingival and subgingival plaque and saliva of 30 patients with untreated CP. Multiplex PCR was used to determine prevalence rates, which were then compared using a chi-square test. Significance level was set at p<0.05. Mean and standard deviation values were used to evaluate variations in prevalence according to site. RESULTS: The prevalence of S. mutans was 70% in saliva; 60% in samples collected from the tongue dorsum; 50% in samples collected from the buccal mucosa; 56.5% in the supragingival plaque; and 53.5% in the subgingival plaque. The prevalence of E. faecalis ranged from 3.5% to 13.5% in all intraoral microenvironment. The highest prevalence of P. gingivalis was found in subgingival plaque (53.5%), and of P. intermedia in supragingival plaque (33.5%), subgingival plaque (30%) and tongue dorsum (33.5%). The prevalence of bacteria did not vary significantly among the intraoral sites. CONCLUSIONS: All studied bacteria were identified in intraoral sites. S. mutans, P. gingivalis and P. intermedia had high prevalence rates, but the prevalence of E. faecalis was low. Multiplex PCR proved to be an adequate method for epidemiological studies

Mouthwashes for the control of supragingival biofilm and gingivitis in orthodontic patients: evidence-based recommendations for clinicians

Properly performed daily mechanical biofilm control is the most important prevention strategy for periodontal diseases. However, proper mechanical biofilm control is not performed effectively by the majority of the population, mainly due to lack of motivation and of manual dexterity. Local biofilm retention factors may aggravate home oral hygiene quality. For this reason, patients wearing fixed orthodontic appliances comprise a group that may benefit from the daily use of mouthwashes. The purpose of this review was to perform a systematic search in the literature on antiseptics used to control supragingival biofilm and gingivitis in orthodontic patients. Six studies investigating the effect of chlorhexidine and 5 studies evaluating the effect of the daily use of antiseptics were found. Chlorhexidine showed better results in reducing plaque and gingivitis. However, because of its adverse effects after continuous use, it should not be indicated for long-term periods. Among the agents considered for daily use, the fixed combination of essential oils was the only one evaluated in a clinical trial, in which a comparative group presented a statistically significant clinical impact. There is no direct evidence supporting the indication of antiseptic agents for orthodontic patients other than chlorhexidine and essential oils. It can be concluded that, for patients undergoing orthodontic treatment, chlorhexidine should be considered for treating acute gingival inflammation, whereas essential oils should be indicated for long-term daily use in controlling supragingival biofilm