Effect of Cyclin-Dependent Kinase 4/6 Inhibitors on Circulating Cells in Patients with Metastatic Breast Cancer.

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2- advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i and ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 patients with ER+/HER2- mBC treated with CDK4/6i+ET in either first or second line. Peripheral blood samples were collected before (baseline) and 3 months (t2) after therapy. Immune cell's subsets were quantified by flow cytometry, and microfluidic-captured CTCs were counted and classified according to the expression of cytokeratin and/or vimentin. Patients were categorized according to response as responders (progression-free survival [PFS] ≥ 6.0 months; 79.1%) and non-responders (PFS < 6.0 months; 20.9%). CDK4/6i+ET resulted in significant changes in the hematological parameters, including decreased hemoglobin levels and increased mean corpuscular volume, as well as reductions in neutrophil, eosinophil, and basophil counts. Specific immune cell subsets, such as early-stage myeloid-derived suppressor cells, central memory CD4+ T cells, and Vδ2+ T cells expressing NKG2D, decreased 3 months after CDK4/6i+ET. Additionally, correlations between the presence of CTCs and immune cell populations were observed, highlighting the interplay between immune dysfunction and tumor dissemination. This study provides insights into the immunomodulatory effects of CDK4/6i+ET, underscoring the importance of considering immune dynamics in the management of ER+/HER2- mBC.

Gender Dysphoria: Concepts, Diagnosis and Clinical Management.

Gender dysphoria is defined as a condition characterized by mental suffering associated with the incongruence between one's experienced gender and their birth-assigned sex. Gender as a construct and gender dysphoria as a condition in need of multidisciplinary intervention have developed as swiftly as their visibility in society, making it mandatory to promote the literacy and education of all healthcare professionals in this area. This article aims to review information based on scientific evidence on people with gender dysphoria and its clinical approach, while contributing to a safe, inclusive, and non-discriminatory practice of healthcare.

Red blood cell membrane-camouflaged gold-core silica shell nanorods for cancer drug delivery and photothermal therapy.

Gold core mesoporous silica shell (AuMSS) nanorods are multifunctional nanomedicines that can act simultaneously as photothermal, drug delivery, and bioimaging agents. Nevertheless, it is reported that once administrated, nanoparticles can be coated with blood proteins, forming a protein corona, that directly impacts on nanomedicines' circulation time, biodistribution, and therapeutic performance. Therefore, it become crucial to develop novel alternatives to improve nanoparticles' half-life in the bloodstream. In this work, Polyethylenimine (PEI) and Red blood cells (RBC)-derived membranes were combined for the first time to functionalize AuMSS nanorods and simultaneously load acridine orange (AO). The obtained results revealed that the RBC-derived membranes promoted the neutralization of the AuMSS' surface charge and consequently improved the colloidal stability and biocompatibility of the nanocarriers. Indeed, the in vitro data revealed that PEI/RBC-derived membranes' functionalization also improved the nanoparticles' cellular internalization and was capable of mitigating the hemolytic effects of AuMSS and AuMSS/PEI nanorods. In turn, the combinatorial chemo-photothermal therapy mediated by AuMSS/PEI/RBC_AO nanorods was able to completely eliminate HeLa cells, contrasting with the less efficient standalone therapies. Such data reinforce the potential of AuMSS nanomaterials to act simultaneously as photothermal and chemotherapeutic agents.

Neurological manifestation of Brazilian spotted fever in childhood.

Rocky Mountain Spotted Fever is a rickettsial disease caused by the bacteria Rickettsia rickettsii. In Brazil, the disease is known as Brazilian spotted fever (BSF), being the most significant tick-borne disease in the country. Among the affected patients, only 5% of cases occur in children aged one to nine years. Typical symptoms of the disease are fever, rash, headache and digestive symptoms. Neurological manifestations such as seizures, aphasia and hemiparesis have been described in few patients. This study aimed to describe the case of an infant diagnosed with BSF who presented severe signs of neurological manifestation.

Engineering A-type Dye-Decolorizing Peroxidases by Modification of a Conserved Glutamate Residue.

Dye-decolorizing peroxidases (DyPs) are recently identified microbial enzymes that have been used in several Biotechnology applications from wastewater treatment to lignin valorization. However, their properties and mechanism of action still have many open questions. Their heme-containing active site is buried by three conserved flexible loops with a putative role in modulating substrate access and enzyme catalysis. Here, we investigated the role of a conserved glutamate residue in stabilizing interactions in loop 2 of A-type DyPs. First, we did site saturation mutagenesis of this residue, replacing it with all possible amino acids in bacterial DyPs from Bacillus subtilis (BsDyP) and from Kitasatospora aureofaciens (KaDyP1), the latter being characterized here for the first time. We screened the resulting libraries of variants for activity towards ABTS and identified variants with increased catalytic efficiency. The selected variants were purified and characterized for activity and stability. We furthermore used Molecular Dynamics simulations to rationalize the increased catalytic efficiency and found that the main reason is the electron channeling becoming easier from surface-exposed tryptophans. Based on our findings, we also propose that this glutamate could work as a pH switch in the wild-type enzyme, preventing intracellular damage.

Spectroelectrochemistry for determination of the redox potential in heme enzymes: Dye-decolorizing peroxidases.

Dye-decolorizing peroxidases (DyPs) are heme-containing enzymes that are structurally unrelated to other peroxidases. Some DyPs show high potential for applications in biotechnology, which critically depends on the stability and redox potential (E°') of the enzyme. Here we provide a comparative analysis of UV-Vis- and surface-enhanced resonance Raman-based spectroelectrochemical methods for determination of the E°' of DyPs from two different organisms, and their variants generated targeting E°' upshift. We show that substituting the highly conserved Arginine in the distal side of the heme pocket by hydrophobic amino acid residues impacts the heme architecture and redox potential of DyPs from the two organisms in a very distinct manner. We demonstrate the advantages and drawbacks of the used spectroelectrochemical approaches, which is relevant for other heme proteins that contain multiple heme centers or spin populations.

TLR10: An Intriguing Toll-Like Receptor with Many Unanswered Questions.

BACKGROUND: Toll-like receptors (TLRs) are one of the first pattern recognition receptors found in the innate immune system. The TLR family has 12 members (TLR1-TLR9, TLR11-TLR13) in mice and 10 members (TLR1-TLR10) in humans, with TLR10 being the latest identified. SUMMARY: Considerable research has been performed on TLRs; however, TLR10 is known as an orphan receptor for the lack of information on its signalling, role, and ligands. Even though there are recent studies pointing towards the potential TLR10 ligands, their function and signalling pathway are yet to be determined. KEY MESSAGES: This review gives an insight into recent findings on TLR10's pro- and anti-inflammatory properties, with the goal of outlining existing results and indicating future research topics on this receptor.

In situ formation of alginic acid-gold nanohybrids for application in cancer photothermal therapy.

Gold-based nanoparticles present excellent optical properties that propelled their widespread application in biomedicine, from bioimaging to photothermal applications. Nevertheless, commonly employed manufacturing methods for gold-based nanoparticles require long periods and laborious protocols that reduce cost-effectiveness and scalability. Herein, a novel methodology was used for producing gold-alginic acid nanohybrids (Au-Alg-NH) with photothermal capabilities. This was accomplished by promoting the in situ reduction and nucleation of gold ions throughout a matrix of alginic acid by using ascorbic acid. The results obtained reveal that the Au-Alg-NHs present a uniform size distribution and a spike-like shape. Moreover, the nanomaterials were capable to mediate a temperature increase of ≈11°C in response to the irradiation with a near-infrared region (NIR) laser (808 nm, 1.7 W cm-2 ). The in vitro assays showed that Au-Alg-NHs were able to perform a NIR light-triggered ablation of cancer cells (MCF-7), being observed a reduction in the cell viability to ≈27%. Therefore, the results demonstrate that this novel methodology holds the potential for producing Au-Alg-NH with photothermal capacity and higher translatability to the clinical practice, namely for cancer therapy.

Elaboração e validação de um protocolo de pontos de acupuntura auricular para cefaleia / Preparation and validation of an auricular acupuncture point protocol for headaches / Elaboración y validación de un protocolo de puntos de acupuntura auricular para la cefalea

RESUMO Objetivo: Elaborar e validar o conteúdo de um protocolo de pontos de acupuntura auricular para o tratamento de cefaleia. Método: Estudo metodológico, realizado em junho de 2023, em Montes Claros, Minas Gerais, Brasil. Estruturando em três etapas: planejamento (levantamento bibliográfico e identificação das variáveis de estudo), construção dos instrumentos (caracterização dos experts, protocolo de pontos e regime de tratamento) e validação de conteúdo por 15 experts. Na análise de dados utilizou-se a porcentagem de concordância absoluta igual ou superior a 80%. Resultados: O protocolo de acupuntura auricular para o tratamento de cefaleia, validado pelos experts, foi composto pelos seguintes pontos: "Porta da Mente" (93,3%), Rim (86,7%), Simpático (86,7%), Ansiedade (86,7%), Subcórtex (86,7%), Tronco Cerebral (86,7%), Frontal (86,7%), Occipital (86,7%), Temporal (86,7%) e Fígado (80%). Conclusão: o protocolo de acupuntura auricular para o tratamento de cefaleia foi considerado válido, o que permitirá sua utilização na prática clínica e em pesquisas.

ABSTRACT Objective: To develop and validate the content of an auricular acupuncture point protocol for the treatment of headaches. Method: A methodological study, carried out in June 2023 in Montes Claros, Minas Gerais, Brazil. It was structured in three stages: Planning (bibliographic survey and identification of the study variables); Construction of the instruments (characterization of the experts, point protocol and treatment regime); and Content validation in charge of 15 experts. In the data analysis, an absolute agreement percentage equal to or greater than 80% was used. Results: The auricular acupuncture protocol for the treatment of headaches that was validated by experts consisted of the following points: "Door of the Mind" (93.3%), Kidney (86.7%), Sympathetic (86.7%), Anxiety (86.7%), Subcortex (86.7%), Brainstem (86.7%), Frontal (86.7%), Occipital (86.7%), Temporal (86.7%) and Liver (80%). Conclusion: the auricular acupuncture protocol for the treatment of headaches was considered valid, which will allow its use in the clinical practice and research studies.

RESUMEN Objetivo: Elaborar y validar el contenido de un protocolo de puntos de acupuntura auricular para el tratamiento de la cefalea. Método: Estudio metodológico, realizado en junio de 2023, en Montes Claros, Minas Gerais, Brasil. Estructurado en tres etapas: planificación (relevamiento bibliográfico e identificación de variables de estudio), elaboración de instrumentos (caracterización de expertos, protocolo de puntos y régimen de tratamiento) y validación de contenido por 15 expertos. En el análisis de los datos se utilizó un porcentaje de concordancia absoluta igual o mayor al 80%. Resultados: El protocolo de acupuntura auricular para el tratamiento de la cefalea, validado por expertos, estuvo compuesto por los siguientes puntos: "Puerta de la Mente" (93,3%), Riñón (86,7%), Simpático (86,7%), Ansiedad (86,7%), Subcórtex (86,7%), Tronco Encefálico (86,7%), Frontal (86,7%), Occipital (86,7%), Temporal (86,7%) e Hígado (80%). Conclusión: Se consideró válido el protocolo de acupuntura auricular para el tratamiento de la cefalea, lo que permitirá su uso en la práctica clínica y en la investigación.

Neurological manifestation of Brazilian spotted fever in childhood

ABSTRACT Rocky Mountain Spotted Fever is a rickettsial disease caused by the bacteria Rickettsia rickettsii. In Brazil, the disease is known as Brazilian spotted fever (BSF), being the most significant tick-borne disease in the country. Among the affected patients, only 5% of cases occur in children aged one to nine years. Typical symptoms of the disease are fever, rash, headache and digestive symptoms. Neurological manifestations such as seizures, aphasia and hemiparesis have been described in few patients. This study aimed to describe the case of an infant diagnosed with BSF who presented severe signs of neurological manifestation.

Effects of Humic Substances and Mycorrhizal Fungi on Drought-Stressed Cactus: Focus on Growth, Physiology, and Biochemistry.

Utilizing water resources rationally has become critical due to the expected increase in water scarcity. Cacti are capable of surviving with minimal water requirements and in poor soils. Despite being highly drought-resistant, cacti still faces limitations in realizing its full potential under drought-stress conditions. To this end, we investigated the interactive effect of humic substances (Hs) and arbuscular mycorrhizal fungi (AMF) on cactus plants under drought stress. In the study, a cactus pot experiment had three irrigation levels (W1: no irrigation, W2: 15% of field capacity, and W3: 30% of field capacity) and two biostimulants (Hs soil amendment and AMF inoculation), applied alone or combined. The findings show that the W1 and W2 regimes affected cactus performance. However, Hs and/or AMF significantly improved growth. Our results revealed that drought increased the generation of reactive oxygen species. However, Hs and/or AMF application improved nutrient uptake and increased anthocyanin content and free amino acids. Furthermore, the soil's organic matter, phosphorus, nitrogen, and potassium contents were improved by the application of these biostimulants. Altogether, using Hs alone or in combination with AMF can be an effective and sustainable approach to enhance the tolerance of cactus plants to drought conditions, while also improving the soil quality.

Incremento na prática de exercícios físicos ao ar livre após o início da pandemia covid-19 entre acadêmicos de medicina / Increase in the practice of outdoor physical exercises after the beginning of the pandemic among medicine students

Introdução: A atividade física é uma ferramenta importante para a manutenção e promoção da saúde física e mental, porém, diante da pandemia instalada mundialmente pelo coronavírus e consequentemente o distanciamento social para o controle de sua disseminação, foram necessárias adaptações na prática de exercícios físicos, como sua maior realização em ambientes abertos. Objetivo: Investigar se houve incremento na prática de exercícios físicos ao ar livre após o início da pandemia entre acadêmicos de Medicina de uma faculdade do noroeste paulista. Método: Trata-se de estudo transversal descritivo, com abordagem quantitativa dos dados, realizado através de um questionário on-line. Resultados: No total, 189 estudantes participaram da pesquisa. Os resultados indicaram que 74,60% dos participantes afirmaram que se exercitaram ao ar livre neste período, sendo que 29,63% não tinham esse hábito anteriormente, além disso, a frequência dessas atividades aumentou, já que durante a pandemia, 41% dos estudantes relataram se exercitar quatro ou mais vezes por semana ao ar livre, enquanto anteriormente essa proporção era de 22,75%, sendo a principal motivação, a preocupação com a saúde mental (60,67%). Conclusão: Foram identificadas mudanças na prática de exercício físico pelos estudantes de medicina, através da realização desta ao ar livre e com aumento de sua periodicidade

Introduction: Physical activity is an important tool for maintaining and promoting physical and mental health, however, in view of the pandemic installed worldwide by the coronavirus and consequently social distancing to control its spread, adaptations were necessary in the practice of physical exercises, as his greatest achievement in open environments. Objective: To investigate whether there was an increase in outdoor physical exercise after the start of the pandemic among medical students at a college in the northwest of São Paulo. Method: This is a descriptive cross-sectional study, with a quantitative approach to the data, carried out through an online questionnaire. Results: In total, 189 students participated in the survey. The results indicated that 74.60% of the participants stated that they exercised outdoors during this period, with 29.63% not having this habit before, in addition, the frequency of these activities increased, since during the pandemic, 41% of students reported exercising four or more times a week outdoors, while previously this proportion was 22.75%, the main motivation being concern for mental health (60.67%). Conclusion: Changes were identified in the practice of physical exercise by medical students, by performing it outdoors and with increased frequency

Introducción: La actividad física es una herramienta importante para el mantenimiento y promoción de la salud física y mental, sin embargo, ante la pandemia instalada a nivel mundial por el coronavirus y consecuentemente el distanciamiento social para controlar su propagación, fueron necesarias adaptaciones en la práctica de ejercicios físicos, como su mayor logro en ambientes abiertos. Objetivo: Investigar si hubo un aumento del ejercicio físico al aire libre después del inicio de la pandemia entre los estudiantes de medicina de una facultad del noroeste de São Paulo. Método: Se trata de un estudio descriptivo transversal, con abordaje cuantitativo de los datos, realizado a través de un cuestionario online. Resultados: En total, 189 estudiantes participaron en la encuesta. Los resultados indicaron que el 74,60% de los participantes manifestaron realizar ejercicio al aire libre durante este período, siendo que el 29,63% no tenían este hábito antes, además, aumentó la frecuencia de estas actividades, ya que durante la pandemia, el 41% de los estudiantes reportaron realizar ejercicio de cuatro o más veces a la semana al aire libre, mientras que antes esta proporción era del 22,75%, siendo la principal motivación la preocupación por la salud mental (60,67%). Conclusión: Se identificaron cambios en la práctica de ejercicio físico de los estudiantes de medicina, al realizarlo al aire libre y con mayor frecuencia

From Prevention to Care: Unveiling a Parasitic Leiomyoma Within a Gigantic Abdominal Mass.

Leiomyomas are non-cancerous tumors emerging from the smooth muscle cells and fibroblasts of the myometrium. They are the most common pelvic tumors in females and are usually asymptomatic. Parasitic leiomyomas have been defined as unusual variants of pedunculated leiomyomas. When symptomatic, leiomyomas can cause abnormal uterine bleeding, pelvic pain/pressure, and reproductive effects, such as infertility or adverse pregnancy outcomes. Treatment varies depending on age, symptoms, and the preference to preserve fertility. In this article, we describe the case of a 58-year-old woman who presented for a scheduled cervical cancer screening in primary healthcare. Upon objective examination, the patient exhibited a distended and tense abdomen, along with edema in the lower limbs. These symptoms were associated with fatigue and weight gain over the last few months. Subsequent investigation led to an exploratory laparotomy which revealed a massive abdominal mass, measuring approximately 45 cm in diameter and weighing 35 kg. The findings were suggestive of a parasitic leiomyoma.

Construção e divulgação de um podcast como ferramenta para promoção da saúde de gestantes e puérperas: relato de experiência / Construction and dissemination of a podcast as a tool to promote the health of pregnant and puerperal women: experience report

O objetivo deste estudo é relatar a experiência da construção e divulgação de um podcast como ferramenta para promoção a saúde de gestantes e puérperas. Trata-se de estudo descritivo, na modalidade de relato de experiência sobre o podcast "Saber para nascer.cast". O desenvolvimento dessa ferramenta ocorreu em 03 etapas: referencial teórico; criação e desenvolvimento do podcast e divulgação dos episódios. O Saber para Nascer.cast contou com a produção de onze episódios que contemplaram: apresentação dos projetos que deram origem ao podcast; pré-natal; imagem corporal; saúde mental; alimentação; exercícios físicos; apego materno-fetal; aleitamento materno; violência obstétrica; trabalho de parto e relato de experiência de uma gestante. O Saber para Nascer.cast como prática educativa complementar às consultas de pré-natal permitiu a divulgação de informações de cunho científico e de fácil acesso, com intuito de construir conhecimentos e aprendizados acerca dos temas disponibilizados com ênfase nos cuidados à saúde das gestantes e puérperas.

The objective of this study is to report the experience of building and disseminating a podcast as a tool to promote the health of pregnant and postpartum women. This is a descriptive study, in the form of an experience report on the podcast "Saber para Nascer.cast". The development of the podcast took place in three stages: theoretical framework, creation and development of the podcast, and dissemination of the episodes. Saber para Nascer.cast The study examined the production of 11 episodes which featured the following topics: presentation of the projects that gave rise to the podcast, prenatal, body image, mental health, food, physical exercises, maternal-fetal attachment, breastfeeding, obstetric violence, labor, and a woman's account of her overall pregnancy experience. Saber para Nascer.cast. The podcast aims to provide a complementary educational practice to prenatal consultations through the dissemination of scientific and easily accessible information. The aim is to build knowledge and learn about the topics available, with an emphasis on health care for pregnant and postpartum women.

Effects of Different Irrigation Regimes, Nitrogen Levels and Storage Conditions on Volatiles of 'Gala' Apple.

With a characteristic flavour and aroma, "Maçã de Alcobaça" are apples produced in the western region of the mainland of Portugal. Given the known influence of pre-harvest cultural techniques and post-harvest conservation methods on fruit quality, this work evaluated the effect of cultural factors and conservation methods on the volatile profile of 'Gala' apples. Tests were carried out during four seasons (2018 to 2021) in two 'Gala' apple orchards (F and S) maintained with different irrigation rates and nitrogen fertilisation [normal irrigation and normal nitrogen (Control, NINN), normal irrigation and excess nitrogen (NIEN), excess irrigation and normal nitrogen (EINN), excess irrigation and excess nitrogen (EIEN)], and under three storage conditions [Controlled Atmosphere + 1-methylcyclopropene (CA+1-MCP), Dynamic Controlled Atmosphere (DCA) and DCA+1-MCP]. The intact fruit volatiles were isolated by headspace solid-phase microextraction (HS-SPME) and analysed by Gas Chromatography with Flame Ionisation Detection and Gas Chromatography-Mass Spectrometry at harvest (T0) and after 8 months of storage (T8). HS-SPME volatiles from 'Gala' apples, obtained at T0 in control conditions, were characterised by trans,trans-α-farnesene dominance (36-69%), followed by hexyl acetate (5-23%) and hexyl hexanoate (3-9%). The four irrigation and nitrogen treatments did not evidence main changes in the apple volatile profile. Instead, storage conditions changed the ratio between compounds; previously undetected compounds attained high percentages and decreased the intensity of the dominant compounds in the control conditions. Although all storage conditions tested changed the volatile profile and emanation intensity, the effect was more accentuated in storage for 8 months with DCA+1-MCP.

CD34 Protein: Its expression and function in inflammation.

CD34 has spear-headed the field of basic research and clinical transplantation since the first reports of its expression on hematopoietic stem cells (HSCs). Expressed in mice, humans, rats and other species, CD34 has been used for more than 40 years as a hematopoietic stem and progenitor cell marker. It was later found that muscle satellite cells and epidermal precursors can also be identified with the aid of CD34. Despite the usefulness of CD34 as a marker of HSCs, its overall purpose in animal physiology has remained unclear. This review recaptures CD34 structure, evolutionary conservation, proposed functions, and role in lung inflammation, to describe current research findings and to provide guidance for future studies on CD34.

Bothrops atrox venom: Biochemical properties and cellular phenotypes of three highly toxic classes of toxins.

Snake venoms have a complex mixture of compounds that are conserved across species and act synergistically, triggering severe local and systemic effects. Identification of the toxin classes that are most damaging to cell homeostasis would be a powerful approach to focus on the main activities that underpin envenomation. Here, we focus on the venom of Bothrops atrox, snake responsible for most of the accidents in Amazon region of South America. We identified the key cytotoxic toxin fractions from B. atrox venom and mapped their biochemical properties, protein composition and cell damage. Five fractions were obtained by mass exclusion chromatography and contained either a single class of enzymatic activity (i.e., L-amino acid oxidases or Hyaluronidases) or different activities co-distributed in two or more protein fractions (e.g., Metalloproteinases, Serine Proteases, or Phospholipases A2). Only three protein fractions reduced cell viability of primary human cells. Strikingly, such activity is accompanied by disruption of cell attachment to substratum and to neighbouring cells. Such strong perturbation of morphological cell features indicates likely defects in tissue integrity in vivo. Mass spectrometry identified the main classes of toxins that contribute to these phenotypes. We provide here a strategy for the selection of key cytotoxic proteins for targeted investigation of their mechanism of action and potential synergism during snakebite envenomation. Our data highlights putative toxins (or combinations of) that may be the focus of future therapeutic interference.

Pleural effusion-related Nocardia otitidiscaviarum, Anaplasma platys and Ehrlichia canis coinfection in a dog.

The coinfections by some microorganisms have been related to severe diseases in humans and animals, where immunosuppressive agents favor opportunistic behavior of other pathogens. A 4-month-old, female mixed-breed dog with a two-week history of inappetence, prostration, emaciation, and respiratory distress was admitted at a veterinary hospital in Brazil. Tachycardia, pale mucous membranes, severe respiratory distress, and a large number of ticks (Rhipicephalus sanguineus s.l.) in different body regions were observed at clinical examination. Hematological examination of dog showed leukocytosis, neutrophilia, mild anemia, and thrombocytopenia, whereas unremarkable values in biochemical tests. Thoracic radiography revealed a pleural effusion image. Blood and the pleural fluid (purulent aspect) samples were subjected to qPCR (16S rRNA and dsb genes) and sequencing, which identified Ehrlichia canis and Anaplasma platys coinfection. An aggregate of coccoid-to-branching or long filamentous microorganisms, surrounded by pyogranulomatous inflammatory reaction was seen at the cytology of the pleural fluid. Bacteriological culture of pleural effusion showed colonies compatible with the genus Nocardia, which revealed gram-positive filamentous organisms with a tendency of fragmentation and were identified as Nocardia otitidiscaviarum in mass spectrometry (MALDI-TOF MS). Therapy of N. otitidiscaviarum isolate using levofloxacin (supported by a previous in vitro susceptibility testing) and doxycycline for E. canis and A. platys resulted in complete resolution of the clinical picture. Here, we report for the first time a triple coinfection by Nocardia otitidiscaviarum, A. platys, and E. canis in a dog with pleural effusion, where debilitating or immunosuppressive conditions induced by A. platys and E. canis coinfection probably contributed to the opportunistic behavior of N. otitidiscaviarum.

Clinical Validation of a Size-Based Microfluidic Device for Circulating Tumor Cell Isolation and Analysis in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) presents as metastatic disease in one third of cases. Research on circulating tumor cells (CTCs) and liquid biopsies is improving the understanding of RCC biology and metastases formation. However, a standardized, sensitive, specific, and cost-effective CTC detection technique is lacking. The use of platforms solely relying on epithelial markers is inappropriate in RCC due to the frequent epithelial-mesenchymal transition that CTCs undergo. This study aimed to test and clinically validate RUBYchip™, a microfluidic label-free CTC detection platform, in RCC patients. The average CTC capture efficiency of the device was 74.9% in spiking experiments using three different RCC cell lines. Clinical validation was performed in a cohort of 18 patients, eight non-metastatic (M0), five metastatic treatment-naïve (M1TN), and five metastatic progressing-under-treatment (M1TP). An average CTC detection rate of 77.8% was found and the average (range) total CTC count was 6.4 (0-27), 101.8 (0-255), and 3.2 (0-10), and the average mesenchymal CTC count (both single and clustered cells) was zero, 97.6 (0-255), and 0.2 (0-1) for M0, M1TN, and M1TP, respectively. CTC clusters were detected in 25% and 60% of M0 and M1TN patients, respectively. These results show that RUBYchip™ is an effective CTC detection platform in RCC.

Current Applications of Bionanocomposites in Food Processing and Packaging.

Nanotechnology advances are rapidly spreading through the food science field; however, their major application has been focused on the development of novel packaging materials reinforced with nanoparticles. Bionanocomposites are formed with a bio-based polymeric material incorporated with components at a nanoscale size. These bionanocomposites can also be applied to preparing an encapsulation system aimed at the controlled release of active compounds, which is more related to the development of novel ingredients in the food science and technology field. The fast development of this knowledge is driven by consumer demand for more natural and environmentally friendly products, which explains the preference for biodegradable materials and additives obtained from natural sources. In this review, the latest developments of bionanocomposites for food processing (encapsulation technology) and food packaging applications are gathered.