Helminth-derived molecules improve 5-fluorouracil treatment on experimental colon tumorigenesis.

Colorectal cancer (CRC) is one of the most prevalent fatal neoplasias worldwide. Despite efforts to improve the early diagnosis of CRC, the mortality rate of patients is still nearly 50%. The primary treatment strategy for CRC is surgery, which may be accompanied by chemotherapy and radiotherapy. The conventional and first-line chemotherapeutic agent utilized is 5-fluorouracil (5FU). However, it has low efficiency. Combination treatment with leucovorin and oxaliplatin or irinotecan improves the effectiveness of 5FU therapy. Unfortunately, most patients develop drug resistance, leading to disease progression. Here, we evaluated the effect of a potential alternative adjuvant treatment for 5FU, helminth-derived Taenia crassiceps (TcES) molecules, on treating advanced colitis-associated colon cancer. The use of TcES enhanced the effects of 5FU on established colonic tumors by downregulating the expression of the immunoregulatory cytokines, Il-10 and Tgf-ß, and proinflammatory cytokines, Tnf-α and Il-17a, and reducing the levels of molecular markers associated with malignancy, cyclin D1, and Ki67, both involved in apoptosis inhibition and the signaling pathway of ß-catenin. TcES+5FU therapy promoted NK cell recruitment and the release of Granzyme B1 at the tumor site, consequently inducing tumor cell death. Additionally, it restored P53 activity which relates to decreased Mdm2 expression. In vitro assays with human colon cancer cell lines showed that therapy with TcES+5FU significantly reduced cell proliferation and migration by modulating the P53 and P21 signaling pathways. Our findings demonstrate, for the first time in vivo, that helminth-derived excreted/secreted products may potentiate the effect of 5FU on established colon tumors.

Aspergillosis in a colony of Humboldt penguins (Spheniscus humboldti) in a french zoological park: evaluation of environmental exposure.

Aspergillosis is a major health problem in captive penguins due to the inhalation and the development of airborne spores of opportunistic environmental molds of the genus Aspergillus. Diagnosis is often delayed and treatments, based on the use of azole antifungals, are not fully effective. This study assesses the risk of exposure to Aspergillus sp. and determines the environmental reservoirs in the direct environment of a colony of Humboldt penguins (Spheniscus humboldti) in a zoological park in Paris, and the risk of contamination with resistant isolates. Every 15 days between February and May 2022, environmental samples (air and subtract from the nests, pond water, pigeon and penguin droppings) were carried out in the penguin enclosure as well as clinical samples (one-time non-invasive sampling on chicks), and screened for Aspergillus sp. conidia. From 191 environmental samples, 264 strains of Aspergillus including 221 strains of A. fumigatus were isolated, mostly from ambient air, in the nests, and pond water. No "at risk" areas in the penguin environment have been highlighted, nor an increased risk because of the proximity with urban wild birds. However, the load of airborne Aspergillus in the nests increased significantly with outdoor temperature. Of the 221 strains isolated, we identified only one azole-resistant strain, displaying the TR34/L98H mutation in the cyp51A gene. This low prevalence of resistant strains may probably be partly explained by the urban location of the zoological park, surrounded by kilometers of urban areas without agricultural activities.

Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet).

Colorectal cancer (CRC) represents the second deadliest malignancy worldwide. Around 75% of CRC patients exhibit high levels of chromosome instability that result in the accumulation of somatic copy number alterations. These alterations are associated with the amplification of oncogenes and deletion of tumor-ppressor genes and contribute to the tumoral phenotype in different malignancies. Even though this relationship is well known, much remains to be investigated regarding the effect of said alterations in long non-coding RNAs (lncRNAs) and, in turn, the impact these alterations have on the tumor phenotype. The present study aimed to evaluate the role of differentially expressed lncRNAs coded in regions with copy number alterations in colorectal cancer patient samples. We downloaded RNA-seq files of the Colorectal Adenocarcinoma Project from the The Cancer Genome Atlas (TCGA) repository (285 sequenced tumor tissues and 41 non-tumor tissues), evaluated differential expression, and mapped them over genome sequencing data with regions presenting copy number alterations. We obtained 78 differentially expressed (LFC > 1|< -1, padj < 0.05) lncRNAs, 410 miRNAs, and 5028 mRNAs and constructed a competing endogenous RNA (ceRNA) network, predicting significant lncRNA-miRNA-mRNA interactions. Said network consisted of 30 lncRNAs, 19 miRNAs, and 77 mRNAs. To understand the role that our ceRNA network played, we performed KEGG and GO analysis and found several oncogenic and anti-oncogenic processes enriched by the molecular players in our network. Finally, to evaluate the clinical relevance of the lncRNA expression, we performed survival analysis and found that C5orf64, HOTAIR, and RRN3P3 correlated with overall patient survival. Our results showed that lncRNAs coded in regions affected by SCNAs form a complex gene regulatory network in CCR.

Vitamin D levels in the pre- and post-COVID-19 pandemic periods in pediatric patients with chronic kidney disease.

Introduction: Vitamin D (VD) deficiency is common in children with chronic kidney disease (CKD) because of multiple factors. During the coronavirus disease 2019 (COVID-19) pandemic, it increased because of medicine shortage and no enough medical service for patients with non-COVID-19 diseases. Objective: To analyze the effects of the COVID-19 pandemic-related lockdown on the serum levels and status of 25-hydroxyvitamin D3 (25-[OH]D) in children with CKD. Materials and methods: This retrospective study included patients (6-18 years old) who were diagnosed with CKD stage 2-5 and routinely measured for serum VD levels between May 2019 and December 2022. Serum 25-(OH)D levels were measured before, during, and after the pandemic (2019, 2020-2021, and 2022, respectively). The daily dose of cholecalciferol supplementation and the readjustment (if required) were recorded. Results: This study included 171 patients (median age: 12 years). Before the pandemic, the median serum VD level was 25.0 ng/mL (19.3% VD deficiency). Then, VD supplementation was adjusted to 400-1,200 UI daily in 98.8% (n = 169) of patients. During the pandemic, the median VD level decreased to 22.5 ng/mL (43.3% VD deficiency). Hence, the supplementation was readjusted, and after the pandemic, the level was 28.7 ng/mL (18.7% VD deficiency), indicating a statistically significant increase in serum VD levels from the prepandemic period (p = 0.007). Conclusion: Decreased serum VD levels and increased VD deficiency frequency were observed in patients with CKD during the COVID-19 but improved after readjustment of supplementation.

A triple-drug combination induces apoptosis in cervical cancer-derived cell lines.

Introduction: Cervical cancer is a worldwide health problem due to the number of deaths caused by this neoplasm. In particular, in 2020, 30,000 deaths of this type of tumor were reported in Latin America. Treatments used to manage patients diagnosed in the early stages have excellent results as measured by different clinical outcomes. Existing first-line treatments are not enough to avoid cancer recurrence, progression, or metastasis in locally advanced and advanced stages. Therefore, there is a need to continue with the proposal of new therapies. Drug repositioning is a strategy to explore known medicines as treatments for other diseases. In this scenario, drugs used in other pathologies that have antitumor activity, such as metformin and sodium oxamate, are analyzed. Methods: In this research, we combined the drugs metformin and sodium oxamate with doxorubicin (named triple therapy or TT) based on their mechanism of action and previous investigation of our group against three CC cell lines. Results: Through flow cytometry, Western blot, and protein microarray experiments, we found TT-induced apoptosis on HeLa, CaSki, and SiHa through the caspase 3 intrinsic pathway, including the critical proapoptotic proteins BAD, BAX, cytochrome-C, and p21. In addition, mTOR and S6K phosphorylated proteins were inhibited in the three cell lines. Also, we show an anti-migratory activity of the TT, suggesting other targets of the drug combination in the late CC stages. Discussion: These results, together with our former studies, conclude that TT inhibits the mTOR pathway leading to cell death by apoptosis. Our work provides new evidence of TT against cervical cancer as a promising antineoplastic therapy.

A case of feline gastrointestinal eosinophilic sclerosing fibroplasia associated with fungal colonisation: endoscopic features, treatment and follow-up.

Case summary: A 5-year-old castrated male domestic shorthair cat presented with a 3-month history of weight loss, chronic diarrhoea and vomiting. Examination revealed a large proximal duodenal lesion eventually diagnosed as feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF) associated with fungal filaments. Histological examination was performed following endoscopic biopsy. Direct examination and mycological culture of the duodenal biopsies revealed the presence of a siphomycetous fungus, which was further identified as Rhizopus microsporus. Treatment with prednisolone and ciclosporin for 3 months led to complete resolution of the clinical signs and marked improvement of the endoscopic lesions. Specific fungal treatment with amphotericin B was poorly tolerated. Relevance and novel information: To the best of our knowledge, this is the first report of the characterisation of a siphomycetous fungus associated with FGESF lesions, and the first endoscopic description and diagnosis of FGESF without surgical biopsies. We hypothesise that the presence of R microsporus occurred because of disrupted mucosal integrity.

Mexican Colorectal Cancer Research Consortium (MEX-CCRC): Etiology, Diagnosis/Prognosis, and Innovative Therapies.

In 2013, recognizing that Colorectal Cancer (CRC) is the second leading cause of death by cancer worldwide and that it was a neglected disease increasing rapidly in Mexico, the community of researchers at the Biomedicine Research Unit of the Facultad de Estudios Superiores Iztacala from the Universidad Nacional Autónoma de México (UNAM) established an intramural consortium that involves a multidisciplinary group of researchers, technicians, and postgraduate students to contribute to the understanding of this pathology in Mexico. This article is about the work developed by the Mexican Colorectal Cancer Research Consortium (MEX-CCRC): how the Consortium was created, its members, and its short- and long-term goals. Moreover, it is a narrative of the accomplishments of this project. Finally, we reflect on possible strategies against CRC in Mexico and contrast all the data presented with another international strategy to prevent and treat CRC. We believe that the Consortium's characteristics must be maintained to initiate a national strategy, and the reported data could be useful to establish future collaborations with other countries in Latin America and the world.

Toxoplasma gondii and Alternaria sp.: An Original Association in an Immunosuppressed Dog with Persistent Skin Lesions.

Dogs and cats may suffer from a variety of diseases, mainly immune mediated, that require the administration of immunosuppressive drugs. Such therapies can cause adverse effects either by the toxicity of the drugs or as a consequence of immune suppression and associated opportunistic infections. Here we present an, yet unknown, association of Toxoplasma gondii and Alternaria fungus, within cutaneous lesions in a dog under long-term immunosuppressive therapy. The diagnosis of such infections is laborious and not obvious at first glance, since the clinical signs of cutaneous toxoplasmosis, neosporosis or alternariosis are not specific. A further laboratory confirmation is needed. Therefore, we currently recommend that dogs and cats should undergo serologic testing for toxoplasmosis or neosporosis prior to immunosuppressive therapy and a regular dermatological evaluation during the immunosuppressive therapy.

Analysis of antibiotic resistance and genetic profile of conjunctival bacteria flora before and after cataract surgery.

PURPOSE: To analyze antibiotic resistance and genetic profile of conjunctival bacteria flora before and after cataract surgery with the focus on coagulase-negative staphylococci (CNS) during cataract surgery and discuss the implications of this colonization as a potential risk of acquiring endophthalmitis. METHODS: After approval of the institutional review board and informed consent from patients had been obtained, conjunctival swabs for culture from 59 patients undergoing cataract surgery were taken of the fellow eye at baseline (C0) and from the eye to be operated before (T0) and after (T1) irrigation with povine-iodine 5%, and at the end of surgery (T2). Genes responsible for virulence (mecA, ica and atlE) and antibiotic profile were determined; strain clonality of persistent colonizing Staphylococcus epidermidis strains was established by the Multi-locus sequence typing (MLST). RESULTS: The frequency of CNS was significantly reduced in T1 (13.6%) from 81.4% in T0 and 86.4% in C0. The frequency of mecA, ica and atlE genes was 34.4%, 37.5% and 61.4%, respectively; and methicillin phenotypic resistance was 35.4%. S. epidermidis was the most frequent species isolated in every time point. MLST revealed in 7 patients 100% coincidence of the seven alleles of the S. epidermidis isolated previous to povine-iodine 5% disinfection and at the end of the surgery. CNS isolates from T1 or T2 corresponded to the same species, antibiotic and virulence profile as those isolates from C0 or T0. CONCLUSION: Povidone-iodine 5% prophylaxis before surgery significantly reduced conjunctival contamination; in those that persisted, the source of contamination was mostly the patient's microbiota confirmed by the MLST system.

Efectividad de la Terapia Física en Mujeres con Disfunción Sexual: Scoping Review / Effectiveness of Physical Therapy in Women with Sexual Dysfunction: Scoping Review

Introducción. Las disfunciones sexuales femeninas son altamente prevalentes a lo largo de la vida, sin embargo, no son de fácil abordaje para los profesionales de salud. Los aspectos físicos de las disfunciones sexuales y su tratamiento, frecuentemente son subvalorados, porque la evidencia sobre la terapia física en estas disfunciones es limitada. Lo que genera que sean parcialmente tratadas y su sintomatología se pueda mantener y/o aumentar en el tiempo, impactando en la función sexual y en la calidad de vida. Objetivo. Revisar la literatura disponible sobre la terapia física en disfunciones sexuales femeninas y establecer su efectividad. Metodología. Se realizaron búsquedas bibliográficas, entre los años 2012 y 2022 en inglés y portugués, disponibles en diferentes bases de datos como; Pubmed, Scielo, Cochrane, Pedro y en Google Scholar. Se incluyeron los registros que hicieran referencia a la terapia física en las disfunciones sexuales femeninas y que cumplieran con nuestros criterios de inclusión y exclusión. Resultados. Se incluyeron 8 registros en la síntesis cualitativa. Se identificaron 3 modalidades: herramientas de terapia física, valoración de la función sexual y del dolor. Conclusión. La terapia física demuestra ser efectiva para el tratamiento de las disfunciones sexuales femeninas. La evidencia disponible que demuestre su uso y efectividad aún es escasa, lo que limita su difusión para ser considerada en el abordaje multidisciplinario habitual. Se requiere aumentar la investigación en esta área, enfocada en el rol de la terapia física y sus modalidades terapéuticas, en el tratamiento de las disfunciones sexuales femeninas.

Background. Female sexual dysfunction is highly prevail throughout our life, nevertheless, they are not easily addressed by health professionals. The physical aspects of sexual dysfunctions and their treatment are frequently undervalued because the evidence about physical therapy in these dysfunctions is limited. What causes them to be partly treated and their symptoms can be maintained and/or increased over time and having an impact on sexual function and quality of life. Objetive. To review through literature about physical therapy in female sexual dysfunction and to establish its effectiveness. Methods. Through 2012 and 2012 it was carried out bibliographic searches in English and Portuguese, available in different databases, such as Pubmed, Scielo, Cochrane, Pedro and Google Scholar. Records referring to physical therapy in female sexual dysfunction and that fulfill our requirements of inclusion and exclusion criteria were included. Results. Eight records were included in the qualitative synthesis. Three modalities were identified: physical therapy tools, assessment of sexual function and pain. Conclusion. Physical therapy proves to be effective for the treatment of female sexual dysfunctions. The available evidence that demonstrates its use and effectiveness is still scarce, which limits its diffusion to be considered in the regular multidisciplinary approach. More researches are demand in this area, focused on the role of physical therapy and its therapeutic modalities, in the treatment of female sexual dysfunctions.

Inflammatory-Metal Profile as a Hallmark for COVID-19 Severity During Pregnancy.

Pregnancy makes women more susceptible to infectious agents; however, available data on the effect of SARS-CoV-2 on pregnant women are limited. To date, inflammatory responses and changes in serum metal concentration have been reported in COVID-19 patients, but few associations between metal ions and cytokines have been described. The aim of this study was to evaluate correlations between inflammatory markers and serum metal ions in third-trimester pregnant women with varying COVID-19 disease severity. Patients with severe symptoms had increased concentrations of serum magnesium, copper, and calcium ions and decreased concentrations of iron, zinc, and sodium ions. Potassium ions were unaffected. Pro-inflammatory cytokines IL-6, TNF-α, IL-8, IL-1α, anti-inflammatory cytokine IL-4, and the IP-10 chemokine were induced in the severe presentation of COVID-19 during pregnancy. Robust negative correlations between iron/magnesium and zinc/IL-6, and a positive correlation between copper/IP-10 were observed in pregnant women with the severe form of the disease. Thus, coordinated alterations of serum metal ions and inflammatory markers - suggestive of underlying pathophysiological interactions-occur during SARS-CoV-2 infection in pregnancy.

Assessment of the Safety and Efficacy of an Oral Probiotic-Based Vaccine Against Aspergillus Infection in Captive-Bred Humboldt Penguins (Spheniscus humboldti).

Aspergillosis is a fungal infection caused mainly by Aspergillus fumigatus that often results in respiratory disease in birds. Aspergillosis is a major cause of morbidity and mortality in captive-bred penguin species. Currently, there is no registered vaccine to prevent aspergillosis. Recent research demonstrated that oral administration of gram-negative bacteria expressing high levels of galactose-α-1,3-galactose (α-Gal) modulates anti-α-Gal immunity and protects turkeys from clinical aspergillosis caused by experimental A. fumigatus infection. The role of anti-α-Gal immunity in penguins has not been studied. Here, we tested the distribution of α-1,3-galactosyltransferase (α1,3GT) genes in the fecal microbiome of Humboldt penguins (Spheniscus humboldti). The occurrence of natural anti-α-Gal antibodies (Abs) in sera and eggs of healthy Humboldt penguins was also assessed. A trial was then conducted to test whether oral administration of Escherichia coli Nissle, expressing high α-Gal levels, modulates anti-α-Gal immunity in a colony of Humboldt penguins. Animals in the vaccination and placebo groups were evaluated before the trial and followed for one year for aspergillosis detection using a diagnostic panel including computed tomography scans, capillary zone electrophoresis, 3-hydroxybutyrate levels, and anti-A. fumigatus Abs. Anti-α-Gal Abs were detected in sera (IgM and IgY) and eggs (IgY) of healthy penguins. Microbiota analysis and functional predictions revealed the presence of α1,3GT genes in the microbiota of Humboldt penguins and other penguin species. A strong decrease in anti-α-Gal IgM levels was observed in all animals in the placebo group three months after vaccination protocol. This decrease was not observed in E. coli Nissle-treated penguins. After the vaccination protocol, we found a positive correlation between anti-E. coli IgY and anti-α-Gal IgY in the E. coli Nissle group, suggesting a correlation between the presence of the bacteria and these Abs. During the study period, three penguins exhibited respiratory signs consistent with aspergillosis. Two were from the placebo group whose symptoms resolved with specific treatments, while a single vaccinated individual developed fatal respiratory aspergillosis eight months after the trial. We conclude that E. coli Nissle represents a safe potential probiotic with a protective effect against aspergillosis in Humboldt penguins that deserves to be further explored for therapeutic uses in these animals.

Safety and effectiveness of telerehabilitation program in people with severe haemophilia in Chile. A qualitative study.

INTRODUCTION: Little is known about how people with haemophilia (PWH) perceive and assess the usefulness, safety and effectiveness of telerehabilitation. OBJECTIVE: To describe usefulness, safety, effectiveness and limitations of a telerehabilitation program applied in people with severe haemophilia implemented during the COVID-19 pandemic in Chile. DESIGN AND METHODS: A qualitative study was conducted based on a focus group. Four analytical categories were predefined, three of which involved elements of Donabedian's model for quality assessment in health care (structure, process and results). RESULTS: One of the most important aspects according to all of the participants is the sense of safety they experienced while being taken care of by a physiotherapist specializing in PWH rehabilitation. This facilitated trust in the professional and adherence to treatment. All participants reported improvements in their physical condition and sense of well-being. The lack of adequate equipment at home, the limited length of the sessions, the perception that the physiotherapist may not be able to perform an appropriate physical examination and the lack of direct supervision were described as disadvantages. CONCLUSIONS: The findings underscored that telerehabilitation had high satisfaction among PWH. Telerehabilitation was perceived by PWH as a safe and effective intervention to improve physical condition. Telerehabilitation could be further supported and improved, and coverage could be enhanced, including rural and remote areas, which suffer from chronic inequalities in access to rehabilitation. The lack of face-to-face supervision and physical examination were perceived as the principal disadvantages. These results may help to improve telerehabilitation programs in PWH elsewhere.

"I don't want to be a burden" A qualitative study of the beliefs of women with chronic low back pain in relation to their painful experience.

BACKGROUND: Women's pain is still poorly understood. Moreover, maladaptive pain beliefs contribute to the disability associated with low back pain and play a key role in the transition from acute to chronic symptoms. OBJECTIVES: To explore the beliefs of women with non-specific chronic low back pain in terms of nature of symptoms, fears associated with pain, expectations for recovery, family, social and work-related limitations, and perceived self-efficacy. DESIGN AND METHODS: A qualitative study with an interpretative approach was undertaken. Face-to-face, semi-structured individual interviews were performed. Study participants were 10 women with non-specific chronic low back pain living in the Metropolitan Region of Chile. Thematic analysis was used to analyze the data. A deductive process was used to code the text and categorize the data. RESULTS: Participants described maladaptive beliefs about pain, leading to fearful attitudes and low expectations for recovery. These beliefs seemed to perpetuate pain and limit engagement in daily tasks and meaningful activities. Some of these beliefs were associated with information provided by healthcare professions. Despite having maladaptive beliefs, women perceived themselves as self-effective. CONCLUSION: Women with chronic low back pain described a range of different pain beliefs across a complex categorial structure. The contents of such structure may interfere with their decisions about therapeutic options. Their beliefs were often ungrounded in scientific principles, even if the information may have been provided by healthcare providers. Physical therapists would benefit from these findings to improve communication with their patients and assess the role of beliefs in decision-making.

Toxocara cati and Toxoplasma gondii in French Birds of Prey.

Parasites have developed many strategies to ensure their development, multiplication, and dissemination, including the use of reservoir hosts that are often nondomesticated species. Despite drastic reductions in their populations, wild birds remain widespread worldwide and could constitute some of these reservoirs. We focused on the identification of wild bird species harboring parasite stages in their muscles. Breast muscles of 327 birds of 27 different species were collected at three different sites in France. After artificial digestion, isolated nematode larvae were identified by PCR sequencing or restriction fragment length polymorphism (PCR-RFLP). Toxocara cati was identified mainly in birds of prey. The presence of anti-Toxoplasma antibodies was investigated by modified agglutination test on muscle fluids. Anti-Toxoplasma antibodies were detected in 65 out of 166 samples from various bird species. Avifauna, particularly birds of prey, could help on the surveillance of parasite circulation and play a role as sentinel species.

Parte 5: Enfoques Teórico-metodológicos de la Investigación Cualitativa en Salud / Part 5: Theoretical-methodological Approaches to Qualitative Health Research

Las metodologías cualitativas de investigación están siendo cada vez más utilizadas en el ámbito de la salud. Estas metodologías son útiles cuando se quiere estudiar fenómenos sociales complejos que difícilmente pueden ser estudiados mediante técnicas estadísticas o cuantitativas. Para llevar a cabo estudios cualitativos de buena calidad es necesario que los investigadores/as tengan sólidos conocimientos de la metodología y de los enfoques teóricos-metodológicos que la sustentan. Estos enfoques reflejan un posicionamiento teórico-filosófico acerca de la construcción de los fenómenos sociales y posee un cuerpo de conocimientos y procedimientos propios. Los enfoques teórico-metodológicos más utilizados en las investigaciones cualitativas en salud son la etnografía, la fenomenología y la teoría fundamentada. La recomendación es fortalecer la formación metodológica de los investigadores/as cualitativos, aumentar el rigor de los procesos investigativos y procurar la coherencia epistemológica de los estudios a través de la elección adecuada del enfoque teórico-metodológico.

Qualitative research methodologies are being increasingly used in the field of health. These methodologies are useful when you want to study complex social phenomena that can hardly be studied using statistical or quantitative techniques. To carry out qualitative studies of good quality, it is necessary for the researchers to have solid knowledge of the methodology and of the theoretical-methodological approaches that support it. These approaches reflect a theoretical-philosophical position on the construction of social phenomena and have a body of knowledge and procedures of their own. The most widely used theoretical-methodological approaches in qualitative health research are ethnography, phenomenology, and grounded theory. The recommendation is to strengthen the methodological training of qualitative researchers, increase the rigor of the investigative processes and ensure the epistemological coherence of the studies through the appropriate choice of the theoretical-methodological approach.

Investigations upon the Improvement of Dermatophyte Identification Using an Online Mass Spectrometry Application.

Online MALDI-TOF mass spectrometry applications, such as MSI-2, have been shown to help identify dermatophytes, but recurrent errors are still observed between phylogenetically close species. The objective of this study was to assess different approaches to reduce the occurrence of such errors by adding new reference spectra to the MSI-2 application. Nine libraries were set up, comprising an increasing number of spectra obtained from reference strains that were submitted to various culture durations on two distinct culture media: Sabouraud gentamicin chloramphenicol medium and IDFP Conidia medium. The final library included spectra from 111 strains of 20 species obtained from cultures on both media collected every three days after the appearance of the colony. The performance of each library was then analyzed using a cross-validation approach. The spectra acquisitions were carried out using a Microflex Bruker spectrometer. Diversifying the references and adding spectra from various culture media and culture durations improved identification performance. The percentage of correct identification at the species level rose from 63.4 to 91.7% when combining all approaches. Nevertheless, residual confusion between close species, such as Trichophyton rubrum, Trichophyton violaceum and Trichophyton soudanense, remained. To distinguish between these species, mass spectrometry identification should take into account basic morphological and/or clinico-epidemiological features.

An Intensive Care Unit Team Reflects on End-of-Life Experiences With Patients and Families in Chile.

BACKGROUND: Deaths in the intensive care unit (ICU) represent an experience of suffering for patients, their families, and professionals. End-of-life (EOL) care has been added to the responsibilities of the ICU team, but the evidence supporting EOL care is scarce, and there are many barriers to implementing the clinical recommendations that do exist. OBJECTIVES: To explore the experiences and perspectives of the various members of an ICU care team in Chile regarding the EOL care of their patients. METHODS: A qualitative study was performed in the ICU of a high-complexity academic urban hospital. The study used purposive sampling with focus groups as a data collection method. A narrative analysis based on grounded theory was done. RESULTS: Four discipline-specific focus groups were conducted; participants included 8 nurses, 6 nursing assistants, 8 junior physicians, and 6 senior physicians. The main themes that emerged in the analysis were emotional impact and barriers to carrying out EOL care. The main barriers identified were cultural difficulties related to decision-making, lack of interprofessional clinical practice, and lack of effective communication. Communication difficulties within the team were described along with lack of self-efficacy for family-centered communication. CONCLUSION: These qualitative findings expose gaps in care that must be filled to achieve high-quality EOL care in the ICU. Significant emotional impact, barriers related to EOL decision-making, limited interprofessional clinical practice, and communication difficulties were the main findings cross-referenced.

Two New Adenosine Derivatives and their Antiproliferative Properties: An In Vitro Evaluation.

BACKGROUND: Adenosine is a natural nucleoside present in a variety of organs and tissues, where it acts as a modulator of diverse physiological and pathophysiological processes. These actions are mediated by at least four G protein-coupled receptors, which are widely and differentially expressed in tissues. Interestingly, high concentrations of adenosine have been reported in a variety of tumors. In this context, the final output of adenosine in tumorigenesis will likely depend on the constellation of adenosine receptors expressed by tumor and stromal cells. Notably, activation of the A3 receptor can reduce the proliferative capacity of various cancer cells. OBJECTIVE: This study aimed to describe the anti-proliferative effects of two previously synthesized adenosine derivatives with A3 agonist action (compounds 2b and 2f) through in vitro assays. METHODS: We used gastric and breast cancer cell lines expressing the A3 receptor as in vitro models and theoretical experiments for molecular dynamics and determination of ADME properties. RESULTS: The antiproliferative effects of adenosine derivatives (after determining IC50 values) were comparable or even higher than those described for IB-MECA, a commercially available A3 agonist. Among possible mechanisms involved, apoptosis was found to be induced in MCF-7 cells but not in AGS or MDA-MB-231 cells. Surprisingly, we were unable to observe cellular senescence induction upon treatment with compounds 2b and 2f in any of the cell lines studied, although we cannot rule out other forms of cell cycles exit at this point. CONCLUSION: Both adenosine derivatives showed antiproliferative effects on gastric and breast cancer cell lines, and were able to induce apoptosis, at least in the MCF-7 cell line. Further studies will be necessary to unveil receptor specificity and mechanisms accounting for the antiproliferative properties of these novel semi-synthetic compounds.