Baricitinib or imatinib in hospitalized COVID-19 patients: Results from COVINIB, an exploratory randomized clinical trial.

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.

Reflective based learning for nursing ethical competency during clinical practices.

BACKGROUND: A combination of theoretical and practical approaches is required to learn and acquire ethical competencies in caring. Occasionally, reflection on practical action differs from theoretical learning. In the context of reflective learning, issues such as ethical values can be discussed since they evoke conflict among nursing students. AIM: To identify ethical conflicts encountered by nursing students during clinical placements and to determine their cooperation strategies. RESEARCH DESIGN: Qualitative study with a content analysis according to Elo and Kinglas framework. PARTICIPANTS AND RESEARCH CONTEXT: Students enrolled in a nursing program at a Spanish university aged between 22 and 35, mainly women. METHODOLOGY: The study includes 134 ethical reflections from nursing students in the last year of the nursing program, written during their clinical practices in a variety of learning environments. The research team analyzed the reflections using an inductive content analysis method. ETHICAL CONSIDERATIONS: Ethical permission was obtained by the management center according to Law 3/2028, and all the participants accepted to participate through the informed consent form. FINDINGS: Three main categories emerged from the analysis of the ethical reflections: (1) evaluation of professional performance and patient care; (2) the student as the protagonist of the dilemma; (3) student coping. Student dilemmas and concerns are related to ignorance, student-patient communication, mistakes made and self-confidence. Some situations conflict with the autonomy of patients and their rights, and can contribute to stressful situations for patients. Stress factors include hospital routines, which the patient cannot modify, and asymmetric relationships with staff, which encourage passivity. CONCLUSION: All ethical problems detected by the students begin with the professional-patient relationship, including issues related to bad news, errors or malpractice. Reflection on the ethical values of nursing, both in the classroom and in clinical practices, allows students to develop a greater ethical awareness of care, enhancing their decision-making skills in ethical dilemmas.

Digital Impression Taking for Maxillary Full-Arch Restoration With Immediate Loading: A Case Report.

The aim of this clinical report is to describe a maxillary full-arch implant supported restoration with immediate loading performed by means of an entirely digital work flow with photogrammetric system and intraoral scanning. A female patient with an edentulous maxillary arch attended the dental clinic seeking a maxillary fixed restoration. After treatment planning, 6 implants were placed using a surgical splint fabricated digitally by intraoral scanning of her previous removable prosthesis. Multiunit abutments were fitted, and 2 digital impressions were taken, one with a photogrammetric system for determining implant positions and the other with an intraoral scanner for soft tissue registration. The acrylic resin structure of the immediate prosthesis was milled and placed within 8 hours of implant surgery. This provisional structure fitted correctly and provided adequate esthetics and function. Radiographic and clinical follow-up after 24 months observed adequate implant evolution.

Contact Lens Discomfort Management: Outcomes of Common Interventions.

PURPOSE: To assess the consecutive implementation of habitual contact lens discomfort (CLD) management strategies: lid hygiene, daily disposable CL (DDCL) fitting, and artificial tear (AT) supplementation. METHODS: Contact lens (CL) wearers with CLD symptoms (CLDEQ-8 ≥12 points) were included in the study. Subjects with Meibomian gland dysfunction (MGD) were instructed to perform lid hygiene. All participants were fitted with a DDCL (delefilcon A) and evaluated 1 month later. After, half of them were randomly assigned to use AT (Povidone-2%) at least three times/day, and all participants were evaluated 1 month later. Tests performed were: lower tear meniscus area (LTMA), bulbar, limbal, and tarsal hyperemia, noninvasive tear break-up time (NITBUT), and corneal and conjunctival staining. Weighted combined clinical scores (CS) were created to analyze signs. Changes in symptoms (CLDEQ-8) and CS were analyzed using linear mixed models. RESULTS: Forty-two subjects (mean age: 23.2±4.9 years) completed the study. Two CS were created, CS 1 was composed of bulbar, limbal, and tarsal hyperemia and corneal staining, and CS 2 by NITBUT, LTMA, and conjunctival staining. CLDEQ-8 was reduced after lid hygiene (mean: -2.73±2.13; P=0.012) and DDCL use (mean: -10.1±3.54; P<0.01), but not after AT use (P=0.62). CS 1 did not change after any intervention. CS-2 was higher (P=0.04) in DGM subjects after lid hygiene, it decreased (P=0.04) after DDCL use. CONCLUSIONS: Lid hygiene is effective for reducing CLD symptoms in MGD patients. Refitting subjects with delefilcon A is an effective intervention for CLD to reduce symptoms and achieve a healthier ocular surface. Simultaneous administration of AT did not further improve CLD.

Determination of antibiotics in meat samples using analytical methodologies: A review.

Antibiotics are widely used to prevent or treat some diseases in human and veterinary medicine and also as animal growth promoters. The presence of these compounds in foods derived from food-producing animals can be a risk for human health. Consequently, regulatory agencies have set maximum residue limits for antibiotics in food samples. Therefore, the development of novel methodologies for its determination in food samples is required. Specifically, the analysis and quantification of these substances in meat tissues is a challenge for the analytical chemistry research community. This is due to the complexity of the matrix and the low detection limits required by the regulatory agencies. In this sense, a comprehensive review on the development of new sample preparation treatments involving extraction, cleanup, and enrichment steps of antibiotics in meat samples in combination with sensitive and sophisticated determination techniques that have been carry out in the last years is necessary. Therefore, the aim of this work is to summarize the published methodologies for the determination of antibiotics from 2016 until the beginning of the second semester of 2020. The first part of this review includes an introduction about antibiotic families, followed by sample preparation and determination techniques applied to the different families. Finally, a detailed discussion of the current trends and the future possible perspectives in this field are also included.

Roadmap of cocoa quality and authenticity control in the industry: A review of conventional and alternative methods.

Cocoa (Theobroma cacao L.) and its derivatives are appreciated for their aroma, color, and healthy properties, and are commodities of high economic value worldwide. Wide ranges of conventional methods have been used for years to guarantee cocoa quality. Recently, however, demand for global cocoa and the requirements of sensory, functional, and safety cocoa attributes have changed. On the one hand, society and health authorities are increasingly demanding new more accurate quality control tests, including not only the analysis of physicochemical and sensory parameters, but also determinations of functional compounds and contaminants (some of which come in trace quantities). On the other hand, increased production forces industries to seek quality control techniques based on fast, nondestructive online methods. Finally, an increase in global cocoa demand and a consequent rise in prices can lead to future cases of fraud. For this reason, new analytes, technologies, and ways to analyze data are being researched, developed, and implemented into research or quality laboratories to control cocoa quality and authenticity. The main advances made in destructive techniques focus on developing new and more sensitive methods such as chromatographic analysis to detect metabolites and contaminants in trace quantities. These methods are used to assess cocoa quality; study new functional properties; control cocoa authenticity; or detect frequent emerging frauds. Regarding nondestructive methods, spectroscopy is the most explored technique, which is conducted within the near infrared range, and also within the medium infrared range to a lesser extent. It is applied mainly in the postharvest stage of cocoa beans to analyze different biochemical parameters or to assess the authenticity of cocoa and its derivatives.

Nurses' emotions on care relationship: A qualitative study.

AIMS: To describe nurses' experiences regarding the care relationship built with medical-surgical patients in acute hospitalization units and the association with their clinical practice. BACKGROUND: Nurses' commitment to care and their relationships as well are the core of quality of care. Nurses consider that the emotional commitment is essential to the profession, thus accepting to be exposed to emotional distress. METHODS: In-depth interviews were conducted to explore the experience of 23 nurses from seven Spanish hospitals. Taped interviews were transcribed verbatim and analysed according to inductive content analysis. RESULTS: Six subcategories emerged from the data analysis: Fulfilling experiences, Feeling the pain of others, Emotional distress, Stepping back, Seeking professional support, and Evolution of emotions, which were combined in two main categories: Nurses' emotions and Nurses' coping strategies. Patient's suffering, work environment and interprofessional relations influence the care relationship. CONCLUSIONS: Positive and negative emotions emerge spontaneously in professional relationships of experienced nurses. Lack of time and high workloads are factors that hinder the nurse-patient relationship. This care relationship is often the reason that fulfils them. Despite their level of expertise and having coping strategies, these are not always effective and, sometimes, nurses need professional help. IMPLICATIONS FOR NURSING MANAGEMENT: Nurses will continue performing their job with commitment; therefore, nursing managers should take care of their staff and pay attention to the emotional competence related to patients' relationships. Promoting self-care and a good working environment could improve their coping mechanisms.

Proteomic fingerprinting of apple fruit, juice, and cider via combinatorial peptide ligand libraries and MS analysis.

Combinatorial peptide ligand libraries coupled to MS was applied to extensively map the proteome of apple fruit, and to detect its presence in commercial apple juice and cider to evaluate their authenticity and genuineness. Using the Uniprot_Malus database, 96 proteins were detected in apples, among which 30 proteins were specifically captured via combinatorial peptide ligand libraries. Next, three proteins, previously recognized in fruits, were found in apple juice, which were involved in cellular metabolism of fruit maturation and in allergenic reactions. On the other hand, only one Malus allergen was identified in cider beads eluate, demonstrating that the industrial processes did not prevent any negative effects in sensitive subjects. Thus, the present study not only increases the knowledge of the apple proteome but also offers a reliable analytical method to assess quality and genuineness of commercial products, which could be also used to inform consumers about the presence of allergens.

The sigma factor SigD of Mycobacterium tuberculosis putatively enhances gene expression of the septum site determining protein under stressful environments.

This work examined the expression of the septum site determining gene (ssd) of Mycobacterium tuberculosis CDC1551 and its ∆sigD mutant under different growing conditions. The results showed an up-regulation of ssd during stationary phase and starvation conditions, but not during in vitro dormancy, suggesting a putative role for SigD in the control of ssd expression mainly under lack-of-nutrients environments. Furthermore, we elucidated a putative link between ssd expression and cell elongation of bacilli at stationary phase. In addition, a -35 sigD consensus sequence was found for the ssd promoter region, reinforcing the putative regulation of ssd by SigD, and in turn, supporting this protein role during the adaptation of M. tuberculosis to some stressful environments.

Emended description of Mycobacterium abscessus, Mycobacterium abscessus subsp. abscessus and Mycobacteriumabscessus subsp. bolletii and designation of Mycobacteriumabscessus subsp. massiliense comb. nov.

The taxonomic position of members of the Mycobacterium abscessus complex has been the subject of intensive investigation and, in some aspects confusion, in recent years as a result of varying approaches to genetic data interpretation. Currently, the former species Mycobacterium massiliense and Mycobacterium bolletii are grouped together as Mycobacterium abscessus subsp. bolletii. They differ greatly, however, as the former M. bolletii has a functional erm(41) gene that confers inducible resistance to macrolides, the primary therapeutic antimicrobials for M. abscessus, while in the former M. massiliense the erm(41) gene is non-functional. Furthermore, previous whole genome studies of the M. abscessus group support the separation of M. bolletii and M. massiliense. To shed further light on the population structure of Mycobacterium abscessus, 43 strains and three genomes retrieved from GenBank were subjected to pairwise comparisons using three computational approaches: verage ucleotide dentity, enome to enome istance and single nucleotide polymorphism analysis. The three methods produced overlapping results, each demonstrating three clusters of strains corresponding to the same number of taxonomic entities. The distances were insufficient to warrant distinction at the species level, but met the criteria for differentiation at the subspecies level. Based on prior erm(41)-related phenotypic data and current genomic data, we conclude that the species M. abscessus encompasses, in adjunct to the presently recognized subspecies M. abscessus subsp. abscessus and M. abscessus subsp. bolletii, a third subspecies for which we suggest the name M. abscessus subsp. massiliense comb. nov. (type strain CCUG 48898T=CIP 108297T=DSM 45103T=KCTC 19086T).

Corneal Sensitivity and Inflammatory Biomarkers in Contact Lens Discomfort.

PURPOSE: The aim of this study was to analyze whether symptoms of discomfort in hydrogel contact lens (HCL) wearers were associated with changes in corneal sensitivity or levels of tear inflammatory mediators. METHODS: Sixty-six subjects were included: 47 HCL wearers, further divided into 24 symptomatic and 23 asymptomatic wearers by the Contact Lens Dry Eye Questionnaire short form and 19 non-contact lens wearers. At least 24 h after HCL removal, we obtained scores from the Ocular Surface Disease Index and mechanical, hot, and cold corneal thresholds using a Belmonte esthesiometer. We collected 4 µl of tears with a capillary micropipette and measured levels of 12 inflammatory markers using a bead-based array: epidermal growth factor, fractalkine, interleukin-10 (IL-10), IL-1ß, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, monocyte chemoattractant protein 1, tumor necrosis factor-α, and matrix metalloproteinase 9. RESULTS: There were no significant differences between groups in corneal sensitivity thresholds and levels of tear molecules. The following significant correlations were found in the total sample pooled: Ocular Surface Disease Index correlated with mechanical threshold (p < 0.01; rho = -0.324) and epidermal growth factor (p < 0.01, rho = -0.330), and mechanical threshold correlated with heat threshold (p < 0.01, rho = -0.321). CONCLUSIONS: Twenty-four hours after HCL removal, symptoms of discomfort in HCL wearers are not related to changes in corneal sensitivity or tear inflammatory mediator levels. This might indicate either that HCL wear has no effect on these parameters or that ocular surfaces recover from HCL-caused effects during the first hours after HCL removal. However, there were correlations for associations between symptoms, corneal sensitivity, and some molecules in tears.

Fracture Load Before and After Veneering Zirconia Posterior Fixed Dental Prostheses.

PURPOSE: To evaluate the fracture load of 3-unit zirconia-based posterior fixed dental prostheses (FDPs) before and after veneering the frameworks. MATERIALS AND METHODS: Forty standardized stainless-steel master dies were fabricated (height: 5 mm, convergence: 6º, chamfer: 1 mm) and randomly screwed in pairs onto metal bases. The bases were randomly divided into two groups (n = 20 each) according to the zirconia CAD/CAM system used for constructing 3-unit structures for FDPs: group 1 (L): Lava All-ceramic, group 2 (Z): IPS e.max ZirCAD. Half of the zirconia structures per group were randomly selected and veneered, while the remaining half was left unveneered. The specimens were luted in standard fashion onto the stainless steel master dies using conventional glass ionomer cement. All specimens were tested for fracture load (FL). Specimens were subjected to a three-point bending test until fracture by applying an axial compressive load at the central fossa of the pontics with a universal testing machine at a 0.5 mm/min crosshead speed. Wilcoxon's rank-sum test and Weibull statistics were used for statistical analysis (α = 0.05). RESULTS: L structures recorded significantly higher values of load to fracture than the Z group both before and after veneering. Within each ceramic group, no differences were found between unveneered and veneered frameworks. CONCLUSIONS: Although further studies are necessary to corroborate these findings, both zirconia systems could be recommended for restoring posterior teeth on the basis of the fracture load values recorded in this experiment (>1000 N). The veneering procedure did not affect the overall load to fracture in any group.

According to the CPLL proteome sheriffs, not all aperitifs are created equal!

Combinatorial peptide ligand libraries (CPLLs) have been adopted for investigating the proteome of a popular aperitif in Northern Italy, called "Amaro Branzi", stated to be an infusion of a secret herbal mixture, of which some ingredients are declared on the label, namely Angelica officinalis, Gentiana lutea and orange peel, sweetened by a final addition of honey. In order to assess the genuineness of this commercial liqueur, we have prepared extracts of the three vegetable ingredients, assessed their proteomes, and compared them to the one found in the aperitif. The amaro's proteome was identified via prior capture with CPLLs at two different pH values (2.2 and 4.8). Via mass spectrometry analysis of the recovered fractions, after elution of the captured populations in 4% boiling SDS, we could confirm the presence of the following: six proteins originating from honey, 11 from orange peels, 29 from G. lutea and 46 from A. officinalis (including shared species), plus 33 species which could not be attributed to the other secret ingredients, due to paucity of genomic data on plant proteins, for a total of 93 unique gene products (merging shared proteins). This fully confirmed the genuineness of the product. Considering that most of these species could be present in trace amounts, undetectable by conventional techniques, the CPLL methodology, due to its ability to enhance the signal of trace components up to 3 to 4 orders of magnitude, could represent a powerful tool for investigating the genuineness and natural origin of commercial beverages in order to protect consumers from adulterated products.

[Adolescent support networks in a health care context: the interface between health, family and education]. / Redes de apoio ao adolescente no contexto do cuidado à saúde: interface entre saúde, família e educação.

OBJECTIVE: Analyze adolescents' perceptions about support networks and their health needs. METHOD: Analytical and interpretive study using focus groups conducted in municipal state schools in Fortaleza, in the State of Ceará during the first semester of 2012. The sample comprised 36 male and female adolescents aged between 13 and 16 years attending the ninth grade of the second phase of elementary school. RESULTS: Thematic analysis revealed that the health care support network and interaction between health professionals, education professionals and family members was insufficient, constituting a lack of an integrated network to enable and provide support for health promotion. CONCLUSION: Coordination between education, health and family services has the potential to act as a support network to help meet adolescents' healthcare needs and demands.

Classification of olive leaves and pulps according to their cultivar by using protein profiles established by capillary gel electrophoresis.

A method to classify olive leaves and pulps according to their cultivar using protein profiles obtained by capillary gel electrophoresis (CGE) has been developed. For this purpose, proteins were extracted using an enzyme-assisted method, which provided higher protein recoveries than other previously described methods. Ten and nine common peaks, for leaf and pulp samples, respectively, were identified in the 12 cultivars studied in this work. In addition, and using linear discriminant analysis of the CGE data, olive leaf and pulp samples belonging to 12 cultivars from different Spanish regions were correctly classified with an excellent resolution among all the categories, which demonstrated that protein profiles were characteristic of each cultivar.

Experiences of nursing students in A peer mentoring program during their clinical practices. A qualitative study.

BACKGROUND: Clinical placements allow nursing students to develop the skills and attitudes necessary to provide care. Peer mentoring programmes seem to facilitate these achievements, but there are very few studies on the effects of peer mentoring on clinical placements and what it can bring to both mentors and mentees. AIM: To describe the perspectives of nursing students on a peer mentoring programme during their clinical placements. DESIGN: A qualitative descriptive and exploratory study. SETTINGS AND PARTICIPANTS: First year and third year nursing students were included. METHODS: Focus groups were conducted with students after they participated in a peer mentoring programme during their clinical practice rotation. RESULTS: The support received from the student mentors was very important both academically and personally. Mentors also acknowledged having improved their teaching and leadership skills. CONCLUSIONS: Our results can be applied to future studies to inform peer mentoring programmes as a complementary teaching tool in clinical placements to improve leadership and empowerment in nursing students.

Tear Cytokines as Predictive Biomarkers of Success in Contact Lens Discomfort Management.

PURPOSE: To analyze changes in tear levels of inflammatory mediators in symptomatic contact lens (CL) wearers after refitting with daily disposable CLs and to identify potential biomarkers of success in CL discomfort (CLD) management. METHODS: Symptomatic CL wearers (CLDEQ-8 ≥ 12) were refitted (V1) with daily disposable CLs (Delefilcon A). After one month (V2), participants were classified into the post-fitting non-symptomatic (CLDEQ <12) and symptomatic (CLDEQ ≥12) groups. At each visit, the participants were clinically evaluated, tears were collected, and 20 inflammatory mediators and substance P (SP) were measured using multiplex immunobead analysis and ELISA, respectively. The detection rates and concentrations were compared between visits and groups, and logistic regression models were performed. RESULTS: Forty-three subjects (32 women/11 men; mean age: 23.2 ± 4.9 years) were enrolled. The IL-1ß and IL-9 detection rates were higher at V2 (p ≤ 0.044). The detection rates of IL-1ß, IL-9, MIP-1α/CCL3, and MMP-9 at V1 (p ≤ 0.045) and IL-17A at V2 (p ≤ 0.014) were higher in the post-fitting symptomatic group. The tear IL-9 concentration was increased at V2 (p = 0.018). The tear concentrations of fractalkine/CX3CL1, IL-2, IL-6, IL-10, MCP-3/CCL7, MIP-1ß, NGF, RANTES/CCL5, and TNF-α were higher in the post-fitting symptomatic group (p ≤ 0.044). Additionally, levels of fractalkine/CX3CL1, IL-2, IL-6, IL-10, RANTES/CCL5, and TNF-α at V1 were significantly associated with the post-fitting grouping (p ≤ 0.044). CONCLUSIONS: Low tear concentrations of specific inflammatory mediators may be used as a predictive biomarker of success for refitting symptomatic CL wearers with daily disposable CLs. However, complementary treatments might be required for symptomatic CL wearers with higher levels of these inflammatory molecules.

Autofluorescence as a tool for structural analysis of biofilms formed by nonpigmented rapidly growing mycobacteria.

The structure of biofilms formed by seven nonpigmented rapidly growing mycobacteria, including saprophytes and opportunistic species, was analyzed. Analysis included amount of covered surface, thickness, cell viability, and presence of intrinsic autofluorescence at different times using confocal laser scanning microscopy and image analysis. Autofluorescence was detected inside and outside cells of all mycobacteria.

Oral health-related quality of life in complete denture wearers depending on their socio-demographic background, prosthetic-related factors and clinical condition.

OBJECTIVES: To investigate the differences in impact on oral health-related quality of life (OHRQoL) among complete denture wearers depending on their socio-demographic characteristics, prosthetic-related factors and oral status. STUDY DESIGN: 51 patients aged 50-90 years treated, from 2005 to 2010, with at least one complete denture at the Department of Buccofacial Prostheses of the Complutense University (Madrid) were enrolled in this cross-sectional study. All of the participants answered the Oral Health Impact Profile (OHIP-14sp) questionnaire. The additive scoring method was used. The prevalence of impacts was calculated by using the occasional threshold (OHIP-14sp score ≥ 2). Socio-demographic and prosthetic-related variables were gathered. Patients underwent clinical examination to assess their oral condition. Descriptive probes and Chi-Square tests were run (p ≤ 0.05). RESULTS: The predominant participants' profile was that of a man with a mean age of 69 years wearing complete dentures in both the maxilla and the mandible. The prevalence of impact was 23.5%, showing an average score of 19 ± 9.8. The most affected domains were "functional limitation" and "physical pain", followed by "physical disability". Minor impacts were recorded for the psychological and social subscales ("psychological discomfort", "psychological disability", "social disability" and "handicap"). The prosthesis' location significantly influenced the overall patient satisfaction, the lower dentures being the less comfortable. Having a complete removable denture as antagonist significantly hampered the patient satisfaction. Patients without prosthetic stomatitis and those who need repairing or changing their prostheses, recorded significantly higher OHIP-14sp total scores. CONCLUSIONS: The use of conventional complete dentures brings negative impacts in the OHRQoL of elderly patients, mainly in case of lower prostheses that required reparation or substitution, with a removable total denture as antagonist. The prosthetic stomatitis in this study was always associated to other severe illness, which may have influenced the self-perceived discomfort with the prostheses, as those patients were daily medicated with painkillers.