In the present study, the synthesis of gold nanoparticles (AuNPs) loaded with methotrexate (MTX) has been carried out in order to obtain controlled size and monodispersed nanocarriers of around 20 ...nm. The characterization study shows metallic AuNPs with MTX polydispersed on the surface. MTX is linked by the replacement of citrate by the MTX carboxyl group. The drug release profiles show faster MTX release when it is conjugated, which leads to the best control of plasma concentration. Moreover, the enhanced release observed at pH 5 could take advantage of the pH gradients that exist in tumor microenvironments to achieve high local drug concentrations. AuNP-MTX conjugates were tested by flow cytometry against lung (A-549) and colon (HTC-116) cancer cell lines. Results for A-549 showed a weaker dose-response effect than for colon cancer ones. This could be related to the presence of folate receptors in line HTC-116 in comparison to line A-549, supporting the specific uptake of folate-conjugated AuNP-MTX by folate receptor positive tumor cells. Conjugates exhibited considerably higher cytotoxic effects compared with the effects of equal doses of free MTX. Annexin V-PI tests sustained the cell death mechanism of apoptosis, which is normally disabled in cancer cells.
We investigated whether peripheral blood levels of SARS‐CoV‐2 Spike (S) receptor binding domain antibodies (anti‐RBD), neutralizing antibodies (NtAb) targeting Omicron S, and S‐reactive‐interferon ...(IFN)‐γ‐producing CD4+ and CD8+ T cells measured after a homologous booster dose (3D) with the Comirnaty® vaccine was associated with the likelihood of subsequent breakthrough infections due to the Omicron variant. An observational study including 146 nursing home residents (median age, 80 years; range, 66–99; 109 female) evaluated for an immunological response after 3D (at a median of 16 days). Anti‐RBD total antibodies were measured by chemiluminescent immunoassay. NtAb were quantified by an Omicron S pseudotyped virus neutralization assay. SARS‐CoV‐2‐S specific‐IFNγ‐producing CD4+ and CD8+ T cells were enumerated by whole‐blood flow cytometry for intracellular cytokine staining. In total, 33/146 participants contracted breakthrough Omicron infection (symptomatic in 30/33) within 4 months after 3D. Anti‐RBD antibody levels were comparable in infected and uninfected participants (21 123 vs. 24 723 BAU/ml; p = 0.34). Likewise, NtAb titers (reciprocal IC50 titer, 157 vs. 95; p = 0.32) and frequency of virus‐reactive CD4+ (p = 0.82) and CD8+ (p = 0.91) T cells were similar across participants in both groups. anti‐RBD antibody levels and NtAb titers estimated at around the time of infection were also comparable (3445 vs. 4345 BAU/ml; p = 0.59 and 188.5 vs. 88.9; p = 0.70, respectively). Having detectable NtAb against Omicron or SARS‐CoV‐2‐S‐reactive‐IFNγ‐producing CD4+ or CD8+ T cells after 3D was not correlated with increased protection from breakthrough infection (OR, 1.50; p = 0.54; OR, 0.0; p = 0.99 and OR 3.70; p = 0.23, respectively). None of the immune parameters evaluated herein, including NtAb titers against the Omicron variant, may reliably predict at the individual level the risk of contracting COVID‐19 due to the Omicron variant in nursing home residents.
The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been ...thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.
Genetic interventions on microbiomes, for clinical or biotechnological purposes, remain challenging. Conjugation-based delivery of genetic cargo is still unspecific and limited by low conjugation ...rates. Here we report an approach to overcome these problems, based on a synthetic bacterial adhesion system. Mating assemblers consist on a synthetic adhesion formed by the expression on the surface of donor and target cells of specific nanobodies (Nb) and their cognate antigen (Ag). The Nb-Ag bridge increased 1-3 logs transfer of a variety of plasmids, especially in liquid media, confirming that cell-cell docking is a main determinant limiting mating efficiency. Synthetic cell-to-cell adhesion allows efficient conjugation to targeted recipients, enhancing delivery of desired genes to a predefined subset of prey species, or even specific pathogenic strains such as enterohemorrhagic Escherichia coli (EHEC), within a bacterial community. The synthetic conjugation enhancer presented here optimizes plasmid delivery by selecting the target hosts with high selectivity.
The first cluster of patients suffering from coronavirus disease 2019 (COVID-19) was identified on December 21, 2019, and as of July 29, 2020, severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2) infections have been linked with 664,333 deaths and number at least 16,932,996 worldwide. Unprecedented in global societal impact, the COVID-19 pandemic has tested local, national, and international preparedness for viral outbreaks to the limits. Just as it will be vital to identify missed opportunities and improve contingency planning for future outbreaks, we must also highlight key successes and build on them. Concomitant to the emergence of a novel viral disease, there is a 'research and development gap' that poses a threat to the overall pace and quality of outbreak response during its most crucial early phase. Here, we outline key components of an adequate research response to novel viral outbreaks using the example of SARS-CoV-2. We highlight the exceptional recent progress made in fundamental science, resulting in the fastest scientific response to a major infectious disease outbreak or pandemic. We underline the vital role of the international research community, from the implementation of diagnostics and contact tracing procedures to the collective search for vaccines and antiviral therapies, sustained by unique information sharing efforts.
Background
The first wave of the COVID‐19 pandemic caused a shortage of health care staff, forcing the hiring of senior nursing students.
Aims
To describe the psychosocial impact and coping ...strategies used by nursing students during the first outbreak of the COVID‐19 pandemic and to understand the coping strategies they employed.
Method
A qualitative exploratory study was conducted, based on Sandelowski's proposal. Purposive sampling was carried out to recruit 18 students hired during the pandemic. The students were interviewed between 18 March and 15 June 2020. Semi‐structured interviews were conducted using a digital platform. An inductive thematic analysis was performed.
Findings
The students lived alone and isolated during their contract to protect their cohabitants from possible contagion. The impact of working during the pandemic leads to experiences of stress, insomnia, nightmares and anxiety. Nursing students coped with the emotional burden through mental disconnection and the support of co‐workers and family members.
Conclusion
Psychological support and tutoring should be provided by health centres. In addition, in these special circumstances, universities should adapt the training provided.
Summary statement
What is already known about this topic?
In Spain, as in many other countries, a state of alarm was declared during the first wave of COVID 19. The Ministry of Health established measures to manage the health crisis and contain infections, including the hiring of senior nursing students to work.
Working conditions had a high physical and psycho‐emotional impact on health professionals.
The lack of prior experience of students in the context of a pandemic and how they enter the workforce could make it difficult to develop adequate coping strategies, enhancing the presence of mental and emotional disorders.
What this paper adds?
During their work, and in order to avoid contagion, the students lived apart from their families, limited their contacts and were isolated in refuge in rooms or homes. Upon entering the home, they showered, changed clothes and disinfected any surfaces they touched.
The students described feeling stressed due to the lack of protective equipment and staff, heavy workloads and lack of knowledge regarding the unit and work protocols. They worried about making mistakes, doing their jobs poorly or being unable to help patients. When they got home, they had episodes of insomnia and anxiety.
Faced with this situation, students used mental disconnection or distraction as coping strategies. Others shared their fears and uncertainties with other health care professionals and family members, seeking support and understanding. Other times, they tried to be strong and hide their suffering.
The implications of this paper:
The incorporation of students as relief for professionals in a situation of extreme need is not exempt from significant psychosocial risks and should include monitoring programs and psychological evaluation.
The hospitals should monitor and mentor students to facilitate their adaptation to similar situations in the future.
The students required greater support from the administration, including offering them housing where they could live away from family and relatives.
The disruption in healthcare attention to people with alcohol dependence, along with psychological decompensation as a consequence of lockdown derived from the COVID-19 pandemic could have a negative ...impact on people who suffer from alcohol abuse disorder. Observational real world data pre-post study included 9966 men aged >16 years registered as having the diagnosis of alcohol abuse disorder in the electronic medical records (EMR) of the Aragon Regional Health Service (Spain). Clinical (Glutamate-oxaloacetate -GOT-, Glutamate pyruvate -GPT-, creatinine, glomerular filtration, systolic blood pressure -SBP-, diastolic blood pressure -DBP-, total cholesterol, LDL, HDL, triglycerides, and body mass index -BMI-), pharmacological (dose per inhabitant per day, DHD, of drugs used in addictive disorders, benzodiazepines and antidepressants) and health resource use variables (primary and specialized care) were considered. A Student's
-test for matched samples was performed to analyze the changes in clinical variables between alcohol abuse disorder patients with and without COVID-19. Only creatinine and LDL showed a significant but clinically irrelevant change six months after the end of the strict lockdown. The total number of DHDs for all drugs included in the study (except for benzodiazepines), decreased. In the same way, the use of health services by these patients also decreased. The impact of COVID-19 among this group of patients has been moderate. The reorganization of health and social services after the declaration of the state of alarm in our country made possible the maintenance of care for this vulnerable population.
Cocoa and cocoa-based products contain different compounds with beneficial properties for human health. Polyphenols are the most frequently studied, and display antioxidant properties. Moreover, ...protein content is a very interesting source of antioxidant bioactive peptides, which can be used therapeutically for the prevention of age-related diseases.
A bioactive peptide, 13L (DNYDNSAGKWWVT), was obtained from a hydrolyzed cocoa by-product by chromatography. The in vitro inhibition of prolyl endopeptidase (PEP) was used as screening method to select the suitable fraction for peptide identification. Functional analysis of 13L peptide was achieved using the transgenic Caenorhabditis elegans strain CL4176 expressing the human Aβ₁₋₄₂ peptide as a pre-clinical in vivo model for Alzheimer's disease. Among the peptides isolated, peptide 13L (1 µg/mL) showed the highest antioxidant activity (P≤0.001) in the wild-type strain (N2). Furthermore, 13L produced a significant delay in body paralysis in strain CL4176, especially in the 24-47 h period after Aβ₁₋₄₂ peptide induction (P≤0.0001). This observation is in accordance with the reduction of Aβ deposits in CL4176 by western blot. Finally, transcriptomic analysis in wild-type nematodes treated with 13L revealed modulation of the proteosomal and synaptic functions as the main metabolic targets of the peptide.
These findings suggest that the cocoa 13L peptide has antioxidant activity and may reduce Aβ deposition in a C. elegans model of Alzheimer's disease; and therefore has a putative therapeutic potential for prevention of age-related diseases. Further studies in murine models and humans will be essential to analyze the effectiveness of the 13L peptide in higher animals.
Irisin is a myokine with a potential role in cardiometabolic diseases, but previous studies have described inconsistencies between serum irisin and physical activity (PA). Our aim was to analyze the ...relationship between serum irisin and leisure-time PA (LTPA) in a large sample of the general adult population, and secondarily, to evaluate its relationship with two PA-related biomarkers (HDL cholesterol and resistin).
A cross-sectional study was nested in the “CDC of the Canary Islands” cohort participants (n = 3827, 18–75 years, 60% women). PA was collected by administering the Minnesota leisure-time physical activity questionnaire, and physical examination and blood tests (irisin, resistin, HDL-cholesterol) were performed.
Irisin inversely correlated with BMI (p < 0.001 in women) and resistin (p = 0.038 in women, p = 0.004 in men), and directly with HDL cholesterol (p < 0.001in women). There was a direct association of irisin with leisure-time and energy expenditure in light, moderate and vigorous LTPA, which was stronger in women than men. The distribution of leisure-time and PA variables across irisin quintiles showed a significant trend, except for light LPTA in men. Adjusting for age, sex and BMI, the association of irisin with leisure-time and LTPA variables was stronger than the association of these variables with resistin and HDL cholesterol, reaching the strongest association for irisin with the 80th percentile of time of LTPA (OR = 2.57; 95% CI = 2.00–3.31).
There is a direct and independent association between serum irisin levels and LTPA in the general adult population, which is stronger than other biomarkers of PA. Findings on exercise-related irisin support the possibility of irisin health benefits.
Background:
The first wave of the COVID-19 pandemic caused a shortage of qualified nurses in Spain. As a result, the government authorized the hiring of senior students.
Objectives:
To explore the ...ethical dilemmas and ethical conflicts experienced by final-year nursing students who worked during the first outbreak of the COVID-19 pandemic in Spain.
Research design:
A qualitative exploratory study was conducted using purposive sampling. Semi-structured interviews were carried out using a question guide. Interviews took place via a private video chat room platform. A thematic, inductive analysis was performed of the information gathered.
Participants and research context:
Eighteen nursing students were recruited from two universities of Madrid, aged between 18 and 65 years old, enrolled in the fourth year of nursing studies and who were hired under a relief contract for health professionals during the pandemic.
Ethical considerations:
The present study was carried out in accordance with the Declaration of Helsinki, and the study was approved by the Local Ethics Committee of Universidad Rey Juan Carlos.
Results:
Three specific themes emerged: (a) coping with patient triage, (b) difficulties in providing end-of-life care, and (c) coping with patient death. Nursing students participated in the process of patient selection for resource allocation and ICU bed occupancy. They were shown how to care for patients who were not admitted to the ICU, in their last moments and were faced with the difficulties of applying end-of-life care. Finally, the nursing students were confronted with the death of their patients, in overwhelming numbers and under adverse conditions.
Conclusions:
These findings can help shed light on the ethical dilemmas and ethical conflicts faced by novice nursing students, incorporated into the workforce during the COVID-19 pandemic. Moreover, it was described that students may normalize the death due to the exhaustion and overwhelmed routine.
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