Safety and immunogenicity of a recombinant protein RBD fusion heterodimer vaccine against SARS-CoV-2.

In response to COVID-19 pandemic, we have launched a vaccine development program against SARS-CoV-2. Here we report the safety, tolerability, and immunogenicity of a recombinant protein RBD fusion heterodimeric vaccine against SARS-CoV-2 (PHH-1V) evaluated in a phase 1-2a dose-escalation, randomized clinical trial conducted in Catalonia, Spain. 30 young healthy adults were enrolled and received two intramuscular doses, 21 days apart of PHH-1V vaccine formulations [10 µg (n = 5), 20 µg (n = 10), 40 µg (n = 10)] or control [BNT162b2 (n = 5)]. Each PHH-1V group had one safety sentinel and the remaining participants were randomly assigned. The primary endpoint was solicited events within 7 days and unsolicited events within 28 days after each vaccination. Secondary endpoints were humoral and cellular immunogenicity against the variants of concern (VOCs) alpha, beta, delta and gamma. All formulations were safe and well tolerated, with tenderness and pain at the site of injection being the most frequently reported solicited events. Throughout the study, all participants reported having at least one mild to moderate unsolicited event. Two unrelated severe adverse events (AE) were reported and fully resolved. No AE of special interest was reported. Fourteen days after the second vaccine dose, all participants had a >4-fold change in total binding antibodies from baseline. PHH-1V induced robust humoral responses with neutralizing activities against all VOCs assessed (geometric mean fold rise at 35 days p < 0.0001). The specific T-cell response assessed by ELISpot was moderate. This initial evaluation has contributed significantly to the further development of PHH-1V, which is now included in the European vaccine portfolio.ClinicalTrials.gov Identifier NCT05007509EudraCT No. 2021-001411-82.

Usefulness of ultrasound in the diagnosis of crystal deposition diseases.

Gout and calcium pyrophosphate crystal deposition disease (CPPD) are common forms of inflammatory arthritis whose prevalence has increased in recent years. Although the identification of monosodium urate crystals (MSU) and calcium pyrophosphate crystals (CPP) in synovial fluid (SF) by polarized light microscopy are the gold standard for diagnosing these diseases, SF analysis is not always available. An early diagnosis and specific treatment, especially in gout, allows avoiding irreversible structural damage, comorbidities, and a severe impact on the quality of life of patients. Musculoskeletal ultrasound (US) is a noninvasive tool that allows detecting aggregates of microcrystals at multiple anatomical sites and helps to establish a specific diagnosis. The objective of this review is to evaluate the applications of US in the diagnosis and clinical management of the main microcrystalline arthropathies. The US has helped improve our understanding of the natural history of the disease, due to its ability to visualize not only soft tissue inflammation and structural damage, but also the characteristics of MSU and CPP crystal deposition. The anatomical sites of crystal deposition are also a key factor for differential diagnosis in different microcrystalline diseases. The US allows establishing an early diagnosis, especially in asymptomatic hyperuricemia, to discriminate with other inflammatory diseases, to assess the extent of microcrystalline deposition and their sensitivity to change after treatment. Given its increasing availability in clinical practice and strong evidence, US is a bedside imaging technique helping clinicians to improve diagnosis and therapy monitoring in their daily practice.

Transcription Factor DOF4.1 Regulates Seed Longevity in Arabidopsis via Seed Permeability and Modulation of Seed Storage Protein Accumulation.

Seed longevity is modulated by multiple genetic factors in Arabidopsis thaliana. A previous genome-wide association study using the Elevated Partial Pressure of Oxygen (EPPO) aging assay pinpointed a genetic locus associated with this trait. Reverse genetics identified the transcription factor DOF4.1 as a novel seed longevity factor. dof4.1 loss-of-function plants generate seeds exhibiting higher germination after accelerated aging assays. DOF4.1 is expressed during seed development and RNAseq data show several putative factors that could contribute to the dof4.1 seed longevity phenotype. dof4.1 has reduced seed permeability and a higher levels of seed storage proteins mRNAs (cruciferins and napins) in developing seeds, as compared to wild-type seeds. It has been reported that mutant lines defective in cruciferins or napins present reduced seed longevity. The improved longevity of dof4.1 is totally lost in the quadruple mutant dof4.1 cra crb crc, but not in a dof4.1 line depleted of napins, suggesting a prominent role for cruciferins in this process. Moreover, a negative regulation of DOF4.1 expression by the transcription factor DOF1.8 is suggested by co-inoculation assays in Nicotiana benthamiana. Indeed, DOF1.8 expression anticorrelates with that of DOF4.1 during seed development. In summary, modulation of DOF4.1 levels during seed development contributes to regulate seed longevity.

Comparative analysis of wild-type accessions reveals novel determinants of Arabidopsis seed longevity.

Understanding the genetic factors involved in seed longevity is of paramount importance in agricultural and ecological contexts. The polygenic nature of this trait suggests that many of them remain undiscovered. Here, we exploited the contrasting seed longevity found amongst Arabidopsis thaliana accessions to further understand this phenomenon. Concentrations of glutathione were higher in longer-lived than shorter-lived accessions, supporting that redox poise plays a prominent role in seed longevity. However, high seed permeability, normally associated with shorter longevity, is also present in long-lived accessions. Dry seed transcriptome analysis indicated that the contribution to longevity of stored messenger RNA (mRNAs) is complex, including mainly accession-specific mechanisms. The detrimental effect on longevity caused by other factors may be counterbalanced by higher levels of specific mRNAs stored in dry seeds, for instance those of heat-shock proteins. Indeed, loss-of-function mutant analysis demonstrated that heat-shock factors HSF1A and 1B contributed to longevity. Furthermore, mutants of the stress-granule zinc-finger protein TZF9 or the spliceosome subunits MOS4 or MAC3A/MAC3B, extended seed longevity, positioning RNA as a novel player in the regulation of seed viability. mRNAs of proteins with putative relevance to longevity were also abundant in shorter-lived accessions, reinforcing the idea that resistance to ageing is determined by multiple factors.

Interobserver reliability of Masei index validation by a multicenter collaborative group of rheumatologists.

MASEI is the main validated ultrasound score for the evaluation of enthesis. The lack of studies facing the agreement to achieve for the interpretation of the MAdrid Sonographic Enthesis Index (MASEI) among researchers from different centers in multicenter studies is of concern. The aim of this multicenter was to evaluate the interobserver reliability of MASEI. An experienced ultrasonographer-rheumatologist performed ultrasound scans of the areas included in MASEI index in three patients with Ankylosing Spondylitis and Psoriatic Arthritis. Videos were captured. The videos were then evaluated by 24 rheumatologists of the ultrasound working group of the Catalan Society of Rheumatology (EcoCAT). A face-to-face training meeting was held. Ten days after the workshop, the study participants evaluated the videos. A reliability assessment was performed. The ICC for the MASEI scores after the workshop was of 0.97 (95% CI 89-99). Reliability did not vary statistically with examiner experience. Globally, no problems of reliability by structures were seen, and all the ICCs were above 0.90 and improved slightly after the educational program. However, the correlation observed between examiners at plantar aponeursis and triceps tendon was weak. The small variability observed in the results of the index validation in our study, suggests that the MASEI index is reproducible by different observers when those are well trained and show awesome results of the enthesis when examined by ultrasound.

The activity of rheumatology nurses in Spain. / Actividad de la enfermera de reumatología en España.

OBJECTIVE: Describe and analyze nursing activity in rheumatology. MATERIAL AND METHODS: A cross-sectional study was performed in Spanish rheumatology departments. Results were based on surveys administered to rheumatology nurses. We included variables on socio-demographics, the setting and available resources, and the activities they carried out. Each activity was compared in terms of workplace, available resources and dedication exclusively to one field. RESULTS: Sixty-seven surveys were collected from 57 hospitals in 17 Spanish autonomous communities. 97% of the nurses were women, with an average age of 48.9 years and an average nursing experience of 6 years. 56% of the professionals had gained their experience in outpatient clinics, 35% in day hospitals and 9% in inpatient and primary care. As for the availability of resources, 59% had their own office, 77.3% had a phone listing and 60% scheduled and conducted patient visits. Of the 19 activities included, those performed by the highest number of nurses were managing, monitoring and coordinating the use of biological drugs (90.9%), therapy monitoring (89.4%) and training patients in self-medication (89.4%). The activity in which nurses most frequently collaborated with physicians was the administration of local injections (51.5%). Other activities were teaching (50%) and research (78.8%) in their departments and studies in the nursing field (51.5%). Work in outpatient clinics versus day hospitals showed statistically significant differences for health education, nutrition, splinting and bandaging, and collaboration in ultrasound studies. CONCLUSION: These professionals performed a greater number of activities when they worked in outpatient clinics, had their own office and worked exclusively in rheumatology.

Pilot study investigating the age-related decline in ovarian function of regularly menstruating normal women.

OBJECTIVE: To use a pilot study to investigate markers of the age-related decline in ovarian function of regularly menstruating normal women. DESIGN: Prospective. SETTING: Tertiary research center. PATIENT(S): Healthy volunteers (n = 42) aged 18 to 50 years who had regular ovulatory menstrual cycles and a prior pregnancy. INTERVENTION(S): A single 300-IU dose of human recombinant FSH on day 3 of the menstrual cycle. MAIN OUTCOME MEASURE(S): Antral follicle count by transvaginal ultrasound and basal and FSH-stimulated serum markers. RESULT(S): Age correlated most strongly with FSH-stimulated inhibin B (r = -0.660), followed by antral follicle count (r = -0.578), basal FSH (r = 0.509), basal Müllerian inhibiting substance (MIS; r = -0.468), and basal inhibin B (r = -0.358). Total antral follicle count correlated most strongly with basal MIS level (r = 0.642). CONCLUSION(S): Of the parameters tested, FSH-stimulated serum inhibin B level had the strongest correlation with age. Basal serum MIS level had the strongest correlation with total antral follicle count. We confirm a previous report that in normal women, the antral follicle count as determined by transvaginal ultrasound examination correlates better with age than do basal FSH and basal inhibin B levels.

[Malnutrition in hospitalized patients: prevalence and economic impact]. / Desnutrición en pacientes hospitalizados: prevalencia e impacto económico.

BACKGROUND AND OBJECTIVE: Malnutrition constitutes a serious problem of public health. We intended to know the prevalence of undernourishment in our hospital, as well as to assess the expenses generated by its presence. PATIENTS AND METHOD: A study of cohorts was designed to evaluate the nutritional state of randomly selected patients admitted to a third level hospital. We carried out a protocol of nutritional evaluation and quantified the associated costs including drugs, diet, and hospital stay according to diagnosis-related groups. RESULTS: In agreement with anthropometry and the index of corporal mass, the prevalence of malnutrition was 0.3% and 13.4%, respectively. When analyzing the biochemical markers, the prevalence rose to 65.7%. Patients with malnutrition at the time of admission underwent a 59.9% deterioration of their nutritional state. An increase of costs was observed in relation to the length of hospital stay (68.04% compared with normo-nourished patients). Costs related to consumption of medicines, especially antibiotics, were also higher, as well as costs related to nutritional support. CONCLUSIONS: Malnutrition is a phenomenon frequently observed in a hospital setting. Malnutrition associated costs are significant.