Systemic Autoimmune Diseases in Patients Hospitalized with COVID-19 in Spain: A Nation-Wide Registry Study

We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren’s Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet’s Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78–1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04–1.07), heart failure (OR = 1.67, 95% CI 1.10–2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05–1.59) and liver disease (OR = 1.97, 95% CI 1.13–3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis.     

The Influence of Microwave Treatments on Bioactive Compounds and Antioxidant Capacity of Mentha piperita L.

Microwave extraction is becoming a popular option in many fields, especially for bioactive compounds from medicinal plants. This paper addresses the application of microwaves in the process of extracting bioactive compounds (phenols, flavonoids, chlorophyll) from peppermint with antioxidant capacity in order to highlight the influence of the microwave field on the quality of the final product in comparison with the control samples. The Mentha piperita L. is a rich source of phenols. The total phenol content after applying the MW treatments significant increased and varied between 25.000 ± 1.992 and 391.687 ± 20.537 mg GAE/100 g dw compared to the untreated sample (8.089 ± 2.745 mg GAE/100 g dw). The same trend was also recorded in the case of the flavonoid and pigment content in peppermint leaves following the application of microwave treatments. The obtained results were investigated using chemometric multivariate analysis. The main purpose of our research was to compare the possibilities of total or partial substitution of conventional extraction technologies with the microwave extraction technology, and also to highlight the existing differences in the amount of total phenols and flavonoids extracted from peppermint plants in different processing conditions. Through microwave processing, a significant increase in polyphenolic compounds is obtained.     

HIV screening and linkage to care in a health department in Valencia,Spain: Lessons learned from a healthcare quality improvement project

Spain’s rate of new human immunodeficiency virus (HIV) diagnoses exceeds that of the European Economic Area average (8.6 vs 5.6:100,000 in 2018). The country has failed to meet the first of United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets for HIV control by 2020, with 87.0% of people living with HIV knowing their status, and late presentation rates of 47.6% and 51.5% country-wide and in the Valencian autonomous community, respectively. Advancing screening and linkage to care (SLTC) practices is necessary to effectively control the epidemic. The Valencia Viral Screening (CRIVALVIR) project adopted the TEST model for opportunistic and systematic HIV SLTC in individuals aged 18 to 80 who required blood work for any purpose, as of February 2019. SLTC was integrated into routine clinical workflow across primary care centers serving a population of 360,000 people in Valencia, Spain. Our project successfully upscaled total HIV testing by 194% to over 32,000 patients tested in 14 months. We found an overall prevalence of 0.13% (0.08–0.21) among those screened per protocol (n = 13,061), with foreign-born citizens presenting a 12.5 times significantly higher likelihood of acquiring HIV (95% confidence interval 4.63–33.96, P < .0001). We improved late presentation by 18.2 percentage points and prevented an estimated 58 to 70 new secondary infections. HIV screening of the general population in primary care is an effective strategy for achieving timely diagnosis and preventing new infections. Opportunistic, systematic, opt-out approaches are essential to control the HIV epidemic.     

KSR induces RAS‐independent MAPK pathway activation and modulates the efficacy of KRAS inhibitors

The kinase suppressor of rat sarcoma (RAS) proteins (KSR1 and KSR2) have long been considered as scaffolding proteins required for optimal mitogen‐activated protein kinase (MAPK) pathway signalling. However, recent evidence suggests that they play a more complex role within this pathway. Here, we demonstrate that ectopic expression of KSR1 or KSR2 is sufficient to activate the MAPK pathway and to induce cell proliferation in the absence of RAS proteins. In contrast, the ectopic expression of KSR proteins is not sufficient to induce cell proliferation in the absence of either rapidly accelerated fibrosarcoma (RAF) or MAPK‐ERK kinase proteins, indicating that they act upstream of RAF. Indeed, KSR1 requires dimerization with at least one member of the RAF family to stimulate proliferation, an event that results in the translocation of the heterodimerized RAF protein to the cell membrane. Mutations in the conserved aspartic acid–phenylalanine–glycine motif of KSR1 that affect ATP binding impair the induction of cell proliferation. We also show that increased expression levels of KSR1 decrease the responsiveness to the KRAS^G12C inhibitor sotorasib in human cancer cell lines, thus suggesting that increased levels of expression of KSR may make tumour cells less dependent on KRAS oncogenic signalling.     

Hearing Function and Nutritional Status in Aviation Pilots from Spain Exposed to High Acoustic Damage

Noise-induced hearing loss is the most frequent and preventable occupational disease. Aviation pilots are a vulnerable population, as they spend many hours exposed to noise pollution in their working environment. Different studies suggest that certain dietary compounds may play a key role in the etiology and prevention of this pathology. We aimed to study the relationship linking auditory function, dietary intake, and some serum biomarkers in pilots, exposed to noise in the work environment. A total of 235 pilots, who undergo a periodic medical examination at the Centro de Instrucción de Medicina Aeroespacial (Madrid, SPAIN), were evaluated. Auditory function was assessed by tonal audiometry. Energy and nutrient intakes were estimated by 24 h recall (DIAL^TM program). Serum homocysteine (Hcy) was determined in a Cobas 6000^TM multi-analyzer while folate, vitamin B₁₂, and D were analyzed in a Cobas e411^TM. The prevalence of hearing loss (HL) was 64.3%. HL was significantly related to age (r = 0.588, p ≤ 0.001) and flight hours (r = 0.283, p ≤ 0.001). A multiple linear regression model was used to assess the relationship among HL, flight hours, serum folate, and Hcy serum levels. HL was significantly (p < 0.050) associated with flight hours (β = 0.246), serum folate (β = −0.143), and serum Hcy (β = 0.227). Nutritional interventions would be of great interest to monitor and slow down the HL progression in populations exposed to noise pollution in their workplace.     

Collagen and Keratin Hydrolysates to Delay the Setting of Gypsum Plaster

Leather and wool waste represent a high concern due to the low level of valorization and circular economy demands for upcycling of biomass resources. Both biomasses can be easily processed as protein hydrolysates and used as functional additives due to the amphiphilic and tunable properties of collagen and keratin proteins. The chemical, physical, and structural investigations of collagen and keratin hydrolysate properties showed that the chelating abilities due to carboxylic groups can be exploited for gypsum retardant additives. The molecular weights and amino acid compositions of three different hydrolysates showed only slight influences on the setting time of gypsum; all three proteins delayed the setting time of gypsum between 60 and 120 min, as compared to the commercial plaster with a 30 min setting time. Higher molecular weight and more carboxylic active groups showed slight improvements in the setting time of mortars. The improved properties of keratin hydrolysate as compared to low molecular collagen hydrolysate were attributed to foaming and conductive properties. The mechanism of mortar setting delaying through calcium ions complexation by protein hydrolysates was shown by electric conductivity evolution of plasters with and without protein additives over time, supported by foaming properties, amino acid, and functional groups’ composition. Lower bending strength values for the higher concentration of proteins do not reduce the potential to use the protein hydrolysates as retardant additives in mortar fabrication.     

Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral Tissues

Rabies virus (RABV) has a broad host range and infects multiple cell types throughout the infection cycle. Next-generation sequencing (NGS) and minor variant analysis are powerful tools for studying virus populations within specific hosts and tissues, leading to novel insights into the mechanisms of host-switching and key factors for infecting specific cell types. In this study we investigated RABV populations and minor variants in both original (non-passaged) samples and in vitro-passaged isolates of various CNS regions (hippocampus, medulla oblongata and spinal cord) of a fatal human rabies case, and of multiple CNS and non-CNS tissues of experimentally infected mice. No differences in virus populations were detected between the human CNS regions, and only one non-synonymous single nucleotide polymorphism (SNP) was detected in the fifth in vitro passage of virus isolated from the spinal cord. However, the appearance of this SNP shows the importance of sequencing newly passaged virus stocks before further use. Similarly, we did not detect apparent differences in virus populations isolated from different CNS and non-CNS tissues of experimentally infected mice. Sequencing of viruses obtained from pharyngeal swab and salivary gland proved difficult, and we propose methods for improving sampling.