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Utilitarianism has been able to respond to many of the objections raised against it by undertaking a major revision of its theory. Basically, this consisted of recognising that its early normative propositions were only viable for agents very different from flesh-and-blood humans. They then deduced that, given human limitations, it was most useful for everyone if moral agents did not behave as utilitarians and habitually followed certain rules. Important recent advances in neurotechnology suggest that some of these human limitations can be overcome. In this article, after presenting some possible neuro-enhancements, we seek to answer the questions, first, of whether they should be accepted by a utilitarian ethic and, second, if accepted, to what extent they would invalidate the revision that allowed them to escape the objections.

In this work we present the observational study of propagation of blobs (Sheeley et al., 1997) in which detection in the white-light data is favored during solar minimum activity. Therefore, the minimum of the solar cycle 24 was particularly an optimal occasion to perform an observational analysis of the detection of blobs. As blobs are considered to be tracers in white-light data of the slow solar wind, the importance of the study of their propagation has two aims: (1) to known more about their kinematic behavior and (2) to inquire about the local morphology of the solar magnetic field of their origin. The selected periods of observation have permitted the identification of around 100 blob-like structures detected by LASCO and SECCHI coronagraphs on board SOHO and STEREO, respectively. The inferring location of their origin in the inner solar corona was performed by the tridimensional Potential Field Source Surface (PFSS) developed by De Rosa (2003). The results of this study support previous findings that track down the origin of the slow and intermediate solar wind to neighboring regions of helmet streamers and pseudostreamers (Panasenco and Velli, 2016; Riley and Luhmann, 2012, and references therein). In addition, the kinematic of the 3D trajectories of blobs have been used to explore the 'drag-force' model (Borgazzi et al., 2009) which explains the stretching behavior of faster and slower blobs. Finally in this study, we propose a "new" estimation of the Sun-mass-loss taking into account also the blobs mass along an 11-years solar cycle., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

The new biotechnology raises expectations for modifying human behaviour through its use. This article focuses on the ethical analysis of the not so remote possibility of rehabilitating criminals by means of neurotechnological techniques. The analysis is carried out from a synthetic position of, on the one hand, the consequentialist conception of what is right and, on the other hand, the emphasis on individual liberties. As a result, firstly, the ethical appropriateness of adopting a general predisposition for allowing the neurorehabilitation of prisoners only if it is safe and if they give their consent will be defended. But, at the same time, reasons will be given for requiring, in certain circumstances, the exceptional use of neurotechnology to rehabilitate severely psychopathic prisoners, even against their will, from the same ethical perspective., This article was written as a part of the research project Digital Ethics.Moral Enhancement through an Interactive Use of Artificial Intelligence (PID2019-104943RB-I00), funded by the State Research Agency of the Spanish Government. Funding for open access charge: Universidad de Granada / CBUA

Microalgal biomass is a promising feedstock for biofuels, feed/food, and biomaterials. However, while production and commercialization of single-product commodities are still not economically viable, obtaining multiple products in a biomass biorefinery faces several techno-economic challenges. The aim of this study was to identify a suitable source of hydrolytic enzymes for algal biomass saccharification. Screening of twenty-six fungal isolates for secreted enzymes activity on Chlamydomonas reinhardtii biomass resulted in the identification of Aspergillus niger IB-34 as a candidate strain. Solid-state fermentation on wheat bran produced the most active enzyme preparations. From sixty-five proteins identified by liquid chromatography coupled to mass spectrometry (LC-MS) (ProteomeXchange, identifier PXD034998) from A. niger IB-34, the majority corresponded to predicted secreted proteins belonging to the Gene Ontology categories of catalytic activity/hydrolase activity on glycosyl and O-glycosyl compounds. Skimmed biomass of biotechnologically relevant strains towards the production of commodities, Chlorella sorokiniana and Scenedesmus obliquus, was fully saccharified after a mild pretreatment at 80 °C for 10 min, at a high biomass load of 10% (w/v). The soluble liquid stream, after skimming and saccharification of biomass of both strains, was further converted into ethanol by fermentation with Saccharomyces cerevisiae at a theoretical maximum efficiency, in a separated saccharification and fermentation assays. The resulting insoluble protein, after biomass skimming with an organic solvent and enzymatic saccharification, was highly digestible in an in vitro digestion assay. Proof of concept is presented for an enzyme-assisted biomass biorefinery recovering 81% of the main biomass fractions in a likely suitable form for the conversion of lipids and carbohydrates into biofuels and proteins into feed/food. KEY POINTS: • Twenty-six fungal extracts were analyzed for saccharification of microalgal biomass. • Skimmed biomass was fully enzymatically saccharified and fermented into ethanol. • Up to 81% recovery of biomass fractions suitable for biofuels and feed/food.

SARS‑CoV‑2 is a newly discovered member of the betacoronaviruses and the etiological agent of the disease COVID‑19. SARS‑CoV‑2 is responsible for the worldwide pandemic which has been taking place in 2020, and is causing a markedly higher number of infections and deaths compared to previous coronaviruses, such as SARS‑CoV or MERS‑CoV. Based on updated scientific literature, the present review compiles the most relevant knowledge of SARS‑CoV‑2, COVID‑19 and the clinical and typical responses that patients have exhibited against this virus, discussing current and future therapies, and proposing strategies with which to combat the disease and prevent a further global threat. The aggressiveness of SARS‑CoV‑2 arises from its capacity to infect, and spread easily and rapidly through its tight interaction with the human angiotensin‑converting enzyme 2 (ACE‑2) receptor. While not all patients respond in a similar manner and may even be asymptomatic, a wide range of manifestations associated with COVID‑19 have been described, particularly in vulnerable population groups, such as the elderly or individuals with other underlying conditions. The proper function of the immune system plays a key role in an individual's favorable response to SARS‑CoV‑2 infection. A hyperactivated response, on the contrary, could account for the more severe cases of COVID‑19, and this may finally lead to respiratory insufficiency and other complications, such as thrombotic or thromboembolic events. The development of novel therapies and vaccines designed to control and regulate a proper immune system response will be key to clinical management, prevention measures and effective population screening to attenuate the transmission of this novel RNA virus.

Polypyrrole adhesion to indium–tin oxide electrodes was improved by adding pre-hydrolyzed alkoxysilanes to the electrodeposition media. The pyrrole oxidation and film growth rates were studied by potentiostatic polymerization in acidic media. The morphology and thickness of the films were studied by contact profilometry and surface-scanning electron microscopy. The bulk and surface semiquantitative chemical composition was studied by Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. Finally, the adhesion was studied by scotch-tape adhesion test, where both alkoxysilanes showed a significant improvement in adhesion. We proposed a hypothesis for the improvement in adhesion, that involves the formation of siloxane material as well as in situ surface modification of the transparent metal oxide electrode.

ObjectivesTo evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID).MethodsMulticentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year.ResultsWe studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet’s disease (n=10), psoriatic arthritis (n=8), Crohn’s disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1),ConclusionsCZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs.

Background/purposeThe manifestations of uveitis are well established in axial spondyloarthritis (ax-SpA), but not in psoriatic arthritis (PsA). We aimed to assess, in a large unselected series of PsA: (A) the frequency and clinical features of uveitis; (B) its association with PsA activity, the impact of disease and functional disability, and (C) its relationship with the biological treatment. In addition, a literature review was performed.MethodsRetrospective longitudinal study of PsA patients from a single referral hospital. PsA was classified according to the CASPAR criteria, and uveitis was diagnosed by experienced ophthalmologists.ResultsWe studied 406 patients with PsA (46.3±12.3 years). Uveitis was observed in 20 (4.9%). Uveitis was acute in all cases, anterior (80%), unilateral (80%) and recurrent (50%). Patients with uveitis had a higher prevalence of HLA-B27 (45% vs 7.5%, pThe exposure adjusted incidence rate (episodes/100 patients-year) of uveitis before versus after biological treatment decreased with anti-TNFα monoclonal antibodies (56.3 vs 9.4) and increased with etanercept (ETN) (6.03 vs 24.2) and secukinumab (SECU) (0 vs 50) (including only one patient treated in the last two cases).ConclusionThe prevalence of uveitis in patients with PsA was about 5%. The pattern was similar to that observed in ax-SpA. Uveitis was associated with a worse quality of life and greater functional disability. The uveitis exposure adjusted incidence rate decreased with anti-TNFα monoclonal antibodies and increased with ETN and SECU.

Introduction: Elevated plasma α-klotho (αKl) protects against several ageing phenotypes and has been proposed as a biomarker of a good prognosis for different diseases. The beneficial health effects of elevated plasma levels of soluble αKl (SαKl) have been likened to the positive effects of exercise on ageing and chronic disease progression. It has also been established that molecular responses and adaptations differ according to exercise dose. The aim of this study is to compare the acute SαKl response to different exercise interventions, cardiorespiratory, and strength exercise in healthy, physically active men and to examine the behavior of SαKl 72h after acute strength exercise.Methods: In this quasi-experimental study, plasma SαKl was measured before and after a cardiorespiratory exercise session (CR) in 43 men, and strength exercise session (ST) in 39 men. The behavior of SαKl was also examined 24, 48, and 72h after ST.Results: Significant differences (time×group) were detected in SαKl levels (p=0.001; d=0.86) between CR and ST. After the ST intervention, SαKl behavior varied significantly (p=0.009; d=0.663) in that levels dropped between pre- and post-exercises (p=0.025; d=0.756) and were also significantly higher compared to pre ST values at 24h (p=0.033; d=0.717) and at 48h (p=0.015; d=0.827).Conclusions: SαKl levels increased in response to a single bout of cardiorespiratory exercise; while they decreased immediately after strength exercise, levels were elevated after 24h indicating different klotho protein responses to different forms of exercise.

The most prevalent diseases of our time, non-communicable diseases (NCDs) (including obesity, type 2 diabetes, cardiovascular diseases and some types of cancer) are rising worldwide. All of them share the condition of an “inflammatory disorder”, with impaired immune functions frequently caused or accompanied by alterations in gut microbiota. These multifactorial maladies also have in common malnutrition related to physiopathology. In this context, diet is the greatest modulator of immune system–microbiota crosstalk, and much interest, and new challenges, are arising in the area of precision nutrition as a way towards treatment and prevention. It is a fact that the westernized diet (WD) is partly responsible for the increased prevalence of NCDs, negatively affecting both gut microbiota and the immune system. Conversely, other nutritional approaches, such as Mediterranean diet (MD), positively influence immune system and gut microbiota, and is proposed not only as a potential tool in the clinical management of different disease conditions, but also for prevention and health promotion globally. Thus, the purpose of this review is to determine the regulatory role of nutritional components of WD and MD in the gut microbiota and immune system interplay, in order to understand, and create awareness of, the influence of diet over both key components.

Chronic venous disease (CVD) encompasses a set of disorders of the venous system that have a high prevalence in Western societies and are associated with significant sociohealth costs. Pregnancy is a period in which different hormonal and haemodynamic changes occur that lead to significant changes in the cardiovascular system, increasing the risk of developing venous problems, especially during the third trimester of gestation. In turn, CVD involves a series of local and systemic alterations that can have negative repercussions in pregnancy. In this context, the role of oxidative stress in the pathophysiology of this condition has been shown to significantly affect other vascular structures during pregnancy, such as the placenta. However, the effects of oxidative stress on the umbilical cord in women with CVD have not yet been fully elucidated. Thus, the objective of this study was to analyse the gene and protein expression of the enzymes NOX-1, NOX-2 and iNOS, which are involved in the production of reactive oxygen and nitrogen species, respectively. Similarly, the presence of hypoxia-inducible factor 1-alpha (HIF-1α) in the umbilical cord in women with CVD was compared to that of pregnant control women, and the levels of the lipid peroxidation marker malonyldialdehyde (MDA) in cord tissue and blood was also analysed. Our results support a significant increase in the enzymes NOX-1, NOX-2 and iNOS and HIF-1α and MDA in the umbilical cord tissue and blood of women with CVD. For the first time, our work demonstrates an increase in oxidative stress and cellular damage in the umbilical cords of pregnant women who develop this condition, deepening the understanding of the consequences of CVD during pregnancy.

Simple Summary During the recent years, the field of exercise and physical activity have expanded prominently, not only for the prevention but also for the management of different pathologies, including breast cancer. A broad range of studies have been conducted to analyze this relationship, in aim to find the best routines and use of exercise in breast cancer management. Although many works provide contradictory results in these terms, there is less doubt regarding the role of physical activity as a central support for breast cancer patients, due to the systemic benefits of exercise in these women, therefore decreasing the risk of breast cancer-related complications and increasing their quality of life and survival. Future research should be established in order to individualize the physical activity performed by these women based on the available scientific evidence in a multidisciplinary context to maximize the success of breast cancer management. Abstract Breast cancer (BC) is the most common malignancy and the second cause of cancer-related death among women. It is estimated that 9 in 10 cases of BC are due to non-genetic factors, and approximately 25% to 30% of total breast cancer cases should be preventable only by lifestyle interventions. In this context, physical activity represents an excellent and accessible approach not only for the prevention, but also for being a potential support in the management of breast cancer. The present review will collect the current knowledge of physical activity in the background of breast cancer, exploring its systemic and molecular effects, considering important variables in the training of these women and the evidence regarding the benefits of exercise on breast cancer survival and prognosis. We will also summarize the various effects of physical activity as a co-adjuvant therapy in women receiving different treatments to deal with its adverse effects. Finally, we will reveal the impact of physical activity in the enhancement of quality of life of these patients, to conclude the central role that exercise must occupy in breast cancer management, in an adequate context of a healthy lifestyle.

Actinomycosis is a chronic disease that is characterized by the formation of abscesses, fistulas and dense fibrous tissue at the site of involvement. Its distribution is worldwide. However, pelvic actinomycosis has increased in frequency and has been associated with abdominal surgery, intestinal perforation or trauma, due to the destruction of the muscular barrier. The clinical elements of suspicion are the latency of months and even years of symptoms and the history of being a carrier of an intrauterine device. Actinomyces israelli is a rare etiological agent of pelvic inflammatory disease, so it is difficult to reach the diagnosis. A case report is made of a 48-year-old patient with an intrauterine device older than 5 years, who entered the emergency department with abdominal pain syndrome and 7-day evolutionary fever accompanied by dyspareunia. She was hospitalized for antibiotic treatment, presenting an unsatisfactory evolution, with increased leukocytosis and persistent abdominal pain. An exploratory laparotomy with abdominal hysterectomy was performed. The histopathological diagnosis was pelvic inflammatory disease due to actinomyces. We must always suspect in the presence of a pelvic inflammatory disease in any of its clinical forms, the presence of actinomyces as one of the possible causative germs, especially in patients with intrauterine device for more than 5 years.

The case of a 49-year-old patient is reported, with a particular history of obstetric risk, who presented with severe transvaginal hemorrhage, was performed doppler arteriography and ultrasound, finding data suggestive of arteriovenous uterine malformation, surgery was decided due to heavy menstrual bleeding with anemia, the pathology report shows characteristics of an arteriovenous uterine malformation.

The overactive bladder syndrome is a chronic medical condition that affects the quality of life of patients whether men or women, has a prevalence of 16.5%, however, it is known to increase with age, affecting up to 25% of women older than 65 years and up to 80% in the elderly. More than 90% of cases have no apparent cause. The OAB (Overactive Bladder) It is a condition with characteristic symptoms of urinary urgency, usually accompanied by frequency and nocturia, with or without urge incontinence, in the absence of urinary tract infection or other obvious pathology. The different therapeutic steps are not always sufficient to restore the quality of life.

Background Polymorphisms in the proinflammatory cytokine genes tumor necrosis factor-α (TNF) and lymphotoxin-α (LTA, also called TNF-β) have been associated with asthma and atopy in some studies. Parental smoking is a consistent risk factor for childhood asthma. Secondhand smoke and ozone both stimulate TNF production. Objectives Our goal was to investigate whether genetic variation in TNF and LTA is associated with asthma and atopy and whether the association is modified by parental smoking in a Mexican population with high ozone exposure. Methods We genotyped six tagging single nucleotide polymorphisms (SNPs) in TNF and LTA, including functional variants, in 596 nuclear families consisting of asthmatics 4–17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests. Results The A allele of the TNF-308 SNP was associated with increased risk of asthma [relative risk (RR) = 1.54; 95% confidence interval (CI), 1.04–2.28], especially among children of non-smoking parents (RR = 2.06; 95% CI, 1.19–3.55; p for interaction = 0.09). Similarly, the A allele of the TNF-238 SNP was associated with increased asthma risk among children of nonsmoking parents (RR = 2.21; 95% CI, 1.14–4.30; p for interaction = 0.01). LTA SNPs were not associated with asthma. Haplotype analyses reflected the single SNP findings in magnitude and direction. TNF and LTA SNPs were not associated with the degree of atopy. Conclusions Our results suggest that genetic variation in TNF may contribute to childhood asthma and that associations may be modified by parental smoking.

The therapeutic options for patients with metastatic medullary thyroid carcinoma (MTC) have recently increased due to the development of tyrosine kinase inhibitors (TKIs), some of which have achieved remarkable clinical responses in MTC patients. However, the molecular basis for the large variability in TKI responses is unknown. In this exploratory study, we investigated the expression of eight key TKI target proteins (EGFR, KIT, MET, PDGFRB, VEGF (VEGFA), VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4)) by immunohistochemistry in 103 molecularly characterized MTC samples and identified the associated clinical and molecular features. A number of MTC samples exhibited a high expression of VEGFR2 and VEGFR3, which were overexpressed in 57 and 43% of the MTC samples respectively. VEGFR1, PDGFRB, VEGF, KIT, and MET were present in 34–20% of the cases, while EGFR was highly expressed in only 10% of the MTC samples. Some proteins exhibited large differences in expression between sporadic and familial cases, suggesting that differentRETmutations may be associated with the immunohistochemical profiles. MTC samples with the C634RETmutation exhibited a higher expression of VEGFR3 and KIT than the M918TRET-mutated and non-mutatedRETtumor samples (P=0.005 andP=0.007 respectively) and a lower expression of VEGFR1 (P=0.04). Non-mutatedRETMTC cases exhibited a lower expression of PDGFRB (P=0.04). Overall, this is the first study, to our knowledge, to show that multiple TKI targets are highly expressed in a subset of MTCs, suggesting that molecular stratification of patients may have the potential to improve TKI therapies for MTC.

Background S-nitrosothiols are potent endogenous bronchodilators depleted in asthmatic airway lining fluid. S-nitrosoglutathione reductase (GSNOR; also known as alcohol dehydrogenase 5 or formaldehyde dehydrogenase) catalyzes the metabolism of S-nitrosoglutathione (GSNO) and controls intracellular levels of S-nitrosothiols. GSNOR knockout mice have increased lung S-nitrosothiol levels and are therefore protected from airway hyperresponsiveness after methacholine or allergen challenge. Objective We sought to investigate whether genetic variation in GSNOR is associated with childhood asthma and atopy. Methods We genotyped 5 tagging and 2 additional single nucleotide polymorphisms (SNPs) in GSNOR in 532 nuclear families consisting of asthmatic children aged 4 to 17 years and both parents in Mexico City. Atopy was determined by means of skin prick testing. Results Carrying 1 or 2 copies of the minor allele of SNP rs1154404 was associated with decreased risk of asthma (relative risk [RR], 0.77; 95% CI, 0.61-0.97; P = .028 for 1 copy and RR, 0.66; 95% CI, 0.44-0.99; P = .046 for 2 copies). Homozygosity for the minor allele of SNP rs28730619 was associated with increased risk of asthma (RR, 1.60; 95% CI, 1.13-2.26; P = .0077). Haplotype analyses supported the single SNP findings. GSNOR SNPs were not associated with the degree of atopy. Conclusion This is the first study of genetic polymorphisms in GSNOR and asthma. These data suggest that genetic variation in GSNOR might play a role in asthma susceptibility. Clinical implications The association of GSNOR polymorphisms with asthma suggests a potential therapeutic target.

Background A recent microarray study implicated arginase I ( ARG1 ) and arginase II ( ARG2 ) in mouse allergic asthma models and human asthma. Objectives To examine the association between genetic variation in ARG1 and ARG2 and childhood asthma and atopy risk. Methods We enrolled 433 case-parent triads, consisting of patients with asthma 4 to 17 years old and their biologic parents, from the allergy clinic of a public hospital in Mexico City between 1998 and 2003. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped 4 single nucleotide polymorphisms (SNPs) of ARG1 and 4 SNPs of ARG2 with minor allele frequencies higher than 10% by using the TaqMan assay (Roche Molecular Systems, Pleasanton, Calif). Results ARG1 SNPs and haplotypes were not associated with asthma, but all 4 ARG1 SNPs were associated with the number of positive skin tests ( P = .007-.018). Carrying 2 copies of minor alleles for either of 2 highly associated ARG2 SNPs was associated with a statistically significant increased relative risk (RR) of asthma (1.5, 95% CI=1.1-2.1 for arg2s1; RR=1.6, 95% CI=1.1-2.3 for arg2s2). The association was slightly stronger among children with a smoking parent (arg2s1 RR=2.1, 95% CI=1.2 - 3.9 with a smoking parent; RR=1.2, 95% CI=0.8-1.9 without; interaction P = .025). Haplotype analyses reduced the sample size but supported the single SNP results. One ARG2 SNP was related to the number of positive skin tests ( P = .027). Conclusion Variation in arginase genes may contribute to asthma and atopy in children.