The impact of Ibero-American science on global bioethical thinking.

The bioethics research conducted in Ibero-American countries has been very much restricted to its own realm. The aim of this study was to perform a bibliometric evaluation of bioethics papers by authors affiliated with Ibero-American institutions, and to determine how their work influences global bioethics literature. We performed a literature search in the Web of Science Core Collection (WoS CC) and Scopus. We identified a total of 5,975 documents, of which 84.3% were articles, 11.6% reviews and 4.1% book chapters. The median number of citations per paper was higher in English-language journals. Only 10 articles published between 2010 and 2019 in peer-reviewed bioethics journals and produced exclusively by authors from Ibero-American institutions garnered more than 15 citations. Our study suggests that if researchers from Ibero-American institutions want to influence global bioethical thinking, they must make the required leap in quality to be able to publish in high-quality bioethics and mainstream journals.

The Vatican Opinion on Gender Theory.

This article is a reasoned response to the article by Timothy F. Murphy, recently published in the prestigious journal Bioethics, on the supposed opposition between the views of the Catholic Church and what he calls "contemporary science" in relation to certain anthropological issues linked to the gender perspective. To point to "the Vatican" as anchored in an unscientific and anachronistic position, using the term contemporary science to which he attributes a unanimous representation of current scientific thinking on the subject is, in our view, unfounded and completely unacceptable. In his reflection, he does not adequately distinguish between intersex and transgenderism, two clearly different realities with different needs. The author defends the obsolescence of the binary sex/gender model that, in his view, "betrays human sexuality." Furthermore, he does so without providing a plausible justification or a definition of human nature that is able to support the plurality and indeterminacy of sexual conditions, without falling back on untenable dualisms or relativism devoid of scientific objectivity. In our response, we highlight how the dialogue between Faith and Reason, as developed in the recent Magisterium of the Catholic Church, is essential to explain nature, the human being and, in general, all creations. Finally, contemporary science does not provide a monolithic and unquestionable view of the nature of human beings and their sexual identity, as the author claims, with many scientists confirming evidence of a binary human sexuality genetically and phenotypically determined. SUMMARY: This paper is a reasoned response to the supposed opposition between the views of the Catholic Church and "contemporary science" in relation to certain anthropological issues linked to the gender perspective.The dialogue between Faith and Reason, as developed in the recent Magisterium of the Catholic Church, is essential to explain nature, the human being and, in general, all creation, against the opinion of those who defend the obsolescence of the binary sex/gender model that, in their view, "betrays human sexuality".

The Use of NFP When Pregnancy Is Contraindicated?

The Sacred Congregation for the Doctrine of the Faith has declared the moral liceity of hysterectomy when certain medical criteria are met but does not exclude other options, "for example, recourse to infertile periods or total abstinence." Consequently, there may be couples who prefer to use natural family planning (NFP) methods. We shall refer to these in this article. The efficacy of NFP methods is determined by knowing the day of ovulation. To that end, three parameters are used: the presence and consistency of cervical mucus, measurement of the basal body temperature, and the determination of particular hormones in urine. Of the NFP methods used, the so-called sympto-thermal method seems to be the most effective. It has been concluded that the postovulatory or luteal phase of the female menstrual cycle is the safest time to avoid pregnancy if the couple has sexual intercourse during this period. Nevertheless, the use of NFP methods has limitations if the length of the cycles varies, there are fluctuations in the basal temperature, or when there are vaginal infections. Urinary hormone levels can also be altered by the use of antibiotics or psychotropic drugs. In general, however, it can be concluded that NFP methods, if used in the conditions mentioned herein, offer a high degree of reliability, similar to that of artificial contraceptive methods. Accordingly, if pregnancy must be avoided in the medical circumstances to which the Congregation for the Doctrine of the Faith refers, NFP methods can effectively replace hysterectomy, thereby circumventing the medical difficulties of this practice. SUMMARY: The Sacred Congregation for the Doctrine of the Faith has declared the moral liceity of hysterectomy when certain medical criteria are met but does not exclude other options, "for example, recourse to infertile periods or total abstinence." Consequently, there may be couples who prefer to use natural family planning (NFP) methods. We shall refer to these in this article. In general, it can be concluded that NFP methods, if used in the conditions mentioned herein, offer a high degree of reliability, similar to that of artificial contraceptive methods. Accordingly, if pregnancy must be avoided in the medical circumstances to which the Congregation for the Doctrine of the Faith refers, NFP methods can effectively replace hysterectomy, thereby circumventing the medical difficulties of this practice.

The Conception of Synthetic Entities from a Personalist Perspective.

Synthetic biology opens up the possibility of producing new entities not found in nature, whose classification as organisms or machines has been debated. In this paper we are focusing on the delimitation of the moral value of synthetic products, in order to establish the ethically right way to behave towards them. In order to do so, we use personalism as our ethical framework. First, we examine how we can distinguish between organisms and machines. Next, we discuss whether the products of synthetic biology can be considered organisms at all and assess what their moral value is and how should we behave towards them. Finally, we discuss the hypothetical case of synthetic humans.

Gestational Surrogacy: Current View.

Surrogate motherhood is an assisted procreation practice by which a woman gestates an embryo with which she has no biological relationship on behalf of a contracting couple or individual, having to relinquish the child to them after its birth. This practice normally entails a financial remuneration for the pregnant woman; when this is not the case, it is called altruistic surrogacy. From a medical perspective, potential problems for the surrogate and for children born through this practice should be taken into account, especially the existence of possible disabilities in the child. The bioethical aspects are of most interest because the practice of surrogacy objectifies the expectant mother, by using her body for a purpose other than her own good, treating her as a commodity, as a thing. The same is true for the child because it makes him a disposable object, something that can be instrumentalized, similarly objectifying him.

A Personalist Ontological Approach to Synthetic Biology.

Although synthetic biology is a promising discipline, it also raises serious ethical questions that must be addressed in order to prevent unwanted consequences and to ensure that its progress leads toward the good of all. Questions arise about the role of this discipline in a possible redefinition of the concept of life and its creation. With regard to the products of synthetic biology, the moral status that they should be given as well as the ethically correct way to behave towards them are not clear. Moreover, risks that could result from a misuse of this technology or from an accidental release of synthetic organisms into the environment cannot be ignored; concerns about biosecurity and biosafety appear. Here we discuss these and other questions from a personalist ontological framework, which defends human life as an essential value and proposes a set of principles to ensure the safeguarding of this and other values that are based on it.

Does levonorgestrel emergency contraceptive have a post-fertilization effect? A review of its mechanism of action.

BACKGROUND: Recent studies have identified that levonorgestrel administered orally in emergency contraception (LNG-EC) is only efficacious when taken before ovulation. However, the drug does not consistently prevent follicular rupture or impair sperm function. OBJECTIVE: The present systematic review is performed to analyze and more precisely define the extent to which pre-fertilization mechanisms of action may explain the drug's efficacy in pregnancy avoidance. We also examine the available evidence to determine if pre-ovulatory drug administration may be associated with post-fertilization effects. CONCLUSION: The mechanism of action of LNG-EC is reviewed. The drug has no ability to alter sperm function at doses used in vivo and has limited ability to suppress ovulation. Our analysis estimates that the drug's ovulatory inhibition potential could prevent less than 15 percent of potential conceptions, thus making a pre-fertilization mechanism of action significantly less likely than previously thought. Luteal effects (such as decreased progesterone, altered glycodelin levels, and shortened luteal phase) present in the literature may suggest a pre-ovulatory induced post-fertilization drug effect. LAY SUMMARY: Plan B is the most widely used emergency contraceptive available. It is important for patients and physicians to clearly understand the drug's mechanism of action (MOA). The drug was originally thought to work by preventing fertilization. Recent research has cast doubt on this. Our review of the research suggests that it could act in a pre-fertilization capacity, and we estimate that it could prevent ovulation in only 15 percent or less of cases. The drug has no ability to alter sperm function and limited ability to suppress ovulation. Further, data suggest that when administered pre-ovulation, it may have a post-fertilization MOA.

Ethical aspects of nuclear and mitochondrial DNA transfer.

Somatic cell nuclear transfer (SCNT) (cloning), as a reproductive or therapeutic method, and mitochondrial DNA transfer, as a method to prevent the transmission of mitochondrial diseases, are analyzed in this paper from a bioethics perspective. The licit purpose of being able to treat certain diseases, as in the case of SCNT, cannot justify, in any case, resorting to illicit means such as the manipulation, selection, and elimination of human embryos in the blastocyst phase, by using cell lines obtained from them. Crossing this line paves the way (as utilitarian ethics advocates) to assuming any cost in scientific experimentation so long as satisfactory results are obtained. With mitochondrial replacement, either human embryos are directly manipulated (pronuclear transfer) or germline cells are manipulated (maternal spindle transfer); changes in these could be transmitted to the offspring. LAY SUMMARY: This article analyzes somatic cell nuclear transfer (cloning) and mitochondrial DNA transfer techniques, in both reproductive and therapeutic applications, and preventive methods in the transmission of mitochondrial diseases, from a bioethical perspective. The manipulation, selection, and elimination of human embryos delimits the ethical acceptability of these promising techniques.

Ethical considerations of universal vaccination against human papilloma virus.

BACKGROUND: From an epidemiological perspective, the practice of universal vaccination of girls and young women in order to prevent human papilloma virus (HPV) infection and potential development of cervical cancer is widely accepted even though it may lead to the neglect of other preventive strategies against cervical cancer. DISCUSSION: It is argued that removing the deterrent effect--the fear of developing cancer--could encourage teenage sex. This paper reflects on the ethical legitimacy of the universal vaccination of girls and young women against HPV infection, especially regarding safety issues, the need to vaccinate people who have opted to abstain from sex, the presumption of early onset of sexual relations, the commercial interests of the companies that manufacture the vaccine, and the recommendation of universal vaccination in males. SUMMARY: Based on the aforementioned information, we believe that the universal vaccination against HPV in young women is acceptable from an ethical point of view, given the medical advantages it presents.

Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger-Huët anomaly).

Pelger-Huët anomaly (PHA; OMIM *169400) is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes. Affected individuals show hypolobulated neutrophil nuclei with coarse chromatin. Presumed homozygous individuals have ovoid neutrophil nuclei, as well as varying degrees of developmental delay, epilepsy and skeletal abnormalities. Homozygous offspring in an extinct rabbit lineage showed severe chondrodystrophy, developmental anomalies and increased pre- and postnatal mortality. Here we show, by carrying out a genome-wide linkage scan, that PHA is linked to chromosome 1q41-43. We identified four splice-site, two frameshift and two nonsense mutations in LBR, encoding the lamin B receptor. The lamin B receptor (LBR), a member of the sterol reductase family, is evolutionarily conserved and integral to the inner nuclear membrane; it targets heterochromatin and lamins to the nuclear membrane. Lymphoblastoid cells from heterozygous individuals affected with PHA show reduced expression of the lamin B receptor, and cells homozygous with respect to PHA contain only trace amounts of it. We found that expression of the lamin B receptor affects neutrophil nuclear shape and chromatin distribution in a dose-dependent manner. Our findings have implications for understanding nuclear envelope-heterochromatin interactions, the pathogenesis of Pelger-like conditions in leukemia, infection and toxic drug reactions, and the evolution of neutrophil nuclear shape.

Opinion of physicians and the general population on the legalization of euthanasia and assisted suicide.

In some countries, particularly Spain, one of the arguments used to justify the legalization of euthanasia is that there is a strong social demand for it. To try to ascertain the truth of this statement, we review different surveys of physicians and the general public, to determine their opinion on whether or not to legalize this practice. We found that the percentage of respondents who approve this practice varies widely from one country to another, with some countries in which approval is close to 80% and others in which it fails to reach even 40%. It has been suggested that this may be because the questions included in the various surveys differ greatly, since not all use the word ″euthanasia″ directly, replacing it with words or phrases of similar meaning. Thus, some respondents may not quite identify them with euthanasia. We conclude that, in the vast majority of countries, there does not seem to be an objective social demand to justify the legalization of euthanasia.

[CRISPR-CAS9. The greatest advancement in genetic edition techniques requires an ethical reflection]. / CRISPR-CAS9. El mayor avance en técnicas de edición genética requiere una reflexión ética.

The adaptation of the CRISPR system as a genetic editing tool has led to a revolution in many fields of application, as this technique is considerably faster, easier to perform and more efficient than predecessor techniques. However, some of these applications raise objective ethical issues that must be addressed. In this paper we discuss, based on the most recent data, the different issues related to CRISPR applications on the germ line, its introduction in clinical trials, the genetic edition of animals and plants for human consumption and the novel gene drive.

Partial inhibition of platelet thromboxane A2 synthesis by aspirin is associated with myonecrosis in patients with ST-segment elevation myocardial infarction.

Heterogeneity in response to aspirin (ASA) treatment, or "aspirin resistance," could be of importance in patients with ST-segment elevation myocardial infarction (STEMI). Decreased effects of ASA in platelets could be due to partial inhibition of cyclo-oxygenase-1 (COX-1) or to COX-1-independent mechanisms. We evaluated the effect of ASA treatment in patients with STEMI for (1) platelet thromboxane A(2) (TXA(2)) synthesis, (2) platelet recruitment elicited by TXA(2)-dependent and -independent mechanisms, and (3) a possible association of these aspects of platelet reactivity with serum markers of myonecrosis. We studied 62 ASA-treated patients within 48 hours of onset of the acute event and 69 ASA-free and 10 ASA-treated controls. TXA(2) synthesis and platelet recruitment (fluid-phase proaggregate activity of cell-free releasate) were assessed after collagen stimulation (1 micro g/ml) of whole blood. Partial inhibition of TXA(2) by ASA was found in 21 patients (34%). This was associated with significant increases in troponin T, creatine kinase-MB mass, creatine kinase, and recruiting activity versus 41 patients with blocked TXA(2) production. This was independent of fibrinolysis, and platelet COX-2 expression was not augmented. TXA(2) blockade was achieved after subsequent daily treatments or platelet incubation with ASA in vitro, suggesting lower sensitivity of COX-1 to ASA. In addition, 28 patients (45%) had an abnormally increased recruiting activity despite TXA(2) blockade, which was also associated with increased myonecrosis. In conclusion, ASA resistance, elicited by TXA(2)-dependent and TXA(2)-independent mechanisms, was prevalent in patients with STEMI. This study describes, for the first time, the association of partial platelet TXA(2) inhibition with myonecrosis.

Sialic acid is an inflammation marker associated with a history of deep vein thrombosis.

INTRODUCTION: Deep vein thrombosis (DVT) induces a systemic chronic inflammation and it has been associated with atherosclerosis. Increased levels of total sialic acid (TSA) have been shown to correlate with inflammation and atherosclerotic processes. The aim of this study was to investigate whether or not increased levels of TSA are associated with a history of DVT and with inflammation and coagulation markers, as well as with the lipid profile. MATERIALS AND METHODS: TSA, fibrinogen, C-reactive protein (CRP), fibrin D-dimer (D-dimer), prothrombin fragment 1+2 (F1+2), endogenous thrombin generation, cholesterol and triglycerides were measured in 68 patients who had suffered, in the previous 6-12 months, a first episode of idiopathic DVT, and in 68 age- and sex-matched healthy subjects. RESULTS: Levels of TSA, fibrinogen, CRP and D-dimer observed in patients were significantly higher than those detected in healthy subjects. TSA positively correlated with fibrinogen (R=0.47, p<0.01), cholesterol (R=0.46, p<0.01), triglycerides (R=0.38, p<0.01) and CRP (R=0.28, p<0.05). The logistic regression analysis confirmed that both high fibrinogen (> or =340 mg/dl) and cholesterol (> or =267 mg/dl) levels significantly and independently influence the TSA concentration. TSA levels above the 95th percentile of controls (>72 mg/dl) were detected in 33% of patients (OR=8.9; p<0.0001; 95% CI 2.4 to 31.7). CONCLUSIONS: Patients with a history of DVT had associated high levels of TSA. In these patients, TSA correlated to markers of inflammation activity and lipid profile. Thus, TSA appears to be a useful vascular inflammatory marker in idiopathic DVT.

Mitochondrial Modification Techniques and Ethical Issues.

Current strategies for preventing the transmission of mitochondrial disease to offspring include techniques known as mitochondrial replacement and mitochondrial gene editing. This technology has already been applied in humans on several occasions, and the first baby with donor mitochondria has already been born. However, these techniques raise several ethical concerns, among which is the fact that they entail genetic modification of the germline, as well as presenting safety problems in relation to a possible mismatch between the nuclear and mitochondrial DNA, maternal mitochondrial DNA carryover, and the "reversion" phenomenon. In this essay, we discuss these questions, highlighting the advantages of some techniques over others from an ethical point of view, and we conclude that none of these are ready to be safely applied in humans.

Thrombophilic risk factors and homocysteine levels in Behçet's disease in eastern Spain and their association with thrombotic events.

Behçet's disease (BD) is a chronic inflammatory disorder in which thrombosis occurs in about 30% of patients. The prothrombotic mechanisms are unknown. Thrombophilic defects and hyperhomocysteinaemia may be involved in the pathogenesis of thrombotic events, although results have been controversial. Moreover, no information is available on this issue for eastern Spain. We studied the prevalence of inherited and acquired thrombophilic risk factors in 79 patients with BD (43 men, 36 women) who had (n = 23) or did not have (n = 56) thrombosis, and in 84 healthy control subjects (42 men, 42 women). Risk factors examined were antithrombin, protein C and protein S levels, factor V Leiden, the prothrombin G20210A mutation, the methylenetetrahydrofolate reductase C677T polymorphism, and acquired thrombophilic risk factors, including anticardiolipin antibodies, lupus anticoagulant, and serum homocysteine levels. There were no differences between patients and controls in any of the parameters studied. When we studied BD patients with and without thrombotic events, the only thrombophilic defect that differed was the prothrombin G20210A mutation: Three out of 23 patients with thrombosis were carriers, compared with none of 56 patients without thrombosis (p = 0.022). Two of the three carriers developed catastrophic or recurrent thrombotic episodes; one was a homozygous carrier of the G20210A prothrombin mutation and the other was doubly heterozygous for the G20210A prothrombin mutation and factor V Leiden. A meta-analysis demonstrated an association of factor V Leiden and prothrombin mutation with thrombosis in BD. When studies from Turkey were excluded from the meta-analysis, only the prothrombin G20210A mutation was associated with thrombosis.

Effect of doxazosin gastrointestinal therapeutic system on platelet degranulation and platelet-leukocyte microaggregate formation induced by physiologic shear stress in hypertension.

INTRODUCTION: In this prospective, ex vivo, single-blind study, the effect of doxazosin on platelet function was studied in patients with hypertension. MATERIALS AND METHODS: Platelet activation by shear stress was measured in whole blood samples of 22 hypertensive patients and 22 normotensive controls, using flow cytometry. Sheared samples were evaluated for CD62 expression, microaggregate formation, and Ca2+ mobilization. Results were collected at baseline and after 1 and 2 months of single-dose (4 mg/d) extended-release doxazosin gastrointestinal therapeutic system therapy. RESULTS: Doxazosin normalized blood pressure in hypertensive patients after 1 and 2 months of treatment. Hypertensive patients had a higher baseline percentage (mean+/-SD) of degranulated platelets (CD62+) than the normotensive control group (4.14+/-1.05 vs. 2.47+/-0.68, P<0.01). After 2 months of doxazosin gastrointestinal therapeutic system treatment, the percentage of CD62+ in the experimental group significantly decreased (P<0.05). At baseline, the number of platelet-leukocyte aggregates in vivo was greater in hypertensive patients (P<0.01); doxazosin did not normalize this measurement. Following shearing, platelet expression of CD62 increased significantly in the hypertensive group (P<0.001 vs. control). Shear stress-induced platelet activation and microaggregate formation were also greater in hypertensive patients. Intraplatelet-free calcium concentration was higher in hypertensive patients at baseline than in the normotensive group (P<0.001). At 2 months, doxazosin significantly reduced thrombin-stimulated Ca2+ mobilization in hypertensive patients (P<0.01 vs. baseline). CONCLUSIONS: Platelets from hypertensive patients are more readily activated by shear stress and demonstrate significant alterations in cytoplasmic-free calcium mobilization. Doxazosin treatment reduced blood pressure and normalized alterations in platelet function.