Bioethical Conflicts in Current Dermatology: A Narrative Review. / Conflictos bioéticos en la dermatología actual: una revisión narrativa.

Both the functions and equipment of dermatologists have increased over the past few years, some examples being cosmetic dermatology, artificial intelligence, tele-dermatology, and social media, which added to the pharmaceutical industry and cosmetic selling has become a source of bioethical conflicts. The objective of this narrative review is to identify the bioethical conflicts of everyday dermatology practice and highlight the proposed solutions. Therefore, we conducted searches across PubMed, Web of Science and Scopus databases. Also, the main Spanish and American deontological codes of physicians and dermatologists have been revised. The authors recommend declaring all conflicts of interest while respecting the patients' autonomy, confidentiality, and privacy. Cosmetic dermatology, cosmetic selling, artificial intelligence, tele-dermatology, and social media are feasible as long as the same standards of conventional dermatology are applied. Nonetheless, the deontological codes associated with these innovations need to be refurbished.

Pesticide exposure and gender discrepancy in breast cancer.

OBJECTIVE: It is biologically plausible that occupational and environmental pesticide exposure may contribute to breast cancer risk. Persistent chemical compounds, such as pesticides, tend to be lipophilic and are detected in human breast milk and adipose tissue. Therefore, the present systematic review aims to clarify the gender difference in breast cancer concerning pesticide exposure. MATERIALS AND METHODS: A total of 70 studies satisfied the inclusion criteria and were included in the systematic review. RESULTS: From the studies analyzed, it was observed that exposure to pesticides could be a risk factor for breast cancer in women, in particular in young women and in women who experienced menarche at a young age. In contrast, no association was found for breast cancer in men. Female breast cancer is correlated with estrogen receptor-negative tumor characteristics. Breast cancer in men was no correlated with pesticide exposure. CONCLUSIONS: Breast cancer in women has been linked to estrogen receptor positivity, but this positivity appears to be inversely related to fertility. The estrogen-like effects of organochlorine pesticides could be the cause of the observed gender differences.

Identification of new SNPs in native South American populations by resequencing the Y chromosome.

The Y-chromosomal genetic landscape of South America is relatively homogenous. The majority of native Amerindian people are assigned to haplogroup Q and only a small percentage belongs to haplogroup C. With the aim of further differentiating the major Q lineages and thus obtaining new insights into the population history of South America, two individuals, both belonging to the sub-haplogroup Q-M3, were analyzed with next-generation sequencing. Several new candidate SNPs were evaluated and four were confirmed to be new, haplogroup Q-specific, and variable. One of the new SNPs, named MG2, identifies a new sub-haplogroup downstream of Q-M3; the other three (MG11, MG13, MG15) are upstream of Q-M3 but downstream of M242, and describe branches at the same phylogenetic positions as previously known SNPs in the samples tested. These four SNPs were typed in 100 individuals belonging to haplogroup Q.

GHEP-ISFG collaborative exercise on mixture profiles of autosomal STRs (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03): results and evaluation.

One of the main objectives of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the area of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles. Until now, three exercises have been organized (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03), with 32, 24 and 17 participant laboratories respectively. The exercise aims to give a general vision by addressing, through the proposal of mock cases, aspects related to the edition of mixture profiles and the statistical treatment. The main conclusions obtained from these exercises may be summarized as follows. Firstly, the data show an increased tendency of the laboratories toward validation of DNA mixture profiles analysis following international recommendations (ISO/IEC 17025:2005). Secondly, the majority of discrepancies are mainly encountered in stutters positions (53.4%, 96.0% and 74.9%, respectively for the three editions). On the other hand, the results submitted reveal the importance of performing duplicate analysis by using different kits in order to reduce errors as much as possible. Regarding the statistical aspect (GHEP-MIX02 and 03), all participants employed the likelihood ratio (LR) parameter to evaluate the statistical compatibility and the formulas employed were quite similar. When the hypotheses to evaluate the LR value were locked by the coordinators (GHEP-MIX02) the results revealed a minor number of discrepancies that were mainly due to clerical reasons. However, the GHEP-MIX03 exercise allowed the participants to freely come up with their own hypotheses to calculate the LR value. In this situation the laboratories reported several options to explain the mock cases proposed and therefore significant differences between the final LR values were obtained. Complete information concerning the background of the criminal case is a critical aspect in order to select the adequate hypotheses to calculate the LR value. Although this should be a task for the judicial court to decide, it is important for the expert to account for the different possibilities and scenarios, and also offer this expertise to the judge. In addition, continuing education in the analysis and interpretation of mixture DNA profiles may also be a priority for the vast majority of forensic laboratories.

Euroforgen-NoE collaborative exercise on LRmix to demonstrate standardization of the interpretation of complex DNA profiles.

There has been very little work published on the variation of reporting practices of mixtures between laboratories, but it has been previously demonstrated that there is little consistency. This is because there is no current uniformity of practice, so different laboratories will operate using different rules. The interpretation of mixtures is not solely a matter of using some software to provide 'an answer'. An assessment of a case will usually begin with a consideration of the circumstances of a crime. Assumptions made about the numbers of contributors follow from an examination of the electropherogram(s)--and these may differ between the prosecution and the defence hypotheses. There may be a necessity to evaluate several sets of hypotheses for any given case if the circumstances are uncertain. Once the hypotheses are formulated, the mathematical analysis is complex and can only be accomplished by the use of specialist software. In order to obtain meaningful results, it is essential that scientists are trained, not only in the use of the software, but also in the methodology to understand the likelihood ratio concept that is used. The Euroforgen-NoE initiative has developed a training course that utilizes the LRmix program to carry out the calculations. This software encompasses the recommendations of the ISFG DNA commissions on mixture interpretation and is able to interpret samples that may come from two or more contributors and may also be partial profiles. Recently, eighteen different laboratories were trained in the methodology. Afterwards they were asked to independently analyze two different cases with partial mixture DNA evidence and to write a statement court-report. We show that by introducing a structured training programme, it is possible to demonstrate, for the first time, that a high degree of standardization, leading to uniformity of results can be achieved by participating laboratories.

Undergraduate teaching of occupational medicine in European schools of medicine.

PURPOSE: General practitioners play or should play a role in occupational medicine (OM), either in diagnosing occupational diseases or in counseling on return to work. Nevertheless, their training has been reported to be insufficient in most single country studies. AIMS: The objectives of this study were to analyze the content and extent of undergraduate teaching of OM in European medical schools. METHODS: An e-mail questionnaire survey of the teaching of OM to undergraduates was undertaken from December 2010 to April 2011 in all medical schools and medical faculties listed in 27 European countries (n = 305). RESULTS: Among the 305 universities identified, 135 answered to the questionnaire, giving a response rate of 44%. The mean number of hours given to formal instruction in occupational medicine to medical undergraduates was 25.5 h. Nevertheless, this number of hours varied widely between countries, but also within countries. Overall, 27% of medical schools gave their students 10 h of teaching or less, 52% 20 h or less and 69% 30 h or less. Whereas occupational diseases and principles of prevention were covered in most schools, disability and return to work were very poorly represented among the topics that were taught to students. CONCLUSION: Dedicated undergraduate teaching on occupational health or OM in European medical schools is present in most medical schools, usually at a low level, but is very variable between and within countries. Medical schools across Europe are very unequal to provide qualifying doctors education on the topics they will frequently come across in their working lives.

Association between ancient bone preservation and dna yield: a multidisciplinary approach.

Ancient molecular typing depends on DNA survival in archaeological bones. Finding valuable tools to predict DNA presence in ancient samples, which can be measured prior to undertaking a genetic study, has become an important issue as a consequence of the peculiarities of archaeological samples. Since the survival of DNA is explained by complex interrelations of multiple variables, the aim of the present study was to analyze morphological, structural, chemical, and biological aspects of a set of medieval human bones, to provide an accurate reflection of the state of preservation of the bony components and to relate it with DNA presence. Archaeological bones that yielded amplifiable DNA presented high collagen content (generally more than 12%), low racemization values of aspartic acid (lesser than 0.08), leucine and glutamic acid, low infrared splitting factor, small size of crystallite, and more compact appearance of bone in the scanning electron micrographs. Whether these patterns are characteristic of ancient bones or specific of each burial site or specimen requires further investigation.

Genetic uniqueness of the Waorani tribe from the Ecuadorian Amazon.

South America and especially the Amazon basin is known to be home to some of the most isolated human groups in the world. Here, we report on a study of mitochondrial DNA (mtDNA) in the Waorani from Ecuador, probably the most warlike human population known to date. Seeking to look in more depth at the characterization of the genetic diversity of this Native American tribe, molecular markers from the X and Y chromosomes were also analyzed. Only three different mtDNA haplotypes were detected among the Waorani sample. One of them, assigned to Native American haplogroup A2, accounted for more than 94% of the total diversity of the maternal gene pool. Our results for sex chromosome molecular markers failed to find close genetic kinship between individuals, further emphasizing the low genetic diversity of the mtDNA. Bearing in mind the results obtained for both the analysis of the mtDNA control region and complete mitochondrial genomes, we suggest the existence of a 'Waorani-specific' mtDNA lineage. According to current knowledge on the phylogeny of haplogroup A2, we propose that this lineage could be designated as subhaplogroup A2s. Its wide predominance among the Waorani people might have been conditioned by severe genetic drift episodes resulting from founding events, long-term isolation and a traditionally small population size most likely associated with the striking ethnography of this Amazonian community. In all, the Waorani constitute a fine example of how genetic imprint may mirror ethnopsychology and sociocultural features in human populations.

SNPSTR rs59186128_D7S820 polymorphism distribution in European Caucasoid, Hispanic, and Afro-American populations.

Single nucleotide polymorphisms (SNPs) in the flanking regions of microsatellite loci (SNPSTRs) help to increase the power of discrimination of short tandem repeat (STR) loci. SNPs are positions in the genome that have been well-conserved over the course of evolution, so analysing them can help distinguish between STR alleles in which the number of repetitions matches due to descent from those which match by chance. This provides support for the determination of biological paternity and other kinship analyses in which mutation needs to be ruled out as grounds for exclusion. Locus D7S820 shows a variable position, SNP rs59186128, in the 5' flanking region. This study is set out (1) to determine the frequencies of SNP rs59186128 in populations with various geographical origins and (2) to estimate the possible contribution of rs59186128 to the allele discrimination of locus D7S820. To that end, individuals from European Caucasoid, Hispanic, and Afro-American populations are studied using denaturing high-performance liquid chromatography, which enables locus rs59186128 to be quickly and highly cost-effectively screened. Moreover, a method is established for determining the haplotypes of SNPSTR rs59186128_D7820. The results show that SNP rs59186128 has a T allele frequency of more than 0.15 in one of the Afro-American populations studied, and the haplotype analysis shows that there is no preferential association between the alleles of SNPSTR rs59186128_D7S820, which supports the idea that they could be useful in forensic applications.

Association between immunohistochemical markers of myocardial damage and apoptosis.

Cardiac disease is the most common cause of sudden unexpected death. In forensic practice there is a need for more sensitive diagnostic methods for the post-mortem diagnosis of myocardial damage. The aim of this study was to evaluate the association of the markers routinely used for the diagnosis of acute cardiac necrosis (myosin, troponin I and myoglobin with) and the presence of apoptosis, in order to evaluate the utility of apoptosis for use as a diagnostic marker during the early stage of acute myocardial damage. A positive correlation was observed between neovascularization and signs of recent and past necrosis. Not relationship was observed between age at death, post-mortem interval and apoptosis. No statistical association was found between the expression of acute cardiac necrosis markers and the presence of apoptosis.

e-Learning strategies in occupational legal medicine based on problem solving through "CASUS" system.

The use of online teaching tools facilitate the incorporation of self-learning methods. With a view to encouraging convergence in teaching tools and methods in Occupational Legal Medicine, an initiative was set up within the classes of Legal and Forensic Medicine at Saragossa University, as part of the EU funded NetWoRM project, which has been led since 1999 by Ludwig-Maximilians-Universität in Munich (Germany). The interest of medical students in Occupational Legal Medicine has so far been low and in addition different aspects complicate the teaching of Occupational Legal Medicine at medical schools: One reason for the low interest is the limited availability of bedside teaching, one of the students' most favourite and effective way to learn. The reason for that is that most medical schools with occupational departments only have outpatient clinics. "Interesting" patients who be need for educational purposes are therefore only available for a limited part of the day. However, in order to recognize and prevent occupational disorders each medical student and physician needs profound clinical knowledge in Occupational Legal Medicine. This project has proven to be highly efficient in permitting the creation and validation of teaching tools which cover and improve the traditional training of the Occupational Legal Medicine programme imparted in the degree of Medicine.

A preliminary study on the incidence of heteroplasmy in mitochondrial DNA from vitreous humour.

Vitreous humour is routinely sampled in Forensic Medicine as several post-mortem analyses can be performed. However, it is not used for DNA analyses probably due to its scarce cellularity. In these samples, in which the study of nuclear DNA is difficult, the analysis of mtDNA is an alternative approach. The aim of this study was to investigate the utility of vitreous humour for forensic identification purposes. Samples were collected during vitrectomy from retinopathy patients, in collection bags with saline solution. Blood samples were also obtained in order to contrast results. Before DNA organic extraction, several centrifugation steps were needed to concentrate the vitreous humour samples. Unlike blood, direct amplification of 400-bp fragments of the hipervariable regions I and II (HVI and HVII) was not successful, possibly due to damage to the DNA strand caused by the surgery conditions (UV radiation, oxidative stress). Therefore, amplification of two overlapping fragments for each control region was performed in vitreous humour. In order to eliminate undesired products, all samples were purified by an enzymatic method. Thereafter, mtDNA fragments were sequenced using dye terminators in a MegaBACE 500 capillary sequencer. Sequences of HVI and HVII of approximately 400 bp were obtained from all samples. The sequences obtained from each patient matched almost perfectly those from blood. In summary, herein we describe for the first time a methodology suitable for the mtDNA analysis of vitreous humour samples.

Polymorphism C3435T of the MDR1 gene in Central Americans and Spaniards.

The human multidrug resistance gene (MDR1) encodes for P-glycoprotein (P-gp) which is a transmembrane transporter protein that acts as an efflux pump for a number of lypophilic compounds. It plays a protective role for cells against DNA damage. The wobble C3435T polymorphism at exon 26 has been associated with different expression levels and activity. Differences in allele frequency of the C3435T polymorphism have been demonstrated between distinct ethnic groups. In our study we examined these polymorphisms in 433 healthy individuals. From these, 229 were Central American mestizos from Nicaragua (n = 117) and El Salvador (n = 112) to be compared with a group of 204 North Spaniards, with the aim of detecting potential genotypic differences between these populations. The genotypes were determined by PCR-RFLP. The frequencies of the C allele were very similar among Central Americans (0.53) and Spaniards (0.52), which is consistent with the ethnic origin of Central American individuals (Amerindians and European Caucasians). In comparison to other previously studied populations, the C allele frequency in Central Americans was significantly lower than that found in African populations and higher than that observed in the Indian and Southwest Asian populations. These data may be relevant for dose recommendation of P-gp substrate drugs and also for studies of allele disease association in the Central American population.

[Prevalence of methylenetetrahydrofolate reductase C677T mutation among patients with acute ischemic cerebrovascular disease in Aragon]. / Prevalencia de la mutación C677T del gen de la metilentetrahidrofolato reductasa en pacientes con patología isquémica cerebrovascular aguda en la Comunidad Autónoma Aragonesa.

BACKGROUND: Mutation C677T of the methylenetetrahydrofolate reductase (MTHFR) is the main cause of mild hyperhomocysteinemia. Hyperhomocysteinemia is a recognized risk factor for aterothrombosis. MTHFR C677T patients have higher levels of homocysteine in absence of dietary folates. METHODS: Retrospective study over data from patients studied for MTHFR C677T diagnosed of ischemic stroke (IS) younger 50 or older 50 without classic vascular risk factors or with familiar or personal history suggesting thrombophilia in a period of 3 years. MTHFR C677T was screened in 90 healthy blood donors as a control group. Computer database was used for descriptive statistics. RESULTS: Blood samples from 99 patients and from 90 donors (control). Mean age: 44.3 with Standard deviation (SD) 13.9 years in IS group and 39.1 with SD 8.3 years in control group. We found 19 (19.19%) homozygotes for MTHFR C677T in IS group and 14 (15.55%) in control group. CONCLUSIONS: Homozygosis for MTHFR C667T is more frequent in the IS group than in the control one, although there is no significant differences. Anyway, we suggest that, because of the high prevalence of the mutation MTHFR C677T found, screening should be made in the thombophilia studies, so that we could find patients with a risk factor that could be lowered by folates in the diet.

Online reference database of European Y-chromosomal short tandem repeat (STR) haplotypes.

The reference database of highly informative Y-chromosomal short tandem repeat (STR) haplotypes (YHRD), available online at http://ystr.charite.de, represents the largest collection of male-specific genetic profiles currently available for European populations. By September 2000, YHRD contained 4688 9-locus (so-called "minimal") haplotypes, 40% of which have been extended further to include two additional loci. Establishment of YHRD has been facilitated by the joint efforts of 31 forensic and anthropological institutions. All contributing laboratories have agreed to standardize their Y-STR haplotyping protocols and to participate in a quality assurance exercise prior to the inclusion of any data. In view of its collaborative character, and in order to put YHRD to its intended use, viz. the support of forensic caseworkers in their routine decision-making process, the database has been made publicly available via the Internet in February 2000. Online searches for complete or partial Y-STR haplotypes from evidentiary or non-probative material can be performed on a non-commercial basis, and yield observed haplotype counts as well as extrapolated population frequency estimates. In addition, the YHRD website provides information about the quality control test, genotyping protocols, haplotype formats and informativity, population genetic analysis, literature references, and a list of contact addresses of the contributing laboratories.

Population genetics of the STR loci HUMCSF1PO, HUMF13A01, HUMFES/FPS and D12S391 in Asturias (northern Spain).

In order to use genetic loci in forensic identity testing, some population data are needed. This paper presents a report of allele frequency data for the loci HUMCSF1PO, HUMF13A01, HUMFES/FPS and D12S391 in a population sample from Asturias (northern Spain). No deviation from the Hardy-Weinberg equilibrium was detected in any of the four markers investigated and there was no evidence of association between the alleles of these loci. Statistical analysis was also carried out to obtain some parameters of medico-legal interest and comparative studies were carried out with other populations studied to date for these loci. The Asturian sample does not differ substantially from other Caucasian and Spanish populations.

Population genetics of the D1S1656, D12S391, and D18S535 loci in Asturias (North Spain).

Allele and genotype frequencies for three recently described short tandem repeat loci D1S1656, D12S391, and D18S535 were determined in a population sample from Asturias (North Spain). The loci were amplified using a fluorescence based PCR method and were typed automatically. No deviation from Hardy-Weinberg expectations were observed. The three loci proved to be highly discriminating and the allele frequencies observed are similar to those of the other European populations that have been typed for these loci to date.

Genetic variation at six STR loci (HUMTH01, HUMTPOX, HUMCSF1PO, HUMF13A01, HUMFES/FPS, HUMVWFA31) in Aragon (north Spain).

The STR loci HUMTH01, HUMPTPOX, HUMCSF1PO, HUMF13A01, HUMFES/FPS and HUMVWFA31 are widely used in forensic casework analyses and population data are necessary to estimate the frequency of a DNA profile. This paper presents the results of a survey aimed to investigate the allele frequency distribution of these loci in an important Spanish population (Aragon, North Spain). Statistical analysis to determine whether allele frequencies were in Hardy-Weinberg Equilibrium was carried out and also to obtain some parameters of medico-legal interest. There was no evidence of association between the alleles of the loci. The Aragonese sample does not differ substantially from other Caucasian populations.