[Medical teleconsultation. Analysis and recommendations from the ethics department of the Chilean medical association]. / Teleconsulta médica. Análisis y recomendaciones del Departamento de Ética del Colegio Médico de Chile.

The possibility of allowing patients access to health professionals, has been greatly facilitated by advances in technology. Indeed, nowadays it is possible not only direct contact between one health professional with another, but also the possibility of sending images and other tests to consult distant colleagues. This has undoubtedly enabled better health care for many patients. It is also possible for a patient to consult a doctor directly in a remote and synchronous way with oral and visual contact, thus establishing a new form of medical consultation. It is this last way of relationship, which has already spread as a practice in normal times, which arouses apprehensions about the ethical requirements that a consultation must meet. This work by the Ethics Department of the Chilean Medical Association seeks to reflect on the ethical demands of a medical consultation and on the shortcomings that teleconsultation has. It also aims to propose several recommendations, so that this new form of doctor-patient relationship serves as a complement to traditional care, without jeopardizing the objectives of a medical action.

Development of a small panel of SNPs to infer ancestry in Chileans that distinguishes Aymara and Mapuche components.

BACKGROUND: Current South American populations trace their origins mainly to three continental ancestries, i.e. European, Amerindian and African. Individual variation in relative proportions of each of these ancestries may be confounded with socio-economic factors due to population stratification. Therefore, ancestry is a potential confounder variable that should be considered in epidemiologic studies and in public health plans. However, there are few studies that have assessed the ancestry of the current admixed Chilean population. This is partly due to the high cost of genome-scale technologies commonly used to estimate ancestry. In this study we have designed a small panel of SNPs to accurately assess ancestry in the largest sampling to date of the Chilean mestizo population (n = 3349) from eight cities. Our panel is also able to distinguish between the two main Amerindian components of Chileans: Aymara from the north and Mapuche from the south. RESULTS: A panel of 150 ancestry-informative markers (AIMs) of SNP type was selected to maximize ancestry informativeness and genome coverage. Of these, 147 were successfully genotyped by KASPar assays in 2843 samples, with an average missing rate of 0.012, and a 0.95 concordance with microarray data. The ancestries estimated with the panel of AIMs had relative high correlations (0.88 for European, 0.91 for Amerindian, 0.70 for Aymara, and 0.68 for Mapuche components) with those obtained with AXIOM LAT1 array. The country's average ancestry was 0.53 ± 0.14 European, 0.04 ± 0.04 African, and 0.42 ± 0.14 Amerindian, disaggregated into 0.18 ± 0.15 Aymara and 0.25 ± 0.13 Mapuche. However, Mapuche ancestry was highest in the south (40.03%) and Aymara in the north (35.61%) as expected from the historical location of these ethnic groups. We make our results available through an online app and demonstrate how it can be used to adjust for ancestry when testing association between incidence of a disease and nongenetic risk factors. CONCLUSIONS: We have conducted the most extensive sampling, across many different cities, of current Chilean population. Ancestry varied significantly by latitude and human development. The panel of AIMs is available to the community for estimating ancestry at low cost in Chileans and other populations with similar ancestry.

[Ethical aspects of the doctors' behavior towards people on hunger strike: position paper from the Ethics Department of the Chilean Medical Association]. / Aspectos éticos de la conducta del médico ante personas en huelga de hambre: opinión del Departamento de Ética del Colegio Médico de Chile.

Every so often, in Chile there is a discussion about the role of physicians in the care of people on hunger strike (HS). In this document, we review the ethical aspects of health care for persons in HS, aiming to provide guidelines to medical doctors who are required to attend them. First, we make an important distinction between HS and suicide, since the former is used as a protest and denunciation tool, while suicide seeks deliberately to end a life. Then we describe the three roles that the health professional can fulfill: as a treating doctor, as an expert or as an official of a prison. The respect for the autonomy and dignity of the person in HS must prevail whatever the role of the physician. Therefore, we maintain that under no circumstances, people who have autonomously decided to be in HS should be fed by force. Due to the complexity of the issue, we make special considerations about the management of minors and the non-competent persons in HS. In conclusion, we adhere to the principles that inspire the Declaration of Malta, which indicate that it would be preferable to "allow a person on hunger strike to die in dignity, rather than subjecting them to repeated interventions against their will".

Selective intra-dinucleotide interactions and periodicities of bases separated by K sites: a new vision and tool for phylogeny analyses.

Direct tests of the random or non-random distribution of nucleotides on genomes have been devised to test the hypothesis of neutral, nearly-neutral or selective evolution. These tests are based on the direct base distribution and are independent of the functional (coding or non-coding) or structural (repeated or unique sequences) properties of the DNA. The first approach described the longitudinal distribution of bases in tandem repeats under the Bose-Einstein statistics. A huge deviation from randomness was found. A second approach was the study of the base distribution within dinucleotides whose bases were separated by 0, 1, 2… K nucleotides. Again an enormous difference from the random distribution was found with significances out of tables and programs. These test values were periodical and included the 16 dinucleotides. For example a high "positive" (more observed than expected dinucleotides) value, found in dinucleotides whose bases were separated by (3K + 2) sites, was preceded by two smaller "negative" (less observed than expected dinucleotides) values, whose bases were separated by (3K) or (3K + 1) sites. We examined mtDNAs, prokaryote genomes and some eukaryote chromosomes and found that the significant non-random interactions and periodicities were present up to 1000 or more sites of base separation and in human chromosome 21 until separations of more than 10 millions sites. Each nucleotide has its own significant value of its distance to neutrality; this yields 16 hierarchical significances. A three dimensional table with the number of sites of separation between the bases and the 16 significances (the third dimension is the dinucleotide, individual or taxon involved) gives directly an evolutionary state of the analyzed genome that can be used to obtain phylogenies. An example is provided.

[Position paper from the Department of Ethics of the Chilean College of Physicians about conscientious objection]. / El médico y la objeción de conciencia: Opinión del Departamento de Ética del Colegio Médico de Chile A. G.

The Chilean bill that regulates abortion for three cases (Bulletin Nº 9895-11) includes the possibility that health professionals may manifest their conscientious objection (CO) to perform this procedure. Due to the broad impact that the issue of C O had, the Ethics Department of the Chilean College of Physicians considered important to review this concept and its ethical and legal basis, especially in the field of sexual and reproductive health. In the present document, we define the practical limit s of CO, both for the proper fulfillment of the medical profession obligations, and for the due respect and non-discrimination that the professional objector deserves. We analyze the denial of some health institutions to perform abortions if it is legalize d, and we end with recommendations adjusted to the Chilean reality. Specifically, we recognize the right to conscientious objection that all physicians who directly participate in a professional act have. But we a lso recognize that physicians have ineludib le obligations towards their patients, including the obligation to inform about the existence of this service, how to access to it and -as set out in our code of ethics- to ensure that another colleague will continue attending the patient.

The structure of selective dinucleotide interactions and periodicities in D melanogaster mtDNA.

BACKGROUND: We found a strong selective 3-sites periodicity of deviations from randomness of the dinucleotide (DN) distribution, where both bases of DN were separated by 1, 2, K sites in prokaryotes and mtDNA. Three main aspects are studied. I) the specific 3 K-sites periodic structure of the 16 DN. II) to discard the possibility that the periodicity was produced by the highly nonrandom interactive association of contiguous bases, by studying the interaction of non-contiguous bases, the first one chosen each I sites and the second chosen J sites downstream. III) the difference between this selective periodicity of association (distance to randomness) of the four bases with the described fixed periodicities of base sequences. RESULTS: I) The 16 pairs presented a consistent periodicity in the strength of association of both bases of the pairs; the most deviated pairs are those where G and C are involved and the least deviated ones are those where A and T are involved. II) we found significant non-random interactions when the first nucleotide is chosen every I sites and the second J sites downstream until I=J=76. III) we showed conclusive differences between these internucleotide association periodicities and sequence periodicities. CONCLUSIONS: This relational selective periodicity is different from sequence periodicities and indicates that any base strongly interacts with the bases of the residual genome; this interaction and periodicity is highly structured and systematic for every pair of bases. This interaction should be destroyed in few generations by recurrent mutation; it is only compatible with the Synthetic Theory of Evolution and agrees with the Wright's adaptive landscape conception and evolution by shifting balanced adaptive peaks.

Malignant melanoma in Chile: different site distribution between private and state patients.

BACKGROUND: The body site location of primary Malignant Melanoma (MM) has been correlated with prognosis and survival. Ethnic, genetics, sun exposure factors are related to the anatomical distribution of MM. Low and high socioeconomic strata in Chile differ in ethnic, genetic and cultural conditions. The purpose of this study was to analyze the anatomical MM distribution in the Chilean population in both strata searching for differences due to their ethno-genetic-cultural differences. Records of 1148 MM, 575 cases from state hospitals (Low Socioeconomic Strata, LSS) and 573 cases from private clinics (High Socioeconomic Strata, HSS) were analyzed by body site. RESULTS: Females from LSS showed a higher number of MM in soles, cheeks, and around the eye area. Females from the HSS showed a higher number of MM in dorsal feet and dorsal hands. Males from LSS showed a higher number of MM in soles, around the eye area, and cheeks. However, males from HSS showed a higher number of MM in the trunk, and in the arms. Acral MM was significantly higher in LSS than in the HSS in both sexes. The Chilean population from the HSS and LSS showed differences in the distribution of MM by site. Furthermore, gender differences in the proportion of MM analyzed by anatomical site are observed in both strata. CONCLUSIONS: Results show evidence that differential genetics factors, sun exposure, or other environmental or cultural factors of both strata may account for these differences.

The monthly rhythm of incidence and age at menarche: thirty five years of research. The circa-vacation-study expectancy rhythm of incidence and age at menarche.

The hypothesis that the vacation-study-expectancy scholar regime produces most of the monthly rhythm of the age at menarche (AaM) was tested. Studies on monthly menarche incidence (MI) refuted climatic factors as a main factor in this rhythm, and indicated that the main factor of this rhythm is the succession of expectancies of study (Stu-months) or vacation (Vac-months) months within a year. Thus the hypothesis of seasonal circa-annual rhythm should be modified to the circa-[vacation (fiesta)]-[study (non-fiesta)]-expectancies rhythm for the MI and age at menarche annual rhythms. In several countries Vac-months had higher MI than Stu-months. The high MI of Vac-months was followed by a large decrease when girls started their studies and a MI increase occurred as vacations approached. The hypothesis proposes that at the end of vacations and at the beginning of the study period the AaM should be lowest, and then the mean of AaM should increase because of the menarche delay of girls whose menarche was arrested by the initiation of school work. This pattern was found in four independent samples, from Chile, Colombia, USA and Brazil. The probability that this result be due to random fluctuation of means is extraordinarily low (P<10⁻8). I conclude that the influence of the expectancy of vacation and study periods on the monthly rhythm of the age at menarche is a real process that accounts for most of this rhythm.

Foundational errors in the Neutral and Nearly-Neutral theories of evolution in relation to the Synthetic Theory: is a new evolutionary paradigm necessary?

The Neutral Theory of Evolution (NTE) proposes mutation and random genetic drift as the most important evolutionary factors. The most conspicuous feature of evolution is the genomic stability during paleontological eras and lack of variation among taxa; 98% or more of nucleotide sites are monomorphic within a species. NTE explains this homology by random fixation of neutral bases and negative selection (purifying selection) that does not contribute either to evolution or polymorphisms. Purifying selection is insufficient to account for this evolutionary feature and the Nearly-Neutral Theory of Evolution (N-NTE) included negative selection with coefficients as low as mutation rate. These NTE and N-NTE propositions are thermodynamically (tendency to random distributions, second law), biotically (recurrent mutation), logically and mathematically (resilient equilibria instead of fixation by drift) untenable. Recurrent forward and backward mutation and random fluctuations of base frequencies alone in a site make life organization and fixations impossible. Drift is not a directional evolutionary factor, but a directional tendency of matter-energy processes (second law) which threatens the biotic organization. Drift cannot drive evolution. In a site, the mutation rates among bases and selection coefficients determine the resilient equilibrium frequency of bases that genetic drift cannot change. The expected neutral random interaction among nucleotides is zero; however, huge interactions and periodicities were found between bases of dinucleotides separated by 1, 2... and more than 1,000 sites. Every base is co-adapted with the whole genome. Neutralists found that neutral evolution is independent of population size (N); thus neutral evolution should be independent of drift, because drift effect is dependent upon N. Also, chromosome size and shape as well as protein size are far from random.

Response of the G2-prophase checkpoint to genotoxic drugs in lymphocytes from healthy individuals.

We analyzed the in vitro effects of the anti-tumoral drugs doxorubicin, cytosine arabinoside and hydroxyurea on the G2-prophase checkpoint in lymphocytes from healthy individuals. At biologically equivalent concentrations, the induced DNA damage activated the corresponding checkpoint. Thus: i) there was a concentration-dependent delay of G2 time and an increase of both the total DNA lesions produced and repaired before metaphase and; ii) G2-checkpoint adaptation took place as chromosome aberrations (CAs) started to appear in the metaphase, indicating the presence of unrepaired double-strand breaks (DSBs) in the previous G2. The checkpoint ATM/ATR kinases are involved in DSB repair, since the recorded frequency of CAs increased when both kinases were caffeine-abrogated. In genotoxic-treated cells about three-fold higher repair activity was observed in relation to the endogenous background level of DNA lesions. The maximum rate of DNA repaired was 3.4 CAs/100 metaphases/hour, this rise being accompanied by a modest 1.3 fold lengthening of late G2 prophase timing. Because of mitotic chromosome condensation, no DSBs repair can take place until the G1 phase of the next cell cycle, when it occurs by DNA non-homologous end joining (NHEJ). Chromosomal rearrangements formed as a consequence of these error-prone DSB repairs ensure the development of genome instability through the DNA-fusion-bridge cycle. Hence, adaptation of the G2 checkpoint supports the appearance of secondary neoplasia in patients pretreated with genotoxic drugs.

[Scientific ethics and the use of human material or data]. / Ética Científica y uso de material o datos colectados de seres humanos.

A scientific article censured by superposing obstacles to its reading remembers the censure of Galileo made by the Inquisition. The censure followed the failure to obtain the informed consent (IC) to disclose results of old samples. At present, the use of collected data or samples for a new research needs a new IC, in most ethical protocols. The Helsinki Code allows the research ethics committees the authorization for the use of that information. This norm is founded rather in commercial, legal or protective arguments than in ethical bases. This article criticizes this norm from the Scientific Ethics viewpoint because: i) the ownership of the genome and environment that originate a person is not of such person but of the human society and Homo sapiens species, ii) a person is not the unique owner of that information; laboratories, institutions, health services and research teams add constituents to it, iii) several violations to this norm occurring in medical, labor, legal and social practice show it as biased against science, iv) if this stored information and its use are beneficial for humankind (its proper owner) it is ethically obligatory to use it. It is proposed to create an anonymous World Bank for Human Information with open access and universal transparency. This universal collection of data handled under universal accepted ethical norms should prevent exclusive private use of public information, non-publication of negative results, illicit and unethical use of human data.

Heterogeneous periodicity of drosophila mtDNA: new refutations of neutral and nearly neutral evolution.

We found a consistent 3-site periodicity of the X²9 values for the heterogeneity of the distribution of the second base in relation to the first base of dinucleotides separated by 0 (contiguous), 1, 2, 3 ... 17 (K) nucleotide sites in Drosophila mtDNA. Triplets of X²9 values were found where the first was over 300 and the second and third ranged between 37 and 114 (previous studies). In this study, the periodicity was significant until separation of 2011K, and a structure of deviations from randomness among dinucleotides was found. The most deviant dinucleotides were G-G, G-C and C-G for the first, second and third element of the triplet, respectively. In these three cases there were more dinucleotides observed than expected. This inter-bases correlation and periodicity may be related to the tertiary structure of circular DNA, like that of prokaryotes and mitochondria, to protect and preserve it. The mtDNA with 19.517 bp was divided into four equal segments of 4.879 bp. The fourth sub-segment presented a very low proportion of G and C, the internucleotide interaction was weaker in this sub-segment and no periodicity was found. The maintenance of this mtDNA structure and organization for millions of generations, in spite of a high recurrent mutation rate, does not support the notion of neutralism or near neutralism. The high level of internucleotide interaction and periodicity indicate that every nucleotide is co-adapted with the residual genome.

Human sociogenetics.

In three cities of Chile (Santiago, Valparaiso, Valdivia) the A allele and phenotype (ABO blood group) are more frequent in the higher socioeconomic strata (SES) and the O allele and phenotype are in the lower ones. This constitutes a structured sociogenetic cline (SGC). The B allele and phenotypes (B+AB) present a rather erratic or contradictory distribution among SES. This SGC was also found in England. The standard interpretation of the origin and maintenance of this SGC in Chile is founded on socio-ethno-historic-cultural and drift factors followed by socioeconomic assortative mating that has occurred since the origin of Chileans by the admixture of Europeans and Amerindians. This interpretation is insufficient to explain the coincidence of the cline in England and Chile, and for some findings in Chile. 1) The A and Rh(-) frequencies of the highest SES in Chile are significantly higher than those found in Europeans. 2) The B gene and phenotypes (with AB) behave differently and in contradiction to the socio-ethno-cultural-historical process. 3) There is a significant interaction of the SGC with gender in Chile and England. There is not at present a putative relationship between ABO and psycho-social factors that could account for this sociogenetic interaction. This SGC seems to be present in societies with a hierarchical organization in relation to power, prestige, ownership, income and life style, and when sampling includes the most extreme SES. It has not been found in two samples from Ireland and in a sample from Chile taken from a public hospital, probably because those variables and conditions were not ascertained.

[Scientific ethics of the abortion with anencephalic fetus]. / Ética científica del aborto en caso de anencefalia.

author proposes, from the perspective of the Scientific Ethics, to assimilate anencephalic fetuses to non-human fetuses because they have a large deficiency of the brain that is the organ for human specificity. This proposal comes after considering arguments and facts from ontogeny, phylogeny, from the situation of loss of the brain in the adult life and from the organic specificity of the human condition given by the brain. If anencephalic fetuses are not human, the interruption of their pregnancy cannot be considered as abortion, regardless the pregnancy stage.

[Colonization of the oral cavity by group mutans streptococci according to age assessed by a semi-quantitative method in saliva]. / Colonización de la cavidad oral por Streptococcus grupo mutans, según edad, evaluado en saliva por un método semi-cuantitativo.

OBJECTIVE: To evaluate the colonization of group mutans streptococci according to age, measuring the amount of bacteria in saliva with a semi-quantitative method in a population attended in public and private dental centers of the Metropolitan Region, Santiago, Chile. PATIENTS AND METHODS: Saliva samples were obtained from 14,649 patients aged 5 to 40 years, in one public and 5 private dental centers. Bacteria concentration was estimated by the comparison with a standard counting-chart. The concentration of group mutans streptococci in saliva was test by a 3-way ANOVA. RESULTS: Bacterial concentration of Streptococcus mutans related with the age of patients was significant (p < 0.001). Bacterial concentration in the preschool age was 4,7 x 10(5) CFU/mL at 5 years, while 6,0 x10(5) CFU/mL at 12 years of age, with a decrease in patients over 30 years. Bacterial concentration was significantly different in the six centers of the study. CONCLUSIONS: The semi-quantitative method was useful to determine the colonization by Streptococcus mutans according to age. This could help for identifying population at high risk of dental caries and to develop oral health prevention programs in specific populations.

Internucleotide correlations and nucleotide periodicity in Drosophila mtDNA: new evidence for panselective evolution.

Analysis for the homogeneity of the distribution of the second base of dinucleotides in relation to the first, whose bases are separated by 0, 1, 2,... 21 nucleotide sites, was performed with the VIH-1 genome (cDNA), the Drosophila mtDNA, the Drosophila Torso gene and the human p-globin gene. These four DNA segments showed highly significant heterogeneities of base distributions that cannot be accounted for by neutral or nearly neutral evolution or by the "neighbor influence" of nucleotides on mutation rates. High correlations are found in the bases of dinucleotides separated by 0, 1 and more number of sites. A periodicity of three consecutive significance values (measured by the x²9) was found only in Drosophila mtDNA. This periodicity may be due to an unknown structure or organization of mtDNA. This non-random distribution of the two bases of dinucleotides widespread throughout these DNA segments is rather compatible with panselective evolution and generalized internucleotide co-adaptation.

Sexual orientation, handedness, sex ratio and fetomaternal tolerance-rejection.

Fraternal birth order (FBO) appears as a prenatal cause of 15% of homosexual males (gays) through mnemonic maternal anti-male factors. Non-right-handed men seem to be protected from homosexuality. Four hypotheses are proposed: (1) androgenic factors of non-right-handedness neutralize anti-male factors; (2) non-right-handedness and homosexuality are lethal or produce mental impairment; (3) non-right-handed male embryos are insensitive to anti-male factors; (4) mothers of non-right-handed fetuses do not produce anti-male factors. Studies of the sex ratio (SR) of older and younger siblings show: (1) a significant heterogeneity in the SR of siblings of right or non-right handed heterosexual men and women; (2) lesbians are born among siblings with high SR; (3) siblings of right-handed gays show a higher SR than non-right-handed gays that present a low SR. Based on our discovery of maternal tolerance-rejection processes, associated with genetic systems (ABO, Rh), where zygotes or embryos different from their mother induce better pregnancy and maternal tolerance than do those that share antigens with their mothers, I propose a new explanation for sexual relationships, sexual orientation, handedness and sibling SR. Lesbian embryos could induce tolerance from mothers with anti-female factors. Non-right-handedness could induce maternal tolerance, or change the maternal compatibility of "gay" embryos. Alternatively, gay embryos could be poor inducers of maternal tolerance towards male traits.

Fixations of the HIV-1 env gene refute neutralism: New evidence for pan-selective evolution.

We examined 103 nucleotide sequences of the HIV-1 env gene, sampled from 35 countries and tested: I) the random (neutral) distribution of the number of nucleotide changes; II) the proportion of bases at molecular equilibrium; III) the neutral expected homogeneity of the distribution of new fixated bases; IV) the hypothesis of the neighbor influence on the mutation rates in a site. The expected random number of fixations per site was estimated by Bose-Einstein statistics, and the expected frequencies of bases by matrices of mutation-fixation rates. The homogeneity of new fixations was analyzed using χ² and trinomial tests for homogeneity. Fixations of the central base in trinucleotides were used to test the neighbor influence on base substitutions. Neither the number of fixations nor the frequencies of bases fitted the expected neutral distribution. There was a highly significant heterogeneity in the distribution of new fixations, and several sites showed more transversions than transitions, showing that each nucleotide site has its own pattern of change. These three independent results make the neutral theory, the nearly neutral and the neighbor influence hypotheses untenable and indicate that evolution of env is rather highly selective.

Non-random pre-transcriptional evolution in HIV-1. A refutation of the foundational conditions for neutral evolution.

The complete base sequence of HIV-1 virus and GP120 ENV gene were analyzed to establish their distance to the expected neutral random sequence. An especial methodology was devised to achieve this aim. Analyses included: a) proportion of dinucleotides (signatures); b) homogeneity in the distribution of dinucleotides and bases (isochores) by dividing both segments in ten and three sub-segments, respectively; c) probability of runs of bases and No-bases according to the Bose-Einstein distribution. The analyses showed a huge deviation from the random distribution expected from neutral evolution and neutral-neighbor influence of nucleotide sites. The most significant result is the tremendous lack of CG dinucleotides (p < 10(-50) ), a selective trait of eukaryote and not of single stranded RNA virus genomes. Results not only refute neutral evolution and neutral neighbor influence, but also strongly indicate that any base at any nucleotide site correlates with all the viral genome or sub-segments. These results suggest that evolution of HIV-1 is pan-selective rather than neutral or nearly neutral.