Biomedical subjects

Cristina Santos

Publications and source records attributed to Cristina Santos.

11 recordsLinked to original sources

PubMed2026

Probability of Mitochondrial DNA heteroplasmy in different tissues from European populations.

Mitochondrial DNA (mtDNA) heteroplasmy complicates genetic analyses due to its variability across individuals and tissues. We analyzed over 400 Spanish blood samples and integrated published Massively Parallel Sequencing (MPS) data from ten additional European tissues. Heteroplasmy was tissue-specific, with skeletal muscle, kidney, and liver showing the highest levels, while the intestines, skin, and cerebellum had the lowest. Blood uniquely displayed more heteroplasmies in coding than non-coding regions. Several conserved positions not previously described as hotspots showed high frequencies. These results establish the first comprehensive tissue-specific heteroplasmic profile of the complete mitochondrial genome in a European population, improving the interpretation of mtDNA variation in forensic and biomedical contexts.

Humans↗

PubMed2024

An easy-to-use pipeline to analyze amplicon-based Next Generation Sequencing results of human mitochondrial DNA from degraded samples.

Genome and transcriptome examinations have become more common due to Next-Generation Sequencing (NGS), which significantly increases throughput and depth coverage while reducing costs and time. Mitochondrial DNA (mtDNA) is often the marker of choice in degraded samples from archaeological and forensic contexts, as its higher number of copies can improve the success of the experiment. Among other sequencing strategies, amplicon-based NGS techniques are currently being used to obtain enough data to be analyzed. There are some pipelines designed for the analysis of ancient mtDNA samples and others for the analysis of amplicon data. However, these pipelines pose a challenge for non-expert users and cannot often address both ancient and forensic DNA particularities and amplicon-based sequencing simultaneously. To overcome these challenges, a user-friendly bioinformatic tool was developed to analyze the non-coding region of human mtDNA from degraded samples recovered in archaeological and forensic contexts. The tool can be easily modified to fit the specifications of other amplicon-based NGS experiments. A comparative analysis between two tools, MarkDuplicates from Picard and dedup parameter from fastp, both designed for duplicate removal was conducted. Additionally, various thresholds of PMDtools, a specialized tool designed for extracting reads affected by post-mortem damage, were used. Finally, the depth coverage of each amplicon was correlated with its level of damage. The results obtained indicated that, for removing duplicates, dedup is a better tool since retains more non-repeated reads, that are removed by MarkDuplicates. On the other hand, a PMDS = 1 in PMDtools was the threshold that allowed better differentiation between present-day and ancient samples, in terms of damage, without losing too many reads in the process. These two bioinformatic tools were added to a pipeline designed to obtain both haplotype and haplogroup of mtDNA. Furthermore, the pipeline presented in the present study generates information about the quality and possible contamination of the sample. This pipeline is designed to automatize mtDNA analysis, however, particularly for ancient samples, some manual analyses may be required to fully validate results since the amplicons that used to be more easily recovered were the ones that had fewer reads with damage, indicating that special care must be taken for poor recovered samples.

DNA, Mitochondrial↗

PubMed2006

Community pharmacy services in Portugal.

OBJECTIVE: To describe the status and outline the trends of community pharmacy services in the Portuguese healthcare system. FINDINGS: The legal framework for Portuguese pharmacies includes geographic and demographic criteria for opening pharmacies and restricting ownership to pharmacists. Since 1975, pharmacy owners have been organized under one association, the Portuguese National Pharmacy Association, which has dealt with pharmacy development over the past 20 years. Securing the economic sustainability of pharmacies was the first milestone. Investing in information software and communication technologies and modernizing the architecture of pharmacies was the next step. Then, professional services such as point-of-care measurements, drug waste management, and needle exchange services were developed. The methadone substitution program was introduced at a later date. Finally, major comprehensive services, including disease management/pharmaceutical care programs, were implemented. DISCUSSION: All Portuguese pharmacies are independent, which means that the decision to provide different services and the extent to which they are attained vary from pharmacy to pharmacy. Recent political changes seem to reinforce the need to pursue the strategies already defined-to expand the traditional scope of pharmacy business to a wider range of health services. CONCLUSIONS: Achievements that have been accomplished and strategies that are in place reflect a high level of organization and unity among Portuguese pharmacies. From a global perspective, pharmacies are reorganizing to be able to compete against other possible agents and are preparing to expand their scope of intervention.

Community Pharmacy Services↗

PubMed2006

A novel mutation in JARID1C gene associated with mental retardation.

X-linked mental retardation (XLMR) is an extremely heterogeneous condition that account for 15-25% of all mentally retarded patients. The number of genes newly reported in relation with this condition has been rapidly increased in the past years. One of the latest is called Jumonji AT-rich interactive domain 1C (JARID1C). This gene encodes for a member of a recently discovered protein family that harbours DNA-binding motifs, suggesting a possible role in transcriptional regulation and in the modification of chromatin structure. In this work we describe the results obtained by screening JARID1C gene in 24 mentally retarded males with history of at least two affected males. Remarkably, we have found a novel missense mutation in exon 10 of the gene that results in a Serine-to-arginine change at amino-acid 451 (S451R). This nucleotide change appears to be restricted to mentally retarded patients, since it has not been detected in control samples. Familial analysis has confirmed the segregation of this mutation with mental retardation. Furthermore, sequence alignment analysis with the different members of the human JARID1 family and with homologous proteins of mouse and fruit fly has revealed that the affected amino acid is conserved. Our data highlights the importance of reporting mutations in this gene since it might support the recent findings that implicates JARID1C with XLMR.

Amino Acid Sequence↗

PubMed2005

Understanding differences between phylogenetic and pedigree-derived mtDNA mutation rate: a model using families from the Azores Islands (Portugal).

We analyzed the control region of the mitochondrial DNA (mtDNA) from maternally related individuals originating from the Azores Islands (Portugal) in order to estimate the mutation rate of mtDNA and to gain insights into the process by which a new mutation arises and segregates into heteroplasmy. Length and/or point heteroplasmies were found at least in one individual of 72% of the studied families. Eleven new point substitutions were found, all of them in heteroplasmy, from which five appear to be somatic mutations and six can be considered germinal, evidencing the high frequency of somatic mutations in mtDNA in healthy young individuals. Different values of the mutation rate according to different assumptions were estimated. When considering all the germinal mutations, the value of the mutation rate obtained is one of the highest reported so far in family studies. However, when corrected for gender (assuming that the mutations present in men have the same evolutionary weight of somatic mutations because they will inevitably be lost) and for the probability of intraindividual fixation, the value for the mutation rate obtained for HVRI and HVRII (0.2415 mutations/site/Myr) was in the upper end of the values provided by phylogenetic estimations. These results indicate that the discrepancy, that has been reported previously, between the human mtDNA mutation rates observed along evolutionary timescales and the estimations obtained using family pedigrees can be minimized when corrections for gender proportions in newborn individuals and for the probability of intraindividual fixation are introduced. The analyses performed support the hypothesis that (1) in a constant, tight bottleneck genetic drift alone can explain different patterns of heteroplasmy segregation and (2) in neutral conditions, the destiny of a new mutation is strictly related to the initial proportion of the new variant. Another important point arising from the data obtained is that, even in the absence of a paternal contribution of mtDNA, recombination may occur between mtDNA molecules present in an individual, which is only observable if it occurs between mtDNA types that differ at two or more positions.

Azores↗

PubMed2005

Survival of Lactobacillus sakei during heating, drying and storage in the dried state when growth has occurred in the presence of sucrose or monosodium glutamate.

Spray-dried cells of Lactobacillus sakei CTC 494 survived ca. 60% longer in the spray dried state when cells were grown in the presence of 20 g sucrose l(-1) or 12.5 g monosodium glutamate l(-1). No significant differences were observed in viability during storage in the freeze dried state with the addition of these compounds to the growth medium, nor in survival during a heat treatment (55 degrees C). Both sucrose and glutamate in the growth medium suppressed intracellular accumulation of total amino acids and changed the overall pattern of the individual amino acids. Glutamate in the growth medium enhanced intracellular glutamate by ca. 38%.

Cell Proliferation↗

PubMed2005

Genetic structure of Flores island (Azores, Portugal) in the 19th century and in the present day: evidence from surname analysis.

The island of Flores is the most westerly of the Azores archipelago (Portugal). Despite its marked geographic isolation and reduced population size, biodemographic and genetic studies conducted so far do not support the idea that its population constitutes a genetic isolate. In this study we conducted a surname analysis of the Flores population for two time periods: the second half of the 19th century and the present day. Our main purposes were (1) to biodemographically and genetically characterize the island, taking into account the strong reduction in population observed from the middle of the 19th century to the present day; and (2) to analyze the influence that the effective population size and geographic distance have on the genetic structure of populations. For both periods analyzed, all indicators of diversity revealed a high level of surname diversity. Our results are in accordance with the diversity estimates obtained from both monoparental genetic markers located in the Y chromosome and frequencies of mtDNA haplogroups. Contrary to what could be expected, considering the strong reduction of population in the last 150 years, we observed that diversity was maintained and that microdifferentiation decreased. Both observations support a higher openness of parishes as a consequence of the increase in communication routes. From the first to the second period analyzed, a change in surname composition is evident, although the more frequent surnames in Flores are almost the same for both periods and some of them are reported to be surnames present in the first settlers of Flores. This result testifies to the impact of founders on the present-day gene pool of Flores island and allows us to infer that the genetic characterization of the present-day population of Flores could provide reliable information about the history of the peopling of the Azores.

Azores↗

PubMed2004

[Influence of three organisational measures on the cesarean section rate in a tertiary care University Hospital].

OBJECTIVE: To evaluate the influence of three organizational measures on the cesarean section rate over two consecutive years, in the Department of Obstetrics and Gynaecology of a tertiary care University Hospital. MATERIAL AND METHODS: Clinical records of births occurring in the years 2001 and 2002 were retrospectively evaluated, in order to identify the annual rate of emergency and elective cesarean sections. Other data recorded were the type of deliveries in each on-call team, newborn 1-min and 5-min Apgar scores, neonatal intensive care unit admissions, principal motive for emergency cesareans, time of day and week-day of emergency cesareans. In the first week of 2002, the results of the first year's evaluation were presented to all staff at the Department. At that time, an information pamphlet was distributed to all health care professionals, reminding them of the risks associated with cesarean section. From then on, all emergency cesareans were discussed on the following work-day, in a clinical meeting involving all obstetrical staff. Statistical analysis was carried out using the chi-squared test, with the level of significance being established at 0.05. RESULTS: In 2001 there were 3009 births, overall cesarean section rate was 36.5%, and emergency cesarean rate was 30.5%. Cesarean section rates varied between 23.3% and 43.4%, amongst the eight on-call teams. In 2002 there were 2959 births, overall cesarean section rate was 27.6%, and emergency cesarean rate was 20.4%. Cesarean section rates in on-call teams varied between 14.3% and 31.5%. Over the two years, a reduction of 8.9 percentage points (p<0.001) in overall cesarean section rate, and of 10.1 points (p<0.001) in emergency cesareans were observed. During the same period elective cesareans increased 1.2 percentage points (p=0.052) and instrumental deliveries increased 3.2 points (p=0.002). There were less cesarean sections due to arrested labour (154 cases) and non-reassuring fetal state (46 cases), although these motives remained preponderant. The number of newborns with low 1-min Apgar decreased significantly, while those with low 5-min Apgar and intensive care unit admission remained constant. CONCLUSIONS: The introduction of three relatively simple organizational measures enabled a significant reduction in the cesarean section rate over a one-year period, without changing the incidence of the main neonatal outcome indicators.

Cesarean Section↗

PubMed2004

Short-term psychological impact of predictive testing for Machado-Joseph disease: depression and anxiety levels in individuals at risk from the Azores (Portugal).

OBJECTIVE: The short-term impact of the pre-symptomatic genetic test (PT) for Machado-Joseph disease (MJD) in the Azores (Portuguese Islands) was assessed in 46 individuals at risk who completed the PT Program. METHODS: Scores for depression and anxiety were used as indicators of the subjects' emotional status immediately before the PT and 1 year after disclosure of the results. RESULTS: Global levels of participation in the Azorean PT Program for MJD were high (20.7%), particularly in Flores Island (35.8%). For the total sample, mean scores of depression and anxiety before and after the PT presented without clinical significance. No differences were found for depression and anxiety scores before and after the PT. Furthermore, when grouped by test results (carriers/non-carriers), there were no differences between pre- and post-test levels. CONCLUSIONS: Results indicate that the test result did not cause a decrease in the psychological well-being of the individuals tested. The high number of participants performing the PT in the small and isolated community of Flores Island, where MJD represents a source of stigma, was interpreted as an indication that in this particular population the PT offers the individuals at risk the possibility of liberating from a stigma, and, hence, from exclusion.

Adult↗

PubMed2004

Determination of human caucasian mitochondrial DNA haplogroups by means of a hierarchical approach.

In this paper we propose a hierarchical approach that allows the screening of mitochondrial DNA (mtDNA) haplogroups in populations that have essentially West Eurasian mtDNA backgrounds but that could have some non-West Eurasian contributions. To develop and validate this scheme, we used data on 18 coding region polymorphisms (17 analyzed by RFLP analysis and 1 by sequencing) and sequences of hypervariable segment I (HVSI) of the mtDNA control region from the Azores Islands (Portugal) population. The proposed scheme allows the characterization of almost all West Eurasian and African major clusters by means of RFLPs. Furthermore, the scheme includes information on situations in which sequencing is pertinent to defining a particular haplogroup. The validity of the scheme is ensured by (1) using relatively stable polymorphic positions, (2) screening more than one position to define a specific haplogroup, and (3) typing confirmatory positions. Dubious samples can be resolved by sequencing. The robustness of this approach was assessed by sequencing all samples for HVSI, taking advantage of the previously established relationships between RFLPs and control region sequence polymorphisms. The use of this hierarchical approach avoids the screening of unnecessary control region polymorphisms and therefore results in a more rapid and cost-efficient screening than one in which all polymorphic positions are analyzed. Even if this approach leads to a lower level of phylogeographic resolution than the sequencing of all samples, it allows us to define population movements on a continental level and can be applied, unlike sequencing all samples, with a low cost in any laboratory.

Azores↗

PubMed2003

Detection of Chlamydia trachomatis in endocervical smears of sexually active women in Manaus-AM, Brazil, by PCR.

Chlamydia trachomatis is now one of the most prevalent bacteria found in classic sexually transmissible diseases (STD), and as such, constitutes a serious public health problem. We examined the prevalence of Chlamydia trachomatis, by polymerase chain reaction (PCR), in 121 sexually active women who sought treatment for STD in the Alfredo da Matta Institute of Dermatology and Venerology and the Institute of Tropical Medicine of Amazonas in Manaus, Brazil. These women were examined by a specific PCR for the chlamydial plasmid, and the nature of the amplicon was determined by restriction analysis and DNA sequencing. The PCR diagnosis revealed a prevalence of 20.7% infected women.

Adolescent↗