Application of participatory design and open source to a sustainable proposal for sorption reactor design.

An implementation proposal that seeks to globalize the scope of the sustainable technologies developed in the University laboratories is presented. This approach uses the generation of triple-impact projects placing people at the center of technological development to bring technical and scientific knowledge into a service design oriented to global sustainable solutions. This research is an approach to what a hub for scientific research, technological implementation, and human needs would look like by designing common environments in which to interact and expand knowledge in an iterated way through the experience of all the actors involved in technological implementation. As a control case, a new technology developed at the Universidad de Buenos Aires, consisting of using sustainable materials as tubular reactor fillers for water treatment was chosen. Based on data obtained within the framework of a University extension project, in which the water quality diagnosis for human consumption was carried out and cross-examined with the mathematical analysis of sorption, design parameters of the reactor, participatory design, and open source concepts application, different virtual environments were generated with distinct objectives: i) open design environment: publishing and mapping of installed sorption reactors, reactor model plans, and useful information related to drinking water quality (aimed at contributors of the open source design environment); ii) platform for academic actors linking: connecting data between prototyping lab for participatory design of sorption reactors (aimed at university research users); iii) information disclosure page: space where the implemented technology impact is displayed and shows options to contact researchers and request a reactor design diagnosis for another community (aimed at beneficiary users). A technological service designed to link the University with the community was proposed, by resolving one of the main gaps related to the possibility for communities to access public financing for self-managed improvement projects, increasing the appropriation of the adopted technology and democratizing public investment, making it sustainable over time.

Benefits and costs of immune memory in Rhodnius prolixus against Trypanosoma cruzi.

There is increasing evidence supporting the immune memory in invertebrates, but the studies are relatively neglected in insect vectors other than mosquitoes. Therefore, we tested two hypotheses: 1) Rhodnius prolixus insects possess immune memory against Trypanosoma cruzi, and 2) their immune memory is costly. The Dm28c and Y strains of T. cruzi were used, the former being more infective than the latter. On the one hand, the triatomines subjected to dual challenges with the Dm28c strain did not show significant differences in survival than those of the heterologous challenge groups control-Dm28c and Y-Dm28c. On the other hand, the insects survived longer after a dual Y-Y challenge than after the corresponding heterologous challenge (control-Y). The Y-Y, Dm28c-Y, and naïve groups showed similar survival. There was more prolonged survival following the Y-Y versus Dm28c-Dm28c dual challenge. The Dm28c-Dm28c group exhibited moulting sooner than the control-Dm28c or naïve group. In contrast, there were no differences in the probability of moulting between the Y-Y and naïve groups. The results suggest that triatomines have immune memory against the Y but not the Dm28c strain. Further investigation on triatomine and T. cruzi interaction is needed to determine if infectivity accelerates or delay growth due to innate immune memory.

Laparoscopic cytoreductive surgery and HIPEC: a comparative matched analysis.

BACKGROUND: Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a procedure that has had encouraging results for peritoneal metastases (PM) from diverse tumour origins, but it is not exempt from high morbidity. Recently, the important role of laparoscopy in oncologic surgeries and its benefits have been evaluated for CRS + HIPEC in selected patients, which has yielded promising results. The aim of our study is to analyse the use of laparoscopy for CRS + HIPEC in patients with limited peritoneal disease. METHODS: We have conducted a retrospective study from a prospective database in our tertiary referral hospital within the period of January 2009 to July 2019, which includes 825 patients who had PM from varying tumour origins. We have compared the patients treated with the laparoscopic approach (L-CRS-HIPEC) to a matched population who have undergone the open approach (O-CRS-HIPEC) and fulfil the same selection criteria. We have analysed the postoperative outcomes and survival results. RESULTS: We have confirmed the homogeneity between the sample of the O-CRS + HIPEC (n = 42) and the L-CRS + HIPEC (n = 18) regarding preoperative and intraoperative features. The L-CRS + HIPEC group had shorter hospital stays, (median of 4 [2-10] days versus 9 [2-19] days) and reduced wait time to return to chemotherapy (median of 4 [3-7] weeks and a median of 8 [4-36] weeks) than the O-CRS + HIPEC group. No differences were found regarding the need for perioperative blood transfusion, surgery time or postoperative morbi-mortality. No early locoregional relapse occurred in the L-CRS + HIPEC group and short term disease-free survival did not differ between groups. CONCLUSIONS: Laparoscopy for CRS + HIPEC is feasible and safe in highly selected patients, with no significant differences concerning postoperative morbi-mortality or early oncological results. We have found that patients who have undergone laparoscopic operations have shorter hospital stays and that they return to adjuvant chemotherapy sooner. Further investigation is required to confirm the benefits of minimally invasive procedures for the management of PM.

Developing classification criteria for skin-predominant dermatomyositis: the Delphi process.

BACKGROUND: The European League Against Rheumatism/American College of Rheumatology classification criteria for inflammatory myopathies are able to classify patients with skin-predominant dermatomyositis (DM). However, approximately 25% of patients with skin-predominant DM do not meet two of the three hallmark skin signs and fail to meet the criteria. OBJECTIVES: To develop a set of skin-focused classification criteria that will distinguish cutaneous DM from mimickers and allow a more inclusive definition of skin-predominant disease. METHODS: An extensive literature review was done to generate items for the Delphi process. Items were grouped into categories of distribution, morphology, symptoms, antibodies, histology and contextual factors. Using REDCap™, participants rated these items in terms of appropriateness and distinguishing ability from mimickers. The relevance score ranged from 1 to 100, and the median score determined a rank-ordered list. A prespecified median score cut-off was decided by the steering committee and the participants. There was a pre-Delphi and two rounds of actual Delphi. RESULTS: There were 50 participating dermatologists and rheumatologists from North America, South America, Europe and Asia. After a cut-off score of 70 during the first round, 37 of the initial 54 items were retained and carried over to the next round. The cut-off was raised to 80 during round two and a list of 25 items was generated. CONCLUSIONS: This project is a key step in the development of prospectively validated classification criteria that will create a more inclusive population of patients with DM for clinical research. What's already known about this topic? Proper classification of patients with skin-predominant dermatomyositis (DM) is indispensable in the appropriate conduct of clinical/translational research in the field. The only validated European League Against Rheumatism/American College of Rheumatology criteria for idiopathic inflammatory myopathies are able to classify skin-predominant DM. However, a quarter of amyopathic patients still fail the criteria and does not meet the disease classification. What does this study add? A list of 25 potential criteria divided into categories of distribution, morphology, symptomatology, pathology and contextual factors has been generated after several rounds of consensus exercise among experts in the field of DM. This Delphi project is a prerequisite to the development of a validated classification criteria set for skin-predominant DM.

Complete laparoscopic pelvic peritonectomy plus hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The aim of our study was to present the technique for, and early results of complete laparoscopic pelvic peritonectomy (LPP) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We conducted a study on consecutive patients who had LPP for limited peritoneal carcinomatosis (peritoneal carcinomatosis index < 10) from ovarian cancer, colon cancer and benign multicystic mesothelioma, from January 2017 to November 2019 at 2 referral centers in Spain. Perioperative, pathologic, 30-day major morbidity and mortality characteristics were analyzed. The surgical technique is shown in the attached video. RESULTS: Twelve LPP + HIPEC were performed. Complete cytoreduction was achieved in 100% of the patients, the median duration of the operation was 450 min (range 360-600 min). There were 2 cases (16%) of IIIa morbidity (trocar hernia and pleural effusion), and no mortality. The median length of hospital stay was 5.5 days (range 4-10 days). The median length of follow-up was 10 months (range 2-30 months). There was a recurrence at the splenic hilum in 1 patient which was treated by laparoscopic splenectomy and one nodal recurrence at 13 months while all other patients are alive and free of disease at last follow-up. CONCLUSIONS: This is the first technical video of a minimally invasive approach for complete pelvic peritonectomy plus omentectomy associated with HIPEC. For highly selected patients, this procedure presents a feasible and safe alternative to the maximally invasive approach.

RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients. METHODS: We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units. RESULTS: A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation. CONCLUSIONS: By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.

A minimally invasive approach for peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC) in limited peritoneal carcinomatosis: The American Society of Peritoneal Surface Malignancies (ASPSM) multi-institution analysis.

BACKGROUND: Minimally invasive surgery is playing an increasing role in the treatment of patients with gastrointestinal and gynaecological malignancies as the data show reduced morbidity, faster recovery and similar oncological outcome when compared to open procedures. MATERIALS AND METHODS: The American Society of Peritoneal Surface Malignancies (ASPSM) conducted a retrospective study to analyse peritonectomy procedures and HIPEC done via the laparoscopic route. A database with standard clinical and pathological parameters was set up and distributed amongst ASPSM members. Rate of relapse, morbidity and mortality were the primary endpoints of the study. RESULTS: A total of 90 patients from 7 centres around the world were identified. Sixty percent were female. Mean age was 50 years. Peritoneal carcinomatosis from appendiceal origin was the most common diagnosis in a 64.9% of patients and colon origin was diagnosed in 16.5% of patients. Mean peritoneal cancer index (PCI) was 4.1 (0-10). Forty-one percent of patients had a bowel resection. Mean operative time was 4.7 h (2.5-8). All patients had a complete cytoreduction and HIPEC. Grade 3 and 4 morbidity was 3.0 and 6.5%, respectively. The most common reason for re-operation was an internal hernia in 2 out of 5 cases. Operative mortality and re-admission rates were 0 and 5%, respectively. Mean hospital stay was 7.4 days (1-18). At a mean follow-up of 31.6 months, 15/90 patients have a disease relapse but loco-regional relapse was identified in only five patients. CONCLUSIONS: Analysis of these data suggests that minimally invasive approach for peritonectomy procedures and HIPEC is feasible, safe and should be considered as part of the armamentarium for highly selected patients with peritoneal surface malignancies with limited tumour burden, defined as PCI of 10 or less and borderline tumours as low-grade pseudomyxoma and benign multicystic mesothelioma.

HIPECT4: multicentre, randomized clinical trial to evaluate safety and efficacy of Hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma.

BACKGROUND: Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4). METHODS/DESIGN: The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection. DISCUSSION: We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma. TRIAL REGISTRATION: NCT02614534 ( clinicaltrial.gov ) Nov-2015.

Itch in dermatomyositis: the role of increased skin interleukin-31.

BACKGROUND: Interleukin (IL)-31 is implicated in pruritus associated with pruritic skin diseases like atopic dermatitis. Although pruritus is a prominent feature in dermatomyositis (DM), few studies have evaluated the pathogenesis of DM-associated itch. OBJECTIVES: To establish the prevalence of itch in DM, and to investigate the role of IL-31 in DM-related itch. METHODS: Pruritus and disease activity of DM were evaluated by a visual analogue scale (VAS) and the Cutaneous Disease and Activity Severity Index (CDASI), respectively. Expression of IL-31 and IL-31 receptor alpha (IL-31RA) in lesional DM, nonlesional DM and healthy control skin was evaluated by quantitative reverse-transcriptase polymerase chain reaction and immunofluorescence. Flow cytometry was performed on skin cells isolated from lesional DM skin to identify cellular sources of IL-31 in DM. RESULTS: Among 191 patients with DM, 50·8% had moderate-to-severe itch, and itch was correlated with increased cutaneous severity (r = 0·34). In patients with itchy DM, gene expression of IL31 and IL31RA in lesional skin was upregulated compared with nonlesional skin and healthy control skin. IL31 mRNA expression positively correlated with VAS itch score (r = 0·67). On immunofluorescence, immunoreactivity for IL-31 and IL-31RA was stronger in lesional skin. Flow cytometry showed that lesional DM skin contained significantly more IL-31-producing cells, and CD4+ cells were the most common cell type. Lenabasum, an emerging treatment for DM, significantly downregulated IL-31 from CpG-stimulated peripheral blood mononuclear cells. CONCLUSIONS: Increased skin IL-31 may play a role in DM-associated itch, and ongoing trials will evaluate the effects of systemic treatment on IL-31 and itch in DM.

Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy (HIPEC) by Minimally Invasive Approach, an Initial Experience.

BACKGROUND: The cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard treatment in patients with carcinomatosis peritoneal from different origins. The use of a minimally invasive approach for this high complex procedure might be an alternative that provides them less morbidity and faster recovery with similar oncologic outcomes. METHODS: We describe the initial experience of CRS and HIPEC done via the laparoscopic route in patients with minimal peritoneal metastases in our Unit from March 2016 to January 2018. RESULTS: A total of eight patients were operated by this minimally invasive approach. The different diagnoses were low-grade pseudomyxoma peritonei (2), benign multicystic mesothelioma (2), primary epithelial ovarian carcinomatosis (2) and locally advanced colon carcinoma T4 (2). The median age was 54 (20-62) years, the median PCI was 3 (2-4), the median operative time was 287 min (240-360), complete cytoreduction CC0 was achieved in all the patients, and no major morbidity was observed. The median length of stay was 4.75 days (4-5). After a median follow-up of 9.5 months, no relapse has been observed. CONCLUSION: The results suggest that this minimally invasive approach for CRS and HIPEC is feasible and safe in a highly selected group of patients with peritoneal surface malignancies.

A genetic cluster of patients with variant xeroderma pigmentosum with two different founder mutations.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare human syndrome associated with hypersensitivity to sunlight and a high frequency of skin tumours at an early age. We identified a community in the state of Goias (central Brazil), a sunny and tropical region, with a high incidence of XP (17 patients among approximately 1000 inhabitants). OBJECTIVES: To identify gene mutations in the affected community and map the distribution of the affected alleles, correlating the mutations with clinical phenotypes. METHODS: Functional analyses of DNA repair capacity and cell-cycle responses after ultraviolet exposure were investigated in cells from local patients with XP, allowing the identification of the mutated gene, which was then sequenced to locate the mutations. A specific assay was designed for mapping the distribution of these mutations in the community. RESULTS: Skin primary fibroblasts showed normal DNA damage removal but abnormal DNA synthesis after ultraviolet irradiation and deficient expression of the Polη protein, which is encoded by POLH. We detected two different POLH mutations: one at the splice donor site of intron 6 (c.764 +1 G>A), and the other in exon 8 (c.907 C>T, p.Arg303X). The mutation at intron 6 is novel, whereas the mutation at exon 8 has been previously described in Europe. Thus, these mutations were likely brought to the community long ago, suggesting two founder effects for this rare disease. CONCLUSIONS: This work describes a genetic cluster involving POLH, and, particularly unexpected, with two independent founder mutations, including one that likely originated in Europe.

A qualitative study about experiences and emotions of emergency medical technicians and out-of-hospital emergency nurses after performing cardiopulmonary resuscitation resulting in death. / Estudio cualitativo sobre las experiencias y emociones de los técnicos y enfermeras de emergencias extrahospitalarias tras la realización de maniobras de reanimación cardiopulmonar con resultado de muerte.

OBJECTIVE: To explore the experiences, emotions and coping skills among emergency medical technicians and emergency nurses after performing out-of-hospital cardiopulmonary resuscitation manoeuvres resulting in death. METHOD: An exploratory qualitative research was performed. Seven emergency medical technicians and six emergency nurses were selected by non-probability sampling among emergency medical system workers. The meetings took place up to information saturation, achieved after six individual interviews and a focal group. The meetings were then transcribed and a manual and inductive analysis of the contents performed. MAIN RESULTS: After a failed resuscitation several short and long-term reactions appear. They can be negatives, such as sadness or uncertainty, or positives, such as the feeling of having done everything possible to save the patient's life. Emotional stress increases when ambulance staff have to talk with the deceased's family or when the patient is a child. The workers don't know of a coping strategy other than talking about their emotions with their colleagues. CONCLUSIONS: Death after a failed resuscitation can be viewed as a traumatic experience for rescuers. Being in contact with the suffering of others is an emotional, stress-generating factor with direct repercussions on the working and personal lives of emergency staff. Nevertheless, structured coping techniques are not common among those professionals.

[Knowledge and attitudes of citizens in the Basque Country (Spain) towards cardiopulmonary resuscitation and automatic external defibrillators]. / Conocimientos y actitudes de los ciudadanos del País Vasco sobre la resucitación cardiopulmonar y los desfibriladores externos automatizados.

AIM: To explore the training, ability and attitudes towards cardiopulmonary resuscitation and the use of automatic defibrillators among the population of the Basque Country (Spain). DESIGN: A face-to-face survey. SCOPE: Capital cities of the Basque Country. PARTICIPANTS: A total of 605 people between 15-64 years of age were randomly selected. MAIN VARIABLES OF INTEREST: Information about the knowledge, perceptions and self-perceived ability to identify and assist cardiopulmonary arrest was requested. RESULTS: A total of 56.4% of the responders were women, 61.8% were occupationally active, and 48.3% had higher education. Thirty-seven percent of the responders claimed to be trained in resuscitation techniques, but only 20.2% considered themselves able to apply such techniques. Public servants were almost 4 times more likely of being trained in defibrillation compared to the rest of workers (OR 3.7; P<.001), while people with elementary studies or no studies were almost 3 times more likely of not being trained in cardiopulmonary resuscitation, in comparison with the rest (OR 2.7; P=.001). A total of 94.7% of the responders considered it "quite or very important" for the general population to be able to apply resuscitation, though 55% considered themselves unable to identify an eye witnessed cardiac arrest, and 40.3% would not recognize a public-access defibrillator. CONCLUSIONS: Citizens of the Basque Country consider the early identification and treatment of cardiorespiratory arrest victims to be important, though their knowledge in cardiopulmonary resuscitation and defibrillation is limited.

Postoperative time course and utility of inflammatory markers in patients with ovarian peritoneal carcinomatosis treated with neoadjuvant chemotherapy, cytoreductive surgery, and HIPEC.

BACKGROUND: Inflammatory markers may help monitor postoperative evolution of surgical patients and detect complications. However, to date, the effect that neoadjuvant chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) may have in the postoperative kinetics of these parameters remains unknown. METHODS: Between July 2011 and June 2014, all patients who underwent neoadjuvant chemotherapy, cytoreductive surgery, and HIPEC for ovarian peritoneal carcinomatosis were studied. Patients were divided into four groups: no complications, noninfective complication, and infective complications during the first and second postoperative weeks. Retrospectively, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), white blood cell count, platelet-to-lymphocyte ratio, and prothrombin ratio were collected from postoperative days 1-14. Postoperative behavior of each parameter was carefully evaluated across groups. RESULTS: The study included 122 patients. Only CRP and NLR showed promising results. CRP presented a mean peak value at 48 h (186.1 mg/L), while NLR peaked at 24 h (10.21 mg/L). Both parameters rose with infective complications. Statistically significant differences were found at several time points compared with uncomplicated patients. A simple test comparing the peak value of CRP with the value when an infective complication was suspected accurately diagnosed these complications with sensitivity of 81 %, specificity of 91 %, and negative and positive predictive value of 93.1 and 76 %, respectively. This comparison presented lower diagnostic performance when NLR was used. CONCLUSIONS: Both CRP and NLR are useful in monitoring postoperative evolution in these patients; however, only CRP is useful for detecting infective complications.

Ataxia and myoclonic epilepsy due to a heterozygous new mutation in KCNA2: proposal for a new channelopathy.

We have recently performed exome analysis in a 7 year boy who presented in infancy with an encephalopathy characterized by ataxia and myoclonic epilepsy. Parents were not consanguineous and there was no family history of the disease. Exome analysis did not show any pathogenic variants in genes known to be associated with seizures and/or ataxia in children, including all known human channelopathies. However, we have identified a mutation in KCNA2 that we believe to be responsible for the disease in our patient. This gene, which encodes a member of the potassium channel, voltage-gated, shaker-related subfamily, has not been previously described as a cause of disease in humans, but mutations of the orthologous gene in mice (Kcna2) are known to cause both ataxia and convulsions. The mutation is c.890C>A, leading to the amino acid substitution p.Arg297Gln, which involves the second of the critical arginines in the S4 voltage sensor. This mutation is characterized as pathogenic by five different prediction programs. RFLP analysis and Sanger sequencing confirmed the presence of the mutation in the patient, but not in his parents, characterizing it as de novo. We believe that this discovery characterizes a new channelopathy.

A multiplex panel of short-amplicon insertion-deletion DNA polymorphisms for forensic analysis.

We have previously developed a panel of 40 insertion-deletion (INDEL) human DNA polymorphisms that was proven to ad-equately cover the span of global human genetic diversity. The panel was found to have very low matching probabilities with respect to both the global and Brazilian populations. To optimize the panel for application with degraded DNA samples, which are commonly encountered in fo-rensic analysis, we have significantly reduced the amplicon size of the INDELs and developed a new multiplex panel. The panel has an ampli-con size ranging from 50 to 153 base pairs, with a mean of 93 base pairs. It could be amplified by polymerase chain reaction in two multiplex re-actions, which were then combined for electrophoretic separation and identification of the individual products in the ABI3130 four-color DNA analyzer. The results of the new panel were fully validated.

Mitochondrial DNA damage is associated with damage accrual and disease duration in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the extent of mitochondrial DNA (mtDNA) damage in systemic lupus erythematosus (SLE) patients compared to healthy subjects and to determine the factors associated with mtDNA damage among SLE patients. METHODS: A cross-sectional study was performed in 86 SLE patients (per American College of Rheumatology classification criteria) and 86 healthy individuals matched for age and gender. Peripheral blood mononuclear cells (PBMCs) were collected from subjects to assess the relative amounts of mtDNA damage. Quantitative polymerase chain reaction assay was used to measure the frequency of mtDNA lesions and mtDNA abundance. Socioeconomic-demographic features, clinical manifestations, pharmacologic treatment, disease activity, and damage accrual were determined. Statistical analyses were performed using t test, pairwise correlation, and Pearson's chi-square test (or Fisher's exact test) as appropriate. RESULTS: Among SLE patients, 93.0% were women. The mean (SD) age was 38.0 (10.4) years and the mean (SD) disease duration was 8.7 (7.5) years. SLE patients exhibited increased levels of mtDNA damage as shown by higher levels of mtDNA lesions and decreased mtDNA abundance as compared to healthy individuals. There was a negative correlation between disease damage and mtDNA abundance and a positive correlation between mtDNA lesions and disease duration. No association was found between disease activity and mtDNA damage. CONCLUSION: PBMCs from SLE patients exhibited more mtDNA damage compared to healthy subjects. Higher levels of mtDNA damage were observed among SLE patients with major organ involvement and damage accrual. These results suggest that mtDNA damage have a potential role in the pathogenesis of SLE.

Pharmacogenomics: accessing important alleles by imputation from commercial genome-wide SNP arrays.

Personalized medicine is becoming a medical reality, as important genotype-phenotype relationships are being unraveled. The availability of pharmacogenomic data is a key element of individualized care. In this study, we explored genotype imputation as a means to infer important pharmacogenomic alleles from a regular commercially available genome-wide SNP array. Using these arrays as a starting point can reduce testing costs, increasing access to these pharmacogenomic data and still retain a larger amount of genome-wide information. IMPUTE2 and MaCH-Admix were used to perform genotype imputation with a dense reference panel from 1000 Genomes data. We were able to correctly infer genotypes for the warfarin-related loci VKORC1 and CYP2C9 alleles 2, 3, 5, and 11 and also clopidogrel-related CYP2C19 alleles 2 and 17 for a small sample of Brazilian individuals, as well as for HapMap samples. The success of an imputation approach in admixed samples using publicly available reference panels can encourage further imputation initiatives in those populations.

MULTINDELS-BOV: Zebu traceback method based on DNA insertion-deletion polymorphisms.

Brazil is a major producer and exporter of beef, with a herd of approximately 210 million animals. For the meat industry, a reliable animal traceback from its origin to the consumer market is paramount. Of all available identification systems, DNA is the only one that survives the slaughterhouse and reaches the dish of the consumer. DNA polymorphisms are already used for cattle traceback, but primarily for the subspecies Bos taurus taurus. However, in Brazil, another subspecies, B. taurus indicus predominates. We describe here the development of a DNA traceback method designed primarily for B. taurus indicus (Zebu), without leaving B. taurus taurus aside. We used insertion/deletion (indel) polymorphisms, which have the advantage of being simple and easily automatable, since in most cases, the variable loci are biallelic. We studied 94 indels, with a difference of two or more base pairs, in DNA pools of 60 Zebu and 60 taurine animals. A set of 22 indels with heterozygosity greater than 0.3 were selected and used to construct two multiplex PCRs. On the basis of the allelic frequency of these indels, the probability of random match was calculated to be 1.12 x 10(-8) for B. taurus indicus and 1.60 x 10(-6) for B. taurus taurus. Moreover, we estimated that an analysis would cost less than US$15.00 per animal. Thus, this system (MULTINDELS-BOV) is perfectly suited for building large genetic databases and offering viable prospects of a national system for cattle traceback DNA in Brazil.