Optic nerve abnormalities in female-restricted Wieacker-Wolff syndrome by a novel variant in the ZC4H2 gene.

BACKGROUND: Wieacker-Wolff syndrome is an ultra-rare disease with X-linked inheritance characterized by arthrogryposis, intellectual disability, microcephaly, and distal limb muscle atrophy. Ophthalmic abnormalities such as ptosis, strabismus, and oculomotor apraxia have been reported in half of the patients. Wieacker-Wolff syndrome female-restricted (WRWFFR) is an even rarer disease recently used for females with a more severe phenotype. MATERIALS AND METHODS: Clinical geneticist and ophthalmic examination, neuroimaging, and exome sequencing. RESULTS: A 4 years-old girl with developmental and language delay, microcephaly, camptodactyly, digital pads, and arthrogryposis was identified by the clinical geneticist. Ophthalmic examination revealed deep-set eyes, high hyperopic astigmatism in both eyes, and reduced retinal nerve fiber layer thickness measured by optical coherence tomography. Exome sequencing identified a novel, probably pathogenic variant in the ZC4H2 gene NM_018684.3:c.145A>T p. (Lys49*) in heterozygosis. DISCUSSION: WRWFFR is an ultra-rare disease with X-linked inheritance by variants in the ZC4H2 gene. This case reports a girl with a novel nonsense variant in the ZC4H2 gene and a severe phenotype; previous reports have identified WRWFFR in females with large deletions and nonsense mutations which could explain the manifestations in the current case report. A complete ophthalmic examination should be considered in patients with WRWFFR to detect the possibly associated optic nerve involvement and other previously described manifestations such as ptosis and strabismus.

Síndrome pilórico en un body packer / Pyloric syndrome in a body packer

Introducción. El embalaje y transporte de estupefacientes dentro del organismo, o body packing, es una práctica frecuente en Centroamérica y el Caribe. Además del riesgo de muerte por la exposición a las sustancias tóxicas, existe el riesgo de complicaciones mecánicas con indicación de manejo quirúrgico. El Hospital de Engativá, por su cercanía al aeropuerto de Bogotá, D.C., Colombia, es el centro de referencia para el tratamiento de estos pacientes. Caso clínico. Un hombre de 65 años traído al hospital por un episodio emético con expulsión de cuatro cápsulas para el transporte de estupefacientes. Al examen físico se encontraron masas palpables en el hemiabdomen superior, sin abdomen agudo. La tomografía de abdomen informó un síndrome pilórico secundario a retención gástrica de cuerpos extraños. Fue llevado a laparotomía y gastrotomía logrando la extracción de 97 objetos cilíndricos de látex que contenían sustancias ilícitas. Discusión. En los body packer asintomáticos, la administración de soluciones laxantes es una estrategia terapéutica segura. Los casos reportados de obstrucción gastrointestinal son infrecuentes y se relacionan con la ingesta de un gran número de cápsulas, por lo que es necesario el tratamiento quirúrgico. Conclusión. El síndrome pilórico es una presentación infrecuente en un body packer. Se debe tener un alto índice de sospecha para garantizar un manejo oportuno

Introduction. Packaging and transportation of narcotic drugs inside a human body, or body packing, is a frequent practice in Central America and the Caribbean. In addition to the risk of death due to exposure to toxic substances, there is a risk of mechanical complications with an indication for surgical management. The Engativá Hospital, due to its proximity to the airport in Bogotá, D.C., Colombia, is the reference center for the treatment of these patients. Clinical case. A 65-year-old man brought to the hospital for an emetic episode with expulsion of four narcotic transport capsules. Physical examination revealed palpable masses in the upper abdomen, without an acute abdomen. Abdominal tomography revealed pyloric syndrome secondary to gastric retention of foreign bodies. He was taken to laparotomy and gastrotomy, achieving the extraction of 97 cylindrical latex objects that contained illicit substances. Discussion. In asymptomatic body packers, the administration of laxative solutions is a safe therapeutic strategy. Reported cases of gastrointestinal obstruction are infrequent and are related to the ingestion of a large number of capsules, for which surgical treatment is necessary. Conclusion. Pyloric syndrome is an uncommon presentation in body packers. A high index of suspicion is required to ensure timely management

Polyautoimmunity in systemic lupus erythematosus patients: New insights from a cross-sectional study.

Objective: To assess the frequency of polyautoimmunity (PolyA) in a cohort of Colombian patients with systemic lupus erythematosus (SLE) and to identify associated factors. Methods: This is an analytical cross-sectional study in a specialized center., a comprehensive review of the medical records of SLE patients was performed from 2015 to 2020 in order to obtain demographic, clinical data, laboratory, and treatment information. Associations between PolyA, demographic, and characteristics of the disease were explored. Results: A total of 463 patients were included in the analysis. The average age was 47.3 ± 15 years. Most of this population were female (87.4%), whom were diagnosed with SLE in a long-term SLE (10.6 ± 10.1 years). Out of the total patients, 34.7% were diagnosed with PolyA. Among the most frequent clinical criteria for SLICC, arthritis (65%), kidney impairment (39.5%), and alopecia (34.8%) were found. The most frequent SLE-associated PolyA were antiphospholipid syndrome (APS) and Sjögren's syndrome (SS) (16.63% and 10.58%, respectively). PolyA-associated factors were age, xerophthalmia, central nervous system occlusion, and deep vein thrombosis (DVT). In contrast, renal impairment was significantly less frequent in PolyA patients after multivariate analysis. Conclusion: The results have showed associated factors with PolyA like age, xerophthalmia, central nervous system occlusion, and deep vein thrombosis in this cohort. On the other hand, lupus nephritis was less frequent in patients with PolyA. This study provides a spotlight of a specific SLE population as real-life evidence for a better characterization of PolyA in the future.

Predictors for limb amputation in war vascular trauma: A 20-years retrospective analysis from the Colombian armed conflict.

BACKGROUND: The Latin American military vascular trauma is virtually unknown. The aim of this study was to describe severe war vascular trauma during the last 20 years of the Colombian armed conflict, and to identify predictors of limb amputation. METHODS: Retrospective analysis of a follow-up cohort from 1999 to 2019 of patients with associated severe vascular injuries (ISS >15) in the Colombian armed conflict treated at the Hospital Militar Central. RESULTS: Out of 5948 patients, 243 had military vascular trauma with 430 vascular injuries. The most frequent trauma mechanisms were gunshot wounds (n = 153; 63%). The most common injured vessels were femoral. 24 (10%) patients required amputations. Mortality was 4.1%. Amputation was associated with arteriovenous lesions (RR 4.82, p = 0.025), compartment syndrome (RR 4.2, p = 0.007), arteriovenous femoropopliteal injuries (RR 3.5, p = 0.0026), multiple arterial injuries (RR 3.35, p = 0.0218), associated fractures (RR 3.1, p = 0.0032). CONCLUSIONS: Concomitant arteriovenous injuries in popliteal and femoropopliteal lesions, multiple arterial lesions, bone fractures, and compartment syndrome are associated with amputation in severe vascular injury.

Mitochondrial dysfunction: The pathological link between psoriasis and insulin resistance?

BACKGROUND: Psoriasis is strongly associated with insulin resistance (IR). Lipid profile disturbances and upregulation of enzymes crucial for fatty acid oxidation have been reported in patients with psoriasis. Mitochondrial ß-oxidation is altered in patients with IR. Common mitochondrial dysfunction may be involved in the origin of both diseases. OBJECTIVE: This study aimed to evaluate mitochondrial ß-oxidation, intermediary metabolism, and mitochondrial content in psoriatic patients with or without IR and compare them to healthy controls. METHODS: The participants were divided into three groups: (1) psoriasis and IR (n = 26); (2) psoriasis without IR (n = 17); and (3) healthy controls (n = 17). Quantification of amino acids and acylcarnitines (AC) by tandem mass spectrometry, determination of urinary organic acids by gas chromatography/mass spectrometry (GC/MS), and mitochondrial DNA quantification were performed in all groups. RESULTS: When comparisons were made between the two psoriatic groups, no differences were found between: C5DC + C6OH, C16:1, Met/Leu, Met/Phe, C16:1/C16, and C5DC + C6OH/C4DC + C5OH ratios. Nine analytes were different: phenylalanine, Cit/Phe, and Cit/Tyr ratios, C0, C3, C5, C6DC, C16, and C18:1OH. There were no correlations between psoriasis area and severity index (PASI), body mass index (BMI) and duration of disease with ACs. A higher proportion of patients with psoriasis showed increased urine levels of uric acid and hippuric acid (p = 0.01). The mtDNA content was significantly higher in cases than in controls, with no differences between IR and non-IR psoriatic patients. CONCLUSIONS: Psoriasis patients with and without IR have a different acylcarnitine profile reflecting impaired ß-oxidation. A distinctive profile of acylcarnitines suggests an involvement of mitochondrial function associated with an increase in stearoyl CoA desaturase (SCD) activity in psoriatic patients with and without IR.

Late-Onset 22q11.2 Deletion Syndrome With Mild Cardiac Phenotype: A Unique Adult Presentation Diagnosed at 45 Years of Age.

This case report presents a detailed exploration of an adult-onset 22q11 deletion syndrome, a rare genetic disorder typically diagnosed in children. The report highlights the diagnostic challenges posed by this atypical presentation, emphasizing the need for clinicians to consider such conditions in differential diagnoses, especially in adults. This case is remarkable for its late onset and mild symptoms, which significantly deviated from the common pediatric presentation, including hypocalcemia due to hypoparathyroidism and a fenestrated atrial septal defect without significant hemodynamic implications. The importance of recognizing the broad phenotypic variability of the syndrome and the implications for clinical practice are discussed, providing insights into the genetic and phenotypic diversity of the condition. In conclusion, this case illuminates the diverse clinical spectrum of adult-onset 22q11 deletion syndrome, emphasizing its relevance to clinical practice.

Chromosomal Abnormalities of Interest in Turner Syndrome: An Update.

Turner syndrome (TS) is caused by the total or partial loss of the second sex chromosome; it occurs in 1 every 2,500-3,000 live births. The clinical phenotype is highly variable and includes short stature and gonadal dysgenesis. In 1959, the chromosomal origin of the syndrome was recognized; patients had 45 chromosomes with a single X chromosome. TS presents numerical and structural abnormalities in the sex chromosomes, interestingly only 40% have a 45, X karyotype. The rest of the chromosomal abnormalities include mosaics, deletions of the short and long arms of the X chromosome, rings, and isochromosomes. Despite multiple studies to establish a relationship between the clinical characteristics and the different chromosomal variants in TS, a clear association cannot yet be established. Currently, different mechanisms involved in the phenotype have been explored. This review focuses to analyze the different chromosomal abnormalities and phenotypes in TS and discusses the possible mechanisms that lead to these abnormalities.

Congenital Heart Diseases: Genetic Risk Variants and Their Methylation Status.

(1) Background: The interaction between single nucleotide variants (SNVs) associated with congenital heart diseases (CHDs) and their gene methylation status has not been well researched. The aim of the present study was to determine if there is a relationship between the methy lation status (MS) of genes and the allelic variants associated with CHDs. (2) Methods: Seven SNVs of the genes AXIN1, TBX1, TBX20, and MTHFR were selected from the literature. DNA extraction, genotyping, and a methylation analysis were performed on healthy subjects and subjects with CHDs. (3) Results: Twenty-two subjects with CHDs were selected as the case group (15 with ventricular septal defects (VSDs) and 7 with atrial septal defects (ASDs)), and 44 healthy subjects comprised the control group. The MTHFR and AXIN1 genes were hypermethylated in the control group when compared to the case group. When analyzed separately, those with atrial septum defects exhibited greater methylation, except for the gene MTHFR where there were no differences. Only the alternate alleles of MTHFR showed a significantly different methylation status in those without cardiopathy. (4) Conclusions: The MTHFR and AXIN genes were hypermethylated in the control group; however, only the alternate alleles of MTHFR (rs1801133 and rs1801131) showed a significantly different methylation status.

Diagnosis and treatment of benign adipocytic tumors in children.

PURPOSE: To describe demographic, clinical, diagnostic and therapeutic aspects of pediatric patients with benign adipocytic tumors admitted to a high complexity teaching hospital from 2007 to 2021. METHODS: Retrospective observational descriptive study. Patient information was retrieved from clinical records. A descriptive analysis was carried out for qualitative data and frequencies were calculated for quantitative data. RESULTS: 76 patients were included with a mean age of 7.5 years old where 60.5% were boys. The main symptom was a mass (73.7%) mostly found in the lower limbs (23.6%). Congenital birth defects were identified in 48.6% of the cases. Preoperative imaging was available in 78.9% of the patients allowing characterization of lesions or differential diagnosis. The therapeutic goal was resection with negative margins, which was feasible in all cases except for one case. The histopathological diagnosis was lipoma in 68.4% of the cases followed by lipoblastoma in 13.1%. The mean follow-up period was 17.9 months. 79.7% of the patients were asymptomatic at their last out-patient visit. CONCLUSION: Benign adipocytic tumors constitute a wide spectrum of lesions, which involve diverse anatomic segments from the neural axis to the inguinoscrotal region. The present work contributes to the general understanding of the clinical presentation and differential diagnosis for these infrequent neoplasms.

Direct Medical Costs and Healthcare Resource Utilization of Treating Patients With Two Clinical Subtypes of Axial Spondyloarthritis in Colombia.

OBJECTIVES: This study aimed to calculate the healthcare resource utilization and direct medical costs in patients with 2 subtypes of axial spondyloarthritis (axSpA) in a rheumatic care center in Colombia. METHODS: This is a retrospective cost-of-illness study. Patients with at least 1 medical consultation associated with an axSpA diagnosis between October 2018 and October 2019 were identified. Patients were classified as having radiographic (r-axSpA) or nonradiographic axSpA (nr-axSpA). Direct medical costs were calculated in Colombian pesos and expressed in American dollars using an exchange rate of 3263 Colombian pesos = 1 US dollar ($). Predictors of total direct costs were identified using a generalized linear model with gamma distribution and log-link. RESULTS: A total of 162 patients with a mean age of 49.6 years (± 13.7) were included in the study. Among these, 147 (90.7%) were considered as having r-axSpA and 15 (9.3%) nr-axSpA, with mean costs of $6600 (± 6203) and $843 (± 1135), respectively (P < .001). The total direct mean cost was calculated at $6067 (± 6144) per patient. Medication costs were the main driver of total costs (97.6%, $5921), with biologic disease-modifying antirheumatic drugs accounting for nearly 92.0% ($5582) of these costs. Rheumatologist (100%) and physiatrist (64.2%) visits were the most frequently used medical service. CONCLUSIONS: The economic burden associated with axSpA in the Colombian setting is substantial. There is a significant difference in direct medical costs between the r-axSpA and the nr-axSpA. Health policies aimed at the comprehensive management of nr-axSpA would have an important role in the reduction of the associated direct medical costs.

Relación entre la cuenta de Twitter @ascolcirugia y las publicaciones de la Revista Colombiana de Cirugía durante la pandemia / Relationship between the Twitter account @ascolcirugia and the publications of the Colombian Journal of Surgery during the pandemic

Introducción. Indicadores alternativos basados en la web 2.0 han tomado importancia para medir el impacto de la producción científica. Previamente se han demostrado correlaciones positivas entre indicadores tradicionales y alternativos. El objetivo de este trabajo fue evaluar la relación de estos indicadores en el campo de la cirugía de nuestro país.Métodos. Análisis retrospectivo de las publicaciones de la Revista Colombiana de Cirugía y "tweets" de la cuenta @ascolcirugia entre marzo 2020 y julio 2021. Se evaluaron comparativamente los artículos con y sin publicación en la cuenta @ascolcirugia. Se determinó la correlación entre indicadores alternativos e indicadores tradicionales de las publicaciones de la revista. Resultados. En total se revisaron 149 artículos y 780 "tweets"; tan sólo el 13,4 % (n=20) de los artículos tuvieron visibilidad en la cuenta @ascolcirugia, con una mediana de 2 "tweets" (RIQ 1-2) por artículo, siendo la mayoría de estos sobre temas de COVID-19 (85 % vs 10 %; p<0,001). Los artículos publicados en @ascolcirugia tuvieron una mayor mediana de descargas (220 vs 116; p<0,001) y citaciones (3,5 vs 0; p<0,001) en comparación con los que no fueron publicados.Conclusión. El uso de las redes sociales tiene un efecto positivo en el número de lectores de la Revista Colombiana de Cirugía y el impacto académico de los autores. Aunque existe una buena correlación entre indicadores alternativos y tradicionales en el contexto nacional, la proporción de artículos de la Revista Colombiana de Cirugía publicados en la cuenta @ascolcirugia es baja.

Introduction. Alternative indicators based on web 2.0 have gained great relevance to measure the impact of scientific production. Positive correlations between traditional and alternative indicators have previously been shown. The objective of our article is to evaluate the relationship of these indicators in the field of surgery in our country.Methods. Retrospective analysis of the publications of the Colombian Journal of Surgery and tweets of the Twitter account (@ascolcirugia) during March 2020 and July 2021. Articles with and without tweets in the account @ascolcirugia were comparatively evaluated. The correlation between alternative indicators and traditional indicators of the journal's publications was determined. Results. A total of 149 articles and 780 tweets were reviewed; only 13.4% (n=20) of the articles had visibility at the @ascolcirugia account, with a median of 2 tweets (RIQ 1-2) per article, most of which were on COVID-19 issues (85% vs 10%; p<0.001). The articles published at the @ascolcirugia account had a higher median number of downloads (220 vs 116; p<0.001) and citations (3.5 vs 0; p<0.001) compared to the articles that were not published. Conclusions. The use of social media has a positive effect on the number of readers of the Colombian Journal of Surgery and the academic impact of the authors. Although there is a good correlation between alternative and traditional indicators, in the national context, the proportion of articles of the Colombian Journal of Surgery published at the @ascolcirugia account is low

Is Tofacitinib Effectiveness in Patients with Rheumatoid Arthritis Better After Conventional Than After Biological Therapy? - A Cohort Study in a Colombian Population.

Purpose: Tofacitinib is recommended for treatment of rheumatoid arthritis (RA) in patients with moderate to severe disease activity, but there is not enough evidence on its effectiveness after conventional DMARDs vs its use after biologics. The aim was evaluating the effectiveness of tofacitinib in RA as first-line treatment (after conventional DMARDs) in a real-life setting in Colombian (Latin-American) patients. Patients and Methods: Retrospective cohort study conducted at a specialized center for RA management. A complete statistical analysis was performed to compare the values of the change in the DAS28 at months 3, 6, and 12 in both treatment groups. Results: A total of 152 RA patients who received tofacitinib: first-line 85 patients (55.9%) after failure on conventional DMARDs or second-line 67 patients (44.1%) after failure on biologic DMARDs. Comparative analysis of response to treatment showed a reduction in DAS28 at 3, 6, and 12 months in both study groups without statistical differences, but a higher proportion of first-line patients achieved remission (45% vs 23%). Nonresponse at three months were associated with no response at six months of follow-up. Baseline DAS28 was significantly associated with response at 12 months (OR: 1.87, 95%CI: 1.06-3.30, p-value 0.028). In second-line patients, response to tofacitinib was not related to number of biologic DMARDs previously used. Conclusion: Tofacitinib is an effective treatment option for patients with RA, maybe better after conventional DMARDs than after biologic therapy failure. Further studies are required to determine the role of tofacitinib in different lines of RA treatment and in other groups of patients.

Proteomic profile of preeclampsia in the first trimester of pregnancy.

OBJECTIVE: Preeclampsia (PE) is a leading cause of pregnancy-associated maternal and neonatal morbidity and mortality. Detection of patients at risk before the clinical onset of PE is a priority. Proteomics have become a valuable tool for the discovery of new biomarkers; however, the understanding of the underlying mechanism is necessary. The aim of the study was to determine differences between proteomic serum profiles of PE and normotensive pregnancies using quantitative and qualitative approaches. STUDY DESIGN: Serum samples from pregnant women were taken at 10-12 weeks of gestation with follow-up to determine PE development. Samples were analyzed using nano 2-D liquid chromatography UPLC and qTOF-MS/MS. RESULTS: A total of 136 women were recruited, of which eight (5.9%) developed PE, and eight normotensive were randomly selected as a control group for comparison. A different profile was obtained between groups. Nine proteins showed quantitative differences with fold-change over 1.5: PRRC2C (217.02), HEATR5A (179.46), ATP6 (162.38), PRRC2B (83.09), RBM25 (5.36), NUP205 (3.38), HLA-I (2.27), ZC3H13 (2.15), and SREK1 (1.66); and two under 0.66: Importin-4 (0.55) and Cytochrome b (0.26). Using bilateral Fisher's exact test for the qualitative approach, LRRK1 had statistical significance (p = .044), while PRRC2B (p = .121), PRRC2C (p = .134), and NUP205 (p = .134) showed a tendency to be present in PE. CONCLUSION: The found proteins have plausibility with the early pathophysiological events that have been associated with this pathology. Further studies should be performed to confirm these findings and elucidate their specific roles.

Certolizumab Can Also Be Effective in Monotherapy for the Treatment of Rheumatoid Arthritis Patients.

OBJECTIVE: Although it is known that methotrexate (MTX) increases the effectiveness of biological drugs (mainly anti-TNFs) in patients with rheumatoid arthritis (RA), in real life, it is known that many patients using anti-TNFs are on monotherapy due to many causes. This article compares the effectiveness of certolizumab as monotherapy as combined with MTX or leflunomide (LFN) in RA patients with failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in a real-world setting. METHODS: A retrospective observational cohort study was conducted at a specialized centre for RA management in Colombia. Patients treated with certolizumab as monotherapy or in combination with MTX, LFN, or MTX+LFN, between 2011 and 2020 with a minimum 3-month follow-up were included. Demographics and RA clinical characteristics were recorded; effectiveness was assessed as the improvement in Disease Activity Score (DAS28) getting remission or low disease activity at 3, 6, and 12 months of treatment. RESULTS: A total of 181 patients were included, 24 received certolizumab as monotherapy, 62 certolizumab plus MTX, 47 certolizumab plus LFN and 48 certolizumab plus MTX+LFN. At 3 months of follow-up, 80% of the patients showed decreased disease activity, with no significant differences between groups; at 12 months of treatment, response in certolizumab monotherapy group was 94.4% compared to 81.8% in combination with MTX, 80.5% in combination with LFN and 51.4% in combination with MTX+LFN. Response at 3 months (OR 4.04; 95% CI 1.28-12.69) and positive anti-CCP (OR 3.83; 95% CI 1.11-13.21) were associated with 12-month response. CONCLUSION: Certolizumab seems to be effective as monotherapy in the treatment of RA patients with failure to csDMARDs.

Maternal Folic Acid Intake and Methylation Status of Genes Associated with Ventricular Septal Defects in Children: Case-Control Study.

BACKGROUND: DNA methylation is the best epigenetic mechanism for explaining the interactions between nutrients and genes involved in intrauterine growth and development programming. A possible contributor of methylation abnormalities to congenital heart disease is the folate methylation regulatory pathway; however, the mechanisms and methylation patterns of VSD-associated genes are not fully understood. OBJECTIVE: To determine if maternal dietary intake of folic acid (FA) is related to the methylation status (MS) of VSD-associated genes (AXIN1, MTHFR, TBX1, and TBX20). METHODS: Prospective case-control study; 48 mothers and their children were evaluated. The mothers' dietary variables were collected through a food frequency questionnaire focusing on FA and the consumption of supplements with FA. The MS of promoters of genes was determined in the children. RESULTS: The intake of FA supplements was significantly higher in the control mothers. In terms of maternal folic acid consumption, significant differences were found in the first trimester of pregnancy. Significant differences were observed in the MS of MTHFR and AXIN1 genes in VSD and control children. A correlation between maternal FA supplementation and MS of AXIN1 and TBX20 genes was found in control and VSD children, respectively. CONCLUSIONS: A lower MS of AXIN1 genes and a higher MS of TBX20 genes is associated with FA maternal supplementation.

Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes Disease.

Menkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper transporting α (ATP7A) gene. Our objective was to identify genomic alterations and circulating proteomic profiles related to MD assessing their potential roles in the clinical features of the disease. We describe the case of a male patient of 8 months of age with silvery hair, tan skin color, hypotonia, alterations in neurodevelopment, presence of seizures, and low values of plasma ceruloplasmin. Trio-whole-exome sequencing (Trio-WES) analysis, plasma proteome screening, and blood cell migration assays were carried out. Trio-WES revealed a hemizygous change c.4190C > T (p.S1397F) in exon 22 of the ATP7A gene. Compared with his parents and with child controls, 11 plasma proteins were upregulated and 59 downregulated in the patient. According to their biological processes, 42 (71.2%) of downregulated proteins had a participation in cellular transport. The immune system process was represented by 35 (59.3%) downregulated proteins (p = 9.44 × 10-11). Additional studies are necessary to validate these findings as hallmarks of MD.

Quantifying Potential Cost-Savings Through an Alternative Imaging-Based Diagnostic Process in Presumptive Seronegative Rheumatoid Arthritis.

BACKGROUND: Seronegative rheumatoid arthritis (SRA) is a condition that is not well understood and difficult to confirm by a conventional diagnostic process. We aimed to quantify the potential cost-savings of an alternative diagnostic process (ADP) imaging-based, for patients with presumptive SRA from everyday clinical practice. METHODS: We performed a retrospective analysis for patients with presumptive SRA who tested negative for both rheumatoid factor and anti-cyclic citrullinated peptide antibodies, through an ADP imaging-based, that is a standard clinical practice in our center. After we confirmed the diagnosis of SRA or reclassified patients in terms of another proper diagnosis, we estimate direct costs in two scenarios: a conventional and ADP. We compared the cost of RA treatment during the first year against the cost of the most misdiagnosed treatment (osteoarthritis) found after applying the ADP to determine potential cost-savings. RESULTS: We included 440 patients with a presumptive diagnosis of SRA. According to the imaging-based ADP, SRA was confirmed in 106/440 (24.1%), unspecified RA in 9/440 (2.0%), and osteoarthritis in 325/440 (73.9%) of those patients. Although the costs of conventional diagnosis per patient is lower than those of ADP ($59,20 USD vs $269,57 USD), we found a potential drug cost-savings of $1,570,775.20 US Dollars after 1 year of correct treatment. CONCLUSION: An alternative diagnosis process, including X-rays, US and MRI imaging, and clinical and blood-test assessment, not only increased diagnostic certainty in patients referred for evaluation of presumptive SRA but also suggested a potential cost-savings in pharmacological treatments avoided in misdiagnosed patients.

miRNAs of Aedes aegypti (Linnaeus 1762) conserved in six orders of the class Insecta.

Aedes aegypti L. is the most important vector of arboviruses such as dengue, Zika, chikungunya, Mayaro, and yellow fever, which impact millions of people's health per year. MicroRNA profile has been described in some mosquito species as being important for biological processes such as digestion of blood, oviposition, sexual differentiation, insecticide resistance, and pathogens dissemination. We identified the miRNAs of Ae. aegypti females, males and eggs of a reference insecticide susceptible strain New Orleans and compared them with those other insects to determine miRNA fingerprint by new-generation sequencing. The sequences were analyzed using data mining tools and categorization, followed by differential expression analysis and conservation with other insects. A total of 55 conserved miRNAs were identified, of which 34 were of holometabolous insects and 21 shared with hemimetabolous insects. Of these miRNAs, 32 had differential expression within the stages analyzed. Three predominant functions of miRNA were related to embryonic development regulation, metamorphosis, and basal functions. The findings of this research describe new information on Ae. aegypti physiology which could be useful for the development of new control strategies, particularly in mosquito development and metamorphosis processes.