Role of Gasotransmitters in Inflammatory Edema.

Significance: Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are, to date, the identified members of the gasotransmitter family, which consists of gaseous signaling molecules that play central roles in the regulation of a wide variety of physiological and pathophysiological processes, including inflammatory edema. Recent Advances: Recent studies show the potential anti-inflammatory and antiedematogenic effects of NO-, CO-, and H2S-donors in vivo. In general, it has been observed that the therapeutical effects of NO-donors are more relevant when administered at low doses at the onset of the inflammatory process. Regarding CO-donors, their antiedematogenic effects are mainly associated with inhibition of proinflammatory mediators (such as inducible NO synthase [iNOS]-derived NO), and the observed protective effects of H2S-donors seem to be mediated by reducing some proinflammatory enzyme activities. Critical Issues: The most recent investigations focus on the interactions among the gasotransmitters under different pathophysiological conditions. However, the biochemical/pharmacological nature of these interactions is neither general nor fully understood, although specifically dependent on the site where the inflammatory edema occurs. Future Directions: Considering the nature of the involved mechanisms, a deeper knowledge of the interactions among the gasotransmitters is mandatory. In addition, the development of new pharmacological tools, either donors or synthesis inhibitors of the three gasotransmitters, will certainly aid the basic investigations and open new strategies for the therapeutic treatment of inflammatory edema. Antioxid. Redox Signal. 40, 272-291.

[Colorectal cancer in pregnancy. Case reports]. / Cáncer colorectal en el embarazo. Reportes de caso.

Colon rectal cancer (CRC) during pregnancy is a rare neoplasia, with an incidence between 0.07-0.1% in the population. For an early diagnosis, a high suspicion is necessary and with it, timely diagnostic tests are carried out. When there is no suspicion and no diagnosis is sought, the prognosis is usually poor since it is often in an advanced state. We present the cases of two pregnant women aged 27 and 31 diagnosed with moderately differentiated colorectal adenocarcinoma at 29 and 30 weeks of gestation, respectively. Due to the importance of making an opportune diagnosis to improve the survival of the patients, a search of information was carried out in the literature in relation to the diagnosis, management and prognosis of this pathology.

Aedes aegypti salivary gland extract alleviates acute itching by blocking TRPA1 channels.

Aedes aegypti (Ae. aegypti) saliva induces a variety of anti-inflammatory and immunomodulatory activities. Interestingly, although it is known that mosquito bites cause allergic reactions in sensitised hosts, the primary exposure of humans to Ae. aegypti does not evoke significant itching. Whether active components in the saliva of Ae. aegypti can counteract the normal itch reaction to injury produced by a histaminergic or non-histaminergic pathway in vertebrate hosts is unknown. This study investigated the effects of Ae. aegypti mosquito salivary gland extract (SGE) on sensitive reactions such as itching and associated skin inflammation. Acute pruritus and plasma extravasation were induced in mice by the intradermal injection of either compound 48/80 (C48/80), the Mas-related G protein-coupled receptor (Mrgpr) agonist chloroquine (CQ), or the transient receptor potential ankyrin 1 (TRPA1) agonist allyl isothiocyanate (AITC). The i.d. co-injection of Ae. aegypti SGE inhibited itching, plasma extravasation, and neutrophil influx evoked by C48/80, but it did not significantly affect mast cell degranulation in situ or in vitro. Additionally, SGE partially reduced CQ- and AITC-induced pruritus in vivo, suggesting that SGE affects pruriceptive nerve firing independently of the histaminergic pathway. Activation of TRPA1 significantly increased intracellular Ca2+ in TRPA-1-transfected HEK293t lineage, which was attenuated by SGE addition. We showed for the first time that Ae. aegypti SGE exerts anti-pruriceptive effects, which are partially regulated by the histamine-independent itch TRPA1 pathway. Thus, SGE may possess bioactive molecules with therapeutic potential for treating nonhistaminergic itch.

Beneficial Effects of Two Hydrogen Sulfide (H2S)-Releasing Derivatives of Dexamethasone with Antioxidant Activity on Atopic Dermatitis in Mice.

Hydrogen sulfide (H2S) is particularly produced in the skin, where it participates in the regulation of inflammation, pruritus, cytoprotection, scarring, and angiogenesis. In this study, we compared the effects of dexamethasone (Dex) with two H2S-releasing Dex derivatives in a murine model of atopic dermatitis (AD) induced by topical application of 2,4-dinitrochlorobenzene (DNCB). After sensitization with DNCB, the animals were topically treated for five consecutive days with either the H2S-releasing compounds 4-hydroxy-thiobenzamide (TBZ) and 5-(p-hydroxyphenyl)-1,2-dithione-3-thione (ADT-OH), Dex, or the derivatives Dex-TBZ or Dex-ADT. Topical treatment with equimolar doses of either Dex, Dex-TBZ, or Dex-ADT resulted in similar reductions in dermatitis score, scratching behavior, edema, eosinophilia, splenomegaly, and histological changes. In contrast with Dex, the H2S-releasing derivatives prevented IL-4 elevation and oxidative modification of skin proteins. On an equimolar dose basis, Dex-TBZ, but not Dex-ADT, promoted the elevation of endogenous H2S production and GPx activity. Neither Dex-TBZ nor Dex-ADT decreased GR activity or caused hyperglycemia, as observed with Dex treatment. We conclude that the presence of H2S-releasing moieties in the Dex structure does not interfere with the anti-inflammatory effects of this corticosteroid and adds beneficial therapeutical actions to the parent compound.

Cáncer colorectal en el embarazo. Reportes de caso

El cáncer colorrectal (CCR) durante el embarazo es una neoplasia poco frecuente, con una incidencia entre el 0,07- 0,1% en la población. Para un diagnóstico preciso es necesaria una alta sospecha y con ello realizar pruebas diagnósticas oportunas. Cuando no se tiene sospecha ni se busca el diagnóstico, el pronóstico suele ser malo, ya que muchas veces se halla en estado avanzado. Presentamos los casos de dos gestantes de 27 y 31 años, diagnosticadas de adenocarcinoma colorrectales medianamente diferenciados a las 29 y 30 semanas de gestación, respectivamente. Debido a la importancia de realizar un diagnóstico oportuno para mejorar la sobrevida de las pacientes, se realizó una búsqueda de información en la literatura en relación con el diagnóstico, manejo y pronóstico de esta patología.

Colon rectal cancer (CRC) during pregnancy is a rare neoplasia, with an incidence between 0.07-0.1% in the population. For an early diagnosis, a high suspicion is necessary and with it, timely diagnostic tests are carried out. When there is no suspicion and no diagnosis is sought, the prognosis is usually poor since it is often in an advanced state. We present the cases of two pregnant women aged 27 and 31 diagnosed with moderately differentiated colorectal adenocarcinoma at 29 and 30 weeks of gestation, respectively. Due to the importance of making an opportune diagnosis to improve the survival of the patients, a search of information was carried out in the literature in relation to the diagnosis, management and prognosis of this pathology.

Localização topográfica da emergência do condóito nasolagrimal medido em tomografia como reparação anatômica para procedimentos de cirurgia maxilofacial / Topographic location of the nasolagrimal conduit emergence measured on ct scans as an anatomical repair for maxillofacial surgery procedures / Ubicación topográfica de la emergencia del conducto nasolagrimal medida en tomografías como reparo anatómico para procedimientos de cirugía maxilofacial

Contexto: Na cirurgia maxilofacial existem procedimentos que envolvem o ducto nasolacrimal, pelo que esta medida é um ponto de referência para evitar a sua lesão. Artigos anteriores tomam como referência o fenótipo anglo-saxão e não a população latino-americana, o que é uma grande limitação quando se extrapola para a cirurgia maxilofacial. Objetivo: Medir a distância do ducto nasolacrimal às estruturas anatômicas adjacentes em uma amostra de tomografias computadorizadas do Hospital Universitário San Ignacio em Bogotá, Colômbia, em 2021. Métodos: Foi realizado um estudo observacional retrospetivo com base em tomografias computadorizadas do HUSI. Foi utilizada uma amostragem não probabilística, na qual foram identificadas 150 tomografias computadorizadas. Informações sobre sexo, idade e distância do ducto nasolacrimal em milímetros foram coletadas em um banco de dados em planilha Excel, tendo como marcos anatômicos o entalhe piriforme, o forame infraorbitário e o assoalho da fossa nasal em cortes axiais, sagitais e coronais. Resultados: A análise das medidas mostrou que nenhuma das distribuições de medidas se comportou de forma diferente da distribuição normal. Em relação à comparação das medidas por sexo, a idade foi semelhante entre homens e mulheres, enquanto nas comparações por idade foram evidenciadas diferenças significativas. Conclusão: Os resultados são consistentes com os dados publicados em estudos anteriores. Em termos de distribuição por sexo, o comprimento do ducto nasolacrimal é maior nos homens do que nas mulheres, e a distribuição por idade indica que, à medida que a idade aumenta, a distância do ducto a estas estruturas diminui... (AU)

Background: In maxillofacial surgery there are procedures that involve the nasolacrimal duct, so this measure is a reference point to avoid its injury. Previous articles take as reference the Anglo-Saxon phenotype and not the Latin American population, which is a great limitation when extrapolating it to maxillofacial surgical procedures. Objective: To measure the distance of the nasolacrimal duct to adjacent anatomical structures in a sample of CT scans from the Hospital Universitario San Ignacio in Bogotá- Colombia in 2021. Methods: A retrospective observational study was performed based on CT scans from HUSI. A non-probabilistic sampling was used in which 150 CT scans were identified. Information on sex, age and distance of the nasolacrimal duct in millimeters was collected in an Excel spreadsheet database, taking as anatomical landmarks the piriform notch, the infraorbital foramen and the floor of the nasal fossa in axial, sagittal and coronal sections. Results: The analysis of the measurements showed that none of the measurement distributions had a behavior different from the normal distribution. In relation to the comparison of the measurements by sex, age was similar in men and women, while significant differences were evidenced in the comparisons by age. Conclusion: The results coincide with the data published in previous studies. Regarding the distribution by sex, the length of the nasolacrimal duct is greater in men than in women, and the distribution by age indicates that as age increases the distance of the duct to these structures decreases... (AU)

Antecedentes: En cirugía maxilofacial existen procedimientos que involucran el conducto nasolagrimal, por lo cual esta medida es un punto de referencia para evitar su lesión. Artículos previos toman como referencia el fenotipo anglosajón y no la población Latinoamericana, lo cual supone una gran limitante al extrapolarlo a intervenciones quirúrgicas maxilofaciales. Objetivo: Medir la distancia del conducto nasolagrimal a estructuras anatómicas adyacentes en una muestra de tomografías del Hospital Universitario San Ignacio en BogotáColombia en 2021. Métodos: Se realizó un estudio observacional retrospectivo basado en tomografías del HUSI. Se utilizó un muestreo no probabilístico en el que se identificaron 150 tomografías. En una base de datos en hoja de cálculo en Excel se recolectó información sobre sexo, edad y distancia del conducto nasolagrimal en milímetros, teniendo como reparo anatómico la escotadura piriforme, el agujero infraorbitario y el piso de la fosa nasal en los cortes axial, sagital y coronal. Resultados: El análisis de las mediciones realizadas mostró que ninguna de las distribuciones de medición tuvo un comportamiento distinto a la distribución normal. En relación con la comparación de las medidas por sexo la edad fue similar en los hombres y mujeres, mientras que se evidenciaron diferencias significativas en las comparaciones por edad. Conclusión: Los resultados coinciden con los datos publicados en estudios previos. En cuanto a la distribución por sexo, la longitud del conducto nasolagrimal es mayor en hombres que en mujeres, y la distribución por edad indica que conforme aumenta la edad la distancia del conducto a estas estructuras disminuye... (AU)

Frequent copy number variants in a cohort of Mexican-Mestizo individuals.

BACKGROUND: The human genome presents variation at distinct levels, copy number variants (CNVs) are DNA segments of variable lengths that range from several base pairs to megabases and are present at a variable number of copies in human genomes. Common CNVs have no apparent influence on the phenotype; however, some rare CNVs have been associated with phenotypic traits, depending on their size and gene content. CNVs are detected by microarrays of different densities and are generally visualized, and their frequencies analysed using the HapMap as default reference population. Nevertheless, this default reference is inadequate when the samples analysed are from people from Mexico, since population with a Hispanic genetic background are minimally represented. In this work, we describe the variation in the frequencies of four common CNVs in Mexican-Mestizo individuals. RESULTS: In a cohort of 147 unrelated Mexican-Mestizo individuals, we found that the common CNVs 2p11.2 (99.6%), 8p11.22 (54.5%), 14q32.33 (100%), and 15q11.2 (71.1%) appeared with unexpectedly high frequencies when contrasted with the HapMap reference (ChAS). Yet, while when comparing to an ethnically related reference population, these differences were significantly reduced or even disappeared. CONCLUSION: The findings in this work contribute to (1) a better description of the CNVs characteristics of the Mexican Mestizo population and enhance the knowledge of genome variation in different ethnic groups. (2) emphasize the importance of contrasting CNVs identified in studied individuals against a reference group that-as best as possible-share the same ethnicity while keeping this relevant information in mind when conducting CNV studies at the population or clinical level.

Características Clínicas y Epidemiológicas en Pacientes Diagnosticados con Síndrome de Sjögren en un Hospital Universitario de Cuarto Nivel

El síndrome de Sjögren es la segunda enfermedad autoinmune crónica más prevalente; factores hereditarios y medioambientales interactúan provocando una "epitelitis autoinmune" que daña el tejido glandular exocrino principalmente, pero también a otros órganos; debido a esta heterogeneidad clínica, el diagnóstico y tratamiento constituyen un desafío. Estudios demuestran que afecta al 0,1-0,6 % de la población, con predilección por el sexo femenino (9:1). En Colombia existen pocos estudios epidemiológicos descriptivos y de caracterización en este síndrome. Caracterizar los parámetros clínicos y epidemiológicos de pacientes con síndrome de Sjögren. Se realizó un estudio observacional descriptivo de corte transversal, se revisaron historias clínicas de 409 pacientes con el síndrome que asistieron al Hospital Universitario San Ignacio entre 2012 y 2019. Los datos se analizaron usando estadística descriptiva. La edad promedio de diagnóstico fue 59 años, la relación mujer: hombre 9:1, (91,7 % y 8,3 % respectivamente). Hubo mayor prevalencia en pacientes de 51 a 60 años (131) seguido por los de 61-70 años (114). La manifestación clínica más común fue la xerostomía (90 %); la biopsia de glándula salival menor fue el examen complementario más solicitado (65 %). El compromiso óseo-articular, fue la enfermedad concomitante más asociada. La etiología de la enfermedad es poco conocida, sin embargo, su caracterización, así como la identificación de medios diagnósticos y terapéuticos ayuda en la comprensión de la clínica; dicha información permitirá el desarrollo de tratamientos cada vez más efectivos y específicos.

Sjögren syndrome is the second most common chronic autoimmune disease, environmental and hereditary mechanisms causes an autoimmune epithelitis that affect the exocrine glandular tissue mainly, but also other organs; because this broad spectrum of clinical characteristics, the diagnostic and treatment become a challenge. Studies has shown that 0.1-0.6 % of the population is affected, with predominance of females over males (9:1). In Colombia there are few descriptive epidemiological studies and characterization of the affected population. Clinical and epidemiological characterization of Sjögren syndrome patients. A descriptive cross-sectional observational study was conducted, 409 clinical histories of patients with the syndrome at San Ignacio University Hospital from 2012 to 2019 were analized. The data collected were subjected to a descriptive statistic. The average age of diagnosis was 59 years, the ratio female: male 9:1 (91.7 % and 8.3 % respectively), the highest frequency of the syndrome was found in the 51 to 60 years old group (131) followed by the 61 to 70 years old group (114). The most common clinical manifestation was xerostomia (90 %), minor salivary gland biopsy was the most frequent test requested (65 %). The osseoarticular involvement was the most frecuent concomitant disease. Although the etiology of Sjögren syndrome is little known, its characterization, as well as the identification of the diagnostic and therapeutic means used, is of great help in understanding the disease; this information will allow the development of increasingly effective and specific treatments. More studies are required, in different locations, which will highlight the differences between populations.

Perfil antibiótico de estreptococos del grupo viridans aislados de cavidad oral en individuos con uso prolongado de antibióticos / Antibiotic profile of viridans streptococci group isolated of oral cavity from patients with prolonged use of antibiotics

RESUMEN Los estreptococos del grupo viridans (EGV) son un grupo heterogéneo de bacterias saprófitas anaerobias facultativas que forman parte de la flora normal de cavidad oral. El incremento de la resistencia antibiótica de este grupo de bacterias cobra importancia en pacientes hospitalizados con terapia antibiótica prolongada, en los cuales estos microorganismos pueden ser sustituidos por bacterias multirresistentes. Objetivos: Determinar el porcentaje de cepas de EGV aisladas de cavidad oral resistentes a los antibióticos utilizados en el tratamiento de diversas patologías infecciosas hospitalarias. Material y Métodos: Estudio observacional descriptivo en el que se incluyeron 60 pacientes hospitalizados con historia de terapia antibiótica por más de 3 semanas. Las muestras se procesaron siguiendo protocolos estandarizados de recolección, aislamiento e identificación para EGV de cavidad oral y un protocolo de pruebas de sensibilidad antibiótica. Los resultados se muestran en tablas y gráficas de frecuencia. Resultados: La principal indicación para terapia antibiótica intrahospitalaria fue infección orofacial: 28,33%. La penicilina fue el antibiótico más utilizado ya sea en terapia única, combinada o múltiple en todos los pacientes. Se aislaron en total 108 cepas de EGV, con un promedio de 1,8 cepas por paciente. La especie predominantemente identificada fue S. mutans. El 96,3% de las cepas de EGV fue sensible a todos los antibióticos incluidos en el panel. Conclusiones: El uso de distintas combinaciones y modalidades de terapia antibiótica no tiene efecto en la susceptibilidad de EGV aislados de cavidad oral en pacientes hospitalizados, independiente de la duración del tratamiento.

ABSTRACT Viridans group streptococci (VGS) are a heterogeneous group of saprophytic facultative anaerobic bacteria that are part of the normal flora of the oral cavity. The increased resistance to multiple antibiotics in this group of bacteria becomes important in prolonged antibiotic therapies inpatient where these common microorganisms are replaced by multi-resistant bacteria. Objectives: To determine the percentage of VGS strains isolated from oral cavity resistant to antibiotics used in hospital infectious diseases. Material and methods: This is a descriptive cross-sectional study that included 60 hospitalized patients with a history of antibiotic therapy for more than 3 weeks. The samples were processed following standardized protocols for collection, isolation and identification of oral cavity VGS and a protocol of antibiotic susceptibility testing. The results are shown in tables and graphics of absolute and relative frequencies. Results: The main indication for antibiotic therapy was orofacial infection with a 28.33%. Penicillin was the antibiotic further used either in single, combined or multiple therapies in all patients. A total of 108 samples (1.8 per patient swabs) were collected. The predominantly identified specie was Streptococcus mutans. The 96.3% of all VGS strains were sensitive to all antibiotics included in the panel. Conclusion: Using different combinations and types of antibiotic therapy inpatient has no effect on the susceptibility of VGS isolated from oral cavity separate from treatment.

Neuralgia del Trigémino, del Glosofaríngeo y Post-herpética en Pacientes del Hospital Universitario San Ignacio (HUSI) Bogota, Colombia / Trigeminal, Glossopharyngeal and Post-Herpetic Neuralgia in Patients of the San Ignacio University Hospital (HUSI) Bogota, Colombia

Determinar las características clínicas, pautas para el diagnóstico, tratamiento y evolución de la neuralgia del trigémino, postherpética y del nervio glosofaríngeo. Se realizó un estudio descriptivo de 119 historias clínicas de pacientes diagnosticados con neuralgia del trigémino, glosofaríngeo y postherpética tratados en el Hospital Universitario San Ignacio, registrando datos de sexo, edad, antecedentes médicos, exámenes complementarios, características clínicas, tratamientos y evolución. Se revisaron 119 historias clínicas, de las cuales 86 pertenecían a mujeres y 33 a hombres, el 84 % correspondían a neuralgias del trigémino, el 11,7 º% a post- herpética, y el 2,5% en el glosofaríngeo. El lado afectado más común fue el lado izquierdo con un 54%, las ramas más afectadas en la neuralgia del trigémino fue la maxilar y mandibular (V2- V3), en la postherpética la oftálmica (V1), la patología concomitante más frecuente hallada en el grupo fue la HTA, el tipo de dolor más frecuente fue el lancinante con un 82,4%. Los medicamentos más utilizados fueron la carbamazepina (60,5%) seguida de pregabalina (29,4%), en tratamientos quirúrgicos la radiofrecuencia fue la más empleada en un 32 %. 30 pacientes presentaron recaídas que en general fueron manejadas con aumento de las dosis de los medicamentos. Este estudio muestra una similitud con la literatura reportada, presentando más casos de neuralgia de trigémino, seguida de la post herpética y por último del glosofaríngeo. Más frecuente en mujeres, con un promedio de edad de 60 años, afectando en mayor proporción la rama mandibular y maxilar en la neuralgia de trigémino y en la postherpética la oftálmica.

To determine the clinical characteristics, guidelines for the diagnosis, treatment and evolution of trigeminal neuralgia, postherpetic neuralgia and glossopharyngeal neu- ralgia. A descriptive study of 119 clinical histories of patients diagnosed with Trigeminal Neoplasia, glossopharyngeal and postherpetic treated at the Hospital Universitario San Ignacio, recording data such as: gender, age, medical history, diagnostic exams, clinical features, branches and side of the face affected, treatments and evolution. 86 clinical records of women and 33 of men were evaluated, 100 with trigeminal neuralgia, 14 postherpetic, 3 glossopharyngeal, the most common affected side was the left side with 51%, the most affected branches in trigeminal neuralgia was the V2-V3, postherpetic V1, the most frequent antecedent of the neuralgias was the AHT, the type of pain that was more frequent was the lancinanting with 82.4%. The most commonly used medication was carbamazepine (60.5%) and pregabalin (29.4%); in surgical treatments radiofrequency was the most used in 32%; 30 patients had relapses that were generally managed with increased doses. This study shows a similarity with the reported literature, presenting more cases of trigeminal neuralgia, followed by the herpetic and finally the glossopharyngeal neuralgia, finding more cases in women than in men, with an average age of 60 years, affecting in Greater proportion the mandibular and maxillary branch in the trigeminal neuralgia and in the postherpetic ophthalmic.

Brainstem Quadruple Aberrant Hyperphosphorylated Tau, Beta-Amyloid, Alpha-Synuclein and TDP-43 Pathology, Stress and Sleep Behavior Disorders.

Quadruple aberrant hyperphosphorylated tau (p-τ), amyloid-ß peptide, alpha-synuclein and TDP-43 brainstem and supratentorial pathology are documented in forensic ≤40y autopsies in Metropolitan Mexico City (MMC), and p-τ is the major aberrant protein. Post-traumatic stress disorder (PTSD) is associated with an elevated risk of subsequent dementia, and rapid eye movement sleep behavior disorder (RBD) is documented in PD, AD, Lewy body dementia and ALS. This study aimed to identify an association between PTSD and potential pRBD in Mexico. An anonymous online survey of 4502 urban college-educated adults, 29.3 ± 10.3 years; MMC, n = 1865; non-MMC, n = 2637, measured PTSD symptoms using the Impact of Event Scale-Revised (IES-R) and pRBD symptoms using the RBD Single-Question. Over 50% of the participants had IES-R scores ≥33 indicating probable PTSD. pRBD was identified in 22.6% of the participants across Mexico and 32.7% in MMC residents with PTSD. MMC subjects with PTSD had an OR 2.6218 [2.5348, 2.7117] of answering yes to the pRBD. PTSD and pRBD were more common in women. This study showed an association between PTSD and pRBD, strengthening the possibility of a connection with misfolded proteinopathies in young urbanites. We need to confirm the RBD diagnosis using an overnight polysomnogram. Mexican women are at high risk for stress and sleep disorders.

Unravelling complex mosaicism of sex chromosomes in a patient with primary amenorrhea through cytogenetic analysis on urothelial cells.

OBJECTIVE: Sex chromosome mosaicism remains challenging in the study of disorders of sex development (DSD). Aneuploid cells in the developing gonad play a major role in sex determination. Therefore, it is necessary acknowledge their presence by different methods. Our aim was to stand out the utility of urothelial cells for unravelling complex and hidden cell lines in DSD patients. CASE REPORT: Herein we report on a 19-year-old female with primary amenorrhea, short stature without ambiguous external genitalia. She had a 45,X/46, XY karyotype in leukocytes. Interphase FISH revealed hidden 45,X/47,XYY/47,XXY/46,XY/46, XX mosaicism in leukocytes and urothelial cells. CONCLUSION: These findings highlight the importance of investigating sex chromosome mosaicism in other tissues. Of particular interest in cases of DSD are the cells from the urinary epithelium, which may reflect the cell composition of the urogenital ridge, the analysis of these cells should be considered within the clinical assessment of DSD patients.

Inhibition of TGFß1 and TGFß3 promotes hematopoiesis in Fanconi anemia.

Fanconi anemia (FA) is a chromosome instability syndrome with congenital abnormalities, cancer predisposition and bone marrow failure (BMF). Although hematopoietic stem and progenitor cell (HSPC) transplantation is the recommended therapy, new therapies are needed for FA patients without suitable donors. BMF in FA is caused, at least in part, by a hyperactive growth-suppressive transforming growth factor ß (TGFß) pathway, regulated by the TGFß1, TGFß2, and TGFß3 ligands. Accordingly, the TGFß pathway is an attractive therapeutic target for FA. While inhibition of TGFß1 and TGFß3 promotes blood cell expansion, inhibition of TGFß2 is known to suppress hematopoiesis. Here, we report the effects of AVID200, a potent TGFß1- and TGFß3-specific inhibitor, on FA hematopoiesis. AVID200 promoted the survival of murine FA HSPCs in vitro. AVID200 also promoted in vitro the survival of human HSPCs from patients with FA, with the strongest effect in patients progressing to severe aplastic anemia or myelodysplastic syndrome (MDS). Previous studies have indicated that the toxic upregulation of the nonhomologous end-joining (NHEJ) pathway accounts, at least in part, for the poor growth of FA HSPCs. AVID200 downregulated the expression of NHEJ-related genes and reduced DNA damage in primary FA HSPC in vitro and in in vivo models. Collectively, AVID200 exhibits activity in FA mouse and human preclinical models. AVID200 may therefore provide a therapeutic approach to improving BMF in FA.

Electrolyzed Oxidizing Water Modulates the Immune Response in BALB/c Mice Experimentally Infected with Trypanosoma cruzi.

Chagas disease is a major public health problem in Latin America. The mixed Th1/Th2 immune response is required against Trypanosoma cruzi. Electrolyzed oxidizing water (EOW) has been shown to have germicidal efficacy. The objective of this study was to evaluate the EOW effectiveness in T. cruzi-infected BALB/c mice clinically, immunologically, and histologically. The severity of the infection was assessed by parasitaemia, general health condition, mortality, mega syndromes, and histological lesions. IgG, TNF-alpha, IFN-gamma, and IL-1 beta levels were quantified. The EOW administration showed a beneficial effect on parasitaemia, general physical condition, and mortality. High levels of IgG1 at 50 days postinfection were observed. Prophylactic EOW treatment was able to induce a predominantly TH1 immune response based on an IgG2a levels increase at the late acute phase, and a 10-fold increase of INF-gamma in whole acute phase. EOW was able to control the acute phase infection as effectively as benznidazole. Splenomegaly was caused by EOW treatment and lymphadenopathy was stimulated by T. cruzi infection in all groups. Severe tissue damage was not prevented by EOW treatments. Moderate efficacy may be due to immunomodulatory properties and not to a direct toxic effect on the parasite.

Análisis bibliométrico de la producción científica en la Delegación IMSS Puebla / Bibliometric analysis of production scientific publications of the IMSS Puebla Delegation

Introducción: estudio bibliométrico enfocado en la producción científica del personal del IMSS del estado de Puebla para analizar su desempeño y efectos durante el período 2013-2017. Objetivo: promover e incrementar el interés por crear nuevos proyectos, tras identificar el grado actual de profesionalización de la comunidad científica y la madurez de los autores. Metodología: se realizó un estudio cienciométrico retrospectivo, descriptivo y cuantitativo. Las variables estudiadas fue- ron: total de artículos publicados por año, promedio de artículos por autor, años más productivos, autores más prolíficos e índice de colaboración. Resultados: el IMSS Puebla registró una producción científica de 170 documentos, con mayor índice en publicaciones de artículos originales. El año más productivo fue el 2017. Se contabilizaron 160 autores firmantes y el índice de colaboración fue de 9.7. Conclusiones: este trabajo intenta alentar a los autores poblanos a incrementar su producción científica para contribuir a la proyección nacional e internacional.

Introduction: This is a bibliometric study focused on the scientific production of the IMSS personnel of the State of Puebla, to analyze their performance and impact during the period 2013-2017. Objective: To promote and increase interest in creating new projects, identifying the current level of professionalization of the scientific community and the maturity of the authors. Methods: A retrospective-descriptive-quantitative scientometric study was performed. The variables studied were: total articles published per year, average articles per author, most productive years, most prolific authors, and the collaboration index. Results: The IMSS Puebla registered a scientific production of 170 documents, with the highest index in publications of original articles. The most productive year was 2017. 160 signatory authors were counted, and the collaboration rate was 9.7. Conclusions: This work tries to motivate the authors from Puebla to create goals tending to increase their scientific production, to contribute to the national and international projection.

DNA Vaccine Treatment in Dogs Experimentally Infected with Trypanosoma cruzi.

Chagas disease is a chronic and potentially lethal disorder caused by the parasite Trypanosoma cruzi, and an effective treatment has not been developed for chronic Chagas disease. The objective of this study was to determine the effectiveness of a therapeutic DNA vaccine containing T. cruzi genes in dogs with experimentally induced Chagas disease through clinical, pathological, and immunological analyses. Infection of Beagle dogs with the H8 T. cruzi strain was performed intraperitoneally with 3500 metacyclic trypomastigotes/kg body weight. Two weeks after infection, plasmid DNA immunotherapy was administered thrice at 15-day intervals. The clinical (physical and cabinet studies), immunological (antibody and cytokine profiles and lymphoproliferation), and macro- and microscopic pathological findings were described. A significant increase in IgG and cell proliferation was recorded after immunotherapy, and the highest stimulation index (3.02) was observed in dogs treated with the pBCSSP4 plasmid. The second treatment with both plasmids induced an increase in IL-1, and the third treatment with the pBCSSP4 plasmid induced an increase in IL-6. The pBCSP plasmid had a good Th1 response regulated by high levels of IFN-gamma and TNF-alpha, whereas the combination of the two plasmids did not have a synergistic effect. Electrocardiographic studies registered lower abnormalities and the lowest number of individuals with abnormalities in each group treated with the therapeutic vaccine. Echocardiograms showed that the pBCSSP4 plasmid immunotherapy preserved cardiac structure and function to a greater extent and prevented cardiomegaly. The two plasmids alone controlled the infection moderately by a reduction in the inflammatory infiltrates in heart tissue. The immunotherapy was able to reduce the magnitude of cardiac lesions and modulate the cellular immune response; the pBCSP treatment showed a clear Th1 response; and pBCSSP4 induced a balanced Th1/Th2 immune response that prevented severe cardiac involvement. The pBCSSP4 plasmid had a better effect on most of the parameters evaluated in this study; therefore, this plasmid can be considered an optional treatment against Chagas disease in naturally infected dogs.

Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort.

OBJECTIVE: Pretreatment HIV-drug resistance (PDR, HIVDR) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is increasing globally. NNRTIs continue to be used as first-line antiretroviral therapy (ART) in some communities due to the cost of dolutegravir-based ART or dolutegravir-associated adverse events. A simplified version of the oligonucleotide ligation assay (OLA) - 'OLA-Simple' - is a low-cost, near point-of-care assay that provides ready-to-use lyophilized reagents and reports HIVDR mutations as colored lines on lateral flow strips. Our objective was to design and validate OLA-Simple for a Mexican cohort. DESIGN: OLA-Simple probes to detect K65R, K103N/S, Y181C, M184V, and G190A were optimized for HIV Mexican sequences. Sixty clinical plasma specimens were analyzed by OLA-Simple by technicians blinded to Illumina-MiSeq sequences, and HIVDR results were compared. METHODS: Plasma RNA was tested using OLA-Simple kits. OLA-Simple lateral flow strips were read by in-house software, and were classified as mutant or wild-type at each codon. The comparison of results by OLA-Simple and Miseq was used to generate receiver-operating characteristic curves. RESULTS: OLA-Simple PCR amplified 59 of 60 specimens and successfully genotyped 287 of 295 codons, with eight of 295 (2.7%) indeterminate results. Compared to MiSeq, OLA-Simple gave five of 295 (1.7%) false-positive and four of 295 (1.4%) false-negative results. Excluding indeterminate results, OLA-Simple classified mutant with an accuracy of 97.4 and 98.8% when using thresholds at 10 and 25% mutant within an individual's HIV quasispecies, respectively. CONCLUSIONS: Compared to MiSeq, OLA-Simple detected HIVDR with high sensitivity and accuracy. OLA-Simple could expand access to affordable and rapid HIVDR testing to guide appropriate ART choices in populations using NNRTI-based ART.

Breast cancer detection in Mexico City during 2017. / Detección del cáncer de mama en la Ciudad de México durante 2017.

BACKGROUND: Breast cancer is the leading cause of death of women in Mexico; its detection is among the priorities of Mexico City's (CDMX) Southern Local Office from the Instituto Mexicano del Seguro Social (IMSS: Mexican Institute for Social Security). OBJECTIVE: To describe the incidence and mortality related to breast cancer detection in the CDMX's Southern Local Office units from IMSS in 2017. MATERIAL AND METHODS: Databases from the Coordination of Prevention and Health Care (CPAS), Information and Strategic Analysis (CIAE) and the Breast Clinic (UDDC Mama) were analyzed. Among data, it was included age, study (mastography, ultrasound and biopsy), and histological type, incidence and mortality. For statistical analysis it was used Student's t, and Spearman correlation (p < 0.05). RESULTS: In a population of 589,683 women (40-69 years), 97,779 mastographs were performed. Out of these, there were 94,883 normal (BI-RADS 1) and 1933 suspicious (BIRADS 3-5). In 436 biopsies, infiltrating ductal carcinoma was the most frequent. The incidence rate was 39.3/100,000 and the mortality rate was 3.54/100,000 inhabitants (in 2015 and 2016 it was 6.84 and 7.02/100,000, respectively). CONCLUSIONS: An increase in the incidence and a decrease in breast cancer mortality has been observed, which is related to improvements in screening programs in 2017. It is important to maintain and optimize screening programs.

INTRODUCCIÓN: El cáncer de mama es la principal causa de muerte de mujeres en México; su detección se ubica entre las prioridades de la Delegación Sur de la Ciudad de México del Instituto Mexicano del Seguro Social (IMSS). OBJETIVO: Describir la incidencia y la mortalidad relacionadas con la detección del cáncer de mama en las unidades de la Delegación Sur de la Ciudad de México del IMSS en 2017. MATERIAL Y MÉTODOS: Se analizaron las bases de datos de las Coordinaciones de Prevención y Atención a la Salud (CPAS), de Información y Análisis Estratégico (CIAE) y de la Clínica de Mama (UDDC Mama). Entre los datos se incluyó edad, estudio (mastografía, ultrasonido y biopsia) y tipo histológico, incidencia y mortalidad. Para el análisis estadístico se empleó t de Student y correlación de Spearman (p ≤ 0.05). RESULTADOS: En una población de 589 683 mujeres (40-69 años), se realizaron 97 779 mastografías. De estas hubo 94 883 normales (BIRADS 1) y 1933 sospechosas (BIRADS 3-5). En 436 biopsias, el carcinoma ductal infiltrante fue el más frecuente. La tasa de incidencia fue 39.3/100 000 y de mortalidad de 3.54/100 000 habitantes (en 2015 y 2016 fue de 6.84 y 7.02/100 000, respectivamente). CONCLUSIONES: Se ha observado un incremento en la incidencia y disminución de mortalidad por cáncer de mama, el cual está relacionado con mejoras en programas de detección en 2017. Es importante mantener y optimizar los programas de detección.

Hydrogen sulfide and dermatological diseases.

Skin diseases constitute a major health problem affecting a high proportion of the population every day and have different aetiologies that include inflammation, infections, and tumours. Hydrogen sulfide (H2 S) is a gaseous signalling molecule recognized as a gasotransmitter together with NO and carbon monoxide. Under physiological conditions, H2 S is produced in the skin by enzymic pathways and plays a physiological role in a variety of functions, such as vasodilatation, cell proliferation, apoptosis, and inflammation. Alterations of H2 S production are implicated in a variety of dermatological diseases, such as psoriasis, melanoma, and other dermatoses. On the other hand, H2 S-releasing-based therapies based on H2 S donor compounds are being developed to treat some of these situations. In this review, we provide an up-to-date overview of the role of H2 S in the normal skin and its clinical and pathological significance, as well as the therapeutic potential of different H2 S donors for treatment of skin diseases. LINKED ARTICLES: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.