Cell surface markers for mesenchymal stem cells related to the skeletal system: A scoping review.

Multipotent mesenchymal stromal cells (MSCs) have been described as bone marrow stromal cells, which can form cartilage, bone or hematopoietic supportive stroma. In 2006, the International Society for Cell Therapy (ISCT) established a set of minimal characteristics to define MSCs. According to their criteria, these cells must express CD73, CD90 and CD105 surface markers; however, it is now known they do not represent true stemness epitopes. The objective of the present work was to determine the surface markers for human MSCs associated with skeletal tissue reported in the literature (1994-2021). To this end, we performed a scoping review for hMSCs in axial and appendicular skeleton. Our findings determined the most widely used markers were CD105 (82.9%), CD90 (75.0%) and CD73 (52.0%) for studies performed in vitro as proposed by the ISCT, followed by CD44 (42.1%), CD166 (30.9%), CD29 (27.6%), STRO-1 (17.7%), CD146 (15.1%) and CD271 (7.9%) in bone marrow and cartilage. On the other hand, only 4% of the articles evaluated in situ cell surface markers. Even though most studies use the ISCT criteria, most publications in adult tissues don't evaluate the characteristics that establish a stem cell (self-renewal and differentiation), which will be necessary to distinguish between a stem cell and progenitor populations. Collectively, MSCs require further understanding of their characteristics if they are intended for clinical use.

The breast cancer immune microenvironment is modified by neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAT) in breast cancer (BC) has been used to reduce tumor burden prior to surgery. However, the impact on prognosis depends on the establishment of Pathological Complete Response (pCR), which is influenced by tumor-infiltrating lymphocyte levels and the activation of the antitumor immune response. Nonetheless, NAT can affect immune infiltration and the quality of the response. Here, we showed that NAT induces dynamic changes in the tumor microenvironment (TME). After NAT, an increase of regulatory T cells and a decrease of CD8+ T cells was found in tumor, correlated with the presence of metastatic cells in lymph nodes. In addition, an increase of polymorphonuclear myeloid-derived suppressor like cells was found in luminal patients post-NAT. pCR patients showed a balance between the immune populations, while non-pCR patients presented an inverse relationship in the frequency of CD68+ versus CD3+, CD8+, and CD20+ cells. Moreover, activated T cells were found in peripheral blood, as well as an increase in T cell clonality with a lower diversity post-NAT. Overall, these results shown that NAT induces an activation of immune response, however, a balance in the TME seems to be related to a better antigenic presentation and therefore a better response to treatment.

RUNX1 gene expression changes in the placentas of women smokers.

The placenta can be affected by environmental factors, such as exposure to cigarette smoke. This exposure in the fetal context is considered a risk factor for the development of short-term postnatal diseases, such as asthma. Asthma is an inflammatory disease characterized by predominant acquisition of CD4 T lymphocytes (TLs) of the Th2 type. Transcription factors such as GATA binding protein 3 (GATA3) and STAT6 actively participate in the differentiation of virgin TLs towards the Th2 profile, while transcription factors such as STAT1, T-Box transcription factor 21 (T-BET), RUNX1 and RUNX3 participate in their differentiation towards the Th1 profile. The objective of the current study was to evaluate the impact of exposure to cigarette smoke on the gene expression of STAT1, T-BET, GATA3, IL-4, RUNX1 and RUNX3 during the gestation period, and to determine whether the expression levels of these genes are associated with changes in global methylation. STAT1, GATA3, RUNX1 and RUNX3 protein and mRNA expression levels in the placental tissue of women smokers and non-smoking women were determined via immunohistochemistry and quantitative PCR (qPCR) respectively. Additionally, T-BET and IL-4 mRNA expression levels were determined by qPCR. On the other hand, global methylation was determined via ELISA. In the present study, significant increases were observed in RUNX1 transcription factor expression in placentas from women smokers when compared with placentas of non-smoking women. Similarly, significant increases in the expression of GATA3, IL-4 and RUNX3 mRNA were observed. The changes in gene expression were not associated with changes in the global methylation levels. Finally, a higher frequency of low-birth-weight infants were identified in cases of exposure to cigarette smoke during pregnancy when compared with infants not exposed to cigarette smoke during pregnancy. Thus, the data of the present study contributed to the understanding of the genetic and clinical impacts of exposure to cigarette smoke during pregnancy and its importance in maternal and fetal health.

Phenotypic Characteristics and Copy Number Variants in a Cohort of Colombian Patients with VACTERL Association.

VACTERL association (OMIM 192350) is a heterogeneous clinical condition characterized by congenital structural defects that include at least 3 of the following features: vertebral abnormalities, anal atresia, heart defects, tracheoesophageal fistula, renal malformations, and limb defects. The nonrandom occurrence of these malformations and some familial cases suggest a possible association with genetic factors such as chromosomal alterations, gene mutations, and inherited syndromes such as Fanconi anemia (FA). In this study, the clinical phenotype and its relationship with the presence of chromosomal abnormalities and FA were evaluated in 18 patients with VACTERL association. For this, a G-banded karyotype, array-comparative genomic hybridization, and chromosomal fragility test for FA were performed. All patients (10 female and 8 male) showed a broad clinical spectrum: 13 (72.2%) had vertebral abnormalities, 8 (44.4%) had anal atresia, 14 (77.8%) had heart defects, 8 (44.4%) had esophageal atresia, 10 (55.6%) had renal abnormalities, and 10 (55.6%) had limb defects. Chromosomal abnormalities and FA were ruled out. In 2 cases, the finding of microalterations, namely del(15)(q11.2) and dup(17)(q12), explained the phenotype; in 8 cases, copy number variations were classified as variants of unknown significance and as not yet described in VACTERL. These variants comprise genes related to important cellular functions and embryonic development.

Frecuencia de DNA-HPV-HR por método automatizado PCR (COBAS®) en muestras cervicouterinas de una población en Proboquilla-Cartagena, Colombia / COBAS® automated PCR – based detection of HR-HPV DNA in cervix samples collected among a population in Proboquilla-Cartagena, Colombia

Determinar ADN-HPV-HR por método automatizado PCR (cobas®) en muestras cervicouterinas de una población en Proboquilla, Cartagena, Colombia. Métodos: serie de casos de mujeres que asistieron a la campaña donde se tomó citología convencional y una segunda muestra en un vial para determinar DNA del HPV-HR mediante la reacción en cadena de la polimerasa (PCR). Resultados: se recolectaron 31 muestras de citología cérvico-uterina, la prueba PCR fue positiva en seis; 4 casos con infección simple y 2 con infección múltiple. Una de estas últimas fue positiva para los tres grupos (HR-HPV, HPV-16, HPV-18)y la otra para dos (HR-HPV y HPV-18). Conclusión: se detectó un grupo de mujeres infectadas por HPVs clasificados de alto riesgo, con infección simple y múltiple, que fueron remitidas a ginecología. Se confirmó la infección por HPV-HR en 5:7 resultados de citología clasificados como ASC-US...

To determine HR-HPV DNA detection using the Cobas® PCR automated method in cervix samples collectedamong women of Proboquilla, Cartagena, Colombia. Methods: case series based on conventional cytology and second samples, in a vial, through polymerase chain reaction (PCR) testing for HR-HPV DNA detection, among women who attended the campaign. Results: we collected 31 cervix cytology samples, PCR test was positive in six; 4 cases had asimple infection and 2 a multiple infection. One of the latter was positive for the three types (HR-HPV, HPV-16, HPV-18) and the other for two (HR-HPV and HPV-18). Conclusion: high risk HPV infection as well as simple and multipleinfections were identified in a group of women and were referred to the gynecology department. HR-HPV infectionwas confirmed in 5:7 ASC-US cytology results...

Alteration of placental haemostatic mechanisms in idiopathicintrauterine growth restriction / Alteración de los mecanismos hemostáticos de la placenta en restricción de crecimiento intrauterino idiopático / Alteração dos mecanismos hemostáticos da placenta em restrição de crescimento intra-uterino idiopático

La restriccióndel crecimiento intrauterino es una complicación del embarazo con alta probabilidad de morbilidad y mortalidad perinatal, que pareceser causada por desarrollo anormal de la vasculatura placentaria. Los procesos hemostáticos son importantes para el desarrollo de laplacenta y el desequilibrio entre factores procoagulantes y anticoagulantes se ha asociado con restricción del crecimiento intrauterino.Objetivo. Evaluar el compromiso hemostático en la placenta de los embarazos complicados con restricción del crecimiento intrauterinoidiopática. Materiales y métodos. Se estudiaron cinco placentas de embarazos con restricción de crecimiento intrauterino idiopática y 19controles. Se realizó examen macroscópico e histológico, y análisis de la expresión de factor tisular y trombomodulina a nivel de ARNmpor PCR en tiempo real y proteínas por ELISA. Resultados. Se evidenció compromiso hemostático en las placentas de embarazos conrestricción de crecimiento intrauterino idiopática, siendo la trombosis de los vasos coriales el hallazgo histológico más importante. Seencontró aumento en la expresión de la proteína del factor tisular (p=0,0411) y en la razón de factor tisular/trombomodulina a nivel deARNm (p=0,0411) y proteína (p=0,0215). No hubo diferencias estadísticamente significativas entre los grupos en los niveles de ARNmde factor tisular o trombomodulina, ni de trombomodulina a nivel de proteína. Conclusión. Se presenta evidencia de alteración de losmecanismos hemostáticos de la placenta, incluyendo la expresión anormal de factor tisular y de la razón factor tisular/trombomodulina,en embarazos complicados con restricción del crecimiento intrauterino idiopática...

Intrauterine growth restriction is a complication of pregnancy with a high probability of perinatal morbidity and mortality. It appears tobe caused by abnormal development of placental vasculature. Haemostatic processes are important for the development of the placenta,and an imbalance between procoagulant and anticoagulant factors has been associated with risk of intrauterine growth restriction.Objective. To evaluate coagulation abnormalities in placenta of pregnancies complicated with idiopathic intrauterine growth restriction.Materials and methods. Five placentas from pregnancies with idiopathic intrauterine growth restriction were compared to 19 controls.We performed gross and histological examination of the placenta. Analysis was made of both mRNA expression by real-time PCRand protein by ELISA of tissue factor and thrombomodulin in placental tissue. Results. Results based on histological evaluation wereconsistent with an increased prothrombotic state in placentas from pregnancies with idiopathic intrauterine growth restriction, andthrombosis of chorionic vessels was the most important finding. The study showed an increased expression of tissue factor protein(p=0.0411) and an increase in the ratio of tissue factor/thrombomodulin mRNA (p=0.0411) and protein (p=0.0215) in placentas frompregnancies with idiopathic intrauterine growth restriction. There were no statistically significant differences neither between cases andcontrols in the mRNA levels of tissue factor or thrombomodulin nor at the protein level of thrombomodulin. Conclusion. Evidence ofalteration of local haemostatic mechanisms at the level of the placenta, including abnormal expression of tissue factor and tissue factor/thrombomodulin ratio, in pregnancies that occur with idiopathic intrauterine growth restriction is presented...

A restrição do crescimentointra-uterino é uma complicação da gravidez com alta probabilidade de morbidade e mortalidade perinatal, que parece ser causada pelodesenvolvimento anormal da vasculatura placentária. Os processos hemostáticos são importantes para o desenvolvimento da placenta,e o desequilíbrio entre fatores pró-coagulantes e anticoagulantes têm sido associadas com a restrição de crescimento intra-uterino.Objetivo. Avaliar o compromisso hemostático na placenta com gestações complicadas com restrição de crescimento intra-uterinoidiopático. Materiais e métodos. Foram estudadas cinco placentas de gestações com restrição de crescimento intra-uterino idiopáticoe 19 controles. Foi realizada uma análise macroscópica e histológica e análise da expressão do factor tecidual e trombomodulina emARNm por PCR em tempo real e de proteína pelo método de ELISA. Resultados. Foi evidente o compromisso hemostático nas placentasde gestações com restrição de crescimento intra-uterino idiopático; a trombose dos vasos coriônicos é o descobrimento histológico maisimportante. Aumentaram a expressão de proteína do fator tecidual (p= 0,0411) e a proporção do fator tecidual/ trombomodulina aonível de ARNm (p= 0,0411) e de proteína (p= 0,0215). Não houve diferenças estatisticamente significativas entre os grupos nos níveisde ARNm do fator tecidual ou trombomodulina, nem de trombomodulina ao nível de proteína. Conclusão. Se apresenta evidência dealteração dos mecanismos hemostáticos da placenta, incluindo a expressão anormal de fator tecidual e da proporção do fator tecidual/trombomodulina, em gestações complicadas com restrição de crescimento intra-uterino idiopático...

Complejo Limb-Body Wall en el Hospital Universitario San Ignacio en Bogotá (Colombia): reporte de caso y revisión de la literatura / Limb-body wall complex in the San Ignacio Teaching Hospital at Bogota, Colombia: a case report and literature review

Introducción: las alteraciones del cordón umbilical están asociadas con diversas complicaciones de la gestación a corto y a largo plazo, algunas con pocas probabilidades de sobrevida y relacionadas con lesiones fetales múltiples. El complejo Limb-Body Wall (LBWC), compuesto por defectos de la pared corporal lateral y anomalías por acortamiento de miembros, es una de tales complicaciones, cuyas aún discutidas etiologías, pobre pronóstico y posibilidad de recurrencia hacen que cobre importancia en el diagnóstico ecográfico, la atención neonatal y el abordaje de la autopsia. Objetivos: reportar un caso de LBWC y revisar la literatura publicada sobre su etiología, características clínicas y diagnóstico, en el contexto de las complicaciones asociadas con las alteraciones del cordón umbilical. Materiales y métodos: se presenta el caso clínico de una recién nacida de primer embarazo de madre adolescente quien consultó a una entidad de nivel referencia y alta complejidad, recién nacida que falleció a los pocos minutos de nacer; presentaba defecto de la pared abdominal, escoliosis y esbozo de miembro superior izquierdo, asociado con cordón umbilical de 6 cm. Se realizó una revisión de la literatura publicada en las bases de datos Medline vía PubMed, Ovid e Hinari. Conclusión: el LBWC se asocia con un índice importante de morbimortalidad y con la expresión de un cordón excesivamente corto; por tanto, cobra gran relevancia hacer un diagnóstico oportuno y brindar asesoría genética adecuada a las familias...

Introduction: umbilical cord alterations are associated with several short and long-term complications during pregnancy, some involving little chance of survival related to multiple foetal lesions. One of those anomalies is the Limb-Body Wall Complex (LBWC) which consists of lateral body wall defects and anomalies due to shortening of the limbs. Its still discussed aetiology, poor prognosis and possible recurrence make it important in ecographic diagnosis, neonatal attention and the approach during autopsy. Objectives: reporting a case of LBWC and reviewing the literature published about its aetiology, clinical characteristics and diagnosis within the context of the complications associated with umbilical cord alterations. Materials and methods: a clinical case of a female newborn resulting from an adolescent mother’s first pregnancy who consulted a reference and high complexity entity is presented. The newborn died a few minutes after being born, presenting a defect of the abdominal wall, scoliosis and upper left limb stump associated with a 6 cm umbilical cord. The literature published in Medline data bases was reviewed using PubMed, Ovid and Hinari. Conclusion: LBWC is an expression of an excessively short cord and is associated with important morbidity-mortality. Thus an early diagnosis must be made and suitable genetic advice given to families...

Implicaciones médicas y legales de la certificación de "nacido vivo" en Colombia / Medical and legal implications of a “life birth” certificate in Colombia

En Colombia se han dado pasos importantes en el abordaje y manejo de los fetos, embriones y recién nacidos fallecidos, no obstante se requiere mayor difusión de las normas y conceptos existentes, además de implementar algunas medidas faltantes. Es necesario hacer claridad sobre los conceptos ya que las implicaciones legales de la certificación de un niño(a) nacido(a) vivo(a), son muy significativas para los pacientes, las familias, las instituciones y la sociedad. El objetivo del presente documento es hacer una reflexión de los aspectos médicos y legales relevantes acerca del tema.

Important steps have been made in Colombia regarding the approach to and handling of fetuses, embryos and the newborn born dead; however, there is still a need for making existing standards and concepts more widely known and implementing those which are lacking. Greater clarity is needed concerning the pertinent concepts since the legal implications of certifying a child born alive are very significant for patients, families, institutions and society. The present document was aimed at reflecting on the relevant medical and legal aspects concerning the topic.

Acondrogénesis tipo IA: reporte de caso / Type IA achondrogenesis: case report

La acondrogénesis tipo IA (#MIM 200600) es una rara y letal displasia esquelética, caracterizada por un grave retardo de la osificación, con modo de herencia autosómico recesivo. Hasta el momento se desconocen sus bases moleculares. En este artículo se reporta el caso de un feto de sexo femenino, de 23 semanas de edad de gestación, de padres no consanguíneos, con diagnóstico ecográfico de hipoplasia torácica, hipoplasia pulmonar, costillas cortas con múltiples fracturas, micromelia grave, hipocalcificación y fractura de huesos largos, pies en varo y manos en garra. En el estudio microscópico se evidencia untrastorno de osificación endocondral. La acondrogénesis pertenece a la forma más crónica de condrodisplasias humanas invariablemente letales. Las bases bioquímicas y molecularesno son claras en la acondrogénesis tipo IA, ya que el diagnóstico se basa en la integración de estudios radiológicos e histológicos en cada caso específico, por lo cual se considera que el caso presentado corresponde a acondrogénesis tipo IA.

Prevalencia de anormalidades citológicas e histológicas de cuello uterino en un grupo de mujeres en Bogotá, Colombia / Prevalence of cytological and histological cervical uterine abnormalities in a group of women in Bogotá, Colombia

Objetivo: Describir la prevalencia de anormalidades citológicas y de neoplasias de cuello uterino en un grupo de mujeres de Bogotá, Colombia. Métodos: Se realizó un estudio descriptivo en el que se incluyeron mujeres atendidas en centros de salud de tres localidades del sur de Bogotá, pertenecientes a estratos socioeconómicos bajos, entre 25 y 59 años de edad y con antecedente de al menos una relación sexual penetrante. Resultados: Se analizaron 4.957 casos. La edad promedio fue 39,2 años. El 69,1% de las 4.957 citologías fueron negativas, 24,7% reportaron ASC-US; 4,3%, LIE-BG; 1,2%, LIE-AG, y 0,1%, lesión sospechosa de carcinoma infiltrante. Se realizaron 762 biopsias (15,4% de la población). De éstas, 48,29% se reportaron como negativas para neoplasia, y 49,08%, con algún cambio neoplásico. La prevalencia global de neoplasias intraepiteliales y de carcinoma infiltrante fue 7,54%. La prevalencia de NIC II y NIC III fue 1,3% (0,4% y 0,9%). Se detectaron dos carcinomas infiltrantes (0,04%). Conclusiones: La prevalencia de anormalidades citológicas fue inusualmente elevada; por el contrario, los hallazgos de anormalidades histológicas (NIC I o mayor) muestran datos de alta confiabilidad, ya que son producto de biopsias tomadas por indicación de tres métodos de tamización (inspección visual, citología o colposcopia). La prevalencia de neoplasias de alto grado (NIC II y III) y cáncer infiltrante observada en nuestro estudio es mayor que la reportada para otros países.

Objective: To describe the prevalence of cytological abnormalities and neoplasias in a group of women from Bogotá, Colombia. Methods: A descriptive analysis was done among women attended health services in a low-resource area of Bogotá. All women had history of sexual onset, aged 25 to 59 years, and were investigated with conventional cytology. Results: 4,957 cases were analyzed. The average age was 39.2 years. In total 69.1% of pap smears were negative, 24.7% reported ASC-US, 4.3% LSIL, 1.2% HSIL, and 0.1% invasive cancer. 762 biopsies were done (48.29% negative and 49,08% neoplasic changes). The global prevalence of intraepithelial neoplasias and carcinoma was 7.54%. The prevalence of CIN 2 and CIN 3 was 1.3% (0.4% y 0.9%). Two invasive carcinomas were detected (0.04%). Conclusions: The prevalence of cytological abnormalities was unusually high. Histological abnormalities were investigated through three different screening methods representing highly reliable data. The prevalence of HSIL (CIN II and CIN III) and invasive cancer observed is higher than previous reports from other countries.

Factores asociados con mortalidad por infección respiratoria aguda en una población de niños menores de cinco años residentes en la ciudad de Bogotá / Factors Affecting Mortality from Acute Respiratory Infections in a Population of Children under Five Years Living in the city of Bogota

Introducción: Las infecciones respiratorias agudas (IRA), principalmente la neumonía y en segundo lugar la bronquiolitis, son la causa infecciosa más frecuente de muerte en niños menores de cinco años de edad. Objetivo: Determinar el papel de potenciales factores de riesgo como predictores de mortalidad por infección respiratoria aguda. Método: Estudio observacional analítico de casos y controles con 258 pacientes pediátricos menores de cinco años con enfermedad respiratoria aguda atendidos en cuatro hospitales de la zona suroriental de Bogotá. Resultados: Los hallazgos de acidosis metabólica, acidemia al momento del ingreso a la unidad de cuidado intensivo (UCI) y el antecedente de ingreso a la UCI en los meses de marzo, abril y mayo, respecto al ingreso en los demás meses del año, fueron predictores de la mortalidad. Entre tanto, la presencia de aleteo nasal y la administración de antibióticos en la segunda consulta, mostraron reducir el riesgo de mortalidad. Palabras clave: neumonía, mortalidad, infección, enfermedad pulmonar intersticial.

Introduction: In acute respiratory infections (ARI), pneumonia in the first place and bronchiolitis in the second place are the most common infectious cause of death in children under five years old. Objective: To establish the role of potential risk factors as predictors of mortality from acute respiratory infection. Method: An observational/analytic case-control study was conducted with 258 pediatric patients younger than five years old with acute respiratory disease (ARD) treated at four south-eastern hospitals in Bogotá. Results: Findings of metabolic acidosis and acidemia at ICU admission, as well as patients’ clinical history at ICU admission were taken as mortality predictors in the months of March, April and May, with regard to their admission in other months, and the presence of nasal flaring and the administration of antibiotics at the second consultation decreased mortality risk. Key words: Pneumonia, mortality, infection, interstitial lung disease.