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Parkinson's disease (PD) caused by SNCA gene triplication (3XSNCA) leads to early onset, rapid progression, and often dementia. Understanding the impact of 3XSNCA and its absence is crucial. This study investigates the differentiation of human induced pluripotent stem cell (hiPSC)-derived floor-plate progenitors into dopaminergic neurons. Three different genotypes were evaluated in this study: patient-derived hiPSCs with 3XSNCA, a gene-edited isogenic line with a frame-shift mutation on all SNCA alleles (SNCA 4KO), and a normal wild-type control. Our aim was to assess how the substantia nigra pars compacta (SNpc) microenvironment, damaged by 6-hydroxydopamine (6-OHDA), influences tyrosine hydroxylase-positive (Th+) neuron differentiation in these genetic variations. This study confirms successful in vitro differentiation into neuronal lineage in all cell lines. However, the SNCA 4KO line showed unusual LIM homeobox transcription factor 1 alpha (Lmx1a) extranuclear distribution. Crucially, both 3XSNCA and SNCA 4KO lines had reduced Th+ neuron expression, despite initial successful neuronal differentiation after two months post-transplantation. This indicates that while the SNpc environment supports early neuronal survival, SNCA gene alterations-either amplification or knock-out-negatively impact Th+ dopaminergic neuron maturation. These findings highlight SNCA's critical role in PD and underscore the value of hiPSC models in studying neurodegenerative diseases.
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Introducción. El objetivo de este estudio fue comparar los desenlaces a corto plazo de la gastrectomía laparoscópica en adultos vs. adultos mayores con cáncer gástrico localmente avanzado en una cohorte de un país occidental. Métodos. Estudio de cohorte prospectivo en pacientes sometidos a gastrectomía laparoscópica por cáncer gástrico localmente avanzado, en el Hospital Universitario Erasmo Meoz, de Cúcuta, Colombia, entre noviembre de 2014 y diciembre de 2018. Se realizó análisis descriptivo, de comparación de grupos y bivariado. Resultados. De un total de 116 pacientes, 51 pacientes (44 %) tenían 65 años o más y 63 pacientes (54 %) eran hombres. No se encontró diferencia estadísticamente significativa al comparar los pacientes menores de 65 años con los de 65 años o más. La mediana del tiempo operatorio fue de 240 minutos en ambos grupos (p>0,05), la mediana de los márgenes de resección macroscópica fue 6 cm vs. 5 cm (p>0,05), la mediana de los ganglios linfáticos disecados fue 25 vs. 19 (p>0,05), la mediana de ganglios linfáticos positivos fue 4 vs. 3 (p>0,05), la mediana de estancia fue de 7 días en ambos grupos (p>0,05). La tasa general de complicaciones posoperatorias no difirió significativamente entre adultos (7%) y adultos mayores (11 %) (p>0,05) y no se observaron diferencias significativas en las tasas de complicaciones menores (Clavien-Dindo grado II; 3-5 % vs. 6-12 %; p>0,05) y graves (Clavien-Dindo ≥ IIIa; 3-5 % vs. 4-8 %; p>0,05). Conclusiones. No se encontraron diferencias estadísticamente significativas en los resultados a corto plazo entre los pacientes adultos y adultos mayores con cáncer gástrico localmente avanzado tratados con gastrectomía laparoscópica. Esta técnica es segura en ancianos.
Introduction. The objective of this study was to compare the short-term outcomes of laparoscopic gastrectomy in adults vs. older patients with locally advanced gastric cancer from a Western country cohort. Methods. Prospective cohort study in patients undergoing laparoscopic gastrectomy for locally advanced gastric cancer at the Hospital Universitario Erasmo Meoz, de Cúcuta, Colombia, between November 2014 and December 2018. Descriptive, group comparison and bivariate analysis was performed. Results. Of a total of 116 patients, 51 patients (44%) were 65 years or older and 63 patients (54%) were men. No statistically significant difference was found when comparing patients under 65 years of age with those 65 years of age or older. The median operating time was 240 minutes in both groups (p>0.05), the median macroscopic resection margins were 6 cm vs. 5 cm (p>0.05), the median number of lymph nodes dissected was 25 vs. 19 (p>0.05), the median number of positive lymph nodes was 4 vs. 3 (p>0.05), the median stay was 7 days in both groups (p>0.05). The overall rate of postoperative complications did not differ significantly between adults (7%) and older adults (11%) (p>0.05) and no significant differences were observed in the rates of minor (Clavien-Dindo grade II; 3-5% vs. 6-12%; p>0.05) and severe complications (Clavien-Dindo ≥ IIIa; 3-5% vs. 4-8%; p>0.05). Conclusions. No statistically differences were found in short-term outcomes between adult and older patients with locally advanced gastric cancer treated with laparoscopic gastrectomy. This technique is safe in the elderly.
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Humanos , Neoplasias Gástricas , Idoso , Gastrectomia , Complicações Pós-Operatórias , Laparoscopia , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
Objetivo: describir los factores de riesgo de trombosis venosa profunda en el personal administrativo de una universidad ecuatoriana. Método: investigación cuantitativa, transversal y descriptiva, con una muestra censal de 71 trabajadores del área administrativa, en Ambato, Ecuador. Para la recolección de datos se utilizó el test que evalúa el manejo de la insuficiencia venosa crónica entre los niveles de atención a la salud. El análisis de datos se realizó mediante estadística descriptiva y el método multivariante de análisis de componentes principales para definir nuevos factores asociados. Resultados: los factores a la TVP son la bipedestación, consumo de tabaco y alcohol, sedestación, coagulación sanguínea, várices congénitas, enfermedades catastróficas, edema, algia, cirugía, anticonceptivos y uso de corticoesteroides. Conclusión: el riesgo de estos pacientes para desarrollar TVP está relacionado con el lugar de trabajo, la movilidad, signos y síntomas que la enfermedad puede causar. En el caso del personal administrativo los factores más asociados a la TVP se relacionan con la posición por largas jornadas de trabajo, no obstante factores de coagulación, patologías previas, signos notorios de la patología, consumo de alcohol y tabaco y el uso de corticoesteroides también aportan en un menor porcentaje al desarrollo.
Objective: to describe the risk factors for deep vein thrombosis in the administrative staff of an ecuadorian university. Method: quantitative, cross-sectional and descriptive research, with a census sample of 71 workers in the administrative area, in Ambato, Ecuador. For data collection, the test that evaluates the management of chronic venous insufficiency between levels of health care was used. Data analysis was performed using descriptive statistics and the multivariate method of principal component analysis to define new associated factors. Results: risk factors for DVT are standing, smoking and drinking alcohol, sitting, blood clotting, congenital varicose veins, catastrophic disease, edema, pain, surgery, contraceptives, and use of corticosteroids. Conclusion: the risk of these patients to develop DVT is related to the workplace, mobility, signs and symptoms that the disease can cause. In the case of administrative staff, the factors most associated with DVT are related to the position due to long working hours, however coagulation factors, previous pathologies, notorious signs of the pathology, alcohol and tobacco consumption, and the use of corticosteroids also contribute to development in a lower percentage.
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Doenças Vasculares , Saúde Ocupacional , Trombose VenosaRESUMO
Transplantation of immature dopaminergic neurons or neural precursors derived from embryonic stem cells (ESCs) into the substantia nigra pars compacta (SNpc) is a potential therapeutic approach for functional restitution of the nigrostriatal pathway in Parkinson's disease (PD). However, further studies are needed to understand the effects of the local microenvironment on the transplanted cells to improve survival and specific differentiation in situ. We have previously reported that the adult SNpc sustains a neurogenic microenvironment. Non-neuralized embryoid body cells (EBCs) from mouse ESCs (mESCs) overexpressing the dopaminergic transcription factor Lmx1a gave rise to many tyrosine hydroxylase (Th+) cells in the intact and damaged adult SNpc, although only for a short-term period. Here, we extended our study by transplanting EBCs from genetically engineered naive human ESC (hESC), overexpressing the dopaminergic transcription factors LMX1A, FOXA2, and OTX2 (hESC-LFO), in the SNpc. Unexpectedly, no graft survival was observed in wild-type hESC EBCs transplants, whereas hESC-LFO EBCs showed viability in the SNpc. Interestingly, neural rosettes, a developmental hallmark of neuroepithelial tissue, emerged at 7- and 15-days post-transplantation (dpt) from the hESC-LFO EBCs. Neural rosettes expressed specification dopaminergic markers (Lmx1a, Otx2), which gave rise to several Th+ cells at 30 dpt. Our results suggest that the SNpc enables the robust initiation of neural differentiation of transplanted human EBCs prompted to differentiate toward the midbrain dopaminergic phenotype.
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La tuberculosis extra pulmonar osteoarticular es una entidad infrecuente (16%), y aquellas de compromiso extravertebral son a su vez muy infrecuentes. Presentamos el caso clínico de un paciente masculino de 68 años de edad, con hipertensión arterial sistémica y enfermedad renal crónica, que presenta aproximadamente 1 año de evolución tórpida con dolor en retropié izquierdo, empeorando luego de infiltración con esteroide, con aumento de volumen, limitación funcional, y lesión ulcerosa con exudado purulento en cara medial. Siendo evaluado de forma clínica y con estudios de imagen por diferentes facultativos, hasta realizar toma de biopsia y cultivo óseo con diagnóstico de Tuberculosis ósea en calcáneo izquierdo. Tratado de manera quirúrgica, y actualmente cumpliendo tratamiento antituberculoso, con evolución satisfactoria recuperando movilidad articular, sin dolor y disminución del volumen de retropié(AU)
Osteoarticular extrapulmonary tuberculosis is a rare entity (16%), and those with extravertebral involvement are in turn very rare. We present the clinical case of a 68-years-old male patient with systemic arterial hypertension and chronic kidney disease, who presents approximately 1 year of torpid evolution with pain in the left hindfoot, worsening after steroid infiltration, with increased volume, limitation functional, and ulcerative lesion with purulent exudate on the medial side. He was being evaluated clinically and with imaging studies by different doctors, until taking a biopsy and bone culture with a diagnosis of Bone Tuberculosis in the left calcaneus. Surgically treated, and currently undergoing antituberculous treatment, with satisfactory evolution recovering joint mobility, without pain and decrease in rearfoot volume(AU)
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Humanos , Masculino , Idoso , Tuberculose Osteoarticular/patologia , Calcâneo , Insuficiência Renal CrônicaRESUMO
Dysfunction of cellular homeostasis can lead to misfolding of proteins thus acquiring conformations prone to polymerization into pathological aggregates. This process is associated with several disorders, including neurodegenerative diseases, such as Parkinson's disease (PD), and endoplasmic reticulum storage disorders (ERSDs), like alpha-1-antitrypsin deficiency (AATD) and hereditary hypofibrinogenemia with hepatic storage (HHHS). Given the shared pathophysiological mechanisms involved in such conditions, it is necessary to deepen our understanding of the basic principles of misfolding and aggregation akin to these diseases which, although heterogeneous in symptomatology, present similarities that could lead to potential mutual treatments. Here, we review: (i) the pathological bases leading to misfolding and aggregation of proteins involved in PD, AATD, and HHHS: alpha-synuclein, alpha-1-antitrypsin, and fibrinogen, respectively, (ii) the evidence linking each protein aggregation to the stress mechanisms occurring in the endoplasmic reticulum (ER) of each pathology, (iii) a comparison of the mechanisms related to dysfunction of proteostasis and regulation of homeostasis between the diseases (such as the unfolded protein response and/or autophagy), (iv) and clinical perspectives regarding possible common treatments focused on improving the defensive responses to protein aggregation for diseases as different as PD, and ERSDs.
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Afibrinogenemia/genética , Fibrinogênio/química , Doença de Parkinson/genética , Deficiência de alfa 1-Antitripsina/genética , alfa 1-Antitripsina/química , alfa-Sinucleína/química , Afibrinogenemia/tratamento farmacológico , Afibrinogenemia/metabolismo , Afibrinogenemia/patologia , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Coagulantes/uso terapêutico , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/patologia , Fibrinogênio/genética , Fibrinogênio/metabolismo , Regulação da Expressão Gênica , Humanos , Fígado/metabolismo , Fígado/patologia , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Inibidores de Proteases/uso terapêutico , Agregados Proteicos/efeitos dos fármacos , Dobramento de Proteína/efeitos dos fármacos , Resposta a Proteínas não Dobradas/efeitos dos fármacos , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/metabolismo , Deficiência de alfa 1-Antitripsina/tratamento farmacológico , Deficiência de alfa 1-Antitripsina/metabolismo , Deficiência de alfa 1-Antitripsina/patologia , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
El COVID-19 inicio en diciembre del 2019 en la ciudad de Wuhan, China. Actualmente estamos aprendiendo sobre la atención de los pacientes, y la adaptación del personal de salud ante la pandemia. El objetivo de esta revisión es fomentar las bases para la elaboración de un protocolo nacional en áreas quirúrgicas ante la presencia del COVID-19. Consta de 14 publicaciones de acceso libre a través de PUBMED y ELSEVIER como buscadores digitales, se enmarcaron a través de las acciones de salud de diferentes instituciones a nivel mundial, y de las labores en áreas quirúrgicas, teniendo como resultado la suspensión de intervenciones no prioritarias, conservación de las cirugías de emergencia y aquellas cuya evolución simbolice complicaciones para el paciente. La utilización adecuada de los equipos de protección personal, y la distribución de las acciones de trabajo en situaciones de riesgo ante pacientes con COVID-19 o probables. Es de destacar la utilización de redes sociales y telemedicina para continuar las actividades académicas y la difusión de información adecuada para pacientes y personal de salud(AU)
COVID-19 started in December 2019 in the city of Wuhan, China. We are currently continuing to learn about patient care, and the adaptation of health personnel to the pandemic. The objective of this review is to promote the bases for the development of a national protocol in surgical areas in the presence of COVID-19. It consists of 14 free access publications through PUBMED and ELSEVIER as digital search engines, they were framed through the health actions of different institutions worldwide, and work in surgical areas, resulting in the suspension of non-priorities surgical interventions, conservation of emergency surgeries and those whose evolution symbolizes complications for the patient. The proper use of personal protective equipment, and the distribution of work actions in risky situations with patients with COVID-19 or probable. It is worth highlighting the use of social networks and telemedicine to continue academic activities and the dissemination of adequate information for patients and health personnel(AU)
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Humanos , Medidas de Segurança , Centros Cirúrgicos/normas , Pessoal de Saúde/normas , COVID-19/transmissão , Procedimentos Cirúrgicos Operatórios , Serviços Médicos de Emergência/normas , Equipamento de Proteção Individual , Assistência ao PacienteRESUMO
Alpha-synuclein (α-syn) is localized in cellular organelles of most neurons, but many of its physiological functions are only partially understood. α-syn accumulation is associated with Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy as well as other synucleinopathies; however, the exact pathomechanisms that underlie these neurodegenerative diseases remain elusive. In this review, we describe what is known about α-syn function and pathophysiological changes in different cellular structures and organelles, including what is known about its behavior as a prion-like protein. We summarize current knowledge of α-syn and its pathological forms, covering its effect on each organelle, including aggregation and toxicity in different model systems, with special interest on the mitochondria due to its relevance during the apoptotic process of dopaminergic neurons. Moreover, we explore the effect that α-syn exerts by interacting with chromatin remodeling proteins that add or remove histone marks, up-regulate its own expression, and resume the impairment that α-syn induces in vesicular traffic by interacting with the endoplasmic reticulum. We then recapitulate the events that lead to Golgi apparatus fragmentation, caused by the presence of α-syn. Finally, we report the recent findings about the accumulation of α-syn, indirectly produced by the endolysosomal system. In conclusion, many important steps into the understanding of α-syn have been made using in vivo and in vitro models; however, the time is right to start integrating observational studies with mechanistic models of α-syn interactions, in order to look at a more complete picture of the pathophysiological processes underlying α-synucleinopathies.
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Introducción. La escisión transanal total del mesorrecto es una alternativa en el tratamiento del cáncer de recto. La cirugía endoscópica transluminal a través de orificios naturales, usando el recto como un acceso en la cirugía colorrectal, es mejor tolerado que otros abordajes. Objetivo. Exponer las ventajas del abordaje transanal en el cáncer de recto. Materiales y métodos. Se expone un caso de abordaje quirúrgico transanal en Colombia. Se practicó una escisión total del mesorrecto por vía transanal, con un tiempo abdominal, en un paciente de sexo masculino de 57 años de edad con una lesión tumoral a 4 cm del margen anal, estudiado con colonoscopia, tomografía computadorizada y resonancia magnética con protocolo para recto. Se administraron quimioterapia y radioterapia neoadyuvante. Resultados. El tiempo quirúrgico total fue de 240 minutos. La ingestión alimentaria se reinició 12 horas después de la intervención y la primera descarga por la ileostomía se obtuvo a las 24 horas. Se dio de alta al quinto día posoperatorio, sin complicaciones y con un puntaje en la escala de dolor de 2/10. En la histopatología se informó una disección completa del mesorrecto con una clasificación patología T2N1. Conclusión. La mejor indicación de la vía transanal es en tumores del tercio inferior del recto (a menos de 6 cm del margen anal), ya que esta vía de abordaje soluciona algunos problemas que plantea la cirugía laparoscópica convencional (sección del recto con margen distal suficiente, disección pélvica), sobre todo en pacientes con características desfavorables para la cirugía laparoscópica (sexo masculino, obesos, pelvis estrecha y tumores voluminosos).
Introduction: Total mesorectal transanal excision is an alternative in the treatment of rectal cancer. Transluminal endoscopic surgery through natural orifices, using the rectum as an access in colorectal surgery is better tolerated than other approaches. Objective: To describe the advantages of transanal approach for rectal cancer. Materials and methods: We report the case of a total excision of the mesorectum via transanal approach in a 57 year-old male with a tumor located 4 cm from the anal verge. Colonoscopy and magnetic resonance imaging protocol was followed. CT of the abdomen, pelvis and chest were negative for metastatic findings. Neoadjuvant chemotherapy and radiotherapy were administered. We practiced a transanal time and an abdominal time and met at the tumor site. Results: The total operative time was 240 minutes, the dietary intake was resumed 12 hours after surgery, and the ileostomy was functional 24 hours after surgery. He was discharged five days after surgery without complications, with a pain scale score of 2/10. Pathology reported a complete mesorrectal dissection classified as PT2N1 pT2N1. Conclusion: The best indication for this approach is lower third (less than 6 cm from the anal margin) located tumors, as this surgical approach gives us solutions to problems posed by conventional laparoscopic surgery (section of the rectum with enough distal margin, pelvic dissection), especially in patients with unfavorable characteristics for laparoscopic surgery (male, obese, narrow pelvis and bulky tumors).
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Neoplasias Retais , Laparoscopia , Cirurgia Endoscópica por Orifício Natural , MesentérioRESUMO
Introducción: La presión arterial (PA) es un signo vital y su registro en los niños y adolescentes es fundamental.Los estudios han mostrado que la hipertensión arterial en la edad pediátrica puede llevar a enfermedadescardiovasculares del adulto que son la primera causa de muerte en muchos países y en Colombia. El objetivo de esteartículo es mostrar los datos de PA en una población escolar de 7 a 18 años, de la ciudad de Cali, Colombia.Métodos: Se realizó un estudio descriptivo transversal en Cali, Colombia, para evaluar factores de riesgo de enfermedades crónicas no transmisibles en una población escolarizada que incluyó antropometría, bioquímica sanguínea, capacidad física de trabajo, salud oral y dieta; además, dos pediatras hicieron un examen físico completo con toma de presión arterial (PA). Para la toma de PA se utilizó método auscultatorio en posición sentada con el brazalete adecuado de acuerdo con los estándares; se tomó y registró la PA en los dos brazos. Se reportaron los datos de PA de esta población escolarizada, su relación con edad, género, talla, estrato socioeconómico, ingesta de sal e índicede masa corporal (IMC). Resultados: Se evaluaron 2,807 escolares de diferentes instituciones educativas del área urbana de Cali. El 92.2% de la población escolar evaluada presentó PA normal inferior a percentil 90%, 3.8% presentó PA entre percentiles 90% a 95% o prehipertensión y 3.2% es hipertenso con tensión arterial superior al percentil 95% para edad, géneroy percentil de talla. La PA sistólica y diastólica aumenta con la edad, la talla y en los varones los valores son ligeramente más altos. No se encontraron diferencias significativas de tensión sistólica y diastólica por estrato socioeconómico. No hubo diferencias entre la tensión en brazo derecho y brazo izquierdo. A mayor ingesta de sodio en la dieta y mayorIMC, mayores los niveles de PA sistólica.