724 research outputs found
Multiple Sclerosis: LIFNano-CD4 for Trojan Horse Delivery of the Neuro-Protective Biologic “LIF” Into the Brain: Preclinical Proof of Concept
Multiple sclerosis (MS) is a demyelinating autoimmune disease that attacks the brain, with year-on-year loss of brain volume, starting late teens and becoming manifest late twenties. There is no cure, and current therapies are immunosuppressive only. LIF is a vital stem cell growth factor active throughout life—and essential for health of the central nervous system (CNS), being tolerogenic, myelinogenic, and neuroprotective. Nano-formulation of LIF (LIFNano) using FDA-approved PLGA captures LIF's compound therapeutic properties, increasing potency 1,000-fold when targeted to CD4 (LIFNano-CD4). Moreover, circulating CD4+ lymphocytes are themselves regulated by LIF to express the Treg phenotype, known to release T cell-derived LIF upon engagement with cognate antigen, perpetuating antigen-specific self-tolerance. With the longer-term aim of treating inflammatory lesions of MS, we asked, does LIFNano-CD4 cross the blood–brain barrier (BBB)? We measure pK and pD using novel methodologies, demonstrate crossing of the BBB, show LIF-cargo-specific anti-inflammatory efficacy in the frontal cortex of the brain, and show safety of intravenous delivery of LIFNano-CD4 at doses known to provide efficacious concentrations of LIF cargo behind the BBB
Pharmacokinetics and Pharmacodynamics of the Nitroimidazole DNDI-0690 in Mouse Models of Cutaneous Leishmaniasis.
The nitroimidazole DNDI-0690 is a clinical drug candidate for visceral leishmaniasis (VL) that also shows potent in vitro and in vivo activity against cutaneous leishmaniasis (CL). To support further development of this compound into a patient-friendly oral or topical formulation for the treatment of CL, we investigated the free drug exposure at the dermal site of infection and subsequent elimination of the causative Leishmania pathogen. This study evaluates the pharmacokinetics (PK) and pharmacodynamics (PD) of DNDI-0690 in mouse models of CL. Skin microdialysis and Franz diffusion cell permeation studies revealed that DNDI-0690 permeated poorly (<1%) into the skin lesion upon topical drug application (0.063% [wt/vol], 30 μl). In contrast, a single oral dose of 50 mg/kg of body weight resulted in the rapid and nearly complete distribution of protein-unbound DNDI-0690 from the plasma into the infected dermis (ratio of the area under the curve [0 to 6 h] of the free DNDI-0690 concentration in skin tissue to blood [fAUC0-6 h, skin tissue/fAUC0-6 h, blood] is greater than 80%). Based on in vivo bioluminescence imaging, two doses of 50 mg/kg DNDI-0690 were sufficient to reduce the Leishmania mexicana parasite load by 100-fold, while 6 such doses were needed to achieve similar killing of L. major; this was confirmed by quantitative PCR. The combination of rapid accumulation and potent activity in the Leishmania-infected dermis indicates the potential of DNDI-0690 as a novel oral treatment for CL
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20
[1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030
Campañas - PU122 201801
El curso integra todos los conocimientos y habilidades que el alumno ha adquirido en los ciclos anteriores y pretende simular el trabajo que se realiza en una agencia de publicidad considerando sus tres áreas principales: Planning, Creatividad y Medios, complementando este aprendizaje con el desarrollo de las competencias especĂficas de Estrategia Comunicacional, Creatividad y EjecuciĂłn Publicitaria que le permitirán diseñar y evaluar estrategias pertinentes de acuerdo a los objetivos establecidos. La comunicaciĂłn publicitaria requiere de estrategias coherentes y consistentes a lo largo del tiempo, trabajadas de manera creativa y difundidas a travĂ©s del mix adecuado de medios de comunicaciĂłn
Campañas - PU122 - 202101
El curso integra todos los conocimientos y habilidades que el alumno ha adquirido en los ciclos anteriores y
pretende simular el trabajo que se realiza en una agencia de publicidad considerando sus tres áreas principales:
Planning, Creatividad y Medios, complementando este aprendizaje con el desarrollo de las competencias
especĂficas de Estrategia Comunicacional, Creatividad y EjecuciĂłn Publicitaria que le permitirán diseñar y
evaluar estrategias pertinentes de acuerdo a los objetivos establecidos.
La comunicaciĂłn publicitaria requiere de estrategias coherentes y consistentes a lo largo del tiempo, trabajadas
de manera creativa y difundidas a través del mix adecuado de medios de comunicación
Campañas - PU122 - 202102
El curso integra todos los conocimientos y habilidades que el alumno ha adquirido en los ciclos anteriores y
pretende simular el trabajo que se realiza en una agencia de publicidad considerando sus tres áreas principales:
Planning, Creatividad y Medios, complementando este aprendizaje con el desarrollo de las competencias
especĂficas de Estrategia Comunicacional, Creatividad y EjecuciĂłn Publicitaria que le permitirán diseñar y
evaluar estrategias pertinentes de acuerdo a los objetivos establecidos.
La comunicaciĂłn publicitaria requiere de estrategias coherentes y consistentes a lo largo del tiempo, trabajadas
de manera creativa y difundidas a través del mix adecuado de medios de comunicación
FĂsica - MA651 - 202102
DescripciĂłn: FĂsica es un curso general que corresponde a la lĂnea de FĂsica para la carrera de Arquitectura, de
carácter teórico-práctico.
Propósito: Este curso está dirigido a estudiantes del segundo ciclo, que busca desarrollar las competencias
generales de razonamiento cuantitativo en el nivel 1. El curso brinda el soporte de conceptos fĂsicos necesarios
para que el estudiante de arquitectura analice, cuantifique magnitudes fĂsicas, desarrolle estrategias y
habilidades básicas para resolver problemas de Fluidos, calor, electricidad, ondas y equilibrio estático, usando
leyes fĂsicas que son esenciales para el estudio de todas las Ciencias Naturales, su aplicaciĂłn en la vida
cotidiana
FĂsica II - MA462 - 202102
1
DescripciĂłn: Es el segundo curso de la lĂnea de FĂsica que desarrolla los principios de electricidad y
magnetismo basada en el cálculo, que son esenciales para el estudio de todas las Ciencias Naturales, su
aplicaciĂłn a la vida cotidiana y la tecnologĂa.
PropĂłsito: El curso de FĂsica II desarrolla la competencia de razonamiento cuantitativo en el nivel 2, está
dirigido a estudiantes del cuarto ciclo para las carreras de IngenierĂa Civil, Industrial, ElectrĂłnica, MecatrĂłnica,
Sistemas de InformaciĂłn y Software, y a estudiantes del quinto ciclo para la carrera de IngenierĂa de GestiĂłn
Minera, cuenta con pre-requisito de FĂsica I. Este curso brinda el soporte de conceptos fĂsicos que requiere el
estudiante de ingenierĂa, necesarios para las asignaturas posteriores propias de cada especialidad
FĂsica I - MA466 - 202102
DescripciĂłn: Es el primer curso de la lĂnea de FĂsica que desarrolla los principios fundamentales de la mecánica
(cinemática, dinámica, leyes de conservación, oscilaciones y elasticidad) basada en el cálculo, que son
esenciales para el estudio de todas las Ciencias Naturales, su aplicaciĂłn en la vida cotidiana y la tecnologĂa.
PropĂłsito: El curso de FĂsica I desarrolla la competencia de razonamiento cuantitativo en el nivel 2, Está
dirigido a estudiantes del tercer ciclo para las carreras de IngenierĂa Civil, ElectrĂłnica, Industrial, MecatrĂłnica,
GestiĂłn Minera, Sistemas de InformaciĂłn y Software y a estudiantes del cuarto ciclo para las carreras de
IngenierĂa de GestiĂłn Empresarial y Ciencias de la ComputaciĂłn, cuenta con pre-requisitos como nivelaciĂłn de
FĂsica y Cálculo I. Este curso brinda una base conceptual sĂłlida de la mecánica, que le permite continuar con el
curso de FĂsica II de la Facultad de IngenierĂa
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