Formulation and evaluation of anion transporters in nanostructured lipid carriers.

Six novel click-tambjamines (1-6) bearing an alkyl chain of varying length linked to the imine moiety have been formulated in nanostructured lipid carriers (NLCs) to evaluate their transmembrane anion transport activity both when free (i.e., not encapsulated) and nanoformulated. Nanostructured lipid carriers (NLCs) are an example of drug delivery systems (DDSs) that stand out because of their versatility. In this work we show that NLCs can be used to efficiently formulate highly lipophilic anionophores and experiments conducted in model liposomes reveal that these formulations are adequate to deliver anionophores without compromising their transport activity. This result paves the way to facilitate the study of highly lipophilic anionophores and their potential use as future drugs.

An Attack on Zawadzki's Quantum Authentication Scheme.

Identification schemes are interactive cryptographic protocols typically involving two parties, a prover, who wants to provide evidence of their identity and a verifier, who checks the provided evidence and decides whether or not it comes from the intended prover. Given the growing interest in quantum computation, it is indeed desirable to have explicit designs for achieving user identification through quantum resources. In this paper, we comment on a recent proposal for quantum identity authentication from Zawadzki. We discuss the applicability of the theoretical impossibility results from Lo, Colbeck and Buhrman et al. and formally prove that the protocol must necessarily be insecure. Moreover, to better illustrate our insecurity claim, we present an attack on Zawadzki's protocol and show that by using a simple strategy an adversary may indeed obtain relevant information on the shared identification secret. Specifically, through the use of the principal of conclusive exclusion on quantum measurements, our attack geometrically reduces the key space resulting in the claimed logarithmic security being reduced effectively by a factor of two after only three verification attempts.

iPSC-Derived Intestinal Organoids from Cystic Fibrosis Patients Acquire CFTR Activity upon TALEN-Mediated Repair of the p.F508del Mutation.

Cystic fibrosis (CF) is the main genetic cause of death among the Caucasian population. The disease is characterized by abnormal fluid and electrolyte mobility across secretory epithelia. The first manifestations occur within hours of birth (meconium ileus), later extending to other organs, generally affecting the respiratory tract. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR encodes a cyclic adenosine monophosphate (cAMP)-dependent, phosphorylation-regulated chloride channel required for transport of chloride and other ions through cell membranes. There are more than 2,000 mutations described in the CFTR gene, but one of them, phenylalanine residue at amino acid position 508 (p.F508del), a recessive allele, is responsible for the vast majority of CF cases worldwide. Here, we present the results of the application of genome-editing techniques to the restoration of CFTR activity in p.F508del patient-derived induced pluripotent stem cells (iPSCs). Gene-edited iPSCs were subsequently used to produce intestinal organoids on which the physiological activity of the restored gene was tested in forskolin-induced swelling tests. The seamless restoration of the p.F508del mutation resulted in normal expression of the mature CFTR glycoprotein, full recovery of CFTR activity, and a normal response of the repaired organoids to treatment with two approved CF therapies: VX-770 and VX-809.

Small molecule anion transporters display in vitro antimicrobial activity against clinically relevant bacterial strains.

Highly active transmembrane anion transporters have demonstrated their activity against antibiotic-resistant and clinically relevant bacterial strains. This type of compound offers promise as a strategy to develop novel antibacterial agents.

A Parasite Biomarker Set for Evaluating Benznidazole Treatment Efficacy in Patients with Chronic Asymptomatic Trypanosoma cruzi Infection.

One of the current greatest challenges of Chagas disease is the establishment of biomarkers to assess the efficacy of drugs in a short period of time. In this context, the reactivity of sera from 66 adults with chronic indeterminate Chagas disease (IND) for a set of four Trypanosoma cruzi antigens (KMP11, PFR2, HSP70, and 3973d) was analyzed before and after benznidazole treatment. The results showed that the reactivity against these antigens decreased at 9, 24, and 48 months after treatment. Moreover, the 42.4% and 68.75% of IND patients met the established standard criteria of therapeutic efficacy (STEC) at 24 and 48 months posttreatment, respectively. Meeting the STEC implied that there was a continuous decrease in the reactivity of the patient sera against the four antigens after treatment and that there was a substantial decrease in the reactivity for at least two of the antigens. This important decrease in reactivity may be associated with a drastic reduction in the parasite load, but it is not necessarily associated with a parasitological cure. After treatment, a positive PCR result was only obtained in patients who did not meet the STEC. The percentage of granzyme B+/perforin+ CD8+ T cells was significantly higher in patients who met the STEC than in those who did not meet the STEC (35.2% versus 2.2%; P < 0.05). Furthermore, the patients who met the STEC exhibited an increased quality of the multifunctional response of the antigen-specific CD8+ T cells compared with that in the patients who did not meet the STEC.

Generation of one iPSC line (IMEDEAi006-A) from an early-onset familial Alzheimer's Disease (fAD) patient carrying the E280A mutation in the PSEN1 gene.

The mutation E280A in PSEN1 (presenilin-1) is the most common cause of early-onset familial Alzheimer's Disease (fAD). It presents autosomal dominant inheritance and frequently leads to the manifestation of the disease in relatively young individuals. Here we report the generation of one PSEN1 E280A iPSC line derived from an early-onset patient. OriP/EBNA1-based episomal plasmids containing OCT3/4, SOX2, KLF4, L-MYC, LIN28, BCL-xL and shp53 were used to reprogram oral mucosa fibroblasts. The iPSC line generated has normal karyotype, carry the E280A mutation, is free of plasmid integration, express high levels of pluripotency markers and can differentiate into all three germ layers.

Tratamiento de la preeclampsia

El objetivo de este trabajo es hacer una evaluación del tratamiento instituido en el servicio de Gíneco-Obstetricia del hospital Enrique Garcés de la ciudad de Quito. El estudio tiene el carácter de retrospectivo, para lo cual se analizaron las historias clínicas de las pacientes ingresadas con presión arterial media de 106 mm de Hg de Hg o más en el período comprendido entre el 10. de enero de 1986 al 30 de junio del mismo año. Se estudió mortalidad materna, mortalidad perinatal, estado del niño al nacimiento y causas de mortalidad perinatal. Se observó que la mortalidad materna fue 0 x 1.000 partos, la mortalidad perinatal fue de 2 x 100 partos, 96.32% de los niños recién nacidos tuvieron APGAR de 8-10 a los cinco minutos; de los recién nacidos fallecidos con membrana hialaina y obito representaon el 66.6%

Eclampsia

Del 10. de enero de 1985 al 30 de junio de 1986 (18 meses) se atendieron en el Hospital Enrique Garcés 5.409 partos, correspondiendo a eclámpticas 14, lo que representa una incidencia de 2,59 x 1000. En el 65% la interrupción del embarazo fue por cesárea. La principal complicación materna fue de tipo neurológico, encefalopatía hipertensiva por hemorragia intracraneal que se presentó en el 28,5%. Una paciente falleció por coagulación intravascular diseminada con el feto intraútero y representa el 71.4%. En base a los resultados consideramos que al conducta para el manejo de la eclampsia en el Hospital Enrique Garcés es adecuada

Epidemiología de la preeclampsia / Epidemiology of preeclampsia

En el presente trabajo se investigan los factores que intervienen en el aparecimiento de los trastornos hipertensivos en el embarazo, en gestantes que asisten a control en el Hospital Enrique Garcés, en el lapso de un año. Las variables estudiadas fueron edad materna, edad gestacional, paridad, factor socioeconómico e hipertensión crónica. Se encontró que la incidencia general fue del 13,58%, siendo los grupos poblacionales más expuestos las pacientes comprendidas entre los 19 y 21 años de edad, gestantes que cursan de 37 a 42 semanas y mujeres de clase socioeconómica baja