Femtosecond laser-assisted cataract surgery versus conventional phacoemulsification: A meta-analysis of randomized controlled trials.

PURPOSE: The main purpose of our study is to compare the adverse events occurrence, complications, and postoperative outcomes of Femtosecond Laser-Assisted Cataract Surgery (FLACS) versus conventional phacoemulsification surgery (CPS) in adult patients undergoing cataract surgery. METHODS: We conducted our research using PubMed, Scopus, and MEDLINE through EBSCOhost from 2012 to July 2022 with English and Spanish language restriction, including only Randomized Controlled Trials (RCTs). The PRISMA guidelines were observed for data abstraction, including a random-effects model for each outcome. RESULTS: We analyzed 4844 eyes from 23 RCTs with some low risk of bias according to RoB 2 tool. We found statistically significant differences between the FLACS and CPS groups for the mean absolute error (MD = -0.12, 95% CI:-0.22-[-0.02], p = 0.01), the circularity of capsulorhexis (MD = 0.04, 95% CI: 0.04-0.05, p ≤ 0.00001), IOL centration (D = -0.07, 95% CI:-0.09-[-0.05], p ≤ 0.00001), CDE count (MD = -1.75, 95% CI: -2.75-[-0.74], p = 0.0006), mean phacoemulsification time (MD = -12.90, 95% CI:-20.89-[-4.92], p = 0.002), EPT (MD = -0.93, 95% CI: -1.68-[-0.019], p = 0.01) and endothelial cell density loss ((MD = -0.6, 95% CI: -1-[-0.19], p = 0.004). Also, the safety analysis showed a lower incidence of posterior capsule tear (PCT) in the FLACS group (OR =0.29, 95% CI: 0.09-1, p = 0.05). CONCLUSIONS: Our results suggest that FLACS might be helpful for patients with relatively dense cataracts and low preoperative endothelial cell values.

Análisis de 5,789 biopsias de trofoectodermo: desenlaces clínicos y probabilidad de embarazo en ciclos con prueba genética preimplantacional para aneuploidias / Analysis of 5,789 trophectoderm biopsies: clinical outcomes and pregnancy probability in preimplantation genetic testing for aneuploidy cycles

Resumen OBJETIVO: Analizar la tasa de euploidia, los desenlaces clínicos y la probabilidad de lograr un embarazo en función de la edad de la madre, los blastocistos biopsiados y la calidad embrionaria. MATERIALES Y MÉTODOS: Estudio retrospectivo y descriptivo efectuado para evaluar las biopsias de trofoectodermo de los ciclos con prueba genética preimplantacional para aneuploidias de pacientes atendidas en Vida Genetics (León, Guanajuato) de noviembre de 2017 a marzo de 2023. RESULTADOS: Se evaluaron 5789 biopsias de trofoectodermo de 1442 ciclos de la prueba genética preimplantacional para aneuploidias mediante secuenciación masiva en mujeres de 18 a 48 años. Tasa global de euploidia por ciclo: 36.3%, aneuploidia: 57.2% y mosaicismmo: 6.5%. La tasa de euploidia disminuyó con el incremento de la edad de las madres (75% en 18 años, 0% en 47-48 años). Los embriones de buena calidad tuvieron mayores tasas de euploidia (50%) comparados con calidad regular (47%) y mala calidad (31.7%) (p < 0.0001). Los embriones con biopsia en día 5 tuvieron tasas de euploidia mayores (42.7%) comparados con los de día 6 (32%) y día 7 (27.2%) (p < 0.0001). La tasa de embarazo clínico fue del 60.4%, implantación 57.2% y aborto espontáneo 11.2%. La probabilidad de lograr, al menos, un embrión euploide fue mayor en las pacientes con mayor cantidad de blastocistos con biopsia. La probabilidad de lograr un embarazo con un embrión euploide se vio afectada por la calidad del embrión transferido. CONCLUSIONES: Se corrobora la asociación entre la edad materna avanzada y la tasa de aneuploidia. Destaca la repercusión de la calidad embrionaria y el día en que se toma la biopsia en los desenlaces de la prueba genética preimplantacional para aneuploidias y la importancia de la calidad del embrión en las tasas de éxito del tratamiento.

Abstract OBJECTIVE: To analyze the rate of euploidy, clinical outcomes, and the probability of achieving pregnancy as a function of maternal age, biopsied blastocysts, and embryo quality. MATERIALS AND METHODS: Retrospective and descriptive study performed to evaluate trophectoderm biopsies from cycles with preimplantation genetic testing for aneuploidy of patients seen at Vida Genetics (León, Guanajuato) from November 2017 to March 2023. RESULTS: 5,789 trophectoderm biopsies from 1,442 cycles of preimplantation genetic testing for aneuploidy by massive sequencing were evaluated in women aged 18 to 48 years. The overall euploidy rate per cycle was 36.3%, aneuploidy 57.2%, and mosaicism 6.5%. The euploidy rate decreased with increasing maternal age (75.0% at 18 years, 0% at 47-48 years). Good quality embryos had a higher euploidy rate (50.0%) compared to fair quality (47.0%) and poor quality (31.7%) (p < 0.0001). Embryos biopsied on day 5 had higher euploidy rates (42.7%) compared to day 6 (32.0%) and day 7 (27.2%) (p < 0.0001). The clinical pregnancy rate was 60.4%, implantation 57.2% and miscarriage 11.2%. The probability of achieving at least one euploid embryo was higher in patients with a higher number of biopsied blastocysts. The probability of achieving pregnancy with a euploid embryo was influenced by the quality of the transferred embryo. CONCLUSIONS: The association between advanced maternal age and the rate of aneuploidy is confirmed. The influence of embryo quality and day of biopsy on the outcome of preimplantation genetic testing for aneuploidy and the importance of embryo quality for treatment success rates are highlighted.

The importance of standardizing criteria for PGT-A interpretation of blastocysts analyzed by next-generation sequencing.

OBJECTIVE: To compare the preimplantation genetic testing for aneuploidy (PGT-A) results using the three most frequent criteria employed by preimplantation genetic laboratories and evaluate its impact on the number of euploid embryos available for transfer. METHODS: Retrospective and descriptive study including patients who underwent PGT-A between January 2018 and December 2020. Five hundred and nine PGT-A cycles and 2,079 blastocysts were analyzed by next-generation sequencing (NGS). We re-assigned the diagnosis of all blastocysts using three different criteria: strict (mosaicism thresholds from 20% to 80%), standard (from 30% to 70%) and excluding (mosaicism is not reported). We compared the euploid, aneuploid and mosaic embryos obtained in each criteria used. RESULTS: We observed PGT-A results discrepancies in 32.5% (165/509) of the cycles when the three different criteria were applied. The standard and excluding criteria showed 92 more euploid embryos (875/2,079) compared to the strict criteria (783/2,079). Evaluating the PGT-A results per cycle with the strict, standard and excluding criteria, the euploidy rates were 34.0%, 38.4% and 38.4% (p<0.001); aneuploidy rates were 59.0%, 55.8% and 61.6% (p<0.001) and mosaic rates were 7.0% and 5.8% (p<0.047), respectively. The mean number of euploid blastocysts available for transfer was 1.54±1.67 with the strict criteria, while the possibility to obtain an euploid embryo was higher if the standard or the excluding criteria were used 1.72±1.78 (p<0.001). CONCLUSIONS: This study highlights the importance of standardizing the criteria used for the interpretation of PGT-A blastocysts. We observed significant differences on PGT-A results associated solely to the criteria used.

Customizably designed multibodies neutralize SARS-CoV-2 in a variant-insensitive manner.

The COVID-19 pandemic evolves constantly, requiring adaptable solutions to combat emerging SARS-CoV-2 variants. To address this, we created a pentameric scaffold based on a mammalian protein, which can be customized with up to 10 protein binding modules. This molecular scaffold spans roughly 20 nm and can simultaneously neutralize SARS-CoV-2 Spike proteins from one or multiple viral particles. Using only two different modules targeting the Spike's RBD domain, this construct outcompetes human antibodies from vaccinated individuals' serum and blocks in vitro cell attachment and pseudotyped virus entry. Additionally, the multibodies inhibit viral replication at low picomolar concentrations, regardless of the variant. This customizable multibody can be easily produced in procaryote systems, providing a new avenue for therapeutic development and detection devices, and contributing to preparedness against rapidly evolving pathogens.

Associations of fertility parameters with fatty acids and DNA methylation in Mexican women undergoing in vitro fertilization.

BACKGROUND: Fatty acids (FA) likely affect human fertility at multiple levels, as deviations from physiological FA profiles are obesogenic, and FA can modify DNA methylation (DNAm). Yet, the interplay of follicular fluid (FF) and serum FA with BMI and percentage body fat (PBF) in human fertility is not completely understood. Also, associations of DNAm with fertility are largely unexplored. METHODS: Reproductive parameters ranging from retrieved oocyte number to infant birth weight, were recorded in Mexican women undergoing in vitro fertilization (n = 88). Multiple regression analysis sought BMI-adjusted and age-adjusted associations. Receiver operating characteristic analysis tested for discrimination between outcomes. RESULTS: Associations of FF and serum FA were markedly distinct. While various FF FA (C16:1, C18:0, C20:2, C20:3, arachidonic acid) were significantly and inversely associated only with retrieved oocyte number, selected serum FA were associated with a broad range of pre-fertilization and post-fertilization parameters. Associations of BMI and FF FA were complex, as arachidonic acid was inversely associated with both BMI and retrieved oocyte number, while oleic acid (OA) was directly associated with BMI and PBF. Ultrasound-assessed clinical pregnancy outcome (CP) was directly associated with serum OA but inversely with its trans isomer elaidic acid (EA) and with BMI. Compounded BMI, serum EA and OA discriminated CP well (AUC = 0.74). Whole blood DNA methylation was significantly associated with and a moderate predictor (AUC = 0.66) of percent fertilized oocytes. CONCLUSIONS: Overall FF FA pool composition rather than FA identity may impact oocyte production and cellular memory of FF FA is lost as the oocyte exits the follicular environment. The contrasting associations of BMI, FF OA and arachidonic acid suggest that the control of oocyte homeostasis by FF FA is uncoupled from BMI. Further studies are warranted to assess the potential of compounding BMI with serum EA and OA to predict CP.

Repetición de la biopsia ante una falla en la amplificación / Repeat biopsy in case of amplification failure

Resumen OBJETIVO: Analizar los posibles factores asociados con las fallas en la amplificación, los desenlaces de la euploidia y clínicos entre los embriones con repetición de la biopsia y los de una sola (grupo control). MATERIALES Y MÉTODOS: Estudio retrospectivo y multicéntrico de análisis de biopsias de blastocistos practicadas en 22 centros de reproducción asistida (noviembre 2017 a febrero 2022). Se analizaron 4,106 blastocistos procedentes de 1,007 ciclos de ICSI con prueba genética para aneuplidias previa a la implantación. En los blastocistos reportados con falla en la amplificación se analizó el Centro donde se practicó la biopsia, el día en que ésta se tomó, la calidad embrionaria y la incidencia de complicaciones durante el procedimiento. Los resultados se compararon con la prueba genética para aneuploidias previa a la implantación y los desenlaces clínicos entre los embriones con repetición de la biopsia y el grupo control. RESULTADOS: En el 96.0% (3,942) de los embriones se obtuvo resultado y en el 4.0% (n = 164) se reportó falla en la amplificación. La biopsia se repitió en las 99 fallas en la amplificación y se obtuvo resultado en el 83.8% de los casos. Las tasas de euploidia fueron similares entre embriones con repetición de la biopsia y los controles (34.9 en comparación con 39.7%; p > 0.05). El Centro fue el único factor que mostró diferencias en las tasas de falla en la amplificación (p < 0.05). No se observaron diferencias en el día de la biopsia o la calidad embrionaria. Las tasas de embarazo (51.0 en comparación con 58.3%), implantación (63.9 en comparación con 61.5%) y aborto (16.9 en comparación con 28.6%) fueron similares entre embriones con una sola biopsia o repetición de ésta, respectivamente. CONCLUSIONES: El Centro fue el principal factor que influyó en las fallas en la amplificación. Las tasas de euploidia y los desenlaces clínicos no difirieron entre el grupo control y los embriones con repetición de la biopsia; por consiguiente, se recomienda repetir la biopsia en los embriones con falla en la amplificación.

Abstract OBJECTIVE: To analyze possible factors associated with amplification failures, euploidy and clinical outcomes between repeat and single biopsy embryos (control group). MATERIALS AND METHODS: Retrospective multicenter study involving 4,106 blastocysts from 1,007 ICSI cycles with preimplantation genetic testing for aneuploidy performed by next generation sequencing. In case of DNA amplification failure, the IVF center where biopsies were performed, the day of biopsy, the embryo quality and the incidence of complications during biopsy were analyzed. Preimplantation genetic testing for aneuploidy results and clinical outcomes were compared between re-biopsied embryos and the control group. RESULTS: Of the 4,106 blastocysts included in this study, 96.0% (3,942) obtained a result while 4.0% (164) had an amplification failure. Ninety-nine embryos with amplification failure were re-biopsied and 83.8% resulted in an informative diagnosis. Euploidy rates were equivalent between re-biopsied and control blastocysts (34.9% vs 39.7%, P>0.05). The only factor significantly affecting the amplification failure rates was the IVF center. No differences were observed between biopsy days or embryo quality. Pregnancy (51.0% vs 58.3%), implantation (63.9% vs 61.5%) and miscarriage rates (16.9% vs 28.6%) were similar between single and repeat biopsied embryos, respectively. CONCLUSIONS: The centre was the main factor influencing amplification failures. Euploidy rates and clinical outcomes did not differ between the control group and repeat biopsied embryos; therefore, repeat biopsy is recommended for embryos with amplification failure.

The Influence of Angle Alpha, Angle Kappa, and Optical Aberrations on Visual Outcomes after the Implantation of a High-Addition Trifocal IOL.

The aim of our investigation was to examine the possible correlations between optical aberrations, angle kappa, angle alpha, and visual outcomes following cataract surgery. In total, 56 eyes of 28 patients were implanted with the Liberty 677MY trifocal intraocular lens (IOL). Pre- and postoperative higher-order aberrations, coma, astigmatism, angle alpha, and angle kappa were registered, along with uncorrected and corrected visual acuities at multiple distances. Visual acuity and contrast sensitivity defocus curves were plotted, and the areas under the curve were calculated 1 and 3 months postoperatively. Excellent visual outcomes were found at all distances. Patients reported low levels of dysphotopsia, and 96.4% of patients achieved complete spectacle independence. While angle kappa significantly decreased during cataract surgery (p = 0.0007), angle alpha remained unchanged (p = 0.5158). Angle alpha correlated with postoperative HOAs and had a negative impact on near vision (p = 0.0543). Preoperative corneal HOA and coma had a strong adverse effect on future intermediate and near vision. Residual astigmatism significantly affected postoperative intermediate vision (p = 0.0091). Our results suggest that angle kappa is not an optimal predictive factor for future visual outcomes, while angle alpha and the preoperative screening of optical aberrations might help patient selection prior to multifocal IOL implantation.

Overcoming the Solubility Problem in E. coli: Available Approaches for Recombinant Protein Production.

Despite the importance of recombinant protein production in the academy and industrial fields, many issues concerning the expression of soluble and homogeneous products are still unsolved. Several strategies were developed to overcome these obstacles; however, at present, there is no magic bullet that can be applied for all cases. Indeed, several key expression parameters need to be evaluated for each protein. Among the different hosts for protein expression, Escherichia coli is by far the most widely used. In this chapter, we review many of the different tools employed to circumvent protein insolubility problems.

Production, purification and characterization of a double-tagged TEV protease.

Many recombinant proteins are products of great value in biomedical and industrial fields. The use of solubility and affinity tags are commonly used to increase yields and facilitate the purification process. However, it is of paramount importance in several applications to remove the fusion tag from the final product. In this regard, the Tobacco Etch Virus protease (TEV) is one of the most widely used for tag removal. The presence in the TEV of the same tag to be removed facilitates the separation of TEV and the tag from the cleaved recombinant protein in a single purification step. We generated a double-tagged (StrepTagII and HisTag) TEV variant with reported mutations that improve the activity, the expression yield in E.coli, and that decrease the auto-proteolysis. This TEV can be easily purified by two consecutive affinity chromatography steps with high yields and purity. The cleavage reaction can be done to almost completeness in as fast as 15 min at room temperature and the removal of the protease and tags is performed in a single purification step, independent of the previous presence of a StrepTagII or a HisTag on the target.

Somatic hypermutation profiles in stereotyped IGHV4-34 receptors from South American chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) is the most common mature B-cell neoplasm in the West. IGHV4-34 is one of the most frequently used genes in CLL patients, which usually display an indolent outcome. In this study, we explored the mutational profile of CLL patients expressing IGHV4-34 within different stereotypes and their association with prognostic factors and clinical outcome. A multi-institutional cohort of unselected 1444 CLL patients was analyzed by RT-PCR and bidirectional sequencing. Cytogenetics and molecular cytogenetics analyses were also performed. We identified 144 (10%) IGHV4-34 expressing cases, 119 mutated (M), 44 of them with stereotyped B-cell receptors. Subset #4 was the most frequent (56.8% of cases) followed by subsets #16 (13.6%), #29 (6.8%), and #201 (2.3%), with different distribution among countries. Analysis of somatic hypermutation profile showed significant differences among stereotyped subsets for G28>D/E, P45>S, E55>Q, and S64>I changes (p < 0.01) and high frequency of disruption of the glycosylation motif in the VH CDR2 region. All stereotyped IGHV4-34 cases showed normal karyotypes. Deletion 13q14 as a sole alteration was present in 42.8% of stereotyped cases with a different distribution among subsets. A shorter time to first treatment was found in non-stereotyped vs. stereotyped M-IGHV4-34 patients (p = 0.034). Our results add new information supporting the importance of recurrent amino acid changes at particular positions, contributing to refine the molecular characterization of South American CLL patients.

Safety and efficacy of lotilaner ophthalmic solution, 0.25% for the treatment of blepharitis due to demodex infestation: A randomized, controlled, double-masked clinical trial.

PURPOSE: To evaluate the safety and efficacy of lotilaner ophthalmic solution, 0.25% for the treatment of blepharitis due to Demodex infestation compared to vehicle control. METHODS: In this phase II, randomized, controlled, double-masked clinical trial, 60 eligible participants with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either topical lotilaner ophthalmic solution, 0.25% (Tarsus Pharmaceuticals, Inc., Irvine, CA) (study group) or the vehicle without lotilaner (control group) bilaterally twice a day for 28 days. Participants were followed at Days 7, 14, 28, 60 and 90. The efficacy parameters were change in collarette grade and Demodex density at Day 28. Safety parameters were adverse events, changes in corrected distance visual acuity (CDVA), intraocular pressure (IOP) and slit-lamp biomicroscopy. RESULTS: The study group showed a statistically significant decrease in collarette grade compared to the control group beginning at Day 14 (p = 0.003) in the upper eyelid and at Day 28 (p = 0.003) in the lower eyelid. Decreases in both lids were maintained through Day 90 (p < 0.001). At Day 28, mite eradication was achieved in 66.7% and 25.9% of eyes in the study and control group (p = 0.005); at Day 90, these proportions were 68.2% and 18.5% (p = 0.001), respectively. No serious adverse events or clinically significant changes in CDVA and IOP were observed. CONCLUSION: For Demodex blepharitis, treatment with lotilaner ophthalmic solution, 0.25% for 4 weeks is safe and effective. The improvement in collarette grade and mite density observed during the treatment period persisted for at least two months following treatment cessation.

Safety and Efficacy of Topical Lotilaner Ophthalmic Solution 0.25% for the Treatment of Demodex Blepharitis: A Pilot Study.

PURPOSE: Evaluate safety and efficacy of topical lotilaner ophthalmic solution, 0.25% for the treatment of Demodex blepharitis. Patients and Methods. 15 patients with Demodex blepharitis, defined as >10 collarettes on the upper lid, lid margin erythema, and Demodex density of ≥1.5 mites/lash on microscopy, were treated bid for 28 days with lotilaner ophthalmic solution, 0.25%. Contact lens wear, artificial eyelashes, and lid structural abnormalities were among the exclusion criteria. No other antibacterial, antiparasitic, or anti-inflammatory treatment or lid hygiene products were permitted. Patients were assessed on Days 7, 14, 28, 60, and 90. Outcome measures were changes in collarette grade and mite density on Day 28. Adverse events and changes in intraocular pressure (IOP), corrected distance visual acuity (CDVA), and slit-lamp biomicroscopy were assessed. RESULTS: Mean collarette grade (upper lids) improved from 3.07 ± 0.21 to 0.79 ± 0.19 on Day 28; the change was statistically significant for both upper and lower lids from Day 14 on. Mean mite density per lash decreased from 2.28 ± 0.16 at baseline to 0.14 ± 0.05 at Day 28 (p < 0.0001). Mite eradication (0 mites) was documented in 57.1% of eyes. The effects were durable through Day 90. There were no adverse events and little to no change in CDVA or IOP. The drop was well tolerated, with no discontinuations due to ocular irritation. CONCLUSION: Topical lotilaner ophthalmic solution, 0.25% for 4 weeks, showed promising efficacy for the treatment of Demodex blepharitis. This novel treatment appears to be safe and well tolerated. Randomized controlled studies are needed to confirm the results.

Impact of correlation of angle α with ocular biometry variables.

PURPOSE: To analyze the association between angle α and ocular biometry in the general population at a third-level ophthalmology hospital. SETTING: Anterior Segment Surgery Department, Asociación para Evitar la Ceguera en México I.A.P., Mexico City, Mexico. DESIGN: Prospective, cross-sectional study. METHODS: Healthy subjects who attended the hospital for a comprehensive ophthalmological evaluation were examined, and general data were collected. A complete ophthalmological assessment and biomicroscopy evaluation were performed and biometry and clinical data were obtained, including visual acuity, axial length (AL), keratometry (K), white-to-white (WTW) measurement. An OPD-Scan III analyzer was used to assess both the angle α distance and biometry parameters. RESULTS: 74 eyes from the same number of patients were included; 43 (58.10%) were women. A statistically significant inverse correlation was found between the angle α and the AL (r = -0.585; P < .0001) and between the WTW distance and the mean K (r = 0.557; P < .0001). A significant correlation was found between the mean K and the angle α (r = 0.271; P = .019). A significant inverse correlation was observed regarding the WTW distance and angle α (r = -0.359; P = .001). By contrast, a direct correlation was evidenced between the WTW and the AL (r = 0.385; P = .0007). CONCLUSIONS: There was a significant inverse correlation between the AL and the angle α magnitude. Hyperopic patients demonstrated significantly higher angle α values when compared with those of myopic patients. In addition, hyperopic eyes with steeper mean K and lesser WTW distance were associated with an increased angle α.

Collarette Elimination and Demodex Mite Eradication with Topical Lotilaner Ophthalmic Solution, 0.25.

Purpose: To evaluate the efficacy of topical lotilaner ophthalmic solution, 0.25%, in patients with Demodex blepharitis. Methods: Eighteen adults with Demodex blepharitis, defined as >10 collarettes on the upper lid and/or mite density of ≥1.5 mites per lash (upper and lower), were treated bid for 42 days with the topical lotilaner ophthalmic solution, 0.25%. Contact lens wear, artificial eyelashes, and lid structural abnormalities were among the exclusion criteria. No other antibacterial, antiparasitic, or anti-inflammatory treatment or lid hygiene products were permitted. One eye of each patient was selected for analysis and assessed on day 7, 14, 28, and 42. Collarettes were graded at each visit, and mite density was evaluated by microscopy at each visit except day 7. Outcome measures were collarette elimination (≤2 lashes with collarettes) and mite eradication (0 mites). Drop tolerability, adverse events, visual acuity, and slit-lamp biomicroscopy were assessed. Results: Collarette elimination was achieved in 13/18 participants (72.2%) by day 42. Mean collarette grade (upper lid) declined from 3.56 ± 0.17 to 0.28 ± 0.11. Mite eradication was achieved in 14/18 participants (77.8%) by day 42. Mean mite density decreased from 2.63 ± 0.39 to 0.12 ± 0.08 mites/lash. Participants reported good tolerability. Adverse events were mild and transient and did not result in treatment discontinuation. Conclusion: Six weeks of at-home topical therapy with the lotilaner ophthalmic solution, 0.25%, was effective in eliminating the most common objective signs of Demodex blepharitis, with a collarette elimination rate of 72% and mite eradication in 78% of eyes by day 42. ISRCTN registration #: 24398865.

Docetaxel in chitosan-based nanocapsules conjugated with an anti-Tn antigen mouse/human chimeric antibody as a promising targeting strategy of lung tumors.

The aim of this work was to evaluate the physicochemical and biological properties of docetaxel (DCX) loaded chitosan nanocapsules (CS Nc) functionalized with the monoclonal antibody Chi-Tn (CS-PEG-ChiTn mAb Nc) as a potential improvement treatment for cancer therapy. The Tn antigen is highly specific for carcinomas, and this is the first time that such structure is targeted for drug delivery. The nanocapsules (Ncs), formed as a polymeric shell around an oily core, allowed a 99.9% encapsulation efficiency of DCX with a monodispersity particle size in the range of 200 nm and a high positive surface charge that provide substantial stability to the nanosystems. Release profile of DCX from Ncs showed a sustained and pH dependent behavior with a faster release at acidic pH, which could be favorable in the intracellular drug delivery. We have designed PEGylated CS Nc modified with a monoclonal antibody which recognize Tn antigen, one of the most specific tumor associated antigen. A biotin-avidin approach achieved the successful attachment of the antibody to the nanocapsules. Uptake studies and viability assay conducted in A549 human lung cancer cell line in vitro demonstrate that ChiTn mAb enhance nanoparticles internalization and cell viability reduction. Consequently, these ChiTn functionalized nanocapsules are promising carriers for the active targeting of DCX to Tn expressing carcinomas.

CUTie2: The Attack of the Cyclic Nucleotide Sensor Clones.

The detection of small molecules in living cells using genetically encoded FRET sensors has revolutionized our understanding of signaling pathways at the sub-cellular level. However, engineering fluorescent proteins and specific binding domains to create new sensors remains challenging because of the difficulties associated with the large size of the polypeptides involved, and their intrinsically huge conformational variability. Indeed, FRET sensors' design still relies on vague structural notions, and trial and error combinations of linkers and protein modules. We recently designed a FRET sensor for the second messenger cAMP named CUTie (Cyclic nucleotide Universal Tag for imaging experiments), which granted sub-micrometer resolution in living cells. Here we apply a combination of sequence/structure analysis to produce a new-generation FRET sensor for the second messenger cGMP based on Protein kinase G I (PKGI), which we named CUTie2. Coarse-grained molecular dynamics simulations achieved an exhaustive sampling of the relevant spatio-temporal coordinates providing a quasi-quantitative prediction of the FRET efficiency, as confirmed by in vitro experiments. Moreover, biochemical characterization showed that the cGMP binding module maintains virtually the same affinity and selectivity for its ligand thant the full-length protein. The computational approach proposed here is easily generalizable to other allosteric protein modules, providing a cost effective-strategy for the custom design of FRET sensors.

New Orodispersible Mini Tablets of Enalapril Maleate by Direct Compression for Pediatric Patients.

BACKGROUND: In many countries, hypertension in the pediatric population is considered a serious risk of mortality and morbidity. In this respect, it is central to design and develop new pharmaceutical forms for pediatric patients with hypertension. The development of Orodispersible Mini-Tablets (ODMTs) for pediatric use has gained importance in recent years. Therefore, regulations for developing suitable and palatable dosage forms for pediatric patients have been established by WHO authorities. OBJECTIVE: This study aimed to design and develop orodispersible mini tablets of enalapril maleate (EnM ODMTs) for pediatric use. METHODS: Five pharmaceutical formulations (A, B, C, D and E, shown in Table 1) were designed. The effects of different co-processed excipients and active pharmaceutical ingredients at different doses were studied. Lactose co-processed excipients selected were the following: Tablettose® 80, Microce- Lac® 100 and StarLac®. The micromeritic properties for all the physical mixtures were examined. The mini tablets were obtained by direct compression. Quality control parameters were determined in accordance with US Pharmacopeia. RESULTS: Three OMDTs with StarLac® showed good results of hardness, flow ability and fast disintegration. The formulation with 0.1 mg of enalapril maleate presented the best results for the official parameters of hardness (4.0 kp), friability (< 1%), disintegration time (28 s), drug content uniformity (103.6 %), and wetting time (23 s). CONCLUSION: The three OMDTs with StarLac® showed good quality parameters, according to official requirements. Formulation A exhibited the best wetting time, complying with the dose recommended for pediatric patients. This formulation could be considered eligible for being manufactured at industrial scale.

Oocyte maturation arrest produced by TUBB8 mutations: impact of genetic disorders in infertility treatment.

Oocyte maturation defect is a challenging situation in the management of infertility, the etiology may be related to endocrine causes, protocols used in ovarian stimulation, oocyte intrinsic defects or procedures in embryology laboratory. We report three Mexican females in treatment for primary infertility with non-mature oocytes after ovary stimulation and oocyte capture in whom a genetic diagnosis of TUBB8-oocyte maturation defect was revealed by exome sequencing. Two couples achieved pregnancies though oocyte donation after establishing the genetic etiology. Our results expand the role of TUBB8-disorders in patients of non-Asian ethnicity. Oocyte maturation defects of monogenic origin are a growing group of disorders that endocrinologists and reproductive medicine specialists should be aware in order to provide referral to genetics for establish a correct and opportune diagnosis.

Influence of Angle κ and Higher-Order Aberrations on Visual Quality Employing Two Diffractive Trifocal IOLs.

Prospective, randomized, comparative, and controlled study to estimate the association between angle κ distance and higher-order aberrations (HOAs) with postoperative visual acuity after presbyopia-correcting IOL implantation. Forty-three eyes from 43 patients were included and randomly assigned in two groups for either AT LISA tri 839MP or Acrysof IQ PanOptix IOL implantation. The OPD-Scan III analyzer was utilized to assess the angle κ distance and higher-order aberration (HOAs). Twenty-three eyes were in the Acrysof IQ PanOptix group and 20 patients in the AT LISA tri 839MP group. The uncorrected distance visual acuity (UDVA) for the PanOptix group was 0.092 ± 0.10, whereas for AT LISA tri was 0.050 ± 0.06 (P=0.229). The uncorrected intermediate visual acuity (UIVA) for the PanOptix group was 0.173 ± 0.18, whereas for AT LISA tri, it was 0.182 ± 0.11 (P=0.669). Uncorrected near visual acuity (UNVA) was 0.068 ± 0.04 and 0.085 ± 0.07, respectively (P=0.221). Also, correlation coefficient between HOAs and the Strehl ratio for each group were -0.768 (P < 0.0001) and -0.863 (P=0.0001). Patients implanted with both trifocal IOLs showed excellent postoperative visual performance at all distances at the six-month follow-up visit. No association was found between angle κ distance and postoperative visual acuity regardless of the angle κ magnitude or the two trifocal IOLs inner optical diameter. Also, internal aberrations demonstrated a significant inverse correlation with the Strehl ratio for both trifocal IOLs.