The Design and Manufacture of Custom Ocular Prostheses (COPs) Based on Computer-Aided Semi-automation Workflow

Background: It is important to correct the ocular disfigurement by wearing prostheses as soon as possible after healing from the eye enucleation surgery. This study aimed to develop a new computer-aided approach to fabricate custom ocular prostheses (COPs) with higher accuracy and efficiency and to fit different anophthalmia sockets. Results: Five patients underwent enucleation surgery from November 2018 to October 2020 were enrolled in the study. The semi-automatic design and fabrication workflow of COPs was based on the conjunctival sac impression, combined with Computer-aided design/Computer-aided manufacture (CAD/CAM) workflow, which involves computer image analysis, reverse engineering (RE), and 3-dimensional (3D) printing technologies. The height of palpebral fissure in the artificial eye group was 0.8000 ± 0.09529, N=5.The height of palpebral fissure in the healthy eye group was 0.7660 ± 0.1147, N=5, and there was no statistical difference between the two groups (p>0.05). The artificial eye in the conjunctival sac had a good effect on the reconstruction of orbital fullness. Both of the vertical activity and horizontal activity of COPs is smaller than that of healthy eyes (p<0.05).Conclusions: COPs made by RE and 3D printing technologies can effectively make the COPs suitable for patients' conjunctival sac. This workflow improved the accuracy of the COPs, and also reduced patients’ waiting time, which is worthy to be popularized and applied.

Thymoquinone lipid nanoparticles cut the Gordian knots of depression via neuroprotective BDNF and downregulation of neuro-inflammatory NF-κB, IL-6, and TNF-α in LPS treated rats

Background: In over 300 million clinical cases, antidepressant drugs seem to provide only symptomatic relief and limited protection in life-threatening depressive events. Objective: To compare neuronal-signaling mechanism and neuroprotective roles of Thymoquinone (TQ) suspension and its SLN (TQSLN) against standard antidepressant drug fluoxetine. Results: As compared to fluoxetine, TQ reporteda significantly better docking score (-6.83 v/s -6.22) and a better lower free binding energy of (-34.715 Kcal/mol v/s -28.537 Kcal/mol). While poorly oral bioavailable and P-gp substrate TQ reported approximately 250% higher gut permeation if delivered as TQSLN formulation. In locomotor studies, as compared to TQS, TQSLN favored more prominent (p < 0.010) elevation in average time, horizontal-activity, average-velocity, and total-movement with reduced rest time LPS treated groups. However, in the tail suspension test, TQSLN significantly reduced immobility time (p<0.010). Similarly, In the modified force swimming test, TQSLN also significantly reduced immobility time (p<0.010), but swimming time (p<0.010) and climbing time (p<0.050) were significantly elevated. Conclusion: Despite the poor bioavailability of TQ, TQSLN potentially attenuates neuroinflammatory transmitters and favors BDNF to modulate depressive neurobehavioral states.

Fine-Tuning the PI3K/Akt Signaling Pathway Intensity by Sex and Genotype-Load: Sex-Dependent Homozygotic Threshold for Somatic Growth but Feminization of Anxious Phenotype in Middle-Aged PDK1 K465E Knock-In and Heterozygous Mice

According to the Research Domain Criteria (RDoC), phenotypic differences among disorders may be explained by variations in the nature and degree of neural circuitry disruptions and/or dysfunctions modulated by several biological and environmental factors. We recently demonstrated the in vivo behavioral translation of tweaking the PI3K/Akt signaling, an essential pathway for regulating cellular processes and physiology, and its modulation through aging. Here we describe, for the first time, the in vivo behavioral impact of the sex and genetic-load tweaking this pathway. The anxiety-like phenotypes of 61 mature (11–14-month-old) male and female PDK1 K465E knock-in, heterozygous, and WT mice were studied. Forced (open-field) anxiogenic environmental conditions were sensitive to detect sex and genetic-load differences at middle age. Despite similar neophobia and horizontal activity among the six groups, females exhibited faster ethograms than males, with increased thigmotaxis, increased wall and bizarre rearing. Genotype-load unveiled increased anxiety in males, resembling female performances. The performance of mutants in naturalistic conditions (marble test) was normal. Homozygotic-load was needed for reduced somatic growth only in males. Factor interactions indicated the complex interplay in the elicitation of different negative valence system’s items and the fine-tuning of PI3K/Akt signaling pathway intensity by genotype-load and sex.

The Design and Manufacture of Custom Ocular Prostheses (COPs) Based on Computer-Aided Semi-automation Workflow

Background It is important to correct the ocular disfigurement by wearing prostheses as soon as possible after healing from the eye enucleation surgery. This study aimed to develop a new computer-aided approach to fabricate custom ocular prostheses (COPs) with higher accuracy and efficiency and to fit different anophthalmia sockets. Results Five patients underwent enucleation surgery from November 2018 to October 2020 were enrolled in the study. The semi-automatic design and fabrication workflow of COPs was based on the conjunctival sac impression, combined with Computer-aided design/Computer-aided manufacture (CAD/CAM) workflow, which involves computer image analysis, reverse engineering (RE), and 3-dimensional (3D) printing technologies. The height of palpebral fissure in the artificial eye group was 0.8000 ± 0.09529, N = 5.The height of palpebral fissure in the healthy eye group was 0.7660 ± 0.1147, N = 5, and there was no statistical difference between the two groups (p > 0.05). The artificial eye in the conjunctival sac had a good effect on the reconstruction of orbital fullness. Both of the vertical activity and horizontal activity of COPs is smaller than that of healthy eyes (p < 0.05). Conclusions COPs made by RE and 3D printing technologies can effectively make the COPs suitable for patients' conjunctival sac. This workflow improved the accuracy of the COPs, and also reduced patients’ waiting time, which is worthy to be popularized and applied.

Culture and university entrepreneurship

Latin American universities typically fulfil the functions of teaching, research and the dissemination of culture. To become entrepreneurial universities, they incorporate knowledge transfer or, more generally, the commercialization of academic research and involvement in socio-economic development. However, proposals have been made to treat culture as a horizontal activity that also encompasses the creation of university cultural enterprises. To achieve this requires the crossing of the Arts and Sciences and the promotion of the resulting knowledge transfer. Here, an exploratory study of 16 cultural firms in Mexico allows us to identify strategies aimed at enhancing the entrepreneurial potential of the universities’ cultural activities in the country.

Study of the new 4-phenylpyrrolidinone-2 derivative pharmacokinetics and neuroprotective effect in the ischemic stroke animal model

The development of methods of drug therapy and rehabilitation in different periods of ischemic cerebral lesion is currently an urgent problem. Our study was aimed to investigate the pharmacokinetics and anti-ischemic effect of the new 4-phenylpyrrolidone-2 derivative in rats. To study the drug pharmacokinetics, the Wistar rats were once administered with the substance at a dose of 250 mg/kg, then, the substance distribution in blood and cerebral cortex was evaluated. Elimination half-life value was determined, which was 83.2 min. The substance remained in the brain tissue for 24 hours. To assess the anti-ischemic effect, the stroke was modeled by endovascular middle brain artery transition occlusion, and the drug was administered intravenously for 5 days at two doses, 250 and 125 mg/kg. After that the lesion focus volume was evaluated by MRI, as well as the neurological deficit severity, locomotor and explorative behavior. The studied drug significantly decreased the neurological deficit in model animals compared to control group (1.72 vs 4.4, p < 0.05). According to the MRI data, the effect on the ischemic focus was negligible, while the explorative behavior significantly increased under the influence of the 4-phenylpyrrolidone-2 derivative (hole board test, horizontal activity 12.1 ± 6.8, 22.5 ±10.5, p < 0.05). The data obtained allow us to conclude that the studied substance penetrates the blood-brain barrier (BBB), and accumulates in the brain tissue promoting the neurological deficit correction and increasing the explorative behavior in the ischemic stroke model animals.

Effect of famotidine in combination with antiepileptic drugs on locomotor activity in mice

Histamine type 2 receptor antagonists are one of the most commonly used agents to treat peptic ulcer disease. Since patients with epilepsy may have many comorbidities, the aim of this study was to investigate the influence of one of the strongest second generation histamine type 2 receptor antagonist, famotidine, on the exploratory and spontaneous activity in mice after 1 or 7 days treatment. Additionally, the interaction between famotidine and antiepileptics: carbamazepine, phenytoin, phenobarbital or valproate and their effect on animals activity was also evaluated. Locomotor activity was monitored electronically using a Digiscan analyzer in relation to ambulatory and rearing activities, as well as total distance travelled by animals during 15 minute periods. Results of our study indicate that famotidine administered alone did not modulate three variables of exploratory motor activity (horizontal activity, total distance and vertical activity) in mice. On the other hand, famotidine co-administered with valproate (1 day) or phenobarbital (1 day or 7 days) worsened vertical activity in mice in exploratory time. Similarly, impairment in horizontal activity in mice was observed when famotidine was given with phenobarbital (1 or 7 days). An increase in total distance in mice after famotidine alone or in combination with tested antiepileptic drugs was also shown. Moreover, famotidine alone or together with antiepileptic agents significantly impaired spontaneous locomotor activity in mice. The presented results show that famotidine administration to patients with epilepsy should be considered as potentially hazardous.

Chemostratigraphic and depositional characterization of the Niobrara Formation: Techniques for assessing lateral heterogeneity, CEMEX Quarry, Lyons, Colorado, Denver-Julesburg Basin

The Late Cretaceous (89–82 Ma) Niobrara Formation is the primary target for unconventional horizontal well activity in the Denver Basin. With an abundance of horizontal activity, the question of well-length scale lateral heterogeneity becomes paramount addressing steering practices, completion, and ultimately well performance. We have incorporated detailed core description, high-resolution chemostratigraphy, and petrophysical logs from four near-surface cores taken at the CEMEX Lyons Quarry to assess lateral heterogeneity. Cores were originally intended to determine the geochemistry and areal extent of the Fort Hays Limestone Member of the Niobrara Formation, CEMEX’s primary target for cement production. However, due to the cores’ proximity to one another (91.4–609.6 m [300–2000 ft]) and the presence of not only the Fort Hays Limestone but also the petroliferous chalks and marls of the Lower Smoky Hill Member (including the D Chalk, C Marl, and a portion of the C Chalk), the data set can also be used as a proxy to model changes along a pseudohorizontal wellbore. Observations include lateral bentonite discontinuity, trace element and organic carbon variations, and distinct changes in sedimentary structures. Well-length sedimentological and stratigraphic changes may have unique implications for unconventional oil and gas development.

The Effect of Subchronic Dosing of Ciproxifan and Clobenpropit on Dopamine and Histamine Levels in Rats

The present study was designed to investigate the effect of once daily for 7-day (subchronic treatment) dosing of histamine H3 receptor antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p), including clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively, on MK-801(0.2 mg/kg, i.p.)-induced locomotor activity, and dopamine and histamine levels in rats. Dopamine and histamine levels were measured in striatum and hypothalamus, respectively, of rat brain. Atypical and typical antipsychotics were used to serve as clinically relevant reference agents to compare the effects of the H3 receptor antagonists. MK-801-induced increase of horizontal activity was reduced with CPX and CBP. The attenuation of MK-801-induced locomotor hyperactivity produced by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised dopamine levels in the striatum, which was reduced in rats pretreated with CPX and CBP. CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increase in histamine levels in the hypothalamus compared to the MK-801 treatment alone. Histamine H3 receptor agonist, R-OC methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP. In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.