New Frontiers: Precise Editing of Allergen Genes Using CRISPR

Genome engineering with clustered regularly interspaced short palindromic repeats (CRISPR) technology offers the unique potential for unequivocally deleting allergen genes at the source. Compared to prior gene editing approaches, CRISPR boasts substantial improvements in editing efficiency, throughput, and precision. CRISPR has demonstrated success in several clinical applications such as sickle cell disease and β-thalassemia, and preliminary knockout studies of allergenic proteins using CRISPR editing show promise. Given the advantages of CRISPR, as well as specific DNA targets in the allergen genes, CRISPR gene editing is a viable approach for tackling allergy, which may lead to significant disease improvement. This review will highlight recent applications of CRISPR editing of allergens, particularly cat allergen Fel d 1, and will discuss the advantages and limitations of this approach compared to existing treatment options.

Hydrophilic nanoparticles that kill bacteria while sparing mammalian cells reveal the antibiotic role of nanostructures

To dissect the antibiotic role of nanostructures from chemical moieties belligerent to both bacterial and mammalian cells, here we show the antimicrobial activity and cytotoxicity of nanoparticle-pinched polymer brushes (NPPBs) consisting of chemically inert silica nanospheres of systematically varied diameters covalently grafted with hydrophilic polymer brushes that are non-toxic and non-bactericidal. Assembly of the hydrophilic polymers into nanostructured NPPBs doesn’t alter their amicability with mammalian cells, but it incurs a transformation of their antimicrobial potential against bacteria, including clinical multidrug-resistant strains, that depends critically on the nanoparticle sizes. The acquired antimicrobial potency intensifies with small nanoparticles but subsides quickly with large ones. We identify a threshold size (dsilica ~ 50 nm) only beneath which NPPBs remodel bacteria-mimicking membrane into 2D columnar phase, the epitome of membrane pore formation. This study illuminates nanoengineering as a viable approach to develop nanoantibiotics that kill bacteria upon contact yet remain nontoxic when engulfed by mammalian cells.

Reflections on Popular Culture and Philosophy

Contributions to the philosophical genre of popular culture and philosophy aim to popularize philosophical ideas with the help of references to the products of popular (mass) culture with TV series like The Simpsons, Hollywood blockbusters like The Matrix and Jurassic Park, or popular music groups like Metallica. While being commercially successful, books in this comparatively new genre are often criticized for lacking scientific rigor, providing a shallow cultural commentary, and having little didactic value to foster philosophical understanding. This paper discusses some of these methodological and didactic objections and seeks to encourage a constructive discussion of concerns with the genre. It shows how the genre similar to previous attempts to foster public understanding of philosophy and that it is a methodologically viable approach to reach a broad range of readers with diverse informational preferences and educational backgrounds. Considering what makes this approach to the popularization of philosophical thinking successful will shed light on some of the criteria for popularization of philosophy in general.

A clinical trial to evaluate the dayzz smartphone app on employee sleep, health, and productivity at a large US employer

Sleep deficiency is a hidden cost of our 24–7 society, with 70% of adults in the US admitting that they routinely obtain insufficient sleep. Further, it is estimated that 50–70 million adults in the US have a sleep disorder. Undiagnosed and untreated sleep disorders are associated with diminished health for the individual and increased costs for the employer. Research has shown that adverse impacts on employees and employers can be mitigated through sleep health education and sleep disorder screening and treatment programs. Smartphone applications (app) are increasingly commonplace and represent promising, scalable modalities for such programs. The dayzz app is a personalized sleep training program that incorporates assessment of sleep disorders and offers a personalized comprehensive sleep improvement solution. Using a sample of day workers affiliated with a large institution of higher education, we will conduct a single-site, parallel-group, randomized, waitlist control trial. Participants will be randomly assigned to either use the dayzz app throughout the study or receive the dayzz app at the end of the study. We will collect data on feasibility and acceptability of the dayzz app; employee sleep, including sleep behavioral changes, sleep duration, regularity, and quality; employee presenteeism, absenteeism, and performance; employee mood; adverse and safety outcomes; and healthcare utilization on a monthly basis throughout the study, as well as collect more granular daily data from the employee during pre-specified intervals. Our results will illuminate whether a personalized smartphone app is a viable approach for improving employee sleep, health, and productivity. Trial registration: ClinicalTrials.gov Identifier: NCT04224285.

Efficacy of intrauterine insemination in women with endometrioma-associated subfertility: analysis using propensity score matching

Background Intrauterine insemination (IUI) treatment is recommended in subfertile women with AFS/ASRM stage I/II endometriosis. However, the efficacy of IUI in women with ovarian endometriomas with tubal patency is uncertain. We explored the efficacy of IUI for the treatment of endometrioma-associated subfertility. Methods We performed a retrospective matched cohort study using propensity matching (PSM) analysis. Subfertile couples undergoing IUI with and without ovarian stimulation between January 1, 2015, and May 30, 2020 were reviewed. Results After PSM, 56 women with endometrioma alone were matched to 173 patients with unexplained subfertility. The per-cycle pregnancy rate (PR) was comparable between women with endometrioma-associated subfertility (n = 56, 87 cycles) and women with unexplained subfertility (n = 173, 280 cycles) (9.2% vs. 17.9%, OR 0.47; 95% CI, 0.21–1.03). Subgroup analyses based on IUI with or without stimulation also resulted in comparable results. A trend toward a lower cumulative pregnancy rates (CPRs) was seen in women with endometrioma (14.3%, 8/56) compared with women with unexplained subfertility (28.9%, 50/173), but the differences were not significant (HR 0.49; 95% CI, 0.23–1.15). However, patients with endometrioma were nearly twice as likely to converse to IVF treatment compared with those without the disease (60.7% versus 43.9%; OR 1.97; 95% CI, 1.07–3.65). Conclusion IUI may be a viable approach for subfertile women with endometrioma and no other identifiable infertility factor. More studies are needed to reassure the findings.

Robust hydrogel-integrated microsystems enabled by enhanced interfacial bonding strength

Noncovalent hydrogels, compared to covalent hydrogels, have distinctive advantages including biocompatibility and self-healing property but tend to have poor mechanical robustness, thus restricting their application spectrum. A clue to increase utility of such soft hydrogels without chemical bulk modification can be witnessed in biological organ walls where soft mucous epithelial layers are juxtaposed with tough connective tissues. Perhaps, similarly, bonding noncovalent hydrogels to stronger materials, such as tough hydrogels, might be a viable approach for increasing stability and scalability as well as creating novel functions for hydrogel-based systems. However when attempting to bond these two materials, each of the four existing hydrogel-hydrogel bonding method has practical shortcomings. In this work, we introduce a mucosa-inspired bonding method that realizes interfacial bonding of noncovalent hydrogels to tough, hybrid hydrogels without external glue or bulk modification of the noncovalent gel while preserving interfacial micropatterns. The procedure is simple and we confirmed broad applicability with various noncovalent hydrogels and tough hydrogels. We demonstrated the utility of our bonding method with novel applications regarding in vitro assay, soft robotics and biologically inspired systems.

Primary repair of multiligament knee injury with InternalBrace ligament augmentation

Multiligament injury of the knee usually occurs as a result of high-energy trauma causing tibiofemoral dislocation. These are rare but potentially limb-threatening injuries, frequently involving nerve or arterial damage and often leading to severe complex instability. Management generally favours surgical reconstruction of the affected ligaments, with controversy regarding optimal treatment. We present a severe multiligament knee injury (Schenk classification KD-IV involving both cruciate and both collateral ligaments) in a competitive showjumper. A combined arthroscopic/open technique of single-stage surgical repair and suture augmentation was used, repairing all affected ligaments. The patient made an excellent recovery, returning to work after 12 weeks and riding after 22 weeks. After 5-year follow-up, she has regained her previous level of competition without subsequent injury. Multiligament repair with suture augmentation is a viable approach to the management of knee dislocation injuries. We propose that this could provide superior outcomes to traditional reconstruction techniques using autograft or synthetic reconstruction.

Beyond Tools and Procedures

As artificial intelligence (AI) is increasingly being deployed in almost all aspects of our daily lives, the discourse around the pervasiveness of algorithmic tools and automated decision-making appears to be almost a trivial one. This chapter investigates limits and opportunities within existing debates and examines the rapidly evolving legal landscape and recent court cases. The authors suggest that a viable approach to fairness, which ultimately remains a choice that organizations have to make, could be rooted in a new measurable and accountable responsible business framework.

Institutional development of child care in armenia: structural-organizational, or value-systemic approach?

Discussions on the transformation of social issues, particularly the lack of a viable approach to responding to the shortcomings of family care, from the Soviet era are still relevant thirty years later. In particular, education, care and protection of children in institutions and to accommodate changing practices used in the process of forming a latent attitude system based on children's rights, non-formal resistance discussion interesting to understand what potential they have undertaken an organizational structural transformation of values desired to bring about change. Will these transformations be able to influence the changing practices of helping children in need outside of the family environment something that continues to be the subject of unspoken agreement between the three parent-decision-making parties today, ignoring children's rights and interests?

Multidisciplinary Approach to Complicated Crown-root Fracture Treatment: A Case Report

SUMMARY Treatment of complicated crown-root fractures is one of the most challenging within the various types of dental trauma and requires a multidisciplinary approach. This paper reports the complicated crown-root fracture of a maxillary right central incisor, in which there was esthetic, functional, and biologic (endodontic and biologic width invasion) involvement. A 15-year-old male patient presented to the dental clinic one month after suffering trauma with a complicated crown-root fracture on tooth 8. The patient had previously undergone endodontic treatment and was sent to have periodontal surgery to reestablish the biological width on the palatal surface. Following the surgery, a fiberglass post was cemented, and the fragment was reattached. This approach allows the exposure of the cervical margin, adequate isolation, and subsequent fragment reattachment in the same clinical appointment. Fragment reattachment is a viable approach as it is a simple and conservative procedure that restores the natural esthetic of the tooth and has superior resistance compared to a composite restoration. The patient’s cooperation in understanding the limitations of the treatment and maintaining adequate oral hygiene are very important to achieving a good prognosis of the case. After a 2-year clinical and radiographic follow-up period, the clinical protocol was found to be successful, and the tooth remained functional, esthetically favorable and asymptomatic.