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Background and aims. There is an increasing number of patients with cardiovascular diseases who require anticoagulant treatment to address the underlying disease. Types of anticoagulants include vitamin K antagonists, such as warfarin and coumarin derivatives, and also newer oral anticoagulants, including rivaroxaban, apixaban, edoxaban, and dabigatran. The use of these anticoagulants may impact the condition of patients undergoing oral surgery. If the treatment is discontinued, the patient may be at risk of thrombosis. On the other hand, if the treatment is continued, the patient may experience a postoperative bleeding episode, placing them at risk of both thrombosis and bleeding. Method. The present article systematically reviews two different therapeutic regimens and their influence on hemorrhagic and thromboembolic events. The review included research from three databases and four specialized journals. The regimens examined were continuous versus discontinuous anticoagulant treatment and continuous versus interruption and switch to bridging therapy. Results. The most common surgical procedure examined in the review was tooth extraction, with a few studies also including soft tissue procedures. A total of seven eligible articles were identified, with five using the first treatment regimen of continuous versus discontinuous anticoagulant. These studies reported several cases of bleeding under continuous anticoagulant treatment during surgery. Two articles used the second treatment regimen of continuous versus interruption and switch to bridging therapy. Conclusions. The results of both treatment categories (continuous versus discontinuous anticoagulant and continuous versus interruption and switch to bridging therapy) showed no significant differences in terms of bleeding events. However, the use of scores that assess the risk of thrombosis and bleeding can assist surgeons in anticipating the degree of ostoperative complications and making informed treatment decisions.

Streptomyces albus J1074 has been established by us as a convenient model to study different aspects of tRNALeuUAA-dependent regulatory mechanisms, that take place in genus Streptomyces. These mechanisms are important for proper morphological and physiological transitions of streptomycete colonies, such as the onset of antibiotic production in stationary phase of growth. The genes for post-transcriptional modification of adenosine residue in 37th position of tRNAXXA family (so called mia genes) were shown to be important for the aforementioned processes, most likely because they impact tRNALeuUAA among other tRNAs. Our results were largely consistent with what is known about mia mutations in the other model systems, such as yeast and enterobacteria. Nevertheless, we also revealed several differences from the model systems, such as decreased susceptibility to hydrogen peroxide. This prompted us to look deeper into the behavior of the mia mutants, particularly their response to different stress factors. Here we report that S. albus mia mutants exhibit increased mistranslation rate as compared to their parental strain. These mutants are more susceptible than the parental strain to disulfide stress inducer diamide and DNA repair stressor caffeine. In summary, although the deficiency in certain tRNA modification appears to cause identical or very similar response (such as elevated mistranslation) across all so far studied bacterial systems, it also induces species- or genus-specific effects (such as disparate effects on H2O2 susceptibility). These differences could be attributed to the peculiarities of organization/function of regulatory pathway governing the response to a given stress. The observed results are further discussed in the wider context of the role of tRNA modification pathway in bacterial biology.

Cranio-maxillofacial surgery boosted the development of medical 3D printing due to intensive use of patient-specific medical devices. The aim of this paper is to describe and assess a hospital-based design method for a mandibular reconstruction and to give an overview on in-house virtual surgical planning (VSP). Design was demonstrated on a case of mandibular osteonecrosis fracture using a dedicated software in a step-by-step manner. Evaluation was done by model surgery followed by a dimensional accuracy evaluation of the experimental model surgery result in comparison with the virtually planned reconstruction. Model scanning and dedicated software were used to assess deviations, including potential printing errors. Based on the obtained results and previous published data, items related to opportunities and limitations of the promoted method were discussed focusing on accuracy, time, costs and regulations. The in-house protocol led to a two-day production period for all the patient-specific surgical gear, with an 11.7 EUR cost of printing material and an estimated initial investment of over 24,000 EUR. Accuracy evaluation by comparing the 3D scanned result with the virtual planned reconstruction suggested most deviations between ± 1.2 mm with most concentrated deviations around + 0.20 mm. Limited exceptions were recorded out of ± 2.2 mm range. Based on the analyzed data, we consider our method a viable alternative solution to outsourced VSP because the surgeon can independently implement the workflow in the hospital, ensuring immediate availability of patient-specific medical devices. However, further clinical, cost-effectiveness and device safety evaluations need to be performed.

Background Alpelisib is an oral α-specific phosphatidylinositol 3-kinase (PI3K) inhibitor use in combination with fulvestrant to treat postmenopausal women with HR+/HER2−, PIK3CA-mutated, advanced or metastatic breast cancer that has acquired resistance to endocrine-based therapy. (1)Alpelisib interferes with the PI3K/Akt signalling pathway resulting in impaired peripheral glucose uptake, increased liver glycogenolysis, loss of beta-cell mass and insulin secretion dysfunction(2). Hyperglycemia is a frequent adverse effect of alpelisib but diabetic ketoacidosis (DKA) is considered a rare occurrence. We describe a patient without a previous history of diabetes who developed DKA after 2 months on alpelisib.Clinical caseA 81 year-old woman with metastatic ER+ PR – Her2 - breast cancer, presented with a 1 week history of nausea, vomiting, and polyuria. Her hemoglobin A1C was 5.5% on two separate occasions last year. She had started alpelisib at 300 mg/day 7 weeks prior to presentation. She presented with a blood glucose (BG) of 659 mg/dL, anion gap of 21, serum bicarbonate 17 mmol/L, beta-hydroxybutyrate 3.82 mmol/L (normal < 0.27 mmol/L), serum osmolarity 319 mOsm/kg, serum creatinine 2.83 mg/dL (baseline 1.38 mg/dL), C-peptide 4.3 ng/mL (normal 1.1–4.4 ng/mL), negative GAD-65 antibodies and Islet Antigen 2 antibodies, septic workup were non-revealing, leading to the diagnosis of alpelisib-associated DKA. Alpelisib was held, and she was treated with intravenous insulin and hydration. DKA resolved in 12 hours, however, she had persistent hyperglycemia. She was started with insulin regimen of 0.2 units/kg and discharged with Humalog 75/25 5 units twice daily. Conclusion Patients with no pre-existing history of diabetes mellitus can also be at risk for DKA which may develop within weeks to months of initiation of alpelisib. Risk factors for development of DKA are yet to be identified, but would be useful to help tailor frequency of BG monitoring. This warrants further research. The hyperglycemic effects of alpelisib appear to be reversible upon drug discontinuation, however when DKA is the presenting syndrome, insulin therapy is indicated. Reference André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu YS, Inoue K, Takahashi M, Pápai Z, Longin AS, Mills D, Wilke C, Hirawat S, Juric D; SOLAR-1 Study Group. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019 May 16;380(20): 1929-1940. doi: 10.1056/NEJMoa1813904. PMID: 31091374. Nguyen P, Musa A, Samantray J. Alpelisib-Induced Diabetic Ketoacidosis. Cureus. 2021 May 1;13(5): e14796. doi: 10.7759/cureus.14796. PMID: 34084688; PMCID: PMC8166359. Presentation: Saturday, June 11, 2022 1:36 p.m. - 1:41 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

This article explores the motives underlying corporate responses to the COVID-19 pandemic. The analysis begins with Thomas Dunfee’s Statement of Minimum Moral Obligation (SMMO), which specifies, more precisely than any other contribution to the business ethics canon, the level of corporate beneficence required during a pandemic. The analysis then turns to Milton Friedman’s neoliberal understanding of human nature, critically contrasting it with the notion of stoic virtue that informs the works of Adam Smith. Friedman contends that beneficence should play no role in corporate settings. Smith, by contrast, emphasizes the need for prudence, beneficence and self-command in all human endeavours. The article then uses these competing frameworks to reflect on a published survey of 145 corporate responses to COVID-19. In many of these responses, the benefit to a non-financial stakeholder is clear, while the financial consequence to the firm remains nebulous. This supports the contention that during a pandemic, beneficence provides a more complete explanation of many corporate actions than the profit motive alone. The article contests Friedman’s Chicago School profit imperative and goes beyond Dunfee’s SMMO by endorsing the more full-throated embrace of beneficence and stoic virtue found in the works of Smith.

Background and aims. The principles of biomechanics comprise all the interactions between the body (tissues) and the forces acting upon it (directly or via different medical devices). Besides the mechanical aspects, the tissues response is also studied. Understanding and applying these principles is vital for the researchers in the field of oral implantology, but itthey must be equally known by the practitioners. From the planning stages to the final prosthetic restoration, they are involved in each and every aspect. Ignoring them inevitably leads to failure. Method. The first part of this paper includes a review of our current research in oral implantology (mechanical, digital and biological testing), while the second part includes a review of the available literature on certain biomechanical aspects and their implications in everyday practice. Results. Our research opens new study directions and provides increased chances of success for dental implant therapy. The practical aspects of our findings, combined with the available literature (from the basic principles described more than 40 years ago to the most recent studies and technologies) can serve as a guide to practitioners for increasing their success rate. Conclusion. While no therapy is without failure risk, a good understanding of the biomechanics involved in oral implantology can lead to higher success rates in implant supported prosthetic restorations.

This article joins a somewhat nascent, but growing, body of scholarship addressing the ethical obligation to pay tax. The analysis is grounded to the ethical duty to obey law generally and highlights two competing orientations to statutory interpretation. The norms of self-interested advocacy suggest that tax planners should assert that interpretation that will generate the most wealth for the client. The norms of professional advising, by contrast, direct the tax planner to interpret tax law with reference to plain meaning, interpretive maxims, court precedents, and legislative purpose. When the two orientations differ, the ethical duty to obey law requires the tax planner to recommend, and for the taxpayer to follow, the latter view. Case studies drawn from a Louisiana sales tax avoidance scheme and from Google’s profit-shifting activities illustrate the ethical issues incumbent in tax interpretation.

The argument in this chapter is that Dickinson’s poetics of inner life makes us see anew the long-standing philosophical problem of expression. Dickinson’s poetry invests itself in an understanding of subjectivity that rearranges the anchors we often turn to in thinking about how lives and identities take on shape in expressive forms. Poetry forces this essentially inward poet to conclude that introspection leads to blindness and rather than to self-knowledge and understanding. Dickinson presents us with a new picture of a human subject unable to find comfort or satisfaction in pursuing itself on the inside. Poetry, instead, gives Dickinson evidence of herself and allows her to encounter the particular what and how of her own inner life as it takes shape outside of her. What literature and philosophy at their crossroads can gain by engaging the idea that poems probe hypotheses about subjectivity is a central concern in the readings.

This essay discusses pedagogical approaches to teaching Austen’s Persuasion as a novel situated at the intersection of literature and philosophy. It focuses on how Persuasion takes up, talks back to, and helps illuminate classic philosophical questions about personhood, sociality, ethics, consciousness, and the space of inner life. It discusses classroom strategies, assignments, and exercises that connect Austen’s ideas about “knowledge” or “subjectivity” to more than fictions: What kinds of rhetorical and stylistic decisions does Austen make? How can we connect those decisions with her sense of what is important, knowable, and significant in the world? No character in Austen’s novels is as silently intelligent and quietly reflective as Anne Elliot, and the emphasis in my approach pivots on the class’s patiently staying with her character. I show how students come to see that staging Anne’s slow emergence out of the quiet discontent of her own inner world is Persuasion’s central concern. As Anne comes to find forms of expression (linguistic, social, emotional, bodily) that capture the impulses of her rich inner life, she also takes on the dimensions of a heroine. Our classroom inquiry centers on what Austen wants to suggest about personhood, subjectivity, acknowledgment, and love through this unveiling of a character.

The argument in this essay is that Dickinson’s poetics of inner life makes us see anew the long-standing philosophical problem of expression. Dickinson’s poetry invests itself in an understanding of subjectivity that rearranges the anchors we often turn to in thinking about how lives and identities take on shape in expressive forms. Poetry forces this essentially inward poet to conclude that introspection leads to blindness and rather than to self-knowledge and understanding. Dickinson presents us with a new picture of a human subject unable to find comfort or satisfaction in pursuing itself on the inside. Poetry, instead, gives Dickinson evidence of herself and allows her to encounter the particular what and how of her own inner life as it takes shape outside of her. What literature and philosophy at their crossroads can gain by engag- ing the idea that poems probe hypotheses about subjectivity is a central concern in the readings.

Reconstruction of cranial defects is an arduous task for craniomaxillofacial surgeons. Additive manufacturing (AM) or three-dimensional (3D) printing of titanium patient-specific implants (PSIs) made its way into cranioplasty, improving the clinical outcomes in complex surgical procedures. There has been a significant interest within the medical community in redesigning implants based on natural analogies. This paper proposes a workflow to create a biomimetic patient-specific cranial prosthesis with an interconnected strut macrostructure mimicking bone trabeculae. The method implements an interactive generative design approach based on the Voronoi diagram or tessellations. Furthermore, the quasi-self-supporting fabrication feasibility of the biomimetic, lightweight titanium cranial prosthesis design is assessed using Selective Laser Melting (SLM) technology.

In his recent essays on art, philosophy, and the concept of intention in criticism, Walter Benn Michaels suggests that the opacity of a photograph with regard to the photographer’s intention, and photography’s taking up intention and chance as central animating problems, account for the medium’s increasing art-historical importance over the last several decades. In what specific and concrete sense, Michaels asks, is the taking of a photograph an intentional act? This essay responds to Michaels’ essays on art and the philosophy of Elizabeth Anscombe and shows how, for Michaels, artists in the postwar and contemporary periods overwhelmingly are better and more incisive thinkers on aesthetic questions than philosophers and literary theorists.