Covid-19 vaccine dissemination: A public health ethical evaluation of Pennsylvania's plan during Phase 1A.

Background: The novel COVID-19 pandemic afforded public health leaders an opportunity to expedite vaccine development and dissemination. The United States found itself faced with the arduous task of ensuring swift and equitable distribution of limited resources, in the midst of often-competing priorities, including public health ethics, medical ethics, economic demands, and societal strains. Methodology: Using the American Public Health Association's (APHA) newly revised public health code of ethics, which provides a decision-making framework and guidance for ethical analysis, we analyzed how Pennsylvania's COVID-19 vaccine dissemination plan aligned with the four core functions of public health ethics inquiry. Results/Discussion: Upon investigation, the state's plan evidenced use of public health ethics in goal setting and design. However, the core public health value given the highest priority, promoting health and safety, competed with the other core public health values of inclusivity and engagement, health justice and equity, and professionalism and trust. Despite known social disparities and risk factors, the state plan for COVID-19 vaccine dissemination aligned closely with federal guidance and prioritized all healthcare personnel and long-term care facility populations over high-risk individuals residing in the community. Conclusion/Perspectives: Should another pandemic necessitate allocation of scarce resources, especially preventative measures such as vaccines, decision-making agencies must consider disparate populations in planning and dissemination of material to the public. Any anticipated limitations in the ability to fulfill public health ethical principles should be clearly communicated to the public prior to implementation, thereby increasing trust.

Periosteal Fixation Procedures in the Management of Incomitant Strabismus.

Managing a case of incomitant strabismus from nerve palsy or extraocular muscle loss is a major challenge. Among possible management options are globe or extraocular muscle fixation to the orbital wall coupled with weakening or strengthening of the relevant antagonist. Extraocular muscle fixation to the orbital wall can also be used in cases of abnormal synkinesis to eliminate the abnormal eye movements of a misfiring extraocular muscle, which thereby allows the use of standard paralytic strabismus surgery techniques. This review article summarizes indications and techniques of periosteal fixation procedures for incomitant strabismus.

Trypanocidal activity of synthetic heterocyclic derivatives of active quinones from Tabebuia sp.

Continuing a program on the chemistry and biological activity of compounds from the Brazilian flora, the lytic activity against bloodstream forms of T. cruzi of nine new heterocyclic naphthooxazole and naphthoimidazole derivatives obtained from the reaction of naphtoquinones isolated from Tabebuia sp. (Tecoma) with amino-containing reagents has been studied. Also for the first time the biological activity of allyl derivatives of lawsone, a natural quinone from Lausonia alba inactive against T. cruzi, is reported. The introduction of an allyl group in lawsone gives rise to O-allyl-lawsone and C-allyl-lawsone that showed activity against the parasite, with ID50 values of 420.7 +/- 71.1 and 330.7 +/- 62.4 mumol/l, respectively. The trypanocidal activity of the naphtho heterocyclics synthesized from the original quinones showed no concordant behavior in relation to the parent compound. Six of nine of the synthesized compounds presented lower ID50 values than crystal violet, indicating a general trend of activity among naphthalenic heterocyclics of the oxazole/imidazole type. However, their chemical structures do not endow them with the capacity of free radical generation by biological reduction as the quinoidal moiety, nor do they have chemical reducible appendage like the nitro group of nifurtimox and benznidazole, responsible for such behaviour. As a hypothesis, the pattern of their biological actions should be focused in other aspects of their chemical structures. Because of their polycyclic planar topology, these derivatives are potential candidates for experimental tests as DNA intercalating agents.

Chemical reactivity studies with naphthoquinones from Tabebuia with anti-trypanosomal efficacy.

The biological activities of the naphthoquinones lapachol and its cyclization product beta-lapachone, extracted from trees of the genus Tabebuia, have been intensively studied. Given continuity to the studies about heterocyclic derivatives obtained from the reaction of these naphtoquinones with amino-containing reagents, 22 derivatives of beta-lapachone, nor-beta-lapachone and lapachol were synthesised and their activities against trypomastigote forms of T. cruzi were evaluated. The compounds were grouped as oxazolic, imidazolic, phenoxazinic, indolic, pyranic and cyclopentenic derivatives. The variability of the new structures is based on the great electrophilicity of 1,2-quinoidal carbonyls towards reagents containing nitrogen or carbon as nucleophilic centres. In relation to the trypanocidal activity of the synthesised compounds, in view of their structural diversity, tendencies only could be verified. Among the cyclofunctionalised products the oxazolic and imidazolic derivatives showed +/- 1.5 to 34.8 times higher activity than crystal violet, the standard drug for the sterilization of stored blood. These results corroborate the tendency of trypanocidal activity in imidazolic skeletons, and indicate that this moiety could be used as a guide for architectural delineation of molecules with potential value for the chemotherapy of Chagas disease.

Evaluation of some organic compounds on bloodstream forms of Trypanosoma cruzi.

Accidental transmission of Chagas' disease to man by blood transfusion is a serious problem in Latin-America. This paper describes the testing of several synthetic, semi-synthetic, and natural compounds for their activity against blood trypomastigotes in vitro at 4 degrees C. The compounds embody several types of chemical structures: benzoquinone, naphthoquinone, anthracenequinone, phenanthrenequinone, imidazole, piperazine, quinoline, xanthene, and simple benzenic and naphthalenic derivatives. Some of them are for the first time tested against Trypanosoma cruzi. The toxic effect of these compounds on this parasite was done by two quite distinct sets of experiments. In one set, the compounds were added to infected blood as ethanolic solution. In this situation the most active one was a furan-1,2-naphthoquinone, in the same range as gentian violet, a new fact to be considered in the assessment of structure-activity relationships in this class of compounds. In other set, we tentatively evaluated the biological activity of water insoluble compounds by adding them in a pure form without solvent into infected blood. In this way some appear to be very active and it was postulated that the effectiveness of such compounds must result from interactions between them and specific blood components.

Evaluation of some organic compounds on bloodstream forms of Trypanosoma cruzi

Accidental transmission of Chagas' disease to man by blood transfusion is a serious problem in Latin-America. This paper describes the testing of several synthetic, semi-synthetic, and natural compounds for their activity against blood trypomastigotes in vitro at 4-C. The compounds embody several types of chemical structures: benzoquinone, naphthoquinone, anthracenequinone, phenanthrenequinone, imidazole, piperazine, quinoline, xanthene, and simple benzenic and naphthalenic derivates. Some of them are for the first time tested against Trypanosoma cruzi. The toxic effect these compounds on this parasite was done by two quite distinct sets of experiments. In one set, the compounds were added to infected blood as ethanolic solution. In this situation the most active one was a furan-1, 2-naphthoquinone, in the same range as gentian violet, a new fact to be considered in the assessment of structure-activity relationships in this class of compounds. In other set, we tentatively evaluated the biological activity of water insoluble compounds by adding them in a pure form without solvent into infected blood. In this way some appear to be very active and it was postulated that the effectiveness of such compounds must result from interactions between them and specific blood components