Mucoadhesive Polymeric Polyologels Designed for the Treatment of Periodontal and Related Diseases of the Oral Cavity.

The study objective was to design and characterise herein unreported polyologels composed of a range of diol and triol solvents and polyvinyl methyl ether-co-maleic acid (PVM/MA) and, determine their potential suitability for the treatment of periodontal and related diseases in the oral cavity using suitable in vitro methodologies. Polyologel flow and viscoelastic properties were controlled by the choice of solvent and the concentration of polymer. At equivalent polymer concentrations, polyologels prepared with glycerol (a triol) exhibited the greatest elasticity and resistance to deformation. Within the diol solvents (PEG 400, pentane 1,5-diol, propane 1,2-diol, propane 1,3-diol, and ethylene glycol), PEG 400 polyologels possessed the greatest elasticity and resistance to deformation, suggesting the importance of distance of separation between the diol groups. Using Raman spectroscopy bond formation between the polymer carbonyl group and the diol hydroxyl groups was observed. Polyologel mucoadhesion was influenced by viscoelasticity; maximum mucoadhesion was shown by glycerol polyologels at the highest polymer concentration (20% w/w). Similarly, the choice of solvent and concentration of PVM/MA affected the release of tetracycline from the polyologels. The controlled release of tetracycline for at least 10 h was observed for several polyologels, which, in combination with their excellent mucoadhesion and flow properties, offer possibilities for the clinical use of these systems to treat diseases within the oral cavity.

"The Water in Which We Swim:" A Unique, Post-Clerkship Multidisciplinary Course.

OBJECTIVE: To improve patient outcomes and promote health equity, medical students must be taught not only biomedicine, but also the social sciences to understand the larger contexts in which patients live and health care operates. Yet, most undergraduate medical education does not explicitly cover these topics in a required, longitudinal curriculum. METHODS: In January 2015 at Harvard Medical School, we created a two-part sequence (pre- and post-clerkship) of required, 4-week multidisciplinary courses-"Essentials of the Profession I and II"-to fill this gap. "Essentials of the Profession II (EOP2)" is an advanced social sciences course anchored in patient narratives and the lived experiences of students and includes clinical epidemiology and population health, healthcare delivery and leadership, health policy, medical ethics and professionalism, and social medicine that engages students to conduct structural analyses to be effective healers, advocates, and leaders. RESULTS: Per student course evaluations, the overall course rating was 1.7 (SD 0.9, 1 = excellent and 5 = poor); its overall rating has improved over time; and it has scored well even when run virtually. It was rated highly in application of critical thinking, integration of the disciplines, and relevance for clinical work. Qualitative analyses of student responses revealed the following key course strengths: breadth of topics, teaching faculty and guest speakers, and small group discussions. The weaknesses included workload, lack of diversity of opinions, repetition, and time spent in lectures. CONCLUSIONS: We argue that EOP2 is "essential" for post-clerkship medical education. It offers an opportunity to re-ignite and enhance humanism and activism; remind students why they chose the medical profession; equip them with frameworks and toolkits to help them to overcome challenges; and devise solutions to improve health care and patient outcomes that are applicable to their future training and ongoing practice of medicine.

The historical sociology of medicine in India: Introduction to the special section.

This introduction to a special section brings together three papers first presented at a panel, 'Medical Professions in South Asia: Historical and Contemporary Analyses', at the 26th European Conference on South Asian Studies, held in Vienna, Austria and online, in July 2021. All three papers deal with aspects of the professionalisation of biomedical doctors in India since its independence in 1947. The authors bring together historical and sociological approaches to illuminate the growth of specialisms, patterns of practitioner-patient interactions and efforts to maintain occupational closure and maintain status in the face of growing challenges. The introduction concludes with a discussion of the relevance of these papers for the sociology of health and illness in India and beyond.

Learning Harmony: Medical Student Reflections on the Intersection of the Arts & Humanities and Medicine, A Mixed Methods Study.

Background: The arts and humanities form a critical part of medical education. In this study, we explore medical students' reflections following an arts and humanities experience. An intensive day and a half long program focused on music and reflection was designed for first-year students at Harvard Medical School. Methods: Students completed an evaluation of the experience with both open-ended and Likert scale questions. Data were analyzed using a mixed methods approach. Descriptive statistics were used to analyze quantitative data and inductive content analysis for qualitative data. Results: 168 first-year medical and dental students participated in the activity. Survey response rate was 73% (n =122). Quantitatively, the overall quality of the experience was assessed at a mean value of 4.86 points (SD = 0.37 points) out of a maximum of 5, with 5 being excellent. The qualitative evaluation illustrated how the arts and humanities experience encouraged students to reflect on their leadership and doctoring skills, taking a holistic approach to their medical education, and integrating the lessons of the arts and humanities into their medical practice. Conclusion: The arts and humanities program encouraged student reflection on profound questions in medicine related to empathy, vulnerability, and authenticity. This experience broadened students' perspectives regarding the relationship between medicine and the arts and humanities.

An Ethical Framework for Research Using Genetic Ancestry.

A wide range of research uses patterns of genetic variation to infer genetic similarity between individuals, typically referred to as genetic ancestry. This research includes inference of human demographic history, understanding the genetic architecture of traits, and predicting disease risk. Researchers are not just structuring an intellectual inquiry when using genetic ancestry, they are also creating analytical frameworks with broader societal ramifications. This essay presents an ethics framework in the spirit of virtue ethics for these researchers: rather than focus on rule following, the framework is designed to build researchers' capacities to react to the ethical dimensions of their work. The authors identify one overarching principle of intellectual freedom and responsibility, noting that freedom in all its guises comes with responsibility, and they identify and define four principles that collectively uphold researchers' intellectual responsibility: truthfulness, justice and fairness, anti-racism, and public beneficence. Researchers should bring their practices into alignment with these principles, and to aid this, the authors name three common ways research practices infringe these principles, suggest a step-by-step process for aligning research choices with the principles, provide rules of thumb for achieving alignment, and give a worked case. The essay concludes by identifying support needed by researchers to act in accord with the proposed framework.

Changes of heart: Debating the role of cardiology and cardiac surgery in India, 1948-1968.

In 1950, the leaders of independent India celebrated the contributions that surgeons could make to modernising India. Surgeons, however, faced a difficult choice. Some wanted to invest in generalist surgeons to make basic surgical care available to all Indians. Others wanted to invest in specialists to ensure that India participated in cutting-edge surgical research and care. These debates shaped the emergence of cardiac surgery at two centres: the Christian Medical College in Vellore and the King Edward Memorial Hospital in Bombay. CMC invested in thoracic surgery in the 1940s to offer new treatments for tuberculosis. This gave surgeons the opportunity to explore new techniques of cardiac surgery. Debate quickly emerged about whether investments in cardiology and cardiac surgery made sense. In the end, the specialities were supported in order to attract paying patients. A parallel controversy took place at KEM, where the dean debated the Bombay Municipal Corporation about the role of surgical research at a public hospital. The Rockefeller Foundation influenced both sites, offering financial support if they adopted an American model of full-time faculty clinician-researchers. The two case studies reveal how unusual dynamics could contribute to the establishment of new medical specialities in India.

Malaria transmission-blocking vaccines Pfs230D1-EPA and Pfs25-EPA in Alhydrogel in healthy Malian adults; a phase 1, randomised, controlled trial.

BACKGROUND: Malaria transmission-blocking vaccines target mosquito-stage parasites and will support elimination programmes. Gamete vaccine Pfs230D1-EPA/Alhydrogel induced superior activity to zygote vaccine Pfs25-EPA/Alhydrogel in malaria-naive US adults. Here, we compared these vaccines in malaria-experienced Malians. METHODS: We did a pilot safety study then double-blind, block-randomised, comparator-controlled main-phase trial in malaria-intense Bancoumana, Mali. 18-50-year-old healthy non-pregnant, non-breastfeeding consenting adult residents were randomly assigned (1:1:1:1) to receive four doses at months 0, 1, 4·5, and 16·5 of either 47 µg Pfs25, 40 µg Pfs230D1 or comparator (Twinrix or Menactra)-all co-administered with normal saline for blinding-or 47 µg Pfs25 plus 40 µg Pfs230D1 co-administered. We documented safety and tolerability (primary endpoint in the as-treated populations) and immunogenicity (secondary endpoint in the as-treated populations: ELISA, standard-membrane-feeding assay, and mosquito direct skin feed assay). This trial is registered at ClinicalTrials.gov, NCT02334462. FINDINGS: Between March 19, and June 2, 2015, we screened 471 individuals. Of 225 enrolled for the pilot and main cohorts, we randomly assigned 25 participants to pilot safety cohort groups of five (20%) to receive a two-dose series of Pfs25-EPA/Alhydrogel (16 µg), Pfs230D1-EPA/Alhydrogel (15 µg) or comparator, followed by Pfs25-EPA/Alhydrogel (16 µg) plus Pfs230D1-EPA/Alhydrogel (15 µg) or comparator plus saline. For the main cohort, we enrolled 200 participants between May 11 and June 2, 2015, to receive a four-dose series of 47 µg Pfs25-EPA/Alhydrogel plus saline (n=50 [25%]; Pfs25), 40 µg Pfs230D1-EPA/Alhydrogel plus saline (n=49 [25%]; Pfs230D1), 47 µg Pfs25-EPA/Alhydrogel plus 40 µg Pfs230D1-EPA/Alhydrogel (n=50 [25%]; Pfs25 plus Pfs230D1), or comparator (Twinrix or Menactra) plus saline (n=51 [25%]). Vaccinations were well tolerated in the pilot safety and main phases. Most vaccinees became seropositive after two Pfs230D1 or three Pfs25 doses; peak titres increased with each dose thereafter (Pfs230D1 geometric mean: 77·8 [95% CI 56·9-106·3], 146·4 [108·3-198·0], and 410·2 [301·6-558·0]; Pfs25 geometric mean 177·7 [130·3-242·4] and 315·7 [209·9-474·6]). Functional activity (mean peak transmission-reducing activity) appeared for Pfs230D1 (74·5% [66·6-82·5]) and Pfs25 plus Pfs230D1 (68·6% [57·3-79·8]), after the third dose and after the fourth dose (88·9% [81·7-96·2] for Pfs230D1 and 85·0% [78·4-91·5] Pfs25 plus Pfs230D1) but not for Pfs25 (58·2% [49·1-67·3] after the third dose and 58·2% [48·5-67·9] after the fourth dose). Pfs230D1 transmission-reducing activity (73·7% [64·1-83·3]) persisted 10 weeks after the fourth dose. Transmission-reducing activity of 80% was estimated at 1659 ELISA units for Pfs25, 218 for Pfs230D1, and 223 for Pfs230D1 plus Pfs25. After 3850 direct skin feed assays, 35 participants (12 Pfs25, eight Pfs230D1, five Pfs25 plus Pfs230D1, and ten comparator) had transmitted parasites at least once. The proportion of positive assays in vaccine groups (Pfs25 33 [3%] of 982 [-0·013 to 0·014], Pfs230D1 22 [2%] of 954 [-0·005 to 0·027], and combination 11 [1%] of 940 [-0·024 to 0·002]) did not differ from that of the comparator (22 [2%] of 974), nor did Pfs230D1 and combination groups differ (-0·024 to 0·001). INTERPRETATION: Pfs230D1 but not Pfs25 vaccine induces durable serum functional activity in Malian adults. Direct skin feed assays detect parasite transmission to mosquitoes but increased event rates are needed to assess vaccine effectiveness. FUNDING: Intramural Research Program of the National Institute of Allergy and Infectious Diseases and US National Institutes of Health.

Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles.

Development of a malaria vaccine that blocks transmission of different parasite stages to humans and mosquitoes is considered critical for elimination efforts. A vaccine using Pfs25, a protein on the surface of zygotes and ookinetes, is under investigation as a transmission-blocking vaccine (TBV) that would interrupt parasite passage from mosquitoes to humans. The most extensively studied Pfs25 TBVs use Pichia pastoris-produced recombinant forms of Pfs25, chemically conjugated to a recombinant carrier protein, ExoProtein A (EPA). The recombinant form of Pfs25 first used in humans was identified as Pfs25H, which contained a total of 14 heterologous amino acid residues located at the amino- and carboxyl-termini including a His6 affinity tag. A second recombinant Pfs25, identified as Pfs25M, was produced to remove the heterologous amino acid residues and conjugated to EPA (Pfs25M-EPA). Here, monomeric Pfs25M was characterized biochemically and biophysically for identity, purity, and integrity including protein structure to assess its comparability with Pfs25H. Although the biological activities of Pfs25H and Pfs25M, whether generated by monomeric forms or conjugated nanoparticles, appeared similar, fine-mapping studies with two transmission-blocking monoclonal antibodies detected structural and immunological differences. In addition, evaluation of antisera generated against conjugated Pfs25H or Pfs25M nanoparticles in nonhuman primates identified polyclonal IgG that recognized these structural differences.

Variations in how medical researchers report patient demographics: a retrospective analysis of published articles.

Background: The use of demographic variables in the medical literature has been a topic of much recent debate. Recent studies found that race and socioeconomic status (SES) are inconsistently reported. Best-practice use of sex and gender has been contentious. We aimed to characterise the state of medical demographic reporting in greater detail, especially regarding geography and specific terms used in articles. Methods: Original articles were included from issues of the New England Journal of Medicine (NEJM), JAMA, The Lancet, and the American Journal of Epidemiology (AJE) published from 1 January to 31 December 2020 (n = 640). Articles without human participants, case reports, or with only aggregate data were excluded, leaving 594 articles. Use of age, sex, gender, race, ethnicity, and SES were coded, as well as corresponding author and participant geography. Findings: 99.0% of articles reported age. While 92.9% reported sex alone, only 4.7% used the term gender and 1.0% transgender. 47.8% of articles reported race and 29.6% reported ethnicity. Studies with U.S. corresponding authors or participants were significantly more likely to report race (72.9% and 73.7% respectively) or ethnicity (47.3% and 45.3% respectively) than those without (25.9% and 25.6% for race, 14.2% and 16.3% for ethnicity), p < 0.01 for all. Of articles reporting race, 40.9% used only a Black-white binary; of those reporting ethnicity, 85.2% included two or fewer terms. Under 5.0% of all articles used Office of Management and Budget (OMB) categories. Across all articles, 33.0% reported SES, from 15.2% in NEJM to 80.2% in AJE. Interpretation: We found that while some factors (age, sex) are reported consistently, others (gender, race, ethnicity, SES) are not, despite recent attention. Authors often rely on binary or limited categories that inadequately capture human diversity. The presence of U.S. researchers or participants increased the reporting of race and/or ethnicity, highlighting wide variations that persist even as multinational collaborations become widespread. Researchers should reflect on their use of these terms, justify their decisions, and report results with care. Funding: None.

Therapeutic deep eutectic solvents: A comprehensive review of their thermodynamics, microstructure and drug delivery applications.

Deep eutectic solvents (DES) are multicomponent liquids that are usually formed by coupling a hydrogen bond donor and acceptor leading to strong non-covalent (NC) intermolecular networking and profound depression in the melting point of the system. Pharmaceutically, this phenomenon has been exploited to improve drugs' physicochemical properties, with an established DES therapeutic subcategory, therapeutic deep eutectic solvents (THEDES). THEDES preparation is usually via straightforward synthetic processes with little involvement of sophisticated techniques, which, in addition to its thermodynamic stability, make these multi-component molecular adducts a very attractive alternative for drug enabling purposes. Other NC bonded binary systems (e.g., co-crystals and ionic liquids) are utilized in the pharmaceutical field for enhancing drug's behaviours. However, a clear distinction between these systems and THEDES is scarcely discussed in the current literature. Accordingly, this review provides a structure-based categorization for DES formers, a discussion of its thermodynamic properties and phase behaviour, and it clarifies the physicochemical and microstructure boundaries between DES and other NC systems. Additionally, a summary of its preparation techniques and their experimental conditions preparation is supplied. Instrumental analysis techniques can be used to characterize and differentiate DES from other NC mixtures, hence this review draws a road map to for this purpose. Since this work mainly focuses on pharmaceutical applications of DES, all types of THEDES including the highly discussed types (conventional, drugs dissolved in DES and polymer based) in addition to the less discussed categories are covered. Finally, the regulatory status of THEDES was investigated despite the current unclear situation.

The Under-representation and Stagnation of Female, Black, and Hispanic Authorship in the Journal of the American Medical Association and the New England Journal of Medicine.

Publication in leading medical journals is critical to knowledge dissemination and academic advancement alike. Leveraging a novel dataset comprised of nearly all articles published in JAMA and NEJM from 1990 to 2020, along with established reference works for name identification, we explore changing authorship demographics in two of the world's leading medical journals. Our main outcomes are the annual proportion of male and female authors and the proportion of racial/ethnic identities in junior and senior authorship positions for articles published in JAMA and NEJM since 1990. We found that women remain under-represented in research authorship in both JAMA (at its peak, 38.1% of articles had a female first author in 2011) and NEJM (peaking at 28.2% in 2002). The rate of increase is so slow that it will take more than a century for both journals to reach gender parity. Black and Hispanic researchers have likewise remained under-represented as first and last authors in both journals, even using the best-case scenario. Their appearance as authors has remained stagnant for three decades, despite attention to structural inequalities in medical academia. Thus, analysis of authorship demographics in JAMA and NEJM over the past three decades reveals the existence of inequalities in high-impact medical journal authorship. Gender and racial/ethnic disparities in authorship may both reflect and further contribute to disparities in academic advancement.