Pandemic Forms.

Narrative structures, though invisible to the naked eye, guide our understanding of pandemics. Like curves and graphs, we can plot them, identify their patterns and organizing principles. These structures act upon our understanding of social and biological events just as much as the rhythms of viral replication and mutation. They order not only themselves but also social and health outcomes. This essay uses narrative precision to expand beyond Charles Rosenberg's influential dramaturgic model and develops new pandemic forms, scaled from the level of an individual line break to the multi-part series: Arc, a form of sequence. Cycle, a form of repetition. Sequel, a form of elongation. Caesura, a form of break. It investigates the potentialities and limitations of these forms, how they intersect, collide, and contradict, and how analysis of these interactions contributes to a deeper understanding of pandemics, their effects, and the diverse perspectives defining their structures. In doing so, it prototypes how literary methods offer conceptual frameworks for pandemic historiography and how a transdisciplinary, medical humanities analysis produces novel understandings at the intersection of health, culture, and society.

Virtuosic craft or clerical labour: the rise of the electronic health record and challenges to physicians' professional identity (1950-2022).

The electronic health record (EHR) is a focus of contentious debate, having become as essential to contemporary clinical practice as it is polarising. Debates about the EHR raise questions about physicians' professional identity, the nature of clinical work, evolution of the patient/practitioner relationship, and narratives of technological optimism and pessimism. The metaphors by which clinicians stake our identities-are we historians, detectives, educators, technicians, or something else?-animate the history of the early computer-based medical record in the mid-to-late twentieth-century USA. Proponents and detractors were equally interested in what the EHR revealed about clinician identity, and how it might fundamentally reshape it. This paper follows key moments in the history of the early computer-based patient record from the late 1950s to the EHR of the present day. In linking physician identity development, clinical epistemological structures, and the rise of the computer-based medical record in the USA in the mid-to-late twentieth century, we ask why the EHR is such a polarising entity in contemporary medicine, and situate clinician/EHR tensions in a longer history of aspirational physician identity and a kind of technological optimism that soon gave way to pessimism surrounding computer-based clinical work.

The Case of the Peculiar Story: Medical Investigation and the Detective in Edgar Allan Poe and Marguerite Duras.

In "The Murders in the Rue Morgue" (1841), Poe invents the detective story in English, introducing his gentleman sleuth Auguste Dupin as he solves the locked-room mystery of two women found brutally murdered in a Paris apartment. In L'Amante Anglaise (1967), Duras revisits the detective form, fictionalizing the true 1949 crime of a woman murdering and dismembering her cousin in Viorne, France. These literary detective stories highlight the powerful but unspoken role of affective experience in driving what appears, on the surface, to be a forensic medical or psychological investigation. In both tales, peculiarity is an affective and cognitive force that, contrary to what the majority of affect literature argues, inherently moves toward resolution and closure. Using peculiarity as an analytical concept, we argue that the concealment / discovery binary must acknowledge its affective origins, breaking a barrier between narrative scholarship and medical practice.

A Pilot Study to Understand the Role of Medical Humanities in Medical Education.

Over the past 20 years, the number of colleges offering programs in medical humanities has increased, and through the Medical Humanities Initiative at Georgetown University, this pilot study sought to understand students perceived benefits of a medical humanities curriculum. Based on a qualitative thematic analysis of free-response survey reflections from students enrolled in three unique medical humanities courses, six themes emerged. The themes help capture the role that a medical humanities education can play in shaping future clinicians and demonstrate that these courses not only provided a distinct teaching methodology from the scientific classroom but also appeared to deepen the students' understanding of the humanistic aspects of medicine and its many facets.

Maternal Immune Cell and Cytokine Profiles to Predict Cardiovascular Risk Six Months after Preeclampsia.

Women who develop preeclampsia (PE) are at high risk for cardiovascular disease (CVD). Early identification of women with PE who may benefit the most from early cardiovascular risk screening and interventions remains challenging. Our objective was to assess whether cytokine and immune cell profiles after PE are helpful in distinguishing women at low and high CVD risk at 6-months postpartum. Individuals who developed PE were followed for immune cell phenotyping and plasma cytokine quantification at delivery, at 3-months, and at 6-months postpartum. Lifetime CVD risk was assessed at 6-months postpartum, and the immune cell and cytokine profiles were compared between risk groups at each time point. Among 31 participants, 18 (58.1%) exhibited high CVD-risk profiles at 6-months postpartum. The proportion of circulating NK-cells was significantly lower in high-risk participants at delivery (p = 0.04). At 3-months postpartum, high-risk participants exhibited a lower proportion of FoxP3+ regulatory T-cells (p = 0.01), a greater proportion of CD8+ T cells (p = 0.02) and a lower CD4+:CD8+ ratio (p = 0.02). There were no differences in immune cell populations at 6-months postpartum. There were no differences in plasma cytokines levels between risk groups at any time point. Subtle differences in immune cell profiles may help distinguish individuals at low and high CVD risk in the early postpartum period and warrants further investigation.

Roles of natural resistance-associated macrophage protein-1 in modulating bacterial distribution and immune responses during Salmonella enterica serovar Typhimurium infection in murine pregnancy.

PROBLEM: Salmonella enterica serovar Typhimurium (S.Tm) infection in Nramp1+/+ mice during pregnancy can lead to profound bacterial growth in the feto-placental unit and adverse pregnancy outcomes, including fetal loss, maternal illness and death. The kinetics and mechanisms by which S.Tm gains entry within individual feto-placental unit, and disseminates through tissues leading to placental resorption and fetal demise remain unclear. METHOD OF STUDY: Mice were systemically infected with S.Tm. Bacterial burden within spleen and individual placentas, and placental/fetal resorptions were quantified. Flow cytometric analysis of immune cell types in the spleen and individual placentas was performed. Cytokine expression in maternal serum was determined through cytometric bead array. RESULTS: Systemic infection with S.Tm resulted in preferential bacterial proliferation in placentas compared to the spleen in Nramp1+/+ mice. At 24 h post-infection, the mean infection rate of individual placentas per mouse was ∼50%, increasing to >75% by 72 h post-infection, suggesting that initial infection in few sites progresses to rapid spread of infection through the uterine milieu. This correlated with a steady increase in placental/fetal resorption rates. Placental infection was associated with local increased neutrophil percentages, whereas numbers and percentages in the spleen remained unchanged, suggesting dichotomous modulation of inflammation between the systemic compartment and the feto-maternal interface. Reduced survival rates of pregnant mice during infection correlated with decreased serum IFN-γ but increased IL-10 levels relative to non-pregnant controls. CONCLUSION: Pregnancy compromises host resistance conferred by Nramp1 against S.Tm through compartment-specific regulation of maternal and placental cellular responses, and modulation of systemic cytokine expression.

A prospective evaluation of breast thermography enhanced by a novel machine learning technique for screening breast abnormalities in a general population of women presenting to a secondary care hospital.

Objective: Artificial intelligence-enhanced breast thermography is being evaluated as an ancillary modality in the evaluation of breast disease. The objective of this study was to evaluate the clinical performance of Thermalytix, a CE-marked, AI-based thermal imaging test, with respect to conventional mammography. Methods: A prospective, comparative study performed between 15 December 2018 and 06 January 2020 evaluated the performance of Thermalytix in 459 women with both dense and nondense breast tissue. Both symptomatic and asymptomatic women, aged 30-80 years, presenting to the hospital underwent Thermalytix followed by 2-D mammography and appropriate confirmatory investigations to confirm malignancy. The radiologist interpreting the mammograms and the technician using the Thermalytix tool were blinded to the others' findings. The statistical analysis was performed by a third party. Results: A total of 687 women were recruited, of whom 459 fulfilled the inclusion criteria. Twenty-one malignancies were detected (21/459, 4.6%). The overall sensitivity of Thermalytix was 95.24% (95% CI, 76.18-99.88), and the specificity was 88.58% (95% CI, 85.23-91.41). In women with dense breasts (n = 168, 36.6%), the sensitivity was 100% (95% CI, 69.15-100), and the specificity was 81.65% (95% CI, 74.72-87.35). Among these 168 women, 37 women (22%) were reported as BI-RADS 0 on mammography; in this subset, the sensitivity of Thermalytix was 100% (95% CI, 69.15-100), and the specificity was 77.22% (95% CI, 69.88-83.50). Conclusion: Thermalytix showed acceptable sensitivity and specificity with respect to mammography in the overall patient population. Thermalytix outperformed mammography in women with dense breasts and those reported as BI-RADS 0.

Immunogenic and efficacious SARS-CoV-2 vaccine based on resistin-trimerized spike antigen SmT1 and SLA archaeosome adjuvant.

The huge worldwide demand for vaccines targeting SARS-CoV-2 has necessitated the continued development of novel improved formulations capable of reducing the burden of the COVID-19 pandemic. Herein, we evaluated novel protein subunit vaccine formulations containing a resistin-trimerized spike antigen, SmT1. When combined with sulfated lactosyl archaeol (SLA) archaeosome adjuvant, formulations induced robust antigen-specific humoral and cellular immune responses in mice. Antibodies had strong neutralizing activity, preventing viral spike binding and viral infection. In addition, the formulations were highly efficacious in a hamster challenge model reducing viral load and body weight loss even after a single vaccination. The antigen-specific antibodies generated by our vaccine formulations had stronger neutralizing activity than human convalescent plasma, neutralizing the spike proteins of the B.1.1.7 and B.1.351 variants of concern. As such, our SmT1 antigen along with SLA archaeosome adjuvant comprise a promising platform for the development of efficacious protein subunit vaccine formulations for SARS-CoV-2.

Person Under Investigation: Detecting Malingering and a Diagnostics of Suspicion in Fin-de-Siècle Britain.

In 1889, The British Medical Journal published a piece titled, "Detective Medicine," which describes feats of medical detection performed by physicians attending malingering prisoners. Though simulating illness had a long history, the medicalization of malingering at the fin de siècle led to a proliferation of such case histories and cheerful records of pathological feigners thwarted.

Effectiveness of two sensory-based health education methods on oral hygiene of adolescent with autism spectrum disorders: An interventional study.

AIM: This study was undertaken with an aim to evaluate the effectiveness of two sensory-based interventions namely - Visual pedagogy and Mobile based application (Brush Up) on oral health education in promoting oral health status among 13-17 year old school going adolescents with Autism Spectrum Disorder (ASD) in Chennai city. METHODOLOGY: An interventional parallel arm study consisting of 13- to 17-year-old school going adolescent with ASD in Chennai city. Plaque Index (Sillness and Loe, 1964) and gingival index (Loe and Sillness, 1963) were assessed at baseline, 6th week and after 12th week. RESULTS: A significant difference in plaque (p = < 0.001) and gingival scores (p = < 0.001) were seen among the groups after 6 and 12 weeks post-intervention. There was no statistically significant difference in dental plaque (p = 0.912, 1.023, 0.812) and gingival scores (p = 0.932, 0.264, 0.283) between the groups at all the timelines. CONCLUSION: In this present study we found that both the visual cards and mobile based application (Brush Up) had significantly reduced the dental plaque and gingival scores; hence both the modalities can be used as an effective tool in educating these children and thus improve their oral hygiene.

IFN-alpha receptor deficiency enhances host resistance to oral Salmonella enterica serovar Typhimurium infection during murine pregnancy.

PROBLEM: Maternal tolerance during pregnancy increases the risk of infection with certain intracellular pathogens. Systemic Salmonella enterica serovar Typhimurium (S.Tm) infection during pregnancy in normally resistant 129X1/SvJ mice leads to severe placental infection, as well as fetal and maternal deaths. However, the effect of oral infection with S.Tm in pregnant mice and the roles of infection-induced inflammation and cell death pathways in contributing to susceptibility to infection are unclear. METHOD OF STUDY: Non-pregnant and pregnant C57BL/6J wild-type (WT) and cell death pathway-altered mice (IFNAR1-/- , Caspase-1, 11-/- , RIP3-/- ) were infected orally with S.Tm. Host survival and fetal resorption were determined. Bacterial burden in mesenteric lymph nodes (MLNs), spleen, liver, and placentas was enumerated at various time points post-infection. Serum cytokine expression was measured through cytometric bead array. RESULTS: Oral infection of WT mice with S.Tm on days 9-10 of gestation resulted in systemic dissemination of the bacteria, substantial placental colonization, and fetal loss 5 days post-infection. Histopathological examination of the placentas indicated that infection-induced widespread focal necrosis and neutrophil infiltration throughout the spongiotrophoblast (SpT) layer. In the non-pregnant state, IFNAR1-/- mice exhibited increased survival following oral S.Tm infection relative to Caspase-1, 11-/- , RIP3-/- , and WT mice. The increased resistance to S.Tm infection in IFNAR1-/- mice was seen during pregnancy as well, with decreased bacterial burden within MLNs, spleen, and placenta, which correlated with the decreased resorptions relative to WT and Caspase-1, 11-/- mice. CONCLUSION: Oral S.Tm exposure leads to placental infection, inflammation, and resorption, whereas IFNAR1 deficiency enhances host resistance both in the non-pregnant and pregnant states.

Sulfated Lactosyl Archaeol Archaeosomes Synergize with Poly(I:C) to Enhance the Immunogenicity and Efficacy of a Synthetic Long Peptide-Based Vaccine in a Melanoma Tumor Model.

Cancer remains a leading cause of morbidity and mortality worldwide. While novel treatments have improved survival outcomes for some patients, new treatment modalities/platforms are needed to combat a wider variety of tumor types. Cancer vaccines harness the power of the immune system to generate targeted tumor-specific immune responses. Liposomes composed of glycolipids derived from archaea (i.e., archaeosomes) have been shown to be potent adjuvants, inducing robust, long-lasting humoral and cell-mediated immune responses to a variety of antigens. Herein, we evaluated the ability of archaeosomes composed of sulfated lactosyl archaeol (SLA), a semi-synthetic archaeal glycolipid, to enhance the immunogenicity of a synthetic long peptide-based vaccine formulation containing the dominant CD8+ T cell epitope, SIINFEKL, from the weakly immunogenic model antigen ovalbumin. One advantage of immunizing with long peptides is the ability to include multiple epitopes, for example, the long peptide antigen was also designed to include the immediately adjacent CD4+ epitope, TEWTSSNVMEER. SLA archaeosomes were tested alone or in combination with the toll-like receptor 3 (TLR3) agonist Poly(I:C). Overall, SLA archaeosomes synergized strongly with Poly(I:C) to induce robust antigen-specific CD8+ T cell responses, which were highly functional in an in vivo cytolytic assay. Furthermore, immunization with this vaccine formulation suppressed tumor growth and extended mouse survival in a mouse melanoma tumor model. Overall, the combination of SLA archaeosomes and Poly(I:C) appears to be a promising adjuvant system when used along with long peptide-based antigens targeting cancer.

The Synergistic Effects of Sulfated Lactosyl Archaeol Archaeosomes When Combined with Different Adjuvants in a Murine Model.

Archaeosomes, composed of sulfated lactosyl archaeol (SLA) glycolipids, have been proven to be an effective vaccine adjuvant in multiple preclinical models of infectious disease or cancer. SLA archaeosomes are a promising adjuvant candidate due to their ability to strongly stimulate both humoral and cytotoxic immune responses when simply admixed with an antigen. In the present study, we evaluated whether the adjuvant effects of SLA archaeosomes could be further enhanced when combined with other adjuvants. SLA archaeosomes were co-administered with five different Toll-like Receptor (TLR) agonists or the saponin QS-21 using ovalbumin as a model antigen in mice. Both humoral and cellular immune responses were greatly enhanced compared to either adjuvant alone when SLA archaeosomes were combined with either the TLR3 agonist poly(I:C) or the TLR9 agonist CpG. These results were also confirmed in a separate study using Hepatitis B surface antigen (HBsAg) and support the further evaluation of these adjuvant combinations.

When Recurring Infections Mask an Atypical Presentation of Inflammatory Bowel Disease (IBD): A Re-Visitation and Literature Review.

Pyoderma gangrenosum (PG) is an uncommon and severe extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD). Head or scalp involvement in this condition is exceedingly rare. Approximately one-third of presentations can be precipitated by skin trauma or infection, a phenomenon known as pathergy. These ulcers develop acutely, do not necessarily correlate with IBD activity, and can precede IBD diagnosis. Here, we present an atypical presentation of PG that became a cornerstone finding in the subsequent diagnosis of IBD.

Assessment of stability of sulphated lactosyl archaeol archaeosomes for use as a vaccine adjuvant.

Archaeosomes, composed of sulphated lactosyl archaeol (SLA) glycolipids, have been proven to be an effective vaccine adjuvant in multiple preclinical models of infectious disease or cancer. In addition to efficacy, the stability of vaccine components including the adjuvant is an important parameter to consider when developing novel vaccine formulations. To properly evaluate the potential of SLA glycolipids to be used as vaccine adjuvants in a clinical setting, a comprehensive evaluation of their stability is required. Herein, we evaluated the long term stability of preformed empty SLA archaeosomes prior to admixing with antigen at 4 °C or 37 °C for up to 6 months. In addition, the stability of adjuvant and antigen was evaluated for up to 1 month following admixing. Multiple analytical parameters evaluating the molecular integrity of SLA and the liposomal profile were assessed. Following incubation at 4 °C or 37 °C, the SLA glycolipid did not show any pattern of degradation as determined by mass spectroscopy, nuclear magnetic resonance (NMR) and thin layer chromatography (TLC). In addition, SLA archaeosome vesicle characteristics, such as size, zeta potential, membrane fluidity and vesicular morphology, were largely consistent throughout the course of the study. Importantly, following storage for 6 months at both 4 °C and 37 °C, the adjuvant properties of empty SLA archaeosomes were unchanged, and following admixing with antigen, the immunogenicity of the vaccine formulations was also unchanged when stored at both 4 °C and 37 °C for up to 1 month. Overall this indicates that SLA archaeosomes are highly stable adjuvants that retain their activity over an extended period of time even when stored at high temperatures.

Observational Study to Evaluate the Clinical Efficacy of Thermalytix for Detecting Breast Cancer in Symptomatic and Asymptomatic Women.

PURPOSE: To evaluate the sensitivity and specificity of Thermalytix, an artificial intelligence-based computer-aided diagnostics (CADx) engine, to detect breast malignancy by comparing the CADx output with the final diagnosis derived using standard screening modalities. METHODS: This multisite observational study included 470 symptomatic and asymptomatic women who presented for a breast health checkup in two centers. Among them, 238 women had symptoms such as breast lump, nipple discharge, or breast pain, and the rest were asymptomatic. All participants underwent a Thermalytix test and one or more standard-of-care tests for breast cancer screening, as recommended by the radiologists. Results from Thermalytix and standard modalities were obtained independently in a blinded fashion for comparison. The ground truth used for analysis (normal or malignant) was the final impression of an expert clinician based on the symptoms and the available reports of standard modalities (mammography, ultrasonography, elastography, biopsy, fine-needle aspiration cytology, and so on). RESULTS: For the 470 women, Thermalytix resulted in a sensitivity of 91.02% (symptomatic, 89.85%; asymptomatic, 100%) and specificity of 82.39% (symptomatic, 69.04%; asymptomatic, 92.41%) in detection of breast malignancy. Thermalytix showed an overall area under the curve (AUC) of 0.90, with an AUC of 0.82 for symptomatic and 0.98 for asymptomatic women. CONCLUSION: High sensitivity and high AUC of Thermalytix in women of all age groups demonstrates the efficacy of the tool for breast cancer screening. Thermalytix, with its automated scoring and image annotations of potential malignancies and vascularity, can assist the clinician in better decision making and improve quality of care in an affordable and radiation-free manner. Thus, we believe Thermalytix is poised to be a promising modality for breast cancer screening.

Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations.

Archaeosomes are liposomes formulated using total polar lipids (TPLs) or semi-synthetic glycolipids derived from archaea. Conventional archaeosomes with entrapped antigen exhibit robust adjuvant activity as demonstrated by increased antigen-specific humoral and cell-mediated responses and enhanced protective immunity in various murine infection and cancer models. However, antigen entrapment efficiency can vary greatly resulting in antigen loss during formulation and variable antigen:lipid ratios. In order to circumvent this, we recently developed an admixed archaeosome formulation composed of a single semi-synthetic archaeal lipid (SLA, sulfated lactosylarchaeol) which can induce similarly robust adjuvant activity as an encapsulated formulation. Herein, we evaluate and compare the mechanisms involved in the induction of early innate and antigen-specific responses by both admixed (Adm) and encapsulated (Enc) SLA archaeosomes. We demonstrate that both archaeosome formulations result in increased immune cell infiltration, enhanced antigen retention at injection site and increased antigen uptake by antigen-presenting cells and other immune cell types, including neutrophils and monocytes following intramuscular injection to mice using ovalbumin as a model antigen. In vitro studies demonstrate SLA in either formulation is preferentially taken up by macrophages. Although the encapsulated formulation was better able to induce antigen-specific CD8+ T cell activation by dendritic cells in vitro, both encapsulated and admixed formulations gave equivalently enhanced protection from tumor challenge when tested in vivo using a B16-OVA melanoma model. Despite some differences in the immunostimulatory profile relative to the SLA (Enc) formulation, SLA (Adm) induces strong in vivo immunogenicity and efficacy, while offering an ease of formulation.

Barriers to utilisation of dental care services among children with special needs: A systematic review.

BACKGROUND: Disabled population accounts for 2.86 Crore of total Indian population. Among these 27.4% of population consists of children within age group of age 0 to 19 years. Studies have shown oral health status of children with special needs is lower than children without special needs. Though there are various attributing factors, access to dental care delivery and difficulties faced during dental treatment delivery are of major concern. Therefore the aim of this systematic review was set to assess the barriers faced by children with special needs during utilization of dental services; through caregiver's perception. MATERIALS AND METHODS: For this review MEDLINE, EBSCO, COCHRANE, EMBASE and Google Scholar were the electronic data bases searched based on the PICO. PRISMA guidelines were followed for final inclusion of articles. RESULTS: The search generated a total of 259 articles from five different electronic bases: PUBMED, EMBASE, EBSCO, COCHRANE and GOOGLE SCHOLAR. Based on inclusion criteria, 7 articles made it to final analysis. All the 7 studies reported that dentist were unwilling to treat children with special needs as a major barrier followed by fear towards dentist by the children with special needs. CONCLUSION: The cross sectional studies of this review were assessed for quality using a modified Newcastle Ottawa Scale, proposed by Egger et al. in 2003. Even though the available literature forms a lower standard of evidence, further evaluation of barriers are recommended using better designed studies to substantiate the in equal access to healthcare facilities by these marginalized population.