Human distal lung maps and lineage hierarchies reveal a bipotent progenitor.

Mapping the spatial distribution and molecular identity of constituent cells is essential for understanding tissue dynamics in health and disease. We lack a comprehensive map of human distal airways, including the terminal and respiratory bronchioles (TRBs), which are implicated in respiratory diseases1-4. Here, using spatial transcriptomics and single-cell profiling of microdissected distal airways, we identify molecularly distinct TRB cell types that have not-to our knowledge-been previously characterized. These include airway-associated LGR5+ fibroblasts and TRB-specific alveolar type-0 (AT0) cells and TRB secretory cells (TRB-SCs). Connectome maps and organoid-based co-cultures reveal that LGR5+ fibroblasts form a signalling hub in the airway niche. AT0 cells and TRB-SCs are conserved in primates and emerge dynamically during human lung development. Using a non-human primate model of lung injury, together with human organoids and tissue specimens, we show that alveolar type-2 cells in regenerating lungs transiently acquire an AT0 state from which they can differentiate into either alveolar type-1 cells or TRB-SCs. This differentiation programme is distinct from that identified in the mouse lung5-7. Our study also reveals mechanisms that drive the differentiation of the bipotent AT0 cell state into normal or pathological states. In sum, our findings revise human lung cell maps and lineage trajectories, and implicate an epithelial transitional state in primate lung regeneration and disease.

Three million images and morphological profiles of cells treated with matched chemical and genetic perturbations.

The identification of genetic and chemical perturbations with similar impacts on cell morphology can elucidate compounds' mechanisms of action or novel regulators of genetic pathways. Research on methods for identifying such similarities has lagged due to a lack of carefully designed and well-annotated image sets of cells treated with chemical and genetic perturbations. Here we create such a Resource dataset, CPJUMP1, in which each perturbed gene's product is a known target of at least two chemical compounds in the dataset. We systematically explore the directionality of correlations among perturbations that target the same protein encoded by a given gene, and we find that identifying matches between chemical and genetic perturbations is a challenging task. Our dataset and baseline analyses provide a benchmark for evaluating methods that measure perturbation similarities and impact, and more generally, learn effective representations of cellular state from microscopy images. Such advancements would accelerate the applications of image-based profiling of cellular states, such as uncovering drug mode of action or probing functional genomics.

Chorioamnionitis accelerates granule cell and oligodendrocyte maturation in the cerebellum of preterm nonhuman primates.

BACKGROUND: Preterm birth is often associated with chorioamnionitis and leads to increased risk of neurodevelopmental disorders, such as autism. Preterm birth can lead to cerebellar underdevelopment, but the mechanisms of disrupted cerebellar development in preterm infants are not well understood. The cerebellum is consistently affected in people with autism spectrum disorders, showing reduction of Purkinje cells, decreased cerebellar grey matter, and altered connectivity. METHODS: Preterm rhesus macaque fetuses were exposed to intra-amniotic LPS (1 mg, E. coli O55:B5) at 127 days (80%) gestation and delivered by c-section 5 days after injections. Maternal and fetal plasma were sampled for cytokine measurements. Chorio-decidua was analyzed for immune cell populations by flow cytometry. Fetal cerebellum was sampled for histology and molecular analysis by single-nuclei RNA-sequencing (snRNA-seq) on a 10× chromium platform. snRNA-seq data were analyzed for differences in cell populations, cell-type specific gene expression, and inferred cellular communications. RESULTS: We leveraged snRNA-seq of the cerebellum in a clinically relevant rhesus macaque model of chorioamnionitis and preterm birth, to show that chorioamnionitis leads to Purkinje cell loss and disrupted maturation of granule cells and oligodendrocytes in the fetal cerebellum at late gestation. Purkinje cell loss is accompanied by decreased sonic hedgehog signaling from Purkinje cells to granule cells, which show an accelerated maturation, and to oligodendrocytes, which show accelerated maturation from pre-oligodendrocytes into myelinating oligodendrocytes. CONCLUSION: These findings suggest a role of chorioamnionitis on disrupted cerebellar maturation associated with preterm birth and on the pathogenesis of neurodevelopmental disorders among preterm infants.

The induction of preterm labor in rhesus macaques is determined by the strength of immune response to intrauterine infection.

Intrauterine infection/inflammation (IUI) is a major contributor to preterm labor (PTL). However, IUI does not invariably cause PTL. We hypothesized that quantitative and qualitative differences in immune response exist in subjects with or without PTL. To define the triggers for PTL, we developed rhesus macaque models of IUI driven by lipopolysaccharide (LPS) or live Escherichia coli. PTL did not occur in LPS challenged rhesus macaques, while E. coli-infected animals frequently delivered preterm. Although LPS and live E. coli both caused immune cell infiltration, E. coli-infected animals showed higher levels of inflammatory mediators, particularly interleukin 6 (IL-6) and prostaglandins, in the chorioamnion-decidua and amniotic fluid (AF). Neutrophil infiltration in the chorio-decidua was a common feature to both LPS and E. coli. However, neutrophilic infiltration and IL6 and PTGS2 expression in the amnion was specifically induced by live E. coli. RNA sequencing (RNA-seq) analysis of fetal membranes revealed that specific pathways involved in augmentation of inflammation including type I interferon (IFN) response, chemotaxis, sumoylation, and iron homeostasis were up-regulated in the E. coli group compared to the LPS group. Our data suggest that the intensity of the host immune response to IUI may determine susceptibility to PTL.

Scholarly Activity and Gender of an Applicant for a General Surgery Residency.

INTRODUCTION: Applying to general surgery residency is undoubtedly a competitive process. Participation in scholarly activity (SCA) has been cited as a criterion when selecting applicants for interview and in the ranking process. This study aims to evaluate the association between gender of applicants to surgery residency and SCA and to characterize trends in SCAs over time. METHODS: We analyzed the SCA of applicants interviewed at a general surgery residency program over 6-interview cycles (2016-2021). Eight SCA categories were included: (1) Poster Presentation, (2) Oral Presentation, (3) Peer-Reviewed (PR) Journal Articles/Abstracts, (4) PR Journal Articles/Abstracts (Other than Published), (5) PR Online Publication, (6) PR Book Chapter, (7) Nonpeer reviewed Online Publication, and (8) Other Articles/Scientific Monograph. RESULTS: Of a total of 335 interviewed applicants, 288 (86%) had at least one count of SCA. Overall, no difference between male and female applicants was noticed (n = 178, 84.8% versus n = 110, 88%, P = 0.409) and no change in percentage of SCA over the six cycles (P = 0.239). The most reported SCAs were poster presentations (n = 242, 72.2%), oral presentations (n = 159, 47.5%), PR journal articles/abstracts (n = 159, 47.5%). Female applicants have marginally higher median (interquartile range) for SCAs compared to male applicants (5 [3, 8] versus 4 [3, 8], P value 0.272). CONCLUSIONS: No association between gender and SCA among applicants for general surgery residency positions was observed. While more than three-fourths of applicants have at least one SCA, only a small fraction of applicants were published. Students should be made aware of the importance of SCA early in graduate medical education.

Implementing Canada's first national virtual phone based overdose prevention service: lessons learned from creating the National Overdose Response Service (NORS).

The opioid epidemic remains one of the largest public health crises in North America to date. While there have been many diverse strategies developed to reduce the harms associated with substance use, these are primarily concentrated within a few large urban centers. As a result, there have been increased calls for equitable access to harm reduction services for those who cannot or choose not to access in-person harm reduction services. In December 2020, Canada's National Overdose Response Service (NORS) a telephone based overdose response hotline and virtual supervised consumption service, was established in collaboration with various agencies and people with lived and living experience of substance use (PWLLE) across Canada to expand access to harm reduction services using novel Opioid Response Technology. In this manuscript we explore the lessons learned from the establishment and continued operation of the service exploring topics related to the initial establishment of the service, securing a phone line, routing technology, EMS dispatch solutions, peer and volunteer recruitment, legal and ethical support, policy and procedure development, securing funding, and marketing. Furthermore, we detail how this service has grown and changed in response to the various needs of service users.

Medical student perceptions of assessments of clinical reasoning in a general surgery clerkship.

BACKGROUND: Components factoring into general surgery clerkship grades vary by institution, and while evaluators attempt to remain unbiased when evaluating medical student performance, subjectivity and implicit bias remain an issue. Our institution recently implemented a case-based structured oral examination to provide the general surgery clerkship director objective insight into students' clinical reasoning skills. We hypothesized that medical students believe this exam, along with graded clinical documentation and the Observed Standardized Clinical Encounter (OSCE), are fair assessments and increase students' awareness of their clinical reasoning skills. METHODS: A survey was sent to third-year medical students in the classes of 2023 and 2024 at our institution who had completed their general surgery clerkship. Students rated five grading assessments (i.e., preceptor evaluations, the oral examination, clinical documentation, the OSCE, and the shelf exam) on fairness and the ability of the assessment to give them insight into their clinical reasoning on a five-point Likert scale 1-5 (with 1 = Strongly Agree, 5 = Strongly Disagree). RESULTS: One hundred and ten of 162 (67.9%) students responded to the survey. The shelf examination was the most highly regarded assessment tool followed by the oral examination. Seventy-three percent agreed or strongly agreed that the oral exam was a fair assessment, and 80% agreed or strongly agreed that it gave them insight into their clinical reasoning skills. Alternatively, only 41.8% of students agreed or strongly agreed that preceptor evaluations were fair assessments and 42.7% agreed or strongly agreed that it gave them insight into their clinical reasoning. CONCLUSIONS: Third-year medical students on a general surgery clerkship favor the shelf examination and a case-based oral examination over other assessment tools regarding fairness and perception of their clinical reasoning. This type of examination can provide general surgery clerkship directors with additional objective data to assess medical students more fairly and improve students' clinical reasoning.

Effect of photobiomodulation therapy as a multimodal approach to treatment of dermal abrasions in cownose rays (Rhinoptera bonasus).

Photobiomodulation therapy (PBMT) has become increasingly utilized in the zoo and aquarium fields to treat ailments in various species; however, its use in teleosts and elasmobranchs is relatively underrepresented in the literature. This study examined the efficacy of PBMT as an adjunct treatment to reduce the healing time of dermal abrasions in cownose rays (Rhinoptera bonasus). Ten cownose rays were included in this study and separated into control (n = 5) and treatment groups (n = 5). Animals in both treatment and control groups received intramuscular injections of enrofloxacin every 72 h to provide broad-spectrum antibiotic coverage. Cownose rays in the treatment group additionally received PBMT using the Companion® CTC-12 unit using the large, noncontact head. Control group rays were subjected to identical handling without the use of PBMT. A total of 196 Joules were delivered at a power of 2 W based on a dose of 5 J/cm2 at each session. Observational analysis revealed a lack of appreciable difference in healing time between the treatment and control groups in the aforementioned settings; however, it is recommended that PBMT protocols should be re-evaluated if there is little to no response in healing after three to four sessions. PBMT use on acute superficial dermal abrasions in cownose rays was well-tolerated in this study and may have utility in a multimodal treatment approach to wound healing. This study also produced a wound scoring metric based on photographs captured at each treatment. Future studies should utilize increased fluence (J/cm2) and irradiance (W/cm2) and incorporate synchronous histological analysis and increased sample size.

Association of drug overdoses and user characteristics of Canada's national mobile/virtual overdose response hotline: the National Overdose Response Service (NORS).

BACKGROUND: Several novel overdose response technology interventions, also known as mobile overdose response services (MORS), have emerged as adjunct measures to reduce the harms associated with the drug poisoning epidemic. This retrospective observational study aims to identify the characteristics and outcomes of individuals utilizing one such service, the National Overdose Response Service (NORS). METHODS: A retrospective analysis was conducted using NORS call logs from December 2020 to April 2023 imputed by operators. A variety of variables were examined including demographics, substance use and route, location, and call outcomes. Odds ratios and 95% confidence intervals were calculated around variables of interest to test the association between key indicators and drug poisonings. RESULTS: Of the 6528 completed calls on the line, 3994 (61.2%) were for supervised drug consumption, 1703 (26.1%) were for mental health support, 354 (5.42%) were for harm reduction education or resources, and 477 (7.31%) were for other purposes. Overall, there were 77 (1.18%) overdose events requiring a physical/ in-person intervention. Of the total calls, 3235 (49.5%) were from women, and 1070 (16.3%) were from people who identified as gender diverse. Calls mostly originated from urban locations (n = 5796, 88.7%) and the province of Ontario (n = 4137, 63.3%). Odds ratios indicate that using opioids (OR 6.72, CI 95% 3.69-13.52), opioids in combination with methamphetamine (OR 9.70, CI 95% 3.24-23.06), multiple consumption routes (OR 6.54, CI 95% 2.46-14.37), and calls occurring in British Columbia (B.C) (OR 3.55, CI 95% 1.46-7.33) had a significantly higher likelihood of a drug poisoning. No deaths were recorded and only 3 false callouts had occurred. The overall drug poisoning event incidence to phone calls was 1.2%. CONCLUSION: NORS presents a complimentary opportunity to access harm reduction services for individuals that prefer to use alone or face barriers to accessing in-person supervised consumption services especially gender minorities with high-risk use patterns.

Home-prepared meals among college students at-risk for food insecurity: A mixed-methods study.

The ability to prepare meals at home is an important life skill with potential to improve dietary quality and reduce costs and thus may be particularly important for college students with food insecurity. However, heavy time demands, limited financial resources, and therefore other barriers such as lack of motivation to follow a healthy diet may constrain meal preparation skills. To gain greater insight into this issue, we conducted a mixed-methods study. The quantitative component assessed relationships among food security, motivation, and meal preparation skills. The qualitative component used focus groups to more closely consider college students' perceptions, values, and barriers surrounding preparing meals at home, including current practices, desired future practices, and the ways in which the campus could support their efforts. The survey (n = 226) assessed food security, meal preparation skills, and motivation (i.e., perceived ability and willingness) to consume a healthy diet. Ten focus groups (n = 60) discussed food choice, meal preparation practices, and ways in which the campus could help students develop meal preparation skills. Students with food insecurity had lower meal preparation skills and lower perceived ability to consume a healthy diet. However, a) willingness to consume a healthy diet and b) the impact of both willingness and perceived ability did not differ by food security status. Focus group data indicated that in-person and online cooking classes, information cards in the food pantry, and incentives (e.g., kitchen equipment and vouchers from local grocery stores) were popular ideas for improving home-meal preparation. A greater understanding of meal preparation skills and their interconnectedness to food choice and the campus environment may inform effective ways to support the ability and willingness of college students with food insecurity to prepare meals at home.

The Impact of Homemade Laparoscopic Box Trainers on Medical Student Surgical Skills: A Randomized Control Pilot Study.

Objective: While instructional videos are commonly used in surgical education, there is a paucity of data on home laparoscopic box trainers. This pilot study evaluated impacts of augmenting instructional videos with these devices. Design: This was a randomized controlled pilot study evaluating laparoscopic surgical performance on the LapSim virtual surgical simulator before and after a 2 week curriculum of instructional videos alone (n = 8, 47.1%) vs videos plus a home laparoscopic box trainer (n = 9, 52.9%). The LapSim recorded mistake number, time, and instrument path length to complete each task. Participants completed surveys about their perceptions of surgery before and after the course. Participants: Preclinical medical students were recruited. Those with extensive surgical experience or did not complete the course were excluded. Results: For the box trainer group vs the videos alone group: mean change in mistakes was -10.0 (standard deviation [SD]:17.1) vs +.5 (SD:21.59) (P = .28); mean change in time was -433.24 (SD:304.67) seconds vs -366.16 (SD:240.10) seconds (P = .62); mean change in instrument path length was -4.27 (SD:4.38) meters vs -3.19 (SD:4.86) meters (P = .64). The box trainer group ranked "I feel as though surgery comes naturally" 1.58 points higher (95% confidence interval [CI]: .85, 2.32; P < .01) and "I am worried about being skilled at surgery" 1.26 points lower (95% CI: 2.29, -.24; P = .02) upon completing the study. The videos alone group reported no significant changes in survey responses. Conclusion: Home laparoscopic box trainers can generate confidence and reduce anxiety regarding surgical fields. This study provides a framework for future larger scale works.

Genomic Characterization of Group A Streptococci Causing Pharyngitis and Invasive Disease in Colorado, USA, June 2016- April 2017.

BACKGROUND: The genomic features and transmission link of circulating Group A Streptococcus (GAS) strains causing different disease types, such as pharyngitis and invasive disease, are not well understood. METHODS: We used whole-genome sequencing to characterize GAS isolates recovered from persons with pharyngitis and invasive disease in the Denver metropolitan area from June 2016 to April 2017. RESULTS: The GAS isolates were cultured from 236 invasive and 417 pharyngitis infections. Whole-genome sequencing identified 34 emm types. Compared with pharyngitis isolates, invasive isolates were more likely to carry the erm family genes (23% vs 7.4%, P<.001), which confer resistance to erythromycin and clindamycin (including inducible resistance), and covS gene inactivation (7% vs 0.5%, P<.001). Whole-genome sequencing identified 97 genomic clusters (433 isolates; 2-65 isolates per cluster) that consisted of genomically closely related isolates (median single-nucleotide polymorphism=3 [interquartile range, 1-4] within cluster). Thirty genomic clusters (200 isolates; 31% of all isolates) contained both pharyngitis and invasive isolates and were found in 11 emm types. CONCLUSIONS: In the Denver metropolitan population, mixed disease types were commonly seen in clusters of closely related isolates, indicative of overlapping transmission networks. Antibiotic-resistance and covS inactivation was disproportionally associated with invasive disease.

Fezolinetant: A New Nonhormonal Treatment for Vasomotor Symptoms.

Objective: To review the safety, efficacy, and tolerability of fezolinetant for the treatment of vasomotor symptoms associated with menopause. Data Sources: A literature search was conducted through PubMed using the following search terms: fezolinetant, ES259564, SKYLIGHT, vasomotor symptoms, and menopause. Study Selection and Data Extraction: Selected articles included those which described clinical studies of the pharmacology, pharmacokinetics, efficacy, safety, or tolerability of fezolinetant. Data Synthesis: Fezolinetant works by inhibiting neurokinin B from binding to its receptor in the hypothalamus, thereby decreasing the occurrence of vasomotor symptoms. Clinical trials have demonstrated fezolinetant is superior to placebo in decreasing the frequency and severity of vasomotor symptoms. Common adverse effects associated with the use of fezolinetant include headache and gastrointestinal disturbances, as well as elevations in liver transaminase levels. Conclusions: Clinical practice guidelines for the treatment of vasomotor symptoms associated with menopause recommend hormone therapy as the most effective treatment option. Risks associated with hormone use may limit the use of this option in some patients. Neurokinin B inhibitors, like fezolinetant, target the physiologic cause of vasomotor symptoms. With the approval of fezolinetant, as well as elinzanetant which is currently in phase 3 clinical trials, providers and patients have additional nonhormonal treatment options for vasomotor symptoms associated with menopause.

Learning-related changes in cellular activity within mouse dentate gyrus during trace eyeblink conditioning.

Because the dentate gyrus serves as the first site for information processing in the hippocampal trisynaptic circuit, it an important structure for the formation of associative memories. Previous findings in rabbit had recorded populations of cells within dentate gyrus that may bridge the temporal gap between stimuli to support memory formation during trace eyeblink conditioning, an associative learning task. However, this previous work was unable to identify the types of cells demonstrating this type of activity. To explore these changes further, we did in vivo single-neuron recording in conjunction with physiological determination of cell types to investigate the functional role of granule cells, mossy cells, and interneurons in dentate gyrus during learning. Tetrode recordings were performed in young-adult mice during training on trace eyeblink conditioning, a hippocampal-dependent temporal associative memory task. Conditioned mice were able to successfully learn the task, with male mice learning at a faster rate than female mice. In the conditioned group, granule cells tended to show an increase in firing rate during conditioned stimulus presentation while mossy cells showed a decrease in firing rate during the trace interval and the unconditioned stimulus. Interestingly, populations of interneurons demonstrated learning-related increases and decreases in activity that began at onset of the conditioned stimulus and persisted through the trace interval. The current study also found a significant increase in theta power during stimuli presentation in conditioned animals, and this change in theta decreased over time. Ultimately, these data suggest unique involvement of granule cells, mossy cells, and interneurons in dentate gyrus in the formation of a trace associative memory. This work expands our knowledge of dentate gyrus function, helping to discern how aging and disease might disrupt this process.

Segmented assimilation as a mechanism to explain the dietary acculturation paradox.

Latinos have disproportionately high rates of diet-related diseases which are associated with acculturation to the U.S. This negative shift in dietary quality is paradoxical in light of gains in income and education that would be expected to lead to better diet. We examined the extent to which the dietary acculturation paradox among Mexican Americans can be explained by segmented assimilation, a theory that considers how immigrants' and their descendants' trajectories of integration are influenced by a complex interplay of individual, social, and structural factors. First, we performed confirmatory cluster analysis to identify three assimilation segments (classic, underclass, and selective) based on education, income, and an acculturation proxy derived from language, nativity, and time in the U.S. among Mexican-origin participants (N = 4475) of the 2007-2016 National Health and Nutrition Examination Survey (NHANES). These segments were then used as independent variables in linear regression models to estimate the relationship between cluster and dietary quality (assessed by the Health Eating Index (HEI)) and the interaction between cluster and gender, controlling for marital status. There were strong effects of cluster on dietary quality, consistent with hypotheses per segmented assimilation theory. The classic assimilation segment had the poorest diet, despite having higher income and education than the underclass segment. The selective segment had higher or similar dietary quality to the underclass segment. Consistent with expectations, this difference was driven by the relatively higher consumption of greens and beans and whole grains of those in the selective and underclass segments. Overall, women had better diets than men; however, the strongest gender contrast was in the underclass segment. This study advances understanding of dietary acculturation and potential disparities in diet-related health outcomes.

Dietitian Involvement Improves Consumption of Oral Nutrition Supplements in Hospitalized Patients.

Hospitalized patients are at an increased risk of malnutrition due to multiple factors including, but not limited to, acute and chronic diseases especially those affecting gastrointestinal tract, surgery, appetite, and frequent nil per os while undergoing diagnostic workup. Because of this, guidelines suggest the use of oral nutritional supplements (ONS) in hospitalized patients to reduce the risk of malnutrition and its complications. The current report aims to highlights key findings from a cross-sectional survey of 99 hospitalized patients who were at risk for or diagnosed with malnutrition and prescribed ONS. Data regarding ONS prescriber information as well as number ordered and consumed were collected. Of the 2.4 ± 1.5 supplements ordered per person each day, only 1.3 ± 1.1 were consumed, and there was 48% wastage of prescribed ONS. However, dietitian involvement was associated with significant reduction in wastage. Given the need and benefit, it is imperative for the nutrition community to further explore best practices to improve ONS consumption.

Better together: Coalitions committed to advancing health equity.

The Future of Nursing 2020-2030 report identifies coalitions as a driving force for advancing health equity. Five coalitions provided insight into their accomplishments, lessons learned, and role in advancing health equity. The exemplar coalitions included Latinx Advocacy Team and Interdisciplinary Network for COVID-19, Black Coalition Against COVID, Camden Coalition, National Coalition of Ethnic Minority Nurse Associations, and The Future of Nursing: Campaign for Action. While all exemplar coalitions, credited relationship building and partnerships to their success, they used unique strategies for striving to meet their populations' needs, whether the needs arose from COVID-19, racial and/or ethnic disparities, socioeconomic disparities, or other barriers to health. Research and policy implications for coalitions are discussed. Nurses play a critical role in every highlighted coalition and in the national effort to make health and health care more equitable.

Copper stabilizes antiparallel ß-sheet fibrils of the amyloid ß40 (Aß40)-Iowa variant.

Cerebral amyloid angiopathy (CAA) is a vascular disorder that primarily involves deposition of the 40-residue-long ß-amyloid peptide (Aß40) in and along small blood vessels of the brain. CAA is often associated with Alzheimer's disease (AD), which is characterized by amyloid plaques in the brain parenchyma enriched in the Aß42 peptide. Several recent studies have suggested a structural origin that underlies the differences between the vascular amyloid deposits in CAA and the parenchymal plaques in AD. We previously have found that amyloid fibrils in vascular amyloid contain antiparallel ß-sheet, whereas previous studies by other researchers have reported parallel ß-sheet in fibrils from parenchymal amyloid. Using X-ray fluorescence microscopy, here we found that copper strongly co-localizes with vascular amyloid in human sporadic CAA and familial Iowa-type CAA brains compared with control brain blood vessels lacking amyloid deposits. We show that binding of Cu(II) ions to antiparallel fibrils can block the conversion of these fibrils to the more stable parallel, in-register conformation and enhances their ability to serve as templates for seeded growth. These results provide an explanation for how thermodynamically less stable antiparallel fibrils may form amyloid in or on cerebral vessels by using Cu(II) as a structural cofactor.

Adult Population Coverage With Influenza Vaccine and Influenza Hospitalization Rates-Is There a Role for Active Outreach to Immunize At-Risk Neighborhoods?

We evaluated whether Denver neighborhoods with elevated rates of adult hospitalizations for laboratory-confirmed influenza had lower adult coverage with influenza vaccine. Overall vaccine coverage was low. Hospitalization rates were associated with demographic and socioeconomic characteristics. Active immunization of at-risk neighborhoods may be necessary to address disparities in influenza hospitalization rates.

A knowledge-based, structural-aided discovery of a novel class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors.

Through an internal virtual screen at GlaxoSmithKline a distinct class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors were discovered. Careful evaluation of crystal structures and SAR led to a novel, potent, and orally active imidazopyridine inhibitor of H-PGDS, 20b. Herein, describes the identification of 2 classes of inhibitors, their syntheses, and their challenges.