Search

Vaccination remains key to reducing the risk of COVID-19–related severe illness and death. Because of historic medical exclusion and barriers to access, Black communities have had lower rates of COVID-19 vaccination than White communities. We describe the efforts of an academic medical institution to implement community-based COVID-19 vaccine clinics in medically underserved neighborhoods in Philadelphia, Pennsylvania. Over a 13-month period (April 2021–April 2022), the initiative delivered 9038 vaccine doses to community members, a majority of whom (57%) identified as Black. (Am J Public Health. 2022;112(12):1721–1725. https://doi.org/10.2105/AJPH.2022.307030 )

PURPOSE: We undertook a study to examine how stigma influences the uptake of training on medication for opioid use disorder (MOUD) in primary care academic programs. METHODS: We conducted a qualitative study of 23 key stakeholders responsible for implementing MOUD training in their academic primary care training programs that were participants in a learning collaborative in 2018. We assessed barriers to and facilitators of successful program implementation and used an integrated approach to develop a codebook and analyze the data. RESULTS: Participants represented the family medicine, internal medicine, and physician assistant fields, and they included trainees. Most participants described clinician and institutional attitudes, misperceptions, and biases that enabled or hindered MOUD training. Perceptions included concerns that patients with OUD are “manipulative” or “drug seeking.” Elements of stigma in the origin domain (ie, beliefs by primary care clinicians or the community that OUD is a choice and not a disease), the enacted domain (eg, hospital bylaws banning MOUD and clinicians declining to obtain an X-Waiver to prescribe MOUD), and the intersectional domain (eg, inadequate attention to patient needs) were perceived as major barriers to MOUD training by most respondents. Participants described strategies that improved the uptake of training, including giving attention to clinician concerns, clarifying the biology of OUD, and ameliorating clinician fears of being ill equipped to provide care for patients. CONCLUSIONS: OUD-related stigma was commonly reported in training programs and impeded the uptake of MOUD training. Potential strategies to address stigma in the training context, beyond providing content on effective evidence-based treatments, include addressing the concerns of primary care clinicians and incorporating the chronic care framework into OUD treatment.

ImportanceThe COVID-19 pandemic has claimed nearly 6 million lives globally as of February 2022. While pandemic control efforts, including contact tracing, have traditionally been the purview of state and local health departments, the COVID-19 pandemic outpaced health department capacity, necessitating actions by private health systems to investigate and control outbreaks, mitigate transmission, and support patients and communities.ObjectiveTo investigate the process of designing and implementing a volunteer-staffed contact tracing program at a large academic health system from April 2020 to May 2021, including program structure, lessons learned through implementation, results of case investigation and contact tracing efforts, and reflections on how constrained resources may be best allocated in the current pandemic or future public health emergencies.Design, Setting, and ParticipantsThis case series study was conducted among patients at the University of Pennsylvania Health System and in partnership with the Philadelphia Department of Public Health. Patients who tested positive for COVID-19 were contacted to counsel them regarding safe isolation practices, identify and support quarantine of their close contacts, and provide resources, such as food and medicine, needed during isolation or quarantine.ResultsOf 5470 individuals who tested positive for COVID-19 and received calls from a volunteer, 2982 individuals (54.5%; median [range] age, 42 [18-97] years; 1628 [59.4%] women among 2741 cases with sex data) were interviewed; among 2683 cases with race data, there were 110 Asian individuals (3.9%), 1476 Black individuals (52.7%), and 817 White individuals (29.2%), and among 2667 cases with ethnicity data, there were 366 Hispanic individuals (13.1%) and 2301 individuals who were not Hispanic (82.6%). Most individuals lived in a household with 2 to 5 people (2125 of 2904 individuals with household data [71.6%]). Of 3222 unique contacts, 1780 close contacts (55.2%; median [range] age, 40 [18-97] years; 866 [55.3%] women among 1565 contacts with sex data) were interviewed; among 1523 contacts with race data, there were 69 Asian individuals (4.2%), 705 Black individuals (43.2%), and 573 White individuals (35.1%), and among 1514 contacts with ethnicity data, there were 202 Hispanic individuals (12.8%) and 1312 individuals (83.4%) who were not Hispanic. Most contacts lived in a household with 2 to 5 people (1123 of 1418 individuals with household data [79.2%]). Of 3324 cases and contacts who completed a questionnaire on unmet social needs, 907 (27.3%) experienced material hardships that would make it difficult for them to isolate or quarantine safely. Such hardship was significantly less common among White compared with Black participants (odds ratio, 0.20; 95% CI, 0.16-0.25).Conclusions and RelevanceThese findings demonstrate the feasibility and challenges of implementing a case investigation and contact tracing program at an academic health system. In addition to successfully engaging most assigned COVID-19 cases and close contacts, contact tracers shared health information and material resources to support isolation and quarantine, thus filling local public health system gaps and supporting local pandemic control.

BACKGROUND Limited data describe poisoning exposures in pregnant women. Previous studies are limited to inpatient populations, those seen only by toxicologists, or single poison centers. This study aimed to describe poison exposures reported to U.S. poison control centers in pregnant patients compared to non-pregnant controls. METHODS This was a retrospective observational study of exposures reported to the American Association of Poison Control Centers National Poison Data System from 2000 through 2019. Pregnant patients were included from 15-44 years along with a random sampling of 5:1 age and year matched control group of non-pregnant exposures. Demographics, primary substance, and known medical outcomes were described. Chi square analysis was performed for comparisons. RESULTS From 2000 to 2019, a total of 131,619 pregnant cases and 658,095 non-pregnant controls were identified. The median age was 27 years (IQR: 22, 31) for the matched groups. For known trimester of pregnancy: 29.8, 37.0, and 28.2% were in the first, second, and third trimester, respectively. Most common exposures were analgesics and cleaning products. Intentional exposures were more common in non-pregnant compared to pregnant cases (41.2 vs 21.9%; OR 2.71, 95% CI 2.67-2.75), mostly self-harm attempts (31.5 vs. 15.8%). Notably, there was a large discrepancy in the proportion of environmental exposures, with fewer in non-pregnant controls compared with pregnant cases (3.8 vs. 12.1%; OR 0.29, 95% CI 0.28-0.29). More non-pregnant cases had multiple substance exposures compared with pregnant cases (22.2 vs. 10.9%; OR 2.34, 95% CI 2.29-2.38). There were more moderate effect outcomes in non-pregnant compared with pregnant cases (13.2 vs. 6.3%; OR 2.25, 95% CI 2.20-2.30). CONCLUSIONS Outcomes of poisoning exposures in pregnant patients reported to U.S. poison centers are less serious compared to non-pregnant controls, likely due to the lower rates of intentional abuse and self-harm exposures and greater number of minimally toxic environmental exposures.

Drug overdose death rates from opioid use have risen steadily since 1999 and reached epidemic levels, slowing for the first time in 2018, though not for many forms of opioid use. Yet evidence-based approaches to combating OUD, such as medication-assisted treatment for OUD (MT-OUD), are still inaccessible to many. Primary care providers are well-positioned to offer these services; however, training and education in OUD care remains inadequate. The National Center for Integrated Behavioral Health interviewed the Health Resources Service Administration (HRSA) awardees of federal funding to implement an MT-OUD curriculum in their primary care residency training programs to identify barriers and facilitators to implementation. Awardees were interviewed at program launch and one year later. Results showed the importance of leadership willingness to participate, effective treatment integration into existing workflow, curriculum and clinical flexibility, and supportive interdisciplinary and community partnerships. Recommendations for best practices of MT-OUD training in primary care are identified.

In his insightful monograph on Don Juan, Bernard Beatty emphasises the discursive nature of the poem which ‘invokes such diverse categories as epic, comedy, satire, romance, burlesque and novel’.1 ...

Please download the article PDF or view it in HTML.

Treatment regimens of pancreatic ductal adenocarcinoma (PDAC) are limited and minimally effective which potentiates the importance of discovering novel potential drug targets. We discovered widespread dysregulation of alternative polyadenylation (APA) in PDAC patients. APA is a pre-mRNA processing mechanism that generates mRNAs isoforms with distinct 3’ untranslated regions (3’UTRs). These isoforms contribute to the expression and function of mRNAs and proteins. Our recent study revealed that APA alterations in PDAC drive dysregulation of PDAC-promoting genes and present a reliable prognostic marker. APA is controlled by a suite of genes, including cleavage and polyadenylation specificity factor 3 (CPSF3). Because CPSF3 is the endonuclease that catalyzes mRNA cleavage, we here sought to target CPSF3 in PDAC. We show that CPSF3 expression is significantly upregulated and associated with unfavorable prognosis in PDAC patients. Loss of CPSF3 decreases PDAC cell proliferation, clonogenicity and tumor growth. We show that CPSF3 loss causes APA changes of tumor-associated genes and validate the tumor suppressing activity of one APA-altered gene, FHL1. Using JTE-607, a chemical inhibitor of CPSF3, we find that PDAC cells are preferentially sensitive while non-transformed cell lines are resistant to CPSF3 inhibition. Notably, we show that JTE-607 decreases proliferation-dependent histone expression and disrupts nucleosome assembly. Finally, we find that JTE-607 arrests cells in early to mid S-phase of the cell cycle, resembling histone defect-induced cell cycle arrest. Overall, we reveal alternative polyadenylation and histone processing as two distinct mechanisms underlying CPSF3-induced attenuation of cell proliferation and identify CPSF3 as a potential therapeutic target in PDAC. Citation Format: Abdulrahman A. Alahmari, Aditi Chaubey, Arwen Tisdale, Carla Schwarz, Abigail Cornwell, Kathryn Maraszek, Emily Paterson, Minsuh Kim, Swati Venkat, Eduardo Cortes Gomez, Jianmin Wang, Katerina Gurova, Michael E. Feigin. Inhibition of CPSF3 attenuates pancreatic cancer cell proliferation through disruption of histone processing [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B042.

Endometrial cancer (EC) is the most common gynaecological malignancy in the developed world, and concerningly incidence is rising, particularly in younger people. Therefore, there is increased interest in novel diagnostic and prognostic biomarkers. Extracellular vesicles (EVs) are membrane-bound particles present in bodily fluids that have the potential to facilitate non-invasive, early diagnosis of EC and could aid with monitoring of recurrence and treatment response. EV cargo provides molecular insight into the tumor, with the lipid bilayer providing stability for RNA species usually prone to degradation. miRNAs have recently become a focus for EV biomarker research due to their ability to regulate cancer related pathways and influence cancer development and progression. This review evaluates the current literature on EV miRNA biomarkers with a focus on EC, and discusses the challenges facing this research. This review finally highlights areas of focus for EV miRNA biomarker research going forward, such as standardization of normalization approaches, sample storage and processing, extensive reporting of methodologies and moving away from single miRNA biomarkers.

This is the first of a series of short guidance pieces on international academic standards which the Sudan Journal of Medical Sciences will be producing for researchers over the coming year. As the Senior Editor at KnE Publishing, I am honoured to have been invited to write the inaugural guest editorial in this series.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with few effective treatment options. Therefore, the need for new therapeutic interventions is urgent. Recently, we have revealed that the gene regulatory process alternative polyadenylation (APA) is highly dysregulated in PDAC patients. APA is a co-transcriptional process that generates distinct transcript isoforms with different 3’ untranslated region (UTR) length, which regulates mRNA stability and gene and protein expression. We found that APA promotes dysregulation of PDAC-promoting genes, predicts poor prognosis in PDAC patients and identified a novel APA-regulated drug target (Venkat et al., Genome Research, 2020). These findings raise the question of whether targeting APA could be a viable therapeutic strategy for PDAC treatment. APA is controlled by a large protein complex assembled on the pre-mRNA, including the cleavage and polyadenylation specificity factor 3 (CPSF3). CPSF3 is an endonuclease that cleaves the pre-mRNA before addition of the polyA tail. Notably, CPSF3 is also a subunit of the histone pre-mRNA processing complex and is critical for the cleavage and processing of core histones. Recently, it was determined that JTE-607, a drug with a long history of safety in humans but no known mechanism of action, is a CPSF3 inhibitor. Subsequently, CPSF3 has been shown to be required for growth of acute myeloid leukemia and Ewing sarcoma cells. However, whether CPSF3 is a potential target in adenocarcinoma is yet to be explored. In PDAC patients, CPSF3 is highly expressed and is associated with unfavorable prognosis. Knockdown or inhibition of CPSF3 decreases PDAC cell proliferation and clonogenicity while having no effect on the growth of non-transformed pancreatic cell lines. Cell cycle analysis and BrdU incorporation assays determined that CPSF3 inhibition arrests cells in early S-phase of the cell cycle. As maintenance of high histone levels are important for the packaging of newly synthesized DNA and progression through the cell cycle, we hypothesized that CPSF3 inhibition decreases PDAC cell proliferation by reducing histone levels. Indeed, CPSF3 inhibition decreased core histone protein levels in a time- and dose-dependent manner. High throughput screening revealed a synergistic effect between JTE-607 and Abexinostat, an HDAC inhibitor, suggesting a novel therapeutic strategy. Therefore, we identify CPSF3 as a druggable target in PDAC and reveal a novel mechanism by which CPSF3 disruption attenuates cell proliferation. Citation Format: Abdulrahman A. Alahmari, Carla Schwarz, Emily Paterson, Swati Venkat, Arwen Tisdale, Michael E. Feigin. CPSF3 inhibition halts pancreatic cancer cell proliferation by limiting core histone supplies [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-034.

OBJECTIVE: Little research has focused on the treatment of adults with substance use disorders in primary care despite the high occurrence, morbidity, and mortality associated with these disorders. METHODS: A survey was administered to primary care providers to assess screening and treatment practices and comfort managing opioid use, alcohol use, and depressive disorders. A total of 146 providers completed the survey. RESULTS: Providers were significantly less likely to screen for or treat both opioid use disorders and alcohol use disorders relative to depression. Similarly, providers were significantly less confident, reported feeling less prepared, less expected to treat, less sure of the appropriateness of treating, and less able to navigate community resources in the treatment of opioid and alcohol use disorders relative to depression. CONCLUSIONS: Given the preponderance of substance use disorders among primary care patients, increased attention to equipping primary care providers to treat these conditions is warranted.

Byron often sneered at ‘S[outhey]’s unsaleables’, particularly Thalaba the Destroyer . Indeed, he states in one footnote that Thalaba will never be read until all great works are gone and forgotten. However, despite the frequent animadversions upon Thalaba and its author, Byron was not averse to appropriating ideas and images from the poem. This article examines a previously unconsidered instance of this, discussing how Byron’s presentation of the Upas Tree in Childe Harold’s Pilgrimage owes far more to Southey’s depiction of the myth than it does to Erasmus Darwin’s ‘Loves of the Plants’ (as has been previously supposed). Southey could, in turn, have been influenced by Byron’s reconfiguration of his own style and imagery, and the parallels between Childe Harold Canto IV, 126 and Southey’s later use of the Upas motif in A Tale of Paraguay Canto 3, 2 are striking.

After a swift re-shuffle of parts due to late arrivals, the Nottingham Byron Confer- ence started with the annual evening poetry reading. This year's poem was Byron's Siege of Corinth, and after Bernard Beatty stepped into the breach with a sprightly and surprisingly feminine performance, the evening went smoothly, bar a brief struggle between Peter Cochran and Peter Francev over whose lines were whose. Afterwards the conference attendees enjoyed a supper and became increasingly raucous as the evening progressed.The following morning, somewhat worse for wear, there was a small delay due to road closures, and the opening plenary took place in our hotel rather than at Nottingham Trent University. This was given by Stephen Minta (York), who provided a detailed and wide-ranging insight into the role of nostalgia in Byron's writings, linking the poet's fears of incipient middle age and mental decline with reminiscences of his bygone social glories when lionised in London. Minta considered various definitions of this nostalgia, variously interpreted as a disease, the hope of return to a former state, home- sickness, bygone friendships, the innocence of childhood, and the fantasy of returning to Eden or an Edenic state. Focusing on Byron's earlier works, Minta examined the association of death and rejection with nostalgia, and Byron's presentation of nostalgia as a form of therapy triggered by both pain and pleasure, before turning his attention to the central role Greece played both in Byron's pervasive nostalgia and the nineteenth century public en mass.After overcoming various traffic obstructions and delays, the attendees were at last able to get to the aptly named Ada Byron King building for the main body of the conference. The first session opened with Christine Kenyon Jones's (King's College London) consideration of the deliberately 'Romantic' aspects of the numerous portraits of Byron which both created and sustained his public persona. These included those creations favoured by Byron such as that of the windswept adventurer, the carefully posed dandy, against the backdrop of naval settings and gothic landscapes. This was followed by a discussion of Byron's inability to control his public image and his futile attempts to stop the proliferation of pictorial personas which did not meet with his approval. In particular, Murray's repeated commissioning of images of Byron as the louche yet tortured poet en dishabilles, and engravings in pirated editions of his poems which presented a more satanic, debauched figure, complete with sullen frown, length- ened nose and pointed chin. Monika Coghen (Krakow) followed with an inspection of the role played by publishers and editors, writers and poets, in Byron's evolution into the central Romantic poet on the Continent, paying particular attention to Byron's influence on authors such as de Stael and Stendhal, and how their perceptions of Byron, reflected in their works, entered the wider European consciousness. Agustin Coletes Blanco (Oviedo) continued this theme in his amusing and unusual discussion of the interrelation of the concepts of lost or fictional papers and fictional Byron. He revealed the presence of these concepts in works ranging from literary stalwarts such as Henry James's The Aspern Papers, to Robert Nye's provocative first-person presentation of Byron's sexual exploits in The Memoirs of Lord Byron, and Tom Holland's The Vampire: The Secret History of Lord Byron, in which Byron is discovered to still be among us as a member of the un-dead fraternity.The parallel session 2A, chaired by Agustin Coletes Blanco, opened with Peter Francev's (Leicester) argument that, far from emulating Wordsworth's veneration of nature, Childe Harold's Pilgrimage Canto III is rather a challenge to the reverential Wordsworthian stance. Instead, Canto III is a reflection of the exuberant joy inspired by the power of nature's overwhelming vastness which takes hold of Byron. Francev argued that much of the text exhibits Byronic transcendence rather than Wordsworth's transcendentalism as seen in 'Tintern Abbey'. …

‘I am not a Manichean - nor an Any-chean’ stated Byron during the furore surrounding his poem Cain: A Mystery. Yet many still insisted on ‘accusing [him] of irreligion’, labelling him an ‘infidel’ because of the presence of heresy in his poetry. Assuming for the moment that these allegations were based on actual heretical doctrines present in his poems, from where did Byron gain his extensive knowledge? There is one source which has not been considered, which is Byron's translations of 3 Corinthians and its companion Epistle from the Corinthians, found in the Armenian Apocrypha, but not in the Bibles of Western Christianity. This article examines the importance of these Armenian translations with relation to Byron's understanding of heretical doctrines. It also contains passages from the diary of his Armenian tutor, Pascal Aucher, which have not previously been translated into English, providing a fascinating insight into Byron's interaction with these Epistles.

It is the inherent ambiguity of the imagery in Genesis 3.24 and Matthew 10.34 that provides the focus of this article, addressing the theme of Sacred and Sacrilegious by investigating how these biblical passages were used to express negative apprehensions of God and Christianity. The poets Lord Byron, Percy Bysshe Shelley, and Thomas Love Peacock, along with the artist J.M.W. Turner, take the sacred images of the Sword of God and the avenging angel, literal representations of the Glory of God, and reinterpret them in a sacrilegious manner.

Our viewpoint this issue is a collection of personal experiences of these who spoke in the New Voices category at the IMI conference 2010.Though I am a general clinical photographer my particular i...