PfSPZ Vaccine induces focused humoral immune response in HIV positive and negative Tanzanian adults.

BACKGROUND: PfSPZ Vaccine, a promising pre-erythrocytic stage malaria vaccine candidate based on whole, radiation-attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), has proven safe and effective in mediating sterile protection from malaria in malaria-naïve and exposed healthy adults. Vaccine-induced protection presumably depends on cellular responses to early parasite liver stages, but humoral immunity contributes. METHODS: On custom-made Pf protein microarrays, we profiled IgG and IgM responses to PfSPZ Vaccine and subsequent homologous controlled human malaria infection (CHMI) in 21 Tanzanian adults with (n = 12) or without (n = 9) HIV infection. Expression of the main identified immunogens in the pre-erythrocytic parasite stage was verified by immunofluorescence detection using freshly purified PfSPZ and an in vitro model of primary human hepatocytes. FINDINGS: Independent of HIV infection status, immunisation induced focused IgG and IgM responses to circumsporozoite surface protein (PfCSP) and merozoite surface protein 5 (PfMSP5). We show that PfMSP5 is detectable on the surface and in the apical complex of PfSPZ. INTERPRETATION: Our data demonstrate that HIV infection does not affect the quantity of the total IgG and IgM antibody responses to PfCSP and PfMSP5 after immunization with PfSPZ Vaccine. PfMSP5 represents a highly immunogenic, so far underexplored, target for vaccine-induced antibodies in malaria pre-exposed volunteers. FUNDING: This work was supported by the Equatorial Guinea Malaria Vaccine Initiative (EGMVI), the Clinical Trial Platform of the German Center for Infection Research (TTU 03.702), the Swiss Government Excellence Scholarships for Foreign Scholars and Artists (grant 2016.0056) and the Interdisciplinary Center for Clinical Research doctoral program of the Tübingen University Hospital. The funders had no role in design, analysis, or reporting of this study.

Long Term Impact of Regionalization of Thoracic Oncology Surgery.

BACKGROUND: In 2007, Cancer Care Ontario created Thoracic Surgical Oncology Standards for the delivery of surgery including lobectomy, esophagectomy and pneumonectomy. These standards regionalized thoracic surgery into designated centers and mandated physical and human resources. This analysis seeks to identify the impact of these standards, hereafter referred to as "regionalization", on outcomes after thoracic oncology surgery in Ontario, Canada. METHODS: Population-level analysis of patients undergoing lobectomy, esophagectomy or pneumonectomy, using multi-level regression models to compare 30- and 90-day mortality and length of stay length of stay, before, during and after regionalization. Interrupted time series models were used to assess for an impact of regionalization, controlling for ongoing trends. RESULTS: A total of 22,195 surgeries (14,902 lobectomies, 4,958 esophagectomies, and 2,408 pneumonectomies) were performed within the study period. >99% of cases were performed at a designated center post-regionalization. Mean annual volumes per designated center increased post-regionalization for lobectomy and esophagectomy, and decreased for pneumonectomy. 30- and 90-day mortality and length of stay improved for lobectomy and esophagectomy over the study period, as did 90-day mortality for pneumonectomy. However, the interrupted time series analysis did not demonstrate any statistically significant effect of regionalization on these outcomes, separate from pre-existing trends. CONCLUSIONS: Consistent improvements in mortality and length of stay in thoracic surgical oncology occurred on a provincial level between 2003-2020, although this analysis does not attribute these improvements to implementation of Thoracic Surgical Oncology Standards including regionalization.

Educational priorities of low-and middle-income country medical diaspora organisations: A critical discourse analysis.

Rising global migration levels have led to growing diaspora populations. There has been interest in the role of diaspora healthcare professionals (HCPs) from low- and middle-income countries (LMICs) in development aid to their origin countries, although there has been comparatively less focus on their educational activities. This study examined the stated educational priorities of LMIC medical diaspora organisations, with a particular focus on the tension between promoting professional opportunities afforded by medical migration and contributing to healthcare workforce shortages due to migration away from LMICs.We gathered a textual archive from webpages and public documents of 89 LMIC medical diaspora organisations in high income countries, predominantly the US and UK. We employed Foucauldian critical discourse analysis to examine presented rationales around educational policies and practices, with a focus on encouragement towards, and discouragement from, medical migration. Two discourses dominated this archive. The first was of preservation and framed the educational work of these organisations as a means of providing unity and social networks to diaspora HCPs, with a focus on maintaining their cultural identity and heritage, and medical connections with their origin countries. The second was of aspiration and framed their educational work as providing support to diaspora HCPs to advance their careers and maximise training opportunities, often through directly enabling and supporting migration to high income countries. There was a discursive absence around brain drain with no policies or practices that overtly sought to deter against, or offset the negative effects of, medical migration. Notwithstanding the valuable contributions that LMIC medical diaspora organisations make in global health, the discursive framings that shape their educational work are linked primarily to protecting and progressing diaspora HCPs rather than on LMIC workforce challenges. Further research is needed to examine potential impacts of these positions on HCP migratory behaviours.

The natural history of isolated common femoral endarterectomy for chronic limb-threatening ischemia.

OBJECTIVE: Occlusive disease of the common femoral artery can generate profound lower extremity ischemia as the normal collateral pathways from the profunda to the superficial femoral artery cannot adequately develop. In patients with lifestyle-limiting claudication, isolated common femoral endarterectomy (CFE) is highly effective. Because CFE does not provide direct, in-line flow to the plantar arch, it has been felt to provide inadequate revascularization to patients with chronic limb-threatening ischemia (CLTI). The purpose of this retrospective clinical study was to report and assess the natural history of selected patients with CLTI treated with isolated CFE (without concomitant infrainguinal revascularization). METHODS: Consecutive CFEs performed in a large, urban hospital for CLTI between 2014 and 2021 were reviewed. Patient characteristics, limb, and anatomical stages using the Wound, Ischemia, foot Infection (WIfI) and Global Limb Anatomic Staging System were tabulated. Limb-specific and survival-related end points were analyzed. RESULTS: Fifty-eight patients presenting with CLTI underwent isolated CFE (mean age, 74 ± 10 years; 62% male, 90% current or prior smoker). Comorbidities included diabetes (52%), coronary artery disease (55%), congestive heart failure (22%), and end-stage renal failure on hemodialysis (5%). Patients presented with either rest pain (36%) or tissue loss (64%); the latter group exhibited advanced limb threat (68% in WIfI stage 3 or 4). The majority of patients had associated severe infrainguinal disease (50% Global Limb Anatomic Staging Systems 3). After a median follow-up of 17 months (range, 10-29 months), vascular reintervention was required in 7 patients (12%). One patient (2%) required major limb amputation after presentation in WIfI stage 4 (W3I3fI0). Indeed, WIfI stage 4 was a significant univariate predictor of the need for subsequent infrainguinal bypass (P = .034). CONCLUSIONS: Isolated CFE as primary therapy in highly selected patients with CLTI was safe and effective. Index limb stage is predictive of the need for associated infrainguinal revascularization in this complex population.

Power and place: Uncovering the politics of global medical education.

CONTEXT: Politics is characterised by power relations, and the deployment of power is inescapably political. In an increasingly globalised and interconnected modern world, politics is shaping the field of medical education more than ever before. Global frameworks that classify peoples and places are political tools that are fundamentally shaped by hegemonic knowledge systems. Despite this, they continue to form the basis for global thinking and practices, including in medical education. Political analysis can help to expose and challenge such thinking. APPROACH: To better understand impacts of globalisation in medical education, we explore the previously under-examined political dimensions that underpin it, focusing particularly on deconstructing power relations. We situate our analysis of global medical education in political terms, including through examination of ideology, economics, market and the enduring effects of colonialism. We interrogate the construct of the Global South (GS), considering the geopolitical and historical ideas that have enabled it to be widely propagated. We go on to examine the consequences of the GS construct in medical education and consider what this tells us about how power is enacted in the field. CONCLUSIONS: In analysing the politics of global medical education, we shed light on how power is exerted and draw attention to forces that permit and enable trends, policies and positions. Notwithstanding the emancipatory rhetoric that has been associated with the GS construct, we highlight its reductive potential and argue that it can lead to an oversimplification of power relations and vested interests. Given the growing recognition that educational approaches do not transfer well across countries and cultures, we encourage the medical education community to consider why ideas from more dominant countries continue to be imitated so routinely. In doing so, we urge them to use political lenses to recognise the influence of multiple complex and interconnected forces of global power that shape all aspects of medical education.

An opportunity to be grateful for? Exploring discourses about international medical graduates from India and Pakistan to the UK between 1960 and 1980.

INTRODUCTION: Following India and Pakistan gaining independence from British colonial rule, many doctors from these countries migrated to the UK and supported its fledgling National Health Service (NHS). Although this contribution is now widely celebrated, these doctors often faced hardship and hostility at the time and continue to face discrimination and racism in UK medical education. This study sought to examine discursive framings about Indian and Pakistani International Medical Graduates (IPIMGs) in the early period of their migration to the UK, between 1960 and 1980. METHODS: We assembled a textual archive of publications relating to IPIMGs in the UK during this time period in The BMJ. We employed critical discourse analysis to examine knowledge and power relations in these texts, drawing on postcolonialism through the contrapuntal approach developed by Edward Said. RESULTS: The dominant discourse in this archive was one of opportunity. This included the opportunity for training, which was not available to IPIMGs in an equitable way, the missed opportunity to frame IPIMGs as saviours of the NHS rather than 'cheap labour', and the opportunity these doctors were framed to be held by being in the 'superior' British system, for which they should be grateful. Notably, there was also an opportunity to oppose, as IPIMGs challenged notions of incompetence directed at them. CONCLUSION: As IPIMGs in the UK continue to face discrimination, we shed light on how their cultural positioning has been historically founded and engrained in the imagination of the British medical profession by examining discursive trends to uncover historical tensions and contradictions.

Medical education needs a new model for global leadership.

BACKGROUND: Like other fields in medicine, medical education relies on collaboration and cooperation between countries and regions of the world, although no single institution or position unifies the global medical education community in the way that the WHO does in public health, for example. Recent research in medical education has drawn attention to many injustices that exist in the field, where power and influence is held in relatively few Global North countries, although most practice happens in Global South countries. METHODS: In this article, we examine three positions that hold global prominence in medical education, including the presidents of the World Federation for Medical Education and the Association for Medical Education in Europe, and winners of the Karolinska Institutet Prize for Research in Medical Education. FINDINGS: We highlight that these positions have problematic histories and have perpetuated the current power disparities in the field. We argue that an alternative model for global leadership is required that should be determined democratically by those involved in medical education all around the world. Such a model should prioritise diversity and inclusivity, empowering leaders from countries who have previously been peripheral to the decision-making platforms in the field. CONCLUSION: Given the shortcomings of existing leadership positions and organisations, we suggest that a new institution is required to realise this new vision, and that the principles that govern it should be determined through debate and democracy, with a focus on inviting those voices that have not previously been heard in global medical education circles.

Pilot deployment of a community health care worker in distributing and offering the COVID-19 AgRDT in Tanzania.

A pilot implementation of the rapid diagnostic test program was performed to collect evidence of the feasibility, acceptability, and uptake of the COVID-19 AgRDT in Tanzania. We conducted a prospective cross-sectional study in the community to provide quantitative details of the pilot implementation of the antigen rapid diagnostic test (AgRDT) in Tanzania. This study was undertaken between March 2022 and September 2022. The pilot was implemented by distributing and offering test kits to people suspected of having COVID-19 in Dar es Salaam through community health workers. A total of 1039 participants consented to participate in the survey. All the participants reported having heard about the disease. The radio was the main source (93.2%) of information on COVID-19. With regard to prevention measures, approximately 930 (89.5%) of the respondents thought that COVID-19 could be prevented. Approximately 1035 (99.6%) participants reported that they were willing to have a COVID-19 AgRDT test and wait for 20 min for the results. With regard to the participants' opinions on the AgRDT device, the majority 907 (87.3%) felt comfortable with the test, and 1,029 (99.0%) were very likely to recommend the AgRDT test to their friends. The majority of participants 848 (83.1%) mentioned that they would be willing to pay for the test if it was not available for free. The results suggest overall good acceptance of the COVID-19 AgRDT test. It is evident that the use of trained community healthcare workers allows easy screening of all possible suspects and helps them receive early treatment.

Moving Together, Apart: Impacts of Travel Restrictions on a UK-Egypt Collaboration in Health Profession Education.

Objective: University College London (UCL) and Newgiza University (NGU) have been in an academic collaboration since 2016 to establish undergraduate healthcare programmes in Egypt with an underlying ethos of capacity building and co-development. We explored impacts of pandemic-related travel restrictions on staff across both organisations. Methods: We conducted 30 semi-structured interviews with academic and professional services staff from UCL and NGU schools of medicine, dentistry, and pharmacy. Data were jointly coded using reflexive thematic analysis and categorised according to the American Council on Education's Comprehensive Internationalisation Framework. Results: Nine themes were identified, which related to each of the six components of the framework. In addition to mobility, participants' experiences also spread across the other five components (institutional commitment, leadership, curriculum, faculty support, and partnerships). Successful adaptations were made and staff felt able to 'keep the show on the road'. However, staff remained keen to keep in-person engagement a priority when possible, especially for quality management site visits. Conclusions: Travel restrictions can have widespread impacts on all aspects of international collaborations. In this well-established relationship, there was sufficient resilience to withstand these impacts and, many positive unintended consequences emerged. A hybrid engagement model should be prioritised in future partnerships.

Assessing the Impact of Smoking Cessation Interventions on Periodontal Health and Gingival Inflammation in Smokers with Periodontitis.

Background: Smoking is a well-established risk factor for periodontitis, a chronic inflammatory disease of the oral cavity. While smoking cessation has been linked to improved overall health, its specific impact on periodontal health and gingival inflammation in individuals with periodontitis remains less explored. Materials and Methods: We conducted a prospective cohort study involving 200 smokers diagnosed with periodontitis. Participants were divided into two groups: Group A received comprehensive smoking cessation interventions, including counseling and pharmacotherapy, while group B continued smoking without intervention. Periodontal health was assessed through clinical parameters, including probing depth (PD) and clinical attachment level (CAL), at baseline and 6 months post intervention. Gingival inflammation was evaluated using the Gingival Index (GI). Results: After 6 months, group A exhibited a significant reduction in mean PD (from 4.5 mm to 3.2 mm) and CAL (from 5.0 mm to 3.5 mm) compared to group B. Conversely, group B showed no significant change in these parameters. The GI score significantly decreased in group A (from 2.8 to 1.2) but remained unchanged in group B. Furthermore, group A demonstrated a higher rate of smoking cessation (72%) compared to group B (14%). Conclusion: Smoking cessation interventions play a crucial role in improving periodontal health and reducing gingival inflammation in smokers with periodontitis. The observed reductions in PD, CAL, and gingival inflammation highlight the potential benefits of smoking cessation on oral health outcomes in this high-risk population.

Comparison of Different Suturing Techniques in Post-Extraction Socket Healing.

Background: The process of post-extraction socket healing is critical for ensuring proper tissue repair and minimizing complications in dental practice. Suturing techniques play a pivotal role in this process, influencing wound closure, hemostasis, and overall healing. Materials and Methods: This prospective clinical trial involved 80 participants who required single-tooth extractions. Patients were randomly assigned to four groups, each receiving a distinct suturing technique: simple interrupted sutures, horizontal mattress sutures, vertical mattress sutures, and continuous sutures. Standardized assessments, including clinical examination and cone-beam computed tomography (CBCT) scans, were performed at baseline, 1 week, and 4 weeks post-extraction. Wound dehiscence, soft tissue healing, and bone preservation were evaluated. Results: At 1-week post-extraction, the continuous suture group exhibited the lowest rate of wound dehiscence (5%) compared to other groups (simple interrupted, 15%; horizontal mattress, 10%; vertical mattress, 12%). Soft tissue healing scores at 4 weeks were significantly higher in the continuous suture group (8.7 ± 0.5) than in the other groups (simple interrupted, 7.2 ± 0.8; horizontal mattress, 7.8 ± 0.7; vertical mattress, 7.5 ± 0.6). CBCT analysis revealed superior bone preservation in the continuous suture group (98% remaining bone volume) compared to the other groups (simple interrupted, 92%; horizontal mattress, 95%; vertical mattress, 94%). Conclusion: This study demonstrates that the continuous suturing technique offers advantages in post-extraction socket healing, including reduced wound dehiscence, improved soft tissue healing, and better bone preservation.

Surgical vs. Non-Surgical Management of Temporomandibular Joint Disorders: Clinical Outcomes.

Background: Temporomandibular joint disorders (TMDs) encompass a range of clinical conditions affecting the temporomandibular joint (TMJ) and associated structures. Management approaches for TMDs vary and include both surgical and non-surgical interventions. Materials and Methods: In this retrospective cohort study, medical records of 150 patients diagnosed with TMDs were reviewed. Patients were categorized into two groups: surgical intervention and non-surgical intervention. The surgical group underwent various surgical procedures, including arthroscopy, arthroplasty, and joint replacement, while the non-surgical group received conservative treatments such as physical therapy, pharmacotherapy, and occlusal splints. Pain levels, TMJ function, quality of life (QoL), and patient satisfaction were assessed at baseline and post-treatment (6 months and 1 year). Results: At the 6-month follow-up, both groups experienced a significant reduction in pain scores (surgical group: 6.3 ± 1.2 to 2.4 ± 0.9, non-surgical group: 6.1 ± 1.1 to 3.2 ± 1.0). TMJ function improved in both groups (surgical group: 2.5 ± 0.8 to 4.8 ± 0.6, non-surgical group: 2.6 ± 0.7 to 4.2 ± 0.9). QoL scores increased (surgical group: 35.2 ± 4.6 to 50.3 ± 5.1, non-surgical group: 35.5 ± 4.2 to 45.7 ± 4.8), and patient satisfaction rates were high (surgical group: 92%, non-surgical group: 87%) at the 1-year follow-up. Conclusion: Both surgical and non-surgical management approaches demonstrated significant improvements in pain relief, TMJ function, QoL, and patient satisfaction for individuals with TMDs.

Prenatal incidence of cleft lip/palate and cocaine abuse in parents: a systematic review and meta-analysis.

BACKGROUND: The study aimed to investigate the association between maternal cocaine abuse during pregnancy and the prevalence of cleft lip/palate (CL/P) in offspring, synthesizing existing evidence through a systematic review and meta-analysis. CL/P is a congenital craniofacial anomaly with complex etiology, and prior research has suggested potential links between maternal cocaine use and CL/P. However, these associations remain inconclusive. METHODS: A comprehensive literature search was conducted to identify relevant studies published up to the study's cutoff date in September 2021. Several databases were systematically searched using predefined search terms. Inclusion criteria were set to encompass studies reporting on the prevalence of CL/P in infants born to mothers with a history of cocaine use during pregnancy, with a comparison group of non-cocaine-using mothers. Data were extracted, and a meta-analysis was performed using a random-effects model to calculate pooled odds ratios (OR) and relative risks (RR) with their respective 95% confidence intervals (CI). RESULTS: The review included data from 4 studies that met the inclusion criteria. The combined OR from two studies was 0.05 (95% CI: 0.00, 4.41), which does not suggest a statistically significant association between prenatal cocaine exposure and the incidence of CL/P due to the confidence interval crossing the null value. Additionally, the combined RR was 0.17 (95% CI: 0.04, 0.66), indicating a statistically significant decrease in the risk of CL/P associated with prenatal cocaine exposure. These results, with an OR that is not statistically significant and an RR suggesting decreased risk, should be interpreted with caution due to considerable heterogeneity and variability among the included studies' findings. Further research is needed to clarify these associations. CONCLUSION: The findings from this systematic review and meta-analysis suggest that maternal cocaine use during pregnancy is not a statistically significant independent risk factor for the development of CL/P in offspring. These results underscore the multifactorial nature of CL/P etiology and emphasize the importance of considering other genetic, environmental, and nutritional factors in understanding the condition's origins. While the study provides important insights, limitations such as data heterogeneity and potential confounders should be acknowledged. Future research should adopt rigorous study designs and explore a broader range of potential risk factors to comprehensively elucidate CL/P development.

3D-Printable Sustainable Bioplastics from Gluten and Keratin.

Bioplastic films comprising both plant- and animal-derived proteins have the potential to integrate the optimal characteristics inherent to the specific domain, which offers enormous potential to develop polymer alternatives to petroleum-based plastic. Herein, we present a facile strategy to develop hybrid films comprised of both wheat gluten and wool keratin proteins for the first time, employing a ruthenium-based photocrosslinking strategy. This approach addresses the demand for sustainable materials, reducing the environmental impact by using proteins from renewable and biodegradable sources. Gluten film was fabricated from an alcohol-water mixture soluble fraction, largely comprised of gliadin proteins. Co-crosslinking hydrolyzed low-molecular-weight keratin with gluten enhanced its hydrophilic properties and enabled the tuning of its physicochemical properties. Furthermore, the hierarchical structure of the fabricated films was studied using neutron scattering techniques, which revealed the presence of both hydrophobic and hydrophilic nanodomains, gliadin nanoclusters, and interconnected micropores in the matrix. The films exhibited a largely (>40%) ß-sheet secondary structure, with diminishing gliadin aggregate intensity and increasing micropore size (from 1.2 to 2.2 µm) with an increase in keratin content. The hybrid films displayed improved molecular chain mobility, as evidenced by the decrease in the glass-transition temperature from ~179.7 °C to ~173.5 °C. Amongst the fabricated films, the G14K6 hybrid sample showed superior water uptake (6.80% after 30 days) compared to the pristine G20 sample (1.04%). The suitability of the developed system for multilayer 3D printing has also been demonstrated, with the 10-layer 3D-printed film exhibiting >92% accuracy, which has the potential for use in packaging, agricultural, and biomedical applications.

Safety and protective efficacy of PfSPZ Vaccine administered to HIV-negative and -positive Tanzanian adults.

BACKGROUNDSanaria PfSPZ Vaccine, composed of attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), protects against malaria. We conducted this clinical trial to assess the safety and efficacy of PfSPZ Vaccine in HIV-positive (HIV+) individuals, since the HIV-infection status of participants in mass vaccination programs may be unknown.METHODSThis randomized, double-blind, placebo-controlled trial enrolled 18- to 45-year-old HIV-negative (HIV-) and well-controlled HIV+ Tanzanians (HIV viral load <40 copies/mL, CD4 counts >500 cells/µL). Participants received 5 doses of PfSPZ Vaccine or normal saline (NS) over 28 days, followed by controlled human malaria infection (CHMI) 3 weeks later.RESULTSThere were no solicited adverse events in the 9 HIV- and 12 HIV+ participants. After CHMI, 6 of 6 NS controls, 1 of 5 HIV- vaccinees, and 4 of 4 HIV+ vaccinees were Pf positive by quantitative PCR (qPCR). After immunization, anti-Pf circumsporozoite protein (anti-PfCSP) (isotype and IgG subclass) and anti-PfSPZ antibodies, anti-PfSPZ CD4+ T cell responses, and Vδ2+ γδ CD3+ T cells were nonsignificantly higher in HIV- than in HIV+ vaccinees. Sera from HIV- vaccinees had significantly higher inhibition of PfSPZ invasion of hepatocytes in vitro and antibody-dependent complement deposition (ADCD) and Fcγ3B binding by anti-PfCSP and ADCD by anti-cell-traversal protein for ookinetes and SPZ (anti-PfCelTOS) antibodies.CONCLUSIONSPfSPZ Vaccine was safe and well tolerated in HIV+ vaccinees, but not protective. Vaccine efficacy was 80% in HIV- vaccinees (P = 0.012), whose sera had significantly higher inhibition of PfSPZ invasion of hepatocytes and enrichment of multifunctional PfCSP antibodies. A more potent PfSPZ vaccine or regimen is needed to protect those living with HIV against Pf infection in Africa.TRIAL REGISTRATIONClinicalTrials.gov NCT03420053.FUNDINGEquatorial Guinea Malaria Vaccine Initiative (EGMVI), made up of the Government of Equatorial Guinea Ministries of Mines and Hydrocarbons, and Health and Social Welfare, Marathon Equatorial Guinea Production Limited, Noble Energy, Atlantic Methanol Production Company, and EG LNG; Swiss government, through ESKAS scholarship grant no. 2016.0056; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH; NIH grant 1U01AI155354-01.