In-Bath 3D Printing of Anisotropic Shape-Memory Cryogels Functionalized with Bone-Bioactive Nanoparticles.

Cryogels exhibit unique shape memory with full recovery and structural stability features after multiple injections. These constructs also possess enhanced cell permeability and nutrient diffusion when compared to typical bulk hydrogels. Volumetric processing of cryogels functionalized with nanosized units has potential to widen their biomedical applications, however this has remained challenging and relatively underexplored. In this study, we report a novel methodology that combines suspension 3D printing with directional freezing for the fabrication of nanocomposite cryogels with configurable anisotropy. When compared to conventional bulk or freeze-dried hydrogels, nanocomposite cryogel formulations exhibit excellent shape recovery (>95%) and higher pore connectivity. Suspension printing, assisted with a prechilled metal grid, was optimized to induce anisotropy. The addition of calcium- and phosphate-doped mesoporous silica nanoparticles into the cryogel matrix enhanced bioactivity toward orthopedic applications without hindering the printing process. Notably, the nanocomposite 3D printed cryogels exhibit injectable shape memory while also featuring a lamellar topography. The fabrication of these constructs was highly reproducible and exhibited potential for a cell-delivery injectable cryogel with no cytotoxicity to human-derived adipose stem cells. Hence, in this work, it was possible to combine a gravity defying 3D printed methodology with injectable and controlled anisotropic macroporous structures containing bioactive nanoparticles. This methodology ameliorates highly tunable injectable 3D printed anisotropic nanocomposite cryogels with a user-programmable degree of structural complexity.

Encapsulation of pristine and silica-coated human adipose-derived mesenchymal stem cells in gelatin colloidal hydrogels for tissue engineering and bioprinting applications.

Colloidal gels assembled from gelatin nanoparticles (GNPs) as particulate building blocks show strong promise to solve challenges in cell delivery and biofabrication, such as low cell survival and limited spatial retention. These gels offer evident advantages to facilitate cell encapsulation, but research on this topic is still limited, which hampers our understanding of the relationship between the physicochemical and biological properties of cell-laden colloidal gels. Human adipose-derived mesenchymal stem cells were successfully encapsulated in gelatin colloidal gels and evaluated their mechanical and biological performance over 7 days. The cells dispersed well within the gels without compromising gel cohesiveness, remained viable, and spread throughout the gels. Cells partially coated with silica were introduced into these gels, which increased their storage moduli and decreased their self-healing capacity after 7 days. This finding demonstrates the ability to modulate gel stiffness by incorporating cells partially coated with silica, without altering the solid content or introducing additional particles. Our work presents an efficient method for cell encapsulation while preserving gel integrity, expanding the applicability of colloidal hydrogels for tissue engineering and bioprinting. Overall, our study contributes to the design of improved cell delivery systems and biofabrication techniques.

Trust matters: The Addressing Vaccine Hesitancy in Europe Study.

This article presents the design of a seven-country study focusing on childhood vaccines, Addressing Vaccine Hesitancy in Europe (VAX-TRUST), developed during the COVID-19 pandemic. The study consists of (a) situation analysis of vaccine hesitancy (examination of individual, socio-demographic and macro-level factors of vaccine hesitancy and analysis of media coverage on vaccines and vaccination and (b) participant observation and in-depth interviews of healthcare professionals and vaccine-hesitant parents. These analyses were used to design interventions aimed at increasing awareness on the complexity of vaccine hesitancy among healthcare professionals involved in discussing childhood vaccines with parents. We present the selection of countries and regions, the conceptual basis of the study, details of the data collection and the process of designing and evaluating the interventions, as well as the potential impact of the study. Laying out our research design serves as an example of how to translate complex public health issues into social scientific study and methods.

The workforce crisis in healthcare: Moving the debate to bridge evidence and policy.

This Special Issue aims to advance the healthcare workforce (HCWF) debate by directing its attention to the implementation of policy recommendations and identifying weaknesses. The selection of articles highlights a wide range of HCWF policies and interventions across various countries. The challenges faced often stem from policy failures and governance gaps at the macro-, meso- and micro-levels of health systems. Recommendations to mitigate the HCWF crisis include interconnected strategies, multi-/transsectoral policies, solidarity-based efforts, collaboration, skill-mix reforms, equity measures, global approaches, and crucially, strong political will. In addition, specific policy solutions are explored, such as community-centred action and employment of community health workers, mental health support initiatives, inclusion of refugees and displaced healthcare workers into the labour market, and preparing the HCWF for the impact of climate change. This Special Issue calls for transformative HCWF policies and multi-level transsectoral governance as essential components needed to effectively address the crisis. This will only be possible, if HCWF policy moves higher up in the public policy arena leading, among other things, to the establishment of HCWF research as a distinct academic field.

The mental health needs of healthcare workers: When evidence does not guide policy. A comparative assessment of selected European countries.

BACKGROUND: The healthcare workforce (HCWF) globally is facing high stress levels and deteriorating mental health due to workplace, labour market and policy deficiencies that further exacerbate the existing crisis. However, comprehensive and effective action is missing. AIMS: We adopt a health system and governance perspective to address the mental health needs of healthcare workers (HCWs), considering the nature of interventions and the levels and actors involved in governance. The aim is to move the debate forward by identifying governance gaps hampering the implementation of health workforce policies and exploring strategies to effectively increase mental health support. MATERIAL AND METHODS: A qualitative comparative methodology is applied based on a case study design utilising a multi-level intersectoral governance matrix. We conducted a rapid assessment of HCWF developments in the European context (Germany, Portugal, Romania, Switzerland and the United Kingdom), drawing on secondary sources and country experts. RESULTS AND DISCUSSION: Awareness of mental health threats among HCWs increased, but policy discourse is driven by service delivery and labour market demands. The attention to HCWs' needs is stronger on the international level and weakest at national/regional levels. Although organisations and professions demonstrate varying degrees of activity, their efforts are scattered and lack sustainability. Similar challenges were identified across healthcare systems, including limited action, disconnected actors, missing coordination, and a lack of attention to governance gaps and system weaknesses. CONCLUSION: Adopting a health system approach is important but not sufficient. Successful mental health policy implementation needs multi-level governance and coherent coordination mechanisms.

Preparing for the 'next pandemic': Why we need to escape from our silos.

The COVID-19 pandemic revealed major failings in many countries. We argue that one of the reasons, at global, national, and local levels, was that those involved were working in silos, unable to bring together the many diverse perspectives needed to respond to this complex problem. This is despite a growing recognition of the importance of adopting a Health For All Policies approach. Silo working, and the problems it creates, are not unique to health policy so there are opportunities to learn from those organisations that have tackled this issue.

Assessment of the Implementation of the International Health Regulations during the COVID-19 Pandemic: Portugal as a Case Study.

INTRODUCTION: The International Health Regulations (IHR) were developed to prepare countries to deal with public health emergencies. The spread of SARS-CoV-2 underlined the need for international coordination, although few attempts were made to evaluate the integrated implementation of the IHR's core capacities in response to the COVID-19 pandemic. The aim of this study was to evaluate whether IHR shortcomings stem from non-compliance or regulatory issues, using Portugal as a European case study due to its size, organization, and previous discrepancies between self-reporting and peer assessment of the IHR's core capacities. METHODS: Fifteen public health medical residents involved in contact tracing in mainland Portugal interpreted the effectiveness of the IHR's core capabilities by reviewing the publicly available evidence and reflecting on their own field experience, then grading each core capability according to the IHR Monitoring Framework. The assessment of IHR enforcement considered efforts made before and after the onset of the pandemic, covering the period up to July 2021. RESULTS: Four out of nine core IHR capacities (surveillance; response; risk communication; and human resource capacity) were classified as level 1, the lowest. Only two were graded level 3 (preparedness; and laboratory), the highest. The remaining three) (national legislation, policy & financing; coordination and national focal point communication; and points of entry) were classified as level 2. CONCLUSION: Portugal exemplifies the extent to which implementation of the IHR was not fully achieved, which has resulted in the underperformance of several core capacities. There is a need to improve preparedness and international cooperation in order to harmonize and strengthen the global response to public health emergencies, with better political, institutional, and financial support.

Global research publications on cardiovascular and pulmonary rehabilitation and their alignment with population rehabilitation needs: An ecological study.

PURPOSE: Towards informing health research policy and planning, this article evaluates the relationship of the research publications in cardiac rehabilitation (CR) and pulmonary rehabilitation (PR) with the rehabilitation needs arising from cardiovascular diseases (except stroke) and chronic respiratory diseases, over time (1990-2017). METHODS: Ecological study using a secondary analysis and linear regressions of public domain data to associate two datasets of population-level data: (1) research publications for CR and PR (data from the PubMed database); and (2) global need for CR and PR (data from the Global Burden of Disease study). RESULTS: The percentage of both CR and PR publications (among total rehabilitation research) significantly decreased from 1990 to 2017 (both: p < 0.01). PR needs and research publications were aligned: around 5% of total rehabilitation needs and rehabilitation research. For CR needs (around 2%, but significantly increasing since 1990), we found a greater portion of CR research publications (6.5% or over). Finally, we found an inverse association among the percentage of CR research publications and CR needs (b = -6.08; r2  = 0.37, p = 0.001). CONCLUSION: The portion of CR and PR research (among total rehabilitation research) is declining over time. Yearly percentage of CR publications were greater than those of PR but for lower level of rehabilitation need, but the disparate trend was significantly decreasing over time. Population rehabilitation needs and their alignment with research volume must be one factor in the design of population-centred, equitable health research priorities.

Neoadjuvant chemotherapy for muscle-invasive bladder cancer: does variant histology matter?

PURPOSE: The most frequent histology of bladder tumors is urothelial carcinoma. Most are pure urothelial carcinomas (PUC) but up to one-third of the cases present variant histological (VH) features. The aim of this study was to evaluate the role of variant histology in neoadjuvant chemotherapy (NAC) response in patients with urothelial muscle-invasive bladder cancer. METHODS: We retrospectively analyzed data from 77 patients with bladder cancer who performed neoadjuvant chemotherapy at two institutions. RESULTS: Complete pathological response (ypT0) was higher in patients with PUC (38.5%), comparing with VH (12%). Logistic regression analysis demonstrated that variant histology is associated with an 89% lesser likelihood of tumor downstaging, with advanced clinical T stages and positive smoking history as independent predictors. The estimated mean cancer-specific survival was 68.91 months for PUC patients and 50.23 months for VH patients (log rank test, P = 0.024). Multivariate Cox regression analysis demonstrated that VH and clinical T stage were independent predictors of cancer-specific survival, indicating a worse outcome for patients with VH and advanced clinical T stages. CONCLUSIONS: There are only a few retrospective studies evaluating the clinical impact of variant histology tumors, which are mainly managed as PUC. Our results demonstrate that VH is associated with a worse likelihood of tumor downstaging after NAC and a worse cancer-specific survival in bladder cancer patients. There is a need for further studies and genetic analysis to identify the patients most likely to achieve ypT0 status and downstaging after NAC.

Microparticles orchestrating cell fate in bottom-up approaches.

The modulation of cells in tissue formation is still one of the hardest tasks to achieve in Tissue Engineering. To control the cell response when undergoing their normal functions such as adhesion, differentiation, assembly, or maturation is vital the development of more successful solutions. Herein, we discuss how microparticles are being overlooked in their potential for controlling the cellular response. Until now, their role was quite often restricted to a reservoir of chemical compounds or as carriers for cell expansion. Nevertheless, microparticles design with the introduction of biophysical and biochemical cues can effectively modulate cell response.

Schwannoma of Seminal Vesicle: A Case Report.

Seminal vesicle neoplasms are extremely rare. Schwannoma is a benign tumor of the peripherical nerve sheath composed of Schwann cells. Most of these tumors are silent and become symptomatic with compression of adjacent organs and nerves. We present a case of a 72-year-old man who presented with a several months history of predominant storage lower urinary tract symptoms and painful ejaculation. Prostate-specific antigen (PSA) was within normal ranges, and imaging documented a retrovesical nodular lesion adjacent to the right seminal vesicle with 5 cm in width. We successfully performed a robotic-assisted laparoscopic surgery to excise the lesion. Anatomopathological analysis revealed a schwannoma.

The Global South political economy of health financing and spending landscape - history and presence.

The Global South nations and their statehoods have presented a driving force of economic and social development through most of the written history of humankind. China and India have been traditionally accounted as the economic powerhouses of the past. In recent decades, we have witnessed reestablishment of the traditional world economic structure as per Agnus Maddison Project data. These profound changes have led to accelerated real GDP growth across many LMICs and emerging countries of the Global South. This evolution had a profound impact on an evolving health financing landscape. This review revealed hidden patterns and explained the driving forces behind the political economy of health spending in these vast world regions. The medical device and pharmaceutical industry play a crucial role in addressing the unmet medical needs of rising middle class citizens across Asia, Latin America, and Africa. Domestic manufacturing has only been partially meeting this ever rising demand for medical services and medicines. The rest was complemented by the participation of multinational pharmaceutical industry, whose focus on investment into East Asia and ASEAN nations remains part of long-term market access strategies. Understanding of the past remains essential for the development of successful health strategies for the present. Political economy has been driving the evolution of health financing landscape since the establishment of early modern health systems in these countries. Fiscal gaps these governments face in diverse ways might be partially overcome with the spreading of cost-effectiveness based decision-making and health technology assessment capacities. The considerable remaining challenges ranging from insufficient reimbursement rates, large out-of-pocket spending, and lengthy lag in the introduction of cutting-edge technologies such as monoclonal antibodies, biosimilars, or targeted oncology agents, might be partially resolved only in the long run.

Health workforce protection and preparedness during the COVID-19 pandemic: a tool for the rapid assessment of EU health systems.

This article is dedicated to the WHO International Year of Health and Care Workers in 2021 in recognition of their commitment during the COVID-19 pandemic. The study aims to strengthen health workforce preparedness, protection and ultimately resilience during a pandemic. We argue for a health system approach and introduce a tool for rapid comparative assessment based on integrated multi-level governance. We draw on secondary sources and expert information, including material from Denmark, Germany, Portugal and Romania. The results reveal similar developments across countries: action has been taken to improve physical protection, digitalization and prioritization of healthcare worker vaccination, whereas social and mental health support programmes were weak or missing. Developments were more diverse in relation to occupational and organizational preparedness: some ad-hoc transformations of work routines and tasks were observed in all countries, yet skill-mix innovation and collaboration were strongest in Demark and weak in Portugal and Romania. Major governance gaps exist in relation to education and health integration, surveillance, social and mental health support programmes, gendered issues of health workforce capacity and integration of migrant healthcare workers (HCW). There is a need to step up efforts and make health systems more accountable to the needs of HCW during global public health emergencies.