When intervention becomes imperative: a case report of spontaneous vulvar edema during pregnancy.

Spontaneous idiopathic vulvar edema during the second trimester is a rare condition. The approach to managing this condition involves relieving symptoms, identifying underlying causes, and implementing appropriate treatment. Managing such cases during pregnancy is challenging because of concerns for potential adverse fetal outcomes. Conservative management expects the condition to be relieved spontaneously postpartum, whereas invasive treatment offers a more rapid resolution. Treatment choices are controversial because each method has its pros and cons and influences the delivery process to a certain extent. Surgical drainage becomes a viable option when patients are not responsive to medications. We report a case of spontaneous massive vulvar edema in a 22-year-old primigravida in her 23rd week of pregnancy. After ruling out other notable causes of vulvar edema, we decided to intervene using an invasive procedure because she complained of progressive symptoms and discomfort. Subsequently, the edema subsided postprocedure, and the patient experienced successful labor with no complications. This report aims to alert clinicians that drainage attempts should be considered in pregnant patients with worsening symptoms.

Barriers and enablers to people-centred viral hepatitis care in Vietnam and the Philippines: Results of a patient journey mapping study.

In Vietnam and the Philippines, viral hepatitis is the leading cause of cirrhosis and liver cancer. This study aims to understand the barriers and enablers of people receiving care for hepatitis B and C to support both countries' efforts to eliminate viral hepatitis as a public health threat by 2030. Retrospective, semi-structured interviews were conducted with a purposive, quota-based sample of 63 people living with hepatitis B or C in one province of Vietnam and one region of the Philippines. A rapid deductive approach to thematic analysis produced key findings among the three phases of care: (1) pre-awareness and testing, (2) linkage and treatment initiation and (3) ongoing treatment and recovery. The research found that participants followed five typical journeys, from a variety of entry points. Barriers during the pre-awareness and testing phase included limited awareness about hepatitis and its management, stigma and psychological impacts. Enablers included being familiar with the health system and/or patients benefiting from social connections within the health systems. During the linkage and treatment initiation phase, barriers included difficult physical access, complex navigation and inadequate counselling. In this phase, family support emerged as a critical enabler. During the ongoing treatment and recovery phase, the cost of care and socially and culturally informed perceptions of the disease and medication use were both barriers and enablers. Exploring peoples' journeys with hepatitis B and C in Vietnam and the Philippines revealed many similarities despite the different cultural and health system contexts. Insights from this study may help generate a contextualized, people-centred evidence base to inform the design and improvement of primary care services for hepatitis in both research sites.

Prevalence of obstructive sleep apnea in patients with chronic obstructive pulmonary disease in Vietnam.

PURPOSE: Chronic obstructive pulmonary disease and obstructive sleep apnea are two common respiratory diseases. Chronic obstructive pulmonary disease patients co-morbid with obstructive sleep apnea are associated with increased cardiovascular adverse events, frequent acute exacerbations, and higher mortality. Only a few studies on obstructive sleep apnea among patients with chronic obstructive pulmonary disease are available in Vietnam. The study aims to determine the prevalence of obstructive sleep apnea in patients with chronic obstructive pulmonary disease in Vietnam. METHODS: This is a cross-sectional study in patients with chronic obstructive pulmonary disease at multi-sites in Vietnam: the People's Hospital of Gia Dinh, Bach Mai Hospital, Phoi Viet Clinics, and Lam Dong Medical College using type 3 sleep monitoring device at sleep labs to diagnose obstructive sleep apnea in all study participants. RESULTS: Two hundred seventy-eight patients with chronic obstructive pulmonary disease were enrolled. Among the patients, 93.2% were male, with an average age of 66.9 ± 9.3 and a BMI of 21.9 ± 3.8 kg/m2; 82.0% were symptomatic including 44.6% in group B and 37.4% in group D with average post-FEV1 of 49.8 ± 18.3% predicted values. One hundred seventeen patients (42.1%) with chronic obstructive pulmonary disease presented obstructive sleep apnea defined by AHI ≥ 15 events/h. CONCLUSIONS: The prevalence of obstructive sleep apnea in patients with chronic obstructive pulmonary disease in Vietnam was 42.1% for an AHI of ≥ 15 events/h.

Digital roots: harnessing digital platforms in advancing traditional and complementary medicine for cancer care in Sub-Saharan Africa.

The rise in cancer rates in Sub-Saharan Africa (SSA), combined with limited access to Western pharmaceuticals, has sparked growing adoption of traditional and complementary medicine (T&CM) for cancer treatment in the region. However, many challenges exist, including the lack of reliable evidence-based research on these products, scarcity of standardized documentation as part of cancer registries, limited physician expertise, and negative effects on mortality. Nonetheless, herbal medicines also present opportunities for further research, development, and stakeholder education, potentially benefiting the regional healthcare systems in SSA countries and global health as whole. Recent trends highlight the willingness of patients to use mobile-based applications that provide accurate information on herbal therapeutics, reflecting the increasing adoption of internet and smart/mobile phone services in SSA. To maximize the potential benefits of traditional and complementary medicine, it is necessary to bridge the trust gap between the public, local practitioners, and Western healthcare providers. Sustained funding and policy support are needed to complement these initiatives. Our preliminary survey hopes to inspire the community and policymakers to embrace innovative solutions, fostering a forward-looking approach to cancer care in SSA.

Blood-Stream Infections: Causative Agents, Antibiotic Resistance and Associated Factors in Older Patients.

Background: The rate of multi-drug antibiotic resistance in nosocomial bloodstream infections in elderly patients is increasing. This study examined the data for bloodstream infections to gain a better understanding of bacterial antibiotic resistance. Methods: This was a retrospective study of 817 patients with the first positive blood culture between January 1, 2016 and December 31, 2019. Results: Moyen's age was 77.4 ± 9.8 years, male (52.4%) and SOFA 5.0 ± 4. ESBL(+) rate was 78/817 (9.5%). ESBL(+) rate for Escherichia coli and Klebsiella pneumoniae was 69/141 (48.9%) and 9/52 (17.3%), respectively. The most common isolates were Escherichia coli (17.3%), Stenotrophomonas maltophilia (13.7%), and Staphylococcus species (23.1%). The rate of septic shock and mortality accounted for 22.3% and 28.9%, respectively. Escherichia coli is highly sensitive to carbapenem, and resistant (>50%) with quinolone and aminoside. Klebsiella pneumoniae and Pseudomonas aeruginosa were highly sensitive to carbapenem. Acinetobacter baumannii was resistant to meropenem (75%). Stenotrophomonas maltophilia was sensitive to quinolone (13.8 %), and highly resistant to remaining antibiotics. Methicillin-resistant Staphylococcus aureus had a low resistance rate for vancomycin, teicoplanin, and linezolid. Multivariate analysis showed that the significant factors associated with mortality were age >75; SOFA >7; respiratory infection; intensive care unit treatment and presentation with septic shock. Conclusion: The mortality rate was still high, especially for antibiotic-resistant agents.

Evaluating the relationship between contouring variability and modelled treatment outcome for prostate bed radiotherapy.

Objectives.Contouring similarity metrics are often used in studies of inter-observer variation and automatic segmentation but do not provide an assessment of clinical impact. This study focused on post-prostatectomy radiotherapy and aimed to (1) identify if there is a relationship between variations in commonly used contouring similarity metrics and resulting dosimetry and (2) identify the variation in clinical target volume (CTV) contouring that significantly impacts dosimetry.Approach.The study retrospectively analysed CT scans of 10 patients from the TROG 08.03 RAVES trial. The CTV, rectum, and bladder were contoured independently by three experienced observers. Using these contours reference simultaneous truth and performance level estimation (STAPLE) volumes were established. Additional CTVs were generated using an atlas algorithm based on a single benchmark case with 42 manual contours. Volumetric-modulated arc therapy (VMAT) treatment plans were generated for the observer, atlas, and reference volumes. The dosimetry was evaluated using radiobiological metrics. Correlations between contouring similarity and dosimetry metrics were calculated using Spearman coefficient (Γ). To access impact of variations in planning target volume (PTV) margin, the STAPLE PTV was uniformly contracted and expanded, with plans created for each PTV volume. STAPLE dose-volume histograms (DVHs) were exported for plans generated based on the contracted/expanded volumes, and dose-volume metrics assessed.Mainresults. The study found no strong correlations between the considered similarity metrics and modelled outcomes. Moderate correlations (0.5 <Γ< 0.7) were observed for Dice similarity coefficient, Jaccard, and mean distance to agreement metrics and rectum toxicities. The observations of this study indicate a tendency for variations in CTV contraction/expansion below 5 mm to result in minor dosimetric impacts.Significance. Contouring similarity metrics must be used with caution when interpreting them as indicators of treatment plan variation. For post-prostatectomy VMAT patients, this work showed variations in contours with an expansion/contraction of less than 5 mm did not lead to notable dosimetric differences, this should be explored in a larger dataset to assess generalisability.

Coffee Husk By-Product as Novel Ingredients for Cascara Kombucha Production.

Kombucha, a fermented beverage, is gaining popularity due to its numerous beneficial health effects. Various substrates such as herbs, fruits, flowers, and vegetables, have been used for kombucha fermentation in order to enhance the flavor, aroma, and nutritional composition. This study aims to investigate the potential suitability of cascara as a novel ingredient for kombucha production. Our findings suggested that cascara is a suitable substrate for kombucha production. Fermentation elevated the total phenolic and flavonoid content in cascara, which enhanced the antioxidant, antibacterial, and prebiotic characteristics of the product. Furthermore, the accumulation of acetic acid-induced the pH lowering reached 2.7 after 14 days of fermentation, which achieved the microbiological safety of the product. Moreover, 14 days of fermentation resulted in a balanced amalgamation of acidity, sweetness, and fragrance according to sensory evaluation. Our findings not only highlight the potential of cascara kombucha as a novel substrate for kombucha production but also contribute to repurposing coffee by-products, promoting environmentally friendly and sustainable agricultural development.

Dynamic models augmented by hierarchical data: an application of estimating HIV epidemics at sub-national level.

Dynamic models have been successfully used in producing estimates of HIV epidemics at the national level due to their epidemiological nature and their ability to estimate prevalence, incidence, and mortality rates simultaneously. Recently, HIV interventions and policies have required more information at sub-national levels to support local planning, decision-making and resource allocation. Unfortunately, many areas lack sufficient data for deriving stable and reliable results, and this is a critical technical barrier to more stratified estimates. One solution is to borrow information from other areas within the same country. However, directly assuming hierarchical structures within the HIV dynamic models is complicated and computationally time-consuming. In this article, we propose a simple and innovative way to incorporate hierarchical information into the dynamical systems by using auxiliary data. The proposed method efficiently uses information from multiple areas within each country without increasing the computational burden. As a result, the new model improves predictive ability and uncertainty assessment.

Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission.

Anaplastic thyroid carcinoma (ATC) has a 100% disease-specific mortality rate. The JAK1/2-STAT3 pathway presents a promising target for treating hematologic and solid tumors. However, it is unknown whether the JAK1/2-STAT3 pathway is activated in ATC, and the anti-cancer effects and the mechanism of action of its inhibitor, ruxolitinib (Ruxo, a clinical JAK1/2 inhibitor), remain elusive. Our data indicated that the JAK1/2-STAT3 signaling pathway is significantly upregulated in ATC tumor tissues than in normal thyroid and papillary thyroid cancer tissues. Apoptosis and GSDME-pyroptosis were observed in ATC cells following the in vitro and in vivo administration of Ruxo. Mechanistically, Ruxo suppresses the phosphorylation of STAT3, resulting in the repression of DRP1 transactivation and causing mitochondrial fission deficiency. This deficiency is essential for activating caspase 9/3-dependent apoptosis and GSDME-mediated pyroptosis within ATC cells. In conclusion, our findings indicate DRP1 is directly regulated and transactivated by STAT3; this exhibits a novel and crucial aspect of JAK1/2-STAT3 on the regulation of mitochondrial dynamics. In ATC, the transcriptional inhibition of DRP1 by Ruxo hampered mitochondrial division and triggered apoptosis and GSDME-pyroptosis through caspase 9/3-dependent mechanisms. These results provide compelling evidence for the potential therapeutic effectiveness of Ruxo in treating ATC.

Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.

The last decade (2013-2023) has seen unprecedented successes in the clinical translation of therapeutic antisense oligonucleotides (ASOs). Eight such molecules have been granted marketing approval by the United States Food and Drug Administration (US FDA) during the decade, after the first ASO drug, fomivirsen, was approved much earlier, in 1998. Splice-modulating ASOs have also been developed for the therapy of inborn errors of metabolism (IEMs), due to their ability to redirect aberrant splicing caused by mutations, thus recovering the expression of normal transcripts, and correcting the deficiency of functional proteins. The feasibility of treating IEM patients with splice-switching ASOs has been supported by FDA permission (2018) of the first "N-of-1" study of milasen, an investigational ASO drug for Batten disease. Although for IEM, owing to the rarity of individual disease and/or pathogenic mutation, only a low number of patients may be treated by ASOs that specifically suppress the aberrant splicing pattern of mutant precursor mRNA (pre-mRNA), splice-switching ASOs represent superior individualized molecular therapeutics for IEM. In this work, we first summarize the ASO technology with respect to its mechanisms of action, chemical modifications of nucleotides, and rational design of modified oligonucleotides; following that, we precisely provide a review of the current understanding of developing splice-modulating ASO-based therapeutics for IEM. In the concluding section, we suggest potential ways to improve and/or optimize the development of ASOs targeting IEM.

Multimorbidity impacts cardiovascular disease risk following percutaneous coronary intervention: latent class analysis of the Melbourne Interventional Group (MIG) registry.

BACKGROUND: Multimorbidity is strongly associated with disability or functional decline, poor quality of life and high consumption of health care services. This study aimed (1) To identify patterns of multimorbidity among patients undergoing first recorded percutaneous coronary intervention (PCI); (2) To explore the association between the identified patterns of multimorbidity on length of hospital stay, 30-day and 12- month risk of major adverse cardiac and cerebrovascular events (MACCE) after PCI. METHODS: A retrospective cohort study of the Melbourne Interventional Group (MIG) registry. This study included 14,025 participants who underwent their first PCI from 2005 to 2015 in Victoria, Australia. Based on a probabilistic modelling approach, Latent class analysis was adopted to classify clusters of people who shared similar combinations and magnitude of the comorbidity of interest. Logistic regression models were used to estimate odd ratios and 95% confidence interval (CI) for the 30-day and 12-month MACCE. RESULTS: More than two-thirds of patients had multimorbidity, with the most prevalent conditions being hypertension (59%) and dyslipidaemia (60%). Four distinctive multimorbidity clusters were identified each with significant associations for higher risk of 30-day and 12-month MACCE. The cluster B had the highest risk of 30-day MACCE event that was characterised by a high prevalence of reduced estimated glomerular filtration rate (92%), hypertension (73%) and reduced ejection fraction (EF) (57%). The cluster C, characterised by a high prevalence of hypertension (94%), dyslipidaemia (88%), reduced eGFR (87%), diabetes (73%) and reduced EF (65%) had the highest risk of 12-month MACCE and highest length of hospital stay. CONCLUSION: Hypertension and dyslipidaemia are prevalent in at least four in ten patients undergoing coronary angioplasty. This study showed that clusters of patients with multimorbidity had significantly different risk of 30-day and 12-month MACCE after PCI. This suggests the necessity for treatment approaches that are more personalised and customised to enhance patient outcomes and the quality of care delivered to patients in various comorbidity clusters. These results should be validated in a prospective cohort and to evaluate the potential impacts of these clusters on the prevention of MACCE after PCI.

Embedding viral hepatitis into primary healthcare: results of a strategic landscape analysis in Vietnam and the Philippines.

Chronic viral hepatitis is a significant public health concern in the Western Pacific, including in Vietnam and the Philippines. To accelerate progress toward meeting the 2030 elimination goals, the World Health Organization (WHO) encourages countries to adopt an integrated, people-centered health sector response to hepatitis, grounded in Primary Health Care (PHC). A review of the academic and grey literature, along with policy documents, was conducted to describe the national health system and PHC response to hepatitis B and C in Vietnam and the Philippines. Information was analyzed against the four strategic levers of the WHO Operational Framework for PHC to identify challenges and opportunities. The findings suggest that both countries have relatively robust policy frameworks, with some room for improvement. Vietnam may have stronger political commitment and funding than the Philippines, while the Philippines appears to be stronger in community engagement. Both countries share challenges and opportunities for learning to actualize viral hepatitis elimination utilizing a PHC approach.

A Vessel Wall MRI Investigation in Patients With Moyamoya or Quasi-Moyamoya Disease: Diagnosis, Features, and Outcomes.

BACKGROUND AND PURPOSE: None of the previous studies have investigated the pathologic authenticity of affected arteries in moyamoya disease (MMD) and Quasi-MMD diagnosed by angiography. This study aimed to confirm the angiographic diagnosis of moyamoya as well as investigate the pathologic mechanisms in angiographically proven MMD and Quasi-MMD using high-resolution magnetic resonance imaging (MRI) in a large sample. METHODS: We prospectively studied 116 patients who had angiographically proven MMD and Quasi-MMD. Each affected internal carotid artery, and middle cerebral artery was independently evaluated. In addition, clinical features and postoperative outcomes were compared between hemispheres with MMD and moyamoya syndrome (MMS). RESULTS: Among 116 patients analyzed, 88 and 22 patients had angiographically proven MMD and Quasi-MMD, respectively. high-resolution magnetic resonance imaging confirmed bilateral MMD in 73 (83.0%) patients, 1 hemisphere with MMD and the other with intracranial atherosclerotic disease (ICAD) in 10 (11.4%) patients, and bilateral hemispheres with different vasculopathies in 5 (5.7%) patients. Detailed analysis of 204 affected hemispheres showed that several combinations of different vasculopathies were observed in the internal carotid artery and middle cerebral artery of the same hemisphere, such as ICAD-ICAD, ICAD-MMD, dissection-ICAD, and dissection-MMD. Hemispheres were assigned to MMD and MMS groups according to their vasculopathies. Transient ischemic attack occurred more frequently in hemispheres with MMD (48.1% versus 21.1%, P =0.024), whereas symptomatic ischemia was more common in hemispheres with MMS (57.9% versus 24.9%, P =0.002). However, postoperative cerebral infarction, symptom improvement and neo-formative collaterals showed no significant difference between hemispheres with MMD and MMS ( P >0.05). CONCLUSIONS: Patients with angiographically proven MMD or Quasi-MMD needed more accurate evaluation combined with high-resolution magnetic resonance imaging. Highly selected patients with MMS might also obtain benefits from surgical revascularization.

Involvement of a Rarely Used Splicing SD2b Site in the Regulation of HIV-1 vif mRNA Production as Revealed by a Growth-Adaptive Mutation.

We have previously reported an HIV-1 mutant designated NL-Y226tac that expresses Vif at an ultra-low level, being replication-defective in high-APOBEC3G cells, such as H9. It carries a synonymous mutation within the splicing SA1 site relative to its parental clone. In order to determine whether a certain mutant(s) emerges during multi-infection cycles, we maintained H9 cells infected with a relatively low or high input of NL-Y226tac for extended time periods. Unexpectedly, we reproducibly identified a g5061a mutation in the SD2b site in the two independent long-term culture experiments that partially increases Vif expression and replication ability. Importantly, the adaptive mutation g5061a was demonstrated to enhance vif mRNA production by activation of the SA1 site mediated through increasing usage of a rarely used SD2b site. In the long-term culture initiated by a high virus input, we additionally found a Y226Fttc mutation at the original Y226tac site in SA1 that fully restores Vif expression and replication ability. As expected, the adaptive mutation Y226Fttc enhances vif mRNA production through increasing the splicing site usage of SA1. Our results here revealed the importance of the SD2b nucleotide sequence in producing vif mRNA involved in the HIV-1 adaptation and of mutual antagonism between Vif and APOBEC3 proteins in HIV-1 adaptation/evolution and survival.

MASSAI: Multi-agent system for simulating sustainable agricultural intensification of smallholder farms in Africa.

The research and development needed to achieve sustainability of African smallholder agricultural and natural systems has led to a wide array of theoretical frameworks for conceptualising socioecological processes and functions. However, there are few analytical tools for spatio-temporal empirical approaches to implement use cases, which is a prerequisite to understand the performance of smallholder farms in the real world. This study builds a multi-agent system (MAS) to operationalise the Sustainable Agricultural Intensification (SAI) theoretical framework (MASSAI). This is an essential tool for spatio-temporal simulation of farm productivity to evaluate sustainability trends into the future at fine scale of a managed plot. MASSAI evaluates dynamic nutrient transfer using smallholder nutrient monitoring functions which have been calibrated with parameters from Malawi and the region. It integrates two modules: the Environmental (EM) and Behavioural (BM) ones.•The EM assess dynamic natural nutrient inputs (sedimentation and atmospheric deposition) and outputs (leaching, erosion and gaseous loses) as a product of bioclimatic factors and land use activities.•An integrated BM assess the impact of farmer decisions which influence farm-level inputs (fertilizer, manure, biological N fixation) and outputs (crop yields and associated grain).•A use case of input subsidies, common in Africa, markedly influence fertilizer access and the impact of different policy scenarios on decision-making, crop productivity, and nutrient balance are simulated. This is of use for empirical analysis smallholder's sustainability trajectories given the pro-poor development policy support.

Health staff's job motivation post COVID-19 pandemic: A case study in Vietnam.

Objectives: Vietnam has witnessed a severe shortage of qualified staff in the public health sector after the COVID-19 pandemic. Our cross-sectional study aimed to identify job motivation and associated factors among experienced frontline health staff working in public health in order to have preventive measures in the event of future pandemics. Methods: A cross-sectional study, from March 2022 to November 2022 at a Vietnamese public hospital, on the job motivation and the predicted factors of 381 healthcare workers who participated in the frontlines of the COVID-19 pandemic from 2020 to 2021. The survey tool, developed by Mbindyo Patrick (2009), includes three components: (i) job satisfaction, (ii) organizational commitment, and (iii) conscientiousness. The survey tool was revalidated in our study with structural equation model for the construction of job motivation model and confirmatory factor analysis for certifying the elementary three components (factors) of the tool. And the tool's reliability was evaluated by Cronbach's Alpha. Bivariate analysis and multiple logistic regression were used to identify the predicted factors with the job motivation cutoff of 4.0. Results: The tool for job motivation constructs showed all specifications were good fit indices and the Cronbach's Alpha was 0.85. The job motivation of health staff decreased dramatically in all dimensions post COVID-19 pandemic, with a mean score of 3.26. Job satisfaction and organizational commitment were the most negatively impacted areas, with scores of 3.02 and 3.00, respectively. The predicted factors of low job motivation were young age (less than 30 years old), low monthly income (less than $400), high qualification, and non-managerial positions with odds ratio of 2.27, 2.5, 2.09, and 3.61, respectively. Conclusion: Following the COVID-19 outbreak in Vietnam, healthcare workers who had been in the frontlines of the COVID-19 pandemic, had experienced a significant decline in their job motivation, despite their continued employment at public hospitals.

Comparison of the radioprotective effects of the liposomal forms of five natural radioprotectants in alleviating the adverse effects of ionising irradiation on human lymphocytes and skin cells in radiotherapy.

This study aims to evaluate the radioprotective effects of liposomes encapsulating curcumin (Lip-CUR), silibinin (Lip-SIL), α-tocopherol (Lip-TOC), quercetin (Lip-QUE) and resveratrol (Lip-RES) in alleviating the adverse effects of ionising irradiation on human lymphoctyes and skin cells in radiotherapy. Liposomes encapsulating the above natural radioprotectants (Lip-NRPs) were prepared by the film hydration method combined with sonication. Their radioprotective effects for the cells against X-irradiation was evaluated using trypan-blue assay and γ-H2AX assay. All prepared Lip-NRPs had a mean diameter less than 240 nm, polydispersity index less than 0.32, and zeta potential more than -23 mV. Among them, the radioprotective effect of Lip-RES was lowest, while that of Lip-QUE was highest. Lip-SIL also exhibited a high radioprotective effect despite its low DPPH-radical scavenging activity (12.9%). The radioprotective effects of Lip-NRPs do not solely depend on the free radical scavenging activity of NRPs but also on their ability to activate cellular mechanisms.

Alginate-gelatin hydrogel supplemented with platelet concentrates can be used as bioinks for scaffold printing.

Background: Owing to the growing global demand for organ replacement and tissue regeneration, three-dimensional (3D) printing is widely recognized as an essential technology in tissue engineering. Biomaterials become a potential source of raw materials for printing ink by containing factors that promote tissue regeneration. Platelet concentrates are autologous biological products that are capable of doing that. Objectives: This study was carried out to create bioinks capable of providing biological signals by combining gelatin-alginate with platelet concentrates. Methods: This study combined platelet concentrates, including platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), with gelatin and alginate to create bioinks. Bioink properties, including gelatinization and pH, were assessed before printing. After that, the scaffolds were done, and the growth factor (GF) release and cytotoxicity from these scaffolds were performed. Results: Results showed that all the three bioinks, including alginate-gelatin (AG), alginate-gelatin-PRP (AGP), and alginate-gelatin-PRF (AGF) were gelatinized right at the end of bioink fabrication and had a pH around 7. The scaffolds from bioinks supplemented with platelet concentrates secreted GFs that remained for 12 d, and the extracts from them were not cytotoxic for the L929 cell line. Conclusion: In summary, bioinks were made by combining AG with platelet concentrates and had properties suitable for creating scaffolds with cell-oriented grafts in the development of artificial tissues and organs.

Fibroblasts mediate endothelium response to angiogenic cues in a newly developed 3D stroma engineered model.

Three-dimensional stroma engineered models would enable fundamental and applicative studies of human tissues interaction and remodeling in both physiological and pathological conditions. In this work, we propose a 3D vascularized stroma model to be used as in vitro platform for drug testing. A pullulan/dextran-based porous scaffold containing pre-patterned microchannels of 100 µm diameter is used for co-culturing of fibroblasts within the matrix pores and endothelial cells to form the lumen. Optical clearing of the constructs by hyperhydration allows for in-depth imaging of the model up to 1 mm by lightsheet and confocal microscopy. Our 3D vascularized stroma model allows for higher viability, metabolism and cytokines expression compared to a monocultured vascular model. Stroma-endothelium cross-talk is then investigated by exposing the system to pro and anti-angiogenic molecules. The results highlight the protective role played by fibroblasts on the vasculature, as demonstrated by decreased cytotoxicity, restoration of nitric oxide levels upon challenge, and sustained expression of endothelial markers CD31, vWF and VEGF. Our tissue model provides a 3D engineered platform for in vitro studies of stroma remodeling in angiogenesis-driven events, known to be a leading mechanism in diseased conditions, such as metastatic cancers, retinopathies and ischemia, and to investigate related potential therapies.

Effect of Blood Gel Derivatives on Wound Healing in Mouse Injured Tissue Models.

Several previous studies in the field of assisted reproduction have focused on the use of blood gel derivatives, such as platelet-rich fibrin (PRF), as a treatment for endometrial rehabilitation. However, the ability to release growth factors and the gel form of this product led to the evolution of platelet lysates. In this study, blood gel derivatives, including PRF lysate, which was in liquid form, and PRF gel, were collected and evaluated for growth factors. It was shown to be effective in endometrial wound healing and regeneration in mouse injured uterine tissue models through structure and function (pinopode expression, embryo implantation) evaluation. The results demonstrated that the concentrations of growth factors, including PDGF-AB and VEGF-A, were higher in the PRF lysate compared to the PRF gel (p < 0.05). PRF lysate could release these growth factors for 8 days. Furthermore, both PRF gel and PRF lysate restored the morphology of injured endometrial tissues in terms of luminal and glandular epithelia, as well as uterine gland secretory activity. However, the presence of pinopodes and embryonic implantation were only observed in the PRF lysate group. It can be concluded that PRF lysate promotes wound healing in mouse injured tissue models in vitro, which can act as healing products in tissue repair.