Developing a Biomimetic 3D Neointimal Layer as a Prothrombotic Substrate for a Humanized In Vitro Model of Atherothrombosis.

Acute cardiovascular events result from clots caused by the rupture and erosion of atherosclerotic plaques. This paper aimed to produce a functional biomimetic hydrogel of the neointimal layer of the atherosclerotic plaque that can support thrombogenesis upon exposure to human blood. A biomimetic hydrogel of the neointima was produced by culturing THP-1-derived foam cells within 3D collagen hydrogels in the presence or absence of atorvastatin. Prothrombin time and platelet aggregation onset were measured after exposure of the neointimal models to platelet-poor plasma and washed platelet suspensions prepared from blood of healthy, medication-free volunteers. Activity of the extrinsic coagulation pathway was measured using the fluorogenic substrate SN-17. Foam cell formation was observed following preincubation of the neointimal biomimetic hydrogels with oxidized LDL, and this was inhibited by pretreatment with atorvastatin. The neointimal biomimetic hydrogel was able to trigger platelet aggregation and blood coagulation upon exposure to human blood products. Atorvastatin pretreatment of the neointimal biomimetic layer significantly reduced its pro-aggregatory and pro-coagulant properties. In the future, this 3D neointimal biomimetic hydrogel can be incorporated as an additional layer within our current thrombus-on-a-chip model to permit the study of atherosclerosis development and the screening of anti-thrombotic drugs as an alternative to current animal models.

Development of a Unified IoT Platform for Assessing Meteorological and Air Quality Data in a Tropical Environment.

In developing nations, outdated technologies and sulfur-rich heavy fossil fuel usage are major contributors to air pollution, affecting urban air quality and public health. In addition, the limited resources hinder the adoption of advanced monitoring systems crucial for informed public health policies. This study addresses this challenge by introducing an affordable internet of things (IoT) monitoring system capable of tracking atmospheric pollutants and meteorological parameters. The IoT platform combines a Bresser 5-in-1 weather station with a previously developed air quality monitoring device equipped with Alphasense gas sensors. Utilizing MQTT, Node-RED, InfluxDB, and Grafana, a Raspberry Pi collects, processes, and visualizes the data it receives from the measuring device by LoRa. To validate system performance, a 15-day field campaign was conducted in Santa Clara, Cuba, using a Libelium Smart Environment Pro as a reference. The system, with a development cost several times lower than Libelium and measuring a greater number of variables, provided reliable data to address air quality issues and support health-related decision making, overcoming resource and budget constraints. The results showed that the IoT architecture has the capacity to process measurements in tropical conditions. The meteorological data provide deeper insights into events of poorer air quality.

Multiparametric modulation of magnetic transduction for biomolecular sensing in liquids.

The recent COVID19 pandemic has remarkably boosted the research on in vitro diagnosis assays to detect biomarkers in biological fluids. Specificity and sensitivity are mandatory for diagnostic kits aiming to reach clinical stages. Whilst the modulation of sensitivity can significantly improve the detection of biomarkers in liquids, this has been scarcely explored. Here, we report on the proof of concept and parametrization of a novel biosensing methodology based on the changes of AC magnetic hysteresis areas observed for magnetic nanoparticles following biomolecular recognition in liquids. Several parameters are shown to significantly modulate the transducing capacity of magnetic nanoparticles to detect analytes dispersed in saline buffer at concentrations of clinical relevance. Magnetic nanoparticles were bio-conjugated with an engineered recognition peptide as a receptor. Analytes are engineered tetratricopeptide binding domains fused to the fluorescent protein whose dimerization state allows mono- or divalent variants. Our results unveil that the number of receptors per particle, analyte valency and concentration, nanoparticle composition and concentration, and field conditions play a key role in the formation of assemblies driven by biomolecular recognition. Consequently, all these parameters modulate the nanoparticle transduction capacity. Our study provides essential insights into the potential of AC magnetometry for customizing biomarker detection in liquids.

Optical Microscopy Using the Faraday Effect Reveals in Situ Magnetization Dynamics of Magnetic Nanoparticles in Biological Samples.

The study of exogenous and endogenous nanoscale magnetic material in biology is important for developing biomedical nanotechnology as well as for understanding fundamental biological processes such as iron metabolism and biomineralization. Here, we exploit the magneto-optical Faraday effect to probe intracellular magnetic properties and perform magnetic imaging, revealing the location-specific magnetization dynamics of exogenous magnetic nanoparticles within cells. The opportunities enabled by this method are shown in the context of magnetic hyperthermia; an effect where local heating is generated in magnetic nanoparticles exposed to high-frequency AC magnetic fields. Magnetic hyperthermia has the potential to be used as a cellular-level thermotherapy for cancer, as well as for other biomedical applications that target heat-sensitive cellular function. However, previous experiments have suggested that the cellular environment modifies the magnetization dynamics of nanoparticles, thus dramatically altering their heating efficiency. By combining magneto-optical and fluorescence measurements, we demonstrate a form of biological microscopy that we used here to study the magnetization dynamics of nanoparticles in situ, in both histological samples and living cancer cells. Correlative magnetic and fluorescence imaging identified aggregated magnetic nanoparticles colocalized with cellular lysosomes. Nanoparticles aggregated within these lysosomes displayed reduced AC magnetic coercivity compared to the same particles measured in an aqueous suspension or aggregated in other areas of the cells. Such measurements reveal the power of this approach, enabling investigations of how cellular location, nanoparticle aggregation, and interparticle magnetic interactions affect the magnetization dynamics and consequently the heating response of nanoparticles in the biological milieu.

Magnetic coagulometry: towards a new nanotechnological tool for ex vivo monitoring coagulation in human whole blood.

Blood clotting disorders consisting of unwanted blood clot formation or excessive bleeding are some of the main causes of death worldwide. However, there are significant limitations in the current methods used to clinically monitor the dynamics of clot formation in human whole blood ex vivo. Here a new magnetic coagulometry platform for testing ex vivo coagulation is described. This platform exploits the sensitivity of the out-of-phase component of alternating current (AC) magnetic susceptibility (χ'') to variations in mobility and agglomeration of magnetic nanoparticles when trapped during blood clot formation. By labelling human whole blood with magnetic nanoparticles, the out-of-phase component of AC magnetic susceptibility shows that the dynamics of blood clot formation correlates with a decrease in the out-of-phase component χ'' over time activation of coagulation. This is caused by a rapid immobilisation of nanoparticles upon blood coagulation and compaction. In contrast, this rapid fall in the out-of-phase component χ'' is significantly slowed down when blood is pre-treated with three different anticoagulant drugs. Remarkably, the system showed sensitivity towards the effect of clinically used direct oral anticoagulation (DOAC) drugs in whole blood coagulation, in contrast to the inability of clinical routine tests prothrombin time (PT) and partial thromboplastin time (PTT) to efficiently monitor this effect. Translation of this nanomagnetic approach into clinic can provide a superior method for monitoring blood coagulation and improve the efficiency of the current diagnostic techniques.

Gender-inclusive practice in pregnancy determination for transgender, gender diverse and non-binary patients in medical imaging.

In recent years, there has been an increased awareness and understanding of the varying gender identities within our society. Consequently, there has also been a need for healthcare providers to be cognizant of the unique needs of a gender-diverse population. Determining the pregnancy status of transgender, gender-diverse and non-binary patients in medical imaging settings has been poorly handled, and there is a lack of standardisation in the Australian and Aotearoa New Zealand setting. The potential risk of exposing a gender-diverse pregnant patient to ionising radiation increases the need for guidance to ensure potentially pregnant persons are not missed during screening questionnaires. This review article explores various approaches to pregnancy status determination for gender-diverse patients, recognising the complexities involved and emphasising the need for future work to establish a widely accepted solution.

INTRAGASTRIC BALLOON AND IMPACT ON WEIGHT LOSS: EXPERIENCE IN QUITO, EQUADOR.

BACKGROUND: Obesity is associated with different medical conditions, such as cardiologic, respiratory, gastrointestinal, and genitourinary, and constitutes a severe health problem. AIMS: This study aimed to evaluate the use of intragastric fluid-filled balloon in the reduction of weight and other measurements related to body composition. METHODS: This is a retrospective, monocentric study involving all patients who opted for the intragastric balloon Spatz® placement from January 2018 to July 2019, with fulfillment of inclusion and exclusion criteria. The patients were analyzed after 6 and 12 months after the intragastric fluid-filled balloon placed. RESULTS: A total of 121 subjects were included in this study, with 83 (68.6%) females and 38 (31.4%) males. The mean age was 36 years and height was 1.64±0.09. Weight mean and standard deviation was 89.85±14.65 kg, and body mass index was 33.05±4.03; body mass index decreased to 29.4 kg/m2 with a mean weight of 79.83 kg, after 12 months of follow-up. There were statistical differences between body mass index and the 12 months in fat percentage, fat-free mass (kg), visceral fat area, and basal metabolic rate. There was a significant variation according to gender, with males having highest reduction. The percentage of excess weight loss was 46.19, and the total weight loss was 9.24 at the end of the study. CONCLUSIONS: The study demonstrated a benefit of intragastric fluid-filled balloon on weight loss after 12 months. At the end of treatment, body mass index and the measurements of body composition were significantly lower. Men benefited more than women from the treatment.

Gender-Affirming Hormone Therapy for the Trans, Gender Diverse, and Nonbinary Community: Coordinating World Professional Association for Transgender Health and Informed Consent Models of Care.

Purpose: Before commencing gender-affirming hormone therapy, people undergo assessments through the World Professional Association for Transgender Health (WPATH) model (typically with a mental health clinician), or an informed consent (IC) model (without a formal mental health assessment). Despite growing demand, these remain poorly coordinated in Australia. We aimed to compare clients attending WPATH and IC services; compare binary and nonbinary clients; and characterize clients with psychiatric diagnoses or longer assessments. Methods: Cross-sectional audit of clients approved for gender-affirming treatment (March 2017-2019) at a specialist clinic (WPATH model, n=212) or a primary care clinic (IC model, n=265). Sociodemographic, mental health, and clinical data were collected from electronic records, and analyzed with pairwise comparisons and multivariable regression. Results: WPATH model clients had more psychiatric diagnoses (mean 1.4 vs. 1.1, p<0.001) and longer assessments for hormones (median 5 vs. 2 sessions, p<0.001) than IC model clients. More IC model clients than WPATH model clients were nonbinary (27% vs. 15%, p=0.016). Nonbinary clients had more psychiatric diagnoses (mean 1.7 vs. 1.1, p<0.001) and longer IC assessments (median 3 vs. 2 sessions, p<0.001) than binary clients. Total psychiatric diagnoses were associated with nonbinary identities (ß 0.7, p=0.001) and health care cards (ß 0.4, p=0.017); depression diagnoses were associated with regional/remote residence (adjusted odds ratio [aOR] 2.2, p=0.011); and anxiety disorders were associated with nonbinary identities (aOR 2.8, p=0.012) and inversely associated with employment (aOR 0.5, p=0.016). Conclusion: WPATH model clients are more likely to have binary identities, mental health diagnoses, and longer assessments than IC model clients. Better coordination is needed to ensure timely gender-affirming care.

Pandemic Diaries: Lived Experiences of Loneliness, Loss, and Hope Among Older Adults During COVID-19.

BACKGROUND AND OBJECTIVES: While research on loneliness in later life has increased during the coronavirus disease 2019 (COVID-19) pandemic, we still lack diverse qualitative approaches capturing lived experiences of lonely older adults. Approaches to research with older adults instead of on them are also scant in gerontological literature on loneliness. Through solicited diaries, this study aimed to explore how older Australians who were already lonely before the pandemic managed lockdowns (stay-at-home orders) in Victoria, Australia, which lived through one of the longest lockdowns in the world. RESEARCH DESIGN AND METHODS: This article is based on qualitative diaries completed by 32 older adults (aged 65 and older). Diaries provide a 'live' document where participants become active research partners, recording and sharing their perceptions and experiences. This method is useful to capture sensitive issues, but to the best of our knowledge has not been employed in loneliness studies. Data were thematically analyzed through the identification of themes within and across diaries. RESULTS: Loneliness was defined by participants as a detrimental absence of companionship and meaningful social interactions. For most, lockdowns exacerbated loneliness, presented new triggers, and upended coping strategies. The disruption of the 'emotion work' involved with managing loneliness led to a reconfiguration of response strategies, including through digital technology, which brought both challenges (e.g., digital ageism) and opportunities (e.g., novel communication forms). DISCUSSION AND IMPLICATIONS: Understanding how older people living alone define and respond to loneliness in diverse contexts-for example, before and during a pandemic that restricts social interaction-provides critical insights to inform interventions to tackle loneliness.

Intragastric balloon and impact on weight loss: experience in quito, equador / Balão intragástrico e impacto na perda de peso: experiência em quito, equador

ABSTRACT BACKGROUND: Obesity is associated with different medical conditions, such as cardiologic, respiratory, gastrointestinal, and genitourinary, and constitutes a severe health problem. AIMS: This study aimed to evaluate the use of intragastric fluid-filled balloon in the reduction of weight and other measurements related to body composition. METHODS: This is a retrospective, monocentric study involving all patients who opted for the intragastric balloon Spatz® placement from January 2018 to July 2019, with fulfillment of inclusion and exclusion criteria. The patients were analyzed after 6 and 12 months after the intragastric fluid-filled balloon placed. RESULTS: A total of 121 subjects were included in this study, with 83 (68.6%) females and 38 (31.4%) males. The mean age was 36 years and height was 1.64±0.09. Weight mean and standard deviation was 89.85±14.65 kg, and body mass index was 33.05±4.03; body mass index decreased to 29.4 kg/m2 with a mean weight of 79.83 kg, after 12 months of follow-up. There were statistical differences between body mass index and the 12 months in fat percentage, fat-free mass (kg), visceral fat area, and basal metabolic rate. There was a significant variation according to gender, with males having highest reduction. The percentage of excess weight loss was 46.19, and the total weight loss was 9.24 at the end of the study. CONCLUSIONS: The study demonstrated a benefit of intragastric fluid-filled balloon on weight loss after 12 months. At the end of treatment, body mass index and the measurements of body composition were significantly lower. Men benefited more than women from the treatment.

RESUMO RACIONAL: A obesidade está associada a diferentes condições médicas, tais como cardiológicas, respiratórias, gastrointestinais, geniturinárias entre outras e constituem um grave problema de saúde. OBJETIVOS: Avaliar o emprêgo do balão intragástrico na redução de peso e em outras medidas relacionadas à composição corporal. MÉTODOS: Estudo retrospectivo, monocêntrico, incluindo todos os pacientes que optaram pela colocação de balão intragástrico Spatz® entre janeiro de 2018 e julho de 2019, com cumprimento dos critérios de inclusão e exclusão. RESULTADOS: Cento e vinte e um indivíduos foram recrutados neste estudo. A média de idade foi de 36 anos e estatura de 1,64±0,09, sendo 83 (68,6%) do sexo feminino e 38 (31,4%) do sexo masculino. A média do peso e o desvio padrão foram de 89,85±14,65 kg e o índice de massa corporal foi de 33,05±4,03. Após 12 meses, o índice de massa corporal diminuiu para 29,4 kg/m2 com um peso médio de 79,83 kg. Foram registradas diferenças estatísticas no índice de massa corporal, no percentual de gordura, massa livre de gordura (kg), área de gordura visceral e taxa metabólica basal. Houve variação significativa de acordo com o sexo, sendo o masculino com maior redução. O porcentual de perda de excesso de peso foi de 46,19% e de perda de peso total de 9,24 %ao final do estudo. CONCLUSÕES: O estudo demonstrou benefícios do balão intragástrico na perda de peso após 12 meses de colocação do balão. Ao final do tratamento, o índice de massa corporal e as medidas de composição corporal foram significativamente menores. Os homens se beneficiaram mais do que as mulheres do tratamento.

Clot-targeted magnetic hyperthermia permeabilizes blood clots to make them more susceptible to thrombolysis.

BACKGROUND: Thrombolysis is a frontline treatment for stroke, which involves the application of tissue plasminogen activator (tPA) to trigger endogenous clot-degradation pathways. However, it is only effective within 4.5 h of symptom onset because of clot contraction preventing tPA permeation into the clot. Magnetic hyperthermia (MH) mediated by tumor-targeted magnetic nanoparticles is used to treat cancer by using local heat generation to trigger apoptosis of cancer cells. OBJECTIVES: To develop clot-targeting magnetic nanoparticles to deliver MH to the surface of human blood clots, and to assess whether this can improve the efficacy of thrombolysis of contracted blood clots. METHODS: Clot-targeting magnetic nanoparticles were developed by functionalizing iron oxide nanoparticles with an antibody recognizing activated integrin αIIbß3 (PAC-1). The magnetic properties of the PAC-1-tagged magnetic nanoparticles were characterized and optimized to deliver clot-targeted MH. RESULTS: Clot-targeted MH increases the efficacy of tPA-mediated thrombolysis in contracted human blood clots, leading to a reduction in clot weight. MH increases the permeability of the clots to tPA, facilitating their breakdown. Scanning electron microscopy reveals that this effect is elicited through enhanced fibrin breakdown and triggering the disruption of red blood cells on the surface of the clot. Importantly, endothelial cells viability in a three-dimensional blood vessel model is unaffected by exposure to MH. CONCLUSIONS: This study demonstrates that clot-targeted MH can enhance the thrombolysis of contracted human blood clots and can be safely applied to enhance the timeframe in which thrombolysis is effective.

Superparamagnetic-blocked state transition under alternating magnetic fields: towards determining the magnetic anisotropy in magnetic suspensions.

The potential of magnetic nanoparticles for acting as efficient catalysts, imaging tracers or heating mediators relays on their superparamagnetic behaviour under alternating magnetic fields. In spite of the relevance of this magnetic phenomenon, the identification of specific fingerprints to unequivocally assign superparamagnetic behaviour to nanomaterials is still lacking. Herein, we report on novel experimental and theoretical evidences related to the superparamagnetism observed in magnetic iron oxide nanoparticle suspensions at room temperature. AC magnetization measurements in a broad field frequency range from mHz to kHz and field intensities up to 40 kA m-1 unambiguously demonstrate the transition from superparamagnetic to blocked states at room temperature. Our experimental observations are supported by a theoretical model based on the stochastic Landau-Liftshitz-Gilbert equation. An empirical expression is proposed to determine the effective magnetic anisotropy from the field frequency value beyond which AC magnetization shows hysteretic behaviour. Our results significantly improve the understanding and description of the superparamagnetism of iron oxide nanoparticles, paving the way towards a more efficient exploitation of their unique magnetic properties.

Exploring the potential of delivering mental health care services using digital technologies in Bangladesh: A qualitative analysis.

Background: Bangladesh is a lower-middle-income country affected by a severe lack of mental health service availability due to a scarcity of mental health experts, limited mental health literacy, and community stigma. In other low and middle-income countries, the online provision of mental health care services has addressed issues affecting service availability, accessibility, mass awareness of services, and stigma. Objective: The current study sought to understand stakeholders' perceptions of the potential of digital media-based mental health care delivery in strengthening Bangladesh's mental health system. Method: Online in-depth interviews were conducted with seven psychiatrists and eleven people with lived experiences of mental health issues. In addition, two online focus groups were conducted with ten psychologists and nine mental health entrepreneurs. A thematic analysis of the audio transcriptions was used to identify themes. Result: Stakeholders perceived that the benefits of digital media-based mental health services included the potential of increasing the awareness, availability, and accessibility of mental health services. Participants recommended: the rehabilitation of existing pathways; the use of social media to raise awareness; and the implementation of strategies that integrate different digital-based services to strengthen the mental health system and foster positive mental health-seeking behaviors. Conclusion: Growing mental health awareness, combined with the appropriate use of digital media as a platform for distributing information and offering mental services, can help to promote mental health care. To strengthen mental health services in Bangladesh, tailored services, increased network coverage, and training are required on digital mental health.

Learning Process Effectiveness During the COVID-19 Pandemic: Teleproctoring Advanced Endoscopic Skills by Training Endoscopists in Endoscopic Sleeve Gastroplasty Procedure.

BACKGROUND AND AIMS: The COVID-19 pandemic has led health institutions to cancel many of the activities including training in different fields. Most practices and training programs have been encouraged to use teleproctoring as an alternative method to enhance physician's ability and assure training. We aimed to evaluate remote training program for endoscopy sleeve gastroplasty (ESG). METHODS: Ten consecutive patients underwent an endoscopic sleeve gastroplasty procedure guided by a proctor expert using an online platform. A stepwise approach was created to assure skill acquisition. RESULTS: All cases were safely performed with no serious adverse events under teleproctoring. The average surgical and suturing times significantly decreased during the training model. From the first 5 cases to the last 5 ones, the endoscopic procedure time decreased from 120 to 93.4 min while suturing time from 92.8 to 68.4 min. The effect size was large in both cases, and the changes were meaningful according to the fitted learning curves. CONCLUSIONS: The proposed teleproctoring program was effective to deliver advanced endoscopic skills such as endosuturing for ESG, despite the restrictions imposed by the COVID-19 pandemic.

Examining the role of governmsent in shaping disability inclusiveness around COVID-19: a framework analysis of Australian guidelines.

BACKGROUND: The COVID-19 pandemic has uncovered the ways in which disabled people are made more vulnerable due to structural inequalities. These vulnerabilities are the result of the interaction between individual and structural factors that shape how risk is experienced by disabled people. In Australia, these vulnerabilities are influenced by the way disability services and care for disabled people are delivered through a consumer-directed approach. We analysed the policies and documentation made by the Australian Government and state and territory governments during the pandemic to explore whether these were disability-inclusive. We aimed to unpack how these policies shaped disabled people as vulnerable citizens. METHODS: Guided by documentary research, we used framework analysis to examine the policies of the Australian Government and state and territory governments. We analysed legislation that was given royal assent by the federal, state and territory governments, and documents (reports, fact sheets, guidance documents, etc.) published by the federal government and the state of Victoria (given that this state experienced the brunt of the epidemic in Australia) between February 2020 to August of 2020. RESULTS: We found that most of the resources were not aimed at disabled people, but at carers and workers within disability services. In addition, most policies formulated by the Australian Government were related to the expansion of welfare services and the creation of economic stimulus schemes. However, while the stimulus included unemployed people, the expansion of benefits explicitly excluded disabled people who were not employed. Most of the legislation and documents offered accessibility options, though most of these options were only available in English. Disability oriented agencies offered more extensive accessibility options. CONCLUSIONS: The findings indicate a large number of documents addressing the needs of disabled people. However, disability-inclusiveness appeared to be inconsistent and not fully considered, leaving disabled people exposed to greater risk of COVID-19. Neoliberal policies in the health and welfare sector in Australia have led to an individualisation of the responsibility to remain healthy and a reliance on people as independent consumers. Governments need to take a clear stance towards the emergence of such a discourse that actively disvalues disabled people.

Continuous Intraoperative Neurophysiological Monitoring of the Motor Pathways Using Depth Electrodes During Surgical Resection of an Epileptogenic Lesion: A Novel Technique.

BACKGROUND AND IMPORTANCE: Intraoperative neurophysiological monitoring of the motor pathways during epilepsy surgery is essential to safely achieve maximal resection of the epileptogenic zone. Motor evoked potential (MEP) recording is usually performed intermittently during resection using a handheld stimulator or continuously through an electrode array placed on the motor cortex. We present a novel variation of continuous MEP acquisition through previously implanted depth electrodes in the perirolandic cortex. CLINICAL PRESENTATION: A 60-yr-old woman with a history of a left frontal meningioma (World Health Organization [WHO] grade II) treated with surgical resection and radiation presented with residual right hemiparesis and refractory epilepsy. Imaging demonstrated a perirolandic lesion with surrounding edema and mass effect in the prior surgical site, suspicious for radiation necrosis versus tumor recurrence. Presurgical electrocorticography (ECoG) with orthogonal, stereotactically implanted depth electrodes (stereoelectroencephalography [SEEG]) of the perirolandic cortex captured seizure onsets from the supplementary motor area (SMA) and primary motor cortex (PMC). The patient underwent a left frontal craniotomy for repeat resection and tissue diagnosis. Intraoperative ECoG and MEPs were obtained continuously with direct cortical stimulation through the indwelling SEEG electrodes in the PMC. Maximal resection was achieved with preservation of direct cortical MEPs and without deterioration of her baseline hemiparesis. Biopsy revealed radiation necrosis. At 30-mo follow-up, the patient had only rare seizures (Engel class IIB). CONCLUSION: Intraoperative cortical MEP acquisition through implanted SEEG electrode arrays is a potentially safe and effective alternative approach to continuously monitor the motor pathways during the resection of a perirolandic epileptogenic lesion, without the need for surgical interruptions.

Involvement of Mesenchymal Stem Cells in Oral Mucosal Bacterial Immunotherapy.

Recent clinical observations indicate that bacterial vaccines induce cross-protection against infections produced by different microorganisms. MV130, a polyvalent bacterial sublingual preparation designed to prevent recurrent respiratory infectious diseases, reduces the infection rate in patients with recurrent respiratory tract infections. On the other hand, mesenchymal stem cells (MSCs) are key cell components that contribute to the maintenance of tissue homeostasis and exert both immunostimulatory and immunosuppressive functions. Herein, we study the effects of MV130 in human MSC functionality as a potential mechanism that contributes to its clinical benefits. We provide evidence that during MV130 sublingual immunization of mice, resident oral mucosa MSCs can take up MV130 components and their numbers remain unchanged after vaccination, in contrast to granulocytes that are recruited from extramucosal tissues. MSCs treated in vitro with MV130 show an increased viability without affecting their differentiation potential. In the short-term, MSC treatment with MV130 induces higher leukocyte recruitment and T cell expansion. In contrast, once T-cell activation is initiated, MV130 stimulation induces an up-regulated expression of immunosuppressor factors in MSCs. Accordingly, MV130-primed MSCs reduce T lymphocyte proliferation, induce the differentiation of dendritic cells with immunosuppressive features and favor M2-like macrophage polarization, thus counterbalancing the immune response. In addition, MSCs trained with MV130 undergo functional changes, enhancing their immunomodulatory response to a secondary stimulus. Finally, we show that MSCs are able to uptake, process and retain a reservoir of the TLR ligands derived from MV130 digestion which can be subsequently transferred to dendritic cells, an additional feature that also may be associated to trained immunity.

Epidemiological assessment of acetabular fractures in a level one trauma centre: A 7-Year observational study.

PURPOSE: The present study was conducted to evaluate the epidemiological characteristics of the Acetabular fractures treated in a level one trauma centre of India. This study is one of the largest to provide first-hand information regarding the demography, fracture patterns, other associated injuries, and the hospital stay of acetabular fractures in India. METHOD: Patients admitted with the diagnosis of acetabular fractures between January 2013 and November 2019 were retrospectively analyzed in terms of demographic data such as age and sex, mechanism of injury, other associated injuries, and the duration of hospital stay. RESULTS: A total of 305 patients with 313 fractures of the acetabulum were included in the study. Among the 305 patients, 268 (87.8%) were male and 37 (12.1%) were female, with a declining male to female ratio over the years. The mean age was 37.1 ± 13.2 years (range 14-84 years). During the seven years, the mean age of presentation progressively increased. Linear regression showed an increase from 33 to 40 years from 2013 to 2019 (R2 = 0.027). Road traffic injuries were the most common mechanism of injury, contributing to about 77.4% of all cases. Associated injuries were seen in 62% of total cases with multiple system involvement in 26.6% of patients. The most frequent pattern in this epidemiological study was an isolated posterior wall fracture (21.4%) while the isolated anterior wall was the least frequent (0.95%). CONCLUSION: Acetabular fractures are increasing in numbers and with increasing knowledge so is their surgical management in our country. It shall be prudent to establish an integrated electronic national trauma registry to maintain complete documentation in all institutions dealing with trauma management to ascertain the changing trends of acetabular fracture patterns in the country over time.

Controlling human platelet activation with calcium-binding nanoparticles.

Human platelets aggregate at sites of blood vessel damage in response to a rise in their cytosolic calcium concentration. Controlling these cytosolic calcium rises would provide a method to inhibit platelet activation and prevent the unwanted blood clots that causes heart attack and strokes. Previously we have predicted that calcium accumulation within the lumen of an infolded portion of the platelet plasma membrane called the open canalicular system (OCS) is essential for maintaining this cytosolic calcium rise. Due to its nanometer dimensions of the OCS, it has been difficult to measure or interfere with the predicted luminal calcium accumulation. Here we utilise iron oxide magnetic nanoparticles coated with the known calcium chelator, citrate, to create calcium-binding nanoparticles. These were used to assess whether an OCS calcium store plays a role in controlling the dynamics of human platelet activation and aggregation. We demonstrate that citrate-coated nanoparticles are rapidly and selectively uptaken into the OCS of activated human platelets, where they act to buffer the accumulation of calcium there. Treatment with these calcium-binding nanoparticles reduced thrombin-evoked cytosolic calcium rises, and slowed platelet aggregation and clot retraction in human platelets. In contrast, nanoparticles that cannot bind calcium have no effect. This study demonstrates that the OCS acts as a key source of calcium for maintaining cytosolic calcium rises and accelerating platelet aggregation, and that calcium-binding nanoparticles targeted to the OCS could provide an anti-platelet therapy to treat patients at risk of suffering heart attacks or strokes.

Esterase-Cleavable 2D Assemblies of Magnetic Iron Oxide Nanocubes: Exploiting Enzymatic Polymer Disassembling To Improve Magnetic Hyperthermia Heat Losses.

Here, we report a nanoplatform based on iron oxide nanocubes (IONCs) coated with a bioresorbable polymer that, upon exposure to lytic enzymes, can be disassembled increasing the heat performances in comparison with the initial clusters. We have developed two-dimensional (2D) clusters by exploiting benchmark IONCs as heat mediators for magnetic hyperthermia and a polyhydroxyalkanoate (PHA) copolymer, a biodegradable polymer produced by bacteria that can be digested by intracellular esterase enzymes. The comparison of magnetic heat performance of the 2D assemblies with 3D centrosymmetrical assemblies or single IONCs emphasizes the benefit of the 2D assembly. Moreover, the heat losses of 2D assemblies dispersed in water are better than the 3D assemblies but worse than for single nanocubes. On the other hand, when the 2D magnetic beads (2D-MNBs) are incubated with the esterase enzyme at a physiological temperature, their magnetic heat performances began to progressively increase. After 2 h of incubation, specific absorption rate values of the 2D assembly double the ones of individually coated nanocubes. Such an increase can be mainly correlated to the splitting of the 2D-MNBs into smaller size clusters with a chain-like configuration containing few nanocubes. Moreover, 2D-MNBs exhibited nonvariable heat performances even after intentionally inducing their aggregation. Magnetophoresis measurements indicate a comparable response of 3D and 2D clusters to external magnets (0.3 T) that is by far faster than that of single nanocubes. This feature is crucial for a physical accumulation of magnetic materials in the presence of magnetic field gradients. This system is the first example of a nanoplatform that, upon exposure to lytic enzymes, such as those present in a tumor environment, can be disassembled from the initial 2D-MNB organization to chain-like assemblies with clear improvement of the heat magnetic losses resulting in better heat dissipation performances. The potential application of 2D nanoassemblies based on the cleavable PHAs for preserving their magnetic losses inside cells will benefit hyperthermia therapies mediated by magnetic nanoparticles under alternating magnetic fields.