Search

Viral hepatitis is among the top four causes of mortality globally, causing 1.4 million deaths each year, exceeding tuberculosis, malaria and human immunodeficiency virus. Hepatitis B and C are responsible for 90% of hepatitis deaths, and the remaining 10% are caused by other hepatitis viruses. The annual number of deaths from hepatitis C is declining, whereas the numbers of deaths from hepatitis B and D are increasing. Hepatitis B alone represents the seven highest cause of mortality worldwide. Spurred on by development of curative antivirals for hepatitis C and expanding access to hepatitis B virus (HBV) vaccination, the World Health Organization has committed to eliminating viral hepatitis as a public health threat by 2030. Like the majority of current antivirals, those available for HBV are virostatic. They are capable of suppressing viral replication but cannot eliminate the virus from infected patients. Therefore, treatment is lifelong. Long-term adherence to medication continues to represent a major challenge. Importantly, HBV often reactivates, leading to potential life-threatening events in immunosuppressed patients. Therapeutic options are limited for hepatitis D; however, promising new, effective antivirals are on the horizon. Recent advances have emerged in medicinal chemistry and drug delivery approaches to produce ultra-long-acting (XLA) antivirals. These can extend antiviral activity from months to 1 year or even longer. These new formulations can overcome the challenges of daily dosing and maximize drug exposure. The development of XLA antivirals targeting viral hepatitis may also facilitate cure strategies.

Background The advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has been associated with a significant decline in coronavirus disease 2019 (COVID-19) hospitalizations and deaths. However, little is known about the benefits experienced by different population groups and/or using distinct vaccines. Methods The Spanish public registry was analyzed to examine associations between weekly vaccination scale-up and the incidence of COVID-19 hospitalizations by age, sex, and vaccine modality. The study period extended from January 2020 to June 2021. Results A total of 363 960 COVID-19 hospitalizations were recorded in Spain during the study period, with three peaks in March 2020, November 2020, and January 2021. The incidence of COVID-19 hospitalizations per 100 000 population increased exponentially with age, on average 71.5% for each decade older. Overall, individuals older than 60 years of age accounted for 65% of all COVID-19 hospitalizations. The speedy vaccination rollout since the end of 2020, with prioritization of the elderly groups, resulted in a rapid fall in COVID-19 hospitalizations starting in February 2021. The benefit was already noticed 3–4 weeks after the first dose, regardless of the vaccine modality. Conclusions COVID-19 hospitalizations increased exponentially with age in all three peaks of SARS-CoV-2 infection in Spain. Early mass vaccination of people over 60 years of age prevented a fourth wave of COVID-19 hospitalizations during the spring of 2021.

Current treatment of chronic wounds has been critically limited by various factors, including bacterial infection, biofilm formation, impaired angiogenesis, and prolonged inflammation. Addressing these challenges, we developed a multifunctional wound dressing-based three-pronged approach for accelerating wound healing. The multifunctional wound dressing, composed of nanofibers, functional nanoparticles, natural biopolymers, and selected protein and peptide, can target multiple endogenous repair mechanisms and represents a promising alternative to current wound healing products.

Objective To implement a multifaceted wellness program in an academic radiology department to prevent burnout and to assess initial outcomes with special focus on the challenges related to the coronavirus disease 2019 (COVID-19) pandemic. Methods A wellness program was established to address institutional and personal factors of burnout. The program focused on interventions to improve efficiency of practice, provide personal and career support, and create a culture of wellness. The components of the program were designed with input from radiology faculty, and the program was financially supported by the hospital’s physician organization. A survey was performed 6 months after the initiation of the program to determine radiologist engagement and satisfaction. With the onset of the COVID-19 pandemic, a new survey was administered to identify needs of faculty and adjust initiatives. This study was exempt from institutional review board approval. Results The majority of radiologists (79%) agreed or strongly agreed that the wellness program provided opportunities to connect with coworkers. All radiologists agreed that the program was helpful and should be continued. During the COVID-19 pandemic, 49% of physicians requested initiatives focused on well-being, emotional health, and mindfulness to support them during the crisis. Conclusions The implementation of a faculty wellness program in an academic radiology department addressed institutional and personal factors of burnout, allowed faculty to connect with coworkers, and was found to be helpful by all radiologists. The COVID-19 pandemic shifted needs to well-being and emotional health initiatives. Follow-up data are necessary to assess its effect on burnout reduction.

One of the main challenges of cardiovascular tissue engineering is the development of bioresorbable and compliant small-diameter vascular grafts (SDVG) for patients where autologous grafts are not an option. In this work, electrospun bilayered bioresorbable SDVG based on blends of poly(L-lactic acid) (PLLA) and segmented polyurethane (PHD) were prepared and evaluated. The inner layer of these SDVG was surface-modified with heparin, following a methodology involving PHD urethane functional groups. Heparin was selected as anticoagulant agent, and also due to its ability to promote human umbilical vein endothelial cells (HUVECs) growth and to inhibit smooth muscle cells over-proliferation, main cause of neointimal hyperplasia and restenosis. Immobilized heparin was quantified and changes in SDVG microstructure were investigated through SEM. Tensile properties of the heparin-functionalized SDVG resembled those of saphenous vein. Vascular grafts were seeded with HUVECs and cultured on a flow-perfusion bioreactor to analyze the effect of heparin on graft endothelization under simulated physiological-like conditions. The analysis of endothelial cells attachment and gene expression (Real-Time PCR) pointed out that the surface functionalization with heparin successfully promoted a stable and functional endothelial cell layer.

Atropine is an old-known drug which is gaining increasing attention due to the myriad of therapeutic effects it may trigger on eye structures. Nevertheless, novel applications may require more adequate topical formulations.This review aims to gather the existing knowledge about atropine and its clinical applications in the ophthalmological field when administered topically. Atropine ocular pharmacokinetics is paid a special attention, including recent evidences of the capability of the drug to access to the posterior segment. Ocular bioavailability and systemic bioavailability are counterbalanced. Finally, limitations of traditional dosage forms and potential advantages of under investigation delivery systems are analyzed.Mydriasis and cyclopegia have been widely exploited for eye examination, management of anterior segment diseases, and more recently as antidotes of chemical weapons. Improved knowledge on drug receptors and related pathways explains atropine repositioning as an outstanding tool to prevent myopia. The ease with which atropine penetrates ocular tissues is a double edged sword, that is, while it ensures therapeutic levels in the posterior segment, the unspecific distribution causes a wide variety of untoward effects. The design of formulations that can selectively deliver atropine to the target tissue for each specific application is an urgent unmet need.

Background: Uncontrolled hypertension is a significant risk factor for cardiovascu­lar morbidity and mortality. In the United States, many patients remain uncontrolled, in part, due to poor medication adherence. Efforts to improve hypertension control include not only attending to medical management of the disease but also the social determinants of health, which impact medication adherence, and ultimately blood pressure control.Purpose: To determine which social deter­minants – health care access or community and social stressors - explain medication adherence.Methods: In this cross-sectional analysis, we used baseline data (N=1820, col­lected August 2017 to October 2019) from a pragmatic trial, which compares the effectiveness of a multi-level intervention including collaborative care and a stepped approach with enhanced standard of care for improving blood pressure. We used logistic regression analyses to examine the association between patient experiences of care and community and social stressors with medication adherence.Results: The participants represented a diverse sample: mean age of 60 years; 59% female; 57.3% Black, 9.6% Hispanic, and 33.2% White. All participants had a blood pressure reading ≥140/90 mm Hg (mean blood pressure – 152/85 mm Hg). Half of the participants reported some level of non-adherence to medication. Regression analy­sis showed that, compared with Whites, Blacks (AOR .47; 95% CIs: .37-.60, P

Objectives: The use of collaborative care teams, comprising nurse care managers and community health workers, has emerged as a promising strategy to tackle hyperten­sion disparities by addressing patients’ social determinants of health. We sought to identify which social determinants of health are associated with a patient’s likelihood of engaging with collaborative care team members and with the nurse care manager’s likelihood of enlisting community health workers (CHW) to provide additional sup­port to patients. Methods: We conducted a within-group longitudinal analysis of patients assigned to receive a collaborative care intervention in a pragmatic, cluster randomized trial that aims to reduce disparities in hypertension control (N=888). Generalized estimating equations were used to identify which social deter­minants of health, reported on the study’s baseline survey, were associated with the odds of patients engaging with the col­laborative care intervention, and of nurses deploying community health workers. Results: Patients who were unable to work and those with higher health literacy were less likely to engage with the collaborative care team than those who were employed full time or had lower health literacy, respectively. Patients had a greater likeli­hood of being referred to a community health worker by their care manager if they reported higher health literacy, perceived stress, or food insecurity, while those report­ing higher numeracy had lower odds of receiving a CHW referral. Implications/Conclusions: A patient’s social determinants of health influence the extent of engagement in a collaborative care intervention and nurse care manager appraisals of the need for supplementary support provided by community health workers. Ethn Dis. 2021;31(1):47-56; doi:10.18865/ed.31.1.47

Poly-3-hydroxybutyrate (PHB) is a biocompatible polymer produced by a wide variety of bacteria from different carbon sources. However, the carbon source effects on PHB properties are largely unknown. This study aimed to characterize PHB produced by Paraburkholderia xenovorans LB400 supplied with glucose (PHBg), mannitol (PHBm), or xylose (PHBx) as sole carbon sources and to evaluate their potential application as the main component of scaffolds obtained by electrospinning. The PHBs produced by strain LB400 had different molecular weights; the largest value corresponded to PHBm. The XRD-spectra revealed that PHB produced by strain LB400 from the three carbon sources are less crystalline than the commercially available polymer (PHBc). Moreover, the electrospinning process decreases even further their degree of crystallinity, which could lead to an improvement in the mechanical properties of the polymers. Relevantly, PHBx-microfibers exhibited mechanical characteristics similar to those of human skin. None of the scaffolds made of PHBs from strain LB400 grown in different carbon sources showed adverse effects on fibroblast cell growth. Thus, modifying the sugar used as the carbon source may be useful to tune the structural properties of PHB and its performance as a component of electrospun scaffolds, which may better fit specific biomedical applications.

Introduction: As anti-immigrant hostility toward Latino populations grows, more fervent attention is needed to consider strength-based approaches to attenuate the effects of perceived discrimination. This systematic review synthesizes the evidence about the effects of racial/ethnic discrimination on mental, physical, and health behaviors of Latinos and examines the coping mechanisms and cultural factors that attenuate the negative association between discrimination and health among adult Latinos living in the United States. Method: The search criteria included articles that (a) examined ethnic/racial discrimination in relationship to a health outcome, (b) had study samples composed of least 25% Latino adults, and (c) were written in English. Results: A total of 33 studies were included in the review. Our findings demonstrated the negative relationship between perceived discrimination, mental health, and health behaviors. The evidence for the relationship between perceived discrimination and physical health was less robust. For mental health, greater feeling of ethnic pride and belonging attenuated the negative relationship between perceived discrimination and mental health. Conclusions: Our findings highlight the potential for building on ethnic identity for addressing mental health and perceived discrimination. Future research directions are outlined to address identified gaps.

Osteosarcoma(OS) represents the main cancer affecting bone tissue, and one of the most frequent in children. In this review we discuss the major pathological hallmarks of this pathology, its current therapeutics, new active biomolecules, as well as the nanotechnology outbreak applied to the development of innovative strategies for selective OS targeting. Small RNA molecules play a role as key-regulator molecules capable of orchestrate different responses in what concerns cancer initiation, proliferation, migration and invasiveness. Frequently associated with lung metastasis, new strategies are urgent to upgrade the therapeutic outcomes and the life-expectancy prospects. Hence, the prominent rise of micelleplexes as multifaceted and efficient structures for nucleic acid delivery and selective drug targeting is revisited here with special emphasis on ligand-mediated active targeting. Future landmarks toward the development of novel nanostrategies for both OS diagnosis and OS therapy improvements are also discussed.

ImportanceTo our knowledge, this is the first study to analyze long–term passage (6 months after immunization) of specific antibodies induced by BNT162b2 COVID-19 vaccine through breast milk.ObjectivesMain objective: to determine SARS-CoV-2 vaccine induced antibody levels in the breast milk of lactating women 4 weeks after mRNA BNT162b2 Pfizer-BioNTech COVID-19 complete vaccination.Secondary objectives: to analyze SARS-CoV-2 antibody levels (breast milk and serum) at different time-points after vaccination, examine the correlation of SARS-CoV-2 antibody levels between serum and breast milk, describe adverse events related to vaccination (AErV) in both mothers and infants and determine the rate of COVID-19 infections.DesignProspective cohort study between February and September 2021.SettingParc Sanitari Sant Joan de Déu, an urban hospital in Spain.ParticipantsDuring our health worker vaccination campaign at our hospital between January and March 2, we recruited 33 lactating women vaccinated with BNT162b2 Pfizer-BioNTech COVID-19.ResultsA total of 33 volunteers were included in the study. The median (IQR) age of mothers was 38 (36-39) years and 15 (10-22) months for the infants.Primary end-point: at 4 w after second dose median (IQR) IgG-S1 levels for serum–milk pairs were 12,478 (6,870-20,801) to 50.4 (24.3-104) arbitrary units (AU) per mL.Secondary end-pointsSARS-CoV-2 antibody levels at different time-points were (serum-milk): 519 (234-937) to 1 (0-2.9) AU/mL at 2w after first dose, 18,644 (9,923-29,264) to 78 (33.7-128) AU/mL at 2w, 4,094 (2,413-8,480) to 19.9 (10.8-51.9) AU/mL at 12w, and 1,350 (831-2,298) to 8.9 (7.8-31.5) at 24w after second dose.We found a positive correlation of SARS-CoV-2 antibody levels between serum and breast milk (Pearson correlation coefficient 0.68).No serious AErV were observed.We found two (6%) COVID-19 vaccine breakthrough infections.ConclusionsPfizer-BioNTech COVID-19 vaccination is safe during breastfeeding and it transmits antibodies into breast milk with a positive correlation with serum levels, and both decrease over time in a 6-month follow-up. Infants of breastfeeding vaccinated women could be protected for at least six months after vaccination and serum determination of SARS-CoV-2 IgG-S1 could indicate the breastmilk levels of antibodies during this period.

Introduction/Background* Women with germline mutations in the BRCA ½ genes have a lifetime increased risk of ovarian cancer, 36 - 63% and 10-27% respectively. Accordingly, once childbearing is completed, Risk Reduction Salpingo-oophorectomy (RRSO) is recommended in this group of patients. The purpose of this study was to determine the presurgical findings and the incidence of Serous Tubal intraepithelial carcinoma (STIC) and occult carcinomas in BRCA mutations carriers in whom a RRSO was performed. Methodology Prospective study that included patients with documented BRCA mutation who accepted RRSO between January 2011 to January 2021 at the Hospital Universitario 12 de Octubre. The study was approved by the ethics committee of the institution. During the month prior to surgery, a systematic ultrasound (US) and determination of serum Ca 125 levels were performed. Specialized gynecologists performed RRSO by laparoscopy. Unilateral or bilateral adnexectomy was performed according to the surgical history of each patient. Pelvic washing was done in all cases at the beginning of the procedure and tubes were removed at the uterine insertion. All the histologic exams were performed by pathologists subspecialized in Gynecologic Oncology and the sectioning and extensively examining of the fimbriated end protocol (SEE-FIM protocol) was applied. STIC was defined using a combination of morphologic evaluations to distinguish in from p53 signatures, STIL and invasive carcinoma. All statistical analysis was performed by Stata/IC 13.0 for Windows. Result(s)* A total of 115 were included. Of them, 50.4% had BRCA 1 mutation and 49.6% BRCA 2 mutation. Mean (+/- Standard deviation, SD) age at surgery was 49.2 (5.8) years. Of note, 40.9% underwent surgical menopause. The median Ca-125 value prior to surgery was 29.4 u/L. Adnexal findings in presurgery ultrasound were normal (104, 90.4%) or benign cyst (11, 17.4%). Also, endometrial polyps were found in 3.5% (3) of patients. Pathologic exam showed STIC in 5 (4.5%) patients and invasive ovarian carcinoma in 1 (0.9%). Conclusion* Currently, RRSO is the only tool to reduce the risk of ovarian cancer in BRCA mutations carriers. However, the incidence of STIC after RRSO is not very high.

The goal of this work was to synthesize hybrid thin films prepared combining polyamide-6 (N6) and microcellulose (CE) at various weight ratios. Products exhibited improved mechanical properties, temperature-tunable hydrophilicity, and antimicrobial features. The obtained N6@CE films were grafted with N-vinylcaprolactam (NVCL) using gamma-rays, providing temperature responsiveness in a range of 37–38 °C. The grafting degree was studied as a function of CE percentage on the film, monomer concentration, and absorbed dose. The grafting degree increased with the percentage of CE on the film, and the maximum grafting was achieved at monomer concentration and the irradiation dose of 20% NVCL and 20 kGy, respectively. NVCL grafting was confirmed by SEM, 13C-CPMAS NMR, FTIR-ATR, and XPS. SEM images attested formation of nanopores on the structure, caused by the grafting process, that consequently triggering on the new characteristics of the final materials. Potential performance of the composites as wound dressings was investigated in terms of their capability to loading and release of antimicrobial agents, such as vancomycin and benzalkonium chloride. NVCL grafting enhanced the uptake of both drugs, especially benzalkonium chloride, and regulated their release demonstrating antimicrobial effectiveness against Staphylococcus aureus.

Cancer is a leading cause of death worldwide. Despite the advances in prevention, detection, diagnosis, and treatment, many tumors relapse and become resistant to conventional treatments. Theranostics and real-time molecular imaging using nanoscale materials, such as polymeric micelles, are being widely explored as promising gold standard approaches in a personalized medicine perspective for cancer. Theranostics is intended for the three-in-one purpose of simultaneously diagnose, treat, and monitor tumor evolution. Compared to the conventional treatments, theranostic functional polymeric micelles have demonstrated great potential to improve and monitor the delivery of pharmacological agents following administration, which can enhance therapeutic efficacy and minimize off-target toxicity. This review provides an overview of the current state of the art related to the use of polymeric micelles as theranostic multicarriers targeting the cancer cells and tumor microenvironment. Some future directions toward the design of nanotheranostic platforms are also proposed. In particular, we focused our attention on Pluronics and Tetronics as they advantageously present sol-gel transition, which makes them smart nanosystems suitable for oral theranostic administration and sustained depots, increasing patient compliance.

Strategies to load prednisolone or dexamethasone in preformed poly(L-lactic acid) (PLA) filaments and 3D printed scaffolds were explored as a way of personalizing the drug, the dose and the release profile for regenerative medicine purposes. Instead of starting from a PLA filament preloaded with a given content of drug, we explored two more versatile strategies. The first one involved the soaking of PLA filaments into a drug solution prepared in a solvent that reversibly swelled PLA; during 3D printing the melting of PLA contributed to the efficient integration (encapsulation) of the drug inside the printed strand. The second strategy consisted in first printing the 3D PLA scaffolds followed by soaking in a suitable drug solution in order to exploit the higher specific surface of the printed strands compared to the filament. Sustained release profiles were recorded when either prednisolone or dexamethasone were loaded in preformed PLA filaments, while rapid release was recorded for 3D PLA scaffolds loaded after printing. The combination of the two proposed methods reported here opened the possibility of creating concentration gradients of different drugs in the same scaffold exhibiting distinct release patterns. Namely, the strand core contained an active ingredient to be slowly released, while the surface was covered with other active ingredient that could be rapidly delivered. The feasibility of this approach was confirmed through dual loading of dexamethasone in the filament and of prednisolone on the preformed scaffold. Drug-loaded scaffolds were characterized in terms of printability, structural characteristics (DSC, XRD), mechanical properties, biodegradation, and ability to promote cell attachment and proliferation. Finally, anti-inflammatory response and osteoinductive properties were verified in cell cultures.

Bone scaffolds prepared with porogens and bioactive agents can accelerate bone tissue formation by providing a suitable 3D-porous structure that promotes cell colonization and differentiation towards the osteogenic lineage. In this work, scaffolds containing poly(e-caprolactone) (PCL) as biopolymeric matrix, silk fibroin as cell adhesion promoter, and dexamethasone as osteogenic differentiation agent, were prepared by supercritical foaming (37 °C, 140 bar, 1 h), a solvent-free method providing a straightforward and effective route for the processing of bioactive grafts. Silk fibroin aerogels in the form of submicron-sized particles were herein developed for the first time and evaluated as porosity inducers. These aerogels incorporated in the scaffolds refined the porous structure and facilitated cell infiltration and the biological fluid transport. Dexamethasone was used in two different forms (base, DX and phosphate salt, DS) to unveil their role in bone regeneration. The morphology of the scaffolds was evaluated using mercury intrusion porosimetry, helium pycnometry and in silico structure modelling. Different release profiles were recorded when using DX or DS. The biological performance was assessed in in vivo tests in calvarial defects using a rat model. Results unveiled the interesting morphological properties of the scaffolds in terms of porosity, pore size distribution and interconnectivity, which are compatible with their application in bone repair. In vivo tests showed the importance of the dexamethasone form and release profile in promoting the bone tissue regeneration with a significant increase in the number of ossification foci and in bone repair extent 14 weeks post-implantation for certain formulations.

Medical devices are becoming key players on health monitoring and treatment. Advances in materials science and electronics have paved the way to the design of advanced wearable, insertable, and implantable medical devices suitable for the prevention and cure of diseases and the physical or functional replacement of damaged tissues or organs. However, intimate and prolonged contact of the medical devices with the human body increases the risks of adverse foreign-body reactions and biofilm formation. Drugs can be included in/on the medical device not only to minimize the risks but also to improve the therapeutic outcomes. Drug-eluting medical devices can deliver the drug in the place where it is needed using lower doses and avoiding systemic effects. Drug-device combination products that release the drug following preestablished rates have already demonstrated their clinical relevance. The aim of this mini-review is to bring attention to medical devices that can actively regulate drug release as a function of tiny changes in their environment, caused by the pathology itself, microorganisms adhesion or some external events. Thus, endowing medical devices with stimuli-responsiveness should allow for precise, on-demand, regulated release of the ancillary drugs to expand the therapeutic performance of the medical device and also should serve as a first step to offer personalized solutions to each patient. Main sections deal with smart drug-eluting medical devices that are sensitive to infection-related stimuli, natural healing processes, mechanical forces, electric fields, ultrasound, near-infrared radiation, or chemicals such as vitamin C.

Polymeric micelles represent nowadays an interesting formulative approach for ocular drug delivery, as they act as solubility enhancers of poorly soluble drugs and promote drug transport across cornea and sclera. In particular, in the last 5 years polymeric nanomicelles have been increasingly investigated to overcome some of the important challenges of the topical treatment of ocular diseases.The aim of this review was to gather up-to-date information on the different roles that polymeric micelles (commonly in the nanosize scale) can play in ocular delivery. Thus, after a general description of ocular barriers and micelles features, the attention is focused on those properties that are relevant for ophthalmic application. Finally, their efficacy in improving the ocular delivery of different classes of therapeutics (anti-inflammatory, immunosuppressant, antiglaucoma, antifungal, and antiviral drugs) are reported.Although still a few, in vivo experiments have clearly demonstrated the capability of polymeric nanomicelles to overcome a variety of hurdles associated to ocular therapy, notably increasing drug bioavailability. However, there are still some very important issues to be solved, such as tolerability and stability; additionally, the role of micelles in drug uptake by the ocular tissues and their potential for the treatment of posterior eye diseases still need to be clarified/verified.

2-Hydroxyethyl methacrylate (HEMA) and N-vinylcaprolactam (NVCL) were grafted onto polypropylene films (PP) by radiation-induced grafting, using gamma-radiation (from a 60Co gamma source) with the aim of improving their surface properties and endow the films with the ability to act as drug-eluting materials. Different γ-radiation doses, reaction temperatures, and monomer concentrations were tested to understand the effect that each variable had on the grafting yield of each compound in separate, and to identify the optimum grafting conditions. The PP films were grafted using the pre-irradiation oxidative method, in a one- and two-step procedure, to obtain binary grafts of various architectures, namely (PP-g-HEMA)-g-NVCL, (PP-g-NVCL)-g-HEMA, and PP-g-(HEMA-co-NVCL). The untreated and modified PP films were characterized by infrared spectroscopy (FTIR-ATR), thermal analyses (DSC and TGA), swelling degree, and contact angle measurements. The temperature responsiveness of the films was evaluated through changes induced at the lower critical solution temperature (LCST), which allowed the material to load and release benzalkonium chloride and ciprofloxacin.

The COVID-19 pandemic has raised questions among individuals who are breastfeeding, both because of the possibility of viral transmission to infants during breastfeeding and, more recently, of the potential risks and benefits of vaccination in this specific population. Previous studies have reported the presence of anti–SARS-CoV-2 antibodies in breast milk of COVID-19–infected lactating women,1 and recently several studies have demonstrated the passage of postvaccine antibodies through breast milk in women vaccinated with novel mRNA-based vaccines.1,2 In the present study, conducted between February and March 2021 at Parc Sanitari Sant Joan de Deu, an urban hospital in Spain, we sought to characterize the levels of specific SARS-CoV-2 antibodies in the breast milk of mRNA-vaccinated women across time, as well as their correlation with serum antibody levels.

Pseudophakic cystoid macular edema (PCME), caused by chronic inflammation, is the most common cause of visual impairment in the medium-term after cataract surgery. Therefore, the prophylactic topical administration of combined steroidal and non-steroidal anti-inflammatory drugs is commonly done. Drug-eluting intraocular lenses (IOLs) gained interest as an efficient way to overcome the compliance issues related to the use of ocular drops without the need for additional surgical steps. The incorporation of functional monomers and molecular imprinting were herein applied to design hydrogels suitable as IOLs and able to co-deliver steroidal (dexamethasone sodium phosphate) and non-steroidal (bromfenac sodium) drugs. The incorporation of N-(2-aminopropyl) methacrylamide (APMA) increased the drug uptake and improved the in vitro release kinetics. Imprinting with bromfenac resulted in a decreased drug release due to permanent drug bonding, while imprinting with dexamethasone increased the amount of dexamethasone released after dual-drug loading. The application of a mathematical model to predict the in vivo drug release behavior suggests the feasibility of achieving therapeutic drug concentrations of bromfenac and dexamethasone in the aqueous humor for about 2 and 8 weeks, respectively, which is compatible with the current topical prophylaxis after cataract surgery This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 813440 (OR-BITAL—Ocular Research by Integrated Training and Learning) and is also supported by Fundação para a Ciência e Tecnologia (FCT) [UID/QUI/00100/2019, UIDB/00100/2020, and UID/BIM/04585/2020]. SI

Age-related eye disorders are chronic diseases that affect millions of people worldwide. They cause visual impairment and, in some cases, irreversible blindness. Drug targeting to the retina is still a challenge due to the difficulties with drug distribution, crossing eye barriers, and reaching intraocular tissues in an effective therapeutic concentration. Although intravitreal injections can directly deliver drugs to the posterior segment of the eye, it remains an invasive technique and leads to several side effects. Conventional formulations such as emulsions, suspensions, or ointments have been related to frequent instillation and inability to reach intraocular tissues. New drug delivery systems and medical devices have also been designed. Nevertheless, these treatments are not always effective and sometimes require the presence of a specialist for the administration of the dose. Therefore, treatments for age-related ocular diseases remain as one of the major unmet clinical needs to manage these widespread eye conditions. Nanotechnology may become the adequate tool for developing effective and non-invasive therapies suitable for self-administration. In this review, we discuss emerging therapeutic options based on nanoengineering of cyclodextrin nanocarriers for the treatment of age-related eye disorders, including their pathophysiology, pharmacological options, and feasibility of clinical translation.

Vaccines are the most effective medical intervention due to their continual success in preventing infections and improving mortality worldwide. Early vaccines were developed empirically however, rational design of vaccines can allow us to optimise their efficacy, by tailoring the immune response. Establishing the immune correlates of protection greatly informs the rational design of vaccines. This facilitates the selection of the best vaccine antigens and the most appropriate vaccine adjuvant to generate optimal memory immune T cell and B cell responses. This review outlines the range of vaccine types that are currently authorised and those under development. We outline the optimal immunological correlates of protection that can be targeted. Finally we review approaches to rational antigen selection and rational vaccine adjuvant design. Harnessing current knowledge on protective immune responses in combination with critical vaccine components is imperative to the prevention of future life-threatening diseases.

Purpose Coronavirus disease 2019 and the publicly documented deaths of countless Black individuals have highlighted the need to confront systemic racism, address racial/ethnic disparities, and improve diversity and inclusion in radiology. Several radiology departments have begun to create diversity, equity, and inclusion (DEI) committees to systematically address DEI issues in radiology. However, there are few articles that provide departments with guidance on how to create DEI committees to comprehensively address DEI issues in radiology. The purpose of this review is to provide readers with a framework and practical tips for creating a comprehensive, institutionally aligned radiology DEI committee. Methods The authors describe key components of the strategic planning process and lessons learned in the creation of a radiology DEI committee, on the basis of the experience of an integrated, academic northeastern radiology department. Results A hospital-based strategic planning process defining the DEI vision, mission, goals, and strategies was used to inform the formation of the radiology department DEI committee. The radiology department performed gap analyses by conducting internal and external research. Strengths, weaknesses, opportunities, and threats analyses were performed on the basis of consultations with institutional and other departmental DEI leaders as well as DEI leaders from other academic medical centers. This framework served as the basis for the creation of the radiology departmental DEI committee, including a steering committee and four task forces (education, research, patient experience, and workforce development), each charged with addressing specific institutional goals and strategies. Conclusions This review provides academic radiology departments with a blueprint to create a comprehensive, institutionally aligned radiology DEI committee.

BACKGROUND Disproportionally high rates of COVID-19 have been noted among communities with limited English proficiency (LEP), resulting in an unmet need for improved multilingual care and interpreter services. To enhance multilingual care, we created a freely available web app (RadTranslate™) that provides multilingual radiology exam instructions. The purpose of this study was to evaluate the implementation of this intervention in radiology. METHODS The device-agnostic web app leverages artificial-intelligence text-to-speech to provide standardized, human-like spoken exam instructions in the patient’s preferred language. Standardized phrases were collected from a consensus group consisting of technologists, radiologists, and ancillary staff. RadTranslate was piloted in Spanish for chest radiographs (CXR) performed at a COVID-19 triage outpatient center that served a predominantly Spanish-speaking Latine community. Implementation included a tablet displaying the app in the CXR room. Imaging appointment duration (IAD) was measured and compared between pre- and post-implementation groups. RESULTS In the 63-day test period following launch, there were 1267 app uses, with technologists voluntarily switching exclusively to RadTranslate for Spanish-speaking patients. The most used phrases were a general explanation of the exam (30% of total) followed by instructions to disrobe and remove any jewelry (12%). There was no significant difference in the IAD, 11±7 min (mean ± standard deviation) and 12±3 for standard-of-care versus RadTranslate, respectively; however, variability was significantly lower when RadTranslate was used (p=0.003). CONCLUSION AI-aided multilingual audio instructions were successfully integrated into imaging workflows, reducing strain on medical interpreters and variance in throughput resulting in more reliable average exam length., RadTranslate (www.radtranslate.com), a web-based tool, allows standardized audio imaging exam instructions to be given in a patient’s native language via a simple interface, and reduces variability in exam times among non-English patients receiving chest radiographs.

Objectives Adoptive cell therapy (ACT) with mature T cells modified with a chimeric antigen receptor has demonstrated improved outcome for B‐cell malignancies. However, its application for others such as Hodgkin lymphoma remains a clinical challenge. CD30 antigen, expressed in Hodgkin lymphoma cells, is absent in most healthy tissues, representing an ideal target of ACT for this disease. Despite that, efficacy of CD30‐chimeric antigen receptor (CAR) T cells for Hodgkin lymphoma remains modest. Here, we have developed and tested a novel CD30‐CAR T to improve efficacy of CD30‐CAR therapy, using a targeting epitope within the non‐cleavable part of CD30 receptor, and memory stem T cells (TSCM) to improve engraftment, persistence and antitumor activity. Methods TSCM‐like cultures were generated and expanded ex vivo and transduced at day 1 or 2 with a lentiviral vector encoding the CD30‐CAR. Therapeutic in vivo experiments were performed using NSG mice injected with L540 (sc) or L428 (iv) and treated with CD30‐CAR T cells when the tumor was established. Results CD30‐CAR TSCM‐like cells generated and expanded ex vivo, despite CD30 expression and fratricide killing of CD30+ CAR T cells, were not impaired by soluble CD30 and completely eradicated Hodgkin lymphoma in vivo, showing high persistence and long‐lasting immunity. In addition, highly enriched CD30‐CAR TSCM‐like products confer a survival advantage in vivo, in contrast to more differentiated CAR T cells, with higher tumor infiltration and enhanced antitumor effect. Conclusion This study supports the use of a refined CD30‐CAR T cells with highly enriched TSCM‐like products to improve clinical efficacy of CAR T for Hodgkin lymphoma., We have studied the efficacy of a redesigned CD30‐chimeric antigen receptor (CAR) targeting a proximal epitope to enhance the antitumor efficacy. CD30‐CAR T cells show potent in vivo antitumor effect in different Hodgkin lymphoma models, and overcome inhibition by soluble CD30. CD30‐CAR memory stem T‐cell products show long‐term persistence, improved tumor homing and long‐lasting immunity.

Cross-reactive vaccines recognize common molecular patterns in pathogens and are able to confer broad spectrum protection against different infections. Antigens common to pathogenic bacteria that induce broad immune responses, such as the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of the genera Listeria, Mycobacterium, or Streptococcus, whose sequences present more than 95% homology at the N-terminal GAPDH peptide, are putative candidates for universal vaccines. Here, we explore vaccine formulations based on dendritic cells (DC) loaded with two molecular forms of Listeria monocytogenes GAPDH (LM-GAPDH), such as mRNA carriers or recombinant proteins, and compare them with the same molecular forms of three other antigens used in experimental vaccines, listeriolysin O of Listeria monocytogeness, Ag85A of Mycobacterium marinum, and pneumolysin of Streptococcus pneumoniae. DC loaded with LM-GAPDH recombinant proteins proved to be the safest and most immunogenic vaccine vectors, followed by mRNA encoding LM-GAPDH conjugated to lipid carriers. In addition, macrophages lacked sufficient safety as vaccines for all LM-GAPDH molecular forms. The ability of DC loaded with LM-GAPDH recombinant proteins to induce non-specific DC activation explains their adjuvant potency and their capacity to trigger strong CD4 and CD8 T cell responses explains their high immunogenicity. Moreover, their capacity to confer protection in vaccinated mice against challenges with L. monocytogenes, M. marinum, or S. pneumoniae validated their efficiency as cross-reactive vaccines. Cross-protection appears to involve the induction of high percentages of GAPDH specific CD4 and CD8 T cells stained for intracellular IFN-γ, and significant levels of peptide-specific antibodies in vaccinated mice. We concluded that DC vaccines loaded with L. monocytogenes GAPDH recombinant proteins are cross-reactive vaccines that seem to be valuable tools in adult vaccination against Listeria, Mycobacterium, and Streptococcus taxonomic groups., CICYT program of the Ministry of Science and Innovation, grant number SAF2012-34203, co-funded in part with the European FEDER funds A new way of making Europe, the COST European action ENOVA, the Instituto de Salud Carlos III (ISCIII

The permeability through the cornea determines the ability of a drug or any topically applied compound to cross the tissue and reach the intraocular area. Most of the permeability values found in the literature are obtained considering topical drug formulations, and therefore, refer to the drug permeability inward the eye. However, due to the asymmetry of the corneal tissue, outward drug permeability constitutes a more meaningful parameter when dealing with intraocular drug-delivery systems (i.e., drug-loaded intraocular lenses, intraocular implants or injections). Herein, the permeability coefficients of two commonly administered anti-inflammatory drugs (i.e., bromfenac sodium and dexamethasone sodium) were determined ex vivo using Franz diffusion cells and porcine corneas in both inward and outward configurations. A significantly higher drug accumulation in the cornea was detected in the outward direction, which is consistent with the different characteristics of the corneal layers. Coherently, a higher permeability coefficient was obtained for bromfenac sodium in the outward direction, but no differences were detected for dexamethasone sodium in the two directions. Drug accumulation in the cornea can prolong the therapeutic effect of intraocular drug-release system This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 813440 (ORBITAL—Ocular Research by Integrated Training And Learning) and is also supported by the Fundação para a Ciência e Tecnologia (FCT) [UID/QUI/00100/2019, UIDB/00100/2020 and UID/BIM/04585/2020] SI

International audience; Chemokines such as stromal cell-derived factor-1α (SDF-1α) regulate the migration of cancer cells that can spread from their primary tumor site by migrating up an SDF-1α concentration gradient, facilitating their local invasion and metastasis. Therefore, the implantation of SDF-1α-releasing scaffolds can be a useful strategy to trap cancer cells expressing the CXCR4 receptor. In this work, SDF-1α was encapsulated into poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles and subsequently electrospun with chitosan to produce nanofibrous scaffolds of average fiber diameter of 261 ± 45 nm, intended for trapping glioblastoma (GBM) cells. The encapsulated SDF-1α maintained its biological activity after the electrospinning process as assessed by its capacity to induce the migration of cancer cells. The scaffolds could also provide sustained release of SDF-1α for at least 5 weeks. Using NIH3T3 mouse fibroblasts, human Thp-1 macrophages, and rat primary astrocytes we showed that the scaffolds possessed high cytocompatibility in vitro. Furthermore, a 7-day follow-up of Fischer rats bearing implanted scaffolds demonstrated the absence of adverse effects in vivo. In addition, the nanofibrous structure of the scaffolds provided excellent anchoring sites to support the adhesion of human GBM cells by extension of their pseudopodia. The scaffolds also demonstrated slow degradation kinetics, which may be useful in maximizing the time window for trapping GBM cells. As surgical resection does not permit a complete removal of GBM tumors, our results support the future implantation of these scaffolds into the walls of the resection cavity to evaluate their capacity to attract and trap the residual GBM cells in the brain.

Cancer ranks amongst the most deadliest diseases, associated with significant burden, often fatal prognosis and huge clinical challenge [1]. Cancer management has substantially improved mainly on cancer diagnostics and therapeutics, resulting in extended survival rates and decreased mortality worldwide. Chemotherapy, along with radiotherapy and surgery, represents one of the major therapeutic approaches for cancer cells eradication, however associated with several shortcomings, as poor cancer tissue biodistribution, accelerated drug degradation and clearance, insufficient cancer targetability and still high systemic toxicity, overall compromising efficacy and safety [2, 3].

Objective To implement a mentoring program for early career faculty in an academic radiology department and to assess its impact on career development. Methods A formal departmental mentoring program for early career faculty (instructors) who were paired with senior radiologists outside of their division was implemented. The program provided structured one-on-one mentoring, creation of a mentoring network, and opportunities for peer mentoring. A survey was conducted before and 1 year after initiation of the program. Historical data on promotion over 5 years before the implementation of the program was used to determine the impact on the rate of promotion. The study was exempt from institutional review board approval. Results Before and 1 year after implementation of the mentoring program, 57% versus 86% of instructors were satisfied with their mentor (P = .04); 43% versus 90% felt that by encouraging mentorship, the department valued their professional development (P = .001); 38% versus 86% felt that the department created an environment that promoted feedback and sharing of information (P = .002); and 43% versus 76% felt that faculty strove to support each other (P = .03). Since implementation of the program, 43% of instructors received grant funding, 50% received other awards, and 10 instructors were promoted to assistant professor, compared with an average of 4.2/y over the past 5 years. Of those, three were underrepresented minorities in medicine versus none in the previous 5 years. Conclusions A mentoring program helped to advance the careers of early career and minority radiology faculty and helped create an atmosphere of more openness and support in the department.

© 2020 Alvarez-Dominguez, Salcines-Cuevas, Teran-Navarro, Calderon-Gonzalez, Tobes, Garcia, Grijalvo, Paradela, Seoane, Sangari, Fresno, Calvo-Montes, Pérez Del Molino Bernal and Yañez-Diaz., The glycolytic enzyme and bacterial virulence factor of Listeria monocytogenes, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH, Lmo2459), ADP-ribosylated the small GTPase, Rab5a, and blocked phagosome maturation. This inhibitory activity localized within the NAD binding domain of GAPDH at the N-terminal 1–22 peptides, also conferred listeriosis protection when used in dendritic cell-based vaccines. In this study, we explore GAPDH of Listeria, Mycobacterium, and Streptococcus spp. taxonomic groups to search for epitopes that confer broad protection against pathogenic strains of these bacteria. GAPDH multivalent epitopes are selected if they induce inhibitory actions and wide-ranging immune responses. Proteomic isolation of GAPDH from dendritic cells infected with Listeria, Mycobacterium, or Streptococcus confirmed similar enzymatic, Rab5a inhibitory and immune stimulation abilities. We identified by bioinformatics and functional analyses GAPDH N-terminal 1–22 peptides from Listeria, Mycobacterium, and Streptococcus that shared 95% sequence homology, enzymatic activity, and B and T cell immune domains. Sera obtained from patients or mice infected with hypervirulent pathogenic Listeria, Mycobacterium, or Streptococcus presented high levels of anti-GAPDH 1–22 antibodies and Th2 cytokines. Monocyte derived dendritic cells from healthy donors loaded with GAPDH 1–22 peptides from Listeria, Mycobacterium, or Streptococcus showed activation patterns that correspond to cross-immunity abilities. In summary, GAPDH 1–22 peptides appeared as putative candidates to include in multivalent dendritic based vaccine platforms for Listeria, Mycobacterium, or Streptococcus., This research was funded by the CICYT program of the Ministry of Science and Innovation, grant number SAF2012-34203, the Instituto de Salud Carlos III (ISCIII) grant numbers, DTS18-00022 and PI19-01580 to CA-D, the intramural CIBER-BNN grant number, CIB16-NM009 to IG and CA-D, to the Bio-health Research Program of Cantabria Government, grant number INNVAL19/26 to SY-D, CM, and CA-D; SAF2016-75988-R “Comunidad de Madrid (S2017/BMD-3671. INFLAMUNECM) and Fondo de Investigaciones Sanitarias” (BIOIMID) to MF and a Predoctoral contract to DS-C by Bio-health research program of Cantabria government. This study was co-funded in part with European FEDER funds, "A new way of making Europe" as well as funds from the COST European action ENOVA.

The delivery of bioactive agents using active wound dressings for the management of pain and infections offers improved performances in the treatment of wound complications. In this work, solid lipid microparticles (SLMPs) loaded with lidocaine hydrochloride (LID) were processed and the formulation was evaluated regarding its ability to deliver the drug at the wound site and through the skin barrier. The SLMPs of glyceryl monostearate (GMS) were prepared with different LID contents (0, 1, 2, 4, and 10 wt.%) using the solvent-free and one-step PGSS (Particles from Gas-Saturated Solutions) technique. PGSS exploits the use of supercritical CO2 (scCO2) as a plasticizer for lipids and as pressurizing agent for the atomization of particles. The SLMPs were characterized in terms of shape, size, and morphology (SEM), physicochemical properties (ATR-IR, XRD), and drug content and release behavior. An in vitro test for the evaluation of the influence of the wound environment on the LID release rate from SLMPs was studied using different bioengineered human skin substitutes obtained by 3D-bioprinting. Finally, the antimicrobial activity of the SLMPs was evaluated against three relevant bacteria in wound infections (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa). SLMPs processed with 10 wt.% of LID showed a remarkable performance to provide effective doses for pain relief and preventive infection effects This research was funded by Xunta de Galicia [ED431F 2016/010], MCIUN [RTI2018-094131-A-I00], Agrupación Estratégica de Materiales [AeMAT-BIOMEDCO2, ED431E 2018/08], Agencia Estatal de Investigación [AEI] and FEDER funds. C.A.G.-G. acknowledges to MINECO for a Ramón y Cajal Fellowship [RYC2014-15239]. This work was partially supported by Programa de Actividades de I+D entre Grupos de Investigación de la Comunidad de Madrid [S2018/BAA-4480, Biopieltec-CM], Programa Estatal de I+D+I Orientada a los Retos de la Sociedad [RTI2018-101627-B-I00] and Cátedra Fundación Ramón Areces SI

Over 5% of the world's population has disabling hearing loss, which affects approximately one third of individuals over 65 years. Hearing aids are commonly used in this population group, but prolonged use of these devices may cause ear infections. We describe for the first time, the use of 3D printing to fabricate hearing aids loaded with two antibiotics, ciprofloxacin and fluocinolone acetonide. Digital light processing 3D printing was employed to manufacture hearing aids from two polymer resins, ENG hard and Flexible. The inclusion of the antibiotics did not affect the mechanical properties of the hearing aids. All multi-drug-loaded devices exhibited a hydrophilic surface, excellent blood compatibility and anti-biofilm activity against P. aeruginosa and S. aureus. Hearing aids loaded with ciprofloxacin (6% w/w) and fluocinolone acetonide (0.5% w/w) sustained drug release for more than two weeks and inhibited biofilm formation on the surface of the devices and bacteria growth in the surrounding medium. In summary, this work highlights the potential of vat photopolymerization 3D printing as a versatile manufacturing approach to fabricate high-fidelity patient-specific medical devices with anti-bacterial properties.