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Due to the theragnostic potential of mesoporous silica nanoparticles (MSNs), these were extensively investigated as a novel approach to improve clinical outcomes. Boasting an impressive array of formulations and modifications, MSNs demonstrate significant in vivo efficacy when used to identify or treat myriad malignant diseases in preclinical models. As MSNs continue transitioning into clinical trials, a thorough understanding of the characteristics of effective MSNs is necessary. This review highlights recent discoveries and advances in MSN understanding and technology. Specific focus is given to cancer theragnostic approaches using MSNs. Characteristics of MSNs such as size, shape, and surface properties are discussed in relation to effective nanomedicine practice and projected clinical efficacy. Additionally, tumor-targeting options used with MSNs are presented with extensive discussion on active-targeting molecules. Methods for decreasing MSN toxicity, improving site-specific delivery, and controlling release of loaded molecules are further explained. Challenges facing the field and translation to clinical environments are presented alongside potential avenues for continuing investigations.

Metallacrowns are a versatile class of inorganic compounds with uses in several areas of chemistry. Students engage in a multiweek, upper-division inorganic laboratory that explores four different metallacrown compounds: Fe[superscript III](O[subscript 2]CCH[subscript 3])[subscript 3][9-MC[subscript Fe][superscript III][subscript (N)shi]-3](CH[subscript 3]OH)[subscript 3][dot]3CH[subscript 3]OH, Mn[superscript II](O[subscript 2]CCH[subscript 3])[subscript 2][12-MC[subscript Mn[superscript III](N)shi]-4](C[subscript 3]H[subscript 7]NO)[subscript 6][dot]2C[subscript 3]H[subscript 7]NO, [(CH[subscript 3])[subscript 4]N][subscript 2]{Cu[superscript II][12-MC[subscript Cu[superscript II](N)shi]-4]}[dot]C[subscript 3]H[subscript 7]NO, and Mn[superscript II](O[subscript 2]CCH[subscript 3])[subscript 2][15-MC[subscript Mn[super script III](N)shi]-5](C[subscript 5]H[subscript 5]N)[subscript 6][dot]CH[subscript 3]OH. The syntheses are straightforward, and the compounds are characterized by cyclic voltammetry, solid-state magnetic susceptibility, FT-IR, UV-vis, and paramagnetically shifted [superscript 1]H NMR. Students are provided with a research-like experience in which they can successfully synthesize a metallacrown, conduct a literature search, develop characterization parameters based on departmental resources, interpret experimental results and compare them to the primary literature, analyze the crystallographic structures of the compounds, and finally present an oral seminar detailing their results and analysis.

Abstract Background Pharmacogenomics of hydroxyurea is an important aspect in the management of sickle cell disease (SCD), especially in the era of genomic medicine. Genetic variations in loci associated with HbF induction and drug metabolism are prime targets for hydroxyurea (HU) pharmacogenomics, as these can significantly impact the therapeutic efficacy and safety of HU in SCD patients. Methods This study involved designing of a custom panel targeting BCL11A, ARG2, HBB, HBG1, WAC, HBG2, HAO2, MYB, SAR1A, KLF10, CYP2C9, CYP2E1 and NOS1 as potential HU pharmacogenomics targets. These genes were selected based on their known roles in HbF induction and HU metabolism. The panel was designed using the Illumina Design Studio (Illumina, San Diego, CA, USA) and achieved a total coverage of 96% of all genomic targets over a span of 51.6 kilobases (kb). This custom panel was then sequenced using the Illumina MiSeq platform to ensure high coverage and accuracy. Results We are reporting a successfully designed Illumina (MiSeq) HU pharmacogenomics custom panel encompassing 51.6 kilobases. The designed panel achieved greater than 1000x amplicon coverage which is sufficient for genomic analysis. Conclusions This study provides a valuable tool for research in HU pharmacogenomics, especially in Africa where SCD is highly prevalent, and personalized medicine approaches are crucial for improving patient outcomes. The custom-designed Illumina (MiSeq) panel, with its extensive coverage and high sequencing depth, provides a robust platform for studying genetic variations associated with HU response. This panel can contribute to the development of tailored therapeutic strategies, ultimately enhancing the management of SCD through more effective and safer use of hydroxyurea.

Antibodies are critical tools for research into extracellular vesicles (EVs) and other extracellular nanoparticles (ENPs), where they can be used for their identification, characterization, and isolation. However, the lack of a centralized antibody platform where researchers can share validation results thus minimizing wasted personnel time and reagents, has been a significant obstacle. Moreover, because the performance of antibodies varies among assay types and conditions, detailed information on assay variables and protocols is also of value. To facilitate sharing of results on antibodies that are relevant to EV/ENP research, the EV Antibody Database has been developed by the investigators of the Extracellular RNA Communication Consortium (ERCC). Hosted by the ExRNA Portal (https://exrna.org/resources/evabdb/), this interactive database aggregates and shares results from antibodies that have been tested by research groups in the EV/ENP field. Currently, the EV Antibody Database includes modules for antibodies tested for western Blot, EV Flow Cytometry, and EV Sandwich Assays, and holds 110 records contributed by 6 laboratories from the ERCC. Detailed information on antibody sources, assay conditions, and results is provided, including negative results. We encourage ongoing expert input and community feedback to enhance the database's utility, making it a valuable resource for comprehensive validation data on antibodies and protocols in EV biology.

As the economic burden associated with vision loss and ocular damage continues to rise, there is a need to explore novel treatment strategies. Extracellular vesicles (EVs) are enriched with various biological cargo, and there is abundant literature supporting the reparative and immunomodulatory properties of stem cell EVs across a broad range of pathologies. However, one area that requires further attention is the reparative effects of stem cell EVs in the context of ocular damage. Additionally, most of the literature focuses on EVs isolated from primary stem cells; the use of EVs isolated from human telomerase reverse transcriptase (hTERT)-immortalized stem cells has not been thoroughly examined. Using our large-scale EV-manufacturing platform, we reproducibly manufactured EVs from hTERT-immortalized mesenchymal stem cells (MSCs) and employed various methods to characterize and profile their associated cargo. We also utilized well-established cell-based assays to compare the effects of these EVs on both healthy and damaged retinal pigment epithelial cells. To the best of our knowledge, this is the first study to establish proof of concept for reproducible, large-scale manufacturing of hTERT-immortalized MSC EVs and to investigate their potential reparative properties against damaged retinal cells. The results from our studies confirm that hTERT-immortalized MSC EVs exert reparative effects in vitro that are similar to those observed in primary MSC EVs. Therefore, hTERT-immortalized MSCs may represent a more consistent and reproducible platform than primary MSCs for generating EVs with therapeutic potential.

Background and purpose: Incidental thyroid gland irradiation frequently occurs in breast cancer patients who receive regional nodal irradiation (RNI) to the supraclavicular (SCV) region. Recent studies suggest hypothyroidism (HT) is a complication of radiation therapy (RT) that includes SCV fields. We retrospectively analyzed patients who received RNI to evaluate thyroid gland evolution following RT as well as its association with the development of HT. Materials and methods: 61 breast cancer patients received SCV-directed RT between 2007 and 2019 and met inclusion criteria. Thyroid glands were retrospectively contoured on CT simulation and follow-up images. Individual dose-volume histograms were analyzed to determine thyroid volume within and outside specific isodose lines. Relative thyroid volume changes based on different radiation doses were estimated by fusing post-RT scans with CT simulation. Logistic regression was performed to assess thyroid volume changes as a factor in the development of HT. Results: Median pre-treatment thyroid volume was 11.8 cc (range: 6.3–74.1 cc) with a median of 42.2 % within the 20 Gy and 23.2 % within the 40 Gy isodose lines. A significant decrease in thyroid volume was noted by 1-year post-treatment (p

Children differ widely in their early language development, and this variability has important implications for later life outcomes. Parent language input is a strong experiential factor predicting the variability in children’s early language skills. However, little is known about the brain or cognitive mechanisms that underlie the relationship. In addressing this gap, we used longitudinal data spanning 15 years to examine the role of early parental language input that children receive during preschool years in the development of brain structures that support language processing during school years. Using naturalistic parent–child interactions, we measured parental language input (amount and complexity) to children between the ages of 18 and 42 months (n = 23). We then assessed longitudinal changes in children’s cortical thickness measured at five time points between 9 and 16 years of age. We focused on specific regions of interest (ROIs) that have been shown to play a role in language processing. Our results support the view that, even after accounting for important covariates such as parental intelligence quotient (IQ) and education, the amount and complexity of language input to a young child prior to school forecasts the rate of change in cortical thickness during the 7-year period from 5½ to 12½ years later. Examining the proximal correlates of change in brain and cognitive differences has the potential to inform targets for effective prevention and intervention strategies.

Tobacco industry marketing is a primary factor influencing cigarette smoking behavior and the cigarette pack has become an important marketing vehicle for tobacco companies. Standardized "plain" cigarette packaging is advocated as a public health policy to prevent and reduce morbidity and mortality caused by smoking by reducing youth smoking initiation and promoting cessation among smokers. Plain packaging was implemented in Australia in December 2012, and several other countries are considering doing so, but each faces foreseeable legal resistance from opponents to such measures. Tobacco companies have challenged these public health policies, citing international trade agreements and intellectual property laws. Decision-making in these court cases will hinge in part on whether the evidence indicates the public health benefits of plain packaging outweigh any potential harm to tobacco manufacturers' interests. We reviewed the available evidence in support of plain packaging, finding evidence from observational, experimental, and population-based studies. Results indicate that plain packaging can reduce positive perceptions of smoking and dissuade tobacco use. Governments deciding to implement plain cigarette packaging measures can rely on this evidence to help make a strong case that plain packaging plays an important role in the context of comprehensive smoking prevention efforts. [ABSTRACT FROM AUTHOR]

Hemolytic Uremic Syndrome (HUS) is a constellation of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Shiga toxin-producing Escherichia coli- (STEC-) mediated HUS is a common cause of acute renal failure in children and can rarely result in severe neurological complications such as encephalopathy, seizures, cerebrovascular accidents, and coma. Current literature supports use of eculizumab, a monoclonal antibody that blocks complement activation, in atypical HUS (aHUS). However, those with neurologic complications from STEC-HUS have complement activation and deposition of aggregates in microvasculature and may be treated with eculizumab. In this case report, we describe a 3-year-old boy with diarrhea-positive STEC-HUS who developed severe neurologic involvement in addition to acute renal failure requiring renal replacement therapy. He was initiated on eculizumab therapy, with clinical improvement and organ recovery. This case highlights systemic complications of STEC-HUS in a pediatric patient. The current literature is limited but has suggested a role for complement mediation in cases with severe complications. We review the importance of early recognition of complications, use of eculizumab, and current data available.

Due to the theragnostic potential of mesoporous silica nanoparticles (MSNs), these were extensively investigated as a novel approach to improve clinical outcomes. Boasting an impressive array of formulations and modifications, MSNs demonstrate significant in vivo efficacy when used to identify or treat myriad malignant diseases in preclinical models. As MSNs continue transitioning into clinical trials, a thorough understanding of the characteristics of effective MSNs is necessary. This review highlights recent discoveries and advances in MSN understanding and technology. Specific focus is given to cancer theragnostic approaches using MSNs. Characteristics of MSNs such as size, shape, and surface properties are discussed in relation to effective nanomedicine practice and projected clinical efficacy. Additionally, tumor-targeting options used with MSNs are presented with extensive discussion on active-targeting molecules. Methods for decreasing MSN toxicity, improving site-specific delivery, and controlling release of loaded molecules are further explained. Challenges facing the field and translation to clinical environments are presented alongside potential avenues for continuing investigations. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis is a major but neglected parasitic zoonosis and despite several decades of efforts there is still no vaccine available worldwide to control the disease which affects humans and dogs. An efficient vaccine to protect clogs in enzootic and outbreak susceptible areas would not only be an invaluable tool in veterinary medicine but would also significatively reduce the incidence of zoonotic visceral leishmaniasis in humans. New vaccine approaches against vector-borne diseases are now taking into account the key role of insect vectors in the context of the mammalian immune response against the pathogens. As Leishmania infantum is transmitted during the blood meal of sand flies in their mammalian host, we have focused on the role of Lutzomyia Iongipalpis salivary proteins as potential vaccine candidates in dogs against Leishmania infantum infection. Using a novel approach termed reverse antigen screening, we isolated two salivary antigens eliciting a strong cellular immunity in dogs, either molecule inducing high IgG2 antibody levels and significant γ-IFN production following in vitro stimulation of PBMC with salivary gland homogenate. Upon stimulation with sand fly saliva, lymphocytes from immunized dogs were able to trigger Leishmania killing within autologous macrophages. As sand fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission, their inclusion in an anti-Leishmania vaccine would exploit anti-saliva immunity following an infective sand fly bite and set the stage for a protective anti-Leishmania immune response. [ABSTRACT FROM AUTHOR]

Vaccine development by the public sector is severely hampered by limited access to safe and effective adjuvants and by inadequate expertise in antigen formulation. Inappropriate use of adjuvants has lead to the failure of several vaccine development programs, which has accounted for wasted massive sums of public funds and may have resulted in viable vaccine candidates being abandoned. A laboratory on vaccine formulation has been recently established at University of Lausanne and is aiming at providing support to public research sector for adjuvant development. The laboratory is a World Health Organization (WHO) Collaborating Center and is undertaking the following activities: (i) generation of harmonized procedures to permit pre-clinical selection of vaccine adjuvants, (ii) establishment of a service center for open-access and characterization of existing adjuvants, in order to take them forward to GMP production and clinical studies, (iii) assistance to external R&D groups in highlighting pitfalls of vaccine formulation, (iv) technology transfer of an inactivated polio vaccine to India, and (v) development of a training program on adjuvant development. [ABSTRACT FROM AUTHOR]

An abstract of the article "Using Out-of-Programme Training to Establish Interventional Radiology Training for Current and Future Surgeons," by A. R. Weale et al is presented.

Critical consciousness (CC) has been heralded as an antidote to oppression. Developed by the Brazilian educator, Paulo Freire, CC represents the process by which individuals gain awareness of societal inequities and subsequently take action to dismantle the systems and institutions that sustain them. Empirically supported instruments intended to assess this important construct have only been recently introduced to the literature and have focused specifically on racism, classism, and heterosexism. The purpose of this project was to develop a psychometrically sound measure of CC that expands assessment into sexism, cissexism (genderism/transphobia), and ableism. Two studies with a total of 569 observations provided initial reliability and validity evidence on the Contemporary Critical Consciousness Measure II (CCCMII). Results from exploratory and confirmatory factor analyses suggest that the final 37-item CCCMII provides a general index of CC as well as assesses CC associated with sexism and ableism above and beyond the general factor. Results support the internal consistency and factor structure of the measure. Expected relationships between the CCCMII and existing measures of sexism, cissexism, and ableism provide evidence for the validity of the instrument. Limitations, future directions for research, and counseling implications are discussed. [ABSTRACT FROM AUTHOR]