Expanding the Chemistry Palette for Radiotracer Synthesis.

The synthesis, characterisation and application of radiolabelled compounds for use in diagnostic and therapeutic medicine requires a diverse skill set. This article highlights a selection of our ongoing projects that aim to provide new synthetic methods and radiochemical tools for building molecular imaging agents with various radionuclides.

Karyotypic Evolution in Malagasy Flying Foxes (Pteropodidae, Chiroptera) and Their Hipposiderid Relatives as Determined by Comparative Chromosome Painting.

Pteropodidae and Hipposideridae are 2 of the 9 chiropteran families that occur on Madagascar. Despite major advancements in the systematic study of the island's bat fauna, few karyotypic data exist for endemic species. We utilized G- and C-banding in combination with chromosome painting with Myotismyotis probes to establish a genome-wide homology among Malagasy species belonging to the families Pteropodidae (Pteropus rufus 2n = 38; Rousettus madagascariensis, 2n = 36), Hipposideridae (Hipposideros commersoni s.s., 2n = 52), and a single South African representative of the Rhinolophidae (Rhinolophus clivosus, 2n = 58). Painting probes of M. myotis detected 26, 28, 28, and 29 regions of homology in R. madagascariensis, P. rufus, H. commersoni s.s, and R. clivosus, respectively. Translocations, pericentric inversions, and heterochromatin additions were responsible for karyotypic differences amongst the Malagasy pteropodids. Comparative chromosome painting revealed a novel pericentric inversion on P. rufus chromosome 4. Chromosomal characters suggest a close evolutionary relationship between Rousettus and Pteropus. H. commersoni s.s. shared several chromosomal characters with extralimital congeners but did not exhibit 2 chromosomal synapomorphies proposed for Hipposideridae. This study provides further insight into the ancestral karyotypes of pteropodid and hipposiderid bats and corroborates certain molecular phylogenetic hypotheses.

ITS2 secondary structure for species circumscription: case study in southern African Strychnos L. (Loganiaceae).

Recently developed computational tools in ITS2 sequence-structure phylogenetics are improving tree robustness by exploitation of the added information content of the secondary structure. Despite this strength, however, their adoption for species-level clarifications in angiosperms has been slow. We investigate the utility of combining ITS2 sequence and secondary structure to separate species of southern African Strychnos, and assess correlation between compensatory base changes (CBCs) and currently recognised species boundaries. Combined phylogenetic analysis of sequence and secondary structure datasets performed better, in terms of robustness and species resolution, than analysis involving primary sequences only, achieving 100 and 88.2 % taxa discriminations respectively. Further, the Strychnos madagascariensis complex is well-resolved by sequence-structure phylogenetic analysis. The 17 Strychnos species corresponded to 14 ITS2 CBC clades. Four of the five taxa in section Densiflorae belong to a single CBC clade, whose members tend to form natural hybrids. Our finding supports the application of ITS2 as a complementary barcoding marker for species identification. It also highlights the potential of comparative studies of ITS2 CBC features among prospective parental pairs in breeding experiments as a rapid proxy for cross compatibility assessment. This could save valuable time in crop improvement. Patterns of CBC evolution and species boundaries in Strychnos suggests a positive correlation. We conclude that the CBC pattern coupled with observed ITS2 sequence paraphyly in section Densiflorae points to a speciation work-in-progress.

Cryptic diversity in Hipposideros commersoni sensu stricto (Chiroptera: Hipposideridae) in the western portion of Madagascar.

BACKGROUND: The Commerson's leaf-nosed bat, Hipposideros commersoni sensu stricto, is endemic to Madagascar and is relatively common in the western portion of the island, where it is found in areas, including forested zones, from sea level to 1325 m. A previous study on morphological patterns of geographic variation within the species highlighted the presence of two distinct morphotypes; larger individuals in the north portion of the island and smaller individuals in the south. The main aim of this study was to use a combination of craniodental morphology and molecular data (mitochondrial and nuclear) to test previous hypotheses based on morphology and clarify the evolutionary history of the species group. METHODS: We sequenced mitochondrial and nuclear genes from Hipposideros commersoni obtained from the western portion of Madagascar, and compared them with other African species as outgroups. We analyzed the sequence data using Maximum Likelihood and Bayesian phylogenetic inference. Divergence dates were estimated using Bayesian molecular clock approach. Variation in craniodental variables was also assessed from sequenced individuals. RESULTS: The molecular analyses suggest that H. commersoni is not monophyletic, with strong support for the presence of several independently evolving lineages. Two individuals amongst those sequenced from Isalo (south central) and Itampolo (southwest) form a separate clade (Clade A), distinct from other H. commersoni, and sister to continental African H. vittatus and H. gigas. Within the H. commersoni clade, the molecular data support two geographically distributed clades; one from the south (Clade B) and the other from the north (Clade C), which diverged approximately 3.38 million years ago. Morphometric data were consistent with the molecular analyses, suggesting a north-south break within H. commersoni. However, at some localities, animals from both clades occurred in sympatry and these individuals could not be differentiated based on external and craniodental measurements. CONCLUSIONS: Using a combination of molecular and morphological characters, this study presents evidence of cryptic diversity in H. commersoni on Madagascar. Further fine-scale phylogeographic studies are needed to fully resolve the systematics of H. commersoni. This study highlights the utility of the combined approach in employing both morphological and molecular data to provide insights into the evolutionary history of Malagasy population currently assigned to H. commersoni.

Assessment of infrastructure, behaviours, and user satisfaction of guardian waiting shelters for secondary level hospitals in southern Malawi.

Guardian Waiting Shelters (GWSs) are an essential component of the Malawi's health care system as they serve as a temporary home for patient guardians while taking care of their relatives admitted to the hospital, and expectant mothers. Although GWSs play a crucial role in Malawi's healthcare system, past studies have primarily concentrated on maternity waiting homes, neglecting the role and importance of GWSs. The study examines GWS management structures and conditions, as well as guardian satisfaction and perception of health risks related to GWS use. In this explanatory sequential mixed methods design, we assessed 12 GWSs from southern region of Malawi. Qualitative data included interviews (n = 149) and focus group discussions with patient guardians (n = 72), interviews with GWS caretakers (n = 5), representatives from Hospital Management (n = 12) and Hospital Advisory Committees (n = 11). Lack of guidelines and standards for GWSs resulted in creating a customized facility checklist to quantitatively assess infrastructure present at GWSs (n = 12). Descriptive statistics and qualitative thematic analysis were utilized for data analysis, and a problem tree analysis was used to triangulate and summarize the findings. A total of 249 participants participated in the study. Each GWS had an average of 100 users daily, primarily adult females (71%). No one was accountable for GWS operation and maintenance due to the lack of a management hierarchy. GWS infrastructure conditions were poor, with inadequate functional sleeping rooms, insufficient access to water, sanitation and hygiene facilities. Notably, 50% of the GWSs lacked water access, and a quarter had non-functional toilets. Guardians felt unsafe and at risk of disease transmission when staying within GWS. Study findings highlight lack of clear, consistent GWS ownership as a root cause of challenges in GWSs. Clear policy and operational standards must be established for effective management and smooth functioning of GWSs.

Lessons from the deployment and management of public handwashing stations in response to the COVID-19 pandemic in Kenya: A cross-sectional, observational study.

During the COVID-19 pandemic in Kenya, 5,311 handwashing stations were distributed by the National Business Compact Coalition (NBCC) to help combat the virus. This study evaluated 316 of these stations across five counties, assessing functionality, usability, and accessibility. Quantitative data, including spot checks and surveys, revealed that 83.9% of the evaluated stations were functional, with paid caretakers, which is associated with higher functionality rates. Qualitative insights underscored challenges such as inadequate signage and limited soap and water availability, particularly affecting individuals with disabilities. Despite initial success, only 61% of stations remained functional 6-8 months post-distribution, often due to relocation by caretakers. Future distributions should prioritize long-term support for caretakers to sustain station functionality. This study highlights the importance of ongoing monitoring and support for public handwashing facilities in pandemic response efforts.

Using Wash'Em to Design Handwashing Programmes for Crisis-Affected Populations in Zimbabwe: A Process Evaluation.

Wash'Em is a process that supports humanitarians in assessing and designing rapid but context-specific hygiene programmes in crises or outbreaks. The process consists of training implementers, using tools to learn from populations, and entering findings into a software which generates contextualised activities. A process evaluation of Wash'Em use was conducted in a drought-affected area in Midland province, Zimbabwe. Data were collected during the programme design and following implementation using a mix of qualitative methods. Findings were classified against the intended stages of Wash'Em, and the evaluation domains were defined by the UKRI Medical Research Council. The Wash'Em process was not fully implemented as intended. An abridged training was utilised, some of the tools for learning from populations were omitted, many of the recommended activities were not implemented, the delivery modalities were different from intended, the budget available was minimal, and the number of people exposed to activities were fewer than hoped. Despite these 'on the ground' challenges and adaptations, the Wash'Em process was considered feasible by implementers and was seen to be less top-down than most programme design approaches. The populations exposed to the intervention found the activities engaging, understood the content, and reportedly took action to improve handwashing behaviour. Programmes such as Wash'Em, which facilitate community participation and are underpinned by theory and evidence, are likely to yield positive results even if processes are followed imperfectly.

A new, narrowly endemic species of swamp-dwelling dusky salamander (Plethodontidae: Desmognathus) from the Gulf Coastal Plain of Mississippi and Alabama.

We describe a new, narrowly endemic species of swamp-dwelling dusky salamander (Plethodontidae: Desmognathus pascagoula sp. nov.) from the Gulf Coastal Plain of southeastern Mississippi and southwestern Alabama based on linear morphometrics, mitochondrial DNA, and single nucleotide polymorphisms from 881 loci produced using genotype-by-sequencing. Some populations of the new species were historically referred to as D. auriculatus, a polyphyletic assemblage of at least three species in the Atlantic and Gulf Coastal Plain from Texas to North Carolina. Populations of D. auriculatus from the Gulf Coastal Plain in Louisiana and Mississippi were recently described as D. valentinei. The new species includes populations that were tentatively referred to D. valentinei, but we find it is morphologically, genetically, and geographically distinct. It is smaller, has a more defined dorsal color pattern, more irregular whitish portholes in up to three rows on the lateral surfaces of the body and tail, and a brighter orange or yellowish orange postocular stripe. At present, the new species is known from only six extant populations in the lower Pascagoula, Escatawpa, and Mobile drainages. The latter represents a distinct phylogeographic lineage. We also refer a historical collection from the northeastern side of the Mobile-Tensaw River Delta to this species, suggesting a much broader range in the past. We suspect that more populations remain to be discovered in the area, and their potential species-level distinctiveness should be tested further. This discovery increases knowledge of the biodiversity in the southeastern United States Coastal Plain, a candidate region meeting the global criteria for a biodiversity hotspot, and underscores the amount of cryptic diversity likely remaining to be discovered and described in Nearctic salamanders.

Genetic monitoring detects an overlooked cryptic species and reveals the diversity and distribution of three invasive Rattus congeners in South Africa.

BACKGROUND: South Africa's long and extensive trade activity has ensured ample opportunities for exotic species introduction. Whereas the rich biodiversity of endemic southern African fauna has been the focus of many studies, invasive vertebrates are generally overlooked despite potential impacts on biodiversity, health and agriculture. Genetic monitoring of commensal rodents in South Africa which uncovered the presence of Rattus tanezumi, a South-East Asian endemic not previously known to occur in Africa, provided the impetus for expanded studies on all invasive Rattus species present. RESULTS: To this end, intensified sampling at 28 South African localities and at one site in Swaziland, identified 149 Rattus specimens. Cytochrome b gene sequencing revealed the presence of two R. tanezumi, seven Rattus rattus and five Rattus norvegicus haplotypes in south Africa. Phylogenetic results were consistent with a single, recent R. tanezumi introduction and indicated that R. norvegicus and R. rattus probably became established following at least two and three independent introductions, respectively. Intra- and inter-specific diversity was highest in informal human settlements, with all three species occurring at a single metropolitan township site. Rattus norvegicus and R. rattus each occurred sympatrically with Rattus tanezumi at one and five sites, respectively. Karyotyping of selected R. rattus and R. tanezumi individuals identified diploid numbers consistent with those reported previously for these cryptic species. Ordination of bioclimatic variables and MaxEnt ecological niche modelling confirmed that the bioclimatic niche occupied by R. tanezumi in south Africa was distinct from that occupied in its naturalised range in south-east Asia suggesting that factors other than climate may influence the distribution of this species. CONCLUSIONS: This study has highlighted the value of genetic typing for detecting cryptic invasive species, providing historical insights into introductions and for directing future sampling. The apparent ease with which a cryptic species can become established signals the need for broader implementation of genetic monitoring programmes. In addition to providing baseline data and potentially identifying high-risk introduction routes, the predictive power of ecological niche modelling is enhanced when species records are genetically verified.

Cross-species chromosome painting in bats from Madagascar: the contribution of Myzopodidae to revealing ancestral syntenies in Chiroptera.

The chiropteran fauna of Madagascar comprises eight of the 19 recognized families of bats, including the endemic Myzopodidae. While recent systematic studies of Malagasy bats have contributed to our understanding of the morphological and genetic diversity of the island's fauna, little is known about their cytosystematics. Here we investigate karyotypic relationships among four species, representing four families of Chiroptera endemic to the Malagasy region using cross-species chromosome painting with painting probes of Myotis myotis: Myzopodidae (Myzopoda aurita, 2n = 26), Molossidae (Mormopterus jugularis, 2n = 48), Miniopteridae (Miniopterus griveaudi, 2n = 46), and Vespertilionidae (Myotis goudoti, 2n = 44). This study represents the first time a member of the family Myzopodidae has been investigated using chromosome painting. Painting probes of M. myotis were used to delimit 29, 24, 23, and 22 homologous chromosomal segments in the genomes of M. aurita, M. jugularis, M. griveaudi, and M. goudoti, respectively. Comparison of GTG-banded homologous chromosomes/chromosomal segments among the four species revealed the genome of M. aurita has been structured through 14 fusions of chromosomes and chromosomal segments of M. myotis chromosomes leading to a karyotype consisting solely of bi-armed chromosomes. In addition, chromosome painting revealed a novel X-autosome translocation in M. aurita. Comparison of our results with published chromosome maps provided further evidence for karyotypic conservatism within the genera Mormopterus, Miniopterus, and Myotis. Mapping of chromosomal rearrangements onto a molecular consensus phylogeny revealed ancestral syntenies shared between Myzopoda and other bat species of the infraorders Pteropodiformes and Vespertilioniformes. Our study provides further evidence for the involvement of Robertsonian (Rb) translocations and fusions/fissions in chromosomal evolution within Chiroptera.

Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling.

Kinase inhibitors constitute an important new class of cancer drugs, whose selective efficacy is largely determined by underlying tumor cell genetics. We established a high-throughput platform to profile 500 cell lines derived from diverse epithelial cancers for sensitivity to 14 kinase inhibitors. Most inhibitors were ineffective against unselected cell lines but exhibited dramatic cell killing of small nonoverlapping subsets. Cells with exquisite sensitivity to EGFR, HER2, MET, or BRAF kinase inhibitors were marked by activating mutations or amplification of the drug target. Although most cell lines recapitulated known tumor-associated genotypes, the screen revealed low-frequency drug-sensitizing genotypes in tumor types not previously associated with drug susceptibility. Furthermore, comparing drugs thought to target the same kinase revealed striking differences, predictive of clinical efficacy. Genetically defined cancer subsets, irrespective of tissue type, predict response to kinase inhibitors, and provide an important preclinical model to guide early clinical applications of novel targeted inhibitors.

Salamanders and other amphibians are aglow with biofluorescence.

Biofluorescence is the absorption of electromagnetic radiation (light) at one wavelength followed by its reemission at a lower energy and longer wavelength by a living organism. Previous studies have documented the widespread presence of biofluorescence in some animals, including cnidarians, arthropods, and cartilaginous and ray-finned fishes. Many studies on biofluorescence have focused on marine animals (cnidarians, cartilaginous and ray-finned fishes) but we know comparatively little about the presence of biofluorescence in tetrapods. We show for the first time that biofluorescence is widespread across Amphibia, with a focus on salamanders (Caudata), which are a diverse group with a primarily Holarctic distribution. We find that biofluorescence is not restricted to any particular family of salamanders, there is striking variation in their fluorescent patterning, and the primary wavelengths emitted in response to blue excitation light are within the spectrum of green light. Widespread biofluorescence across the amphibian radiation is a previously undocumented phenomenon that could have significant ramifications for the ecology and evolution of these diverse and declining vertebrates. Our results provide a roadmap for future studies on the characterization of molecular mechanisms of biofluorescence in amphibians, as well as directions for investigations into the potential impact of biofluorescence on the visual ecology and behavior of biofluorescent amphibians.

Effectiveness, cost-effectiveness and safety of gabapentin versus placebo as an adjunct to multimodal pain regimens in surgical patients: protocol of a placebo controlled randomised controlled trial with blinding (GAP study).

INTRODUCTION: Gabapentin is an antiepileptic drug currently licensed to treat epilepsy and neuropathic pain but has been used off-label to treat acute postoperative pain. The GAP study will compare the effectiveness, cost-effectiveness and safety of gabapentin as an adjunct to standard multimodal analgesia versus placebo for the management of pain after major surgery. METHODS AND ANALYSIS: The GAP study is a multicentre, double-blind, randomised controlled trial in patients aged 18 years and over, undergoing different types of major surgery (cardiac, thoracic or abdominal). Patients will be randomised in a 1:1 ratio to receive either gabapentin (600 mg just before surgery and 600 mg/day for 2 days after surgery) or placebo in addition to usual pain management for each type of surgery. Patients will be followed up daily until hospital discharge and then at 4 weeks and 4 months after surgery. The primary outcome is length of hospital stay following surgery. Secondary outcomes include pain, total opioid use, adverse health events, health related quality of life and costs. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee . Findings will be shared with participating hospitals and disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Patients will be informed of the results through patient organisations and participant newsletters. TRIAL REGISTRATION NUMBER: ISRCTN63614165.

Approach to bullying and victimization.

OBJECTIVE: To review the epidemiology, identification, and management of bullying and victimization among children in the primary care setting. SOURCES OF INFORMATION: Information was obtained from PsycINFO and MEDLINE databases, as well as the authors' own clinical and research experience. Information is based on levels II and III evidence. MAIN MESSAGE: Involvement in bullying is a destructive relationship problem, with important health implications. Physicians need to be aware of the physical and psychosocial symptoms commonly associated with involvement in bullying so that they can screen and identify those children involved. This article presents a review of bullying and associated symptoms, a tool for assessing bullying involvement, and an overview of intervention and management. CONCLUSION: Bullying is a substantial problem affecting Canadian children. With an increased awareness and understanding of bullying as a health problem, physicians can play an instrumental role in identifying children involved in bullying and providing them with the support needed to develop healthy relationships.

Creating change: using the arts to help stop the stigma of mental illness and foster social integration.

Stigma is a social justice problem that plagues persons with psychiatric disabilities, their families, and society. It fuels the fear underlying discrimination; undermines consumer self-efficacy; and blocks rehabilitation, recovery, and social integration. The author hopes to create a passion for change and suggest a way that everyone can help stop stigma. This approach is simple: to nurture the artistic talent many clients possess and connect them with public venues for their artworks. On display, too, will be the "ability" in "disability." This will reduce stigma while building self-efficacy and empowerment. Anecdotal evidence supports this hypothesis. However, research is needed; a design for a study to test this hypothesis is described. Significantly, an antistigmal arts intervention can be conducted by any aware practitioner; one does not need to be an art therapist or have any background in art, only a desire to make a difference and resources on which to draw.

The T790M "gatekeeper" mutation in EGFR mediates resistance to low concentrations of an irreversible EGFR inhibitor.

Patients with non-small cell lung cancer (NSCLC) harboring activating mutations in the epidermal growth factor receptor (EGFR) kinase domain tend to respond well to the tyrosine kinase inhibitors, gefitinib and erlotinib. However, following clinical response, these patients typically relapse within a year of treatment. In many cases, resistance is caused by an acquired secondary EGFR kinase domain mutation, T790M. In vitro studies have shown that a new class of EGFR-irreversible inhibitors could overcome the resistance conferred by T790M. Clinical trials are under way to examine the efficacy of one of these inhibitors, HKI-272, in patients with NSCLC who initially responded to gefitinib/erlotinib and subsequently relapsed. To anticipate the possibility that patients who respond to irreversible inhibitors will develop secondary resistance to such inhibitors, as has been seen in other similar settings, we modeled acquired resistance to the dual EGFR/HER2-irreversible tyrosine kinase inhibitor HKI-272 in a NSCLC cell culture model. We found that HKI-272-resistant clones fall into two biochemical groups based on the retention of EGFR phosphorylation in the presence of the drug. Cells that retain phosphorylated EGFR have acquired the secondary mutation T790M. Moreover, HKI-272 can overcome T790M resistance only at suprapharmacologic concentrations. We further model mutations at EGFR C797 as a mechanism of resistance to irreversible EGFR inhibitors and show that although these mutants are resistant to the irreversible inhibitor, they retain erlotinib sensitivity. Our findings suggest that HKI-272 treatment at maximally tolerated dosing may lead to the emergence of T790M-mediated resistance, whereas treatment with a more potent irreversible inhibitor could yield a resistance mutation at EGFR C797.

Molecular characterization of liver fluke intermediate host lymnaeids (Gastropoda: Pulmonata) snails from selected regions of Okavango Delta of Botswana, KwaZulu-Natal and Mpumalanga provinces of South Africa.

Lymnaeidae snail species are known to be intermediate hosts of human and livestock helminths parasites, especially Fasciola species. Identification of these species and their geographical distribution is important to better understand the epidemiology of the disease. Significant diversity has been observed in the shell morphology of snails from the Lymnaeidae family and the systematics within this family is still unclear, especially when the anatomical traits among various species have been found to be homogeneous. Although there are records of lymnaeid species of southern Africa based on shell morphology and controversial anatomical traits, there is paucity of information on the molecular identification and phylogenetic relationships of the different taxa. Therefore, this study aimed at identifying populations of Lymnaeidae snails from selected sites of the Okavango Delta (OKD) in Botswana, and sites located in the KwaZulu-Natal (KZN) and Mpumalanga (MP) provinces of South Africa using molecular techniques. Lymnaeidae snails were collected from 8 locations from the Okavango delta in Botswana, 9 from KZN and one from MP provinces and were identified based on phylogenetic analysis of the internal transcribed spacer (ITS-2). Analyses based on the ITS-2 marker identified the presence of a well-supported Radix clade containing Radix auricularia, R. natalensis and R. rubiginosa, which were not well resolved. Experimental samples from the OKD and KZN present in this clade were referable to these species. An unidentified experimental taxon from the OKD formed a well-supported sister clade to the Radix clade, although it was not possible to identify it. Galba truncatula was well supported in a sister relationship to a well-supported Pseudosuccinea columella clade which included samples from MP and KZN provinces of South Africa. We observed that P. columella shared the same habitats with R. natalensis and R. auricularia in KZN. Our study contributes new knowledge on the Lymnaeidae species present in Southern Africa and their phylogenetic relationships. The study further identifies the species which are likely to co-exist in the same environment and this information will be of use to those designing control programs for fasciolosis. This is the first study reporting the presence of R. auricularia in the OKD of Botswana and KZN province of South Africa.

Multi-functionalised graphene nanoflakes as tumour-targeting theranostic drug-delivery vehicles.

Graphene nanoflakes (GNFs) consist of a graphene sheet approximately 30 nm in diameter with a pristine aromatic system and an edge terminated with carboxylic acid groups. Their high water solubility and relative ease of functionalisation using carboxylate chemistry means that GNFs are potential scaffolds for the synthesis of theranostic agents. In this work, GNFs were multi-functionalised with derivatives of (i) a peptide-based Glu-NH-C(O)-NH-Lys ligand that binds prostate-specific membrane antigen (PSMA), (ii) a potent anti-mitotic drug (R)-ispinesib, (iii) the chelate desferrioxamine B (DFO), and (iv) an albumin-binding tag reported to extend pharmacokinetic half-life in vivo. Subsequent 68Ga radiochemistry and experiments in vitro and in vivo were used to evaluate the performance of GNFs in theranostic drug design. Efficient 68Ga-radiolabelling was achieved and the particle-loading of (R)-ispinesib and Glu-NH-C(O)-NH-Lys was confirmed using cellular assays. Using dose-response curves and FACS analysis it was shown that GNFs loaded with (R)-ispinesib inhibited the kinesin spindle protein (KSP) and induced G2/M-phase cell cycle arrest. Cellular uptake and blocking experiments demonstrated that GNFs functionalised with the Glu-NH-C(O)-NH-Lys ligand showed specificity toward PSMA expressing cells (LNCaP). The distribution profile and excretion rates of 68Ga-radiolabelled GNFs in athymic nude mice was evaluated using time-activity curves derived from dynamic positron-emission tomography (PET). Image analysis indicated that GNFs have low accumulation and retention in background tissue, with rapid renal clearance. In summary, our study shows that GNFs are suitable candidates for use in theranostic drug design.

Advanced Methods for Radiolabeling Multimodality Nanomedicines for SPECT/MRI and PET/MRI.

The advent of hybrid cameras that combine MRI with either SPECT or PET has stimulated growing interest in developing multimodality imaging probes. Countless options are available for fusing magnetically active species with positron- or γ-ray-emitting radionuclides. The initial problem is one of choice: which chemical systems are a suitable basis for developing hybrid imaging agents? Any attempt to answer this question must also address how the physical, chemical, and biologic properties of a unified imaging agent can be tailored to ensure that optimum specificity and contrast are achieved simultaneously for both imaging modalities. Nanoparticles have emerged as attractive platforms for building multimodality radiotracers for SPECT/MRI and PET/MRI. A wide variety of nanoparticle constructs have been utilized as radiotracers, but irrespective of the particle class, radiolabeling remains a key step. Classic methods for radiolabeling nanoparticles involve functionalization of the particle surface, core, or coating. These modifications typically rely on using traditional metal ion chelate or prosthetic group chemistries. Though seemingly innocuous, appending nanoparticles with these radiolabeling handles can have dramatic effects on important properties such as particle size, charge, and solubility. In turn, alterations in the chemical and physical properties of the nanoparticle often have a negative impact on their pharmacologic profile. A central challenge in radiolabeling nanoparticles is to identify alternative chemical methods that facilitate the introduction of a radioactive nuclide without detrimental effects on the pharmacokinetic and toxicologic properties of the construct. Efforts to solve this challenge have generated a range of innovative chelate-free radiolabeling methods that exploit intrinsic chemical features of nanoparticles. Here, the chemistry of 9 mechanistically distinct methods for radiolabeling nanoparticles is presented. This discourse illustrates the evolution of nanoparticle radiochemistry from classic approaches to modern chelate-free or intrinsic methods.

Bibliometric analysis of authorship trends and collaboration dynamics over the past three decades of BONE's publication history.

The existence of a gender gap in academia has been a hotly debated topic over the past several decades. It has been argued that due to the gender gap, it is more difficult for women to obtain higher positions. Manuscripts serve as an important measurement of one's accomplishments within a particular field of academia. Here, we analyzed, over the past 3 decades, authorship and other trends in manuscripts published in BONE, one of the premier journals in the field of bone and mineral metabolism. For this study, one complete year of manuscripts was evaluated (e.g. 1985, 1995, 2005, 2015) for each decade. A bibliometric analysis was then performed of authorship trends for those manuscripts. Analyzed fields included: average number of authors per manuscript, numerical position of the corresponding author, number of institutions collaborating on each manuscript, number of countries involved with each manuscript, number of references, and number of citations per manuscript. Each of these fields increased significantly over the 30-year time frame (p<10-6). The gender of both the first and corresponding authors was identified and analyzed over time and by region. There was a significant increase in the percentage of female first authors from 23.4% in 1985 to 47.8% in 2015 (p=0.001). The percentage of female corresponding authors also increased from 21.2% in 1985 to 35.4% in 2015 although it was not significant (p=0.07). With such a substantial emphasis being placed on publishing in academic medicine, it is crucial to comprehend the changes in publishing characteristics over time and geographical region. These findings highlight authorship trends in BONE over time as well as by region. Importantly, these findings also highlight where challenges still exist.