Advancing outbreak simulation training: a collaborative pilot study for dual-specialty medical trainees and infection prevention and control professionals.

BACKGROUND: In response to identified gaps in infection prevention and control (IPC) training within Scotland, a Short Life Working Group initiated an innovative outbreak simulation training programme. AIM: To enhance the knowledge and confidence of medical microbiology and infectious diseases trainees and IPC professionals in managing healthcare-associated infection (HAI) outbreaks, employing the National Infection Prevention and Control Manual guidelines. METHODS: Participants completed prerequisite online training in epidemiology and surveillance before engaging in a meticulously crafted vancomycin-resistant enterococci outbreak simulation, which mirrored a real-life incident and adhered to the standards set by the Association for Simulated Practice in Healthcare. The programme incorporated Kolb's experiential learning cycle, fostering an authentic and engaging learning environment. A total of 41 individuals participated in the synchronous online training phase, with eight individuals involved in the pilot outbreak simulation. Evaluation of the training's efficacy followed Kirkpatrick's model, combining quantitative (five-point Likert scales) and qualitative (open-ended questions and participant reflections) data collection methods. FINDINGS: Results demonstrated significant improvements in participants' knowledge, skills, and confidence in outbreak management. Feedback highlighted the realism and educational value of the simulation, with 100% agreement on its efficacy in enhancing outbreak management capabilities. CONCLUSION: The success of this pilot study underscores the potential of simulation training in IPC and paves the way for broader implementation. It emphasizes the effectiveness of structured, experiential learning in equipping healthcare professionals with practical skills and confidence for managing complex HAI outbreaks, contributing to a more competent and prepared workforce.

Behavioral, metabolic, and lipidomic characterization of the 5xFADxTg30 mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is associated with both extracellular amyloid-ß (Aß) plaques and intracellular tau-containing neurofibrillary tangles (NFT). We characterized the behavioral, metabolic and lipidomic phenotype of the 5xFADxTg30 mouse model which contains overexpression of both Aß and tau. Our results independently reproduce several phenotypic traits described previously for this model, while providing additional characterization. This model develops many aspects associated with AD including frailty, decreased survival, initiation of aspects of cognitive decline and alterations to specific lipid classes and molecular lipid species in the plasma and brain. Notably, some sex-specific differences exist in this model and motor impairment with aging in this model does compromise the utility of the model for some movement-based behavioral assessments of cognitive function. These findings provide a reference for individuals interested in using this model to understand the pathology associated with elevated Aß and tau or for testing potential therapeutics for the treatment of AD.

Magnetic Arctic Circle in a Square Ice Qubit Lattice.

Under certain boundary conditions, the square ice model exhibits a phase separation in which the core of the system is disordered while its outer region remains ordered. This phenomenon, known as the "arctic circle," has been studied theoretically in combinatorial mathematics and statistical mechanics. Here, we realize the physics of the arctic circle experimentally for the first time, using a programmable lattice of superconducting qubits, and investigate its properties under the prism of a highly frustrated magnet. Our work reveals two unexpected properties. First, the disordered spin manifold confined within the arctic curve is a spin liquid whose average spin texture resembles that of an antivortex, i.e., it is a topologically charged Coulomb phase. Second, monopole quasiparticle excitations, which are totally absent in theoretical works, can be isolated in a phase-separated system. Remarkably, a monopole segregation mechanism is observed, in which the monopoles are sorted according to the magnetic charge and magnetic moment they carry, without the application of an external driving force.

Near-infrared photoimmunotherapy in the models of hepatocellular carcinomas using cetuximab-IR700.

Epidermal growth factor receptor (EGFR) has emerged as an important therapeutic target in many cancers, and overexpression of EGFR is frequently observed in hepatocellular carcinomas (HCCs). Near-infrared photoimmunotherapy (NIR-PIT) is a new anticancer treatment that selectively damages the cell membrane of cancer cells after NIR light-induced photochemical reaction of IR700, which is bound to a targeting antibody on the cell membrane. NIR-PIT using cetuximab-IR700 has already been approved in Japan, is under review by the US Food and Drug Administration (FDA) for advanced head and neck cancers, and its safety has been established. However, EGFR has not been investigated as a target in NIR-PIT in HCCs. Here, we investigate the application of NIR-PIT using cetuximab-IR700 to HCCs using xenograft mouse models of EGFR-expressing HCC cell lines, Hep3B, HuH-7, and SNU-449. In vitro NIR-PIT using EGFR-targeted cetuximab-IR700 killed cells in a NIR light dose-dependent manner. In vivo NIR-PIT resulted in a delayed growth compared with untreated controls. In addition, in vivo NIR-PIT in both models showed histological signs of cancer cell damage, such as cytoplasmic vacuolation and nuclear dysmorphism. A significant decrease in Ki-67 positivity was also observed after NIR-PIT, indicating decreased cancer cell proliferation. This study suggests that NIR-PIT using cetuximab-IR700 has potential for the treatment of EGFR-expressing HCCs.

Development of Iodinated Indocyanine Green Analogs as a Strategy for Targeted Therapy of Liver Cancer.

Liver cancer is one of the leading causes of cancer-related deaths, with a significant increase in incidence worldwide. Novel therapies are needed to address this unmet clinical need. Indocyanine green (ICG) is a broadly used fluorescence-guided surgery (FGS) agent for liver tumor resection and has significant potential for conversion to a targeted therapy. Here, we report the design, synthesis, and investigation of a series of iodinated ICG analogs (I-ICG), which can be used to develop ICG-based targeted radiopharmaceutical therapy. We applied a CRISPR-based screen to identify the solute carrier transporter, OATP1B3, as a likely mechanism for ICG uptake. Our lead I-ICG compound specifically localizes to tumors in mice bearing liver cancer xenografts. This study introduces the chemistry needed to incorporate iodine onto the ICG scaffold and defines the impact of these modifications on key properties, including targeting liver cancer in vitro and in vivo.

Site-Specifically Conjugated Single-Domain Antibody Successfully Identifies Glypican-3-Expressing Liver Cancer by Immuno-PET.

Primary liver cancer is the third leading cause of cancer-related deaths, and its incidence and mortality are increasing worldwide. Hepatocellular carcinoma (HCC) accounts for 80% of primary liver cancer cases. Glypican-3 (GPC3) is a heparan sulfate proteoglycan that histopathologically defines HCC and represents an attractive tumor-selective marker for radiopharmaceutical imaging and therapy for this disease. Single-domain antibodies are a promising scaffold for imaging because of their favorable pharmacokinetic properties, good tumor penetration, and renal clearance. Although conventional lysine-directed bioconjugation can be used to yield conjugates for radiolabeling full-length antibodies, this stochastic approach risks negatively affecting target binding of the smaller single-domain antibodies. To address this challenge, site-specific approaches have been explored. Here, we used conventional and sortase-based site-specific conjugation methods to engineer GPC3-specific human single-domain antibody (HN3) PET probes. Methods: Bifunctional deferoxamine (DFO) isothiocyanate was used to synthesize native HN3 (nHN3)-DFO. Site-specifically modified HN3 (ssHN3)-DFO was engineered using sortase-mediated conjugation of triglycine-DFO chelator and HN3 containing an LPETG C-terminal tag. Both conjugates were radiolabeled with 89Zr, and their binding affinity in vitro and target engagement of GPC3-positive (GPC3+) tumors in vivo were determined. Results: Both 89Zr-ssHN3 and 89Zr-nHN3 displayed nanomolar affinity for GPC3 in vitro. Biodistribution and PET/CT image analysis in mice bearing isogenic A431 and A431-GPC3+ xenografts, as well as in HepG2 liver cancer xenografts, showed that both conjugates specifically identify GPC3+ tumors. 89Zr-ssHN3 exhibited more favorable biodistribution and pharmacokinetic properties, including higher tumor uptake and lower liver accumulation. Comparative PET/CT studies on mice imaged with both 18F-FDG and 89Zr-ssHN3 showed more consistent tumor accumulation for the single-domain antibody conjugate, further establishing its potential for PET imaging. Conclusion: 89Zr-ssHN3 showed clear advantages in tumor uptake and tumor-to-liver signal ratio over the conventionally modified 89Zr-nHN3 in xenograft models. Our results establish the potential of HN3-based single-domain antibody probes for GPC3-directed PET imaging of liver cancers.

Childhood adversities and risk of posttraumatic stress disorder and major depression following a motor vehicle collision in adulthood.

AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions. METHODS: Data came from n = 999 patients ages 18-75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models. RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43-2.87) and bullying (RR = 1.44; 95% CI = 0.99-2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE. CONCLUSIONS: Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.

Dynamic nomogram for long-term survival in patients with locally advanced oropharyngeal cancer after (chemo)radiotherapy.

PURPOSE: This study aimed to establish a nomogram for predicting overall survival (OS) in oropharyngeal cancer patients treated with curative (chemo)radiotherapy. MATERIALS AND METHODS: The dynamic nomogram was constructed on 273 patients with oropharyngeal squamous cell carcinoma treated in a Tertiary Head and Neck Cancer Unit. The clinical features that were previously reported to be associated with OS were analyzed. The performance of the nomogram was assessed using concordance index (C-index) and calibration curves. RESULTS: The nomogram incorporated three explanatory variables derived from a decision tree approach including HPV status, N classification according to 8th edition TNM and early response to (chemo)radiotherapy. The nomogram was capable to predict OS with a validation C-index of 0.768. The proposed stratification in risk groups allowed significant distinction between Kaplan-Meier curves for OS outcome (p < 0.0001). CONCLUSIONS: The nomogram provided an accurate evaluation of OS for oropharyngeal cancer patients treated with curative (chemo)radiotherapy.

225Ac-MACROPATATE: A Novel α-Particle Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors.

Neuroendocrine tumors (NETs) express somatostatin receptors (SSTRs) 2 and 5. Modified variants of somatostatin, the cognate ligand for SSTR2 and SSTR5, are used in treatment for metastatic and locoregional disease. Peptide receptor radionuclide therapy with 177Lu-DOTATATE (DOTA-octreotate), a ß-particle-emitting somatostatin derivative, has demonstrated survival benefit in patients with SSTR-positive NETs. Despite excellent results, a subset of patients has tumors that are resistant to treatment, and alternative agents are needed. Targeted α-particle therapy has been shown to kill tumors that are resistant to targeted ß-particle therapy, suggesting that targeted α-particle therapy may offer a promising treatment option for patients with 177Lu-DOTATATE-resistant disease. Although DOTATATE can chelate the clinically relevant α-particle-emitting radionuclide 225Ac, the labeling reaction requires high temperatures, and the resulting radioconjugate has suboptimal stability. Methods: We designed and synthesized MACROPATATE (MACROPA-octreotate), a novel radioconjugate capable of chelating 225Ac at room temperature, and assessed its in vitro and in vivo performance. Results: MACROPATATE demonstrated comparable affinity to DOTATATE (dissociation constant, 21 nM) in U2-OS-SSTR2, a SSTR2-positive transfected cell line. 225Ac-MACROPATATE demonstrated superior serum stability at 37°C over time compared with 225Ac-DOTATATE. Biodistribution studies demonstrated higher tumor uptake of 225Ac-MACROPATATE than of 225Ac-DOTATATE in mice engrafted with subcutaneous H69 NETs. Therapy studies showed that 225Ac-MACROPATATE exhibits significant antitumor and survival benefit compared with saline control in mice engrafted with SSTR-positive tumors. However, the increased accumulation of 225Ac-MACROPATATE in liver and kidneys and subsequent toxicity to these organs decreased its therapeutic index compared with 225Ac-DOTATATE. Conclusion: 225Ac-MACROPATATE and 225Ac-DOTATATE exhibit favorable therapeutic efficacy in animal models. Because of elevated liver and kidney accumulation and lower administered activity for dose-limiting toxicity of 225Ac-MACROPATATE, 225Ac-DOTATATE was deemed the superior agent for targeted α-particle peptide receptor radionuclide therapy.

Employing citizen science to enhance active and healthy ageing in urban environments.

Engaging older residents in problem definition and solution-building is key to the success of place-based initiatives endeavouring to increase the age-friendliness of urban environments. This study employed the Our Voice framework, engaging older adult citizen scientists (n = 14) and community stakeholders (n = 15) across the city of Birmingham, UK. With the aim of identifying urban features impacting age friendliness and co-producing recommendations for improving local urban areas, citizen scientists participated in 12 technology-enabled walkability assessments, three in-person discussion groups, two one-to-one online discussions, and two workshops with community stakeholders. Together, citizen scientists co-produced 12 local and six city-wide recommendations. These recommendations were embedded into an implementation framework based on workshop discussions to identify age-friendly pathways in urban environments.

Metal Complexes as Antifungals? From a Crowd-Sourced Compound Library to the First In Vivo Experiments.

There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work, we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or hemolytic properties at similar concentrations. The structures of 21 metal complexes that display high antifungal activity (MIC ≤1.25 µM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been previously tested for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larva model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex Pt1 significantly reduces fungal load in an in vivo G. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.

Clinical features associated with ADB-BUTINACA exposure in patients attending emergency departments in England.

OBJECTIVE: Synthetic cannabinoid receptor agonists (SCRA) are commonly encountered new psychoactive substances. Here we report the recent detection of ADB-BUTINACA in samples from patients attending United Kingdom emergency departments with toxicity after suspected drug misuse and describe the associated clinical features. METHODS: Consenting adults (≥16 y) presenting to participating hospitals with toxicity after suspected drug misuse have been included in the Identification Of Novel psychoActive substances (IONA) study since March 2015. Demographic and clinical features are recorded and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry. RESULTS: By December 2021, analytical data were available for 1279 IONA participants and ADB-BUTINACA was detected in at least one sample from 10 (9 males, age range 16-51 median 45 years), all presenting since February 2021. Smoking 'spice' was reported by four patients, two had ingested edible "cannabis" gums and four reported heroin use (2 intravenous, 1 smoked, 1 route not known). Co-use of pregabalin (oral) and crack cocaine (smoked) were also reported. In 3 cases ADB-BUTINACA was the only substance detected, while in seven other substances of misuse were also detected including other SCRA, opioids, benzodiazepines cocaine and pregabalin. Clinical features reported in these 2 groups respectively included reduced level of consciousness (3/3, 6/7), agitation (0/3, 4/7), tachycardia (0/3, 3/7), seizures (1/3, 1/7), hallucinations (1/3, 1/7), hypotension (1/3, 1/7). Metabolic acidosis (1/3, 0/7) and respiratory acidosis (1/3, 0/7), All 10 patients recovered with supportive care, including intubation and ventilation for one case. The median length of hospital stay was 19 h (range 2.6-131 h). CONCLUSIONS: ADB-BUTINACA has recently emerged as a drug of misuse in England. Clinical features of toxicity are consistent with those of other SCRA and include reduced level of consciousness, respiratory and/or metabolic acidosis, seizures, confusion and hallucinations.

An Anticancer Rhenium Tricarbonyl Targets Fe-S Cluster Biogenesis in Ovarian Cancer Cells.

Target identification remains a critical challenge in inorganic drug discovery to deconvolute potential polypharmacology. Herein, we describe an improved approach to prioritize candidate protein targets based on a combination of dose-dependent chemoproteomics and treatment effects in living cancer cells for the rhenium tricarbonyl compound TRIP. Chemoproteomics revealed 89 distinct dose-dependent targets with concentrations of competitive saturation between 0.1 and 32 µM despite the broad proteotoxic effects of TRIP. Target-response networks revealed two highly probable targets of which the Fe-S cluster biogenesis factor NUBP2 was competitively saturated by free TRIP at nanomolar concentrations. Importantly, TRIP treatment led to a down-regulation of Fe-S cluster containing proteins and upregulated ferritin. Fe-S cluster depletion was further verified by assessing mitochondrial bioenergetics. Consequently, TRIP emerges as a first-in-class modulator of the scaffold protein NUBP2, which disturbs Fe-S cluster biogenesis at sub-cytotoxic concentrations in ovarian cancer cells.

ImpACT+, a coping intervention to improve clinical outcomes for women living with HIV and sexual trauma in South Africa: study protocol for a randomized controlled trial.

BACKGROUND: Addressing sexual trauma in the context of HIV care is essential to improve clinical outcomes and mental health among women in South Africa. Women living with HIV (WLH) report disproportionately high levels of sexual trauma and have higher rates of posttraumatic stress disorder. Adherence to antiretroviral therapy (ART) may be difficult for traumatized women, as sexual trauma compounds the stress associated with managing HIV and is often comorbid with other mental health disorders, further compromising care engagement and adherence. ART initiation represents a unique window of opportunity for intervention to enhance motivation, increase care engagement, and address the negative effects of trauma on avoidant coping behaviors. Mental health interventions delivered by non-specialists in low- and middle-income countries have potential to treat depression, trauma, and effects of intimate partner violence among WLH. This study will examine the effectiveness of Improving AIDS Care after Trauma (ImpACT +), a task-shared, trauma-focused coping intervention, to promote viral suppression among WLH initiating ART in a South African clinic setting. METHODS: This study will be conducted in Khayelitsha, a peri-urban settlement situated near Cape Town, South Africa. Using a hybrid type 1 effectiveness-implementation design, we will randomize 350 WLH initiating ART to the ImpACT + experimental condition or the control condition (three weekly sessions of adapted problem-solving therapy) to examine the effectiveness of ImpACT + on viral suppression, ART adherence, and the degree to which mental health outcomes mediate intervention effects. ImpACT + participants will receive six once-a-week coping intervention sessions and six monthly maintenance sessions over the follow-up period. We will conduct mental health and bio-behavioral assessments at baseline, 4, 8, and 12 months, with care engagement data extracted from medical records. We will explore scalability using the Consolidated Framework for Implementation Research (CFIR). DISCUSSION: This trial is expected to yield important new information on psychologically informed intervention models that benefit the mental health and clinical outcomes of WLH with histories of sexual trauma. The proposed ImpACT + intervention, with its focus on building coping skills to address traumatic stress and engagement in HIV care and treatment, could have widespread impact on the health and wellbeing of individuals and communities in sub-Saharan Africa. TRIAL REGISTRATION: Clinicaltrials.gov NCT04793217 . Retrospectively registered on 11 March 2021.

Community engagement to improve access to healthcare: a comparative case study to advance implementation science for transgender health equity.

BACKGROUND: Recent calls to action have been made for Implementation Science to attend to health inequities at the intersections of race, gender, and social injustice in the United States. Transgender people, particularly Black and Latina transgender women, experience a range of health inequities and social injustices. In this study, we compared two processes of transgender community engagement in Los Angeles and in Chicago as an implementation strategy to address inequitable access to care; we adapted and extended the Exploration Planning Implementation and Sustainment (EPIS) framework for transgender health equity. METHODS: A comparative case method and the EPIS framework were used to examine parallel implementation strategies of transgender community engagement to expand access to care. To foster conceptual development and adaptation of EPIS for trans health equity, the comparative case method required detailed description, exploration, and analyses of the community-engagement processes that led to different interventions to expand access. In both cities, the unit of analysis was a steering committee made up of local transgender and cisgender stakeholders. RESULTS: Both steering committees initiated their exploration processes with World Café-style, transgender community-engaged events in order to assess community needs and structural barriers to healthcare. The steering committees curated activities that amplified the voices of transgender community members among stakeholders, encouraging more effective and collaborative ways to advance transgender health equity. Based on analysis and findings from the Los Angeles town hall, the steering committee worked with a local medical school, extending the transgender medicine curriculum, and incorporating elements of transgender community-engagement. The Chicago steering committee determined from their findings that the most impactful intervention on structural racism and barriers to healthcare access would be to design and pilot an employment program for Black and Latina transgender women. CONCLUSION: In Los Angeles and Chicago, transgender community engagement guided implementation processes and led to critical insights regarding specific, local barriers to healthcare. The steering committee itself represented an important vehicle for individual-, organizational-, and community-level relationship and capacity building. This comparative case study highlights key adaptations of EPIS toward the formation of an implementation science framework for transgender health equity.

H2BZmacropa-NCS: A Bifunctional Chelator for Actinium-225 Targeted Alpha Therapy.

Actinium-225 (225Ac) is one of the most promising radionuclides for targeted alpha therapy (TAT). With a half-life of 9.92 days and a decay chain that emits four high-energy α particles, 225Ac is well-suited for TAT when conjugated to macromolecular targeting vectors that exhibit extended in vivo circulation times. The implementation of 225Ac in these targeted constructs, however, requires a suitable chelator that can bind and retain this radionuclide in vivo. Previous work has demonstrated the suitability of a diaza-18-crown-6 macrocyclic chelator H2macropa for this application. Building upon these prior efforts, in this study, two rigid variants of H2macropa, which contain either one (H2BZmacropa) or two (H2BZ2macropa) benzene rings within the macrocyclic core, were synthesized and investigated for their potential use for 225Ac TAT. The coordination chemistry of these ligands with La3+, used as a nonradioactive model for Ac3+, was carried out. Both NMR spectroscopic and X-ray crystallographic studies of the La3+ complexes of these ligands revealed similar structural features to those found for the related complex of H2macropa. Thermodynamic stability constants of the La3+ complexes, however, were found to be 1 and 2 orders of magnitude lower than those of H2macropa for H2BZmacropa and H2BZ2macropa, respectively. The decrease in thermodynamic stability was rationalized via the use of density functional theory calculations. 225Ac radiolabeling and serum stability studies with H2BZmacropa showed that this chelator compares favorably with H2macropa. Based on these promising results, a bifunctional version of this chelator, H2BZmacropa-NCS, was synthesized and conjugated to the antibody codrituzumab (GC33), which targets the liver cancer biomarker glypican-3 (GPC3). The resulting GC33-BZmacropa conjugate and an analogous GC33-macropa conjugate were evaluated for their 225Ac radiolabeling efficiencies, antigen-binding affinities, and in vivo biodistribution in HepG2 liver cancer tumor-bearing mice. Although both conjugates were comparably effective in their radiolabeling efficiencies, [225Ac]Ac-GC33-BZmacropa showed slightly poorer serum stability and biodistribution than [225Ac]Ac-GC33-macropa. Together, these results establish H2BZmacropa-NCS as a new bifunctional chelator for the preparation of 225Ac radiopharmaceuticals.

Wayfinding and spatial perception among adolescents with mild intellectual disability.

BACKGROUND: The study's aim was to examine whether spatial orientation can be improved in students with cognitive disabilities. METHOD: Participants were 55 boys and girls with attention deficit and mild cognitive impairment from a special education school. The procedure included an intervention for two experimental groups that studied wayfinding and orientation in the environment: group #1 learned to use a map while navigating, and group #2 learned to use a Google navigation app with voice instructions. Two pre-post tests were applied: (1) Mental folding test for children (MFTC) and (2) field test with map. RESULTS: Both groups improved their ability in navigation and wayfinding. No advantage for one learning method over the other was demonstrated, except for shortened navigation time in the group navigating with a map, and a slight though not significant tendency of improvement in the MFTC task in the group learning navigation using a voice app. CONCLUSION: It is worth noting that the study did not examine the students' own preferences for the way of learning, which may have implications for the degree of possible improvement. Also, a longer period of the learning process might yield a clearer understanding concerning the differences between the two teaching methods that were examined.

Elimination of human rabies in Goa, India through an integrated One Health approach.

Dog-mediated rabies kills tens of thousands of people each year in India, representing one third of the estimated global rabies burden. Whilst the World Health Organization (WHO), World Organization for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) have set a target for global dog-mediated human rabies elimination by 2030, examples of large-scale dog vaccination programs demonstrating elimination remain limited in Africa and Asia. We describe the development of a data-driven rabies elimination program from 2013 to 2019 in Goa State, India, culminating in human rabies elimination and a 92% reduction in monthly canine rabies cases. Smartphone technology enabled systematic spatial direction of remote teams to vaccinate over 95,000 dogs at 70% vaccination coverage, and rabies education teams to reach 150,000 children annually. An estimated 2249 disability-adjusted life years (DALYs) were averted over the program period at 526 USD per DALY, making the intervention 'very cost-effective' by WHO definitions. This One Health program demonstrates that human rabies elimination is achievable at the state level in India.