Current European flood-rich period exceptional compared with past 500 years.

There are concerns that recent climate change is altering the frequency and magnitude of river floods in an unprecedented way1. Historical studies have identified flood-rich periods in the past half millennium in various regions of Europe2. However, because of the low temporal resolution of existing datasets and the relatively low number of series, it has remained unclear whether Europe is currently in a flood-rich period from a long-term perspective. Here we analyse how recent decades compare with the flood history of Europe, using a new database composed of more than 100 high-resolution (sub-annual) historical flood series based on documentary evidence covering all major regions of Europe. We show that the past three decades were among the most flood-rich periods in Europe in the past 500 years, and that this period differs from other flood-rich periods in terms of its extent, air temperatures and flood seasonality. We identified nine flood-rich periods and associated regions. Among the periods richest in floods are 1560-1580 (western and central Europe), 1760-1800 (most of Europe), 1840-1870 (western and southern Europe) and 1990-2016 (western and central Europe). In most parts of Europe, previous flood-rich periods occurred during cooler-than-usual phases, but the current flood-rich period has been much warmer. Flood seasonality is also more pronounced in the recent period. For example, during previous flood and interflood periods, 41 per cent and 42 per cent of central European floods occurred in summer, respectively, compared with 55 per cent of floods in the recent period. The exceptional nature of the present-day flood-rich period calls for process-based tools for flood-risk assessment that capture the physical mechanisms involved, and management strategies that can incorporate the recent changes in risk.

Mnk1/2 kinases regulate memory and autism-related behaviours via Syngap1.

MAPK interacting protein kinases 1 and 2 (Mnk1/2) regulate a plethora of functions, presumably via phosphorylation of their best characterized substrate, eukaryotic translation initiation factor 4E (eIF4E) on Ser209. Here, we show that, whereas deletion of Mnk1/2 (Mnk double knockout) impairs synaptic plasticity and memory in mice, ablation of phospho-eIF4E (Ser209) does not affect these processes, suggesting that Mnk1/2 possess additional downstream effectors in the brain. Translational profiling revealed only a small overlap between the Mnk1/2- and phospho-eIF4E(Ser209)-regulated translatome. We identified the synaptic Ras GTPase activating protein 1 (Syngap1), encoded by a syndromic autism gene, as a downstream target of Mnk1 because Syngap1 immunoprecipitated with Mnk1 and showed reduced phosphorylation (S788) in Mnk double knockout mice. Knockdown of Syngap1 reversed memory deficits in Mnk double knockout mice and pharmacological inhibition of Mnks rescued autism-related phenotypes in Syngap1+/- mice. Thus, Syngap1 is a downstream effector of Mnk1, and the Mnks-Syngap1 axis regulates memory formation and autism-related behaviours.

Autistic-like behavior and cerebellar dysfunction in Bmal1 mutant mice ameliorated by mTORC1 inhibition.

Although circadian and sleep disorders are frequently associated with autism spectrum disorders (ASD), it remains elusive whether clock gene disruption can lead to autistic-like phenotypes in animals. The essential clock gene Bmal1 has been associated with human sociability and its missense mutations are identified in ASD. Here we report that global Bmal1 deletion led to significant social impairments, excessive stereotyped and repetitive behaviors, as well as motor learning disabilities in mice, all of which resemble core behavioral deficits in ASD. Furthermore, aberrant cell density and immature morphology of dendritic spines were identified in the cerebellar Purkinje cells (PCs) of Bmal1 knockout (KO) mice. Electrophysiological recordings uncovered enhanced excitatory and inhibitory synaptic transmission and reduced firing rates in the PCs of Bmal1 KO mice. Differential expression of ASD- and ataxia-associated genes (Ntng2, Mfrp, Nr4a2, Thbs1, Atxn1, and Atxn3) and dysregulated pathways of translational control, including hyperactivated mammalian target of rapamycin complex 1 (mTORC1) signaling, were identified in the cerebellum of Bmal1 KO mice. Interestingly, the antidiabetic drug metformin reversed mTORC1 hyperactivation and alleviated major behavioral and PC deficits in Bmal1 KO mice. Importantly, conditional Bmal1 deletion only in cerebellar PCs was sufficient to recapitulate autistic-like behavioral and cellular changes akin to those identified in Bmal1 KO mice. Together, these results unveil a previously unidentified role for Bmal1 disruption in cerebellar dysfunction and autistic-like behaviors. Our findings provide experimental evidence supporting a putative role for dysregulation of circadian clock gene expression in the pathogenesis of ASD.

Meaning-centered group psychotherapy in Portuguese cancer patients: A pilot exploratory trial.

OBJECTIVE: To describe the feasibility of a meaning-centered group psychotherapy (MCGP) adaptation in a sample of Portuguese cancer patients. METHOD: The study was carried out according to four steps: 1st - Transcultural adaptation and validation (focus groups); 2nd - Preliminary study with MCGP original version (to test its feasibility); 3rd - Adaptation of MCGP original version to a 4-session version (and internal pilot study); and 4th - Pilot exploratory trial (MCGP-4 session version), implemented between January 1, 2018 and December 31, 2019. Inclusion criteria were >18 years, psychological complaints, and difficulty to adapt to cancer. Allocation was according to participants' preference: MCGP vs. care as usual (CAU). Primary outcomes were: MCGP adapted version improved quality of life (QoL) and spiritual well-being; secondary outcomes were improvement of depression, anxiety, and distress. Assessments were done at baseline (T1) and 1 month after (T2), with self-report socio-demographic and clinical questionnaires, Distress Thermometer (DT), McGill Quality of Life Questionnaire (MQOL), Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being Scale (FACIT-Sp-12), Hospital Anxiety and Depression Scale, and its subscales (HADS - HADS-D, HADS-A). RESULTS: In the 1st step, and through focus groups, the manual was reformulated and tested. The preliminary study (2nd step) with MCGP original version showed a high number of dropouts which could jeopardize the study and, after reframing the sessions content, MCGP was adapted to a 4-session version, and its feasibility was tested by an internal pilot study (3rd step). The pilot exploratory trial (4th step) had 91 participants. Most socio-demographic and clinical characteristics between the groups (51: MCGP; 40: CAU) had no statistically significant differences. A comparison between the two groups at T2 showed that the MCGP group scored significantly higher in the general (U = 552.00, P < 0.001), and existential (U = 727.50, P = 0.018) domains and total score (U = 717.50, P = 0.015) of QoL, and CAU presented statistical higher levels in DT (U = 608.50, P = 0.001). Comparing the groups between T1 and T2, the MCGP group had a statistically significant improvement in the general (Z = -3.67, P < 0.001) and psychosocial (Z = -2.89, P = 0.004) domains and total score (Z = -2.71, P = 0.007) of QoL, and a statistically significant decrease in DT (Z = -2.40, P = 0.016). In terms of group effects, the MCGP group presented increased general (b = 1.42, P < 0.001, η2p = 0.179), and support (b = 0.80, P = 0.045, η2p = 0.048) domains and total score (b = 0.81, P = 0.013, η2p = 0.073) of QoL (small to elevated dimensions), and decreased levels of depression (b = -1.14, P = 0.044, η2p = 0.048), and distress (b = -1.38, P = 0.001, η2p = 0.127) (small to medium dimensions), compared with CAU. At T2, participants who attended ≥3 sessions (n = 38) had a statistically significant higher score in the general domain (U = 130.50, P = 0.009) of QoL, comparing with those who attended 1 or 2 sessions (n = 13). SIGNIFICANCE OF RESULTS: This study supports the benefits of an MCGP adapted version in improving QoL and psychologic well-being. More studies are necessary to address the limitations of this pilot exploratory trial, as its small sample size.

Process of therapeutic changes in Meaning-Centered Group Psychotherapy adapted to the Portuguese language: A narrative analysis.

OBJECTIVE: The aim was to understand the processes of therapeutic changes in Meaning-Centered Group Psychotherapy (MCGP) in a Portuguese sample. METHOD: Adult cancer patients with distress motivated to participate in MCGP were identified; descriptive and narrative analyses were performed on the session content. RESULTS: The sample had 24 participants (mean age: 63.43 years); the majority were females (75%), with a median academic degree (54%). Breast cancer was most frequent (67%) at the localized stage (71%). The narrative analysis defined seven categories according to the MCGP themes. In "Moments with Meaning (MwM)," the most relevant dimensions were related to interpersonal relations, the moment of diagnosis, and personal achievements. This category established relations with almost all other categories, as did the category "historical sources of meaning (SoM)." The category "identity before and after cancer diagnosis" was only related to "attitudinal SoM" and "transitions." Historical SoM had two dimensions, "past" and "present and future" legacies, in which prominent topics related to family, childhood, achieved goals, and values to pass to others explored. Attitudinal SoM established relations only with the category "creative SoM," in which "courage" and "responsibility" were the main dimensions, which were also related to "MwM," "historical," and "attitudinal SoM." Experiential SoM, with the main dimension "love," was related to "MwM" and "historical SoM." Transitions only established relations with "historical SoM" and "identity before and after cancer." SIGNIFICANCE OF RESULTS: The findings that "MwM" and "historical SoM" were the categories which established a solid pattern of relations suggest that these are the main psychotherapy topics that can have more influence for the participants; one explanation is that these categories imply a concrete way of thinking, which is easier to understand. This process of therapeutic changes must be integrated in a cultural context, as it is well known to have an impact upon the "meaning" of life.

Loss of eIF4E Phosphorylation Engenders Depression-like Behaviors via Selective mRNA Translation.

The MAPK/ERK (mitogen-activated protein kinases/extracellular signal-regulated kinase) pathway is a cardinal regulator of synaptic plasticity, learning, and memory in the hippocampus. One of major endpoints of this signaling cascade is the 5' mRNA cap binding protein eIF4E (eukaryotic Initiation Factor 4E), which is phosphorylated on Ser 209 by MNK (MAPK-interacting protein kinases) and controls mRNA translation. The precise role of phospho-eIF4E in the brain is yet to be determined. Herein, we demonstrate that ablation of eIF4E phosphorylation in male mice (4Eki mice) does not impair long-term spatial or contextual fear memory, or the late phase of LTP. Using unbiased translational profiling in mouse brain, we show that phospho-eIF4E differentially regulates the translation of a subset of mRNAs linked to inflammation, the extracellular matrix, pituitary hormones, and the serotonin pathway. Consequently, 4Eki male mice display exaggerated inflammatory responses and reduced levels of serotonin, concomitant with depression and anxiety-like behaviors. Remarkably, eIF4E phosphorylation is required for the chronic antidepressant action of the selective serotonin reuptake inhibitor fluoxetine. Finally, we propose a novel phospho-eIF4E-dependent translational control mechanism in the brain, via the GAIT complex (gamma IFN activated inhibitor of translation). In summary, our work proposes a novel translational control mechanism involved in the regulation of inflammation and depression, which could be exploited to design novel therapeutics.SIGNIFICANCE STATEMENT We demonstrate that downstream of the MAPK (mitogen-activated protein kinase) pathway, eukaryotic Initiation Factor 4E (eIF4E) Ser209 phosphorylation is not required for classical forms of hippocampal LTP and memory. We reveal a novel role for eIF4E phosphorylation in inflammatory responses and depression-like behaviors. eIF4E phosphorylation is required for the chronic action of antidepressants, such as fluoxetine in mice. These phenotypes are accompanied by selective translation of extracellular matrix, pituitary hormones, and serotonin pathway genes, in eIF4E phospho-mutant mice. We also describe a previously unidentified translational control mechanism in the brain, whereby eIF4E phosphorylation is required for inhibiting the translation of gamma IFN activated inhibitor of translation element-containing mRNAs. These findings can be used to design novel therapeutics for depression.

Sideroflexin 3 is an α-synuclein-dependent mitochondrial protein that regulates synaptic morphology.

α-Synuclein plays a central role in Parkinson's disease, where it contributes to the vulnerability of synapses to degeneration. However, the downstream mechanisms through which α-synuclein controls synaptic stability and degeneration are not fully understood. Here, comparative proteomics on synapses isolated from α-synuclein-/- mouse brain identified mitochondrial proteins as primary targets of α-synuclein, revealing 37 mitochondrial proteins not previously linked to α-synuclein or neurodegeneration pathways. Of these, sideroflexin 3 (SFXN3) was found to be a mitochondrial protein localized to the inner mitochondrial membrane. Loss of SFXN3 did not disturb mitochondrial electron transport chain function in mouse synapses, suggesting that its function in mitochondria is likely to be independent of canonical bioenergetic pathways. In contrast, experimental manipulation of SFXN3 levels disrupted synaptic morphology at the Drosophila neuromuscular junction. These results provide novel insights into α-synuclein-dependent pathways, highlighting an important influence on mitochondrial proteins at the synapse, including SFXN3. We also identify SFXN3 as a new mitochondrial protein capable of regulating synaptic morphology in vivo.

eIF4E phosphorylation recruits ß-catenin to mRNA cap and promotes Wnt pathway translation in dentate gyrus LTP maintenance.

The mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is crucial for translation and regulated by Ser209 phosphorylation. However, the biochemical and physiological role of eIF4E phosphorylation in translational control of long-term synaptic plasticity is unknown. We demonstrate that phospho-ablated Eif4eS209A Knockin mice are profoundly impaired in dentate gyrus LTP maintenance in vivo, whereas basal perforant path-evoked transmission and LTP induction are intact. mRNA cap-pulldown assays show that phosphorylation is required for synaptic activity-induced removal of translational repressors from eIF4E, allowing initiation complex formation. Using ribosome profiling, we identified selective, phospho-eIF4E-dependent translation of the Wnt signaling pathway in LTP. Surprisingly, the canonical Wnt effector, ß-catenin, was massively recruited to the eIF4E cap complex following LTP induction in wild-type, but not Eif4eS209A, mice. These results demonstrate a critical role for activity-evoked eIF4E phosphorylation in dentate gyrus LTP maintenance, remodeling of the mRNA cap-binding complex, and specific translation of the Wnt pathway.

A seeding-based neuronal model of tau aggregation for use in drug discovery.

Intracellular accumulation of tau protein is a hallmark of Alzheimer's Disease and Progressive Supranuclear Palsy, as well as other neurodegenerative disorders collectively known as tauopathies. Despite our increasing understanding of the mechanisms leading to the initiation and progression of tau pathology, the field still lacks appropriate disease models to facilitate drug discovery. Here, we established a novel and modulatable seeding-based neuronal model of full-length 4R tau accumulation using humanized mouse cortical neurons and seeds from P301S human tau transgenic animals. The model shows specific and consistent formation of intraneuronal insoluble full-length 4R tau inclusions, which are positive for known markers of tau pathology (AT8, PHF-1, MC-1), and creates seeding competent tau. The formation of new inclusions can be prevented by treatment with tau siRNA, providing a robust internal control for use in qualifying the assessment of potential therapeutic candidates aimed at reducing the intracellular pool of tau. In addition, the experimental set up and data analysis techniques used provide consistent results in larger-scale designs that required multiple rounds of independent experiments, making this is a versatile and valuable cellular model for fundamental and early pre-clinical research of tau-targeted therapies.

Uncovering memory-related gene expression in contextual fear conditioning using ribosome profiling.

Contextual fear conditioning (CFC) in rodents is the most widely used behavioural paradigm in neuroscience research to elucidate the neurobiological mechanisms underlying learning and memory. It is based on the pairing of an aversive unconditioned stimulus (US; e.g. mild footshock) with a neutral conditioned stimulus (CS; e.g. context of the test chamber) in order to acquire associative long-term memory (LTM), which persists for days and even months. Using genome-wide analysis, several studies have generated lists of genes modulated in response to CFC in an attempt to identify the "memory genes", which orchestrate memory formation. Yet, most studies use naïve animals as a baseline for assessing gene-expression changes, while only few studies have examined the effect of the US alone, without pairing to context, using genome-wide analysis of gene-expression. Herein, using the ribosome profiling methodology, we show that in male mice an immediate shock, which does not lead to LTM formation, elicits pervasive translational and transcriptional changes in the expression of Immediate Early Genes (IEGs) in dorsal hippocampus (such as Fos and Arc), a fact which has been disregarded by the majority of CFC studies. By removing the effect of the immediate shock, we identify and validate a new set of genes, which are translationally and transcriptionally responsive to the association of context-to-footshock in CFC, and thus constitute salient "memory genes".

Monitoring translation in synaptic fractions using a ribosome profiling strategy.

BACKGROUND: The aim of this study was to develop a method to study genome-wide local translation in biochemically isolated synaptic fractions (synaptoneurosomes). This methodology is of particular interest for neurons, due to the cardinal role of local translational control in neuronal sub-compartments, such as dendrites, for plasticity, learning, memory, and for disorders of the nervous system. NEW METHOD: We combined established methods for purifying synaptoneurosomes with translational profiling (ribosome profiling), a method that employs unbiased next generation sequencing to simultaneously assess transcription and translation in a single sample. RESULTS: The two existing methods are compatible to use in combination and yield high quality sequencing data, which are specific to synaptic compartments. This new protocol provides an easy to implement workflow, which combines biochemical isolation of synaptoneurosomes of varying levels of purity (crude or Percoll gradient purified) with the use of a commercial kit to generate sequencing libraries. COMPARISON WITH EXISTING METHODS: Compared to previous studies of the synaptic translatome, our method shows less contamination with non-neuronal cell types or non-synaptic compartments, increasing the specificity of the data obtained. CONCLUSIONS: Combining the isolation of functional synaptic units with ribosome profiling offers a powerful tool to study local translation in synaptic compartments both in health and disease.

Raptor-Mediated Proteasomal Degradation of Deamidated 4E-BP2 Regulates Postnatal Neuronal Translation and NF-κB Activity.

The translation initiation repressor 4E-BP2 is deamidated in the brain on asparagines N99/N102 during early postnatal brain development. This post-translational modification enhances 4E-BP2 association with Raptor, a central component of mTORC1 and alters the kinetics of excitatory synaptic transmission. We show that 4E-BP2 deamidation is neuron specific, occurs in the human brain, and changes 4E-BP2 subcellular localization, but not its disordered structure state. We demonstrate that deamidated 4E-BP2 is ubiquitinated more and degrades faster than the unmodified protein. We find that enhanced deamidated 4E-BP2 degradation is dependent on Raptor binding, concomitant with increased association with a Raptor-CUL4B E3 ubiquitin ligase complex. Deamidated 4E-BP2 stability is promoted by inhibiting mTORC1 or glutamate receptors. We further demonstrate that deamidated 4E-BP2 regulates the translation of a distinct pool of mRNAs linked to cerebral development, mitochondria, and NF-κB activity, and thus may be crucial for postnatal brain development in neurodevelopmental disorders, such as ASD.

The Role of the Eukaryotic Translation Initiation Factor 4E (eIF4E) in Neuropsychiatric Disorders.

Protein synthesis in eukaryotic cells is a complex, multi-step and tightly regulated process. Translation initiation, the rate limiting step in protein synthesis, is dependent on the activity of eukaryotic translation Initiation Factor 4E (eIF4E). eIF4E is the cap-binding protein which, in synergy with proteins such as the helicase eIF4A and the scaffolding protein eIF4G, binds to mRNA, allowing the recruitment of ribosomes and translation initiation. The function of eIF4E is tightly regulated in cells under normal physiological conditions and can be controlled by post-translational modifications, such as phosphorylation, and by the binding of inhibitory proteins, including eIF4E binding proteins (4E-BPs) and CYFIP1. Recent studies have highlighted the importance of eIF4E in normal or aberrant function of the nervous system. In this mini-review, we will highlight the role of eIF4E function and regulation in the pathophysiology of neurodevelopmental and neuropsychiatric disorders.

Translational profiling of dorsal root ganglia and spinal cord in a mouse model of neuropathic pain.

Acute pain serves as a protective mechanism, guiding the organism away from actual or potential tissue injury. In contrast, chronic pain is a debilitating condition without any obvious physiological function. The transition to, and the maintenance of chronic pain require new gene expression to support biochemical and structural changes within the pain pathway. The regulation of gene expression at the level of mRNA translation has emerged as an important step in the control of protein expression in the cell. Recent studies show that signaling pathways upstream of mRNA translation, such as mTORC1 and ERK, are upregulated in chronic pain conditions, and their inhibition effectively alleviates pain in several animal models. Despite this progress, mRNAs whose translation is altered in chronic pain conditions remain largely unknown. Here, we performed genome-wide translational profiling of dorsal root ganglion (DRG) and spinal cord dorsal horn tissues in a mouse model of neuropathic pain, spared nerve injury (SNI), using the ribosome profiling technique. We identified distinct subsets of mRNAs that are differentially translated in response to nerve injury in both tissues. We discovered key converging upstream regulators and pathways linked to mRNA translational control and neuropathic pain. Our data are crucial for the understanding of mechanisms by which mRNA translation promotes persistent hypersensitivity after nerve injury.

Myocardial bridging: retrospective analysis and scintigraphic testing of patients with no angiographically significant atherosclerotic coronary disease.

INTRODUCTION AND OBJECTIVE: The clinical relevance of myocardial bridging (MB) is a matter of debate. The objective of this work was to examine its prevalence, clinical presentation, prognosis, and functional features on scintigraphy in a group of patients with no significant atherosclerotic coronary disease. METHODS: We retrospectively examined 7039 consecutive cardiac angiograms performed between January 1994 and December 2004, selecting cases in which MB was not accompanied by significant coronary disease (defined as luminal stenosis > 50%), valvular heart disease or cardiomyopathy. Patient characteristics such as age, gender, vascular risk factors and clinical presentation were recorded. We then contacted these patients by telephone to determine cardiovascular events since diagnosis (hospitalization, infarction, death) or symptoms of angina, and to invite them for myocardial perfusion scintigraphy (MPS) with stress testing. RESULTS: The prevalence of MB was 0.97% (68 patients). The study population without significant coronary disease, valvular heart disease or cardiomyopathy was composed of 31 subjects, mean age 51.45 +/- 13.77 years, 94% (29 patients) male. Clinical presentations were: non-ST elevation acute coronary syndromes with or without biomarkers of necrosis 34% (14 patients), stable angina 23% (7 patients), atypical chest pain 16% (5 patients), ST-elevation myocardial infarction 13% (4 patients), other 3% (1 patient). Left ventricular function was normal in all patients, and angiography showed MB of the left anterior descending artery, 63% (19 patients) in the mid portion, and 33% (12 patients) in the distal portion. All subjects were treated medically. We were able to contact 24 (77%) of the 31 patients, all of whom underwent MPS; mean time since angiography was 61.25 months, with no cardiovascular events (hospitalization, infarction, death) or symptomatic angina. MPS only identified three patients with findings consistent with anterior wall ischemia. CONCLUSIONS: In this series, 58% of the patients with MB and no significant atherosclerotic coronary disease presented with acute coronary syndromes. In all the subjects contacted, the prognosis had been good during the time since diagnosis. In the majority of them, no signs of ischemia were detected on MPS.

Molecular neuropathology of the synapse in sheep with CLN5 Batten disease.

AIMS: Synapses represent a major pathological target across a broad range of neurodegenerative conditions. Recent studies addressing molecular mechanisms regulating synaptic vulnerability and degeneration have relied heavily on invertebrate and mouse models. Whether similar molecular neuropathological changes underpin synaptic breakdown in large animal models and in human patients with neurodegenerative disease remains unclear. We therefore investigated whether molecular regulators of synaptic pathophysiology, previously identified in Drosophila and mouse models, are similarly present and modified in the brain of sheep with CLN5 Batten disease. METHODS: Gross neuropathological analysis of CLN5 Batten disease sheep and controls was used alongside postmortem MRI imaging to identify affected brain regions. Synaptosome preparations were then generated and quantitative fluorescent Western blotting used to determine and compare levels of synaptic proteins. RESULTS: The cortex was particularly affected by regional neurodegeneration and synaptic loss in CLN5 sheep, whilst the cerebellum was relatively spared. Quantitative assessment of the protein content of synaptosome preparations revealed significant changes in levels of seven out of eight synaptic neurodegeneration proteins investigated in the motor cortex, but not cerebellum, of CLN5 sheep (α-synuclein, CSP-α, neurofascin, ROCK2, calretinin, SIRT2, and UBR4). CONCLUSIONS: Synaptic pathology is a robust correlate of region-specific neurodegeneration in the brain of CLN5 sheep, driven by molecular pathways similar to those reported in Drosophila and rodent models. Thus, large animal models, such as sheep, represent ideal translational systems to develop and test therapeutics aimed at delaying or halting synaptic pathology for a range of human neurodegenerative conditions.

Diagnostic accuracy of combined 99mTc-sulesomab and 99mTc-nanocolloid bone marrow imaging in detecting prosthetic joint infection.

OBJECTIVE(S): Autologous-labeled leukocytes combined with sulfur colloid bone marrow scan is the current nuclear medicine gold standard for the diagnosis of prosthetic joint infection. The goal of this study is to assess the diagnostic accuracy of a new nuclear medicine modality for detecting infection in this context. METHODS: Twenty-seven patients with suspicious hip and knee arthroplasties were enrolled prospectively and underwent nuclear medicine testing using 99mTc-sulesomab and 99mTc-nanocolloids sequentially. These results were then crossed with the final diagnosis to determine the test(s) diagnostic accuracy. RESULTS: An isolated 99mTc-sulesomab scan shows 100% sensitivity (0.40-1) and negative predictive value (0.31-1) but only 20% specificity (0.05-0.48). Combining it with a 99mTc-nanocolloid bone marrow scan increases the specificity (0.75-1) and the positive predictive value (0.40-1) to 100%. Furthermore, the combined test has fewer equivocal readings and higher interreader agreement: κ test value 0.59 vs. 0.44. CONCLUSION: The results support the hypothesis that these technically simpler and ready-to-use products may be an alternative to autologous-labeled leukocytes/sulfur colloid marrow scan.