This study aimed at determining the diagnostic implications of indirect signs of infection at FDG-PET—i.e., hypermetabolisms of the spleen and/or bone marrow (HSBM)—when documented in patients with ...known or suspected infective endocarditis (IE).
HSBM were defined by higher mean standardized uptake values comparatively to that of the liver on FDG-PET images from patients with a high likelihood of IE and prospectively included in a multicenter study.
Among the 129 included patients, IE was ultimately deemed as definite in 88 cases. HSBM was a predictor of definite IE (P = 0.014; odds ratio (OR) 3.2), independently of the criterion of an abnormal cardiac FDG uptake (P = 0.0007; OR 9.68), and a definite IE was documented in 97% (29/30) of patients showing both HSBM and abnormal cardiac uptake, 78% (7/9) of patients with only abnormal cardiac uptake, 67% (42/63) of patients with only HSBM, and 37% (10/27) of patients with neither one.
In this cohort with a high likelihood of IE, HSBM is an additional albeit indirect sign of IE, independently of the criterion of an abnormal cardiac uptake, and could reinforce the suspicion of IE in the absence of any other infectious, inflammatory, or malignant disease.
Somatostatin receptors are overexpressed by inflammatory cells but not by cardiac cells, under normal conditions. This study assesses the detection of acute myocarditis by the ECG-triggered ...digital-PET imaging of somatostatin receptors (68Ga-DOTATOC-PET), as compared to Cardiac Magnetic Resonance (CMR) imaging, which is the reference diagnostic method in this setting.
Fourteen CMR-defined acute myocarditis patients had a first 15-minutes ECG-triggered 68Ga-DOTATOC PET recording, 4.4 ± 3.0 days from peak troponin, and 10 had a second 4.3 ± 0.3 months later. Myocardial/blood SUVmax ratio was analyzed relative to the normal upper limit of 2.18, which had been previously determined from oncology 68Ga-DOTATOC-PET recordings of patients with a similar age range as the myocarditis patients.
An increased myocardial 68Ga-DOTATOC uptake relative to blood activity was invariably observed during the acute phase. SUVmax ratio exceeded 2.18 in all patients during the acute phase but also in 3/10 patients at 4-months, at a time when there were no more signs of active inflammation on CMR. A residual myocardial 68Ga-DOTATOC uptake was still observed on all gated-PET cine loops at 4-months.
These preliminary results suggest that 68Ga-DOTATOC ECG-triggered digital-PET may be as sensitive as CMR at detecting myocarditis during the acute phase and more sensitive at later stages.
Effective therapies are urgently needed to safely target TDP-43 pathology as it is closely associated with the onset and development of devastating diseases such as frontotemporal lobar degeneration ...with TDP-43 pathology (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). In addition, TDP-43 pathology is present as a co-pathology in other neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Our approach is to develop a TDP-43-specific immunotherapy that exploits Fc gamma-mediated removal mechanisms to limit neuronal damage while maintaining physiological TDP-43 function. Thus, using both in vitro mechanistic studies in conjunction with the rNLS8 and CamKIIa inoculation mouse models of TDP-43 proteinopathy, we identified the key targeting domain in TDP-43 to accomplish these therapeutic objectives. Targeting the C-terminal domain of TDP-43 but not the RNA recognition motifs (RRM) reduces TDP-43 pathology and avoids neuronal loss in vivo. We demonstrate that this rescue is dependent on Fc receptor-mediated immune complex uptake by microglia. Furthermore, monoclonal antibody (mAb) treatment enhances phagocytic capacity of ALS patient-derived microglia, providing a mechanism to restore the compromised phagocytic function in ALS and FTD patients. Importantly, these beneficial effects are achieved while preserving physiological TDP-43 activity. Our findings demonstrate that a mAb targeting the C-terminal domain of TDP-43 limits pathology and neurotoxicity, enabling clearance of misfolded TDP-43 through microglia engagement, and supporting the clinical strategy to target TDP-43 by immunotherapy.
TDP-43 pathology is associated with various devastating neurodegenerative disorders with high unmet medical needs such as frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. Thus, safely and effectively targeting pathological TDP-43 represents a key paradigm for biotechnical research as currently there is little in clinical development. After years of research, we have determined that targeting the C-terminal domain of TDP-43 rescues multiple patho-mechanisms involved in disease progression in two animal models of FTD/ALS. In parallel, importantly, our studies establish that this approach does not alter the physiological functions of this ubiquitously expressed and indispensable protein. Together, our findings substantially contribute to the understanding of TDP-43 pathobiology and support the prioritization for clinical testing of immunotherapy approaches targeting TDP-43.
•ACI-5891 binds to C-terminal domain of TDP-43 with picomolar affinity.•ACI-5891 depletes pathological TDP-43 seeds from patient brain extracts.•ACI-5891 lowers neuropathology and shows neuroprotection in mouse models of ALS/FTD.•ACI-5891 exploits Fc gamma receptor-mediated clearance mechanisms for efficacy.•ACI-5891 ameliorates phagocytic function of ALS patient-derived microglia.
RNA silencing is a natural defence mechanism against viruses in plants, and transgenes expressing viral RNA-derived sequences were previously shown to confer silencing-based enhanced resistance ...against the cognate virus in several species. However, RNA silencing was shown to dysfunction at low temperatures in several species, questioning the relevance of this strategy in perennial plants such as grapevines, which are often exposed to low temperatures during the winter season. Here, we show that inverted-repeat (IR) constructs trigger a highly efficient silencing reaction in all somatic tissues in grapevines. Similarly to other plant species, IR-derived siRNAs trigger production of secondary transitive siRNAs. However, and in sharp contrast to other species tested to date where RNA silencing is hindered at low temperature, this process remained active in grapevine cultivated at 4°C. Consistently, siRNA levels remained steady in grapevines cultivated between 26°C and 4°C, whereas they are severely decreased in Arabidopsis grown at 15°C and almost undetectable at 4°C. Altogether, these results demonstrate that RNA silencing operates in grapevine in a conserved manner but is resistant to far lower temperatures than ever described in other species.
Different source of casein depending on their extraction method from milk are available on the market. Sheets from 3 different types of casein (rennet casein, acid casein and sodium caseinate) were ...developed using a dry process: extrusion. Casein sourcing, plasticizer concentration (13.2% w/w or 24.2% w/w) and relative humidity environment were studied for each sheet through color, density and porosity, water sensitivity and mechanical properties evaluation. A wide range of properties seems to be available through casein based sheets depending on casein source, which affected greatly water solubility (caseinates are 100% water soluble compare to acid and rennet casein). Besides, acid and rennet casein have different behaviour with water and even more with higher glycerol amounts. Indeed, rennet casein sheet is less sensitive to water than acid casein sheet at low glycerol concentration (13.2% w/w) but at the opposite, at high glycerol amount in sheets, rennet casein sheet is more hydrophilic than acid casein sheets.
Extrusion is an easy scale up process and it was used to produce casein based sheets with improved water vapor permeability (WVP). These findings can be used to find the suitable food packaging application for each casein based sheet with a low cost and efficient process.
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•New edible films based on rennet casein, acid casein and sodium caseinate, produced by dry process: extrusion.•Film characterization through physical properties, water sensitivity properties and mechanical properties.•Casein sourcing and glycerol concentration were proved to affect film properties.•Wide range of properties available through casein based film implies many food packaging application opportunities.
Our objective was to assess the value of
Ga-DOTATOC and carbidopa-assisted
F-fluorodihydroxyphenylalanine (
F-DOPA) in 21 hypoglycemic patients.
All patients who underwent
Ga-DOTATOC or ...carbidopa-assisted
F-DOPA PET/CT for suspicion of insulinoma from January 2019 to January 2021 were retrospectively analyzed. A final diagnosis of insulinoma was determined by pathologic reports or consensus.
During the study period, 21 patients underwent both
Ga-DOTATOC and
F-DOPA PET/CT. A final diagnosis of insulin-secreting tumor was reached in 12 cases, including 11 insulinomas and 1 small mixed neuroendocrine/nonneuroendocrine neoplasm.
F-DOPA and
Ga-DOTATOC PET/CT were positive in 5 (45%) and 7 (64%) of 11 cases, respectively, with 4 concordant positive findings. Moreover, 1 insulinoma was visualized exclusively by
F-DOPA PET/CT and 3 by
Ga-DOTATOC PET/CT only.
F-DOPA and
Ga-DOTATOC PET/CT were falsely positive in 1 nonfunctioning pancreatic neuroendocrine tumor.
When
Ga-exendin-4 is not available,
Ga-somatostatin receptor PET/CT should be the first choice for insulinoma functional imaging.
This report presents the case of a 61-year-old woman with assessment of fronto-temporo-sphenoidal refractory meningioma before radionuclide therapy with pretherapeutic 68Ga-DOTATOC PET/CT. Given the ...discovery of osteolytic lesions, 18F-FDG PET/CT is planned to search for the primitive origin. Meningioma bone metastasis is confirmed with spine biopsies. The presence of dedifferentiated meningioma lesions indicating that high somatostatin receptor expression does not necessarily coincide with areas of increased glucose metabolism. 18F-FDG and 68Ga-DOTATOC PET/CT allows optimal characterization of tumor heterogeneity and guide targeted therapeutic management before PPRT.
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