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Purpose of Review The purpose of this review is to provide a summary on the status of the art of simultaneous perfusion-innervation imaging by CZT-SPECT and to clarify its potential applications in clinical practice. Recent Findings Introduction of CZT cameras represented a critical breakthrough in nuclear cardiology. Although it has been demonstrated that cardiac innervation may be easily assessed by CZT-SPECT, as for now, there are only few studies investigating cardiac perfusion and innervation with simultaneous dual-isotope imaging by CZT cameras. Summary Perfusion and innervation assessment by CZT camera is a feasible tool, allowing to reduce radiation dose exposure and acquisition time, thanks to CZT better spatial, temporal, and energy resolution, with higher compliance by patients. Moreover, this technique allows to integrate regional evaluation of myocardial perfusion/innervation status, providing more accurate information for risk stratification of different cardiac disease.

Background: During the COVID-19 public health emergency, our breast cancer screening activities have been interrupted. In June 2020, they resumed, calling for mandatory safe procedures to properly manage patients and staff. Methods: A protocol supporting medical activities in breast cancer screening was created, based on six relevant articles published in the literature and in the following National and International guidelines for COVID-19 prevention. The patient population, consisting of both screening and breast ambulatory patients, was classified into one of four categories: 1. Non-COVID-19 patient, 2. Confirmed COVID-19 in an asymptomatic screening patient, 3. suspected COVID-19 in symptomatic or confirmed breast cancer, 4. Confirmed COVID-19 in symptomatic or confirmed breast cancer. The day before the radiological exam, patients are screened for COVID-19 infection through a telephone questionnaire. At a subsequent in person appointment, the body temperature is checked and depending on the clinical scenario at stake, the scenario-specific procedures for medical and paramedical staff are adopted. Results: In total, 203 mammograms, 76 breast ultrasound exams, 4 core needle biopsies, and 6 vacuum-assisted breast biopsies were performed in one month. Neither medical nor paramedical staff were infected on any of these occasions. Conclusion: Our department organization model can represent a case of implementation of National and International guidelines applied in a breast cancer screening program, assisting hospital personnel into COVID-19 infection prevention.

One sentence SummarySUMO conjugation activity causes formation of SUMO nuclear bodies, which strongly overlap with COP1 bodies thanks to a substrate-binding (VP) motif in the E3 ligase SIZ1 that acts as bridge protein.AbstractAttachment of the small ubiquitin-like modifier SUMO to substrate proteins modulates their turnover, activity or interaction partners. An unresolved question is how this SUMO conjugation activity concentrates the enzymes involved and the substrates into uncharacterized nuclear bodies (NBs). We here define the requirements for the formation of SUMO NBs and for their subsequent co-localisation with the master regulator of growth, the E3 ubiquitin ligase COP1. COP1 activity results in degradation of transcription factors, which primes the transcriptional response that underlies elongation growth induced by night-time and high ambient temperatures (skoto- and thermomorphogenesis, respectively). SUMO conjugation activity itself is sufficient to target the SUMO machinery into NBs. Co-localization of these bodies with COP1 requires besides SUMO conjugation activity, a SUMO acceptor site in COP1 and the SUMO E3 ligase SIZ1. We find that SIZ1 docks in the substrate-binding pocket of COP1 via two VP motifs - a known peptide motif of COP1 substrates. The data reveal that SIZ1 physically connects COP1 and SUMO conjugation activity in the same NBs that can also contain the blue-light receptors CRY1 and CRY2. Our findings thus suggest that sumoylation apparently coordinates COP1 activity inside these NBs; a mechanism that potentially explains how SIZ1 and SUMO both control the timing and amplitude of the high-temperature growth response. The strong co-localization of COP1 and SUMO in these NBs might also explain why many COP1 substrates are sumoylated.Funding informationThe Netherlands Scientific Organisation (ALW-VIDI grant 864.10.004 to HvdB) and the Topsector T&U program Better Plants for Demands (grant 1409-036 to HvdB), including the partnering breeding companies, supported this work; FM is financially supported by Keygene N.V. (The Netherlands).

Imaging plays an important role in the detection of coronavirus (COVID-19) pneumonia in both managing the disease and evaluating the complications. Imaging with chest computed tomography (CT) can also have a potential predictive and prognostic role in COVID-19 patient outcomes. The aim of this pictorial review is to describe the role of imaging with chest X-ray (CXR), lung ultrasound (LUS), and CT in the diagnosis and management of COVID-19 pneumonia, the current indications, the scores proposed for each modality, the advantages/limitations of each modality and their role in detecting complications, and the histopathological correlations.

Background: Despite great technical advances in imaging, such as multidetector computed tomography and magnetic resonance imaging (MRI), diagnosing pancreatic solid lesions correctly remains challenging, due to overlapping imaging features with benign lesions. We wanted to evaluate functional MRI to differentiate pancreatic tumors, peritumoral inflammatory tissue, and normal pancreatic parenchyma by means of dynamic contrast-enhanced MRI (DCE-MRI)-, diffusion kurtosis imaging (DKI)-, and intravoxel incoherent motion model (IVIM) diffusion-weighted imaging (DWI)-derived parameters. Methods: We retrospectively analyzed 24 patients, each with histopathological diagnosis of pancreatic tumor, and 24 patients without pancreatic lesions. Functional MRI was acquired using a 1.5 MR scanner. Peritumoral inflammatory tissue was assessed by drawing regions of interest on the tumor contours. DCE-MRI, IVIM and DKI parameters were extracted. Nonparametric tests and receiver operating characteristic (ROC) curves were calculated. Results: There were statistically significant differences in median values among the three groups observed by Kruskal–Wallis test for the DKI mean diffusivity (MD), IVIM perfusion fraction (fp) and IVIM tissue pure diffusivity (Dt). MD had the best results to discriminate normal pancreas plus peritumoral inflammatory tissue versus pancreatic tumor, to separate normal pancreatic parenchyma versus pancreatic tumor and to differentiate peritumoral inflammatory tissue versus pancreatic tumor, respectively, with an accuracy of 84%, 78%, 83% and area under ROC curve (AUC) of 0.85, 0.82, 0.89. The findings were statistically significant compared with those of other parameters ( p value 0.05 at McNemar’s test). Conclusions: Diffusion parameters, mainly MD by DKI, could be helpful for the differentiation of normal pancreatic parenchyma, perilesional inflammation, and pancreatic tumor.

Background To investigate the potential of semiquantitative time-intensity curve parameters compared to textural radiomic features on arterial phase images by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for early prediction of breast cancer neoadjuvant therapy response. Methods A retrospective study of 45 patients subjected to DCE-MRI by public datasets containing examination performed prior to the start of treatment and after the treatment first cycle (‘QIN Breast DCE-MRI’ and ‘QIN-Breast’) was performed. In total, 11 semiquantitative parameters and 50 texture features were extracted. Non-parametric test, receiver operating characteristic analysis with area under the curve (ROC-AUC), Spearman correlation coefficient, and Kruskal-Wallis test with Bonferroni correction were applied. Results Fifteen patients with pathological complete response (pCR) and 30 patients with non-pCR were analysed. Significant differences in median values between pCR patients and non-pCR patients were found for entropy, long-run emphasis, and busyness among the textural features, for maximum signal difference, washout slope, washin slope, and standardised index of shape among the dynamic semiquantitative parameters. The standardised index of shape had the best results with a ROC-AUC of 0.93 to differentiate pCR versus non-pCR patients. Conclusions The standardised index of shape could become a clinical tool to differentiate, in the early stages of treatment, responding to non-responding patients.

Geminiviruses are single-stranded DNA (ssDNA) viruses that infect a wide range of plants. To promote viral replication, geminiviruses manipulate the host cell cycle. The viral protein Rep is essential to reprogram the cell cycle and then initiate viral DNA replication by interacting with a plethora of nuclear host factors. Even though many protein domains of Rep have been characterized, little is known about its nuclear targeting. Here, we show that one conserved lysine in the N-terminal part of Rep is pivotal for nuclear localization of the Rep protein from Tomato yellow leaf curl virus (TYLCV), with two other lysines also contributing to its nuclear import. Previous work had identified that these residues are essential for Rep from Tomato golden mosaic virus (TGMV) to interact with the E2 SUMO-conjugating enzyme (SCE1). We here show that mutating these lysines leads to nuclear exclusion of TYLCV Rep without compromising its interaction with SCE1. Moreover, the ability of TYLCV Rep to promote viral DNA replication also depends on this highly conserved lysine independently of its role in nuclear import of Rep. Our data thus reveal that this lysine potentially has a broad role in geminivirus replication, but its role in nuclear import and SCE1 binding differs depending on the Rep protein examined.IMPORTANCE Nuclear activity of the replication initiator protein (Rep) of geminiviruses is essential for viral replication. We now define that one highly conserved lysine is important for nuclear import of Rep from three different begomoviruses. To our knowledge, this is the first time that nuclear localization has been mapped for any geminiviral Rep protein. Our data add another key function to this lysine residue, besides its roles in viral DNA replication and interaction with host factors, such as the SUMO E2-conjugating enzyme.

To compare diagnostic performance of contrast-enhanced dual-energy digital mammography (CEDM) and digital breast tomosynthesis (DBT) alone and in combination compared to 2D digital mammography (MX) and dynamic contrast-enhanced MRI (DCE-MRI) in women with breast lesions. We enrolled 100 consecutive patients with breast lesions (BIRADS 3-5 at imaging or clinically suspicious). CEDM, DBT, and DCE-MRI 2D were acquired. Synthetized MX was obtained by DBT. A total of 134 lesions were investigated on 111 breasts of 100 enrolled patients: 53 were histopathologically proven as benign and 81 as malignant. Nonparametric statistics and receiver operating characteristic (ROC) curve were performed. Two-dimensional synthetized MX showed an area under ROC curve (AUC) of 0.764 (sensitivity 65%, specificity 80%), while AUC was of 0.845 (sensitivity 80%, specificity 82%) for DBT, of 0.879 (sensitivity 82%, specificity 80%) for CEDM, and of 0.892 (sensitivity 91%, specificity 84%) for CE-MRI. DCE-MRI determined an AUC of 0.934 (sensitivity 96%, specificity 88%). Combined CEDM with DBT findings, we obtained an AUC of 0.890 (sensitivity 89%, specificity 74%). A difference statistically significant was observed only between DCE-MRI and CEDM (P = .03). DBT, CEDM, CEDM combined to tomosynthesis, and DCE-MRI had a high ability to identify multifocal and bilateral lesions with a detection rate of 77%, 85%, 91%, and 95% respectively, while 2D synthetized MX had a detection rate for multifocal lesions of 56%. DBT and CEDM have superior diagnostic accuracy of 2D synthetized MX to identify and classify breast lesions, and CEDM combined with DBT has better diagnostic performance compared with DBT alone. The best results in terms of diagnostic performance were obtained by DCE-MRI. Dynamic information obtained by time-intensity curve including entire phase of contrast agent uptake allows a better detection and classification of breast lesions.

Aim To compare liver-specific EOB-GD-DTPA and liver-non-specific Gd-BT-DO3A MR, in hepatocellular carcinoma (HCC) and liver colorectal metastases. Material and methods Seventy HCC patients with 158 nodules and 90 colorectal liver metastases (mCRC) with 370 lesions were included in the retrospective analysis. HCC patients underwent MR at 0 time (MR0), after 3 (MR3) and 6 months (MR6) using two different CM; 69 mCRC patients underwent MR with Gd-EOB-BTPA and 21 mCRC patients with Gd-BT-DO3A. We evaluated arterial phase hyperenhancement, lesion-to-liver contrast during portal phase, hepatobiliary phase parenchymal hyperenhancement. Results In HCC patients arterial phase hyperenhancement degree was statistically higher (p = 0.03) with Gd-BT-DO3A (mean 4) than GD-EOB-DTPA (mean 2.6), while we found no significant statistical differences among mean (2.6) values at MR0 and MR6 using GD-EOB-DTPA. For all 209 patients underwent Gd-EOB-DTPA, we found that lesion-to-liver contrast during portal phase mean value was 4 while for patients underwent MR with Gd-BT-DO3A was 3 (p = 0.04). For HCC hepatobiliary phase parenchymal hyperenhancement mean value was 2.4. For mCRC patients: among 63 patients underwent previous chemotherapy hepatobiliary phase parenchymal hyperenhancement mean value was 3.1 while for 6 patients no underwent previous chemotherapy was 4 (p = 0.05). Conclusions Gd-EOB-DTPA should be chosen in pre surgical setting in patients with colorectal liver metastases.

To quantitatively assess the dose of Dual energy contrast enhanced digital mammography (CEDM) and digital breast tomosynthesis (DBT) and to investigate the relationship between average absorbed glandular dose (AGD), compressed breast thickness (CBT) and compression force (CF).All CEDM and DBT examinations were performed in cranio-caudal (CC) and medio-lateral oblique (MLO) view. Exposure parameters of 135 mammographic procedures that using AEC (automatic exposure control) mode were recorded. AGDs were calculated. Kruskal Wallis test was performed.CBT population ranged from 23 to 94 mm with a thickness median value of 52 mm in CC view and of 57 mm in MLO views. CEDM AGD median value was significatively lower than DBT AGD in each views (p0.01). AGD showed a positive correlation and linear regression with CBT for both CEDM and DBT while CF did not show a correlation and linear regression with AGD. The highest values were found for MLO view: RDose values of both techniques meet the recommendations for maximum dose in mammography. The results of the present study indicated that there was significant difference between AGD for CEDM and DBT exposure in different views (AGD in CC views had the lowest value) and that CBT could influence the AGD while CF was not correlated to AGD.

Geminiviruses are DNA viruses that replicate in nuclei of infected plant cells using the plant DNA replication machinery, including PCNA (proliferating cellular nuclear antigen), a cofactor that orchestrates genome duplication and maintenance by recruiting crucial players to replication forks. These viruses encode a multifunctional protein, Rep, which is essential for viral replication, induces the accumulation of the host replication machinery, and interacts with several host proteins, including PCNA and the SUMO E2 conjugation enzyme (SCE1). Posttranslational modification of PCNA by ubiquitin or SUMO plays an essential role in the switching of PCNA between interacting partners during DNA metabolism processes (e.g., replication, recombination, and repair, etc.). In yeast, PCNA sumoylation has been associated with DNA repair involving homologous recombination (HR). Previously, we reported that ectopic Rep expression results in very specific changes in the sumoylation pattern of plant cells. In this work, we show, using a reconstituted sumoylation system in Escherichia coli, that tomato PCNA is sumoylated at two residues, K254 and K164, and that coexpression of the geminivirus protein Rep suppresses sumoylation at these lysines. Finally, we confirm that PCNA is sumoylated in planta and that Rep also interferes with PCNA sumoylation in plant cells. IMPORTANCE SUMO adducts have a key role in regulating the activity of animal and yeast PCNA on DNA repair and replication. Our work demonstrates for the first time that sumoylation of plant PCNA occurs in plant cells and that a plant virus interferes with this modification. This work marks the importance of sumoylation in allowing viral infection and replication in plants. Moreover, it constitutes a prime example of how viral proteins interfere with posttranslational modifications of selected host factors to create a proper environment for infection.

Geminiviruses are DNA viruses that replicate in nuclei of infected plant cells using the plant DNA replication machinery, including PCNA (Proliferating cellular nuclear antigen), a cofactor that orchestrates genome duplication and maintenance by recruiting crucial players to replication forks. These viruses encode a multifunctional protein, Rep, which is essential for viral replication, induces the accumulation of the host replication machinery and interacts with several host proteins, including PCNA and the SUMO E2 conjugation enzyme (SCE1). Post-translational modification of PCNA by ubiquitin or SUMO plays an essential role in the switching of PCNA between interacting partners during DNA metabolism processes (e.g. replication, recombination, repair, etc.). In yeast, PCNA sumoylation has been associated to DNA repair involving homologous recombination (HR). Previously, we reported that ectopic Rep expression results in very specific changes in the sumoylation pattern of plant cells. In this work, we show, using a reconstituted sumoylation system inEscherichia coli, that tomato PCNA is sumoylated at two residues, K254 and K164, and that co-expression of the geminivirus protein Rep suppresses sumoylation at these lysines. Finally, we confirm that PCNA is sumoylatedin plantaand that Rep also interferes with PCNA sumoylation in plant cells.ImportanceSUMO adducts have a key role in regulating the activity of animal and yeast PCNA on DNA repair and replication. Our work demonstrates for the first time that sumoylation of plant PCNA occurs in plant cells and that a plant virus interferes with this modification. This work marks the importance of sumoylation in allowing viral infection and replication in plants. Moreover, it constitutes a prime example of viral proteins interfering with post-translational modifications of selected host factors to create a proper environment for infection.

The prognostic value of normal stress myocardial perfusion single-photon emission computed tomography (MPS) in patients with diabetes has only been evaluated in single-center studies of relatively limited sample size. We performed a meta-analysis of published studies, including diabetic patients with known or suspected coronary artery disease (CAD), to assess the predictive value for adverse cardiac ischemic events of normal stress MPS. Studies published between January 1990 and December 2013 were identified by database search. We included studies using stress MPS to evaluate diabetic patients with known or suspected CAD and providing data on clinical outcomes of non-fatal myocardial infarction or cardiac death with a follow-up time ≥12 months. A total of 14 studies were finally included, recruiting 13,493 patients. The negative predictive value (NPV) for non-fatal myocardial infarction and cardiac death of normal MPS was 94.92% (95% confidence interval 93.67-96.05), during a weighted mean follow-up of 36.24 months, resulting in estimated event rate after a negative test equal to 5.08% (95% confidence interval 3.95-6.33). The corresponding annualized event rate after a negative test was 1.60% (95% confidence interval 1.21-2.04). Stress MPS has a high NPV for adverse cardiac events in diabetic patients with known or suspected CAD leading to define a “relatively low-risk” patients category.

Background As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size. Methods We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome. Results Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected. Conclusions The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes. Trial registration ClinicalTrials.gov identifier: NCT00927550

BACKGROUND: Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. METHODS/DESIGN: We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events. DISCUSSION: The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.