Decision-making based on 3D printed models in laparoscopic liver resections with intraoperative ultrasound: a prospective observational study

The aim of this study was to evaluate impact of 3D printed models on decision-making in context of laparoscopic liver resections (LLR) performed with intraoperative ultrasound (IOUS) guidance. Nineteen patients with liver malignances (74% were colorectal cancer metastases) were prospectively qualified for LLR or radiofrequency ablation in a single center from April 2017 to December 2018. Models were 3DP in all cases based on CT and facilitated optical visualization of tumors’ relationships with portal and hepatic veins. Planned surgical extent and its changes were tracked after CT analysis and 3D model inspection, as well as intraoperatively using IOUS. Nineteen patients were included in the analysis. Information from either 3DP or IOUS led to changes in the planned surgical approach in 13/19 (68%) patients. In 5/19 (26%) patients, the 3DP model altered the plan of the surgery preoperatively. In 4/19 (21%) patients, 3DP independently changed the approach. In one patient, IOUS modified the plan post-3DP. In 8/19 (42%) patients, 3DP model did not change the approach, whereas IOUS did. In total, IOUS altered surgical plans in 9 (47%) cases. Most of those changes (6/9; 67%) were caused by detection of additional lesions not visible on CT and 3DP. 3DP can be helpful in planning complex and major LLRs and led to changes in surgical approach in 26.3% (5/19 patients) in our series. 3DP may serve as a useful adjunct to IOUS. • 3D printing can help in decision-making before major and complex resections in patients with liver cancer. • In 5/19 patients, 3D printed model altered surgical plan preoperatively. • Most surgical plan changes based on intraoperative ultrasonography were caused by detection of additional lesions not visible on CT and 3D model.     

New PA/1220/98-like variant of infectious bronchitis virus in Poland

ABSTRACT

The aim of the present study was to report the first detection of a new infectious bronchitis virus (IBV) variant in Polish commercial flocks which is completely different to any previously known in this region. In 2018, samples from Ross 308 breeding hens aged 35 weeks were delivered for IBV diagnosis. IBV presence was detected, but all attempts to amplify the S gene fragment were negative. The field material was analysed using the Illumina MiSeq platform and a 1073-nt fragment of the S1 coding region was obtained. The gCoV/ck/Poland/516/2018 strain shared only 52.7–58.1% nucleotide identity to any known genotype of IBV and shared the highest identity of 81.4% to the unique North American PA/1220/98 variant. Based on the obtained sequence, a specific molecular test was constructed and used for screening of chicken samples from 35 field cases delivered to our laboratory between 2018 and 2019 for IBV diagnosis. Application of this test enabled detection of another three chicken flocks as positive for this new strain. All positives were identified in commercial layers with egg production problems. To date, the virus has not been detected in broiler chickens. Taking into account the proposed criteria for the definition of a new IBV genotype or lineage, it seems that the detected viruses in Poland, together with the unique North American PA/1220/98 variant, may be classified as separate lineages/genotype in the new IBV classification.

RESEARCH HIGHLIGHTS

• The new IBV variant is distantly related to other known GI–GVII IBV genotypes/lineages.

• It affects long-lived birds causing egg production problems.

• The detected IBV and the unique North American PA/1220/98 variant are candidates for separate lineages in the new GVIII genotype.

     

Cortical Mechanisms of Single-Pulse Transcranial Magnetic Stimulation in Migraine

Single-pulse transcranial magnetic stimulation (sTMS) of the occipital cortex is an effective migraine treatment. However, its mechanism of action and cortical effects of sTMS in migraine are yet to be elucidated. Using calcium imaging and GCaMP-expressing mice, sTMS did not depolarise neurons and had no effect on vascular tone. Pre-treatment with sTMS, however, significantly affected some characteristics of the cortical spreading depression (CSD) wave, the correlate of migraine aura. sTMS inhibited spontaneous neuronal firing in the visual cortex in a dose-dependent manner and attenuated l-glutamate-evoked firing, but not in the presence of GABA_A/B antagonists. In the CSD model, sTMS increased the CSD electrical threshold, but not in the presence of GABA_A/B antagonists. We first report here that sTMS at intensities similar to those used in the treatment of migraine, unlike traditional sTMS applied in other neurological fields, does not excite cortical neurons but it reduces spontaneous cortical neuronal activity and suppresses the migraine aura biological substrate, potentially by interacting with GABAergic circuits.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00879-6) contains supplementary material, which is available to authorized users.Key Words: Migraine, transcranial magnetic stimulation, GABA, glutamate, cortex     

Proteasome inhibitors and Smac mimetics cooperate to induce cell death in diffuse large B-cell lymphoma by stabilizing NOXA and triggering mitochondrial apoptosis

Copy number gains and increased expression levels of cellular Inhibitor of Apoptosis protein (cIAP)1 and cIAP2 have been identified in primary diffuse large B-cell lymphoma (DLBCL) tissues. Second mitochondria-derived activator of caspases (Smac) mimetics were designed to antagonize IAP proteins. However, since their effect as single agents is limited, combination treatment represents a strategy for their clinical development. Therefore, we investigated the Smac mimetic BV6 in combination with proteasome inhibitors and analyzed the molecular mechanisms of action. We discovered that BV6 treatment sensitizes DLBCL cells to proteasome inhibition. We show a synergistic decrease in cell viability and induction of apoptosis by BV6/Carfilzomib (CFZ) treatment, which was confirmed by calculation of combination index (CI) and Bliss score. BV6 and CFZ acted together to trigger activation of BAX and BAK, which facilitated cell death, as knockdown of BAX and BAK significantly reduced BV6/CFZ-mediated cell death. Activation of BAX and BAK was accompanied by loss of mitochondrial membrane potential (MMP) and activation of caspases. Pretreatment with the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) rescued BV6/CFZ-induced cell death, confirming caspase dependency. Treatment with CFZ alone or in combination with BV6 caused accumulation of NOXA, which was required for cell death, as gene silencing by siRNA or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-mediated NOXA inactivation inhibited BV6/CFZ-induced cell death. Together, these experiments indicate that BV6 and CFZ cooperatively induce apoptotic cell death via the mitochondrial pathway. These findings emphasize the role of Smac mimetics for sensitizing DLBCL cells to proteasome inhibition with important implications for further (pre)clinical studies.     

Realizing Present and Future Promise of DIY Biology and Medicine through a Trust Architecture

The speed and scale of the COVID-19 pandemic has highlighted the limits of current health systems and the potential promise of non-establishment research such as “DIY” research. We consider one example of how DIY research is responding to the pandemic, discuss the challenges faced by DIY research more generally, and suggest that a “trust architecture” should be developed now to contribute to successful future DIY efforts.     

Silicosi severa da terre di diatomee nella produzione di alginato ad uso odontoiatrico: uno studio necroscopico

«Severe silicosis due to diatomaceous earth in dental alginate: a necropsy study»Background:Severe silicosis from occupational exposure to calcined diatomaceous earth has been observed in the past, due to the high-temperature transformation of amorphous silica in crystalline phases, mainly cristobalite. In dental alginate production and use a silica exposure may be underestimated. Objectives: To describe the clinical picture, the scenario and pattern of occupational exposure to silica and the corresponding necroscopic findings of a case of silicosis in a worker engaged in the production of alginates for dental use.Methods:A commercial sample of calcinated diatomaceous earth and necroscopic lung samples were analysed by scanning electron microscopy (SEM-EDS) and X-ray diffraction (XRD) for the quali-quantitative determination of crystalline silica. Material safety data sheets (MSDSs) of diatomaceous earth produced in 2002 and 2018 were examined to assess the information content on silicosis risk. Clinical findings and post-mortem examinations of the worker are evaluated.Results:A cristobalite concentration of 36% (wt/wt) was determined in the diatomaceous earth sample and a large amount of diatom fragments were observed in lung samples. The DRX spectra indicated the presence of cristobalite either in the bulk sample or in the lung tissues. The MSDS dated 2002 reported the presence of SLC up to 63% with cristobalite concentrations <60%, and the resulting risk of silicosis, while the MSDS dated 2018 and referred to a commercial product currently on the market indicated a concentration of cristobalite <1% and no risk of silicosis. The worker was suffering from a severe silicosis, histologically confirmed by necropsy.Conclusion:The present case-study revealed that the risk of silicosis from calcined diatomaceous earths used to produce dental alginates has been ignored. The lack of engineering controls and personal protection measures led to a high cristobalite lung burden, consistent with the development of a severe silicosis that were a contributing factor of death. A MSDS of a commercial product currently on the market does not report this serious hazard.Key words: Silicosis, diatomaceous earth, dental alginate