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Salt-inducible kinase 2 (SIK2) is an important regulator in various intracellular signaling pathways related to apoptosis, tumorigenesis and metastasis. However, the involvement of SIK2 in gastric tumorigenesis and the functional linkage with gastric cancer (GC) progression remain to be defined. Here, we report that SIK2 was significantly downregulated in human GC tissues, and reduced SIK2 expression was associated with poor prognosis of patients. Overexpression of SIK2 suppressed the migration and invasion of GC cells, whereas knockdown of SIK2 enhanced cell migratory and invasive capability as well as metastatic potential. These changes in the malignant phenotype resulted from the ability of SIK2 to suppress epithelial-mesenchymal transition via inhibition of AKT/GSK3β/β-catenin signaling. The inhibitory effect of SIK2 on AKT/GSK3β/β-catenin signaling was mediated primarily through inactivation of AKT, due to its enhanced dephosphorylation by the upregulated protein phosphatases PHLPP2 and PP2A. The upregulation of PHLPP2 and PP2A was attributable to SIK2 phosphorylation and activation of mTORC1, which inhibited autophagic degradation of these two phosphatases. These results suggest that SIK2 acts as a tumor suppressor in GC and may serve as a novel prognostic biomarker and therapeutic target for this tumor.

The implementation of radiomics and machine learning (ML) techniques on analyzing two-dimensional gamma maps has been demonstrated superior to the conventional gamma analysis for error identification in intensity modulated radiotherapy (IMRT) quality assurance (QA). Recently, the Structural SIMilarity (SSIM) sub-index maps were shown to be able to reveal the error types of the dose distributions. In this study, we aimed to apply radiomics analysis on SSIM sub-index maps and develop ML models to classify delivery errors in patient-specific dynamic IMRT QA.

Twenty-one sliding-window IMRT plans of 180 beams for three treatment sites were involved in this study. Four types of machine-related errors of various magnitudes were simulated for each beam at each control point, including the monitor unit (MU) variations, same-directional and opposite-directional shifts of the multileaf collimators (MLCs) and random mispositioning of the MLCs. In the QA process, a total of 1620 portal dose (PD) images were acquired fecific IMRT QA process.

We proposed an ML-based method for machine-related error identification in patient-specific dynamic IMRT QA, where radiomic analysis on SSIM sub-index maps were used for feature extraction. With extensive validation to select the best features and classifiers, high accuracies in error classification were achieved. Compared with the conventional gamma threshold method, this approach has great potential in error identification for the patient-specific IMRT QA process.

Medical education is committed to promoting empathic communication. Despite this, much research indicates that empathy actually decreases as students progress through medical school. In qualitative terms, relatively little is known about this changing student relationship with the concept of empathy for patients and how teaching affects it. This study explores that knowledge gap.

Adopting a constructivist paradigm, we utilised a research approach new to medical education Love and Breakup Letter Methodology. A purposive sample of 20 medical students were asked to write love and break up letters to 'empathy for patients'. The letters were prompts for the focus group discussions that followed. Forty letters and three focus group discussions were thematically analysed.

The three major themes were art and artifice; empathic burden; and empathy as a virtue. Students were uncomfortable with the common practice of faking empathic statements, a problem exacerbated by the need to 'tick the empathy box' during exaceive as challenging and may promote a more authentic empathic practice.

Medical education should address the problem of inauthentic empathy, including faking empathic s in assessments. Educators should remember the value of non-verbal compassionate communication. The problems of empathic burden, negative role modelling and of finding empathy difficult for challenging patients may account for some of the empathy decline reported in quantitative research. Framing empathy as a virtue may help students utilise empathy more readily when faced with patients they perceive as challenging and may promote a more authentic empathic practice.In systemic lupus erythematosus (SLE) patients, most of the clinical manifestation share a vascular component triggered by endothelial dysfunction. Endothelial cells (ECs) activation occurs both on the arterial and venous side, and the high vascular density of kidneys accounts for the detrimental outcomes of SLE through lupus nephritis (LN). Kidney damage, in turn, exerts a negative feedback on the cardiovascular (CV) system aggravating risk factors for CV diseases such as hypertension, stroke and coronary syndrome among others. Despite the intensive investigation on SLE and LN, the role of endothelial dysfunction, as well as the underlying mechanisms, remains to be fully understood, with no specifically targeted pharmacological treatment. It is not known, in fact, if the activation pathway(s) in venous ECs are similar to the one in arterial ECs and doubts persist on the shared manifestation of microcirculation compared to macrocirculation. In this work, we aim to review the recent literature about the role of endothelial activation and dysfunction in the development of CV complications in SLE and LN patients. We, therefore, focus on arteriovenous similarities and differences and on specific pathways of great vessels compared to capillaries. Critically summarising the available data is of pivotal importance for both basic researchers and clinicians in order to develop and test new pharmacological approaches in the treatment of basic components of SLE and LN.

Task Group Report 195 of the American Association of Physicists in Medicine contains reference datasets for the direct comparison of results among different Monte Carlo (MC) simulation tools for various aspects of imaging research that employs ionizing radiation. While useful for comparing and validating MC codes, that effort did not provide the information needed to compare absolute dose estimates from CT exams. Therefore, the purpose of this work is to extend those efforts by providing a reference dataset for benchmarking fetal dose derived from MC simulations of clinical CT exams.

The reference dataset contains the four necessary elements for validating MC engines for CT dosimetry (a) physical characteristics of the CT scanner, (b) patient information, (c) exam specifications, and (d) fetal dose results from previously validated and published MC simulations methods in tabular form. Scanner characteristics include non-proprietary descriptions of equivalent source cumulative distribution function (CDF) sbasis for comparison to other non-MC approaches, such as deterministic approaches, or to commercial packages that provide estimates of fetal doses from clinical CT exams.

Similar to the work of AAPM Report 195, this work provides a set of reference data for benchmarking fetal dose estimates from clinical CT exams. This provides researchers with an opportunity to compare MC simulation results to a set of published reference data as part of their efforts to validate absolute and normalized fetal dose estimates. This could also be used as a basis for comparison to other non-MC approaches, such as deterministic approaches, or to commercial packages that provide estimates of fetal doses from clinical CT exams.A premature infant with abdominal compartment syndrome underwent cardiopulmonary arrest before receiving decompressive laparotomy, and the effect of cardiopulmonary resuscitation was poor. The abdomen was punctured with an 18-gauge needle, alleviating the distension and resulting in successful cardiopulmonary resuscitation.

The purpose of this study was to evaluate the antifungal activity and toxicological parameters of 8-hydroxyquinoline derivatives PH151 and PH153 using alternative animal models, to understand their behaviour when subjected to in vivo experiments.

We used Toll-deficient Drosophila melanogaster to test the protective effect of compounds against Candida albicans infection. Toxicological parameters were investigated in chicken and zebrafish embryos. PH151 and PH153 showed low toxicity and the treated flies with these compounds had a significantly higher survival rate than untreated flies after 7days of infection. The compounds did not cause interruption of chicken embryogenesis. Zebrafish embryos exposed to compounds showed dose-dependent toxicity.

The data supported the potential of PH151 and PH153 for the treatment of systemic candidiasis and demonstrated to be appropriate drug candidates for further studies using mammalian models.

The increased incidence of Candida infections resistant to antifungals currently available requires acceleration of the discovery of new agents with properties of inhibiting this fungal pathogen. In this study, we have described the antifungal potential and toxicity of two 8-hydroxyquinoline derivatives using in vivo alternative models, and the results confirm their potential to be developed as new drug candidates.

The increased incidence of Candida infections resistant to antifungals currently available requires acceleration of the discovery of new agents with properties of inhibiting this fungal pathogen. In this study, we have described the antifungal potential and toxicity of two 8-hydroxyquinoline derivatives using in vivo alternative models, and the results confirm their potential to be developed as new drug candidates.In India, the deceased kidney transplant program is still in its preliminary stage, and accepting deceased donors with snakebite is just a forward step to expand the donor pool. We report here the outcome of 8 successful renal transplantations from brain-dead donors who died from a neurotoxic snakebite. We accepted them as donors as they had no evidence of hemotoxic snakebite. 7 recipients did well. 1 died due to sepsis with a functioning graft. 1 required renal biopsy that showed acute tubular necrosis. 1 required re-exploration due to graft collection due to a surgical issue. Patient and graft survival in follow-up were similar to other matched deceased donors in our center. According to our experience, utilizing brain-dead donors who died from a neurotoxic snakebite is safe and may dramatically expand the donor pool especially in countries where death due to snakebite is high in numbers.

The gonadotroph tumour (GT) is the most frequently resected pituitary neuroendocrine tumour. Although many symptomatic GT are successfully resected, some recur. We sought to identify histological biomarkers that may predict recurrence and explore biological mechanisms that explain this difference in behaviour.

SF-1 immunohistochemistry of 51 GT, a subset belonging to a longitudinal prospective cohort study (n=25), was reviewed. Four groups were defined Group 1-recently diagnosed GT (n=20), Group 2-non-recurrent GT with long-term follow up (n=11), Group 3-initial resections of GT that recur (n=7) and Group 4-recurrent GT (n=13). The percentage of SF-1 immunolabelling in the lowest staining fields (SF-1 labelling index (SLI)) was assessed and RNA sequencing was performed on 5 GT with SLI <80% and 5 GT with SLI >80%.

Diffuse, strong SF-1 immunolabelling was the most frequent pattern in Groups 1/2, whereas patchy SF-1 staining predominated in Groups 3/4. There was a lower median SLI in Groups 3/4 than 1/2.