Pheochromocytomas and paragangliomas in von hippel–lindau disease: Not a needle in a haystack

Objective: Pheochromocytomas are a hallmark feature of von Hippel–Lindau disease (vHL). To our knowledge, this is the first systematic review with meta-analysis evaluating the frequency of pheochromocytomas and/or paragangliomas (PPGLs) in patients with vHL, as well as among patients with different vHL subtypes. Design: Systematic review with meta-analysis. Methods: We searched on MEDLINE, Scopus, and Web of Science. We included primary studies assessing participants with vHL and reporting on the frequency of PPGL. We performed random-effects meta-analysis to quantitatively assess the frequency of PPGL, followed by meta-regression and subgroup analysis. Risk of bias analysis was performed to assess primary studies’ methodological quality. Results: We included 80 primary studies. In 4263 patients with vHL, the pooled frequency of PPGL was 19.4% (95% CI = 15.9–23.6%, I2 = 86.1%). The frequency increased to 60.0% in patients with vHL type 2 (95% CI = 53.4–66.3%, I2 = 54.6%) and was determined to be of 58.2% in patients with vHL type 2A (95% CI = 49.7–66.3%, I2 = 36.2%), compared to 49.8% in vHL type 2B (95% CI = 39.9–59.7%, I2 = 42.7%), and 84.1% in vHL type 2C (95% CI = 75.1–93.1%, I2 = 0%). In meta-regression analysis, more recent studies were associated with a higher frequency of PPGL. All studies had at least one internal validity item classified as 'high risk of bias,' with 13% studies having low risk of bias in all external validity items. Conclusions: PPGLs are a common manifestation of vHL. Despite methodological limitations and differences across primary studies, our results point to the importance of PPGL screening in patients with vHL

Does training method matter? Evidence for the negative impact of aversive-based methods on companion dog welfare

Dog training methods range broadly from those using mostly positive punishment and negative reinforcement (aversive-based) to those using primarily positive reinforcement (rewardbased). Although aversive-based training has been strongly criticized for negatively affecting dog welfare, there is no comprehensive research focusing on companion dogs and mainstream techniques, and most studies rely on owner-reported assessment of training methods and dog behavior. The aim of the present study was to evaluate the effects of aversive- and reward-based training methods on companion dog welfare within and outside the training context. Ninety-two companion dogs were recruited from three reward-based schools (Group Reward, n = 42), and from four aversive-based schools, two using low proportions of aversive-based methods (Group Mixed, n = 22) and two using high proportions of aversive-based methods (Group Aversive, n = 28). For evaluating welfare during training, dogs were video recorded for three sessions and six saliva samples were collected, three at home (baseline levels) and three after training (post-training levels). Video recordings were used to examine the frequency of stress-related behaviors (e.g., lip lick, yawn) and the overall behavioral state of the dog (e.g., tense, relaxed), and saliva samples were analyzed for cortisol concentration. For evaluating welfare outside the training context, dogs participated in a cognitive bias task. Results showed that dogs from Group Aversive displayed more stress-related behaviors, were more frequently in tense and low behavioral states and panted more during training, and exhibited higher post-training increases in cortisol levels than dogs from Group Reward. Additionally, dogs from Group Aversive were more 'pessimistic' in the cognitive bias task than dogs from Group Reward. Dogs from Group Mixed displayed more stress-related behaviors, were more frequently in tense states and panted more during training than dogs from Group Reward. Finally, although Groups Mixed and Aversive did not differ in their performance in the cognitive bias task nor in cortisol levels, the former displayed more stress-related behaviors and was more frequently in tense and low behavioral states. These findings indicate that aversive-based training methods, especially if used in high proportions, compromise the welfare of companion dogs both within and outside the training context.The current research study was supported by FCT - Fundação Portuguesa para a Ciência e Tecnologia (Fellowship SFRH/BPD/ 111509/2015) and UFAW - Universities Federation for Animal Welfare (Grant 14-16/17), with grants awarded to ACVC. SP was supported by PIPOL - Regione Friuli Venezia Giulia. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. FCT - Fundação Portuguesa para a Ciência e Tecnologia: https://www.fct.pt/index. phtml.pt UFAW - Universities Federation for Animal Welfare: https://www.ufaw.org.uk/

Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-Mediated Listeria monocytogenes Infection of HeLa Cells

The host cytoskeleton is a major target for bacterial pathogens during infection. In particular, pathogens usurp the actin cytoskeleton function to strongly adhere to the host cell surface, to induce plasma membrane remodeling allowing invasion and to spread from cell to cell and disseminate to the whole organism. Keratins are cytoskeletal proteins that are the major components of intermediate filaments in epithelial cells however, their role in bacterial infection has been disregarded. Here we investigate the role of the major epithelial keratins, keratins 8 and 18 (K8 and K18), in the cellular infection by Listeria monocytogenes. We found that K8 and K18 are required for successful InlB/cMet-dependent L. monocytogenes infection, but are dispensable for InlA/E-cadherin-mediated invasion. Both K8 and K18 accumulate at InlB-mediated internalization sites following actin recruitment and modulate actin dynamics at those sites. We also reveal the key role of K8 and K18 in HGF-induced signaling which occurs downstream the activation of cMet. Strikingly, we show here that K18, and at a less extent K8, controls the expression of cMet and other surface receptors such TfR and integrin β1, by promoting the stability of their corresponding transcripts. Together, our results reveal novel functions for major epithelial keratins in the modulation of actin dynamics at the bacterial entry sites and in the control of surface receptors mRNA stability and expression.This work received funding from Norte-01-0145-FEDER-000012 - Structured program on bioengineered therapies for infectious diseases and tissue regeneration, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). Publication Fees were supported by ICBAS, University of Porto. RC received an FCT Doctoral Fellowship (SFRH/BD/90607/2012) and IP-C a FCT Post-Doctoral Fellowship (SFRH/BPD/107901/2015) through FCT/MEC co-funded by QREN and POPH (Programa Operacional Potencial Humano). SS was supported by FCT Investigator program (COMPETE, POPH, and FCT). We thank IBMC facilities for technical assistance

Oxaliplatin toxicity presenting as a liver nodule - case report

BACKGROUND: Oxaliplatin based chemotherapy is often used as adjuvant therapy in colon and rectal cancer. A reported side effect is Sinusoidal Obstruction Syndrome which is characterized by a spectrum of pathologic changes, from sinusoidal dilation, peri-sinusoidal haemorrhage, peliosis and nodular regenerative hyperplasia. Very rarely it can cause the development of liver nodules mimicking liver metastases. Herein, we report a case of Sinusoidal Obstruction Syndrome causing a liver nodule suspicious of liver metastasis on imaging. This is the third reported case of this complication of oxaliplatin toxicity, in which resection was performed and pathological diagnosis confirmed. CASE PRESENTATION: We report the case of a 59 year old man with stage III colon cancer who underwent sigmoidectomy followed by adjuvant chemotherapy with oxaliplatin. One year after surgery a liver nodule was detected and the patient underwent right hepatectomy. Pathology showed no liver nodule and diagnosed sinusoidal obstruction syndrome. CONCLUSION: We describe the third reported case of a liver lesion mimicking a liver metastasis after oxaliplatin-based chemotherapy for colon cancer. We suggest that in patients heavily treated with oxaliplatin with de novo liver nodules, this differential diagnosis should be considered. In particular, in this population of patients an intense imagiologic evaluation and even a preoperative biopsy should be pursued to confirm the diagnosis of malignancy and avoid overtreatment.info:eu-repo/semantics/publishedVersio

Measuring axiomatic soundness of counterfactual image models

We use the axiomatic definition of counterfactual to derive metrics that enable quantifying the correctness of approximate counterfactual inference models. Abstract: We present a general framework for evaluating image counterfactuals. The power and flexibility of deep generative models make them valuable tools for learning mechanisms in structural causal models. However, their flexibility makes counterfactual identifiability impossible in the general case. Motivated by these issues, we revisit Pearl's axiomatic definition of counterfactuals to determine the necessary constraints of any counterfactual inference model: composition, reversibility, and effectiveness. We frame counterfactuals as functions of an input variable, its parents, and counterfactual parents and use the axiomatic constraints to restrict the set of functions that could represent the counterfactual, thus deriving distance metrics between the approximate and ideal functions. We demonstrate how these metrics can be used to compare and choose between different approximate counterfactual inference models and to provide insight into a model's shortcomings and trade-offs

Prevalence of gonorrhea and chlamydia in a community clinic for men who have sex with men in Lisbon, Portugal

Men who have sex with men (MSM) are at greater risk for sexually transmitted infections (STIs). Data on MSM chlamydia and gonorrhea prevalence estimates and associated risk factors are scarce. To our knowledge, this is the first study to describe the prevalence and the determinants of both chlamydia and gonorrhea infections in MSM in Portugal. We conducted a cross-sectional study using data from 1832 visits to CheckpointLX, a community-based center for screening blood-borne viruses and other STIs in MSM. Overall prevalence of chlamydia or gonorrhea in our sample was 16.05%, with 14.23% coinfection and 40.73% asymptomatic presentation among those testing positive. Anorectal infection was most common for chlamydia (67.26%), followed by urethral (24.78%) and oral (19.47%) infection. Oral infection was most common for gonorrhea (55.63%), followed by anal (51.25%) and urethral (17.50%) infection. In multivariate analyses, young age (U = 94684, p = 0.014), being foreign-born (χ2 = 11.724, p = 0.003), reporting STI symptoms (χ2 = 5.316, p = 0.021), inhaled drug use (χ2 = 4.278, p = 0.039) and having a higher number of concurrent (χ2 = 18.769, p < 0.001) or total (χ2 = 5.988, p = 0.050) sexual partners were each associated with higher rates of chlamydia or gonorrhea infection. Young and migrant MSM are a vulnerable population to STIs, as are those who use inhaled drugs and those with a higher number of concurrent or total sexual partners. Although Portugal has no guidelines on chlamydia and gonorrhea screening, our results point toward a need for greater awareness about the importance of high-frequency screening for those at increased risk (i.e., every three to six months).info:eu-repo/semantics/publishedVersio

Modulating spin transfer torque switching dynamics with two orthogonal spin-polarizers by varying the cell aspect ratio

We study in-plane magnetic tunnel junctions with additional perpendicular polarizer for subnanosecond-current-induced switching memories. The spin-transfer-torque switching dynamics was studied as a function of the cell aspect ratio both experimentally and by numerical simulations using the macrospin model. We show that the anisotropy field plays a significant role in the dynamics, along with the relative amplitude of the two spin-torque contributions. This was confirmed by micromagnetic simulations. Real-time measurements of the reversal were performed with samples of low and high aspect ratio. For low aspect ratios, a precessional motion of the magnetization was observed and the effect of temperature on the precession coherence was studied. For high aspect ratios, we observed magnetization reversals in less than 1 ns for high enough current densities, the final state being controlled by the current direction in the magnetic tunnel junction cell.Comment: 6 pages, 7 figure