Impact of Laparoscopic Surgical Management of Deep Endometriosis on Pregnancy Rate

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The kynurenine pathway as a therapeutic target in cognitive and neurodegenerative disorders

Understanding the neurochemical basis for cognitive function is one of the major goals of neuroscience, with a potential impact on the diagnosis, prevention and treatment of a range of psychiatric and neurological disorders. In this review, the focus will be on a biochemical pathway that remains under-recognised in its implications for brain function, even though it can be responsible for moderating the activity of two neurotransmitters fundamentally involved in cognition – glutamate and acetylcholine. Since this pathway – the kynurenine pathway of tryptophan metabolism - is induced by immunological activation and stress it also stands in an unique position to mediate the effects of environmental factors on cognition and behaviour. Targetting the pathway for new drug development could, therefore, be of value not only for the treatment of existing psychiatric conditions, but also for preventing the development of cognitive disorders in response to environmental pressures

Efficacy and safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in ovarian cancer: a systematic review of current evidence

Background: PIPAC is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal carcinomatosis. A systematic review was conducted to assess current evidence on the efficacy and outcomes of PIPAC in patients affected by ovarian cancer. Methods: The study adhered to the PRISMA guidelines. PubMed, Google Scholar and ClinicalTrials.gov were searched up to December 2023. Studies reporting data on patients with OC treated with PIPAC were included in the qualitative analysis. Results: Twenty-one studies and six clinical trials with 932 patients who underwent PIPAC treatment were identified. The reported first access failure was 4.9%. 89.8% of patients underwent one, 60.7% two and 40% received three or more PIPAC cycles. Pathological tumour response was objectivated in 13 studies. Intra-operative complications were reported in 11% of women and post-operative events in 11.5% with a 0.82% of procedure-related mortality. Quality of life scores have been consistently stable or improved during the treatment time. The percentage of OC patients who became amenable for cytoreductive surgery due to the good response after PIPAC treatment for palliative purposes is reported to be 2.3%. Conclusion: The results showed that PIPAC is safe and effective for palliative purposes, with a good pathological tumour response and quality of life. Future prospective studies would be needed to explore the role of this treatment in different stages of the disease, investigating a paradigm shift towards the use of PIPAC with curative intent for women who are not eligible for primary cytoreductive surgery

Canadian Immigration History Syllabus

I. Theory and MethodologyII. Chronological ModulesIII. Thematic ModulesThis syllabus brings together key themes, readings, sources, and questions in the history of migration to, from, and within Canada, offering a resource to educators and students, and valuable historical context for contemporary debates. It is inspired by the example of the #ImmigrationSyllabus created by migration historians in the United States in 2017

Oleogranulomatous Mastitis: A Topical Subject:

Paraffin and petrolatum have been known for more than 100 years as volumizing products. Certain countries still use them despite important complications. The authors report the case of a 39-year-old patient presenting a bilateral oleogranulomatous mastitis. An injection of petrolatum had been realized 2 years ago in Chechnya for cosmetic reasons. Clinically, she presented dense, erythemic, and painful breasts. The radiological examination found diffuse oily cysts. After first abdominal expansion, a bilateral mastectomy with immediate reconstruction was performed. The authors present a literature review about the clinical and radiological data and the possible treatments, and underline the numerous risks of this procedure, which should be strictly forbidden

Development of a methodology for in vivo follow-up of hepatocellular carcinoma in hepatocyte specific Trim24-null mice treated with myo-inositol trispyrophosphate

BACKGROUND: Genetically induced hepatocellular carcinoma (HCC) models are generally used to investigate carcinogenesis pathways, but very few attempts were made to valorize them for pharmacological testing. This study describes a micro-computed tomography (micro-CT) - based methodology for the diagnostic and lifelong follow-up of HCC in the hepatocyte-specific Trim24-null mouse line. Myo-inositol trispyrophosphate (ITPP) was tested as anti-cancer drug. METHODS: Partial hepatectomy was performed in 2 months-old Trim24-null mice, in order to accelerate the carcinogenesis process. HCC diagnosis was obtained by micro-CT scan with double contrast agent: 10 μl/g Fenestra™ LC was injected intraperitoneally 6 h prior to imaging and 10 μl/g Fenestra™ VC was injected intravenously 15 min prior to imaging. Twenty three hepatocyte-specific Trim24-null mice were considered for ITPP testing (3 mg/g/week intraperitoneally during 10 months in 12 mice, versus 11 controls). Lifelong follow-up was performed using micro-CT. Comparative analysis was performed using unpaired t test with Welch correction and survival curves were compared by log-rank test. Gene expression analysis was performed using the RT q-PCR technique. RESULTS: Double contrast micro-CT scan allowed HCC diagnosis as hypodense, isodense or hyperdense nodules. Positive predictive value was 81.3 %. Negative predictive value was 83.3 %. Tumor growth could be objectified by micro-CT scan before the ITPP treatment was started, and at 3 and 9 months follow-up. Significant progression of tumor volume was demonstrated in the both groups, with no difference between groups (p > 0.05). In the ITPP group, a mild decrease in tumor doubling time was first observed (31.9 +/− 12 days, p > 0.05) followed by a significant increase (59.8 +/− 18.3 days, p = 0.008). However, tumor doubling time was not different between groups (p > 0.05). Median survival after treatment initiation was 223 days (controls) versus 296 days (ITPP group, p = 0.0027). HIF1α, VEGF, glutamine synthase, osteopontin expression levels were not significantly modified at the end of follow-up. In the ITPP group, the p53 expression profile was inversed as compared to the control group, higher in non-tumor livers than in tumors. CONCLUSION: ITPP treatment allowed for a two-month survival improvement, with better tolerance of tumor burden and apoptosis increase in non-tumor, pathological livers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0434-8) contains supplementary material, which is available to authorized users

Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase

Liver pyruvate kinase (PKL) has recently emerged as a new target for non-alcoholic fatty liver disease (NAFLD), and inhibitors of this enzyme could represent a new therapeutic option. However, this breakthrough is complicated by selectivity issues since pyruvate kinase exists in four different isoforms. In this work, we report that ellagic acid (EA) and its derivatives, present in numerous fruits and vegetables, can inhibit PKL potently and selectively. Several polyphenolic analogues of EA were synthesized and tested to identify the chemical features responsible for the desired activity. Molecular modelling studies suggested that this inhibition is related to the stabilization of the PKL inactive state. This unique inhibition mechanism could potentially herald the development of new therapeutics for NAFLD.</p