Cerebral hemodynamics on MR perfusion images before and after bypass surgery in patients with giant intracranial aneurysms

Preoperative assessment of the anatomy and dynamics of cerebral circulation for patients with giant intracranial aneurysm can improve both outcome prediction and therapeutic approach. The aim of our study was to use perfusion MR imaging to evaluate cerebral hemodynamics in such patients before and after extraintracranial high-flow bypass surgery. METHODS: Five patients with a giant aneurysm of the intracranial internal carotid artery underwent MR studies before, 1 week after, and 1 month after high-flow bypass surgery. We performed MR and digital subtraction angiography, and conventional and functional MR sequences (diffusion and perfusion). Surgery consisted of middle cerebral artery (MCA)-internal carotid artery bypass with saphenous vein grafts (n = 4) or MCA-external carotid artery bypass (n = 1). RESULTS: In four patients, MR perfusion study showed impaired hemodynamics in the vascular territory supplied by the MCA of the aneurysm side, characterized by significantly reduced mean cerebral blood flow (CBF), whereas mean transit time (MTT) and regional cerebral blood volume (rCBV) were either preserved, reduced, or increased. After surgery, angiography showed good canalization of the bypass graft. MR perfusion data obtained after surgery showed improved cerebral hemodynamics in all cases, with a return of CBF index (CBFi), MTT, and rCBV to nearly normal values. CONCLUSION: Increased MTT with increased or preserved rCBV can be interpreted as a compensatory vasodilatory response to reduced perfusion pressure, presumably from compression and disturbed flow in the giant aneurysmal sac. When maximal vasodilation has occurred, however, the brain can no longer compensate for diminished perfusion by vasodilation, and rCBV and CBFi diminish. Bypass surgery improves hemodynamics, increasing perfusion pressure and, thus, CBFi. Perfusion MR imaging can be used to evaluate cerebral hemodynamics in patients with intracranial giant aneurysm.BACKGROUND AND PURPOSE: Preoperative assessment of the anatomy and dynamics of cerebral circulation for patients with giant intracranial aneurysm can improve both outcome prediction and therapeutic approach. The aim of our study was to use perfusion MR imaging to evaluate cerebral hemodynamics in such patients before and after extraintracranial high-flow bypass surgery. METHODS: Five patients with a giant aneurysm of the intracranial internal carotid artery underwent MR studies before, 1 week after, and 1 month after high-flow bypass surgery. We performed MR and digital subtraction angiography, and conventional and functional MR sequences (diffusion and perfusion). Surgery consisted of middle cerebral artery (MCA)-internal carotid artery bypass with saphenous vein grafts (n = 4) or MCA-external carotid artery bypass (n = 1). RESULTS: In four patients, MR perfusion study showed impaired hemodynamics in the vascular territory supplied by the MCA of the aneurysm side, characterized by significantly reduced mean cerebral blood flow (CBF), whereas mean transit time (MTT) and regional cerebral blood volume (rCBV) were either preserved, reduced, or increased. After surgery, angiography showed good canalization of the bypass graft. MR perfusion data obtained after surgery showed improved cerebral hemodynamics in all cases, with a return of CBF index (CBFi), MTT, and rCBV to nearly normal values. CONCLUSION: Increased MTT with increased or preserved rCBV can be interpreted as a compensatory vasodilatory response to reduced perfusion pressure, presumably from compression and disturbed flow in the giant aneurysmal sac. When maximal vasodilation has occurred, however, the brain can no longer compensate for diminished perfusion by vasodilation, and rCBV and CBFi diminish. Bypass surgery improves hemodynamics, increasing perfusion pressure and, thus, CBFi. Perfusion MR imaging can be used to evaluate cerebral hemodynamics in patients with intracranial giant aneurysm

Ovarian endometriomas and IVF: a retrospective case-control study

We performed this retrospective case-control study analyzing 428 first-attempt in vitro fertilization (IVF) cycles, among which 254 involved women with a previous or present diagnosis of ovarian endometriosis. First, the results of these 254 cycles were compared with 174 cycles involving patients with proven non-endometriotic tubal infertility having similar age and body mass index. Women with ovarian endometriosis had a significantly higher cancellation rate, but similar pregnancy, implantation and delivery rates as patients with tubal infertility. Second, among the women with ovarian endometriosis, the women with a history of laparoscopic surgery for ovarian endometriomas prior to IVF and no visual endometriosis at ovum pick-up (n = 112) were compared with the non-operated women and visual endometriomas at ovum pick-up (n = 142). Patients who underwent ovarian surgery before IVF had significantly shorter period, lower antral follicle count and required higher gonadotropin doses than patients with non-operated endometriomas. The two groups of women with a previous or present ovarian endometriosis did, however, have similar pregnancy, implantation and live birth rates. In conclusion, ovarian endometriosis does not reduce IVF outcome compared with tubal factor. Furthermore, laparoscopic removal of endometriomas does not improve IVF results, but may cause a decrease of ovarian responsiveness to gonadotropins

CASE report: Acute hepatic failure secondary to metastatic LIVER\u2019S infiltration by upper tract urothelial carcinoma

INTRODUCTION: Acute liver failure (ALF) secondary to malignant infiltration of the liver from urothelial carcinoma is a very rare clinical condition and is often diagnosed only after death. Upper tract urothelial carcinoma (UTUC) is a rare, from 5% to 10% of all urothelial tumours, but possible cause of ALF when there is extensive liver metastatic involvement. We report the case of a patient who died in the intensive care unit (ICU) of our hospital from multiple organ failure (MOF) secondary to ALF, as a result of infiltration of the liver from UTUC diagnosed after surgery. PRESENTATION OF THE CASE: A 69-year-old Caucasian man was referred to our hospital for hematuria, melena, right upper quadrant (RUQ) pain and jaundice developed over the previous two weeks. After multidisciplinary discussion, he underwent emergency exploratory laparotomy to perform cholecystectomy because of suspected acute cholecystitis considered as a septic focus within the left kidney. He developed MOF and died on the 6thpostoperative day. DISCUSSION: From the diagnosis of the renal mass and the death of the patient, a few days have passed, and the diagnosis of UTUC has been put only at histological examination.The most common sites of metastases from UTUC are lymph nodes, lungs, liver, bones and peritoneum. Moreover, liver metastases have been identified to have an independent negative impact on overall survival in a patient affected by UTUC. CONCLUSION: The authors suggest that this condition should be taken into account when dealing with patients with evidence of a renal mass and simultaneous ALF. KEYWORDS: Acute liver failure, Upper tract urothelial carcinoma (UTUC), emergency surger

Mechanical phenotyping of K562 cells by the Micropipette Aspiration Technique allows identifying mechanical changes induced by drugs

Mechanical properties of living cells can be used as reliable markers of their state, such as the presence of a pathological state or their differentiation phase. The mechanical behavior of cells depends on the organization of their cytoskeletal network and the main contribution typically comes from the actomyosin contractile system, in both suspended and adherent cells. In the present study, we investigated the effect of a pharmaceutical formulation (OTC - Ossitetraciclina liquida 20%) used as antibiotic, on the mechanical properties of K562 cells by using the Micropipette Aspiration Technique (MAT). This formulation has been shown to increase in a time dependent way the inflammation and toxicity in terms of apoptosis in in vitro experiments on K562 and other types of cells. Here we show that by measuring the mechanical properties of cells exposed to OTC for different incubation times, it is possible to infer modifications induced by the formulation to the actomyosin contractile system. We emphasize that this system is involved in the first stages of the apoptotic process where an increase of the cortical tension leads to the formation of blebs. We discuss the possible relation between the observed mechanical behavior of cells aspirated inside a micropipette and apoptosis

Il ruolo del'ingegneria nella valorizzazione dei prodotti tipici montani

Il presente lavoro si inserisce nell'ambito del progetto "Metodi e sistemi per aumentare il valore aggiunto degli alimenti tradizionali ed a vocazione territoriale" il cui obiettivo è mettere a punto metodi, strumenti e tecnologie per il recupero e la valorizzazione di produzioni tradizionali di aree geografiche sensibili dal punto di vista socio-ambientale, quali le aree montante, al fine di promuoverne lo sviluppo. Lo studio si è articolato in 3 fasi: - definizione della metodologia; - caratterizzazione e analisi del territorio e delle realtà produttive; - ottimizzazione delle produzioni e strategie di sviluppo territoriale. Sono state individuate 5 filiere produttive costituite principalmente da micro-realtà artigianali e di ciascuna sono stati analizzati gli ambiti produttivo, tecnologico, organizzativo e gestionale. L'analisi, oltre a fotografare la situazione attuale, ha evidenziato le criticità igienico-sanitarie delle produzioni alimentati e della sicurezza e benessere degli operatori. In sintesi, i principali obiettivi raggiunti sono stati: - ottimizzazione dell'attuale produzione e messa a punto di linee produttive alternative; - individuazione dell'attuale produzione e messa a punto di linee produttive alternative; - individuazione degli elementi peculiari delle filiere al fine di proporre disciplinari di produzione; - ottimizzazione meccanico-impiantistica dell'efficienza, produttività, sicurezza e benessere degli operatori; - proposta di nuove tipologie di macchine e impianti dedicati; - sostenbilità del processo produttivo atraverso l'utilizzo di fonti energetiche alternative; - recupero e potenziamento delle infrastrutture presenti sul territorio per migliorare la logistica degli approvvigionamenti e della commercializzazione dei prodotti e l'accessibilità al territorio; - definizione di nuovi criteri progettuali delle strutture produttive e di layout innovativi; - messa a punto di sistemi di controllo al fine di garantire la qualità del prodotto. In conclusione la metodologia si è rivelata adeguata nell'analizzare in modo sistematico le filiere, individuandone i limiti. Inoltre ha permesso di suggerire tecnologie e strategie valide per la gestione del passaggio da attività amatoriale ad attività imprenditoriale

Characterization of GECPAR, a noncoding RNA that regulates the transcriptional program of diffuse large B cell lymphoma

Enhancers are regulatory regions of DNA, which play a key role in cell-type specific differentiation and development. Most active enhancers are transcribed into enhancer RNAs (eRNAs) that can regulate transcription of target genes by means of in cis as well as in trans action. eRNAs stabilize contacts between distal genomic regions and mediate the interaction of DNA with master transcription factors. Here, we characterised an enhancer RNA, GECPAR (GErminal Center Proliferative Adapter RNA), that is specifically transcribed in normal and neoplastic germinal center B-cells from the super-enhancer of POU2AF1, a key regulatory gene of the germinal center reaction. Using diffuse large B cell lymphoma cell line models, we demonstrated the tumor suppressor activity of GECPAR, which is mediated via its transcriptional regulation of proliferation and differentiation genes, particularly MYC and the Wnt pathway

Multiple indices on different habitats and descriptors provide consistent assessments of environmental quality in a marine protected area

In the last decades, climate change and human pressures have increasingly and dramatically impacted the ocean worldwide, calling for urgent actions to safeguard coastal marine ecosystems. The European Commission, in particular, has set ambitious targets for member states with two major directives, the Water Framework Directive (WFD) and the Marine Strategy Framework Directive (MSFD), both designed to protect the marine environment in EU waters. Diverse biotic indices have accordingly been developed to assess water and habitat quality. The WFD adopts four Biological Quality Elements (BQEs), whereas the MSFD recommends a set of eleven qualitative descriptors. The borderline between water quality and habitat quality is hard to trace and so far most assessments have involved the use of a few indices and were mainly related to a single BQE or qualitative descriptor. In this study, thanks to the availability of a large dataset encompassing a wide array of descriptors, we compared the performance of 11 biotic indices relative to three habitats/biotic components (reefs, seagrass, and fish) of the Marine Protected Area (MPA) of Capo Carbonara (SE Sardinia, Italy). The aim was to assess whether the indices were consistent in defining the environmental status in the MPA investigated. We used the graphical approach RESQUE (REsilience and QUality of Ecosystem), which enabled us to obtain a single and comprehensive measure of the status of the environment by integrating several metrics. This approach was applied here to different habitats for the first time. All indices were consistent with each other in confirming the good status of Capo Carbonara MPA. The use of RESQUE provided insights to interpret the differences between water quality, defined according to the WFD, and habitat quality, defined according to the MSFD. Differences between the two EU directives, in terms of either requirements or goals, have long been discussed but the present study highlights for the first time that they are congruent in their assessment of the environmental status of marine ecosystems

Kynurenine 3-Monooxygenase Inhibition in Blood Ameliorates Neurodegeneration

SummaryMetabolites in the kynurenine pathway, generated by tryptophan degradation, are thought to play an important role in neurodegenerative disorders, including Alzheimer's and Huntington's diseases. In these disorders, glutamate receptor-mediated excitotoxicity and free radical formation have been correlated with decreased levels of the neuroprotective metabolite kynurenic acid. Here, we describe the synthesis and characterization of JM6, a small-molecule prodrug inhibitor of kynurenine 3-monooxygenase (KMO). Chronic oral administration of JM6 inhibits KMO in the blood, increasing kynurenic acid levels and reducing extracellular glutamate in the brain. In a transgenic mouse model of Alzheimer's disease, JM6 prevents spatial memory deficits, anxiety-related behavior, and synaptic loss. JM6 also extends life span, prevents synaptic loss, and decreases microglial activation in a mouse model of Huntington's disease. These findings support a critical link between tryptophan metabolism in the blood and neurodegeneration, and they provide a foundation for treatment of neurodegenerative diseases

Genetic and phenotypic attributes of splenic marginal zone lymphoma

Splenic marginal zone B-cell lymphoma (SMZL) is a heterogeneous clinico-biological entity. The clinical course is variable, multiple genes are mutated with no unifying mechanism, and essential regulatory pathways and surrounding microenvironments are diverse. We sought to clarify the heterogeneity of SMZL by resolving different subgroups and their underlying genomic abnormalities, pathway signatures, and microenvironment compositions to uncover biomarkers and therapeutic vulnerabilities. We studied 303 SMZL spleen samples collected through the IELSG46 multicenter international study (NCT02945319) by using a multiplatform approach. We carried out genetic and phenotypic analyses, defined self-organized signatures, validated the findings in independent primary tumor metadata and in genetically modified mouse models, and determined correlations with outcome data. We identified 2 prominent genetic clusters in SMZL, termed NNK (58% of cases, harboring NF-κB, NOTCH, and KLF2 modules) and DMT (32% of cases, with DNA-damage response, MAPK, and TLR modules). Genetic aberrations in multiple genes as well as cytogenetic and immunogenetic features distinguished NNK- from DMT-SMZLs. These genetic clusters not only have distinct underpinning biology, as judged by differences in gene-expression signatures, but also different outcomes, with inferior survival in NNK-SMZLs. Digital cytometry and in situ profiling segregated 2 basic types of SMZL immune microenvironments termed immune-suppressive SMZL (50% of cases, associated with inflammatory cells and immune checkpoint activation) and immune-silent SMZL (50% of cases, associated with an immune-excluded phenotype) with distinct mutational and clinical connotations. In summary, we propose a nosology of SMZL that can implement its classification and also aid in the development of rationally targeted treatments