Investigation of microglial diversity in a LRRK2 G2019S mouse model of Parkinson's disease.

Microglia contribute to the outcomes of various pathological conditions including Parkinson's disease (PD). Microglia are heterogenous, with a variety of states recently identified in aging and neurodegenerative disease models. Here, we delved into the diversity of microglia in a preclinical PD model featuring the G2019S mutation in LRRK2, a known pathological mutation associated with PD. Specifically, we investigated the 'dark microglia' (DM) and the 'disease-associated microglia' (DAM) which present a selective enrichment of CLEC7A expression. In the dorsal striatum - a region affected by PD pathology - extensive ultrastructural features of cellular stress as well as reduced direct cellular contacts, were observed for microglia from old LRRK2 G2019S mice versus controls. In addition, DM were more prevalent while CLEC7A-positive microglia had extensive phagocytic ultrastructural characteristics in the LRRK2 G2019S mice. Furthermore, our findings revealed a higher proportion of DM in LRRK2 G2019S mice, and an increased number of CLEC7A-positive cells with age, exacerbated by the pathological mutation. These CLEC7A-positive cells exhibited a selective enrichment of ameboid morphology and tended to cluster in the affected animals. In summary, we provide novel insights into the occurrence and features of recently defined microglial states, CLEC7A-positive cells and DM, in the context of LRRK2 G2019S PD pathology.

The role of personality dimensions, depressive symptoms and other psychosocial variables in predicting postpartum suicidal ideation: a cohort study.

Suicidability has been associated with neuroticism and psychoticism, but its role during perinatal period has not been analyzed. We explore the association between personality dimensions, depressive symptoms, and other psychosocial variables in postpartum suicidal ideation. A cohort of 1795 healthy Spanish women from the general population was assessed for suicidal ideation (EPDS-Item10) in early postpartum, 8 and 32 weeks postpartum. Sociodemographic, obstetric, and reproductive variables, psychiatric history, social support, stressful life-events during pregnancy, depressive symptoms (EPDS), and the Eysenck's personality dimensions (EPQ-RS) were also assessed at baseline. A major depressive episode (DSM-IV) was confirmed in women with EPDS>10 at follow-up assessments. Descriptive, bivariate, and multivariate analyses were conducted. Adjusted logistic regression analysis was reported as odds ratio (ORs) with 95% confidence intervals (CIs). Seven percent of mothers reported suicidal ideation during the first 8 months postpartum. Sixty-two percent of women with suicidal ideation had a major depressive episode at 8 weeks, and 70% at 32 weeks postpartum. Neuroticism and psychoticism predicted suicidal ideation throughout the first 2 weeks after delivery (OR, 1.03; 95%CI 1.01-1.06; and OR, 1.03; 95%CI 1.01-1.05 respectively). Early postpartum depressive symptoms (OR 1.2; 95%CI 1.11-1.26), personal psychiatric history (OR 2.1; 95%CI 1.33-3.27), and stressful life events during pregnancy (OR 1.88; 95%CI 1.12-3.16) also emerged as predictors of postpartum suicidal ideation. Analysis of women for postpartum suicidal ideation should include not only psychiatric symptoms but also psychosocial assessment (i.e., covering psychiatric history, stressful events, or long-standing personality vulnerabilities) in order to identify those in need of early psychosocial or psychiatric care.

Effects of structural damping on acoustic scattering by flexible plates.

We investigate the effects of structural damping on the interaction of a turbulent eddy with flexible plates with respect to the efficiency of aerodynamic noise generation. Potential benefits are studied using a model based on a point-reacting compliant semi-infinite plate on a spring-damper foundation. This scattering problem is solved using the Wiener-Hopf technique. We compare results for semi-infinite compliant plates with finite ones. In both cases, plate vibration lead to reductions of sound radiation, especially at resonance; damping tends to reduce such acoustic benefits. We also present a formulation that considers the effect of structural damping on the acoustic properties of finite elastic plates. Numerical results are obtained by applying a boundary element method to solve the Helmholtz equation subject to the boundary conditions imposed by the plate vibration. Under specific conditions, such as high fluid loading factor and low bending-wave Mach number, the acoustic power scattered by an edge tends to be smaller than that which propagates over the plate as bending waves. Results show that structural damping attenuates these waves and may modify the far-field acoustic pressure, mostly by reducing the scattered sound at structural resonances. All models show that large damping coefficients lead to locally over-damped responses. There is thus an ideal range of structural damping to reduce both plate vibration and acoustic scattering.

Drop-out between the two liver resections of two-stage hepatectomy. Patient selection or loss of chance?

BACKGROUND: Two-stage hepatectomy (TSH) is the present standard for multiple bilobar colorectal liver metastases (CLM), but 25-35% of patients fail to complete the scheduled procedure (drop-out). To elucidate if drop-out of TSH is a patient selection (as usually considered) or a loss of chance. METHODS: All the consecutive patients scheduled for a TSH at the Paul Brousse Hospital between 2000 and 2012 were considered. TSH patients were matched 1:1 with patients receiving a one-stage ultrasound-guided hepatectomy (OSH) at the Humanitas Research Hospital in the same period. Matching criteria were: primary tumor N status; timing of CLM diagnosis; CLM number and distribution into the liver. RESULTS: Sixty-three pairs of patients were analyzed. Demographic and tumor characteristics were similar (median 7 CLM), except for more chemotherapy lines and adjuvant chemotherapy in TSH. Drop-out rate of TSH was 38.1% (0% of OSH). The two groups had similar R0 resection rate (19.0% OSH vs. 15.9% TSH). OSH and completed TSH had similar five-year survival (from CLM diagnosis 49.8% vs. 49.7%, from liver resection 36.1% vs. 44.3%), superior to drop-out (10% three-year survival, p < 0.001). OSH and completed TSH had similar recurrence-free survival (at three years 21.7% vs. 20.5%) and recurrence sites. The completion of resection (drop-out vs. OSH/completed TSH) was the only independent prognostic factor (p = 0.003). CONCLUSIONS: Drop-out of TSH could be a loss of chance rather than a criteria for patient selection. "Unselected" OSH patients had the same outcomes of selected patients who completed TSH. A complete resection is the main determinant of prognosis.

Personality traits and psychiatric comorbidities in alcohol dependence.

Non-adaptive personality traits may constitute risk factors for development of psychiatric disorders such as depression and anxiety. We aim to evaluate associations and the predictive value of personality traits among alcohol-dependent individuals, with or without psychiatric comorbidities. The convenience sample comprised two groups of males over 18 years of age: one with subjects who had an alcohol dependence diagnosis (AG, n=110), and a control group without abuse and/or alcohol dependence diagnosis (CG, n=110). The groups were assessed by means of the Structured Clinical Interview DSM-IV (SCID-IV). AG participants were recruited among outpatients from the university hospital, whereas CG participants were recruited from a primary healthcare program. Data collection was done individually with self-assessment instruments. Parametric statistics were performed, and a significance level of P=0.05 was adopted. A positive correlation was observed between openness and the length of time that alcohol has been consumed, as were significant and negative correlations between conscientiousness and both the length of time alcohol has been consumed and the number of doses. For alcoholics, extraversion emerged as a protective factor against depression development (P=0.008) and tobacco abuse (P=0.007), whereas openness worked as a protective factor against anxiety (P=0.02). The findings point to specific deficits presented by alcoholics in relation to personality traits with or without psychiatric comorbidities and to the understanding that therapeutic approaches should favor procedures and/or preventive measures that allow more refined awareness about the disorder.

Personality traits and psychiatric comorbidities in alcohol dependence

Non-adaptive personality traits may constitute risk factors for development of psychiatric disorders such as depression and anxiety. We aim to evaluate associations and the predictive value of personality traits among alcohol-dependent individuals, with or without psychiatric comorbidities. The convenience sample comprised two groups of males over 18 years of age: one with subjects who had an alcohol dependence diagnosis (AG, n=110), and a control group without abuse and/or alcohol dependence diagnosis (CG, n=110). The groups were assessed by means of the Structured Clinical Interview DSM-IV (SCID-IV). AG participants were recruited among outpatients from the university hospital, whereas CG participants were recruited from a primary healthcare program. Data collection was done individually with self-assessment instruments. Parametric statistics were performed, and a significance level of P=0.05 was adopted. A positive correlation was observed between openness and the length of time that alcohol has been consumed, as were significant and negative correlations between conscientiousness and both the length of time alcohol has been consumed and the number of doses. For alcoholics, extraversion emerged as a protective factor against depression development (P=0.008) and tobacco abuse (P=0.007), whereas openness worked as a protective factor against anxiety (P=0.02). The findings point to specific deficits presented by alcoholics in relation to personality traits with or without psychiatric comorbidities and to the understanding that therapeutic approaches should favor procedures and/or preventive measures that allow more refined awareness about the disorder.

State of the art of intraoperative ultrasound in liver surgery: current use for staging and resection guidance.

The performance of hepatic surgery without a parenchyma-sparing strategy carries significant risks for patient survival because of the not negligible occurrence of postoperative liver failure. In modern liver surgery the use of intraoperative ultrasound (IOUS) includes staging of the liver disease and more importantly resection guidance. IOUS allows the performance of so-called "radical but conservative surgery", which is pivotal in offering a chance of a cure to an increasing number of patients who until a few years ago were considered only for palliative care. The present article details the rationale of IOUS for staging and for resection guidance in liver surgery.

Intraoperative ultrasonographic detection of communicating veins between adjacent hepatic veins during hepatectomy for tumours at the hepatocaval confluence.

BACKGROUND: The presence of communicating veins between adjacent hepatic veins may allow parenchyma-sparing hepatectomy. Taking advantage of improvements in ultrasound technology, such as e-flow modality, a study of the presence of communicating veins was conducted in patients with hepatic tumours at the caval confluence. METHODS: Consecutive patients undergoing surgery between October 2007 and December 2009 for hepatic tumours in contact with or invading a hepatic vein at its caval confluence were included. Communicating vein mapping by means of e-flow intraoperative ultrasonography (EF-IOUS) was carried out. RESULTS: A total of 20 patients were enrolled. Communicating veins between adjacent hepatic veins or with the inferior vena cava were detected in 16 patients. The median number of communicating veins was 1 (range 0-5). The total number of lesions removed was 126 (range 1-46). In 11 of 12 patients requiring resection of a hepatic vein, communicating veins enabled a parenchyma-sparing procedure to be performed. No patient had a formal major hepatectomy. There was no postoperative mortality or major morbidity. CONCLUSION: EF-IOUS estimation of the frequency of communicating veins between adjacent hepatic veins suggests that such veins are common. This may facilitate parenchyma-sparing procedures in patients with hepatic tumours encroaching on major hepatic veins.

[Surgical treatment of liver metastases from colorectal carcinoma]. / Il trattamento chirurgico delle metastasi epatiche da carcinoma del colon-retto.

In patients with colorectal liver metastases, hepatic resection is the treatment of choice, and the 5-year overall survival rate after surgery is now approaching 60%. The multidisciplinary and multimodality approaches that may include preoperative systemic chemotherapy, and the recent innovative surgical techniques that may include complex ultrasound guided hepatic resection, have enabled a large proportion of patients to undergo potentially curative treatment. The definition of resectability has shifted from a focus on tumor characteristics, such as tumor number and size, to determination whether both intrahepatic and extrahepatic disease can be completely resected, and whether such an approach is appropriate from an oncological standpoint. Hepatobiliary surgeons and medical oncologists should work together to evaluate patients with colorectal liver metastases to individualize the treatment strategy to maximize the chances of long-term survival.

Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome.

BACKGROUND: This study evaluated the safety of portal vein embolization (PVE), its impact on future liver remnant (FLR) volume and regeneration, and subsequent effects on outcome after liver resection. METHODS: Records of 112 patients were reviewed. Standardized FLR (sFLR) and degree of hypertrophy (DH; difference between the sFLR before and after PVE), complications and outcomes were analysed to determine cut-offs that predict postoperative hepatic dysfunction. RESULTS: Ten (8.9 per cent) of 112 patients had PVE-related complications. Postoperative complications occurred in 34 (44 per cent) of 78 patients who underwent hepatic resection and the 90-day mortality rate was 3 per cent. A sFLR of 20 per cent or less after PVE or DH of not more than 5 per cent (versus sFLR greater than 20 per cent and DH above 5 per cent) had a sensitivity of 80 per cent and a specificity of 94 per cent in predicting hepatic dysfunction. Overall, major and liver-related complications, hepatic dysfunction or insufficiency, hospital stay and 90-day mortality rate were significantly greater in patients with a sFLR of 20 per cent or less or DH of not more than 5 per cent compared with patients with higher values. CONCLUSION: DH contributes prognostic information additional to that gained by volumetric evaluation in patients undergoing PVE.

Ultrasonographically guided surgical approach to liver tumours involving the hepatic veins close to the caval confluence.

BACKGROUND: Intraoperative ultrasonography (IOUS) may allow a more conservative procedure in patients with liver tumours involving a hepatic vein at the caval confluence. The aim of this study was to determine whether IOUS and colour Doppler IOUS might reduce the rate of major hepatectomy and vascular reconstruction in patients with such tumours. METHODS: Of 133 consecutive patients with a liver tumour who underwent hepatectomy, 22 had involvement of a hepatic vein at the caval confluence. The surgical strategy employed was determined by IOUS findings of the relationship between the tumour and hepatic vein, the presence of accessory veins, and portal flow as measured by colour Doppler IOUS following clamping of the hepatic vein to be resected. Mortality, morbidity, major resection, hepatic vein reconstruction and local recurrence rates were evaluated. RESULTS: There were no hospital deaths and only one patient suffered major morbidity. Although hepatic vein resection was performed in 15 patients, only two underwent major hepatectomy and none had vascular reconstruction. No patients had tumour recurrence at a mean follow-up of 23 months. CONCLUSION: IOUS allowed sparing of the liver parenchyma without tumour recurrence in most patients with a tumour involving a hepatic vein at the caval confluence, avoiding more extensive hepatectomy or vascular reconstruction.

Liver resection for primary hepatic neuroendocrine tumours: report of three cases and review of the literature.

Primary neuroendocrine tumours are rare especially in the liver, which is more often site of metastatic tumours. We report three cases of primary hepatic neuroendocrine tumours, which underwent hepatic resection. Review of the diagnostic and therapeutic approaches to these tumours are discussed.

Utility of the hooking technique for cases of major hepatectomy.

Currently, resective hepatic surgery should be considered an echoguided surgical procedure to guarantee conservative but radical resections. A simple and original technique guided by intraoperative ultrasonography, termed the "hooking technique," had been described previously. It enables the ligation sites of the intrahepatic vessels during systematic segmentectomy to be chosen precisely. This report describes a further application of this technique to allow safe ligation of portal vein main branches invaded by tumor thrombi during major hepatectomies.

Technical tricks for radical but conservative liver resection. The ultrasound guidance.

Rate of major resection is still high in most surgical institutions due to fear of incomplete tumor removal: this is in spite mortality and major morbidity of major hepatectomies, particularly in cirrhotic are still not negligible. Intraoperative ultrasonography (IOUS), when used not only for tumor staging but also for resection guidance, minimises the rate of major hepatectomies maintaining treatment radicality. Maintaining this policy, the rate of major resection in our experience is 15% if major hepatectomy is classified as removal of at least 1 sector or 2 adjacent segments, and 5% if we consider major resections only those which include at least 3 segments. This policy has allowed us a safe surgical approach with no mortality and minimal major morbidity and effective local treatment with no tumor relapses at the site of the resection after a mean follow-up of 18 months. Tricks for safe and radical IOUS-guided liver resections are here discussed.

Radiofrequency of hepatocellular carcinoma in patients with liver cirrhosis: a critical appraisal of the laparoscopic approach.

BACKGROUND: The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are operative candidates. Percutaneous radiofrequency interstitial thermal ablation proved to be effective in the treatment of unresectable HCC. Recent advances in laparoscopic ultrasound have improved the accuracy in detecting small intrahepatic HCC nodules missed by preoperative imaging techniques. Our objective was to evaluate a novel operative combination of laparoscopic ultrasound with laparoscopic radiofrequency (LRF) in the treatment of HCC not amenable to liver resection. The aim of our review was to evaluate the advantages and limits of the laparoscopic approach according the criteria of the evidence-based medicine. CONCLUSIONS: LRF of HCC proved to be a safe and effective technique at least in the short and mid-term. This technique may be indicated in selected cases when the percutaneous approach to the lesion is very difficult or contraindicated.