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Sarcopenia is an age-related disease characterized by loss of muscle strength, mass and performance. Malnutrition contributes to sarcopenia pathogenesis. The aim of this systematic review is to analyze existing evidence on the efficacy of nutritional supplementation on muscle and mitochondrial health among sarcopenic or malnourished older adults. We included randomized controlled trials (RCTs) assessing the effect of branched-chain amino acid (BCAA), vitamin D and/or omega-3 polyunsaturated fatty acid (PUFA) on muscle mass, strength and performance and/or on mitochondrial activity and redox state in older sarcopenic and/or malnourished adults. The literature search was on MEDLINE, Embase and Cochrane Central, restricted to articles published in the last 10 years (2012-2022). Twelve RCTs with a total of 1337 subjects were included. BCAA with vitamin D significantly ameliorates appendicular muscle mass (4 RCTs), hand grip strength (4 RCTs), gait speed (3 RCTs), short physical performance battery (3 RCTs) or chair stand test (3 RCTs) among six out of nine RCTs. BCAA alone (2 RCTs) or PUFA (1 RCT) were not effective in improving muscle health. Mitochondrial function was significantly improved by the administration of BCAA alone (1 RCT) or in association with vitamin D (1 RCT). In conclusion, BCAA in association with vitamin D may be useful in the treatment of sarcopenia and boost mitochondrial bioenergetic and redox activity. PROSPERO CRD42022332288.

Introduction: Increasing life expectancy raises concerns whether the years gained will be spent free of disability. Lately, trends across countries have been heterogeneous. This work examined recent trends in disability-free life expectancy and life expectancy with mild  or severe disability in Switzerland., Methods: Life expectancy was estimated using national life tables, by sex and 5-year age groups. Based on Sullivan's method, disability-free life expectancy and life expectancy with disability were computed using information from the Swiss Health Survey on age- and sex-specific prevalence of mild and severe disability. Life expectancy, disability-free life expectancy and life expectancy with disability were estimated in 2007, 2012, and 2017, at 65 and 80 years of age, for both sexes., Results: Between 2007 and 2017, disability-free life expectancy at 65 and 80 years of age increased by 2.1 and 1.4 years, respectively, in men and by 1.5 and 1.1 years, respectively, in women. Meanwhile, life expectancy with mild disability decreased by 6 months in both sexes at age 65 and in men at age 80, but only 1 month in women at age 80. Life expectancy with severe disability also decreased at both ages, by approximately 6 months in women but only 2 to 3 months in men. The proportion of disability-free life expectancy increased significantly in both sexes and ages. For example, disability-free life expectancy / life expectancy at age 65 increased from 67% (95% confidence interval [CI] 66‒69) to 73% (95% CI 71‒74) in women and from 77% (95% CI 75‒79) to 82% (95% CI 81‒84) in men., Conclusion: From 2007 to 2017, disability-free life expectancy at age 65 and 80 increased in Swiss women and men. These gains outweighed those in life expectancy, reflecting some compression of morbidity.

Objective: The aim of this study was to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in Swiss non-health care employees at a moderate to high risk of exposure: bus drivers and supermarket, laundry service, and mail-sorting center employees., Methods: Data on 455 essential workers included demographics, SARS-CoV-2 exposure and use of protective measures. Anti-SARS-CoV-2 immunoglobulins G and A targeting the spike protein were measured between May and July 2020., Results: The overall crude seroprevalence estimate (15.9%; 95% confidence interval [CI], 12.6% to 19.7%) among essential workers was not significantly higher than that of the general working-age population (11.2%; 95% CI, 7.1% to 15.2%). Seroprevalence ranged from 11.9% (95% CI, 6.3% to 19.8%) among bus drivers to 22.0% (95% CI, 12.6% to 19.7%) among food supermarket employees., Conclusions: We found no significant difference in seroprevalence between our sample of essential workers and local working-age population during the first lockdown phase of the COVID-19 pandemic. Having a seropositive housemate was the strongest predictor of SARS-CoV-2 seropositivity., Competing Interests: Belloni, Dupraz, Butty, Pasquier, Estoppey, Bochud, Gonseth-Nussle, and D'Acremont have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

The management of endometriosis-related infertility is still a challenging issue. Women can be managed with either surgery or in vitro fertilization (IVF). The decision is tailored to the patients considering pros and cons of both approaches. Surgery might increase the chances of natural conception and relieve symptoms. IVF may be more effective, but costs are higher and unoperated women face some peculiar additional risks during the procedure and pregnancy. The unavailability of randomized trials comparing the two strategies hampers the possibility to provide precise estimates. This Randomized Controlled Trial (RCT) aims at filling this gap. This is a multicenter, non-blinded, randomized controlled trial with parallel groups and allocation 1:1. Three Italian Academic Infertility Units will be involved. Main inclusion criteria are infertility for more than one year, age less than 40 years and a sonographic diagnosis of endometriosis (ovarian endometriomas or deep peritoneal lesions). Previous IVF and previous surgery for endometriosis are exclusion criteria. Women will be randomized to either surgery and then natural pregnancy seeking or a standard program of three IVF cycles. The primary aim is the comparison of live birth rate between the two groups (IVF versus surgery) within one year of randomization. The secondary aim is the evaluation of cost-effective profile of the two interventions. The present study can influence the clinical practice of infertility treatment in women with endometriosis. From a public health perspective, information on the more cost-effective clinical management strategy would consent a wiser allocation of resources. Trial registration: NCT04743167, registered on 8 February 2021., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: - Dr. Somigliana reports grants from Ferring, grants and personal fees from Merck-Serono, grants and personal fees from Theramex, OUTSIDE the submitted work.

We have combined an anterior segment (AS) optical coherence tomography (OCT) system and a wavefront-based aberrometer with an approach that senses ocular wavefront aberrations using the OCT beam. Temporal interlacing of the OCT and aberrometer channels allows for OCT images and refractive error measurements to be acquired continuously and in real-time. The system measures refractive error with accuracy and precision comparable to that of clinical autorefractors. The proposed approach provides a compact modular design that is suitable for integrating OCT and wavefront-based autorefraction within the optical head of the ophthalmic surgical microscope for guiding cataract surgery or table-top devices for simultaneous autorefraction and ocular biometry., Competing Interests: The University of Miami and some of the authors (MR, FM, JMP and HD) stand to benefit from intellectual property in the technology used in this study., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

This study investigated whether fear of falling (FOF) measured by two different instruments, the Falls Efficacy Scale-International (FES-I) and the single question on FOF and activity restriction (SQ-FAR), is associated with mortality at 6-year follow-up. Participants ( n  = 1359, 58.6% women) were community-dwelling persons enrolled in the Lausanne cohort 65 + , aged 66 to 71 years at baseline. Covariables assessed at baseline included demographic, cognitive, affective, functional and health status, while date of death was obtained from the office in charge for population registration. Unadjusted Kaplan Meyer curves were performed to show the survival probability for all-cause mortality according to the degree of FOF reported with FES-I and SQ-FAR, respectively. Bivariable and multivariable Cox regression analyses were performed to assess hazard ratios, using time-in-study as the time scale variable and adjusting for variables significantly associated in bivariable analyses. During the 6-year follow-up, 102 (7.5%) participants died. Reporting the highest level of fear at FES-I (crude HR 3.86, 95% CI 2.37-6.29, P  < .001) or "FOF with activity restriction" with SQ-FAR (crude HR 2.42, 95% CI 1.44-4.09, P  = .001) were both associated with increased hazard of death but these associations did not remain significant once adjusting for gender, cognitive, affective and functional status. As a conclusion, although high FOF and related activity restriction, assessed with FES-I and SQ-FAR, identifies young-old community-dwelling people at increased risk of 6-year mortality, this association disappears when adjusting for potential confounders. As a marker of negative health outcomes, FOF should be screened for in order to provide personalized care and reduce subsequent risks., Competing Interests: Conflicts of interestAll the authors- Giulia Belloni, Christophe Büla, Brigitte Santos-Eggimann, Yves Henchoz, Sarah Fustinoni, Laurence Seematter-Bagnoud- report no conflict of interest., (© The Author(s) 2021.)

Objective: To examine the relationship between falls efficacy and the change in gait speed and functional status in older patients undergoing postacute rehabilitation., Design: Prospective cohort study., Setting: Postacute rehabilitation facility., Participants: Patients (N=180) aged 65 years and older (mean age ± SD, 81.3±7.1y)., Interventions: Not applicable., Main Outcome Measures: Data on demographics; functional, cognitive, and affective status; and falls efficacy using a 10-item version of the Falls Efficacy Scale (FES; range, 0-100) were collected upon admission. Data about gait speed and functional status (Barthel Index and Basic Activities of Daily Living [BADL]) were measured at admission and discharge. In addition, BADL performance was self-reported 1 month after discharge., Results: Compared with admission, all rehabilitation outcomes improved at discharge: gait speed (0.41±0.15 m/s vs 0.50±0.16 m/s; P<.001), Barthel Index score (68.4±16.3 vs 82.5±13.6; P<.001), and BADL (3.5±1.6 vs 4.7±1.3; P<.001). Adjusting for baseline status and other potential confounders, baseline FES independently predicted gait speed (adjusted coefficient: 0.002; 95% confidence interval [CI], 0.000-0.004; P=.025) and Barthel index (adjusted coefficient: 0.225; 95% CI, 0.014-0.435; P=.037) at discharge, with higher confidence at baseline predicting greater improvement. Baseline FES was also independently associated with self-reported BADL performance at the 1-month follow-up (adjusted coefficient: 0.020; 95% CI, 0.010-0.031; P<.001)., Conclusions: In older patients, higher falls efficacy predicted better gait and functional rehabilitation outcomes, independently of baseline performance. These results suggest that interventions aiming at falls efficacy improvement during rehabilitation might also contribute to enhancing gait speed and functional status in patients admitted to this setting., (Copyright © 2021 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Fear of falling (FOF) is common in older people and is related to negative outcomes. This study aimed to investigate whether 2 different instruments, the Falls Efficacy Scale-International (FES-I) and the single question on FOF and activity restriction (SQ-FAR), were associated with incident disability at 3 years., Design: Prospective observational study., Setting and Participants: Participants (n = 1219, 57.4% women) were disability-free community-dwelling persons enrolled in the Lausanne cohort 65+, aged 66 to 71 years, in 2005., Measures: Baseline covariates included demographic, cognitive, affective, and health status. Basic activities of daily living (BADL) assessment was recorded annually from a self-administered questionnaire. Disability outcome was defined as reporting difficulty or help needed in ≥1 of 5 BADL in ≥2 consecutive years, or being institutionalized during follow-up., Results: At 3 years, disability was reported by 77 participants (6.3%). Reporting the highest level of fear at FES-I [adjusted odds ratio (aOR) 5.14, 95% confidence interval (CI) 1.82-14.55, P = .002] or "FOF with activity restriction" with SQ-FAR (aOR 3.23, 95% CI 1.29-8.08, P = .012) were both associated with increased odds of disability even after adjusting for covariates. The FES-I model explained incident disability slightly better than the SQ-FAR one [Bayesian information criterion (BIC) values of 466.70 and 469.43, respectively]., Conclusions and Implications: High FOF and related activity restriction, assessed with FES-I and SQ-FAR, are associated with incident disability in young-old community-dwelling people. The SQ-FAR is suitable as a screening tool to proactively detect a potentially reversible risk factor for disability. Using the FES-I may serve additional clinical purposes, such as FOF characterization and management., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Fear of falling (FOF) is common in older persons and related to negative outcomes. This study aimed to investigate the relationship between 2 FOF measures: the Falls Efficacy Scale-International (FES-I) and the single question on FOF and activity restriction (SQ-FAR). Factors associated with disagreement between the 2 measures were further examined., Design: Cross-sectional study., Setting and Participants: Participants (N = 1359) were community-dwelling persons aged 65 to 70 years who were enrolled in the Lausanne cohort 65+., Methods: Data included demographic, functional, cognitive, affective, and health status. FOF was measured with FES-I and the 3-level SQ-FAR (no FOF, FOF without activity restriction (AR, FOF with AR). FES-I concern about falling was categorized as low (score 16-19), moderate (score 20-27), and high (score 28-64)., Results: Weighted agreement between the FES-I and the SQ-FAR was 87.8% (Kappa = 0.57). Using the FES-I as gold standard, the performance of SQ-FAR was good (specificity 86%; sensitivity 74%, negative predicting value 89%, positive predicting value 69%). Among participants with moderate/high FOF according to FES-I, male sex (P = .011) and the absence of previous falls (P < .001) were associated with disagreement between the 2 tools. Among participants with low FOF, female sex (P = .005), falls history (P < .001), and pre-frailty/frailty status (P = .050) were associated with disagreement., Conclusions and Implications: The SQ-FAR has a moderate agreement with FES-I and might be used as a screening tool. The results also may help design a step-by-step strategy to evaluate and address FOF in the clinical setting., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Frailty is a clinical condition characterized by the individual's increased vulnerability to endogenous and exogenous stressors. It is determined by the reduction of homeostatic capacities of the organism and responsible for a marked risk of adverse health outcomes (including functional loss and mortality). Frailty originates from the geriatric background and may pave the way toward a model of care centered on the person, deviating from the traditional and obsolete disease-focused approach. Unfortunately, many controversies have affected the field of frailty over the years and ambiguities have been growing. In particular, the common use of frailty as condition to "exclude" from interventions is a worrisome trend. In fact, the detection of frailty should instead represent the entry point for a more in-depth analysis with the aim of identifying the causes of individual's increased vulnerability and implementing a person-tailored intervention plan. With the aim of promoting a more comprehensive and appropriate assessment of the aging population, the World Health Organization introduced the concept of intrinsic capacity (IC), defined as the composite of all physical and mental capacities that an individual can draw upon during his/her life. Frailty and IC are two constructs stemming from the same need of overcoming traditional medical paradigms that negatively impact on the correct way clinical and research practice should be conducted in older persons. In this article, we describe the similarities and differences between the two constructs, highlighting how geriatric medicine contributed to their development and will be crucial for their further integration in future healthcare models.

Background: Contrary to the most credited theories on laser therapy that see power/energy as the major factors to its effectiveness, a technique using an extremely low power/energy laser stimulation to treat musculoskeletal pain and dysfunction is proposed. The stimulus consists of a 20 s train of modulated pulses with an average power below 0.02 mW and is applied on sequences of acupuncture points selected according to the impaired segment of the patient's body. Methods : Modifications on the extracellular soft tissue matrix and on the "fascia" were sonographically demonstrated. Laboratory and clinical tests confirmed the effectiveness. Results : Responses similar to those experienced in acupuncture were observed. The device-a CE Class IIa certified medical device named Libralux-affords a clinically proven effectiveness exceeding 80% in the treatment of musculoskeletal conditions and associated motor dysfunctions. An average of just three application sessions was generally sufficient to overcome the dysfunction. Conclusions : The development of the method is supported by over 20 years of R&D activities, with a range of experiments discussed in several papers published in indexed peer-reviewed journals. A few considerations regarding the possible physiological action mechanisms involved are proposed in this paper.

An 81-year-old woman was hospitalised for behavioural disorders that had been progressively emerging over a period of few weeks. The symptoms appeared to worsen over time. A diagnosis of vascular dementia, complicated by psychosis, was initially hypothesised. The inefficacy of the antipsychotic/benzodiazepine medications used, along with the presence of hypertension, hypokalaemia and metabolic alkalosis (resistant to pharmacological attempts of correction), as well as the hirsutism and the development of several infections, led us to consider Cushing's syndrome. Endocrinological analysis suggested ectopic adrenocorticotropic hormone (ACTH) secretion. Although endogenous Cushing's syndrome is rare in older people, it should always be considered among the differential diagnosis of behavioural disorders.

The aim of the current study is to investigate the integrity of the Mirror Neurons (MN) network in normal aging, Mild Cognitive Impairment (MCI), and Alzheimer disease (AD). Although AD and MCI are considered "cognitive" diseases, there has been increasing recognition of a link between motor function and AD. More recently the embodied cognition hypothesis has also been developed: it postulates that a part of cognition results from the coupling between action and perception representations. MN represent a neuronal population which links perception, action, and cognition, therefore we decided to characterize MN functioning in neurodegenerative cognitive decline. Three matched groups of 16 subjects (normal elderly-NE, amnesic MCI with hippocampal atrophy and AD) were evaluated with a focused neuropsychological battery and an fMRI task specifically created to test MN: that comprised of an observation run, where subjects were shown movies of a right hand grasping different objects, and of a motor run, where subjects observed visual pictures of objects oriented to be grasped with the right hand. In NE subjects, the conjunction analysis (comparing fMRI activation during observation and execution), showed the activation of a bilateral fronto-parietal network in "classical" MN areas, and of the superior temporal gyrus (STG). The MCI group showed the activation of areas belonging to the same network, however, parietal areas were activated to a lesser extent and the STG was not activated, while the opposite was true for the right Broca's area. We did not observe any activation of the fronto-parietal network in AD participants. They did not perform as well as the NE subjects in all the neuropsychological tests (including tests of functions attributed to MN) whereas the MCI subjects were significantly different from the NE subjects only in episodic memory and semantic fluency. Here we show that the MN network is largely preserved in aging, while it appears involved following an anterior-posterior gradient in neurodegenerative decline. In AD, task performance decays and the MN network appears clearly deficient. The preservation of the anterior part of the MN network in MCI could possibly supplement the initial decay of the posterior part, preserving cognitive performance.

Congenital disorders of glycosylation (CDG) comprise a family of human multisystemic diseases caused by recessive mutations in genes required for protein N-glycosylation. More than 100 distinct forms of CDGs have been identified and most of them cause severe neurological impairment. The Conserved Oligomeric Golgi (COG) complex mediates tethering of vesicles carrying glycosylation enzymes across the Golgi cisternae. Mutations affecting human COG1, COG2 and COG4-COG8 cause monogenic forms of inherited, autosomal recessive CDGs. We have generated a Drosophila COG7-CDG model that closely parallels the pathological characteristics of COG7-CDG patients, including pronounced neuromotor defects associated with altered N-glycome profiles. Consistent with these alterations, larval neuromuscular junctions of Cog7 mutants exhibit a significant reduction in bouton numbers. We demonstrate that the COG complex cooperates with Rab1 and Golgi phosphoprotein 3 to regulate Golgi trafficking and that overexpression of Rab1 can rescue the cytokinesis and locomotor defects associated with loss of Cog7 . Our results suggest that the Drosophila COG7-CDG model can be used to test novel potential therapeutic strategies by modulating trafficking pathways., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Cytokinesis requires a tight coordination between actomyosin ring constriction and new membrane addition along the ingressing cleavage furrow. However, the molecular mechanisms underlying vesicle trafficking to the equatorial site and how this process is coupled with the dynamics of the contractile apparatus are poorly defined. Here we provide evidence for the requirement of Rab1 during cleavage furrow ingression in cytokinesis. We demonstrate that the gene omelette (omt) encodes the Drosophila orthologue of human Rab1 and is required for successful cytokinesis in both mitotic and meiotic dividing cells of Drosophila melanogaster We show that Rab1 protein colocalizes with the conserved oligomeric Golgi (COG) complex Cog7 subunit and the phosphatidylinositol 4-phosphate effector GOLPH3 at the Golgi stacks. Analysis by transmission electron microscopy and 3D-SIM super-resolution microscopy reveals loss of normal Golgi architecture in omt mutant spermatocytes indicating a role for Rab1 in Golgi formation. In dividing cells, Rab1 enables stabilization and contraction of actomyosin rings. We further demonstrate that GTP-bound Rab1 directly interacts with GOLPH3 and controls its localization at the Golgi and at the cleavage site. We propose that Rab1, by associating with GOLPH3, controls membrane trafficking and contractile ring constriction during cytokinesis., (© 2017 The Authors.)

Cytokinesis separates the cytoplasmic organelles and the duplicated genome into two daughter cells at the end of cell division. In animal cell cytokinesis, assembly and constriction of the contractile apparatus must be finely coordinated with plasma membrane remodeling and vesicle trafficking at the cleavage furrow. Accurate control of these events during cell cleavage is a fundamental task in all organisms and is also essential for maintaining ploidy and preventing neoplastic transformation. Drosophila male meiosis provides a well-suited cell system for exploring the molecular mechanisms underlying cytokinesis, combining the powerful tools of Drosophila genetics with unique cytological characteristics. Remarkably the large size of male meiotic cells highly facilitates cytological analysis of cytokinesis. Here we describe the main procedures that we use for fixing and visualizing cleavage furrow proteins in male meiotic cells. Moreover, we detail our protocol to detect protein interactions in fixed dividing spermatocytes by applying in situ proximity ligation assay., (Copyright © 2017 Elsevier Inc. All rights reserved.)

After an excursus on state-of-the-art knowledge for low-level laser therapy (LLLT), Biolite, a patented ultra-low-level laser therapy device used to treat musculoskeletal pain and associated impairments, is presented. The application protocols include short stimulation of sequences of acupuncture points. The observed effects seem, however, to be far from those that might be expected after acupuncture. The primary effect seems more likely to be an extracellular soft-tissue matrix reaction. The development of the technique, the studies performed, and the evidence collected over > 10 years suggest that specifically modulated laser light can interact with human tissues at light fluences well under those previously considered as being capable of having any effect. Musculoskeletal pain very often becomes an autonomous dysfunction that is independent of the original injury and that can be effectively treated using specific peripheral acupuncture-like stimulation. Because such acupuncture is capable of reducing motor control "interferences" from noxious stimuli, it can improve motor control performance, thereby reducing the risk of falls in the elderly individuals. The proposal of acupuncture-derived protocols to be applied by Western physiotherapists using an ultra-low-level laser therapy device is a further "bridge" between two different, and sometimes very different, clinical worlds to better serve our patients., (Copyright © 2015. Published by Elsevier B.V.)

The highly conserved Golgi phosphoprotein 3 (GOLPH3) protein, a component of Trans-Golgi Network (TGN), has been defined as a "first-in-class Golgi oncoprotein" and characterized as a Phosphatidylinositol 4-phosphate [PI(4)P] effector at the Golgi. GOLPH3 is commonly amplified in several solid tumors. Furthermore this protein has been associated with poor prognosis in many cancers. Highly conserved from yeast to humans, GOLPH3 provides an essential function in vesicle trafficking and Golgi structure. Recent data have also implicated this oncoprotein in regulation of cytokinesis, modulation of mitochondrial mass and cellular response to DNA damage. A minute dissection of the molecular pathways that require GOLPH3 protein will be helpful to develop new therapeutic cancer strategies.

Cytokinesis is an intricate process that requires an intimate interplay between actomyosin ring constriction and plasma membrane remodelling at the cleavage furrow. However, the molecular mechanisms involved in coupling the cytoskeleton dynamics with vesicle trafficking during cytokinesis are poorly understood. The highly conserved Golgi phosphoprotein 3 (GOLPH3), functions as a phosphatidylinositol 4-phosphate (PI4P) effector at the Golgi. Recent studies have suggested that GOLPH3 is up-regulated in several cancers and is associated with poor prognosis and more aggressive tumours. In Drosophila melanogaster, GOLPH3 localizes at the cleavage furrow of dividing cells, is required for successful cytokinesis and acts as a key molecule in coupling phosphoinositide (PI) signalling with actomyosin ring dynamics. Because cytokinesis failures have been linked with pre-malignant disease and cancer, the novel connection between GOLPH3 and cytokinesis imposes new fields of investigation in cancer biology and therapy.

The highly conserved Golgi phosphoprotein 3 (GOLPH3) protein has been described as a Phosphatidylinositol 4-phosphate [PI(4)P] effector at the Golgi. GOLPH3 is also known as a potent oncogene, commonly amplified in several human tumors. However, the molecular pathways through which the oncoprotein GOLPH3 acts in malignant transformation are largely unknown. GOLPH3 has never been involved in cytokinesis. Here, we characterize the Drosophila melanogaster homologue of human GOLPH3 during cell division. We show that GOLPH3 accumulates at the cleavage furrow and is required for successful cytokinesis in Drosophila spermatocytes and larval neuroblasts. In premeiotic spermatocytes GOLPH3 protein is required for maintaining the organization of Golgi stacks. In dividing spermatocytes GOLPH3 is essential for both contractile ring and central spindle formation during cytokinesis. Wild type function of GOLPH3 enables maintenance of centralspindlin and Rho1 at cell equator and stabilization of Myosin II and Septin rings. We demonstrate that the molecular mechanism underlying GOLPH3 function in cytokinesis is strictly dependent on the ability of this protein to interact with PI(4)P. Mutations that abolish PI(4)P binding impair recruitment of GOLPH3 to both the Golgi and the cleavage furrow. Moreover telophase cells from mutants with defective GOLPH3-PI(4)P interaction fail to accumulate PI(4)P-and Rab11-associated secretory organelles at the cleavage site. Finally, we show that GOLPH3 protein interacts with components of both cytokinesis and membrane trafficking machineries in Drosophila cells. Based on these results we propose that GOLPH3 acts as a key molecule to coordinate phosphoinositide signaling with actomyosin dynamics and vesicle trafficking during cytokinesis. Because cytokinesis failures have been associated with premalignant disease and cancer, our studies suggest novel insight into molecular circuits involving the oncogene GOLPH3 in cytokinesis.

The conserved oligomeric Golgi (COG) complex plays essential roles in Golgi function, vesicle trafficking and glycosylation. Deletions in the human COG7 gene are associated with a rare multisystemic congenital disorder of glycosylation that causes mortality within the first year of life. In this paper, we characterise the Drosophila orthologue of COG7 (Cog7). Loss-of-function Cog7 mutants are viable but male sterile. The Cog7 gene product is enriched in the Golgi stacks and in Golgi-derived structures throughout spermatogenesis. Mutations in the Cog7 gene disrupt Golgi architecture and reduce the number of Golgi stacks in primary spermatocytes. During spermiogenesis, loss of the Cog7 protein impairs the assembly of the Golgi-derived acroblast in spermatids and affects axoneme architecture. Similar to the Cog5 homologue, four way stop (Fws), Cog7 enables furrow ingression during cytokinesis. We show that the recruitment of the small GTPase Rab11 and the phosphatidylinositol transfer protein Giotto (Gio) to the cleavage site requires a functioning wild-type Cog7 gene. In addition, Gio coimmunoprecipitates with Cog7 and with Rab11 in the testes. Our results altogether implicate Cog7 as an upstream component in a gio-Rab11 pathway controlling membrane addition during cytokinesis.

Cytokinesis separates the cytoplasm and the duplicated genome into two daughter cells at the end of cell division. This process must be finely regulated to maintain ploidy and prevent tumor formation. Drosophila male meiosis provides an excellent cell system for investigating cytokinesis. Mutants affecting this process can be easily identified and spermatocytes are large cells particularly suitable for cytological analysis of cytokinetic structures. Over the past decade, the powerful tools of Drosophila genetics and the unique characteristics of this cell system have led researchers to identify molecular players of the cell cleavage machinery and to address important open questions. Although spermatocyte cytokinesis is incomplete, resulting in formation of stable intercellular bridges, the molecular mechanisms are largely conserved in somatic cells. Thus, studies of Drosophila male meiosis will shed new light on the complex cell circuits regulating furrow ingression and substantially further our knowledge of cancer and other human diseases.

Rab11 is a small GTPase that regulates several aspects of vesicular trafficking. Here, we show that Rab11 accumulates at the cleavage furrow of Drosophila spermatocytes and that it is essential for cytokinesis. Mutant spermatocytes form regular actomyosin rings, but these rings fail to constrict to completion, leading to cytokinesis failures. rab11 spermatocytes also exhibit an abnormal accumulation of Golgi-derived vesicles at the telophase equator, suggesting a defect in membrane-vesicle fusion. These cytokinesis phenotypes are identical to those elicited by mutations in giotto (gio) and four wheel drive (fwd) that encode a phosphatidylinositol transfer protein and a phosphatidylinositol 4-kinase, respectively. Double mutant analysis and immunostaining for Gio and Rab11 indicated that gio, fwd, and rab11 function in the same cytokinetic pathway, with Gio and Fwd acting upstream of Rab11. We propose that Gio and Fwd mediate Rab11 recruitment at the cleavage furrow and that Rab11 facilitates targeted membrane delivery to the advancing furrow.

Study Design: Randomized controlled trial., Objectives: To establish whether the use of mechanical insufflation/exsufflation leads to a significant improve in tracheostomy subjects with upper spinal cord injuries (C1-C7), ASIA classification grade A and bronchial hyper secretion the following parameters: forced vital capacity (FVC), forced exspiratory volume on the first second (FEV1), FEV1/FVC, peak exspiratory flow (PEF), arterious pressure of O(2) (Pa O(2)), arterious pressure of CO(2) (Pa CO(2)), pH, saturation of O(2) (Sa O(2))., Setting: Spinal Cord Unit, Montecatone Rehabilitation Institute, Imola, Italy., Methods: The patients were split into two groups: the experimental group (EG) and the control group (CG). Each patient was given 10 treatments: the EG was given manual respiratory kinesitherapy associated with mechanical insufflation/exsufflation with inhale and exhale pressure between 15 cm H(2)O and 45 cm H(2)O, while the CG was only given manual kinesitherapy. The treatment sessions covered the necessary amount of time in order to achieve sufficient clearance. The study has been approved by the local ethic committee. The patients were informed before being enrolled in that study and gave their written consent., Results: At the end of the treatment associated with the mechanical insufflation/exsufflation, the EG showed a significant increase in FVC, FEV1 and PEF, although it was not possible to compare the latter with the CG. The other parameters were also subject to variations, although not statistically significant. The CG did not show signs of any significant change., Conclusion: The use of mechanical insufflation/exsufflation in subjects with the aforementioned characteristics is shown to be an effective adjunct to manual respiratory kinesitherapy, since it makes it possible to achieve adequate bronco-pulmonary clearance, even removing thick, deep secretions and making it possible to insufflate any areas affected by atelectasis.

A male patient, 29 years old, was admitted to our unit with purpura fulminans, coagulation deficiency, renal failure and subsequent septic shock accompanied by respiratory insufficiency in the absence of meningeal signs. The serum levels of endogenous protein C, ATIII and calcium were well below the norm. The bacteriological examination revealed the presence of gram-negative diplococci. The onset of adult respiratory distress syndrome (ARDS) revealed aa early complication of the meningococcal sepsis. Forty-eight hours after being admitted, the recombinant protein C infusion was started at a dose of 24 microg/kg/h for the duration of 96 h. The skin lesions regressed, starting from the ecchymosis and the edema of the face, trunk and auricular pavilions. A week after the onset of the symptomatology the chest X-ray appeared clear, the renal function had normalised, and the signs of shock had disappeared.

Background and Purpose: Heparin is widely used for acute stroke to prevent thrombus propagation and/or multiple emboli generation, although there is, as yet, no demonstrated efficacy. However, all of the available clinical studies allowed long intervals from stroke to treatment. The purpose of this study was to try an intravenous regimen of unfractionated heparin the acute cerebral infarction starting treatment within the first 3 hours of the onset of symptoms., Methods: The study was an outcome evaluator-blind design trial. Patients had to display signs of a nonlacunar hemispheric infarction. Selected patients were randomly allocated to receive intravenous heparin sodium or saline. Heparin was infused at a rate to maintain activated partial thromboplastin time ratio 2.0 to 2.5 x control for 5 days. The primary end point was recovery of a modified Rankin score zero to 2 at 90 days of stroke at phone interview by a single physician blind to treatment. Safety end points were death, symptomatic intracranial hemorrhages, and major extracranial bleedings by 90 days of stroke., Results: A total of 418 stroke patients were included. In the heparin group, there were more self-independent patients (38.9% versus 28.6%; P=0.025). In addition, in the same group, there were fewer deaths (16.8% versus 21.9%; P=0.189), more symptomatic brain hemorrhages (6.2% versus 1.4%; P=0.008), and more major extracerebral bleedings (2.9% versus 1.4%; P=0.491)., Conclusions: Intravenous heparin sodium could be of help in the earliest treatment of acute nonlacunar hemispheric cerebral infarction, even keeping into account an increased frequency of intracranial symptomatic brain hemorrhages.

Context: Hypoxemia complicates the recovery of 30% to 50% of patients after abdominal surgery; endotracheal intubation and mechanical ventilation may be required in 8% to 10% of cases, increasing morbidity and mortality and prolonging intensive care unit and hospital stay., Objective: To determine the effectiveness of continuous positive airway pressure compared with standard treatment in preventing the need for intubation and mechanical ventilation in patients who develop acute hypoxemia after elective major abdominal surgery., Design and Setting: Randomized, controlled, unblinded study with concealed allocation conducted between June 2002 and November 2003 at 15 intensive care units of the Piedmont Intensive Care Units Network in Italy., Patients: Consecutive patients who developed severe hypoxemia after major elective abdominal surgery. The trial was stopped for efficacy after 209 patients had been enrolled., Interventions: Patients were randomly assigned to receive oxygen (n = 104) or oxygen plus continuous positive airway pressure (n = 105)., Main Outcome Measures: The primary end point was incidence of endotracheal intubation; secondary end points were intensive care unit and hospital lengths of stay, incidence of pneumonia, infection and sepsis, and hospital mortality., Results: Patients who received oxygen plus continuous positive airway pressure had a lower intubation rate (1% vs 10%; P = .005; relative risk [RR], 0.099; 95% confidence interval [CI], 0.01-0.76) and had a lower occurrence rate of pneumonia (2% vs 10%, RR, 0.19; 95% CI, 0.04-0.88; P = .02), infection (3% vs 10%, RR, 0.27; 95% CI, 0.07-0.94; P = .03), and sepsis (2% vs 9%; RR, 0.22; 95% CI, 0.04-0.99; P = .03) than did patients treated with oxygen alone. Patients who received oxygen plus continuous positive airway pressure also spent fewer mean (SD) days in the intensive care unit (1.4 [1.6] vs 2.6 [4.2], P = .09) than patients treated with oxygen alone. The treatments did not affect the mean (SD) days that patients spent in the hospital (15 [13] vs 17 [15], respectively; P = .10). None of those treated with oxygen plus continuous positive airway pressure died in the hospital while 3 deaths occurred among those treated with oxygen alone (P = .12)., Conclusion: Continuous positive airway pressure may decrease the incidence of endotracheal intubation and other severe complications in patients who develop hypoxemia after elective major abdominal surgery.

MAS063D (Atopiclair is a hydrolipidic cream that has been developed for the management of atopic dermatitis (AD). The putative active ingredients of MAS063D are hyaluronic acid, telmesteine, Vitis vinifera, glycyrrhetinic acid. A five-week study in 30 adult patients with mild to moderate AD showed that MAS063D offered significant benefits over a vehicle-only control. MAS063D improved the total body area affected (17.2% --> 13.2%, p < 0.001), itch score (2.7 --> 1.3 on a 10-point scale, p = 0.001) and EASI score (28.3 --> 24.3, p = 0.024) after 22 days treatment compared to baseline. The patients' opinion of MAS063D (patient's view of itch control, and view of study substance) was rated by participating patients as significantly better than control (p = 0.008, p = 0.042 respectively). Based on these preliminary results in a small scale study, it is suggested that MAS063D is a possible new treatment option for improving signs and symptoms in adults with mild to moderate AD.

We performed a functional analysis of fascetto (feo), a Drosophila gene that encodes a protein homologous to the Ase1p/PRC1/MAP65 conserved family of microtubule-associated proteins (MAPs). These MAPs are enriched at the spindle midzone in yeast and mammals and at the fragmoplast in plants, and are essential for the organization and function of these microtubule arrays. Here we show that the Feo protein is specifically enriched at the central-spindle midzone and that its depletion either by mutation or by RNAi results in aberrant central spindles. In Feo-depleted cells, late anaphases showed normal overlap of the antiparallel MTs at the cell equator, but telophases displayed thin MT bundles of uniform width instead of robust hourglass-shaped central spindles. These thin central spindles exhibited diffuse localizations of both the Pav and Asp proteins, suggesting that these spindles comprise improperly oriented MTs. Feo-depleted cells also displayed defects in the contractile apparatus that correlated with those in the central spindle; late anaphase cells formed regular contractile structures, but these structures did not constrict during telophase, leading to failures in cytokinesis. The phenotype of Feo-depleted telophases suggests that Feo interacts with the plus ends of central spindle MTs so as to maintain their precise interdigitation during anaphase-telophase MT elongation and antiparallel sliding.

Ultrasonography is the most commonly used screening modality for focal liver lesions in Europe. Over the past few years, to overcome the inherent limitations of B-mode imaging and colour-Doppler ultrasound in identifying and characterising focal liver lesions, intravenous agents capable of enhancing the ultrasound signal emitted by vascular and parenchymal structures have been developed. From December 1999 to December 2001, about 400 patients with a known tumour, HCV-related chronic cirrhotic liver disease, or with an indeterminate focal liver lesion discovered incidentally were evaluated by ultrasound of the liver parenchyma both in baseline conditions and after administration of contrast material. The ultrasound contrast agents used were: SonoVue (Bracco, Milan-Italy) and Optison (Mallinckrodt, London - UK). Our experience is based on low mechanical-index contrast-enhanced imaging, which acts conservatively, performed with different commercially available algorithms, in grey-scale mode alone (B-mode). We report the morphological patterns displayed by the main benign and malignant liver lesions after the administration of second-generation ultrasound contrast material, and review the main imaging patterns able to provide effective and practical guidance in formulating a diagnosis of benignity or malignancy. Our clinical experience confirmed the literature findings that the introduction of low mechanical index methods in grey-scale imaging has allowed qualitatively better results for detecting and characterising focal liver lesions than those obtained with baseline and colour-Doppler imaging. The ease of use, substantial repeatability and predictability of the enhancement effects obtainable with low mechanical index methods are the main reasons for the success of this approach. Broadening the scope of studies to obtain controlled data and comparisons with the other imaging modalities is crucial for the definitive validation of the method.

To face the aspects connected with VR environments usability for psychotherapeutic applications means to dare a double challenge from a methodological point of view: from one side, the need to adapt and to integrate on a heuristic basis classic usability evaluation methods to specific artefacts such as 3D Virtual Environments for clinical applications; from the other hand, the problems arisen by integration of expert evaluation of VR environments user-based tests carried out in real context of use. The theoretical background of our analytical stance is based upon an ethnomethodological approach, a perspective that gives evidence of how people, in specific social situations, are able to solve complex tasks producing shared meanings and achieving their goals during interaction. According to this perspective, the methodological objective consisted also in the identification of the usability requirements of the specific community of practice. The virtual environments considered were two of the four VR modules in the framework of the VEPSY project: Panic Disorders--Agoraphobia and Eating Disorders.

Background: We implemented a program for continuous renal replacement therapies (CRRT) in intensive care units (ICU) based on the cooperative work of dialysis and ICU personnel. Our aim was to report the main details of this program and compare its cost with that of intermittent hemodiafiltration (IHDF)., Methods: The study referred to 181 ICU patients with renal failure. We considered the costs of both technical devices and assisting personnel. CRRT was performed as continuous veno-venous hemodiafiltration (CVVHDF) (24 hr daily); dialysis and ICU nurses shared surveillance. Only dialysis nurses performed IHDF (as acetate-free biofiltration, 4 hr daily) in the ICU., Results: The daily cost of CRRT was Euro 276.70; of which 79% was for devices and 21% was for human resources. Nurse surveillance required 141 min per day, ICU nurses supplied 55% (77 min) and dialysis nurses 45% (64 min). On average, CRRT surveillance required less than 1 min/nurse/hr for both dialysis and ICU nurses. The daily cost of 4-hr IHDF sessions of was Euro 247.83, of which 44% was for technical devices and 56% was for human resources., Conclusions: The cooperation between dialysis and ICUs improved the use of human resources and allowed us to supply CRRT to all critically ill patients with acute renal failure. The expenditure for CRRT was 12% higher than that for IHDF, due to the cost of technical devices.

The present study is to be considered in the framework of the VEPSY UPDATED project, whose main objective is to prove the technical and clinical viability of using virtual reality therapy (VRT) in clinical psychology by means of portable and shared VR systems. This contribution illustrates the attempt to elaborate a new psychosocial model of usability evaluation analysis, allowing general definitions in the context of the project, by considering areas of VR not yet completely explored from the usability point of view. The theoretical background is based upon an ethnometodological approach, a perspective that gives evidence of how people, in specific social situations, are able to solve complex tasks producing shared meanings and achieving their goals during the interactions, in order to make their actions understandable and successful.

Heterochromatin has been traditionally regarded as a genomic wasteland, but in the last three decades extensive genetic and molecular studies have shown that this ubiquitous component of eukaryotic chromosomes may perform important biological functions. In D. melanogaster, about 30 genes that are essential for viability and/or fertility have been mapped to the heterochromatin of the major autosomes. Thus far, the known essential genes exhibit a peculiar molecular organization. They consist of single-copy exons, while their introns are comprised mainly of degenerate transposons. Moreover, about one hundred predicted genes that escaped previous genetic analyses have been associated with the proximal regions of chromosome arms but it remains to be determined how many of these genes are actually located within the heterochromatin. In this overview, we present available data on the mapping, molecular organization and function of known vital genes embedded in the heterochromatin of chromosomes 2 and 3. Repetitive loci, such as Responder and the ABO elements, which are also located in the heterochromatin of chromosome 2, are not discussed here because they have been reviewed in detail elsewhere.

Genetic and cytological approaches have yielded significant insight into the mapping and organization of genes located in the heterochromatin of Drosophila melanogaster. To date, only a few of these genes have been molecularly characterized in detail, and their function unveiled. As a further step towards the identification of heterochromatic gene functions, we have carried out a cytological analysis of mitotic and meiotic cell divisions in mutants carrying different allelic combinations of 1(2)41Aa, a gene located in the proximal heterochromatin of chromosome 2. Our results showed that larval brains of 1(2)41Aa mutants display a high frequency of cells with irregularly condensed chromosomes. In addition, defective chromosome condensation was detected in male meiosis, consequently affecting chromosome segregation and giving rise to irregular spermatids. Taken together, these findings indicate that 1(2)41Aa is a novel cell cycle gene required for proper chromosome condensation in both somatic and germ line cells.

Background: The differential tolerability profile of various interferon (IFN)-alpha preparations used in combination with ribavirin for the treatment of chronic hepatitis C needs to be elucidated. Approximately 8% of patients receiving recombinant IFNalpha-2b plus ribavirin discontinue treatment because of adverse events. Human leucocyte IFNalpha is deemed to have a better safety profile than recombinant IFNalpha. We therefore compared the safety profile and efficacy of ribavirin combined with leucocyte IFNalpha or with recombinant IFNalpha-2b in treatment-naive patients with chronic hepatitis C., Study Design: We randomised 423 patients to either leucocyte IFNalpha 3MU three times weekly plus ribavirin (210 patients) or the same dose of recombinant IFNalpha-2b plus ribavirin (213 patients). Patients were treated for 24 weeks and followed-up for a further 48 weeks. The primary endpoint was the safety profile of the two therapies; the secondary endpoint was the rate of sustained response., Results: In patients receiving leucocyte IFNalpha, the total number of adverse events was lower than in the group receiving recombinant IFNalpha (259 vs 441 patients), and the percentage of patients discontinuing treatment because of adverse events or laboratory abnormalities was significantly reduced (4% vs 11%; p = 0.013). Sustained response was observed in 47% of patients receiving leucocyte IFNalpha plus ribavirin and in 44% of patients receiving IFNalpha-2b plus ribavirin., Conclusions: Both therapeutic regimens were effective in inducing a sustained response in naive patients. However, the safety profile of leucocyte IFNalpha plus ribavirin was more favourable than that observed with the administration of recombinant IFNalpha-2b plus ribavirin, suggesting that leucocyte IFNalpha may be an alternative option in patients with reduced tolerability to other IFNs.

Objectives: It has been suggested that iron depletion improves the response to interferon in patients with chronic hepatitis C. We aimed to evaluate whether iron reduction by phlebotomy before interferon improves the rate of virological sustained response in previously untreated noncirrhotic patients., Methods: One hundred fourteen hepatitis C virus (HCV) RNA positive patients with hepatic iron concentrations of > or =700 microg/g dry wt (men) and > or =500 microg/g dry wt (women), stratified according to HCV genotype and gamma-glutamyltransferase values, were randomly allocated to interferon alone (6 MU three times a week) (group A) or to phlebotomy until iron depletion followed by interferon (6 MU three times a week) (group B). After 4 months dosage was reduced to 3 MU three times a week for another 8 months., Results: Virological sustained response was observed in 25 patients (22%), nine (15.8%, 95% CI = 7.5-27.9) of group A and 16 (28.1%, 95% CI = 17.0-41.6) of group B. At univariate analysis the variables associated with the response were HCV genotypes 2-3, normal gamma-glutamyltransferase, higher levels of baseline ALT, normal ALT values, and negativity for HCV-RNA at the 3rd month of therapy. At multivariate analysis, genotype and ALT levels at enrollment maintained their association with the response. A trend toward a better response to interferon was observed in patients who received phlebotomy (odds ratio = 2.32, 95% CI = 0.96-6.24, p = 0.082). Patients with hepatic iron concentration of < or = 1100 microg/g dry wt had a trend toward a higher rate of virological sustained response (p = 0.059) when submitted to treatment B., Conclusion: Iron removal by phlebotomy is able to improve the rate of response to interferon, especially in patients with lower hepatic iron deposits; it could be useful as adjuvant therapy to new therapeutic modalities.

Computed axial colonography, usually called virtual colonoscopy, is a new diagnostic method potentially useful for investigating polyps and tumors of the colon and rectum. It uses spiral axial tomography data to build up images similar to those given by conventional colonoscopy, offering advantages in that it causes no adverse reactions, and is accepted well by patients, who do not need to be sedated. Reports to date show its sensitivity and specificity vary in identifying polyps in the colon, and there are still many problems with the new method, such as its cost, its learning curve, the identification of flat lesions, and detection of extracolonic abnormalities. There is a pressing need to establish the accuracy and cost-effectiveness of virtual colonoscopy as a screening method for colorectal tumors, and for post-polypectomy surveillance.

Background: Continuity of care has been monitored rarely in Italian community mental health centres., Aims: To estimate the long-term probability of leaving care in first-contact patients attending an out-patient service, and to identify patients most likely to drop out., Method: All patients who had a first contact with the community mental health centre of Magenta during a 1-year recruitment period were followed up for 24 months. Patients who failed to return after the last out-patient visit were regarded as 'drop-outs'., Results: During the 1-year recruitment period 330 subjects were at their first contact. The 1-year incidence of first-contact patients was nearly 33 per 10 000 inhabitants. At follow-up, 46% of patients had dropped out. In comparison with patients with psychoses, subjects suffering from neurotic (P =0.004) and personality disorders (P=0.029) were more likely to drop out., Conclusions: In the Italian system of community psychiatric care nearly half of the patients are no longer in contact after 2 years. Those who stay in treatment are more likely to suffer from psychosis, suggesting a commitment of Italian out-patient facilities to tackling the needs of patients with more severe disorders.

Objective: To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2,307 patients., Results: The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P< 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P< 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P< 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2,307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P< 0.01) and a lower cumulative hazard for HCC (P< 0.01)., Conclusions: Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.

Objectives: Computed tomographic (CT) colonography or virtual colonoscopy is a new diagnostic method for the colon and rectum, developed on the basis of spiral computed axial tomography and employing virtual reality technology. The aim of this study was to determine the sensitivity, specificity, and diagnostic accuracy of CT colonography compared with colonoscopy in a prospective, blinded study in one single institution in Italy., Methods: Ninety-nine patients randomly selected among those attending the open-access endoscopy unit for diagnostic colonoscopy underwent colonoscopy and spiral CT. The images obtained were transmitted to generate the virtual colonoscopy pictures. A supervisor compared the results with the findings of conventional colonoscopy., Results: CT colonography diagnosed seven of eight tumors, one being missed because the patient had been inadequately prepared. In 28 patients, CT colonography identified 26 polyps of 45 (57.8% sensitivity, 92.6% specificity, 86.7% positive predictive value), regardless of their size. The sensitivity in detecting colonic polyps was 31.8% (7/22) in the first 25 cases and 91.6% (11/12) in the last 20 patients. CT colonography missed one flat adenoma, some angioectasias and colonic lesions because of portal hypertension in one patient, Crohn's disease ulcers in two patients, and ulcerative colitis lesions in three., Conclusions: CT colonography shows poor sensitivity for identifying colonic polyps and does not always detect neoplastic lesions. Flat lesions are impossible to see by this method.

Background: Throughout the world, the cost of critical care medicine is increasing more than the overall health care cost. Thus, a higher attention to improve the efficiency of the use of ICU resources is indispensable. The objective of this study was the development of a simple and reliable tool for the evaluation of the appropriateness of ICU utilization., Design: A repeated cross-sectional data collection was performed twice a week, during a 61-day study period., Setting: Twenty-three Italian general ICUs., Patients: All patients present in the 23 ICUs on the 17 index days., Interventions: On each index day, patients were checked for receiving ventilation/CPAP, pulmonary arterial pressure monitoring, intracranial pressure monitoring, vaso-active drug infusion and hemodialysis-ultrafiltration. Simultaneously, each ICU bed was assessed for its technical and personnel facilities in order to estimate the deliverable level of care., Results: A total of 1250 patients were studied, for a total number of 7533 patient-days. The overall occupancy rate per ICU was 83.8% (-range: 54.4% to 96.1%). The high-level occupancy rate (rate of patients requiring high level of care and actually occupying high-facility beds) was 69.4% (range: 25.0% to 149.0%), while the corresponding low-level occupancy rate was 101.1% (range: 31.3% to 329.4%)., Conclusions: Our model clearly showed up a certain degree of inappropriateness in the use of ICU resources. Most of the ICUs (69.6%) used a very large proportion of their high-facility beds for patients who did not need high-level care. Being very simple, our method could represent a useful tool for continuous evaluation of the appropriateness of resource utilization in the ICU.

Objective: Hepatitis C virus (HCV) infection is associated with increased lipoperoxidation, which may lead to interference with mitochondrial function with possible depletion of mitochondrial DNA (mtDNA). We correlated the ultrastructural findings of liver biopsy specimens with the lipoperoxidation markers and contents of mtDNA in chronic hepatitis C (CHC) patients with a different HCV genotype., Methods: Liver biopsy samples obtained from 75 CHC patients were processed for histological and electron microscopic examination. Twenty-two subjects without known liver disease served as controls. Hepatic glutathione in its reduced (H-GSH) and oxidized (H-GSSG) forms were determined from biopsy specimens by high-performance liquid chromatography. Plasmatic and lymphocytic GSH and erythrocytic malonyldialdehyde (MDA) were also determined, along with the ratio between mtDNA and nuclear DNA (nDNA)., Results: Ultrastructural alterations of the mitochondria were documented in 23 patients with genotype 1b, compared with 15 patients with genotype 2a/2c (p = 0.020) and seven patients with genotype 3a (p < 0.001). A significant depletion of H-GSH and lymphocytic GSH, an increase of H-GSSG and MDA, and a reduction of the mtDNA/nDNA ratio were documented in patients with genotype 1b, compared with patients with genotype 2a/2c and 3a and with controls., Conclusions: In patients with genotype 1b frequent ultrastructural alterations of the mitochondria may be observed, and the depletion of mtDNA in these patients may represent the expression of a greater impairment of the process of oxidative phosphorylation. An increased production of free radicals in patients with genotype 1b may influence the evolution of the liver disease by enhancement of the cytopathic effect of HCV.

Purpose: To assess the efficacy of interferon alpha-2b and ribavirin in combination in the treatment of patients with chronic hepatitis C who had either failed to respond to therapy with interferon alpha (nonresponders), or who had relapsed after interferon therapy (relapsers)., Subjects and Methods: Four hundred patients with chronic hepatitis C (200 nonresponders and 200 relapsers) were randomly assigned in equal numbers to receive either subcutaneous administration of recombinant interferon alpha-2b (3 million units three times per week) and ribavirin (1,000 to 1,200 mg/daily orally) or interferon alpha-2b alone (6 million units three times per week). Both ribavirin and interferon alpha-2b were given for 24 weeks. The patients were then followed for an additional 24 weeks., Results: At the end of the treatment period, normalization of serum alanine aminotransferase levels and absence of hepatitis C virus RNA were seen in 21% of nonresponders and in 39% of relapsers who were treated with interferon alpha-2b and ribavirin, compared with 5% of nonresponders (P = 0.001) and 9% of relapsers treated with interferon alpha-2b alone (P <0.001). At the end of follow-up, 14% of nonresponders and 30% of relapsers treated with the combination therapy had a sustained response, compared with 1% of nonresponders (P = 0.001) and 5% of relapsers treated with interferon alpha alone (P <0.001)., Conclusions: A 24-week course of treatment with interferon alpha-2b and ribavirin offers a chance of sustained response, whereas retreatment with interferon alpha-2b alone does not give satisfactory results. The role of long-term therapy in inducing prolonged remission remains to be explored.

Background/aims: Increased serum ferritin is thought to be responsible for activation of glutathione turnover in patients with chronic hepatitis C. The aim of the study was to evaluate a possible correlation between levels of serum ferritin and concentrations of hepatic, plasmatic and lymphocytic glutathione in a selected cohort of chronic hepatitis C patients in relation to the hepatitis C virus genotype., Methods: The study considered 130 chronic hepatitis C patients and 23 control subjects. Hepatic glutathione was determined from biopsy liver specimens by high performance liquid chromatography. Total Iron Score was assessed by scoring iron separately within hepatocytes, sinusoidal cells and portal tracts. Blood samples were tested for determination of serum ferritin, and plasmatic and lymphocytic glutathione levels. Hepatic and erythocyte malonyldialdehyde were also determined along with peripheral blood mononuclear cell cytotoxic assay., Results: Patients with genotype 1b showed higher levels of serum ferritin compared to patients with genotype 2a/2c and 3a and to controls, along with a significant reduction of the concentrations of hepatic, plasmatic and lymphocytic glutathione and peripheral blood mononuclear cell cytotoxic activity. The levels of serum ferritin correlated significantly to Total Iron Score, to hepatic, plasmatic and lymphocytic glutathione, to hepatic and erythrocyte malonyldialdehyde and to peripheral blood mononuclear cell cytotoxic activity., Conclusions: The levels of serum ferritin correlate significantly to lipoperoxidation markers in chronic hepatitis C patients. The increased production of free radicals with a reduced peripheral blood mononuclear cell cytotoxic activity may represent, especially in patients with genotype 1b, a factor underlying the resistance to interferon therapy and may influence the evolution of the liver disease by enhancement of the cytopathic effect of hepatitis C virus.