Iron supplementation in young iron-deficient females causes gastrointestinal redox imbalance: protective effect of a fermented nutraceutical.

The aim of this study was to assess whether the concomitant supplementation of certified fermented papaya preparation (FPP, ORI, Gifu, Japan) together with iron supplementation could beneficially affect lipid peroxidation either systemically and at a intraluminal gut level in women with low iron stores. Treatment compliance and iron absorption was assessed as well. Fifty-two non-pregnant, fertile, non-smokers, healthy women with iron deficiency were recruited. The women were given iron supplements (100 mg Fe/d as ferrous sulfate) to be taken daily for 12 weeks (group A). Group B patients were also supplemented with 6g/day of a FPP. A detailed life style questionnaire was administered to all subjects. Iron, ferritin, transferrin receptors (Tf R) and malondialdehyde (MDA) in plasma were measured. The RBCs lysate was used for the estimation of superoxide dismutase (SOD) and glutathione peroxidase (GPx). The total and free iron concentration as well as analysis of oxidative stress in the feces was measured. FPP-supplemented subjects showed a significantly lower degree of gastrointestinal discomfort (p less than 0.05) and abolished the iron supplementation-induced increase of MDA (p less than 0.001) and the depletion of SOD and GPx (p less than 0.01). Moreover, the nutraceutical co-administration brought about a significant reduction of gut oxidative damage and lower fecal content of either total and free iron (p less than 0.05 vs group A). Overall, group B showed a better TfR/ferritin ratio response (p less than 0.05 vs group A). While iron supplementation maintains its clinical relevance considering the prevalence of iron deficiency among females, a careful clinical evaluation and a protective nutraceutical co-administration, as our data suggest with FPP, should be considered.

Irritable bowel syndrome: new findings in pathophysiological and therapeutic field.

Irritable bowel syndrome (IBS) is a high prevalence disease, whose symptoms are reported by a large number of young adults with significant effects on quality of life and social costs. Traditionally, IBS has been treated with dietary and lifestyle modification, fiber supplementation, psychological and pharmacological therapy. Since its complex and multifactorial etiopathogenesis is only partially known, therapeutic choices may be difficult and not always effective. New research efforts focused on the role of relationship between central nervous system and gut disorders (brain-gut axis), altered composition of gut microbiota (e.g. an eight times increased risk for IBS after Salmonella infection), immune activation with an increased number of T lymphocytes and mast cells associated with mucosa as well as an increased level of pro-inflammatory cytokines (IL-10 and IL-12, suggesting Th1 polarization), visceral hypersensitivity causing perception of pain even for minimal abdominal distension. Based on these findings, new possibilities of treatment are emerging with encouraging outcomes. Attention is directed to drugs that showed good tolerability profile and poor systemic absorption, which may make them suitable for repeated or long term treatments, as frequently required in patients with IBS. They have been successfully used drugs such as tachykinin receptors antagonists, tryptophan hydroxylase inhibitors, bile acid sequestrants, µ agonist and δ antagonist opioid receptors. Recent studies are discussed in this review, focusing both on new therapeutic approaches and innovative adaptation of previously available treatments.

Early prediction of treatment response to sorafenib with elastosonography in a mice xenograft model of hepatocellular carcinoma: a proof-of-concept study.

PURPOSE: Sorafenib is the reference therapy for advanced hepatocellular carcinoma (HCC). There is no method for predicting in the early period subsequent individual response. Starting from the clinical experience in humans that subcutaneous metastases may rapidly change consistency under sorafenib and that elastosonography allows assessment of tissue elasticity, we investigated the role of this ultrasound-based technique in the early prediction of tumor response to sorafenib in a HCC mice model. MATERIALS AND METHODS: HCC subcutaneous xenografting in mice was utilized. Mice were randomized to vehicle (17 mice) or treatment with sorafenib (19 mice). Strain elastosonography (Esaote, Italy) of the tumor mass was performed at different time points (day 0, + 2 and + 14 from treatment start) until the mice were sacrificed (day + 14). At the same time points, the volume was calculated with ultrasonography. RESULTS: Sorafenib-treated mice showed a smaller increase in tumor size on day + 14 in comparison to vehicle-treated mice (tumor volume increase + 175 % vs. + 382 %, p = 0.009). The median tumor elasticity increased in both groups on day + 2 (+ 5.65 % and + 3.86 %, respectively) and decreased on day + 14 (-3.86 % and -3.63 %, respectively). However, among Sorafenib-treated tumors, 13 mice with a growth percentage delta < 200 % (considered as good treatment response) showed an increase in elasticity on day + 2 (+ 8.9 %, range -12.6 - + 64) while the other 6 with a growth percentage delta > 300 % (considered as poor treatment response) showed a decrease in elasticity (-17 %, range -30.2 - + 15.3) (p = 0.044). CONCLUSION: Elastosonography appears to be a promising noninvasive new technique for the early treatment prediction of HCC tumor response to sorafenib. Specifically, an early increase in tumor elasticity (corresponding to tumors becoming softer) is associated with a good response.

Liver fibrosis: evaluation with diffusion-weighted magnetic resonance imaging in patients with chronic liver disease.

AIM: Liver fibrosis is often a possible evolution of chronic liver disease (CLD), with a risk of progression to cirrhosis. This study was designed to determine if the measure of apparent diffusion coefficient (ADC) is clinically accurate in the staging of fibrosis. METHODS: The study was conducted in the period 2008-2012. We recruited 84 patients with CLD. The control group included 67 patients whose laboratory, ultrasound and magnetic resonance imaging exams demonstrated liver's normal conditions. For ethical reasons, these patients did not undergo liver biopsy. Patients were examined using diffusion-weighted magnetic resonance imaging with a 1.5 Tesla magnet and with single shot echo-planar technique. Patients did undergo liver biopsy and the samples were evaluated with the Metavir score (F0-F4), Ishak score (0-6) and Brunt score (0-6). Patients were divided into three groups according to the different degree of fibrosis and the ADC was compared with U-test of Mann-Whitney. Moreover, it was used the analysis Receiver Operating Characteristic (ROC). RESULTS: A significant difference between group 1 (F0-F1) and group 3 (F3-F4) was found, with P=0.0024 and between group 2 (F2) and group 3, with P=0.027, but there was no significant difference of the ADC values in group 1 and group 2. CONCLUSION: The study showed a correlation between reduction of ADC and increasing of liver fibrosis degree. The ADC seems to be useful in staging liver fibrosis in patients with CLD, in particular to distinguish the later stages of fibrosis from early and intermediate stages.

Bi- and three-dimensional fractal analysis of the brown seaweed Gongolaria montagnei and their relationship with gastropod molluscs assemblage.

Habitat complexity is one of the main influences on biodiversity in marine environments, particularly in coastal areas where foundation seaweeds provide substrate for highly diverse communities. We studied the 2D and 3D fractal dimensions of Gongolaria montagnei (Fucales) over the vegetative season and examine their relationship with the abundance, species richness and morpho-functional groups of the gastropod associated. Overall, the 3D fractal analysis method used here better describes seaweeds structural complexity compared to the traditional 2D fractal analysis, as highlighted by the higher relationship with gastropod assemblage associated to the alga in terms of abundance, number of species and morpho-functional groups. We propose this new method as a valuable tool for understanding the relationship between seaweeds and associated fauna, which is critical for gaining a better understanding of the role that algal species play in a specific habitat and the consequences of their loss.

MicroRNA and hepatocellular carcinoma: biology and prognostic significance.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third most common cause of cancer-related death worldwide. In 90% of cases, HCC arises on a background of cirrhosis which, in turns, results from hepatitis (HBV and HCV) infections, alcohol abuse, metabolic disorders including NASH, and genetic metabolic diseases, autoimmune hepatitis, primary biliary cirrhosis and exposure to environmental carcinogens. The molecular mechanisms underlying HCC development are still only partially known. Despite a high molecular variability, the deregulation of definite oncogenic pathways has been confirmed as a common finding in HCC. Among these, the molecular ways controlling proliferation, apoptosis and migration play a major role. In recent years, a new class of regulatory RNAs, the microRNAs, has been discovered and their deregulated expression has been linked to the molecular pathogenesis of many cancers because of their ability to strongly impact on the expression of crucial messenger RNAs. This review focuses on some of the most relevant evidence concerning the contribution of microRNA aberrant expression to HCC development.

Marine reserves: fish life history and ecological traits matter.

Marine reserves are assumed to protect a wide range of species from deleterious effects stemming from exploitation. However, some species, due to their ecological characteristics, may not respond positively to protection. Very little is known about the effects of life history and ecological traits (e.g., mobility, growth, and habitat) on responses of fish species to marine reserves. Using 40 data sets from 12 European marine reserves, we show that there is significant variation in the response of different species of fish to protection and that this heterogeneity can be explained, in part, by differences in their traits. Densities of targeted size-classes of commercial species were greater in protected than unprotected areas. This effect of protection increased as the maximum body size of the targeted species increased, and it was greater for species that were not obligate schoolers. However, contrary to previous theoretical findings, even mobile species with wide home ranges benefited from protection: the effect of protection was at least as strong for mobile species as it was for sedentary ones. Noncommercial bycatch and unexploited species rarely responded to protection, and when they did (in the case of unexploited bentho-pelagic species), they exhibited the opposite response: their densities were lower inside reserves. The use of marine reserves for marine conservation and fisheries management implies that they should ensure protection for a wide range of species with different life-history and ecological traits. Our results suggest this is not the case, and instead that effects vary with economic value, body size, habitat, depth range, and schooling behavior.

Galileo at Io: results from high-resolution imaging.

During late 1999/early 2000, the solid state imaging experiment on the Galileo spacecraft returned more than 100 high-resolution (5 to 500 meters per pixel) images of volcanically active Io. We observed an active lava lake, an active curtain of lava, active lava flows, calderas, mountains, plateaus, and plains. Several of the sulfur dioxide-rich plumes are erupting from distal flows, rather than from the source of silicate lava (caldera or fissure, often with red pyroclastic deposits). Most of the active flows in equatorial regions are being emplaced slowly beneath insulated crust, but rapidly emplaced channelized flows are also found at all latitudes. There is no evidence for high-viscosity lava, but some bright flows may consist of sulfur rather than mafic silicates. The mountains, plateaus, and calderas are strongly influenced by tectonics and gravitational collapse. Sapping channels and scarps suggest that many portions of the upper approximately 1 kilometer are rich in volatiles.

Behavioural responses of fish groups exposed to a predatory threat under elevated CO2.

Most of the studies dealing with the effects of ocean acidification (OA) on fish behaviour tested individuals in isolation, even when the examined species live in shoals in the wild. Here we evaluated the effects of elevated CO2 concentrations (i.e. ∼900 µatm) on the shelter use and group cohesion of the gregarious damselfish Chromis viridis using groups of sub-adults exposed to a predatory threat. Results showed that, under predatory threat, fish reared at elevated CO2 concentrations displayed a risky behaviour (i.e. decreased shelter use), whereas their group cohesion was unaffected. Our findings add on increasing evidence to account for social dynamics in OA experiments, as living in groups may compensate for CO2-induced risky behaviour.

Biogenic habitat shifts under long-term ocean acidification show nonlinear community responses and unbalanced functions of associated invertebrates.

Experiments have shown that increasing dissolved CO2 concentrations (i.e. Ocean Acidification, OA) in marine ecosystems may act as nutrient for primary producers (e.g. fleshy algae) or a stressor for calcifying species (e.g., coralline algae, corals, molluscs). For the first time, rapid habitat dominance shifts and altered competitive replacement from a reef-forming to a non-reef-forming biogenic habitat were documented over one-year exposure to low pH/high CO2 through a transplant experiment off Vulcano Island CO2 seeps (NE Sicily, Italy). Ocean acidification decreased vermetid reefs complexity via a reduction in the reef-building species density, boosted canopy macroalgae and led to changes in composition, structure and functional diversity of the associated benthic assemblages. OA effects on invertebrate richness and abundance were nonlinear, being maximal at intermediate complexity levels of vermetid reefs and canopy forming algae. Abundance of higher order consumers (e.g. carnivores, suspension feeders) decreased under elevated CO2 levels. Herbivores were non-linearly related to OA conditions, with increasing competitive release only of minor intertidal grazers (e.g. amphipods) under elevated CO2 levels. Our results support the dual role of CO2 (as a stressor and as a resource) in disrupting the state of rocky shore communities, and raise specific concerns about the future of intertidal reef ecosystem under increasing CO2 emissions. We contribute to inform predictions of the complex and nonlinear community effects of OA on biogenic habitats, but at the same time encourage the use of multiple natural CO2 gradients in providing quantitative data on changing community responses to long-term CO2 exposure.

Efficacy of interventional radiology procedures for the treatment of early ureteral complications after kidney transplantation.

UNLABELLED: Ureteral stricture and ureteral leakage are the most common early urological complications after kidney transplantation causing decreased urine output and increased serum creatinine and blood urea nitrogen. We report our experience with internal-external ureteral stent placement and ureteroplasty. MATERIALS AND METHODS: From August 1999 to January 2005, we treated nine patients presenting with stricture or leak. After an anterograde pyelogram, an internal-external nephrostomy catheter was inserted in all patients; in four patients we also performed ureteroplasty. RESULTS: The stricture and leak appeared from 12 to 93 days after kidney transplantation (mean = 39 +/- 29 days). After a mean of 80 +/- 43 days (range 25-141 days), the stent was successfully removed in seven patients (77%); no patient had a recurrence. The success was confirmed by a decline in serum creatinine (from 3.7 +/- 1.4 to 1.6 +/- 0.7 mg/dL) and blood urea nitrogen (from 54 +/- 24 to 28 +/- 7 mg/dL) with resolution of hydronephrosis on sonography. No procedure-related complications were observed. Surgical correction was necessary in two patients due to the persistence of a stricture. At long-term follow-up (50 +/- 17 months), seven kidneys were still functioning and two had failed due to chronic rejection. CONCLUSION: Nephrostomy catheter placement and ureteroplasty are safe, effective alternatives to surgery to treat early ureteral complications after kidney transplantation. Interventional radiology procedures reducing the morbidity and the likelihood of loss of graft function may improve graft and patient survival.

The gut microbiota and its correlations with the central nervous system disorders.

A mutual impact of gastrointestinal tract (GIT) and central nervous system (CNS) functions has been recognized since the mid-twentieth century. It is accepted that the so-called gut-brain axis provides a two-way homeostatic communication, through immunological, hormonal and neuronal signals. A dysfunction of this axis has been associated with the pathogenesis of some diseases both within and outside the GIT, that have shown an increase in incidence over the last decades. Studies comparing germ-free animals and animals exposed to pathogenic bacterial infections, probiotics or antibiotics suggest the participation of the microbiota in this communication and a role in host defense, regulation of immunity and autoimmune disease appearance. The GIT could represent a vulnerable area through which pathogens influence all aspects of physiology and even induce CNS neuro-inflammation. All those concepts may suggest the modulation of the gut microbiota as an achievable strategy for innovative therapies in complex disorders. Moving from this background, the present review discusses the relationship between intestinal microbiota and CNS and the effects in health and disease. We particularly look at how the commensal gut microbiota influences systemic immune response in some neurological disorders, highlighting its impact on pain and cognition in multiple sclerosis, Guillain-Barrè Syndrome, neurodevelopmental and behavioral disorders and Alzheimer's disease. In this review we discuss recent studies showing that the potential microbiota-gut-brain dialogue is implicated in neurodegenerative diseases. Gaining a better understanding of the relationship between microbiota and CNS could provide an insight on the pathogenesis and therapeutic strategies of these disorders.

Comparative analysis and quantitative evaluation of ankle-foot orthoses for foot drop in chronic hemiparetic patients.

BACKGROUND: Ankle-foot-orthoses (AFOs) are frequently prescribed for hemiparetic patients to compensate for the foot drop syndrome. However, there is not a systematic study either on the effectiveness of AFOs in the gait recovery process or pointing out the therapeutic differences among the various types of AFOs available on the market. AIM: To perform a comparative evaluation of solid and dynamic Ankle-Foot-Orthoses (AFOs) on hemiparetic patients affected by foot drop syndrome by means of spatio-temporal, kinematic and electromyographic indicators. DESIGN: Crossover design with randomization for the interventions. SETTING: A rehabilitation center for adults with neurologic disorders. POPULATION: Ten chronic hemiparetic patients with foot drop syndrome met inclusion criteria and volunteered to participate. METHODS: Biomechanical gait analysis was carried out on hemiparetic subjects with foot drop syndrome under 3 conditions with randomized sequences: 1) without AFO; 2) wearing a solid AFO; 3) wearing a dynamic AFO. Significant changes in spatio-temporal, kinematic and electromyographic features of gait were investigated. RESULTS: Gait analysis outcomes showed that there were no significant differences among the solid and the dynamic AFO on the spatio-temporal parameters. Both AFOs led to a reduction of the range of motion of the ankle dorsi-plantar-flexion during stance with respect to the ambulation without AFO. They also had the effect of reducing the asymmetry between the paretic and the contralateral limb in terms of ankle angle at initial contact and hip flexion. The solid AFO generally led to an increase of the co-contraction of the couples of muscles involved in the gait. CONCLUSION: The proposed set of indicators showed that the AFOs were capable of limiting the effect of the foot-drop in hemiparetic patients and balancing the two limbs. Main differences between the two orthoses were related to muscular activity, being the level of co-contraction of the two couples of analysed muscles typically lower when the dynamic AFO was worn and closer to a normal pattern. CLINICAL REHABILITATION IMPACT: A more extensive use of the proposed indicators in the clinical practice is expected in order to enable the definition of clinical guidelines for the prescription of the two devices.

HIV-1 seroconversion in United States Army active duty personnel, 1985-1999.

OBJECTIVE: To monitor HIV-1 infection trends among United States Army personnel, a predominantly young population group, tested between 1985 and 1999 for HIV-1 infection. DESIGN: Demographic correlates of HIV-1 infection were assessed in the cohort via epidemiologic analysis. METHODS: Annual seroconversion incidence rates were calculated per 1000 person-years (PY) of follow-up. Poisson regression was used to assess demographic correlates of HIV-1 seroconversion risk. RESULTS: There were 1275 seroconverters among 2 004 903 active duty Army personnel accounting for 7 700 231 PY of follow-up. The HIV-1 incidence rate (IR) was 0.17/1000 PY [95% confidence interval (CI), 0.16-0.17]. The highest IR was observed in the first year of testing (IR, 0.43/1000 PY; 95% CI, 0.33-0.52). The IR for male and female soldiers was 0.18/1000 PY and 0.08/1000 PY, respectively. HIV-1 incidence declined with age. Significant risk of HIV-1 seroconversion was associated with age [> 30 years old relative risk (RR), 1.51], race (Black RR, 4.61; Hispanic RR, 2.76), gender (male RR, 3.12), marital status (unmarried RR, 2.01) and rank (enlisted RR, 2.50). CONCLUSIONS: HIV-1 seroconversions in the US Army have been low and stable since the early 1990s. Continued HIV-1 incidence surveillance in the US Army provides information on the status of the epidemic in the Army, as well as important corroborative data on HIV-1 infections throughout the US.

Predictors of HIV-1 disease progression in early- and late-stage patients: the U.S. Army Natural History Cohort. Military Medical Consortium for Applied Retrovirology.

HIV-infected individuals in both early and late stages of HIV disease were evaluated over 2 years to assess temporal trends and determinants of disease progression. The Walter Reed (WR) staging system was used to categorize patients into an early-stage cohort (WR Stages 1 and 2, N = 1183) and a late-stage cohort (WR Stage 5, N = 260) based on the initial clinical evaluation. Progression was defined as the occurrence of Stage 5 disease or beyond for the early cohort and Stage 6 disease or beyond for the late cohort. The cumulative incidence of progression was 15.7% (137 events) for the early-stage cohort, and 53.7% (85 events) for the late-stage cohort. Baseline CD4+ T lymphocyte (T4) count was the most significant marker of progression: 26% of WR Stage 1 or 2 patients with T4 lymphocytes below 500/mm3 progressed, compared with 12% with T4 lymphocytes at or above 500/mm3. In late-stage individuals, 83% with T4 lymphocytes under 200/mm3 progressed, compared with 27% with T4 lymphocytes at or above 200/mm3. Older age was associated with progression in both early- and late-stage groups. Differences in the rates of disease progression were not significant between blacks and whites or between men and women. Two-year rates of progression among the late-stage patients dropped from 78 to 47% between 1986 and 1988. This contrasted with progression rates in the early-stage cohort, which remained stable: 18% for those entering follow-up in 1986 and 17% for those entering follow-up in 1988. These data indicate a significant slowing of HIV disease progression rates and mortality rates among individuals with late-stage disease that is temporally associated with the increased availability and use of therapies. With control of T4 lymphocyte count, age, and calendar time, neither gender nor race was significantly associated with progression in either early- or late-stage patients.

Experimental infection of Neotoma albigula (Muridae) with Whitewater Arroyo virus (Arenaviridae).

The Whitewater Arroyo virus (WWA) is a newly described North American arenavirus. The purpose of this study was to elucidate the biology of this virus in its natural rodent host, Neotoma albigula (white-throated woodrat). Thirteen adult, 7 juvenile, and 8 newborn woodrats each were inoculated subcutaneously with 1,000 cell culture infectious dose50 of the WWA virus prototype strain AV 9310135. All 28 animals became infected (as measured by the recovery of infectious virus and/or seroconversion) and no overt illness was associated with infection. Infection and virus shedding in the adult animals were transient (less than 59 days) whereas virus shedding in animals inoculated at birth persisted through 164 days of age. These results indicate that the duration of WWA virus infection in N. albigula is dependent upon the animal's age at the onset of infection and that neonatal infection can result in chronic (perhaps lifelong) virus shedding.

Arenavirus antibody in rodents indigenous to coastal southern California.

The purpose of this study was to extend our knowledge on the geographic and natural rodent host ranges of New World arenaviruses in California. Sera from 1,094 sigmodontine and 112 murine rodents were tested for antibody against Whitewater Arroyo and Amapari viruses. Antibody was found in 55 (4.6%) of the 1,206 rodents: 4 from northwestern San Diego County, 3 from Los Angeles County, and 48 from Orange County. The antibody-positive rodents included 8 (7.8%) of 103 Neotoma fuscipes, 1 (0.6%) of 180 Neotoma lepida, 1 (3.1%) of 32 Peromyscus boylii, 8 (11.0%) of 73 Peromyscus californicus, 1 (1.2%) of 85 Peromyscus eremicus, 30 (8.5%) of 353 Peromyscus maniculatus, and 6 (2.2%) of 268 Reithrodontomys megalotis. This study provides the first evidence that New World arenaviruses occur in Los Angeles and Orange counties and northwestern San Diego County, and the first evidence that Peromyscus and Reithrodontomys species are naturally infected with New World arenaviruses.

Gastrointestinal stromal tumor, uncommitted type, with monosomies 14 and 22 as the only chromosomal abnormalities.

Karyotypic analysis of a gastric stromal tumor with the histologic and immunohistochemical features of a malignant, uncommitted lesion revealed clonal monosomies of chromosomes 14 and 22. Such changes, together with loss of chromosomes 15 and 18, as well as structural rearrangements involved chromosome 1, have been previously reported in gastrointestinal stromal tumors with smooth muscle differentiation. We suggest that monosomies of chromosomes 14 and 22 are early events in the malignant transformation of the mesenchymal cell-originating gastrointestinal stromal tumors.