Concealed by darkness: Combination of NMR and HRMS reveal the molecular nature of dissolved organic matter in fractured-rock groundwater and connected surface waters.

Detailed molecular composition of solid phase extracted dissolved organic matter (SPEDOM) collected from fractured-rock groundwater was compared to connected surface river water at two different watersheds in the unconfined chalk aquifer of Champagne in France using full scan ultrahigh resolution electrospray and photoionization Fourier transform ion cyclotron mass spectrometry (FT-ICR MS), Orbitrap tandem MS (MS/MS) and 1H magnetic resonance spectroscopy (NMR). 1H NMR spectroscopy indicated that groundwater SPEDOM carried a higher contribution of aliphatic compounds while surface river waters SPEDOM were enriched in carboxyl-rich alicyclic molecules (CRAM), acetate derivatives and oxygenated units. Furthermore, we show here that use of photoionization (APPI(+)) in aquifer studies is key, ionizing about eight times more compounds than ESI in surface river water samples, specifically targeting the dissolved organic nitrogen pool, accounting for more than 50% of the total molecular space, as well as a non-polar, more aromatic fraction; with little overlap with compounds detected by ESI(-) FT-ICR MS. On the other hand, groundwater SPEDOM samples did not show similar selectivity as less molecular diversity was observed in APPI compared to ESI. Mass-difference transformation networks (MDiNs) applied to ESI(-) and APPI(+) FT-ICR MS datasets provided an overview of the biogeochemical relationships within the aquifer, revealing chemical diversity and microbial/abiotic reactions. Finally, the combination of ESI(-) FT-ICR MS and detailed Orbitrap MS/MS analysis revealed a pool of polar, anthropogenic sulfur-containing surfactants in the groundwaters, likely originating from agricultural runoff. Overall, our study shows that in this aquifer, groundwater SPEDOM contains a significantly reduced pool of organic compounds compared to surface river waters, possibly related to a combination of lack of sunlight and adsorption of high O/C formulas to mineral surfaces.

Sustainability assessment of waste and wastewater recovery for edible mushroom production through an integrated nexus. A case study in Lazio.

With a global population of eight billion people, improving the sustainability and nutritional quality of diets has become critical. Mushrooms offer a promising solution because of their nutritional value and ability to be grown from agricultural residues, in line with the circular economy. This study, therefore, focuses on assessing the environmental compatibility of Agaricus bisporus mushroom production in Italy, the world's third largest per capita consumer, by using a Life Cycle Assessment (LCA) and an integrated Water-Energy-Nitrogen-Carbon-Food (WENCF) nexus analysis. The LCA results reveal that for a functional unit of 23,000 kg of the substrate, the production process emits 2.55 × 104 kg of CO2 eq. Sensitivity analysis shows that changing input quantities can reduce environmental impacts by about 5 %. In addition, one scenario evaluates the environmental effects of recycling resources by introducing water and ammonium sulfate from scratch instead of continuous recycling, along with water purification. The study shows that sustainable food production can mitigate resource depletion, climate-altering emissions, and intersectoral competition. Using agro residues for mushroom cultivation and optimizing resource management contribute to environmental sustainability. This approach could not only improve the resilience and efficiency of the food system but could also improve the sustainability of diets. In conclusion, this study highlights the importance of adopting sustainable and circular approaches in mushroom production to address global challenges related to food sustainability.

The largest prehistoric mound in Europe is the Bronze-Age Hill of Udine (Italy) and legend linked its origin to Attila the Hun.

Prehistoric monuments often constitute evident landmarks and sometimes, after falling into disuse, fascinated local people enough to stimulate speculations about their origin over time. According to legend, the Hill of Udine (NE Italy) was built by Attila the Hun's soldiers, but its origin (natural or anthropogenic) has been debated until now. Our research analyzed five new 40-m long stratigraphic cores, investigating for the first time the total thickness of the hill and compared the data with the available archaeological information. Moreover, we considered other hills and mounds in northern Italy and other European regions where folklore traditions relate their origin to Attila. The geoarchaeological and ethnographic data prove that the Hill of Udine is a Bronze Age anthropogenic mound erected between 1400 and 1150 BCE and that, later, folklore has transformed the ancestral memory of its origin into legend. By measuring 30 m in height and over 400,000 m3 in volume, the flat-topped hill is the largest prehistoric mound in Europe. This discovery reveals unprecedented skills in earth construction and confirms significant anthropogenic modifications of the environment during Bronze Age.

Secondary aneurysmal bone cyst in Langerhans cell histiocytosis: Case report, literature review.

Langerhans cell histiocytosis (LCH) is a rare disease of the myeloid precursor cells, it predominantly occurs in the skull and long bones as unifocal bone lesions. Aneurysmal bone cysts (ABC) are benign, expansive and lytic bone. Reports of secondary ABC occurring in LCH are rare, having only been reported twice in the skull. Here, we report the first case of LCH masquerading as ABC in a 14-month-old female child who presented with a rapidly growing mass in her left femur. The lesion had typical radiological features of ABC, and only histological examination revealed the presence of cells suggestive of LCH.

Pancake kidney, a rare and often misdiagnosed malformation: a case report and radiological differential diagnosis.

Renal ectopia and fusion anomalies are Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT) that are usually incidentally detected and asymptomatic. Patients affected present a higher risk of complications like recurrent urinary tract infections or obstruction. Pancake kidney (PK) is one of the rarest types of renal anomaly with complete fusion of the superior, mild and inferior poles of both kidneys in the pelvic cavity. Each kidney has its own excretory system with two ureters that do not cross the midline. In the asymptomatic cases, a conservative approach should be performed. Surgical management may be needed when urological problems occur. PK is often associated with congenital anomalies of other organs. Ultrasound is the first line radiological examination for the diagnosis and the follow-up of kidney malformations. The main sonographic findings suggesting PK diagnosis are a large and lobulated renal mass consisting of two fused lateral lobes without an intervening septum located in the pelvic cavity. Each lobe usually has a separate pelvicalyceal system, the renal pelvis is anteriorly placed and the ureters are usually short and enter the bladder normally without crosses the midline. Ultrasonography gives useful information on the morphology and volume of the organ, and on its vascularization through the use of the Color- and Power-Doppler. Computer Tomography and Magnetic Resonance Urography are second level techniques used to confirm the diagnosis and to evaluate the presence of other abnormalities. The knowledge of the imaging findings and the anatomy of congenital renal malformations is important to avoid diagnostic pitfalls and misinterpretations. We report the case of a 14-years old female with PK who was misdiagnosed with a horseshoe kidney (HSK) during an abdominal ultrasound.

Musculoskeletal hydatid disease: report of a rare case with primary and exclusive localization in right hemi-pelvis and femur.

Hydatid Disease (HD), also called Echinococcosis or Hydatidosis, is a parasitic infection caused by the larval stage of the tapeworm Echinococcus: E. granulosus or E. multilocularis. HD occur most frequently in liver or lungs, rarely in brain, skeletal muscles, bones, kidneys, spleen. Bone infestation of Echinococcosis hydatid cysts occurs respectively by haematogenous seeding and progressive invasion into bone by lesions in the adjacent soft tissues. Patients with musculoskeletal HD clinically show the disease in adulthood because the lesions develop very slowly. In some cases, HD is an uncommon cause of soft tissue mass, pain and neurovascular symptoms due to compression or to secondary infection. Diagnostic imaging plays an important role in the diagnosis of HD and in the differential diagnosis with soft tissue tumors. We present a rare case of male patient of 42 year-old with diagnosis of HD with primary and exclusive localization in right hemi-pelvis and femur.

Association of deletion 9p, 46,XY gonadal dysgenesis and autistic spectrum disorder.

Deletions of distal chromosome 9p24 are often associated with 46,XY gonadal dysgenesis and, depending on the extent of the deletion, the monosomy 9p syndrome. We have previously noted that some cases of 46,XY gonadal dysgenesis carry a 9p deletion and exhibit behavioural problems consistent with autistic spectrum disorder. These cases had a small terminal deletion of 9p with limited or no somatic anomalies that are characteristic of the monosomy 9p syndrome. Here, we present a new case of 46,XY partial gonadal dysgenesis and autistic spectrum disorder associated with a de novo deletion of 9p24 that was detected by ultra-high resolution oligo microarray comparative genomic hybridization. The deletion included the candidate sex-determining genes in the region DMRT1 and DMRT3. These data suggest that a gene responsible for autistic spectrum disorder is located within 9p24. It remains to be determined if the gonadal dysgenesis and autistic spectrum disorder are caused by a single gene or if they are caused by distinct genetic entities at 9p24.

Evaluation of two different extraction methods for chromatographic determination of bioactive amines in tomato products.

Bioactive amines are organic bases originating from corresponding amino acid which have undergone decarboxylation by putrefactive bacteria or lactic acid bacteria. When formed by microbial enzymatic decarboxylation of amino acids, they are called " biogenic" and can produce detrimental effects on human health. Many techniques have been developed for extraction and/or clean up of bioactive amines in food, including acidic or organic extraction as well as solid phase extraction. This study deals with the comparison of two different extraction methods, homogenizing and matrix solid phase dispersion, for the chromatographic determination of eight non-volatile bioactive amines in tomato-based products (mashed tomato, biological mashed tomato, concentrated tomato pasta and ketchup) very popular in Italian alimentary habits. In both cases, perchloric acid has been used for analytes extraction and the influence of different parameters affecting amine recoveries have been evaluated. After a derivatization step with dansyl-chloride, samples were analyzed for amines quantitative determination using 1,7-diaminoheptane as internal standard on a C(18)-RP-HPLC-UV system. Method performances were tested and good results of linearity, repeatability and recovery were obtained for all the considered amines. The collected data have shown that ketchup contains the highest levels of amines followed by concentrated tomato pasta, biological mashed tomato and common mashed tomato. Moreover, it has been found that in all samples, putrescine is the most abundant amine followed by tyramine, spermidine and tryptamine.

Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy.

OBJECTIVE: To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS: Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS: The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS: This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

Risk factors for type 2 diabetes in women attending menopause clinics in Italy: a cross-sectional study.

OBJECTIVE: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause. SUBJECTS: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. METHODS: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year. RESULTS: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73). CONCLUSIONS: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

Local and remote ischemia-reperfusion injury is mitigated in mice overexpressing human C1 inhibitor.

Activation of the classical complement pathway is crucially involved in complement-mediated endothelial cell damage in ischemia-reperfusion injury. C1 inhibitor is the only known physiological inhibitor of classical complement pathway activation. Transgenic mice overexpressing human C1 inhibitor were used in a surgical lower torso and a liver ischemia-reperfusion model. Organ-specific endothelial disruption was determined by 125I-tagged albumin extravasation. In the lower torso ischemia-reperfusion model, transgenic mice overexpressing the C1 inhibitor were protected in the muscle and the lungs from endothelial cell damage. In the liver ischemia-reperfusion model, endothelial cell integrity was preserved in transgenic animals in the liver, the gut and the lungs. Our data indicate that inhibiting complement activation by a transgenic approach is effective in protection against ischemia-reperfusion injury.

Determination of free fatty acids and lipase activity in milk: quality and storage markers.

The free fatty acid (FFA) content together with the lipase activity control can be considered as useful indexes of good quality and correct storage of food, especially for milk. The quantitative analysis of FFA in different kinds of milk has been performed by a potentiometric method, using a new extractive methodology outlined herein. The lipase activity has been controlled by a sensitive calorimetric method, previously validated by us, based on the direct measure of the heat quantity involved in the enzymatic reaction. In order to verify the milk quality after the healing treatments and/or during the shelf life, the behaviours of FFA content and of lipase activity have been outlined in function of storage time and pH variations on different typologies of milk. The FFA content in sample of fresh pasteurised milk was found to be quite high after the 5th/6th day of storage at +4 degrees C, meanwhile the pH values were always constant and only after the 9th day begun to decrease. At the same time the lipase activity, directly measured, was found to be appreciable after the 6th day of storage, giving an exothermic answer at the calorimeter, similar to that of a milk sample where only three international units of standard lipase were added.

Primary systemic anaplastic large-cell lymphoma (CD30+): advances in biology and current therapeutic approaches.

In 1985, Stein et al demonstrated the expression of the lymphoid activation antigen CD30/Ki by neoplastic cells. Fifteen years after the first description, anaplastic large-cell lymphomas (ALCL) are now thought to be a heterogeneous group in terms of their clinical, morphologic, phenotypic, cytogenetic, and molecular biology features. However, on the basis of a specific genetic anomaly and expression of a chimeric nucleophosmin anaplastic lymphoma kinase (NPM-ALK) protein and its variants, a distinct clinicopathologic entity defined as "ALK-positive lymphoma" or "ALKoma" can be recognized. Based on molecular and clinical criteria, 3 entities of primary ALCL can be identified: primary systemic ALK positive, primary systemic ALK negative, and primary cutaneous ALCL. This review focuses on advances in the knowledge of primary systemic ALCL biology and discusses therapeutic approaches based on ALK expression. The presence of this protein appears to be an important prognostic factor and, combined with an age-adjusted International Prognostic Index, could allow researchers to design more specific clinical trials aimed at finding new, more efficacious and less toxic treatments.

Clinical activity and safety of combination immunotherapy with IFN-alpha 2a and Rituximab in patients with relapsed low grade non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: To determine the clinical activity and safety of the combination immunotherapy of the chimeric anti-CD20 antibody, Rituximab, and Interferon (IFN)- alpha 2a DESIGN AND METHODS: Sixty-four patients with relapsed low-grade or follicular B-cell non Hodgkin's lymphoma received 4 infusion of Rituximab (375 mg/m(2) x dose) after priming and simultaneous treatment with IFN- alpha 2a. RESULTS: The overall response rate was 70% with 33% complete responses. Median for duration of response is 19 months, after a median follow-up of 22 months. By univariate analysis none of the most common prognostic factors predicted for response to therapy. After treatment 10 patients become bcl-2 negative in the bone marrow, but no correlation between molecular and clinical response was found. Fifty-three patients (83%) had drug related or unknown origin adverse events. The number of adverse events per patient varied from 1 to 21. Considering all 272 events, 231 (85%) were grade 1 or 2, 36 (13%) grade 3 and 5 (2%) grade 4. Twenty-three patients required reduction in the dose and/or short discontinuation of IFN treatment, either during priming or subsequent treatment. The most frequent adverse events were leukopenia, fever, neutropenia, hypotension and thrombocytopenia. INTERPRETATION AND CONCLUSIONS: this report shows that combination immunotherapy Rituximab + IFN- alpha 2a is active and relatively well tolerated. The overall response rate of 70% and the median duration remission of 19 months compare favorable with the results obtained with Rituximab alone in similar subset of patients. Randomized trials, investigating Rituximab versus combination immunotherapy are needed.

Treatment of B-cell non-Hodgkin's lymphoma with anti CD 20 monoclonal antibody Rituximab.

Rituximab is a chimeric anti CD-20 monoclonal antibody containing human IgG1 kappa constant regions, with murine variable regions. The anti-lymphoma effects of Rituximab are probably due to complement and antibody-dependent cell-mediated cytotoxicity, and induction of apoptosis. Phase II trials have demonstrated a strong activity of rituximab alone in indolent B non-Hodgkin lymphoma, especially in patients with follicular lymphoma. The most utilized dose-schedule is 375 mg/m(2) weekly x 4. The association with chemotherapy or with interferon-alpha increases Rituximab efficacy. More recently, Rituximab have showed activity also in diffuse large cell lymphoma, mantle cell lymphoma and in other B-malignancies. Good results have also been obtained utilizing Rituximab for in vivo purging. However, we are still far from having found a definite position for Rituximab in the treatment of lymphoproliferative disorders. The aim of future studies should be to develop new strategies that will hopefully produce the most effective Rituximab-based regimens in order to find the Rituximab key position in the treatment of B-malignancies

Diagnosis of essential thrombocythemia at platelet counts between 400 and 600x10(9)/L. Gruppo Italiano Malattie Mieloproliferative Croniche(GIMMC).

BACKGROUND AND OBJECTIVE: Diagnostic criteria for essential thrombocythemia (ET) remain essentially negative, that is, exclusion of other myeloproliferative diseases and causes of reactive thrombocytosis. A platelet count above 600x10(9)/L is still generally considered an absolute diagnostic criterion although new protocols for positive diagnostic criteria have recently been proposed, reducing the stringency of a definite platelet limit. This study demonstrates that a platelet count 600x10(9)/L is not a reliable diagnostic criterion for ET, especially in the early stages. DESIGN AND METHODS: An ongoing retrospective study by the GIMMC analyzed 2,316 ET patients diagnosed between 1986 and 1995. Of these 2,316 patients, diagnosed according to the PVSG criteria, 68 had a platelet count 600x10(9)/L and were analyzed separately; 37 out of 68 were excluded from this analysis because of a follow-up shorter than 2 years and/or because of treatment with myelosuppressive agents. The remaining 31 patients were the subjects of our study. RESULTS: After a median follow-up of 4.56 years (range 2-9.6 years) none of the 31 patients had a spontaneous decrease of platelets to the normal range. Transformation to a different chronic myeloproliferative disorders was never observed and no patient developed a condition known to produce reactive thrombocytosis. During follow-up, 23 patients (74%) were treated with anti-aggregating drugs, mainly aspirin. The disease did not evolve into acute leukemia in any patient, 1 had a thrombotic event and none presented hemorrhagic episodes. Median platelet count during follow-up was 534x10(9)/L (range 398-997x10(9)/L). INTERPRETATION AND CONCLUSIONS: Long term follow-up has documented that our 31 patients were correctly diagnosed as having ET, although platelet count was 600x10(9)/L. Our patients were probably in a early phase of their disease and following updated PVSG criteria would have been misdiagnosed leading to incomplete recognition of the natural history of the disease. Further, because an early diagnosis could also have a clinical relevance, our results outline the need for new criteria for the diagnosis of ET. The exclusion of patients with a platelet count between 400 and 600x10(9)/L may prevent patients, nevertheless at risk of vascular complications, from being treated.

Orotic acid: a milk constituent Enzymatic determination by means of a new microcalorimetric method.

The presence of orotic acid (a precursor of nucleic acid) in milk is very important in order to ensure its nutritional value and good conservation. In the literature, chromatographic, spectrophotometric and polarographic methods are reviewed. The reported values have a very wide interval range (19-664 mg l(-1)) and a low precision. The new method proposed in this article employs an enzymatic reaction. It has been improved on standards and then tested on milk samples. The same samples were also tested by means of a known spectrophotometric method. The new analytical method for orotic acid determination is reliable; the results are more accurate and more precise if compared with the usual methods, and it shows the same sensibility. The calorimetric analysis is faster and easier, owing to the fact that no sample treatments are required.

Influence of hepatitis G virus coinfection on the clinical course of chronic hepatitis C.

Hepatitis G virus (HGV) is a parenterally transmitted virus, frequently associated with hepatitis C virus infection. Hepatitis G virus RNA was detected by reverse transcription-polymerase chain reaction in the serum of 40 patients with chronic hepatitis C. Nine (22.5%) patients had evidence of hepatitis G virus viraemia. No significant epidemiological or virological differences could be demonstrated between subjects infected with both hepatitis G virus and hepatitis C virus and subjects infected with hepatitis C virus alone. Aminotransferase values were comparable between the two groups, whereas higher levels of cholestatic enzymes (P< 0.001) were reported in the hepatitis G virus/hepatitis C virus-positive patients. A liver biopsy was performed on all 40 patients no later than 6 months before recruitment. The mean histological activity index did not differ between hepatitis G virus-positive and hepatitis G virus-negative patients, whereas specific histological features such as macrovesicular steatosis, portal granulomas, and bile duct damage were more commonly observed among the coinfected patients. The results indicate that coinfection with hepatitis G virus probably does not have a significant effect on hepatitis C virus-induced hepatic damage.

Serum hepatitis G virus (HGV) RNA in multitransfused thalassemics from eastern Sicily.

The prevalence of hepatitis G in a multitransfused population was studied. HGV did not appear to be a major contributor to liver pathology in this group and the prevalence was surprisingly low.

Molecular cloning, gene structure and expression profile of mouse C1 inhibitor.

The gene encoding C1 inhibitor, the major control element of activation of the classical pathway of complement and a major inhibitor of several plasma serine proteases, has been studied only in man, where deficiency of C1 inhibitor results in the dominantly transmitted disease hereditary angioedema. Full-length mouse C1 inhibitor cDNA and genomic clones were isolated and characterized as a first step towards the complete characterization of the pattern of C1 inhibitor expression and the production of an animal model of C1 inhibitor deficiency. Restriction-enzyme and sequence analyses of a full-length genomic clone demonstrated that the mouse gene has the same structure as the human homologue, but differs in size (9 kb versus 17 kb), mostly due to the presence of repetitive Alu elements in the human gene. Sequence comparisons in the promoter region indicate important similarities, i.e. the absence of a TATA box, the presence of an initiator sequence encompassing the transcription-start site and of a gamma-interferon-activated sequence (GAS) element at position -124 of the human sequence. A stretch of about 100 nucleotides in intron 1 reveals an unusually high degree of conservation for non-coding sequences and contains non-canonical but conserved tandemly arranged GAS elements at positions 369 and 388 of the human sequence. This finding supports the conclusions of functional studies on the human C1INH gene indicating a role of this region in modulation of transcription by interferons. The profile of C1 inhibitor expression in mouse liver, lung, heart, kidney, spleen and brain was determined by quantitative northern blot analysis.