A five-gene molecular phylogeny reveals Parapanteles Ashmead (Hymenoptera: Braconidae) to be polyphyletic as currently composed.

Parapanteles Ashmead (Braconidae: Microgastrinae) is a medium-sized genus of microgastrine wasps that was erected over a century ago and lacks a unique synapomorphic character, and its monophyly has not been tested by any means. Parapanteles usually are parasitoids of large, unconcealed caterpillars (macrolepidoptera) and have been reared from an unusually large diversity of hosts for a relatively small microgastrine genus. We used Cytochrome Oxidase I sequences ("DNA barcodes") available for Parapanteles and other microgastrines to sample the generic diversity of described and undescribed species currently placed in Parapanteles, and then sequenced four additional genes for this subsample (wingless, elongation factor 1-alpha, ribosomal subunit 28s, and NADH dehydrogenase subunit 1). We constructed individual gene trees and concatenated Bayesian and maximum-likelihood phylogenies for this 5-gene subsample. In these phylogenies, most Parapanteles species formed a monophyletic clade within another genus, Dolichogenidea, while the remaining Parapanteles species were recovered polyphyletically within several other genera. The latter likely represent misidentified members of other morphologically similar genera. Species in the monophyletic clade containing most Parapanteles parasitized caterpillars from only five families - Erebidae (Arctiinae), Geometridae, Saturniidae, Notodontidae, and Crambidae. We do not make any formal taxonomic decisions here because we were not able to include representatives of type species for Parapanteles or other relevant genera, and because we feel such decisions should be reserved until a comprehensive morphological analysis of the boundaries of these genera is accomplished.

The selection of paired watersheds affects the assessment of wildfire hydrological impacts.

Wildfires strongly alter hydrological processes and surface and groundwater quality in forested environments. The paired-watershed method, consisting of comparing a burnt (altered) watershed with an unburnt (control) watershed, is commonly adopted in studies addressing the hydrological effects of wildfires. This approach requires a calibration period to assess the pre-perturbation differences and relationships between the control and the altered watershed. Unfortunately, in many studies, the calibration phase is lacking due to the unpredictability of wildfires and the large number of processes that should be investigated. So far, no information is available on the possible bias induced by the lack of the calibration period in the paired-watershed method when assessing the hydrological impacts of wildfires. Through a literature review, the consequences of the lack of calibration on the assessment of wildfire hydrological changes were evaluated, along with the most used watershed pairing strategies. The literature analysis showed that if calibration is lacking, misestimation of wildfire impacts is likely, particularly when addressing low-severity or long-term wildfire effects. The Euclidean distance based on physical descriptors (geology, morphology, vegetation) was proposed as a metric of watersheds similarity and tested in mountain watersheds in Central Italy. The Euclidean distance proved to be an effective metric for selecting the most similar watershed pairs. This work raises awareness of biases exerted by lacking calibration in paired-watershed studies and proposes a rigorous and objective methodology for future studies on the hydrological effects of wildfires.

Diffuse neoplasms of the pleural serosa.

This study describes the diffuse neoplastic conditions that may affect pleural membranes. These include mesothelioma, the most important and common malignancy of pleural origin, and metastatic involvement by carcinomas, lymphomas and thymomas. On the basis of diagnostic imaging, we identify the distinctive features of pleural involvement by each of these conditions and provide elements enabling accurate differential diagnosis. Finally, we discuss the best diagnostic approach in the case of suspected primary or secondary neoplastic involvement of pleural membranes.

Adenosine receptors participate in anabolic-androgenic steroid-induced changes on risk assessment/anxiety-like behaviors in male and female rats.

Anabolic-androgenic steroids (AAS) and caffeine can induce several behavioral alterations in humans and rodents. Administration of nandrolone decanoate is known to affect defensive responses to aversive stimuli, generally decreasing inhibitory control and increasing aggressivity but whether caffeine intake influences behavioral changes induced by AAS is unknown. The present study aimed to investigate behavioral effects of caffeine (a non-selective antagonist of adenosine receptors) alone or combined with nandrolone decanoate (one of the most commonly AAS abused) in female and male Lister Hooded rats. Our results indicated that chronic administration of nandrolone decanoate (10 mg/kg, i.m., once a week for 8 weeks) decreased risk assessment/anxiety-like behaviors (in the elevated plus maze test), regardless of sex. These effects were prevented by combined caffeine intake (0.1 g/L, p.o., ad libitum). Overall, the present study heralds a key role for caffeine intake in the modulation of nandrolone decanoate-induced behavioral changes in rats, suggesting adenosine receptors as candidate targets to manage impact of AAS on brain function and behavior.

New York Heart Association class and pulmonary artery pressure as prognostic factors of interstitial lung disease survival.

OBJECTIVE: The aim of this study was to evaluate New York Heart Association (NYHA) class and systolic pulmonary artery pressure (sPAP) as survival predictors in major interstitial lung diseases (ILD) including idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and hypersensitivity pneumonitis (HP) and in other ILD like granulomatosis with polyangiitis (GPA). PATIENTS AND METHODS: We analyzed survival, NYHA class, sPAP, and Octreoscan uptake index (UI) in 104 ILD patients (59 IPF, 19 NSIP, 10 HP and 16 GPA; median age 60.5 years) all referred to a single centre. RESULTS: Median survival was 68 months, with 1- and 2-year survival of 91% and 78%, respectively. Survival was lower among IPF and NSIP vs. HP and GPA patients (p=0.01). NYHA class 3-4 was more frequent among IPF (76.3%) vs. NSIP patients (31.6%; p<0.001). HP and GPA had NYHA class 1-2. NYHA class was negatively associated with survival (class 1=90.3 months vs. class 3=18.3 months and class 4=5.1 months; p=0.001). sPAP was >55 mmHg in 76.3% of patients with IPF and 35-55 mmHg in 63.2% of patients with NSIP. Patients with HP and GPA had sPAP < 55 mmHg. Among patients with IPF, NYHA and sPAP were negatively associated with survival (p<0.01) both showed a parallel trend. High-resolution computed tomography and survival were worse among IPF and NSIP vs. HP and GPA patients (p<0.001). Octreoscan UI was <10, 10-12, and >12 in IPF, NSIP, HP and GPA, respectively. Octreoscan UI was negatively associated with survival (p=0.002). CONCLUSIONS: NYHA class and sPAP are comparable ILD survival predictors. NYHA class is correlated with worse prognosis for IPF and NSIP vs. HP and GPA patients.

Role of integrated PET/CT with [¹8F]-FDG in the management of patients with fever of unknown origin: a single-centre experience.

PURPOSE: Fever of unknown origin (FUO) is a diagnostic challenge for the wide range of possible causes involved. The aim of our work was to evaluate the role of [(18)F]-fluorodeoxyglucose positron emission tomography computed tomography ([¹8F]-FDG-PET/CT) in managing patients with classical FUO. MATERIALS AND METHODS: Twenty-four consecutive patients (16 women, eight men; mean age, 56.5 years) with a diagnosis of FUO based on routine investigations were retrospectively studied. All underwent [¹8F]-FDG-PET/CT, which was considered true positive when the result was in agreement with the final diagnosis. RESULTS: A final diagnosis was reached in 17 of 24 patients (vasculitis, n=5; autoimmune disorder, n=2; neoplasm, n=3; infectious disease, n=6; biliary microlithiasis, n=1). In the remaining seven cases, no final diagnosis was established. PET-CT was useful in identifying aetiology in 11 patients, showing a diagnostic yield of 46% (11/24). Among the 11 cases with a negative PET scan, 10 did not show a worsening of the clinical condition. CONCLUSIONS: This study underlines the crucial role of [¹8F]-FDG-PET/CT in managing patients with FUO. If prospective trials on this topic confirm the present findings, PET/CT should be incorporated in the routine diagnostic work-up of patients with classical FUO.

Quantification of subsurface hydrologic connectivity in four headwater catchments using graph theory.

Hillslope-stream connectivity significantly affects streamflow and water quality responses during rainfall and snowmelt events, but is difficult to quantify. One approach to quantify subsurface hillslope-stream connectivity is graph theory, which considers linear connections between groundwater measurement sites. We quantified subsurface connectivity based on surface topography and shallow groundwater data from four small (<14 ha) headwater catchments in the Italian Dolomites and the Swiss pre-Alps, determined the relation between rainfall, antecedent wetness conditions and subsurface connectivity and assessed the sensitivity of the results to changes in the measurement network. Event total stormflow was correlated to maximum subsurface connectivity. Subsurface connectivity increased during rainfall events but maximum connectivity occurred later than peak streamflow, resulting in anti-clockwise hysteretic relations between the two. Subsurface connectivity was positively correlated to rainfall amount. Maximum subsurface connectivity was related to the sum of total rainfall plus antecedent rainfall for the Dolomitic catchments, but these relations were less clear for the pre-alpine catchments. For the pre-alpine catchments, the fractions of time that the groundwater monitoring sites were connected to the stream were significantly correlated to the upslope site characteristics, such as the Topographic Wetness Index. For the Dolomitic catchments, the fractions of time that the monitoring sites were connected to the stream were correlated to the topographic characteristics of the upslope contributing area for the catchment with the small riparian zone, and with the distance to the nearest stream for the catchment with the large riparian zone. The leave-one-out sensitivity analysis showed that small changes in the structure of the groundwater monitoring networks had a limited influence on the results, suggesting that graph-theory approaches can be used to describe subsurface hydrologic connectivity. However, the proposed graph-theory approach should be verified in other catchments with different groundwater monitoring networks.

Tumors of the retinal pigment epithelium metastasize to inguinal lymph nodes and spleen in tyrosinase-related protein 1/SV40 T antigen transgenic mice.

The pigment epithelium of the retina (RPE) is derived from the optic cup and is essential for function and development of the eye. We produced a transgenic mouse line that expresses simian virus (SV40) transforming sequences under control of the 1.4 kb tyrosinase-related protein 1 (TRP-1) promoter, targeting expression of T antigen (Tag) to the RPE. In transgenic embryos, RPE cells proliferated in the anterior part of the eye and near the optic nerve. This resulted in formation of tumors, which were pigmented and of epithelial origin. In 3 months-old mice, pigmented cells were detected in spleen and inguinal lymph nodes. In spleen, tyrosinase, TRP-1 and SV40 Tag were expressed and tyrosinase was enzymatically active. Pigmented regions were positive for an epithelial marker, cytokeratin. Cell lines were established from tumor and metastases and kept in culture for more than 2 months. These were pigmented, and maintained expression of tyrosinase, TRP-1, cytokeratin and SV40 Tag. This demonstrates that RPE tumor cells metastasize to lymph node and spleen. In conclusion, the metastasis from TRP-1/Tag RPE tumors towards spleen and lymph nodes serves as potential tool to investigate biology and metastasis of tumors derived from the pigment epithelium.

18F-FDG PET/CT in the post-operative monitoring of patients with adrenocortical carcinoma.

CONTEXT: The role of (18)F-labeled 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the post-operative monitoring of patients with adrenocortical carcinoma (ACC) is still unclear. OBJECTIVE: To assess the accuracy of FDG PET/CT to diagnose ACC recurrence in a real world setting. DESIGN AND METHODS: Retrospective evaluation of data of 57 patients with presumed ACC recurrence at CT scan who underwent FDG PET/CT within a median time of 20 days. We compared the results of either FDG PET/CT or CT with a gold standard confirmation of recurrence (positive histopathology report of removed/biopsied lesions or radiological progression of target lesions at follow-up) to assess their diagnostic performance at different body sites to correctly categorize target lesions. We also assessed whether FDG PET/CT findings may be useful to inform the management strategy. RESULTS: In 48 patients with confirmed ACC recurrence, we found that FDG PET/CT had lower sensitivity than CT in diagnosing liver and lung recurrences of ACC. FDG PET/CT had higher specificity than CT in categorizing liver lesions. FDG PET/CT had a greater positive likelihood ratio than CT to identify liver and abdominal ACC recurrences. The management strategy was changed based on FDG PET/CT findings in 12 patients (21.1%). CONCLUSIONS: The greater sensitivity of CT may be partly expected due the specific inclusion criteria of the study; however, the greater specificity of FDG PET/CT was particularly useful in ruling out suspected ACC recurrences found by CT. Thus, use of FDG PET/CT as a second-line test in the post-operative surveillance of ACC patients following CT finding of a potential recurrence may have a significant impact on patient management.

Glomerular involvement in human kala-azar. A light, immunofluorescent, and electron microscopic study based on kidney biopsies.

Glomerular involvement characterized by mesangial cell proliferation with fibrillar thickening of the axial region and deposits of immune complexes is reported in three human cases of kala-azar. IgG was seen in all 3 and Igm in 2 patients. Complement (C3) was detected in the glomeruli in all cases and fibrinogen in the only case in which it was tested for. The deposits appeared mainly along the mesangium and their staining was particularly strong for complement and IgG. Electron microscopy detected granular electron dense deposits mainly close to mesangial cells. In one case clumps made us of electron dense lamellae were seen in the glomerular basal membrane interpreted as evidence of focal membranolysis. No granulocytes were seen in the glomeruli. Attempts to demonstrate antigen were unsuccessful. The pattern of the lesion resembles that described in the kidney of human cases of hepatosplenic schistosomiasis, and the distribution of the deposits suggests that relatively large, poorly soluble complexes formed either in the presence of excess antigen or, under certain circumstances, in the presence of excess antibody, are trapped in the glomerular capillaries. The aggregates are partially shunted to the mesangial cells, which enlarge and proliferate.

Human schistosomiasis: Schistosoma mansoni antigen detection in renal glomeruli.

Twelve kidney, five biopsy and seven necropsy specimens, all from schistosomiasis mansoni patients were studied by light and immunoflurescent microscopy in an attempt to detect antigen in the glomerular walls. Deposits of IgM, IgG,I gA, IgE, complement C3 and fibrinogen were observered in most cases. Antigen was successfully detected in two cases(one biopsy and one necropsy specimen), both exhibiting proliferative glomerulonephritis. The only clinical manifestation was a slight proteinuria. IgG antibodies eluted from the sutopsy kidney homogenates showed specific binding mostly to Schistosoma mansoni gut, thus spggesting that the fixed antibodies (eluates) are, at least partially, consituted by antibodies similar to the anti-circulating antigen. These data reinfroce the hypothesis that renal injury in schistosomiasis is mediated through an immune complex disease.

lacZ transgenic mice to monitor gene expression in embryo and adult.

In transgenic experiments, lacZ can be used as a reporter gene for activity of a given promoter. Its main advantage is the ease of visualization in situ, on sections or in whole mount preparations, and the availability of simple protocols. In the following, we describe our procedure for detecting promoter activity in transgenic mice, including choice of lacZ vectors, generation of the transgenic mice, and analysis of expression. We had recently used this protocol to detect tyrosinase gene promoter activity in embryonic and adult brain.

Acute glomerulonephritis: three episodes demonstrated by light and electron microscopy, and immunofluorescence studies--a case report.

The patient, a white boy, had 3 episodes of recurrent acute glomerulonephritis at 7, 12 and 17 years of age. The episodes were preceded by impetigo and there was a good clinical and laboratorial recovery after all of them. Renal biopsies were performed during the acute episodes, and the light, immunofluorescence and electron microscopy studies showed only lesions typical of acute glomerulonephritis. Four months after the third episode another renal biopsy demonstrated only lesions compatible with the subsiding stages of acute glomerulonephritis.

Primary glomerular diseases in Brazil (1979-1999): is the frequency of focal and segmental glomerulosclerosis increasing?

AIMS: Different patterns of glomerulonephritis (GN) are reported from all over the world and the occurrence of primary GN is changing in the course of time. We report the frequencies of primary GN in a major teaching hospital in Brazil, from 1979-1999. METHODS: The case files of renal biopsies of primary GN were reviewed. The included patients were > 14 years of age, with native kidneys, and the specimens were examined with at least light and immunofluorescence microscopy. We excluded biopsy results of patients with any kind of known secondary glomerular involvement. Differences in proportions of diagnoses between the periods over time were evaluated using Chi-square test for trend. RESULTS: We considered 943 patients for the analysis. Focal and segmental glomerulosclerosis (FSGS) was the most common lesion (n = 279), followed by membranous GN (n = 140), membranoproliferative type I GN (n = 109) and IgA nephropathy (n = 109). FSGS (32.1%) was the most frequent diagnosis among nephrotic patients whereas IgAN (29.4%) predominated in non-nephrotic ones. The occurrence of FSGS increased from the earlier to the later periods: 22.3% (1979-1983), 23.7% (1984-1988), 35.7% (1989-1993), 33.9% (1994-1999), p < 0.05. The increase in frequency of FSGS was proportionally higher in non-nephrotic patients and FSGS became as common as IgA nephropathy in this group (31.6% and 28.0%, respectively) from 1994-1999. CONCLUSIONS: FSGS was the most common pattern of primary glomerulonephritis and its relative frequency seems to be increasing in biopsied patients over time. The reasons for this behavior are unclear and warrant further investigations.

PET in the clinical work-up of patients with spondylodiscitis: a new tool for the clinician?

AIM: The role of 18F-fluorodeoxyglucose-positron-emission tomography (FDG-PET) in the clinical management of patients with inflammatory diseases (e.g., chronic inflammatory diseases, fever of unknown origin, ostemyelitis, prosthesis infections) is still under investigation. The aim of the present study was to evaluate the usefulness of PET in the diagnostic work-up of patients with spondylodiscitis and to compare it with magnetic resonance imaging (MRI). METHODS: This retrospective study included 33 patients with suspected/confirmed spondylodiscitis. Two groups were created: 1) disease definition (n=24); and 2) treatment assessment (N.=16, 21 exams). Disease status was defined on the basis of data collected for symptoms, hematological parameters, imaging studies and histological findings, when available. Qualitative and semiquantitative analysis of the PET images was performed. The minimum duration of follow-up was 6 months. RESULTS: For the Disease Definition group, FDG-PET showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 92.9%, 50%, 72.2%, 83.3%, and 75%, respectively, and MRI showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 50%, 76.9%, 100%, and 81.3%, respectively. For the Treatment Assessment group, FDG-PET showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 90%, 81.8%, 81.8%, 90%, and 85.7%, respectively, and MRI showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 16.7%, 58.3%, 100% and 61.5%, respectively. No significant differences were observed between qualitative and semiquantitative evaluation of PET scans. CONCLUSION: PET and MRI showed similar accuracy in the diagnosis of spondylodiscitis, indicating that PET can be used when MRI is doubtful or unavailable. PET was more accurate and more specific than MRI in treatment assessment, suggesting that PET should be preferred over MRI for determining when treatment can be safely discontinued.

Bone marrow disease detection with FDG-PET/CT and bone marrow biopsy during the staging of malignant lymphoma: results from a large multicentre study.

AIM: To compare the accuracy of bone marrow biopsy (BMb) and positron emission tomography (PET) in bone marrow disease (BMD) detection, in a large multicentre population of patients with new diagnosis of malignant lymphoma. METHODS: PET and BMb were performed to complete disease staging in 337 consecutive patients: 130 Hodgkin's disease (HD), 207 aggressive non Hodgkin's lymphoma (NHL). Sensitivity, specificity and accuracy of both techniques in BMD detection were evaluated and compared. RESULTS: 87 patients with BMD (25 positives at both exams, 27 only at the BMb and 35 only at the PET study). PET vs. BMb were reordered: sensitivity: 69% vs. 59.8%; specificity: 99.2% vs. 100%; accuracy: 91.4% vs. 89.6%; positive predictive value: 96.8% vs. 100%; negative predictive value: 90.2% vs. 87.7%. CONCLUSION: The sensitivity of PET and BMb is similar (69% and 60%, respectively), PET and BMb are complementary: in fact out of 87 patients with confirmed BMD only 25 are positive at both exams, while 27 only at the BMb and 35 only at the PET exam; the integration of PET findings with BMb ones increases the diagnostic accuracy. Consequentially PET is essential during the staging of malignant lymphomas.

FDG-PET in the detection of bone marrow disease in Hodgkin's disease and aggressive non-Hodgkin's lymphoma and its impact on clinical management.

AIM: Identification of bone marrow disease (BMD) is a crucial step in the diagnostic work-up of patients with lymphoma. In lymphoma staging, bone marrow biopsy (BMb) is considered as the gold standard, despite its limitations. The aim of this study was to compare the usefulness of 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) vs BMb in the detection of BMD in patients with Hodgkin's disease (HL) or aggressive non-Hodgkin's lymphoma (NHL) and its impact on therapy. METHODS: A total of 194 consecutive patients with malignant lymphoma were referred for staging. The clinical stage was defined according to the Ann Arbor classification by means of contrast enhanced computed tomography (CT), BMb and whole body FDG-PET/CT scan. Sensitivity, specificity, accuracy in BMD evaluation were calculated for PET and BMb. RESULTS: FDG-PET vs BMb: sensitivity 65.3% vs 55.1%; specificity 98.6% vs 100%; accuracy 90.2% vs 88.7%; positive and negative predictive value 94.1% and 89.3% vs 100% and 86.8%, respectively. Although PET and BMb had similar sensitivity and accuracy, BMD was identified by both methods in only 10 out of 49 patients. There were no significant differences in PET and BMb accuracy between the HL and the NHL patients. Moreover, treatment regimen was changed in 12 patients on the basis of FDG-PET findings. CONCLUSION: Our study demonstrates that BMb and FDG-PET are complementary in the evaluation of BMD. FDG-PET improves the sensitivity of BMb, especially in the presence of focal BMD. Performing FDG-PET before BMb is advised for optimal biopsy site targeting.

Role of whole-body [18F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and conventional techniques in the staging of patients with Hodgkin and aggressive non Hodgkin lymphoma.

PURPOSE: The aim of this study was to evaluate the role of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the staging of Hodgkin's and aggressive non-Hodgkin's lymphoma (HL and NHL), comparing it with conventional diagnostic methods, i.e. contrast-enhanced CT and bone marrow biopsy. MATERIALS AND METHODS: Sixty-five consecutive patients (30 HL and 35 NHL) who underwent conventional disease staging and FDG-PET/CT were included. Concordance between conventional methods and PET was established when both procedures identified the same disease stage. Discordant findings were investigated further by using other diagnostic techniques (ultrasonography or magnetic resonance imaging) and/or clinical follow-up. RESULTS: PET correctly staged 93.8% of enrolled patients (61/65), whereas conventional techniques correctly staged 89.2% (58/65; p=NS, Chi(2) test). There was complete concordance in 54/65 patients (83.1%); among the remaining 11 cases, PET upstaged eight patients (seven true positive and one false positive), and downstaged three (all false negative). In 5/65 patients, chemotherapy treatment was modified on the basis of PET findings. CONCLUSIONS: Our data confirm the high accuracy of FDG-PET/CT in staging HL and NHL. FDG-PET/CT should therefore be used routinely in the initial evaluation of both patient subgroups.