Correlations between cerebrospinal fluid biomarkers, neurocognitive tests, and resting-state electroencephalography (rsEEG) in patients with HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in people living with HIV (PLWH) despite successful treatment with combination antiretroviral therapy (cART). HAND pathogenesis is complex and definitive surrogate biomarkers are not clearly defined. Brain function has been assessed through the evaluation of cortical source rhythms with delta waves associated with neurological impairment. The aim of this study was to assess the correlation between EEG cortical sources, cerebrospinal fluid (CSF) biomarkers, and neurocognitive tests in PLWH with HAND. PLWH with HAND without significant comorbidities were enrolled. Baseline rsEEG-LORETA waves, CSF biomarkers (t-tau, p-tau, ß-amiloid42, neopterin, S100ß), and neurocognitive tests were correlated and compared through non-parametric tests (Spearman's rho and Mann-Whitney); data are presented as medians (interquartile ranges). Fifty-four patients were enrolled. Median time of suppressed HIV-RNA and CD4+ T-lymphocyte were 10 years (5.5-15) and 691/uL (477-929). Thirty-nine participants (72%) underwent CSF collection: abnormal biomarkers were found in a small percentage. Only neopterin showed a statistically significant correlation with delta activity [parietal (rho 0.579; p < 0.001), occipital (rho 0.493; p = 0.007), and global sources (rho 0.464 p = 0.011)]. Seven patients (12.9%) showed an abnormal neopterin level (> 1.5 ng/mL) with significantly higher delta source activity compared to the ones with in-range concentrations. We observed a statistically significant correlation between working memory test Trail Making B with both CSF neopterin levels and delta waves (p values < 0.05). In a small sample of PLWH with HAND, we observed that higher CSF neopterin levels were associated with higher EEG delta waves and worse working memory tests.

Antiretroviral concentrations in the presence and absence of valproic acid.

OBJECTIVES: An unexpected drug-drug interaction has been recently reported between dolutegravir, an HIV integrase inhibitor, and valproic acid. Despite there being several potential underlying mechanisms, plasma protein displacement has been suggested. The aim of this study was to assess plasma concentrations of several antiretrovirals when administered with or without valproic acid. METHODS: We performed a therapeutic drug monitoring registry analysis and identified patients concomitantly taking antiretrovirals and valproic acid and without clinical affecting conditions or interacting drugs. RESULTS: One hundred and thirty-four patients were identified. Median (IQR) age and BMI were 49.7 years (45-56) and 23.4 kg/m2 (20.8-26.3) and 78 were male (58.2%). Despite small groups, we observed no major effect on antiretroviral exposure, even when considering highly protein-bound compounds (such as etravirine), with the exception of dolutegravir trough concentrations [median (IQR) = 132 ng/mL (62-227) in individuals on valproic acid versus 760 ng/mL (333-1407) in those not receiving valproic acid]. CONCLUSIONS: Valproic acid does not have a major effect on antiretrovirals other than dolutegravir. The mechanism of this unexpected drug-drug interaction may be the combination of protein displacement, reduced absorption and CYP3A4 induction.

Serum Trimethylamine-N-oxide Concentrations in People Living with HIV and the Effect of Probiotic Supplementation.

BACKGROUND: The incidence of cardiovascular disorders in people living with HIV (PLWH) is higher than that in non-infected individuals. Traditional and specific risk factors have been described but the role of the gut microbiota-dependent choline metabolite, trimethylamine-N-oxide (TMAO) is still unclear. METHODS: A cross-sectional analysis and a longitudinal analysis (with high-dose probiotic supplementation) were performed to measure serum TMAO concentrations through UHPLC-MS/MS. Stable outpatients living with HIV on highly active antiretroviral treatment with no major cardiovascular disease were enrolled. Non-parametric tests (bivariate and paired tests) and a multivariate linear regression analysis were used. RESULTS: A total of 175 participants were enrolled in the study. Median serum TMAO concentrations were 165 (103-273) ng/mL. An association with age, serum creatinine, number of antiretrovirals, multimorbidity and polypharmacy was observed; at linear logistic regression analysis, multimorbidity was the only independent predictor of TMAO concentrations. Carotid intima media thickness (IMT) was 0.85 (0.71-1.21) mm, with a trend towards higher TMAO concentrations observed in patients with IMT >0.9 mm (P=0.087). In the 25 participants who received probiotic supplementation, TMAO levels did not significantly change after 24 weeks (Wilcoxon paired P=0.220). CONCLUSION: Serum TMAO levels in PLWH were associated with multimorbidity, higher cardiovascular risk and subclinical atherosclerosis and were not affected by 6 months of high-dose probiotic supplementation.

Secondary colonic stent insertion in acute large bowel obstruction following primary stent failure.

INTRODUCTION: Colonic stent insertion has been shown to be an effective treatment for patients with acute large bowel obstruction, either as a bridge to surgery or as definitive treatment. However, little is known of the role of secondary stent insertion following primary stent failure in patients considered inappropriate or high risk for emergency surgery. METHODS: Fourteen patients presenting with acute large bowel obstruction who had previously been treated with colonic stent insertion were studied. All underwent attempted placement of a secondary stent. RESULTS: Technical deployment of the stent was accomplished in 12 patients (86%) but only 9 (64%) achieved clinical decompression. Successful deployment and clinical decompression of a secondary stent was associated with older age (p=0.038). Sex, pathology, site of obstruction, duration of efficacy of initial stent and cause of primary failure were unrelated to outcome. No procedure related morbidity or mortality was noted following repeated intervention. CONCLUSIONS: Secondary colonic stent insertion appears an effective, safe treatment in the majority of patients presenting with acute large bowel obstruction following failure of a primary stent.

Cross-linked hyaluronic acid sub-micron particles: in vitro and in vivo biodistribution study in cancer xenograft model.

This paper focused on the biodistribution of the cross-linked hyaluronic acid (HA-NPs) sub-micron particles in tumor-bearing mice. Solvent-non solvent method followed glutaraldehyde cross-linking utilized for the fabrication of HA-NPs. Size measurement and morphological analysis were performed by dynamic light scattering and electron microscopy, respectively and the size found to be in the range of 200-400 nm. In vitro viability in LNCaP cell line was assessed by water soluble tetrazolium assay after 24 h of exposure to sub-micron particles and no toxicity was found to higher concentration of 3 mg/mL. Internalization of particles in prostate cancer cell LNCaP were studied by confocal microscopy with FITC labeled submicron particles and involvement of hyaluronan receptor mediated uptake/endocytosis was confirmed by competitive assay. Biodistribution studies were performed in xenograft prostate cancer mice model with fluorophore labeled particles and monitored in tumoral parenchyma with strong fluorescence, meanwhile very less signal in liver, kidney and spleen while no fluorescence found in lung after 24 h of systemic administration; that shown ability of this HA based system to recognize cancer tissue. These result fetched that hyaluronic acid based system is selective for tumoral site and can be utilized to deliver bioactives in specific (targeting) and controlled (temporal) manner to cancerous tissue.

Gluten-free diet: a new strategy for management of painful endometriosis related symptoms?

AIM: Pelvic pain affects 4% to 39% of women and accounts for 10-40% of all outpatient gynecologic visits. The etiology of painful endometriosis-related has not been fully delineated. No studies have been published concerning gluten-free diet administered to achieved relief of painful symptoms endometriosis-related. The aim of this retrospective study was to evaluate the effectiveness for the outcomes of endometriosis-related pain and quality of life of gluten-free diet in a follow-up of 12 months in patients with chronic pelvic pain endometriosis-related. METHODS: Two hundred seven patients with severe painful endometriosis-related symptoms entered the study. At enrolment time, the baseline values of painful symptoms were assessed by Visual Analogue Scale (VAS) for dysmenorrhoea, non-menstrual pelvic pain, and dyspareunia. According to VAS, pain severity was scored from 0-10; 0 indicating the absence of pain, and 1-4, 5-7 and 8-10 mild, moderate and severe respectively. A gluten-free diet was submitted to all patients and a new evaluation was performed after 12 months of diet. Student t test was used for statistical analysis. RESULTS: At 12 month follow-up, 156 patients (75%) reported statistically significant change in painful symptoms (P<0.005), 51 patients (25%) reported not improvement of symptoms. No patients reported worsening of pain. A considerable increase of scores for all domains of physical functioning, general health perception, vitality, social functioning, and mental health was observed in all patients (P<0.005). CONCLUSION: In our experience, painful symptoms of endometriosis decrease after 12 months of gluten free diet.

Quantifying methane oxidation in a landfill-cover soil by gas push-pull tests.

Methane (CH(4)) oxidation by aerobic methanotrophs in landfill-cover soils decreases emissions of landfill-produced CH(4) to the atmosphere. To quantify in situ rates of CH(4) oxidation we performed five gas push-pull tests (GPPTs) at each of two locations in the cover soil of the Lindenstock landfill (Liestal, Switzerland) over a 4 week period. GPPTs consist of the injection of a gas mixture containing CH(4), O(2) and noble gas tracers followed by extraction from the same location. Quantification of first-order rate constants was based upon comparison of breakthrough curves of CH(4) with either Ar or CH(4) itself from a subsequent inactive GPPT containing acetylene as an inhibitor of CH(4) oxidation. The maximum calculated first-order rate constant was 24.8+/-0.8 h(-1) at location 1 and 18.9+/-0.6 h(-1) at location 2. In general, location 2 had higher background CH(4) concentrations in vertical profile samples than location 1. High background CH(4) concentrations in the cover soil during some experiments adversely affected GPPT breakthrough curves and data interpretation. Real-time PCR verified the presence of a large population of methanotrophs at the two GPPT locations and comparison of stable carbon isotope fractionation of CH(4) in an active GPPT and a subsequent inactive GPPT confirmed that microbial activity was responsible for the CH(4) oxidation. The GPPT was shown to be a useful tool to reproducibly estimate in situ rates of CH(4) oxidation in a landfill-cover soil when background CH(4) concentrations were low.

Detection of gunshot residues on cadaveric skin using sodium rhodizonate and a counterstain.

We report a staining method for cadaveric tissue using sodium rhodizonate as a skin marker for gunshot residues and a counterstain for the surrounding connective tissue. We studied six well preserved subjects who had died of close range gunshot injury. Skin fragments were removed from the bullet entrance hole including both the disrupted area and adjacent macroscopically intact tissue. Because microscopic examination of postmortem material is difficult after histomorphologic alterations already have occurred as a consequence of postmortem tissue changes, it is necessary to use a staining method that, while detecting gunshot residues, can also make skin cell constituents recognizable from both qualitative and quantitative perspectives. Triphenylmethane dyes (acid fuchsin, aniline blue WS, light green SF yellowish, brilliant green and ethyl green) have proven appropriate for the purpose.

Changes in lead availability affect bacterial community structure but not basal respiration in a microcosm study with forest soils.

This study investigates the effects of Pb during time on the bacterial communities of forest soils using water-extractable Pb concentrations in the soil solution as predictors of Pb bioavailability. In a microcosm experiment we applied increasing concentrations of Pb(NO(3))(2) solutions (0.5, 2, 8, 32 mM) to 5 forest soils of pH<5 and to a calcareous soil of pH>6.5. Sampling of the microcosms was performed after 3, 30 and 90 days of incubation. Community analysis included basal respiration rates and changes in the structure of the bacterial communities through T-RFLP fingerprinting. We also investigated functional stability in terms of resistance, expressed as the effects on basal respiration after 3 days of incubation, and of resilience, expressed as the recovery of bacterial community structure and of respiration rates after 90 days of incubation. Water-extractable Pb increased with time in most of the soils, in parallel with an increase of water-extractable dissolved organic carbon (DOC). The increased concentrations slightly affected bacterial community structure, although OTU (operational taxonomic unit) richness was not significantly reduced with Pb concentrations in any of the soils. The highest Pb treatment (32 mM) caused significant effects on basal respiration in some of the acidic soils, but no clear trend was observed in relation to increased Pb bioavailability with time. Resistance to Pb additions was evident in five of the six soils, but only two showed resilience after 90 days. This is the first study showing the effects of time on Pb bioavailability in soils and on the resulting reactions of the soil microbial communities.

Oncologic emergencies secondary to advanced colorectal cancer successfully treated with oxaliplatin/5-fluorouracil/leucovorin: report of three cases.

Metastatic/advanced colorectal cancer is considered a resistant disease and oncologic emergencies secondary to advanced disease may be regarded with a nihilistic attitude. The objective of this report is to emphasize the efficacy of the oxaliplatin/5-fluorouracil/leucovorin regimen (FOLFOX-4) in three patients presenting oncologic emergencies secondary to advanced colon cancer. The first case was a 40-year-old man with severe respiratory insufficiency due to massive carcinomatous lymphangitis; subsequently a cecal adenocarcinoma was diagnosed. The patient's conditions became life-threatening and he was admitted to the intensive care unit. The second case was a 41-year-old woman presenting with fever, abdominal mass and pain. Ultrasound and CT-scan revealed two hepatic masses (13 x 15 and 15 x 20 cm), diagnosed as liver metastases from colon cancer. The patient's condition deteriorated with intestinal obstruction secondary to the large left liver mass. The third case was a 58-year-old woman presenting with hepatic mass, fever and weight loss. Ultrasound and CT-scan showed a liver lesion occupying the right lobe (12 x 14 cm). Ultrasonically-guided biopsy and colonoscopy showed liver metastases from cecal cancer. A 5-fluorouracil/leucovorin regimen failed to improve her clinical condition and she had disease progression, inferior vena cava neoplastic thrombosis and right hydronephrosis. All three patients rapidly improved after a few cycles of oxaliplatin-containing chemotherapy. These cases demonstrate that even patients with advanced colorectal cancer presenting with oncologic emergencies and life-threatening conditions can be successfully treated with the FOLFOX-4 regimen.

Small particle reagents technique can help to point out wet latent fingerprints.

SPR is a technique performed to detect latent fingerprints left on wet surfaces, based upon the reaction between the fatty components present in the traces and hydrophobic tails of the specific reagents. These tails are linked to a hydrophilic head, which reacts with metal salt to give a white or black precipitate. The literature reports that it is possible identifying latent fingerprints with cyanoacrylate fuming procedure, after drying the surface, but you cannot always do it. In the present report we want to show a casework that can concern a find completely dust covered.

Focal liver lesions in non-Hodgkin's lymphoma: investigation of their prevalence, clinical significance and the role of Hepatitis C virus infection.

Imaging techniques like ultrasonography (US) or computed tomography (CT) allow full liver scanning and the accurate detection of focal lesions of the liver parenchyma. The occurrence of such lesions in concomitance with non-Hodgkin's lymphoma (NHL), both at the onset of the disease and during follow-up, is of great significance, because it affects staging, prognosis and therapeutic choices. Moreover, the occurrence of focal liver lesions in the setting of a lymphoma is generally considered to be a marker of liver involvement. Nonetheless, data on the prevalence and clinical significance of focal liver lesions occurring in these clinical conditions are limited. Therefore, we retrospectively evaluated the prevalence, nature and clinical significance of focal liver lesions diagnosed by imaging techniques (US and CT) in 414 consecutive NHL patients. The nature of the lesions was established either by US-guided biopsy or by evaluation of the response to chemotherapy for the underlying disease and confirmed by clinical and US follow-up. Subtype of NHL (aggressive or indolent) and Hepatitis C virus (HCV) status were also considered. We detected 129 focal liver lesions (76 at onset and 53 during the follow-up). Hepatic involvement by NHL was found in 69 cases (53%). We observed 7 cases of Hepatocellular Carcinoma (HCC) and 3 cases of metastasis. At onset, only 39% of the detected lesions were due to lymphoma and 58% were benign. Conversely, 74% of the liver lesions detected during the follow-up were due to NHL while 15% to a malignancy other than NHL. All HCC cases occurred in HCV-positive patients with chronic liver disease. We concluded that the focal liver lesions detected at onset in NHL patients are frequently benign and unrelated to the underlying disease. Conversely, most focal liver lesions detected during the follow-up period are malignant and the possibility of HCC occurrence in HCV-positive patients should always be considered. Therefore, these lesions should undergo a full diagnostic work-up, including US-guided biopsy.

Palliative and therapeutic activity of IL-2 immunotherapy in unresectable malignant pleural mesothelioma with pleural effusion: Results of a phase II study on 31 consecutive patients.

Malignant pleural mesothelioma is often unresectable at diagnosis, is refractory to cytotoxic agents and is frequently complicated by pleural effusion. The expected survival range for patients with or without involvement of visceral pleura is respectively 1-9 and 9-12 months; mesothelioma-related pleural effusion severely impairs the patients' quality of life and easily relapses after conservative treatments. Intrapleural administration of IL-2 is reported to be effective both in tumor-associated malignant pleurisy and on primary mesothelioma, whereas few data exist about IL-2 systemic administration. In order to assess the palliative and therapeutic activity of IL-2 in unresectable pleural malignant mesothelioma with pleural effusion, we performed a phase II study on 31 consecutive patients (M/F 16/15; median age 61 years, range 40-84; PS ECOG 0 n=7; ECOG 1 n=15; ECOG 2 n=9; stage IA n=13; IB n=9; II n=7; IV=2) who received first-line therapy with intrapleural repeated instillation of 9000000 I.U. IL-2 twice/weekly for 4 weeks, after needle thoracenthesis. In nonprogressing patients, 3000000 I.U. IL-2 were subcutaneously administered thrice weekly for up to 6 months. Toxicity (WHO criteria) with intrapleural IL-2 consisted of grade 3 fever in 6/31 (19%) patients and of cardiac toxicity (failure) grade 3 in one patient (3%); toxicity during subcutaneous treatment was mild to moderate, mainly a flu-like syndrome. In 28/31 (90%) of patients there was no further or minimal (asymptomatic) pleural fluid collection (according to Paladine criteria); pleurisy relapsed only in 1/28 patients after 19 months. Tumor objective response (WHO criteria), evaluated by CT, occurred in seven patients (one CR and six PR; ORR 22%); ten patients achieved SD and 14 patients progressed. Median overall survival was 15 months (range 5-39) in all patients. IL-2 intrapleural administration followed by low-dose IL-2 subcutaneously in pleurisy-complicated malignant mesothelioma is feasible and active both in palliation of pleural effusion and on primary tumor, with manageable toxicity. The overall survival observed in nonprogressing patients warrants further randomized studies with IL-2 aimed to the patient outcome.

[Fascicular ventricular tachycardia]. / La tachicardia ventricolare fascicolare.

Fascicular tachycardia is an uncommon idiopathic ventricular tachycardia, originating from the left ventricle; it usually occurs in young male patients, with a high prevalence in south-east Asiatic people. Electrocardiographic aspects of this unique ventricular tachycardia (right bundle branch block morphology and left or right-axis deviation, with a moderate QRS widening) and verapamil sensitivity make it often difficult the differential diagnosis with other forms of supraventricular tachycardia. Reentry is believed to be the operative mechanism of fascicular tachycardia, with the reentrant circuit located in the Purkinje network, in the region of the left posterior or anterior fascicle. The slow conduction zone participating in the reentry circuit, made up of partially depolarized Purkinje fibers, seems to be located in a relatively wide area, from the basal to the apical left interventricular septum. Intravenous verapamil is elective in acute treatment; however oral verapamil shows poor efficacy in preventing tachycardia relapses. Ablative approach is very effective; success is achieved in approximately 90% of patients, with rare complications. Recently diastolic potentials during fascicular tachycardia have been reported and these findings have given rise to new electrophysiological hypotheses and new indications about the successful ablation site.