B-Cell Responses in Chronic Chagas Disease: Waning of Trypanosoma cruzi-Specific Antibody-Secreting Cells Following Successful Etiological Treatment.

BACKGROUND: A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. METHODS: Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment. RESULTS: T. cruzi-specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment. CONCLUSIONS: T. cruzi-specific antibodies in the circulation of chronically T. cruzi-infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.

Chest CT in patients with shortness of breath: Comparing high pitch CT and conventional CT on respiratory artefacts and dose.

INTRODUCTION: To investigate chest respiratory artefact reduction using High Pitch Dual Source Computed Tomography (HPCT) compared to conventional CT (CCT) in symptomatic patients with shortness of breath. METHODS: Forty patients were prospectively examined on a second-generation Dual Source scanner. They were randomly divided into two groups: twenty patients underwent an experimental HPCT protocol and twenty control cases CCT protocol. Respiratory artefacts were evaluated using an ordinal score (0, 1 and 2) assigned by two readers with five and thirty years of experience. A qualitative assessment was performed using two categorical groups, group 1 = acceptable and group 2 = unacceptable. Dose Length Product (DLP) was compared. RESULTS: The two groups showed a statistical difference in artefacts reduction (p < 0.0001). HPCT demonstrated no artefacts in 82% of cases, while CCT showed no artefacts in 39% of cases. DLP showed no statistical differences (p = 0.6) with mean = 266.9 for HPCT and mean = 282.65 for CCT. HPCT provides high table speed in the z-direction allowing a high temporal resolution, which reduces respiratory artefacts during free-breathing acquisition. Despite the use of two x-ray tubes, the HPCT did not increase the dose to the patient but provided the highest images quality. CONCLUSIONS: In the emergency setting, HPCTs have been critical for achieving good image quality in uncooperative patients. IMPLICATIONS FOR PRACTICE: Acute respiratory failure is a common emergency department presentation, and the choice of high-speed acquisition CT may increase image quality.

Efficacy of continuous versus intermittent administration of nanoformulated benznidazole during the chronic phase of Trypanosoma cruzi Nicaragua infection in mice.

BACKGROUND: Benznidazole and nifurtimox are effective drugs used to treat Chagas' disease; however, their administration in patients in the chronic phase of the disease is still limited, mainly due to their limited efficacy in the later chronic stage of the disease and to the adverse effects related to these drugs. OBJECTIVES: To evaluate the effect of low doses of nanoformulated benznidazole using a chronic model of Trypanosoma cruzi Nicaragua infection in C57BL/6J mice. METHODS: Nanoformulations were administered in two different schemes: one daily dose for 30 days or one dose every 7 days, 13 times. RESULTS: Both treatment schemes showed promising outcomes, such as the elimination of parasitaemia, a reduction in the levels of T. cruzi-specific antibodies and a reduction in T. cruzi-specific IFN-γ-producing cells, as well as an improvement in electrocardiographic alterations and a reduction in inflammation and fibrosis in the heart compared with untreated T. cruzi-infected animals. These results were also compared with those from our previous work on benznidazole administration, which was shown to be effective in the same chronic model. CONCLUSIONS: In this experimental model, intermittently administered benznidazole nanoformulations were as effective as those administered continuously; however, the total dose administered in the intermittent scheme was lower, indicating a promising therapeutic approach to Chagas' disease.

Oxygen saturation or respiratory rate to improve risk stratification in hemodynamically stable patients with acute pulmonary embolism.

Essentials In acute pulmonary embolism (PE), risk stratification is essential to drive clinical management. Improving the 2014-ESC risk stratification strategy is crucial in hemodynamically stable patients. Oxygen saturation and respiratory rate improve risk stratification in hemodynamically stable PE. Simple and routine tests improve risk stratification of hemodynamically stable PE. SUMMARY: Background In patients with acute pulmonary embolism (PE), risk stratification for short-term death is recommended to drive clinical management. A risk stratification strategy combining the simplified Pulmonary Embolism Severity Index (PESI), echocardiography and troponin was proposed by the European Society of Cardiology (ESC) in 2014. The identification of hemodynamically stable patients at increased risk of death by this strategy needs improvement. Objective To assess whether further stratification by serial cut-off values of oxygen saturation or respiratory rate improves the accuracy of the ESC risk stratification strategy in hemodynamically stable PE patients. Methods Prospective cohorts of hemodynamically stable patients with PE were merged in a collaborative database. The accuracy of risk stratification for 30-day mortality by the original and a modified 2014 ESC strategy was assessed. Results Overall, 255 patients (27%) were categorized as low, 510 (54%) as intermediate-low and 181 (19%) as intermediate-high risk according to the original 2014 ESC strategy. Thirty-day mortality was 1.2% in low, 10% in intermediate-low and 11% in intermediate-high-risk patients. By adding oxygen saturation in air of < 88%, the discriminatory power of the 2014 ESC model improved for 30-day mortality (c-statistics, 0.71; 95% confidence interval [CI], 0.65-0.77 vs. 0.63, 95% CI, 0.56-0.69) and for PE-related death (c-statistics, 0.75; 95% CI, 0.69-0.81 vs. 0.63, 95% CI 0.56-0.69). Conclusions Simple and routine tests, such as oxygen saturation or respiratory rate, could be added to the 2014 ESC strategy for risk stratification to identify hemodynamically stable PE patients at increased risk of death who are potentially candidates for more aggressive treatment.

Automated culture of aquatic model organisms: shrimp larvae husbandry for the needs of research and aquaculture.

Modern research makes frequent use of animal models, that is, organisms raised and bred experimentally in order to help the understanding of biological and chemical processes affecting organisms or whole environments. The development of flexible, reprogrammable and modular systems that may help the automatic production of 'not-easy-to-keep' species is important for scientific purposes and for such aquaculture needs as the production of alive foods, the culture of small larvae and the test of new culture procedures. For this reason, we planned and built a programmable experimental system adaptable to the culture of various aquatic organisms, at different developmental stages. The system is based on culture cylinders contained into operational tanks connected to water conditioning tanks. A programmable central processor unit controls the operations, that is, water changes, temperature, light irradiance, the opening and closure of valves for the discharge of unused foods, water circulation and filtration and disinfection systems, according to the information received by various probes. Various devices may be set to modify water circulation and water changes to fulfil the needs of given organisms, to avoid damage of delicate structures, improve feeding performances and reduce the risk of movements over the water surface. The results obtained indicate that the system is effective in the production of shrimp larvae, being able to produce Hippolyte inermis post-larvae with low mortality as compared with the standard operation procedures followed by human operators. Therefore, the patented prototype described in the present study is a possible solution to automate and simplify the rearing of small invertebrates in the laboratory and in production plants.

Neurocognitive Correlates in Driving Under the Influence of Cannabis.

BACKGROUND & OBJECTIVE: Delta (9)-tetrahydrocannabinol (THC) is the main psychoactive compound in cannabis and is frequently identified in blood samples from apprehended drivers suspected for driving under the influence of drugs. Changing social norms towards cannabis and higher acceptability towards the drug emphasize the need for in-depth understanding of the acute neurocognitive and psychomotor effects caused by cannabis and how these effects are correlated to driving skills and performance. METHOD: In this review, PubMed, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE and Google Scholar databases were used to identify and select publications up to January 2017 dealing with acute and chronic neurocognitive effects induced by cannabis and ability to drive. Thirty-six publications were selected for this review. The studies conducted were experimental, using simulators or on-road studies and brain imaging (structural and functional) to better understand the acute and chronic effects on cognitive functions comprised in the short and long-term fitness to drive after cannabis consumption. CONCLUSION: In a case-crossover self-report study a significant odds ratio increase was found for driving- related injury after combined exposure to cannabis and alcohol compared to cannabis alone (OR of 10.9 and 5.8 respectively). Both, experimental and epidemiological studies have revealed that THC affects negatively both, psychomotor skills and cognitive functions. Studies of the acute effects of cannabis on driving have shown that drivers under the influence of this substance are impaired. Indeed, driving under the influence of cannabis doubles or triples the risk of a crash. Specifically, cannabis use impairs critical-tracking tasks, increases lane weaving, decreases reaction time, and divided attention.

Perturbed T cell IL-7 receptor signaling in chronic Chagas disease.

We have previously demonstrated that immune responses in subjects with chronic Trypanosoma cruzi infection display features common to other persistent infections with signs of T cell exhaustion. Alterations in cytokine receptor signal transduction have emerged as one of the cell-intrinsic mechanisms of T cell exhaustion. In this study, we performed an analysis of the expression of IL-7R components (CD127 and CD132) on CD4(+) and CD8(+) T cells and evaluated IL-7-dependent signaling events in patients at different clinical stages of chronic chagasic heart disease. Subjects with no signs of cardiac disease showed a decrease in CD127(+)CD132(+) cells and a reciprocal gain of CD127(-)CD132(+) in CD8(+) and CD4(+) T cells compared with either patients exhibiting heart enlargement or uninfected controls. T. cruzi infection, in vitro, was able to stimulate the downregulation of CD127 and the upregulation of CD132 on T cells. IL-7-induced phosphorylation of STAT5 as well as Bcl-2 and CD25 expression were lower in T. cruzi-infected subjects compared with uninfected controls. The serum levels of IL-7 were also increased in chronic chagasic patients. The present study highlights perturbed IL-7/IL-7R T cell signaling through STAT5 as a potential mechanism of T cell exhaustion in chronic T. cruzi infection.

Not only a clinical nightmare: amniotic fluid embolism in court.

Amniotic fluid embolism (AFE) is an uncommon obstetric condition involving usually women in labour or in the early post-partum period. Clinical consequences of this unpredictable and unpreventable pathology may be extremely serious with high morbidity and mortality rates. Data obtained from the US Amniotic Fluid Embolism Registry show that the process is more similar to anaphylaxis than to embolism, and the term anaphylactoid syndrome of pregnancy has been suggested because foetal tissue or amniotic fluid components are not universally found in women who present signs and symptoms related to AFE. The first aim of this paper has been to focus on the medico-legal aspects concerning the misdiagnosis and the treatment of the AFE and the Authors, with this purpose in mind, reviewed the main national law cases on medical malpractice claims involving both physicians and hospitals. The second aim has been to highlight the need to introduce a National register as a useful tool to raise the awareness of this disease among physicians and to improve the quality of care, which can be achieved through a proper identification and reporting of AFE cases. The application of a national register may limit the number of medico-legal litigations, which according to the national and foreign Jurisprudence are not currently based in favour of the predictability of AFE, but they focus their discussion on the importance of a prompt medical assistance when the effects of this disorder occur.

Permeable Adsorptive Barrier (PAB) for the remediation of groundwater simultaneously contaminated by some chlorinated organic compounds.

In this paper, a Permeable Reactive Barrier (PRB) made with activated carbon, namely a Permeable Adsorptive Barrier (PAB), is put forward as an effective technique for the remediation of aquifers simultaneously contaminated by some chlorinated organic compounds. A design procedure, based on a computer code and including different routines, is presented as a tool to accurately describe mass transport within the aquifer and adsorption/desorption phenomena occurring inside the barrier. The remediation of a contaminated aquifer near a solid waste landfill in the district of Napoli (Italy), where Tetrachloroethylene (PCE) and Trichloroethylene (TCE) are simultaneously present, is considered as a case study. A complete hydrological and geotechnical site characterization, as well as a number of dedicated adsorption laboratory tests for the determination of activated carbon PCE/TCE adsorption capacity in binary systems, are carried out to support the barrier design. By means of a series of numerical simulations it is possible to determine the optimal barrier location, orientation and dimensions. PABs appear to be an effective remediation tool for the in-situ treatment of an aquifer contaminated by PCE and TCE simultaneously, as the concentration of both compounds flowing out of the barrier is everywhere lower than the regulatory limits on groundwater quality.

Remediation of an aquifer polluted with dissolved tetrachloroethylene by an array of wells filled with activated carbon.

In this work, an array of deep passive wells filled with activated carbon, namely a Discontinuous Permeable Adsorptive Barrier (PAB-D), has been proposed for the remediation of an aquifer contaminated by tetrachloroethylene (PCE). The dynamics of the aquifer in the particular PAB-D configuration chosen, including the contaminant transport in the aquifer and the adsorption onto the barrier material, has been accurately performed by means of a computer code which allows describing all the phenomena occurring in the aquifer, simultaneously. A PAB-D design procedure is presented and the main dimensions of the barrier (number and position of passive wells) have been evaluated. Numerical simulations have been carried out over a long time span to follow the contaminant plume and to assess the effectiveness of the remediation method proposed. The model results show that this PAB-D design allows for a complete remediation of the aquifer under a natural hydraulic gradient, the PCE concentrations flowing out of the barrier being always lower than the corresponding Italian regulation limit. Finally, the results have been compared with those obtained for the design of a more traditional continuous barrier (PAB-C) for the same remediation process.

Lateral sellar angiolipomas: a therapeutic challenge. Our experience on two cases and review of the literature.

Angiolipomas are rare benign mesenchymal tumours, most commonly found in the subcutaneous tissue of the extremities. These neoplasms are rarely located in the central nervous system (CNS), with spinal localization being the most common in this group. Intracranial location is extremely infrequent, and only ten cases have been described in the sellar region. We report on two more patients with skull-base (intracranial) angiolipomas, the former presented with a long history of headache and the latter complained diplopia. Both patients were postoperatively verified as angiolipoma. Neuroimaging studies and peroperative features are presented and the role of microsurgery is discussed. On the basis of these tumours' characteristics, the management strategy of choice usually does not consist on surgical total removal, often a partial excision could be satisfying to improve the patient symptomatology. Nowadays, Gamma Knife surgery is standing out as an effective, additional and/or alternative, treatment modality.

In vitro effects of mycophenolic acid on survival, function, and gene expression of pancreatic beta-cells.

Post-transplant diabetes mellitus represents an important complication of prolonged immunosuppressive treatment after solid organ transplantation. The immunosuppressive toxicity, responsible for a persistent impairment of glucose metabolism in pancreatic islet-transplanted patients, is mainly attributed to calcineurin inhibitors and steroids, while other immunosuppressive molecules (azathioprine and mycophenolic acid, MPA) are considered not to have a toxic effect. In the present study, in vitro effects of MPA have been investigated in mouse beta-cell lines (ßTC-1 and ßTC-6) and in purified human pancreatic islets. ßTC-1, ßTC-6, and human pancreatic islets were exposed to various concentrations of MPA for different times. Consequently, we evaluated the viability, the induction of apoptosis, the glucose-stimulated insulin secretion, and the expression of ß-cell function genes (Isl1, Pax6, Glut-2, glucokinase) and apoptosis-related genes (Bax and Bcl2). ßTC-1, ßTC-6, and human islets treated, respectively, for 48 and 72 h with 15-30 nM MPA showed altered islet architecture, as compared with control cells. We observed for ßTC-1 and ßTC-6 almost 70% reduction in cell viability; three to sixfold induction of TUNEL/apoptotic-positive cells quantified by FACS analysis. A twofold increase in apoptotic cells was observed in human islets after MPA exposure associated with strong inhibition of glucose-stimulated insulin secretion. Furthermore, we showed significant down-regulation of gene expression of molecules involved in ß-cell function and increase rate between Bax/Bcl2. Our data demonstrate that MPA has an in vitro diabetogenic effect interfering at multiple levels with survival and function of murine and human pancreatic ß-cells.

Intrathecal baclofen therapy for severe spasticity: analysis on a series of 112 consecutive patients and future prospectives.

OBJECTIVE: Intrathecal baclofen therapy (ITB) is a well-known treatment for spasticity. Despite this fact, several topics have to be still discussed: new indications and screening tools, appropriate surgical timing and complicance avoidance. METHODS: A total of 112 consecutive patients all with a severe, progressive and refractory to medical therapy spasticity from different causes were treated using ITB, after a bolus test. Every patient was assessed by means of Modified Ashworth Scale (MAS), Penn spasm frequency scale (SFS) and Visual Analog Scale for pain. Since available, a Gait analysis was also performed. RESULTS: There were 63 males (56%) and 49 females (44%). Seventy-four (66%) had a quadriparesis, 34 (30.4%) had a paraparesis and 4 (3.6%) were hemiplegic. Among these patients 77 (68.7%) were non ambulatory, while 35 (31.3%) were ambulatory. These patients suffered from spasticity due to many different diseases. Mean follow-up was 55 months. The mean Modified Ashworth score decreased from 4.5±0.5 preoperatively to 1.2±0.4 on chronic intrathecal baclofen. Daily baclofen dose varied between 23 and 500 mcg. Drug-induced complications and catheter related problems occurred, respectively in 7 (6.3%) and 10 patients (8.9%). CONCLUSIONS: Although ITB is a well known and good treatment option in the management of severe spasticity, because of the different goals and subgroups of patients treated, a variety of techniques are needed to evaluate the benefits of this therapy. New indications, effects of ITB on central nervous system and cognitive functions needs yet to be fully clarified.

A procedure to design a Permeable Adsorptive Barrier (PAB) for contaminated groundwater remediation.

A procedure to optimize the design of a Permeable Adsorptive Barrier (PAB) for the remediation of a contaminated aquifer is presented in this paper. A computer code, including different routines that describe the groundwater contaminant transport and the pollutant capture by adsorption in unsteady conditions over the barrier solid surface, has been developed. The complete characterization of the chemical-physical interactions between adsorbing solids and the contaminated water, required by the computer code, has been obtained by experimental measurements. A case study in which the procedure developed has been applied to a tetrachloroethylene (PCE)-contaminated aquifer near a solid waste landfill, in the district of Napoli (Italy), is also presented and the main dimensions of the barrier (length and width) have been evaluated. Model results show that PAB is effective for the remediation of a PCE-contaminated aquifer, since the concentration of PCE flowing out of the barrier is everywhere always lower than the concentration limit provided for in the Italian regulations on groundwater quality.

Spontaneous intraparenchymal tension pneumocephalus triggered by compulsive forceful nose blowing.

The case is described of a 50-year-old man, treated for 10 years in an outpatient psychiatric clinic for an obsessive compulsive disorder, who presented with acute loss of consciousness after forceful nose blowing. A CT scan revealed an intraparenchymal air collection with tension signs in the left frontal lobe and a bone defect in the roof of the ethmoid sinus. After emergency left frontal craniotomy and dura opening, the gaseous collection was evacuated by a ventricular catheter inserted into the brain and the bone defect was repaired with pericranium flap and muscle. The postoperative course was uneventful with neurocognitive improvement and regained motility. Spontaneous tension pneumocephalus is a rare life-threatening condition which is often caused by a bone defect near the tegmen tympani. This case illustrates both an unusual cause and a unique surgical treatment for spontaneous tension intraparenchymal pneumocephalus. It can be a dangerous entity with potential for early mortality and long-term morbidity if not promptly decompressed. The pathogenesis, diagnosis and surgical strategies for spontaneous tension pneumocephalus are briefly discussed.

Ultrasound-guided hyaluronic acid injection in carpometacarpal osteoarthritis: short-term results.

Carpometacarpal osteoarthritis (CMC-OA) is a disabling condition, characterized by pain and functional impairment. The aim of the present study is to evaluate the efficacy of a single ultrasoundguided injection of hyaluronic acid (HA) in patients suffering from CMC-OA. Eighteen patients with CMC-OA, grade 2-3 Kellgren and Lawrence score, attending the Orthopaedic Department of the University Hospital of Chieti, were enrolled. They underwent clinical evaluation at baseline and after one month follow-up, evaluating: grading of pain (VAS at rest and during activities), function (Dreiser Index), grip and pinch strengths Jamar dynamometer), as well as NSAIDs consumption. Each patient received a single ultrasound- guided injection of HA into the articular CMC joint. The results were that pain at rest and during activities decreased from 1.8 +/= 1.07 to 0.5 +/= 0.68 (p < 0.001) and from 8.05 +/= 0.94 to 4.15 +/= 1.42 (p < 0.001), respectively. Dreiser Functional Index showed a significant improvement (+11.59 percent; p < 0.004), as well as pulp pinch strength (24.07 percent; p < 0.001). The consumption of NSAIDs was also clearly reduced, from 16 to 7 patients (-45 percent) and from 2.45 +/= 1.98 to 1.15 +/= 1.30 tablets per week (p < 0.02). Mild local side effects, lasting less than 3 hours, were observed only in 2 cases. A single ultrasound guided injection of HA is a safe and effective procedure in CMC-OA, with a significant improvement in terms of pain and function. However, studies with larger samples and longer term follow-up are warranted.