Calcium Channel-Dependent Induction of Long-Term Synaptic Plasticity at Excitatory Golgi Cell Synapses of Cerebellum.

Golgi cells, together with granule cells and mossy fibers, form a neuronal microcircuit regulating information transfer at the cerebellum input stage. Despite theoretical predictions, little was known about long-term synaptic plasticity at Golgi cell synapses. Here, we have used whole-cell patch-clamp recordings and calcium imaging to investigate long-term synaptic plasticity at excitatory synapses impinging on Golgi cells. In acute mouse cerebellar slices, mossy fiber theta-burst stimulation (TBS) could induce either long-term potentiation (LTP) or long-term depression (LTD) at mossy fiber-Golgi cell and granule cell-Golgi cell synapses. This synaptic plasticity showed a peculiar voltage dependence, with LTD or LTP being favored when TBS induction occurred at depolarized or hyperpolarized potentials, respectively. LTP required, in addition to NMDA channels, activation of T-type Ca2+ channels, while LTD required uniquely activation of L-type Ca2+ channels. Notably, the voltage dependence of plasticity at the mossy fiber-Golgi cell synapses was inverted with respect to pure NMDA receptor-dependent plasticity at the neighboring mossy fiber-granule cell synapse, implying that the mossy fiber presynaptic terminal can activate different induction mechanisms depending on the target cell. In aggregate, this result shows that Golgi cells show cell-specific forms of long-term plasticity at their excitatory synapses, that could play a crucial role in sculpting the response patterns of the cerebellar granular layer.SIGNIFICANCE STATEMENT This article shows for the first time a novel form of Ca2+ channel-dependent synaptic plasticity at the excitatory synapses impinging on cerebellar Golgi cells. This plasticity is bidirectional and inverted with respect to NMDA receptor-dependent paradigms, with long-term depression (LTD) and long-term potentiation (LTP) being favored at depolarized and hyperpolarized potentials, respectively. Furthermore, LTP and LTD induction requires differential involvement of T-type and L-type voltage-gated Ca2+ channels rather than the NMDA receptors alone. These results, along with recent computational predictions, support the idea that Golgi cell plasticity could play a crucial role in controlling information flow through the granular layer along with cerebellar learning and memory.

After Effects of Cerebellar Continuous Theta Burst Stimulation on Reflexive Saccades and Smooth Pursuit in Humans.

The use of cerebellar repetitive transcranial magnetic stimulation has been attempted for perturbing reflexive and voluntary eye movements, but discrepancies are seen between the results of distinct studies possibly due to the different stimulation sites, intensities, and paradigms. We describe the after effects of 20 and 40 s continuous Theta Burst Stimulation (cTBS) as compared to sham stimulation, applied over the lateral cerebellar vermis and paravermis on Reflexive Saccades (RS) and Smooth Pursuit (SP) eye movements, recorded in the 30 min following stimulation. The experiments were carried out in eight healthy volunteers, and eye movements were recorded monocularly with video-oculography. The 40 s cTBS significantly increased the amplitude of ipsilateral RS and the acceleration of the ipsilateral SP, and this effect was detectable all over the 30-min recording period; 40 s cTBS did not modify the other parameters, namely the peak velocity, the duration and the latency of RS, and the latency and the velocity of SP. The 20 s cTBS was ineffective on all RS and SP parameters. Finally, we detected a significant quite-linear reduction of RS peak velocity over time, but this was independent from cTBS and was probably caused by fatigue. The effects of 40 s cTBS in our experiments mimic the disorder of ocular motility in Wallenberg's syndrome and could result from functional impairment of cerebellopontine pathways. This effect lasts 30 min at least, and can provide a useful framework for adaptive ocular motor studies.

Cerebellar theta burst stimulation dissociates memory components in eyeblink classical conditioning.

The cerebellum plays a critical role in forming precisely timed sensory-motor associations. This process is thought to proceed through two learning phases: one leading to memory acquisition; and the other leading more slowly to memory consolidation and saving. It has been proposed that fast acquisition occurs in the cerebellar cortex, while consolidation is dislocated into the deep cerebellar nuclei. However, it was not clear how these two components could be identified in eyeblink classical conditioning (EBCC) in humans, a paradigm commonly used to investigate associative learning. In 22 subjects, we show that EBCC proceeded through a fast acquisition phase, returned toward basal levels during extinction and then was consolidated, as it became evident from the saving effect observed when re-testing the subjects after 1 week of initial training. The results were fitted using a two-state multi-rate learning model extended to account for memory consolidation. Transcranial magnetic stimulation was used to apply continuous theta-burst stimulation (cTBS) to the lateral cerebellum just after the first training session. Half of the subjects received real cTBS and half sham cTBS. After cTBS, but not sham cTBS, consolidation was unaltered but the extinction process was significantly impaired. These data suggest that cTBS can dissociate EBCC extinction (related to the fast learning process) from consolidation (related to the slow learning process), probably by acting through a selective alteration of cerebellar plasticity.

Lifestyle and high density lipoprotein cholesterol in postmenopause.

OBJECTIVES: Menopause is characterized by hormonal and metabolic changes. These are linked to increased risk of cardiovascular disease, for which low blood plasma levels of high density lipoprotein (HDL) cholesterol are an independent risk factor. The present study investigated variables linked with basal plasma HDL cholesterol levels and the effects of aerobic training, on their variations, in 40 postmenopausal women. METHODS: We assessed body composition, dietary habits and maximal aerobic capacity of participants. Characteristics of daily physical activity and plasma lipoproteins were measured. The women walked on 4 days/week, for 14 weeks, at moderate intensity, and they were grouped according to the resulting tertiles of basal plasma HDL cholesterol levels. RESULTS: Logistic regression analysis showed that waist-to-hip ratio and number of daily bouts of moderate-intensity physical activity, held for at least 10 consecutive minutes (B10m/day), are predictive variables of basal plasma HDL cholesterol levels. After the training period, the first and second tertiles increased plasma HDL cholesterol levels, while the third tertile decreased plasma HDL cholesterol levels. The tertiles showed different remodelling of spontaneous physical activity: the third tertile reduced B10m/day, while the others did not. CONCLUSIONS: This study provides knowledge about the relationships of plasma HDL cholesterol levels with characteristics of physical activity. Furthermore, it shows that physical exercise engagement can result in negative compensation of spontaneous physical activity that could counteract or reduce the positive effects of the aerobic training on plasma HDL cholesterol levels.

Late-onset bursts evoked by mossy fibre bundle stimulation in unipolar brush cells: evidence for the involvement of H- and TRP-currents.

Synaptic transmission at central synapses has usually short latency and graded amplitude, thereby regulating threshold crossing and the probability of action potential generation. In the granular layer of the vestibulo-cerebellum, unipolar brush cells (UBCs) receive a giant synapse generating a stereotyped excitatory postsynaptic potential (EPSP)-burst complex with early-onset (∼2 ms) and high reliability. By using patch-clamp recordings in cerebellar slices of the rat vestibulo-cerebellum, we found that mossy fibre bundle stimulation also evoked (in ∼80% of cases) a late-onset burst (after tens to hundreds of milliseconds) independent of EPSP generation. Different from the early-onset, the late-onset burst delay decreased and its duration increased by raising stimulation intensity or the number of impulses. Although depending on synaptic activity, the late-onset response was insensitive to perfusion of APV ((2R)-5-amino-phosphonopentanoate), NBQX (2,3-dioxo-6-nitro-tetrahydrobenzo(f)quinoxaline-7-sulfonamide) and MCPG ((RS)-α-methyl-4-carboxyphenylglycine) and did not therefore depend on conventional glutamatergic transmission mechanisms. The late-onset response was initiated by a slow depolarizing ramp driven by activation of an H-current (sensitive to ZD7288 and Cs(+)) and of a TRP- (transient receptor potential) current (sensitive to SKF96365), while the high voltage-activated and high voltage-activated Ca(2+) currents (sensitive to nimodipine and mibefradil, respectively) played a negligible role. The late-onset burst was occluded by intracellular cAMP. These results indicate that afferent activity can regulate H- and TRP-current gating in UBCs generating synaptically driven EPSP-independent responses, in which the delay rather than amplitude is graded with the intensity of the input pattern. This modality of synaptic transmission may play an important role in regulating UBC activation and granular layer functions in the vestibulo-cerebellum.

Characteristics of spontaneous physical activity and executive functions in postmenopause.

AIM: Executive functions are susceptible to age-related changes, and menopause has also been shown to be linked with their decline. The aim of the present study was to investigate the variables related to executive functions in postmenopausal women not involved in controlled dietary and physical exercise programs and without hormone-replacement therapy. METHODS: Fifty-seven women (58.39 ±4.16 yr) were investigated for their medical history, blood lipids, insulin resistance (HOMA-IR), body composition, blood pressure, executive functions (Digit Span and Trail Making tests), maximal aerobic capacity, dietary habits, and spontaneous physical activity. RESULTS: Cluster analysis performed on the basal data of the Digit Span scores and Trail Making tests identified two subgroups: Group A (N.=24) that showed better executive functions than Group B (N.=33). Although these subgroups differed across several variables of body composition, plasma lipids, dietary habits, spontaneous physical activity, aerobic fitness, and insulin resistance, logistic regression models showed B10m/die as the only predictive variable for subgroup membership. CONCLUSION: In the absence of a physical exercise program, the knowledge of how spontaneous physical activity is organized (B10m/die) is important for executive functions of post-menopausal women. It is the specific moderate to intense physical activity characteristic of B10m/die, rather than generic physical activity, that seems to determine the maintenance or attainment of cognitive health through body movement.

Clinical and molecular detection of inherited colorectal cancers in northeast Italy: a first prospective study of incidence of Lynch syndrome and MUTYH-related colorectal cancer in Italy.

The reported incidence of hereditary colorectal cancers (CRCs) is widely variable. The principal aim of the study was to prospectively evaluate the incidence of familial CRCs in a region of northern Italy using a standardized method. Consecutive CRC patients were prospectively enrolled from October 2002 to December 2003. Patients underwent a structured family history, the microsatellite instability (MSI) test and a screen for MUTYH mutations. Following family history patients were classified as belonging to high, moderate and mild risk families. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins and investigation for MLH1/MSH2 mutations, for MLH1 promoter methylation and for the V600E hotspot BRAF mutation were performed in high MSI (MSI-H) cases. Of the 430 patients enrolled, 17 (4%) were high risk [4 hereditary non-polyposis colorectal cancer (HNPCC), 12 suspected HNPCC and 1 MUTYH-associated adenomatous polyposis coli (MAP)], 53 moderate risk and 360 mild risk cases. The MSI test was performed on 393 tumours, and 46 (12%) of them showed MSI-H. In these patients, one MLH1 pathogenetic mutations and two MSH2 pathogenetic mutations were found. Thirty-two (70%) MSI-H cases demonstrated MLH1 methylation and/or BRAF mutation: None of them showed MLH1/MSH2 mutation. Two biallelic germline MUTYH mutations were found, one with clinical features of MAP. A strong family history of CRC was present in 4% of the enrolled cases; incidence of MLH1/MSH2 or MUTHY mutations was 1.3% and of MSI-H phenotype was 12%. MLH1 methylation and BRAF mutation can exclude 70% of MSI-H cases from gene sequencing.

Soft tissue sarcoma and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome: formulation of an hypothesis.

Hereditary non-polyposis colorectal cancer (HNPCC) is a genetic disorder caused by mutation in one of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) which predisposes to colorectal cancer and other malignances, that not yet include sarcomas. For sustaining that soft tissue sarcomas could be HNPCC related malignances, we report on a HNPCC patient with leiomyosarcoma and review the English literature. Overall, we report on eleven cases of soft tissue malignant tumors involving HNPCC patients, with a mean age of 34 years at diagnosis of sarcomas. In the majority of these tumors loss of MSH2 expression can be found at immunohistochemistry (IHC) and in 10 patients a germline mutation in one of the MMR genes was found (7 cases were MSH2 defective and 3 cases MLH1 defective). Data for supporting our hypothesis are also experimental, epidemiologic, histopathological: excess of sarcomas in PMS2 defective mice; sporadic soft tissue sarcomas are rare, with mean age at onset of 56 years and normal IHC for MMR proteins. In conclusion, the data collected support the hypothesis that soft tissue sarcomas could be included in the spectrum of tumors that, even if rarely, depend on MMR genes deficiency.

Decellularized normal and cancer tissues as tools for cancer research.

Today it is widely accepted that molecular mechanisms triggering cancer initiate with a genetic modification. However, a genetic alteration providing the aberrant clone with a growing advantage over neighboring cells is not sufficient to develop cancer. Currently, tumors are considered a heterogeneous population of cells and an extracellular matrix (ECM) that make up a characteristic microenvironment. Interactions between tumor cells and cancer microenvironment define cancer progression and therapeutic response. To investigate and clarify the role of ECM in the regulation of cancer cell behavior and response to therapy, the decellularization of ECM, a widely used technique in tissue engineering, has been recently employed to develop 3D culture model of disease. In this review, we briefly explore the different components of healthy and pathological ECM and the methods to obtain and characterize the ECM from native bioptic tissue. Finally, we highlight the most relevant applications of ECM in translational cancer research strategies: decellularized ECM, ECM-hydrogel and 3D bioprinting.

Reactions of nitrite with goethite and surface Fe(II)-goethite complexes.

Chemodenitrification-the abiotic (chemical) reduction of nitrite (NO2-) by iron (II)-plays an important role in nitrogen cycling due in part to this process serving as a source of nitrous oxide (N2O). Questions remain about the fate of NO2- in the presence of mineral surfaces formed during chemodenitrification, such as iron(III) (hydr) oxides, particularly relative to dissolved iron(II). In this study, stirred-batch kinetic experiments were conducted under anoxic conditions (to mimic iron(III)-reducing conditions) from pH 5.5-8 to investigate NO2- reactivity with goethite (FeOOH(s)) and Fe(II)-treated goethite using wet chemical and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Nitrite removal from solution by goethite was more rapid at pH 5.5 than at pH 7 and 8. Spectral changes upon nitrite adsorption imply an inner-sphere surface interaction (monodentate and bidentate) at pH 5.5 based on ATR-FTIR spectra of the nitrite-goethite interface over time. In iron(II)-amended experiments at pH 5.5 with high aqueous Fe(II) in equilibrium with goethite, nitrous oxide was generated, indicating that nitrite removal involved a combination of sorption and reduction processes. The presence of a surface complex resembling protonated nitrite (HONO) with an IR peak near ~1258 cm-1 was observed in goethite-only and iron(II)-goethite experiments, with a greater abundance of this species observed in the latter treatment. These results might help explain gaseous losses of nitrogen where nitrite and iron(II)/goethite coexist, with implications for nutrient cycling and release of atmospheric air pollutants.

Prehabilitation and heart failure: perspective in primary outcomes, a randomized controlled trial.

OBJECTIVE: Prehabilitation, intended as a multidisciplinary approach where physical training is combined with educational and counselling training, in cardiology could optimizing care, and has been shown to be able to reduce morbidity and mortality in several diseases. The present study aims to assess the effectiveness of a prehabilitation program in elderly patients (over 65) with chronic heart failure and to evaluate functional and quality indices of life. PATIENTS AND METHODS: This is randomized, single blind controlled trial. Fourteen older adult patients diagnosed with chronic heart failure were enrolled. Patients were randomly assigned into the study or the control group. Patients in the study group underwent physical training organized into 10 twice-weekly meetings, nutritional and lifestyle counseling. RESULTS: In the Study Group, the quality of life improved significantly (EQoL-5D), and between the two groups there is a statistically significant difference in the motor dimension of SF-36. CONCLUSIONS: Because of our preliminary results, prehabilitation program should be included among the management strategies of in elderly patients with chronic heart failure to better manage their disease and to improve their Quality of Life.

[Determinants of short-term memory: is there a difference between young adults and postmenopausal women?]. / Fattori determinanti la memoria a breve termine: esiste una differenza tra giovani donne e donne in postmenopausa?

AIM: The literature indicates that several variables are influencing cognitive health. The aim of the study was to investigate the main determinants of the short-term memory among anthropometric, dietary and performance variables in a sample of healthy women. The role played by the age was also investigated. METHODS: Forty-five healthy overweight women were recruited through general physicians: 23 were young adults (24.63±4.17 years) and 22 were postmenopausal (53.30±2.95 years). Overweight condition was assessed according to the age-adjusted reference values. Participants were analyzed for Digit Span, blood pressure, body composition, aerobic fitness and dietary habits. RESULTS: Young adults and postmenopausal women did not differ either in Digit Span or in dietary habits. In postmenopausal women Digit Span was positively correlated with body weight, body mass index, body fat, waist circumference and daily intake of vitamin D. Linear regression model indicated vitamin D as the only significant predictor variable of Digit Span. In young adults Digit Span had no correlations with the others investigated variables. CONCLUSION: In postmenopause, vitamin D daily intake is important not only for skeletal, but also for cognitive health. Even though young adults and post-menopausal women did not differ for health status, short-term memory in young adulthood seems to be differently linked with the investigated variables than during post-menopause.

Transcranial magnetic stimulation over the cerebellum and eye movements: state of the art.

Transcranial magnetic stimulation (TMS) transiently induces an electrical field in the tissues beneath the area of application, thereby perturbing local cortical activity if applied over the scalp. It can therefore be used to modulate cerebellar function in healthy humans. Even though the role of the cerebellum in eye movement control and adaptation is well known, few experiments have used eye movements to evaluate the effect of TMS over the cerebellum. Single-pulse TMS over the posterior vermis resulted in impaired accuracy of reflexive saccades, acceleration of smooth pursuit, and coordination of saccades and head movements. TMS over the cerebellar hemisphere decreased pursuit gain. Repetitive TMS (rTMS) over the posterior vermis impaired saccade adaptation in a double-step paradigm. Comparing the effects of TMS on different behavioural paradigms could be useful to test cerebellar control of reflexive and voluntary eye movements, and as a probe of cerebellar plasticity. rTMS appears to be especially interesting since its effects outlast the stimulation period and its behavioural consequences can therefore be measured without interfering with the execution of eye movements or with the experimental procedures.

Autism and genius: is there a link? The involvement of central brain loops and hypotheses for functional testing.

Mental processing is the product of the huge number of synaptic interactions that occur in the brain. It is easier to understand how brain functions can deteriorate than how they might be boosted. Lying at the border between the humanities, cognitive science and neurophysiology, some mental diseases offer new angles on this problematic issue. Despite their social deficits, autistic subjects can display unexpected and extraordinary skills in numerous fields, including music, the arts, calculation and memory. The advanced skills found in a subgroup of people with autism may be explained by their special mental functioning, in particular by their weak central coherence, one of the pivotal characteristics of the disorder. As a result of the increasing interest in autistic talent, there has recently emerged a tendency to screen any eccentric artist or scientist for traits of the autistic spectrum. Following this trend, we analyze the eccentricity of the popular pianist Glenn Gould and briefly discuss the major functional hypotheses on autistic hyperfunctioning, advancing proposals for functional testing. In particular, the potential involvement of rhythm-entrained systems and cerebro-cerebellar loops opens up new perspectives for the investigation of autistic disorders and brain hyperfunctioning.

Relationships between physical exercise practice, dietary behaviour and body composition in female university students.

AIM: The relationship between female body composition, total energy expenditure and physical exercise energy expenditure is not very strong because women can compensate by increasing their energy intake. The aim of this study was to investigate the relationship between total minutes of exercise per week, dietary habits and body composition in female university students using physical activity and the habit to cook as covariates. METHODS: Fifty-one female university students were investigated for body composition, dietary habits, aerobic fitness, physical activity and physical exercise practice. Participants were grouped in three sub-samples (1, 2 and 3) according to the 33rd and 66th percentiles of weekly minutes (min/wk) of training. RESULTS: Group 1 had 0.00 min/wk, group 2 had 95±35.59 min/wk and group 3 had 231.66±85.97 min/wk of training. Sub-samples did not differ for IPAQ parameters while differed for aerobic fitness (P=0.001). Group 3 had a higher energy intake (EI) (P=0.008), a higher intake of lipids (P=0.017), saturated (P=0.042) and monounsaturated fat (P=0.024) and a lower intake of carbohydrates (P=0.007). Group 3 maintained the higher EI and the worse composition of lipid intake considering the habit to cook as covariate. Group 3 also had higher muscle mass. CONCLUSION: In order to positively affect body composition, in the sedentary women it is enough to control the energy balance, whereas in those that trained regularly it is necessary to control both energy balance and composition of daily meals.

Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients.

Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels ≥140mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P<0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P<0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P<0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P<0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset.

Does a 6-point scale approach to post-treatment 18F-FDG PET-CT allow to improve response assessment in head and neck squamous cell carcinoma? A multicenter study.

PURPOSE: Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale ("Cuneo score"). METHODS: We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients' information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. RESULTS: Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). CONCLUSIONS: In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

Effect of heliox breathing on flow limitation in chronic heart failure patients.

Patients with chronic heart failure (CHF) exhibit orthopnoea and tidal expiratory flow limitation in the supine position. It is not known whether the flow-limiting segment occurs in the peripheral or central part of the tracheobronchial tree. The location of the flow-limiting segment can be inferred from the effects of heliox (80% helium/20% oxygen) administration. If maximal expiratory flow increases with this low-density mixture, the choke point should be located in the central airways, where the wave-speed mechanism dominates. If the choke point were located in the peripheral airways, where maximal flow is limited by a viscous mechanism, heliox should have no effect on flow limitation and dynamic hyperinflation. Tidal expiratory flow limitation, dynamic hyperinflation and breathing pattern were assessed in 14 stable CHF patients during air and heliox breathing at rest in the sitting and supine position. No patient was flow-limited in the sitting position. In the supine posture, eight patients exhibited tidal expiratory flow limitation on air. Heliox had no effect on flow limitation and dynamic hyperinflation and only minor effects on the breathing pattern. The lack of density dependence of maximal expiratory flow implies that, in CHF patients, the choke point is located in the peripheral airways.

Bacteria-assisted removal of fluoroquinolones from wheat rhizospheres in an agricultural soil.

Extensive fluoroquinolone antibiotics use results in their widespread occurrence in various environments including soil, which threatens the soil ecology and public health. The fate of fluoroquinolones in agricultural soil and the efficacy of enhanced degradation in the presence of an agricultural crops and antibiotic degrading bacteria could be better understood. The current study examined ciprofloxacin (CIP), enrofloxacin (ENR), and levofloxacin (LEV) biodegradation in a Maury Silt Loam soil in greenhouse conditions by bacterial-assisted removal of individual and mixed antibiotics in wheat rhizospheres. Fluoroquinolones were added at rates of 5, 50, and 100 mg kg-1. Three bacterial isolates were applied at 106 CFU g-1 soil individually and in consortium. Antibiotics appeared in wheat tissue, with more accumulation in roots than shoots. Low recoveries (<50%) of CIP, ENR, and LEV were observed at all levels and treatments in a bacteria and wheat-free control compared to the initial concentrations applied Contaminated soil with wheat had greater antibiotic recovery than the wheat-free control. Antibiotic recovery with bacterial inoculum was less than that of the indigenous bacteria. The least antibiotic recovery occurred with wheat and bacterial inoculum together. At concentrations of 5 and 50 mg kg-1, but not at 100 mg kg-1, CIP, ENR, and LEV were below detection limits in soil after 30 days through the combination of wheat and bacteria compared to the control. This synergistic removal of the fluoroquinolone antibiotics is proposed to be due to enhanced antibiotic bioavailability, which suggests it as an environment-friendly approach to biodegradation.

Current Espghan Guidelines for Celiac Disease in Pediatric Age, Tertiary Care Center Experience: A Proposal for Further Simplification.

According to the 2012 ESPGHAN criteria for diagnosis of celiac disease (CD), duodenal biopsy (DB) can be avoided in children with a clear malabsorption syndrome, anti-tissue transglutaminase IgA (tTG2) ≥ 10x the cut-off, anti-endomysium IgA (EMA) and HLA DQ2/DQ8 genes. The aim of this study is to report our experience and evaluate the accuracy of the actual guidelines. PATIENTS AND METHODS: This is a retrospective study conducted on all patients diagnosed CD from 2012 to 2018 in our Center. For all patients enrolled were analyzed: data of family history, symptoms, serology, genetics, Marsh grade and follow-up. RESULTS: A total of 481 children [mean age 6,4 yrs; F:M= 1.8:1] were included in the study. The mean age of patients who were not subject to DB was lower (4.51 yrs) comparing with patients that received DB (6.48 yrs). Out of the 256 patients with anti-tTG2 ≥ 10 fold, 121 underwent DB because of mild symptoms (84/121) or no symptoms (37/121). In all cases Marsh type 3 was found and HLA haplotypes was compatible with CD diagnosis. CONCLUSIONS: Our study confirms that the serology has a primary importance to diagnose CD, regardless of the symptoms. These data suggest that biopsy and HLA haplotypes search, in presence of anti-tTG2 IgA ≥ 10x the cut-off, are wasteful and unhelpful for the patients.