Electrophysiological Correlates of Reward Anticipation in Subjects with Schizophrenia: An ERP Microstate Study.

The current study aimed to investigate alterations of event-related potentials (ERPs) microstate during reward anticipation in subjects with schizophrenia (SCZ), and their association with hedonic experience and negative symptoms. EEG data were recorded in thirty SCZ and twenty-three healthy controls (HC) during the monetary incentive delay task in which reward, loss and neutral cues were presented. Microstate analysis and standardized low-resolution electromagnetic tomography (sLORETA) were applied to EEG data. Furthermore, analyses correlating a topographic index (the ERPs score), calculated to quantify brain activation in relationship to the microstate maps, and scales assessing hedonic experience and negative symptoms were performed. Alterations in the first (125.0-187.5 ms) and second (261.7-414.1 ms) anticipatory cue-related microstate classes were observed. In SCZ, reward cues were associated to shorter duration and earlier offset of the first microstate class as compared to the neutral condition. In the second microstate class, the area under the curve was smaller for both reward and loss anticipation cues in SCZ as compared to HC. Furthermore, significant correlations between ERPs scores and the anticipation of pleasure scores were detected, while no significant association was found with negative symptoms. sLORETA analysis showed that hypo-activation of the cingulate cortex, insula, orbitofrontal and parietal cortex was detected in SCZ as compared to HC. Abnormalities in ERPs could be traced already during the early stages of reward processing and were associated with the anticipation of pleasure, suggesting that these dysfunctions might impair effective evaluation of incoming pleasant experiences. Negative symptoms and anhedonia are partially independent results.

Cervical pessary for preterm birth prevention after an episode of arrested preterm labor: a retrospective cohort study with targeted maximum likelihood estimation of the average treatment effect.

OBJECTIVE: To evaluate whether cervical pessary effectively reduces the preterm birth < 37 weeks rate in patients who have not delivered after an episode of arrested preterm labor. PATIENTS AND METHODS: Retrospective cohort study was conducted on singleton pregnant patients admitted to our institution between January 2016 and June 2021 for threatened preterm labor and who had a cervical length < 25 mm. Women in whom a cervical pessary was placed were considered as exposed, while women in whom expectant management was preferred were considered as unexposed. The primary outcome was the rate of preterm birth before 37 weeks. A targeted maximum likelihood estimation was used to estimate the average treatment effect of cervical pessary by adjusting for a-priori-defined confounders. RESULTS: A cervical pessary was placed in 152 (36.6%) patients (exposed), while the remaining 263 (63.4%) were managed expectantly (unexposed). The adjusted average treatment effect was -14% (-18 to -11%), -17% (-20 to -13%), and -16% (-20 to -12%) for preterm birth < 37 weeks, < 34 weeks, and < 32 weeks, respectively. The average treatment effect for adverse neonatal outcomes was -7% (-8 to -5%). No difference in gestational weeks at delivery between exposed and unexposed emerged when gestational age at first admission was > 30.1 gestational weeks. CONCLUSIONS: The positioning of a cervical pessary placement may be evaluated to reduce the risk of a subsequent preterm birth after an episode of arrested preterm labor in pregnant patients with onset of symptoms before 30 gestational weeks.

8-Hydroxyquinoline-5-sulfonamides are promising antifungal candidates for the topical treatment of dermatomycosis.

AIM: The purpose of this study was to uncover insights into the mechanism of action of the 8-hydroxyquinoline derivatives PH151 and PH153. In addition, with the future perspective of developing a topical drug for the treatment of candidiasis and dermatophytosis, the antifungal activity of a nanoemulsion formulation containing the most active compound (PH151) is also presented here. METHODS AND RESULTS: Sorbitol protection assay and scanning electron microscopy indicate that the 8-hydroxyquinoline derivatives act on the cell wall of Candida sp. and dermatophytes and they inhibit the pseudohyphae formation of C. albicans. These findings demonstrate a strong effect of these compounds on C. albicans morphogenesis, which can be considered a potential mode of action for this molecule. Besides, the nanoemulsion formulation MIC values ranged from 0·5 to 4 µg ml-1 demonstrating the significant antifungal activity when incorporated into a pharmaceutical formulation. CONCLUSIONS: Taken together, the results support the potential of these molecules as promising antifungal candidates for the treatment of candidiasis and dermatophytosis. SIGNIFICANCE AND IMPACT OF THE STUDY: There is an emerging need to fill the pipeline with new antifungal drugs due to the limitations presented by the currently used drugs. In this study, we have described a novel formulation with a 8-hydroxyquinoline-5-sulfonamide derivative which has presented a great potency in providing a finished product. Furthermore, the derivative has shown a selective mechanism of action confirming its potential to be developed into a new drug candidate.

Weak-field H3O+ ion cyclotron resonance alters water refractive index.

Heretofore only observed in living systems, we report that weak-field ion cyclotron resonance (ICR) also occurs in inanimate matter. Weak magnetic field (50 nT) hydronium ICR at the field combination (7.84 Hz, 7.5 µT) markedly changes water structure, as evidenced by finding an altered index of refraction exactly at this combined field. This observation utilizes a novel technique which measures the scattering of a He-Ne laser beam as the sample is exposed to a ramped magnetic field frequency. In addition to the hydronium resonance, we find evidence of ICR coupling to a more massive structure, possibly a tetrahedral combination of three waters and a single hydronium ion. To check our observations, we extended this technique to D2O, successfully predicting the specific ICR charge-to-mass ratio for D3O+ that alters the index of refraction.

Lorentz force in water: evidence that hydronium cyclotron resonance enhances polymorphism.

There is an ongoing question regarding the structure forming capabilities of water at ambient temperatures. To probe for different structures, we studied effects in pure water following magnetic field exposures corresponding to the ion cyclotron resonance of H3O(+). Included were measurements of conductivity and pH. We find that under ion cyclotron resonance (ICR) stimulation, water undergoes a transition to a form that is hydroxonium-like, with the subsequent emission of a transient 48.5 Hz magnetic signal, in the absence of any other measurable field. Our results indicate that hydronium resonance stimulation alters the structure of water, enhancing the concentration of EZ-water. These results are not only consistent with Del Giudice's model of electromagnetically coherent domains, but they can also be interpreted to show that these domains exist in quantized spin states.

50 Hz extremely low frequency electromagnetic fields enhance protein carbonyl groups content in cancer cells: effects on proteasomal systems.

Electromagnetic fields are an assessed cause of prolonging free radicals lifespan. This study was carried out to investigate the influence of extremely low frequency electromagnetic fields on protein oxidation and on the 20S proteasome functionality, the complex responsible for the degradation of oxidized proteins. Caco 2 cells were exposed, for 24-72 hours, to 1 mT, 50 Hz electromagnetic fields. The treatment induced a time-dependent increase both in cell growth and in protein oxidation, more evident in the presence of TPA, while no changes in cell viability were detected. Exposing the cells to 50 Hz electromagnetic fields caused a global activation of the 20S proteasome catalytic components, particularly evident at 72 hours exposure and in the presence of TPA. The finding that EGCG, a natural antioxidant compound, counteracted the field-related pro-oxidant effects demonstrates that the increased proteasome activity was due to an enhancement in intracellular free radicals.

Structural changes induced in proteins by therapeutic ultrasounds.

The structural effect induced by therapeutic ultrasound on proteins in aqueous solution has been investigated with FTIR spectroscopy, UV-VIS spectroscopy, circular dichroism and light scattering. Six proteins (cytochrome, lysozyme, myoglobin, bovine serum albumin, trypsinogen, and alpha-chymotrypsinogen A) with different molecular weight and secondary structure have been studied. The experiment has been performed using an ultrasound source at resonant frequency of 1 MHz and sonication times of 10, 20, 30, 40, 50, and 60 min. A different behaviour of proteins under sonication depends on the dominant secondary structure type (alpha-helix or beta-sheets) and on the grade of the ordered structure. The results suggest that the free radicals, produced by water sonolysis, have an important role in the changes of structural order.

Investigating the Icr Effect in a Zhadin's Cell.

Investigations into the ion cyclotronic resonance (ICR) in living matter confront the so called Zhadin effect (12), whose explanation is not fully achieved. Several attempts have been done to explain this phenomenon, the most interesting of which is based on Quantum Electrodynamics (18): the molecules of water, the ions and the biomolecules form extended mesoscopic regions, called Coherence Domains (CD), where they oscillate in unison between two selected levels of their spectra in tune with a self-produced coherent E.M. field having a well defined frequency, dynamically trapped within the CD. Moreover, it is possible, to induce, by an external applied field (either hydrodynamical or EM) or also by a chemical stimulation, coherent excitations of CD's that give rise to electric currents circulating without friction within the CD's: as a consequence magnetic fields are produced. A resonating magnetic field thus is able to extract the ions from the orbit and push them in the flowing current. Electrochemical investigation of the system suggested that the observed phenomenon involves the transitory activation of the anode due to ICR, followed by anode passivation due to the adsorption of amino acid and its oxidation products (18). This hypothesis induced us to investigate an alternate configuration of the experiment, removing the electrolytic cell and submitting a flask containing the solution into a condenser to be exposed to the proper ICR. Temperature and variable parameters involved in the effect have been investigated in order to overcome the randomness of the effect.

Identification and characterization of a novel expandable adult stem/progenitor cell population in the human exocrine pancreas.

It is a general opinion that tissue-specific stem cells are present in adult tissues but their specific properties remain elusive. They are rare in tissues and heterogeneous; in addition, their identification and the characterization of their progeny has encountered technical difficulties. In particular, the existence of pancreatic stem cells remains elusive because specific markers for their identification are not available. We established a method for the isolation of a population of stem/progenitor cells from the human exocrine pancreas, and propose it as a model for other human compact organs. We also used markers that identified and finally characterized these cells. Spheroids with self-replicative potential were obtained from all specimens. The isolated population contained a subset of CD34+ CD45- cells and was able to generate, in appropriate conditions, colonies that produce insulin. We obtained evidence that most freshly isolated spheroids, when co-cultured with the c-kit positive neuroblastoma cell line LAN 5, produced a c-kit positive progeny of cells larger in their cytoplasmic content than the original spheroid population, with elongated morphology resembling the neuronal phenotype. We identified a novel predominant functional type of stem/progenitor cell within the human exocrine pancreas, able to generate insulin-producing cells and potentially non-pancreatic cells.

Delayed allergy to aminopenicillins: clinical and immunological findings.

Aminopenicillins are the most used beta-lactam antibiotics. Morbilliform or maculopapular rashes are rather frequent during therapy with aminopenicillins. The pathogenesis of these reactions is often due to a cell-mediated allergy. The aim of this work is to characterize patients with cell-mediated allergy to aminopenicillins and to identify alternative beta-lactam drugs that can be safely administered to these patients. We studied 27 subjects affected by cell-mediated allergy to aminopenicillins. The diagnosis was made on the basis of positivity of patch tests with aminopenicillins. These patients then underwent an allergological evaluation (skin and patch tests, oral and/or intramuscular challenge tests) with a wide spectrum of beta-lactam antibiotics. Our work highlights the following main characteristics of cell-mediated allergy to aminopenicillins: time elapsing between drug administration and onset of symptoms of about 2 days; the maculopapular rash and delayed appearance of urticaria/angioedema were the most typical symptoms (82.8 percent of cases); a cross-reactivity with aminocephalosporins is usually absent, or it is limited to cephalexin (in our study, in fact, just 3 out of 20 patients challenged with cephalexin showed a positive oral challenge test); all the beta-lactams, other than aminopenicillins, are well tolerated. Patch tests represent a specific diagnostic tool with a good predictive value of identifying alternative drugs that can be safely administered to patients with beta-lactam allergy. Our patients could tolerate other beta-lactam drugs after a complete allergological evaluation. On the basis of our study, cell-mediated allergy to aminopenicillins should be considered a well-defined nosologic entity.

Micro-cells coverage for mobile telephony: an alternative way to reduce EMF exposures.

The aim of this article is to describe networks that are constituted of micro-cell Based Transceiver Stations (BTS), substituting for the conventional networks that are based on the employment of usual macro plants. Specifically, we present a micro-cells network designed to substitute for a conventional BTS network, in the Don Sturzo Park in the city of Venice, Italy. The lower environmental and healthy impact due to a micro-cells network compared to a conventional network is discussed.

Clastogenicity and aneuploidy in newborn and adult mice exposed to 50 Hz magnetic fields.

PURPOSE: To detect possible clastogenic and aneugenic properties of a 50 Hz, 650 muT magnetic field. MATERIALS AND METHODS: The micronucleus test with CREST (Calcinosis, Raynaud's phenomenon, Esophageal dismotility, Sclerodactility, Telangectasia) antibody staining was performed on liver and peripheral blood sampled from newborn mice exposed to an ELF (Extremely Low Frequency) magnetic field during the whole intra-uterine life (21 days), and on bone marrow and peripheral blood sampled from adult mice exposed to the same magnetic field for the same period. RESULTS: Data obtained in newborn mice show a significant increase in micronuclei frequencies. In absolute terms, most of the induced micronuclei were CREST-negative (i.e., formed by a chromosome fragment). However, in relative terms, ELF exposure caused a two-fold increase in CREST-negative micronuclei and a four-fold increase in CREST-positive micronuclei (i.e., formed by a whole chromosome). No significant effect was recorded on exposed adults. CONCLUSIONS: These findings suggest the need for investigation of aneugenic properties of ELF magnetic fields in order to establish a possible relationship to carcinogenesis.

Autosomal dominant atretic cephalocele with phenotype variability: report of a Brazilian family with six affected in four generations.

Atretic cephalocele is a clinicopathological entity, which is different from the common form of cephalocele. Its etiopathogenesis has not been completely explained and there are only two previous reports of familial recurrence. We report a Brazilian family with autosomal dominant inheritance with variable expressivity.

Dynamics of the ion cyclotron resonance effect on amino acids adsorbed at the interfaces.

In this study we show a reproduction of the Zhadin experiment, which consists of the transient increase of the electrolytic current flow across an aqueous solution of L-arginine and L-glutamic acid induced by a proper low frequency alternating magnetic field superimposed to a static magnetic field of higher strength. We have identified the mechanisms that were at the origin of the so-far poor reproducibility of the above effect: the state of polarization of the electrode turned out to be a key parameter. The electrochemical investigation of the system shows that the observed phenomenon involves the transitory activation of the anode due to ion cyclotron frequency effect, followed again by anode passivation due to the adsorption of amino acid and its oxidation products. The likely occurrence of similar ion cyclotron resonance (ICR) phenomena at biological membranes, the implications on ion circulation in living matter, and the consequent biological impact of environmental magnetic fields are eventually discussed.

Diagnostic value and learning curve of transbronchial needle aspiration in thoracic surgery.

AIM: Transbronchial needle aspiration (TBNA) is particularly indicated in diagnosing mediastinal masses or lymphoadenopathy proximal to the airways. Nowadays TBNA has not been widely accepted among pulmonologist and thoracic surgeons. Since its correct management could reduce patient morbidity we adopted this method. Here is presented an overview of our experience over a 18-months training period. METHODS: Fifty patients underwent TBNA. They presented non diagnosed paratracheal or peribronchial lymphadenopathy or masses of >1 cm. TBNA has been considered in order to spare patients the need for more invasive diagnostic procedures. TBNA has been performed with flexible bronchoscope and 19-gauge or 21-gauge needle. RESULTS: We made diagnosis of disease in 25 of 41 patients whose adequate sampling was obtained. 16 cases showed absence of disease despite criteria for adequacy have been confirmed, 9 cases presented an inadequate specimen. The overall diagnostic yield and sensitivity were 50% and 86%. The overall accuracy was 76%. Considering the last 6 months of the training period diagnostic yield increased from 18.7% to 88.2% (P<0.001),accuracy from 56.2% to 88.2% (P=0.04) and frequency of inadequacy decreased from 43.7% to 11.7% (P=0.046). CONCLUSIONS: TBNA resulted a successful diagnostic tool in selected cases as it is safe and permits to spare patients the need for more invasive procedures. These data revealed that experience is mandatory in order to achieve acceptable RESULTS: We think that an experienced operator should require a training period of approximately 50 procedures to obtain a good technique proficiency.

Exposure to 50 Hz electromagnetic radiation promote early maturation and differentiation in newborn rat cerebellar granule neurons.

The wish of this work is the study of the effect of electromagnetic (EMF) radiations at a frequency of 50 Hz on the development of cerebellar granule neurons (CGN). Granule neurons, prepared from newborn rat cerebellum (8 days after birth), were cultured after plate-seeding in the presence of EMF radiations, with the plan of characterizing their cellular and molecular biochemistry, after exposure to the electromagnetic stimulus. Five days challenge to EMF radiations showed, by the cytotoxic glutamate (Glu) pulse test, a 30% decrease of cells survival, while only 5% of mortality was reported for unexposed sample. Moreover, blocking the glutamate receptor (GluR) with the Glu competitor MK-801, no toxicity effect after CGN challenge to EMF radiations and Glu was detected. By patch-clamp recording technique, the Kainate-induced currents from 6 days old exposed CGN exhibited a significant increase with respect to control cells. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses show that EMF exposure of rats CGN, induces a change in both GluRs proteins and mRNAs expression with respect to control. In addition, the use of monoclonal antibody raised against neurofilament protein (NF-200) reveals an increase in NF-200 synthesis in the exposed CGN. All these results indicate that exposure to non-ionizing radiations contribute to a premature expression of GluRs reducing the life span of CGN, leading to a more rapid cell maturation.

Influence of 50-Hz electromagnetic field on anurian (Xenopus laevis) metamorphosis.

In this study, we show the effect of a 1-mT magnetic field AC at 50 Hz on Xenopus laevis tadpole populations. In the course of a 65-day exposure to the field, tadpole survival showed a small, but significant, decrease (p < 0.0004), together with a striking parallel 6-day shift in tadpole maturation frequency and a significant impairment of their metamorphosis. Particularly, metamorphosis was successful for 85% of individuals in the unirradiated tadpole population and for 45% of individuals in the irradiated tadpole population, respectively.

De novo complex chromosome rearrangement: a study of two patients.

Complex chromosome rearrangements (CCR) involving multiple breaks in two or more chromosomes are rare. We describe a girl with development delay and overgrowth who presents a nine-break apparently balanced de novo rearrangement involving chromosomes 1, 2, 3, 4 and 12, and a boy with developmental delay and seizures with a complex three-chromosome apparently balanced de novo rearrangement involving chromosomes 2, 7 and 13. The relationship between clinical abnormalities and apparently balanced rearrangements is discussed.

SNOM and AFM microscopy techniques to study the effect of non-ionizing radiation on the morphological and biochemical properties of human keratinocytes cell line (HaCaT).

In this study we have employed atomic force microscopy (AFM) and scanning near-field optical microscopy (SNOM) techniques to study the effect of the interaction between human keratinocytes (HaCaT) and electromagnetic fields at low frequency. HaCaT cells were exposed to a sinusoidal magnetic field at a density of 50 Hz, 1 mT. AFM analysis revealed modification in shape and morphology in exposed cells with an increase in the areas of adhesion between cells. This latter finding was confirmed by SNOM indirect immunofluorescence analysis performed with a fluorescent antibody against the adhesion marker beta4 integrin, which revealed an increase of beta4 integrin segregation in the cell membrane of 50-Hz exposed cells, suggesting that a higher percentage of these cells shows a modified pattern of this adhesion marker.

Exposure to 900 MHz electromagnetic field induces an unbalance between pro-apoptotic and pro-survival signals in T-lymphoblastoid leukemia CCRF-CEM cells.

It has been recently established that low-frequency electromagnetic field (EMFs) exposure induces biological changes and could be associated with increased incidence of cancer, while the issue remains unresolved as to whether high-frequency EMFs can have hazardous effect on health. Epidemiological studies on association between childhood cancers, particularly leukemia and brain cancer, and exposure to low- and high-frequency EMF suggested an etiological role of EMFs in inducing adverse health effects. To investigate whether exposure to high-frequency EMFs could affect in vitro cell survival, we cultured acute T-lymphoblastoid leukemia cells (CCRF-CEM) in the presence of unmodulated 900 MHz EMF, generated by a transverse electromagnetic (TEM) cell, at various exposure times. We evaluated the effects of high-frequency EMF on cell growth rate and apoptosis induction, by cell viability (MTT) test, FACS analysis and DNA ladder, and we investigated pro-apoptotic and pro-survival signaling pathways possibly involved as a function of exposure time by Western blot analysis. At short exposure times (2-12 h), unmodulated 900 MHz EMF induced DNA breaks and early activation of both p53-dependent and -independent apoptotic pathways while longer continuous exposure (24-48 h) determined silencing of pro-apoptotic signals and activation of genes involved in both intracellular (Bcl-2) and extracellular (Ras and Akt1) pro-survival signaling. Overall our results indicate that exposure to 900 MHz continuous wave, after inducing an early self-defense response triggered by DNA damage, could confer to the survivor CCRF-CEM cells a further advantage to survive and proliferate.