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1.
Chaos ; 32(8): 083139, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36049927

ABSTRACT

The catalytic electro-oxidation of some small organic molecules is known to display kinetic instabilities, which reflect on potential and/or current oscillations. Under oscillatory conditions, those systems can be considered electrocatalytic oscillators and, therefore, can be described by their amplitude, frequency, and waveform. Just like mechanical oscillators, the electrocatalytic ones can be coupled and their dynamics can be changed by setting different coupling parameters. In the present work, we study the unidirectional coupling of electrocatalytic oscillators, namely, those comprehending the catalytic electro-oxidation of methanol and formic acid on polycrystalline platinum in acidic media under potentiostatic control. Herein, we explore two different scenarios (the coupling of compositionally identical and non-identical oscillators) and investigate the effects of the master's identity and of the coupling constant on the slave's dynamics. For the master (methanol)-slave (methanol) coupling, the oscillators exhibited phase lag synchronization and complete phase synchronization. On the other hand, for the master (formic acid)-slave (methanol) coupling, the oscillators exhibited complete phase synchronization with phase-locking with a 2:3 ratio, complete phase synchronization with phase-locking with a 1:2 ratio, phase lag synchronization, and complete phase synchronization. The obtained results suggest that both the master's identity and the coupling constant (sign and magnitude) are parameters that play an important role on the coupled systems, in such a way that even for completely different systems, synchronization could emerge by setting a suitable coupling constant. To the best of our knowledge, this is the first report concerning the electrical coupling of hidden N-shaped-negative differential resistance type systems.

2.
Respir Res ; 22(1): 319, 2021 Dec 23.
Article in English | MEDLINE | ID: mdl-34949190

ABSTRACT

BACKGROUND: Tidal expiratory flow limitation (EFLT) is common among COPD patients. Whether EFLT changes during sleep and can be abolished during home ventilation is not known. METHODS: COPD patients considered for noninvasive ventilation used a ventilator which measured within-breath reactance change at 5 Hz (∆Xrs) and adjusted EPAP settings to abolish EFLT. Participants flow limited (∆Xrs > 2.8) when supine underwent polysomnography (PSG) and were offered home ventilation for 2 weeks. The EPAP pressure that abolished EFLT was measured and compared to that during supine wakefulness. Ventilator adherence and subjective patient perceptions were obtained after home use. RESULTS: Of 26 patients with supine EFLT, 15 completed overnight PSG and 10 the home study. In single night and 2-week home studies, EFLT within and between participants was highly variable. This was unrelated to sleep stage or body position with only 14.6% of sleep time spent within 1 cmH2O of the awake screening pressure. Over 2 weeks, mean EPAP was almost half the mean maximum EPAP (11.7 vs 6.4 cmH2O respectively). Group mean ∆Xrs was ≤ 2.8 for 77.3% of their home use with a mean time to abolish new EFLT of 5.91 min. Adherence to the ventilator varied between 71 and 100% in prior NIV users and 36-100% for naïve users with most users rating therapy as comfortable. CONCLUSIONS: Tidal expiratory flow limitation varies significant during sleep in COPD patients. This can be controlled by auto-titrating the amount of EPAP delivered. This approach appears to be practical and well tolerated by patients. TRIAL REGISTRATION: The trial was retrospectively registered at CT.gov NCT04725500.


Subject(s)
Exhalation/physiology , Noninvasive Ventilation/methods , Polysomnography/methods , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/therapy , Tidal Volume/physiology , Aged , Female , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/diagnosis , Retrospective Studies
3.
Phys Chem Chem Phys ; 22(26): 15022-15034, 2020 Jul 08.
Article in English | MEDLINE | ID: mdl-32597431

ABSTRACT

Photonic and electronic properties exist inherently in ferroelectric barium titanate (BaTiO3); severe luminescence quenching also exists due to the insufficient confinement of excitons. In this sense, high optical emission can only be achieved by its chemical and structural modification. Thin BaTiO3 and Er:BaTiO3 films were grown by the spin coating method on a glass substrate at room temperature. Self-trapping of excitons in the thin BaTiO3 film and its structural modification due to the doping with Er3+ ions (Er:BaTiO3) are verified using scanning confocal fluorescence microscopy (SCFM), where self-trapping excitons never occured in its pure state. By thermal treatment and doping (BaTiO3 and Er:BaTiO3) we obtained localization of the excitons, which would further induce lattice strain around the surface defects, to accommodate the self-trapped excitons. With such a self-trapped state, the structure of BaTiO3 generates broadband emission of several overlapping bands between 1.95 and 2.65 eV at room temperature, while the structure Er:BaTiO3 showed defined emission bands at 2.24 and 2.35 eV, with very weak contributions of the emission due to the self-trapping state. The influence of the variation of the excitation wavelength using 1PE and 2PE on the emission bands of BaTiO3 and Er:BaTiO3 is also investigated. The results of enhanced emission bands suggest a clear dependence of the emission intensity on the excitation energy, where a ∼3 fold enhancement in emission has been demonstrated under Er3+ (1.55 eV) excitation, which can be attributed to effective energy transfer between the Er3+ ions. As a result, it is concluded that the developed BaTiO3 and Er:BaTiO3 can pave the way for future photonic devices.

4.
J Dairy Sci ; 103(2): 1391-1403, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31785866

ABSTRACT

The aim of this study was to determine the effect of the forage preservation method (silage vs. hay) on volatile compounds and sensory properties of a traditional Caciocavallo cheese during ripening. A brown-midrib sudangrass hybrid was cultivated on a 7-ha field and at harvesting it was half ensiled in plastic silo bags and half dried to hay. Forty-four lactating cows were equally allotted into 2 groups fed a isonitrogenous and isoenergetic total mixed ration containing as the sole forage either sorghum hay (H group) or sorghum silage (S group). Milk from the 2 groups was used to produce 3 batches/diet of Caciocavallo ripened for 30, 60, and 90 d. Milk yield and composition as well as cheese chemical and fatty acid composition were not markedly affected by the diet treatment and ripening time. By contrast, ripening induced increased levels of the appearance attribute "yellowness," along with the "overall flavor," the odor/flavor attributes "butter" and "hay," the "salty," "bitter," and "umami" tastes, and the texture attribute "oiliness," whereas the appearance attribute "uniformity" and the texture attribute "elasticity" were reduced. The silage-based diet induced higher perceived intensities of several attributes such as "yellowness"; "overall flavor"; "butter"; "grass" and "hay" odor/flavors; "salty," "bitter," and "umami" tastes; and "tenderness" and "oiliness" textures. In S cheese we also observed higher amounts of ketones and fatty acids. Conversely, H cheese showed the terpene α-pinene, which was not detected in S cheese, and a higher intensity of the appearance attribute "uniformity." These differences allowed the trained panel to discriminate the products, determined an increased consumer liking for 90-d ripened cheese, and tended to increase consumer liking for hay cheese.


Subject(s)
Animal Feed/analysis , Cattle/physiology , Cheese/analysis , Fatty Acids/analysis , Milk/chemistry , Sorghum , Animals , Diet/veterinary , Female , Lactation , Milk/metabolism , Plant Leaves , Silage/analysis , Taste , Time Factors , Volatile Organic Compounds/analysis
5.
Psychol Med ; 48(8): 1359-1366, 2018 06.
Article in English | MEDLINE | ID: mdl-29017620

ABSTRACT

BACKGROUND: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. METHODS: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. RESULTS: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. CONCLUSIONS: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.


Subject(s)
Cognitive Dysfunction/diagnosis , Family/psychology , Schizophrenia/complications , Schizophrenic Psychology , Adult , Aged , Cognition , Consensus , Female , Humans , Male , Middle Aged , Outpatients/psychology , Psychiatric Status Rating Scales , Psychometrics
6.
J Dairy Sci ; 101(8): 6752-6761, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29803420

ABSTRACT

The aim of this study was to determine the effect of inclusion of fresh forage in diet for lactating buffalo on properties of mozzarella cheese under intensive farming conditions. Thirty-two buffalo cows were equally allotted into 2 groups fed diets with (fresh group, FRS) or without (control group, CTL) fresh sorghum. The study consisted of 2 trials. In the first one, animals from group FRS were fed a diet containing 10 kg of fresh sorghum (10-FRS diet) that was doubled to 20 kg (20-FRS diet) in the second trial. All diets were isonitrogenous and isoenergetic, and fresh forage accounted for 13.4 and 26.5 of dietary dry matter, respectively, for the 10-FRS and 20-FRS diet. In each trial, milk from the 2 groups was used to produce 3 batches/diet of Mozzarella di Bufala Campana Protected Designation of Origin cheese. Milk yield and composition were not influenced by dietary treatment. The use of 10-FRS diet did not affect any properties of mozzarella. As the inclusion rate of fresh sorghum doubled to 20 kg, an increment of unsaturated fatty acid percentages and a lowering of short-chain and saturated fatty acids were observed. Moreover, the sensory characteristics of mozzarella were modified, although no effects were observed on consumer acceptance. We conclude that the use of green fodder can represent a low-cost feeding strategy to improve the healthiness of buffalo mozzarella under intensive farming conditions with no detrimental effect on consumer blind acceptance.


Subject(s)
Animal Feed/analysis , Buffaloes , Cheese/analysis , Diet , Poaceae , Animals , Cheese/standards , Fatty Acids , Female , Lactation , Milk
7.
J Environ Sci Health B ; 53(3): 191-198, 2018 Mar 04.
Article in English | MEDLINE | ID: mdl-29293401

ABSTRACT

Chlorpyrifos is an anticholinesterase organophosphate insecticide widely used in Argentina in the production of food derived from animal, fruit and horticultural origin and is reported as a residue within these products. Local reference values for acetyl and butyrylcholinesterase were determined in Aberdeen Angus bovine and cross bred cattle (n = 25), a requirement to be able to evaluate toxicity of commercial organophosphate and carbamate formulations. The activity of cholinesterase enzymes presented an overall mean of 2,183.00 ± 485.6 IU L-1 for erythrocyte acetylcholinesterase and 203.1 ± 42.06 IU L-1 for plasma butyrylcholinesterase, which are used as reference values for meat steers within a system of intensive production in a semi-arid region. The toxic potential of chlorpyrifos in steers of the same breeds (n = 12) was assessed applying chlorpyrifos 15.00% Tipertox® in a single therapeutic dose of 7.50 mg kg-1 by topical route. Prior to application and then on day 1 and day 21 post-application, both blood cholinesterases, serum chlorpyrifos concentration by ultra-high resolution liquid chromatography with mass detector, analysis of blood counts, total proteins, liver enzymes, urea and creatinine were evaluated. The mean plasma concentration of chlorpyrifos was 27.90 ug L-1 at 24 h. The findings indicate that the therapeutic treatment of castrated male bovines treated with chlorpyrifos, applied by pour-on according to the manufacturer's instructions, does not cause changes in the variables evaluated.


Subject(s)
Acetylcholinesterase/blood , Butyrylcholinesterase/blood , Chlorpyrifos/toxicity , Cholinesterase Inhibitors/toxicity , Animals , Argentina , Cattle , Chromatography, High Pressure Liquid , Erythrocytes/drug effects , Food Contamination , Insecticides/toxicity , Kidney/drug effects , Kidney/physiology , Liver/drug effects , Liver/enzymology , Male , Pesticide Residues/toxicity , Reference Values
8.
Mult Scler ; 21(4): 396-401, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25168208

ABSTRACT

BACKGROUND: Identifying markers of cognitive dysfunction in multiple sclerosis (MS) is extremely challenging since it means supplying potential biomarkers for neuroprotective therapeutic strategies. OBJECTIVE: The aim of this study is to investigate the relationship between fMRI correlates of attention performance and cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels in patients with clinically isolated syndrome (CIS) suggestive of MS. METHODS: Twenty-one untreated, cognitively preserved CIS patients underwent BOLD-fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. CSF NFL was assessed by ELISA technique. SPM8 random-effects models were used for statistical analyses of fMRI data (p<0.05 corrected). RESULTS: Repeated-measures ANOVA on imaging data showed an interaction between attentional control load and NFL levels in the right putamen. At the high level of attentional control demand CIS patients with "low NFL levels" showed greater activity in the putamen compared with subjects with "high NFL levels" (p=0.001). These results are independent of cognitive impairment index. CONCLUSIONS: Our findings suggest a relationship between CSF NFL levels and load-dependent failure of putaminal recruitment pattern during sustained attention in CIS and suggest a role of CSF NFL as a marker of subclinical abnormality of cognitive pathway recruitment in CIS.


Subject(s)
Attention/physiology , Cognition Disorders/etiology , Demyelinating Diseases/cerebrospinal fluid , Demyelinating Diseases/physiopathology , Neurofilament Proteins/cerebrospinal fluid , Adult , Biomarkers/cerebrospinal fluid , Cognition Disorders/diagnosis , Demyelinating Diseases/complications , Enzyme-Linked Immunosorbent Assay , Female , Humans , Magnetic Resonance Imaging , Male , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/complications , Multiple Sclerosis/physiopathology
9.
Pharmacol Res ; 91: 36-46, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25434589

ABSTRACT

Peripheral neuropathy is characterized by abnormal pain responses triggered by the release of several mediators and neuronal hyperexcitability at the spinal cord level. Emerging evidence indicates that the enhanced activity of dorsal horn neurons requires communication with glia and microglia, cells that are physiologically involved in neuronal wellbeing. Prokineticins (PKs), which include PK1 and PK2, represent a novel family of chemokines characterized by a unique structural motif comprising five disulfide bonds. They are expressed in the peripheral and central nervous system. PKs bind two G protein coupled receptors, PKR1 and PKR2, and participate in the regulation of several biological processes, including pain sensation. This study aimed to investigate the anti-nociceptive effect of PC1, a non-peptide PKR1-preferring antagonist, in a mouse model of neuropathic pain. To do this, we assessed the activity of spinal cord nociceptive neurons as well as astrocyte and microglia phenotypes after repeated administration of PC1 in vivo. PC1 treatment strongly delayed the development of thermal hyperalgesia and tactile and mechanical allodynia. It also reduced spinal microglial and glial activation 8 days post injury in spared nerve injury (SNI) mice. Neuropathic mice showed an increased level of PK2 protein in the spinal cord, mostly in astrocytes. PC1 treatment completely reversed the increased responsiveness to mechanical stimuli, the decreased threshold of neuronal activation, and the increased spontaneous activity that were observed in nociceptive specific (NS) neurons of SNI mice.


Subject(s)
Analgesics/therapeutic use , Gastrointestinal Hormones/metabolism , Neuralgia/drug therapy , Neuropeptides/metabolism , Receptors, G-Protein-Coupled/antagonists & inhibitors , Spinal Cord/drug effects , Triazines/therapeutic use , Animals , Astrocytes/drug effects , Astrocytes/metabolism , Behavior, Animal/drug effects , Gastrointestinal Hormones/genetics , Hot Temperature , Hyperalgesia/drug therapy , Hyperalgesia/metabolism , Male , Mice , Neuralgia/metabolism , Neurons/drug effects , Neurons/physiology , Neuropeptides/genetics , Peripheral Nerve Injuries/drug therapy , Peripheral Nerve Injuries/metabolism , RNA, Messenger/metabolism , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Sciatic Nerve/drug effects , Sciatic Nerve/injuries , Sciatic Nerve/metabolism , Spinal Cord/metabolism , Spinal Cord/physiology , Triazines/pharmacology
11.
J Dairy Sci ; 97(4): 1918-28, 2014.
Article in English | MEDLINE | ID: mdl-24534504

ABSTRACT

The effect of season of the year associated with changes in feeding and management system (pasture-based vs. confinement) on milk and cheese fatty acid profile and on sensory properties of Caciocavallo cheese was evaluated on 3 mountain dairy farms. Each farm used a pasture-based feeding system from April to June and from September to October (PS), and a confinement system for the rest of the year (CS). As a consequence of grazing, PS milk showed higher percentages of C18:3, cis-9,trans-11 conjugated linoleic acid, and trans-11 C18:1, and a reduced percentage of C16:0. The fatty acid profile of cheese largely reflected that of the corresponding raw milk from which cheese was made. This led to a significant decrease of atherogenic index in cheeses produced from cows on pasture. Based on sensory analysis, cheese from animals kept on pasture was more yellow and had a lower intensity of butter and smoked odors than did CS cheese. In addition, grazing induced a lower intensity of bitter and a higher intensity of spicy flavors compared with cheese from CS animals. In regard to texture, pasture feeding resulted in higher intensity of friability and graininess. All cheeses performed well in consumer tests; the panel found all samples more than acceptable for overall liking, and for liking according to appearance, taste/flavor, and texture. Overall liking of Caciocavallo cheese, as assessed by slope analysis, was affected primarily by taste/flavor (raw slope k=0.88) and texture (k=0.97), whereas appearance had a lesser effect (k=0.72). The acidic and sensory profiles of cheese were well discriminated, with healthier cheeses produced by grazing cows. Therefore, wider use of pasture should be promoted to accentuate this favorable feature. Based on the specific nutritional and sensory characteristics of mountain Caciocavallo cheese, particularly that obtained from grazing animals, efforts should be made to indicate the quality of this cheese to the consumer and improve product recognition.


Subject(s)
Cheese/analysis , Dairying/methods , Fatty Acids/analysis , Milk/chemistry , Animals , Cattle/physiology , Diet , Female , Italy , Odorants/analysis , Seasons , Taste
12.
Psychol Med ; 43(2): 279-92, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22617427

ABSTRACT

BACKGROUND: Emotion dysregulation is a key feature of schizophrenia, a brain disorder strongly associated with genetic risk and aberrant dopamine signalling. Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene contains a functional polymorphism (COMT Val158Met) associated with differential activity of the enzyme and with brain physiology of emotion processing. The aim of the present study was to investigate whether genetic risk for schizophrenia and COMT Val158Met genotype interact on brain activity during implicit and explicit emotion processing. METHOD: A total of 25 patients with schizophrenia, 23 healthy siblings of patients and 24 comparison subjects genotyped for COMT Val158Met underwent functional magnetic resonance imaging during implicit and explicit processing of facial stimuli with negative emotional valence. RESULTS: We found a main effect of diagnosis in the right amygdala, with decreased activity in patients and siblings compared with control subjects. Furthermore, a genotype × diagnosis interaction was found in the left middle frontal gyrus, such that the effect of genetic risk for schizophrenia was evident in the context of the Val/Val genotype only, i.e. the phenotype of reduced activity was present especially in Val/Val patients and siblings. Finally, a complete inversion of the COMT effect between patients and healthy subjects was found in the left striatum during explicit processing. CONCLUSIONS: Overall, these results suggest complex interactions between genetically determined dopamine signalling and risk for schizophrenia on brain activity in the prefrontal cortex during emotion processing. On the other hand, the effects in the striatum may represent state-related epiphenomena of the disorder itself.


Subject(s)
Catechol O-Methyltransferase/genetics , Emotions/physiology , Prefrontal Cortex/physiopathology , Schizophrenia/genetics , Adult , Amygdala/metabolism , Amygdala/physiopathology , Analysis of Variance , Brain Mapping , Case-Control Studies , Catechol O-Methyltransferase/metabolism , Dopamine/metabolism , Facial Expression , Female , Functional Laterality , Genetic Predisposition to Disease , Genotype , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging/methods , Male , Photic Stimulation , Polymorphism, Single Nucleotide/physiology , Prefrontal Cortex/metabolism , Psychiatric Status Rating Scales , Schizophrenia/metabolism , Schizophrenia/physiopathology , Siblings
13.
Psychol Med ; 43(8): 1661-71, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23111173

ABSTRACT

BACKGROUND: Abnormalities in hippocampal-parahippocampal (H-PH) function are prominent features of schizophrenia and have been associated with deficits in episodic memory. However, it remains unclear whether these abnormalities represent a phenotype related to genetic risk for schizophrenia or whether they are related to disease state. METHOD: We investigated H-PH-mediated behavior and physiology, using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), during episodic memory in a sample of patients with schizophrenia, clinically unaffected siblings and healthy subjects. RESULTS: Patients with schizophrenia and unaffected siblings displayed abnormalities in episodic memory performance. During an fMRI memory encoding task, both patients and siblings demonstrated a similar pattern of reduced H-PH engagement compared with healthy subjects. CONCLUSIONS: Our findings suggest that the pathophysiological mechanism underlying the inability of patients with schizophrenia to properly engage the H-PH during episodic memory is related to genetic risk for the disorder. Therefore, H-PH dysfunction can be assumed as a schizophrenia susceptibility-related phenotype.


Subject(s)
Genetic Predisposition to Disease , Hippocampus/physiopathology , Magnetic Resonance Imaging/methods , Parahippocampal Gyrus/physiology , Schizophrenia/physiopathology , Adult , Brain Mapping , Female , Humans , Male , Memory, Episodic , Middle Aged , Phenotype , Schizophrenia/genetics , Siblings
14.
Mult Scler ; 19(9): 1153-60, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23329700

ABSTRACT

BACKGROUND: Load-related functional magnetic resonance imaging (fMRI) abnormalities of brain activity during performance of attention tasks have been described in definite multiple sclerosis (MS). No data are available in clinically isolated syndrome (CIS) suggestive of MS. OBJECTIVES: The objective of this research is to evaluate in CIS patients the fMRI pattern of brain activation during an attention task and to explore the effect of increasing task load demand on neurofunctional modifications. METHODS: Twenty-seven untreated CIS patients and 32 age- and sex-matched healthy controls (HCs) underwent fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. Random-effects models were used for statistical analyses of fMRI data. RESULTS: CIS patients had reduced accuracy and greater reaction time at the VAC task compared with HCs (p=0.007). On blood oxygenation level-dependent (BOLD)-fMRI, CIS patients had greater activity in the right parietal cortex (p=0.0004) compared with HCs. Furthermore, CIS patients had greater activity at the lower (p=0.05) and reduced activity at the greater (p=0.04) level of attentional control demand in the left putamen, compared with HCs. CONCLUSIONS: This study demonstrates the failure of attentional control processing in CIS. The load-related fMRI dysfunction of the putamen supports the role of basal ganglia in the failure of attention observed at the earliest stage of MS.


Subject(s)
Attention/physiology , Demyelinating Diseases/physiopathology , Putamen/physiopathology , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Multiple Sclerosis/physiopathology , Reaction Time/physiology
15.
Eur J Neurol ; 20(5): 740-7, 2013 May.
Article in English | MEDLINE | ID: mdl-23121321

ABSTRACT

Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by progressive neurological dysfunction. To date, only supportive care aimed to halt the progressive neurodegeneration is available for the treatment. Recently, an improvement of neurological signs during short-term treatment with betamethasone has been reported. To date, the molecular and biochemical mechanisms by which the steroid produces such effects have not yet been elucidated. Therefore, a review of the literature was carried out to define the potential molecular and functional targets of the steroid effects in A-T. Glucocorticoids (GCs) are capable of diffusing into the CNS by crossing the blood-brain barrier (BBB) where they exert effects on the suppression of inflammation or as antioxidant. GCs have been shown to protect post-mitotic neurons from apoptosis. Eventually, GCs may also modulate synaptic plasticity. A better understanding of the mechanisms of action of GCs in the brain is needed, because in A-T during the initial phase of cell loss the neurological impairment may be rescued by interfering in the biochemical pathways. This would open a new window of intervention in this so far incurable disease.


Subject(s)
Ataxia Telangiectasia/drug therapy , Ataxia Telangiectasia/physiopathology , Betamethasone/therapeutic use , Cell Cycle Proteins/physiology , DNA-Binding Proteins/physiology , Glucocorticoids/therapeutic use , Nerve Degeneration/drug therapy , Neuronal Plasticity/drug effects , Protein Serine-Threonine Kinases/physiology , Tumor Suppressor Proteins/physiology , Ataxia Telangiectasia/genetics , Ataxia Telangiectasia Mutated Proteins , Betamethasone/pharmacology , Cell Cycle Proteins/genetics , DNA-Binding Proteins/genetics , Glucocorticoids/physiology , Humans , Models, Genetic , Oxidative Stress/physiology , Protein Serine-Threonine Kinases/genetics , Tumor Suppressor Proteins/genetics
16.
J Dent Res ; 102(3): 340-348, 2023 03.
Article in English | MEDLINE | ID: mdl-36348499

ABSTRACT

Salivary gland (SG) development, maturation, and homeostasis require coordinated roles of transcription factors (TFs) that dictate specific cell identities and fate. The ETS family of proteins are important transcriptional drivers of diverse cell lineages, tissue development, and differentiation programs and hence are also likely to play an important role in the SG. Here we have leveraged genomic and epigenomic data of the SG to examine the expression profile of ETS genes and identified 2 closely related paralogs, Elf5 and Ehf, that are highly expressed in distinct epithelial subpopulations. By using a well-defined mouse knockout model of Elf5, we show that Elf5, despite its enriched expression in the acinar cells, is functionally dispensable for maintaining the homeostatic state of the adult SG epithelium. The lack of a discernible phenotype of the Elf5-null SG might be due to possible functional redundancy with Ehf or other ETS factors. To probe this possibility and to examine the specific consequences of Ehf loss in the SG, we used CRISPR-Cas9 to generate mice in which the DNA-binding ETS domain of Ehf is disrupted due to an insertion mutation. We demonstrate that the Ehf mutant (EhfMut) mice exhibit a distinct cellular phenotype with decreased granular convoluted tubules that are accompanied by an increased accumulation of the intercalated Sox9-positive ductal cell population. Interestingly, the ductal phenotype of the EhfMut animals is highly pronounced in males, reaffirming the established sexual dimorphism of the SG that exists in rodents. Our results show that unlike Elf5, Ehf plays a nonredundant role in directing ductal cell differentiation of the SG and highlights the phenotypic subtlety in mutant mice of closely related TFs and the importance of careful consideration of cell type-specific studies.


Subject(s)
DNA-Binding Proteins , Transcription Factors , Male , Mice , Animals , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Transcription Factors/metabolism , Salivary Glands/metabolism
17.
J Dent Res ; 102(5): 525-535, 2023 05.
Article in English | MEDLINE | ID: mdl-36726292

ABSTRACT

Saliva-secreting and transporting cells are part of the complex cellular milieu of the human salivary gland, where they play important roles in normal glandular physiology and diseased states. However, comprehensive molecular characterization, particularly at single-cell resolution, is still incomplete, in part due to difficulty in procuring normal human tissues. Here, we perform an in-depth analysis of male and female adult human submandibular gland (SMG) samples by bulk RNA sequencing (RNA-seq) and examine the molecular underpinnings of the heterogeneous cell populations by single-cell (sc) RNA-seq. Our results from scRNA-seq highlight the remarkable diversity of clusters of epithelial and nonepithelial cells that reside in the SMG that is also faithfully recapitulated by deconvolution of the bulk-RNA data sets. Our analyses reveal complex transcriptomic heterogeneity within both the ductal and acinar subpopulations and identify atypical SMG cell types, such as mucoacinar cells that are unique to humans and ionocytes that have been recently described in the mouse. We use CellChat to explore ligand-receptor interactome predictions that likely mediate crucial cell-cell communications between the various cell clusters. Finally, we apply a trajectory inference method to investigate specific cellular branching points and topology that offers insights into the dynamic and complex differentiation process of the adult SMG. The data sets and the analyses herein comprise an extensive wealth of high-resolution information and a valuable resource for a deeper mechanistic understanding of human SMG biology and pathophysiology.


Subject(s)
Submandibular Gland , Transcriptome , Humans , Male , Mice , Female , Animals , Salivary Glands , Gene Expression Profiling , Cell Differentiation
18.
Br J Anaesth ; 109(2): 208-15, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22661752

ABSTRACT

BACKGROUND: Most investigators have attributed the reduced postoperative pain or anaesthetic drug requirements in patients receiving i.v. magnesium sulphate (MgSO(4)) infusion during spinal or general anaesthesia to central N-methyl-d-aspartate (NMDA) receptor magnesium (Mg) activity. In this study, we investigated how cerebrospinal fluid (CSF) Mg concentrations change after spinal anaesthesia, and whether peripherally infusing MgSO(4) influences central Mg levels. METHODS: Forty-five patients undergoing continuous spinal anaesthesia for hip arthroplasty were randomly assigned to receive either i.v. MgSO(4) at a dose of 50 mg kg(-1) diluted in 100 ml 0.9% saline solution followed by 15 mg kg(-1) h(-1) for 6 h or saline at the same volume [mean (sd) 64 (10) ml]. The changes in CSF and serum total and ionized Mg concentrations were assessed at six time points before and after spinal anaesthesia. Secondary outcome variables included serum and CSF electrolytes and proteins. RESULTS: Thirty-five patients completed the study. We found that spinal anaesthesia reduced total and ionized Mg concentrations in CSF by about 10%. Increasing serum Mg concentration over 80% of the baseline value left CSF Mg levels unchanged. CONCLUSIONS: Spinal anaesthesia unexpectedly reduced CSF total and ionized Mg concentrations in patients undergoing hip arthroplasty, although the mechanism is unclear. The dose used for peripheral MgSO(4) infusion in this study had no influence on central Mg concentrations in neurologically healthy patients undergoing spinal anaesthesia. If CSF Mg concentration is a reliable marker of Mg brain bioavailability, peripherally infused MgSO(4) during spinal anaesthesia is unlikely to influence central NMDA receptor activity.


Subject(s)
Analgesics/administration & dosage , Anesthesia, Spinal/methods , Arthroplasty, Replacement, Hip , Magnesium Sulfate/administration & dosage , Magnesium/cerebrospinal fluid , Adult , Aged , Aged, 80 and over , Analgesics/pharmacokinetics , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Bupivacaine/analogs & derivatives , Female , Humans , Infusions, Intravenous , Levobupivacaine , Magnesium/blood , Magnesium Sulfate/pharmacokinetics , Male , Middle Aged , Prospective Studies
20.
Foods ; 11(5)2022 Mar 06.
Article in English | MEDLINE | ID: mdl-35267393

ABSTRACT

In Italy, most of the cultivated walnuts belong to the Sorrento ecotype, and they are considered commercially valuable due to their specific organoleptic characteristics. The aim of this study is to evaluate and compare the morphological and compositional characteristics of walnuts sampled from 'Sorrento' trees cultivated in different locations in Campania and trees of both the 'Chandler' and 'Sorrento' varieties derived from the same location. The results demonstrated that 'Sorrento' and 'Chandler' walnuts have different biometric characteristics and a different fat content, with the highest fat content being found in the 'Sorrento' variety. Regarding the fatty acid (FA) composition, the content of monounsaturated and saturated fatty acids (MUFAs and SFAs) was highest in the 'Sorrento' variety (from 13 to 15% for MUFAs and from 11 to 13% for SFAs), while the polyunsaturated fatty acids (PUFAs) content was highest in the 'Chandler' variety (77%). The total phenolics content (TPC) was highest in the 'Sorrento' variety (from 910 to 1230 mg GAE/100 g), while no difference in γ-tocopherol content was found. Furthermore, the influence of walnut area cultivation was shown for fat content, FA composition and TPC. Therefore, both walnut varieties demonstrated good nutritional properties considering the PUFAs and γ-tocopherol content.

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