Aim of this study was to examine the hypothesis that only a subgroup of patients with lesser primary brain damage after severe head injury may benefit from therapeutic hypothermia. We prospectively analysed 72 patients with severe head injury, randomized into groups with (n = 37) and without (n = 35) hypothermia of 34 degrees C maintained for 72 hours. The influence of hypothermia on ICP, CPP and neurological outcome was analysed in the context of the extent of primary brain damage. Patients with normothermia and primary lesions (n = 17) values: GCS on admission 5 (median), ICP 18.9 (mean), CPP 73 (mean), GOS 4 (median). Patients with normothermia and extracerebral hematomas (n = 20): GCS 4, ICP 16, CPP 71, GOS 3. Patients with hypothermia and primary lesions (n = 21): GCS 4,62, ICP 10, 81, CPP 78,1, GOS 4. Patients with hypothermia and extracerebral hematomas (n = 14): GCS 5, ICP 13.2, CPP 78, GOS 5. Hypothermia decreased ICP and increased CPP regardless of the type of brain injury. Hypothermia was not able to improve outcome in patients with primary brain lesions but this pilot study suggests that it significantly improves outcome in patients with extracerebral hematomas.
- MeSH
- Adult MeSH
- Risk Assessment methods MeSH
- Outcome Assessment, Health Care MeSH
- Incidence MeSH
- Intracranial Hypertension mortality therapy MeSH
- Intracranial Pressure * MeSH
- Comorbidity MeSH
- Blood Pressure * MeSH
- Quality of Life MeSH
- Humans MeSH
- Manometry methods statistics & numerical data MeSH
- Survival Rate MeSH
- Recovery of Function MeSH
- Pilot Projects MeSH
- Brain Injuries mortality therapy MeSH
- Prognosis MeSH
- Risk Factors MeSH
- Hypothermia, Induced methods statistics & numerical data MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Geographicals
- Czech Republic epidemiology MeSH
PURPOSE: The present study aimed at measuring the smoothed and non-smoothed cepstral peak prominence (CPPS and CPP) in teachers who considered themselves to have normal voice but some of them had laryngeal pathology. The changes of CPP, CPPS, sound pressure level (SPL) and perceptual ratings with different voice tasks were investigated and the influence of vocal pathology on these measures was studied. METHOD: Eighty-four Finnish female primary school teachers volunteered as participants. Laryngoscopically, 52.4% of these had laryngeal changes (39.3% mild, 13.1% disordered). Sound recordings were made for phonations of comfortable sustained vowel, comfortable speech, and speech produced at increased loudness level as used during teaching. CPP, CPPS and SPL values were extracted using Praat software for all three voice samples. Sound samples were also perceptually evaluated by five voice experts for overall voice quality (10 point scale from poor to excellent) and vocal firmness (10 point scale from breathy to pressed, with normal in the middle). RESULTS: The CPP, CPPS and SPL values were significantly higher for vowels than for comfortable speech and for loud speech compared to comfortable speech (P < 0.001). Significant correlations were found between SPL and cepstral measures. The loud speech was perceived to be firmer and have a better voice quality than comfortable speech. No significant relationships of the laryngeal pathology status with cepstral values, perceptual ratings, or voice SPLs were found (P > 0.05). CONCLUSION: Neither the acoustic measures (CPP, CPPS, and SPL) nor the perceptual evaluations could clearly distinguish teachers with laryngeal changes from laryngeally healthy teachers. Considering no vocal complaints of the subjects, the data could be considered representative of teachers with functionally healthy voice.
- Keywords
- CPP, CPPS, Laryngeal pathologies, Perceptual evaluation, Teachers’ voice, Voice SPL,
- MeSH
- Speech Acoustics * MeSH
- Acoustics * MeSH
- Adult MeSH
- Occupational Health MeSH
- Voice Quality * MeSH
- Laryngoscopy MeSH
- Larynx pathology physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Speech Production Measurement * MeSH
- Occupational Diseases diagnosis physiopathology MeSH
- Voice Disorders diagnosis physiopathology MeSH
- Predictive Value of Tests MeSH
- School Teachers * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Finland MeSH
The extended occurrence of fentanils abuse associated with the dramatic increase in opioid fatal overdoses and dependence strongly emphasizes insufficiencies in opioid addiction treatment. Recently, the growth hormone secretagogue receptor (GHS-R1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in opioid abuse is still unclear. Therefore, the aim of our study was to clarify whether the GHS-R1A antagonist JMV2959 could reduce the fentanyl-induced conditioned place preference (CPP), the fentanyl intravenous self-administration (IVSA), and the tendency to relapse, but also whether JMV2959 could significantly influence the fentanyl-induced dopamine efflux in the nucleus accumbens (NAC) in rats, that importantly participates in opioids' reinforcing effects. Following an ongoing fentanyl self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 minutes before three consequent daily 360-minute IVSA sessions under a fixed ratio FR1, which significantly reduced the number of active lever-pressing, the number of infusions, and the fentanyl intake. Pretreatment with JMV2959 also reduced the fentanyl-seeking/relapse-like behaviour tested in rats on the 12th day of the forced abstinence period. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of fentanyl-CPP. The fentanyl-CPP development was reduced after the simultaneous administration of JMV2959 with fentanyl during conditioning. The JMV2959 significantly reduced the accumbens dopamine release induced by subcutaneous and intravenous fentanyl. Simultaneously, it affected the concentration of byproducts associated with dopamine metabolism in the NAC. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of fentanyl.
- Keywords
- IVSA, addiction, CPP, dopamine, fentanyl, ghrelin antagonism,
- MeSH
- Self Administration MeSH
- Dopamine metabolism MeSH
- Fentanyl administration & dosage adverse effects MeSH
- Ghrelin metabolism MeSH
- Glycine analogs & derivatives pharmacology MeSH
- Administration, Intravenous MeSH
- Rats MeSH
- Narcotics administration & dosage adverse effects MeSH
- Nucleus Accumbens drug effects MeSH
- Conditioning, Operant drug effects MeSH
- Rats, Wistar MeSH
- Receptors, Ghrelin antagonists & inhibitors MeSH
- Triazoles pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Dopamine MeSH
- Fentanyl MeSH
- Ghrelin MeSH
- Glycine MeSH
- N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide MeSH Browser
- Narcotics MeSH
- Receptors, Ghrelin MeSH
- Triazoles MeSH
Chlamydia psittaci pneumonia (CPP) is a lung disease caused by the infection with the Chla-mydia psittaci bacterium, which can lead to severe acute respiratory distress syndrome and systemic symptoms. This study explored the specific mechanisms underlying the impact of reactive oxygen species (ROS) on the Th17/Treg balance in CPP. The levels of ROS and the differentiation ratio of Th17/Treg in the peripheral blood of healthy individuals and CPP patients were measured using ELISA and flow cytometry, respectively. The association between the ROS levels and Th17/Treg was assessed using Pearson correlation analysis. The ROS levels and the Th17/Treg ratio were measured in CD4+ T cells following H2O2 treatment and NLRP3 inhibition. The effects of H2O2 treatment and NLRP3 inhibition on the NLRP3/IL-1β/caspase-1 pathway were observed using immunoblotting. Compared to the healthy group, the CPP group exhibited increased levels of ROS in the peripheral blood, an elevated ratio of Th17 differentiation, and a decreased ratio of Treg differentiation. ROS levels were positively correlated with the Th17 cell proportion but negatively correlated with the Treg cell proportion. The ROS levels and NLRP3/IL-1β/caspase-1 expression were up-regulated in CD4+ T cells after H2O2 treatment. Furthermore, there was an increase in Th17 differentiation and a decrease in Treg differentiation. Conversely, the NLRP3/IL-1β/caspase-1 pathway inhibition reversed the effects of H2O2 treatment, with no significant change in the ROS levels. ROS regulates the Th17/Treg balance in CPP, possibly through the NLRP3/IL-1β/caspase-1 pathway. This study provides a new perspective on the development of immunotherapy for CPP.
- Keywords
- CD4+ T cells, CPP, NLRP3/IL-1β/Caspase-1, ROS, Th17/Treg,
- MeSH
- Cell Differentiation * drug effects MeSH
- Th17 Cells * immunology metabolism MeSH
- Chlamydophila psittaci * MeSH
- Adult MeSH
- Interleukin-1beta * metabolism MeSH
- Caspase 1 * metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Hydrogen Peroxide metabolism MeSH
- NLR Family, Pyrin Domain-Containing 3 Protein * metabolism MeSH
- Psittacosis MeSH
- Reactive Oxygen Species * metabolism MeSH
- T-Lymphocytes, Regulatory * immunology MeSH
- Signal Transduction MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Interleukin-1beta * MeSH
- Caspase 1 * MeSH
- NLRP3 protein, human MeSH Browser
- Hydrogen Peroxide MeSH
- NLR Family, Pyrin Domain-Containing 3 Protein * MeSH
- Reactive Oxygen Species * MeSH
Naphyrone, also known as NRG-1, is a novel psychoactive substance (NPS), a cathinone with stimulatory properties available on the grey/illicit drug market for almost a decade. It is structurally related to infamously known powerful stimulants with the pyrovalerone structure, such as alpha-pyrrolidinovalerophenone (α-PVP) or methylenedioxypyrovalerone (MDPV) that are labeled as a cheap replacement for cocaine and other stimulants. Despite the known addictive potential of α-PVP and MDPV, there are no studies directly evaluating naphyrone's addictive potential e.g., in conditioned place preference (CPP) test or using self-administration. Therefore, our study was designed to evaluate the addictive potential in a CPP test in male Wistar rats and compare its effect to another powerful stimulant with a high addictive potential - methamphetamine. Naphyrone increased time spent in the drug-paired compartment with 5 and 20 mg/kg s.c. being significant and 10 mg/kg s.c. reaching the threshold (p = 0.07); the effect was comparable to that of methamphetamine 1.5 mg/kg s.c. The lowest dose, naphyrone 1 mg/kg s.c., had no effect on CPP. Interestingly, no dose response effect was detected. Based on these data, we are able to conclude that naphyrone has an addictive potential and may possess a significant risk to users.
- Keywords
- Addictive potential, CPP, Conditioned place preference test, Naphyrone, Novel psychoactive substances,
- MeSH
- Alkaloids pharmacology MeSH
- Behavior, Animal drug effects MeSH
- Conditioning, Classical drug effects MeSH
- Rats MeSH
- Methamphetamine administration & dosage pharmacology MeSH
- Disease Models, Animal MeSH
- Pentanones administration & dosage pharmacology MeSH
- Substance-Related Disorders * MeSH
- Rats, Wistar MeSH
- Pyrrolidines administration & dosage pharmacology MeSH
- Central Nervous System Stimulants administration & dosage pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-one MeSH Browser
- Alkaloids MeSH
- cathinone MeSH Browser
- Methamphetamine MeSH
- Pentanones MeSH
- Pyrrolidines MeSH
- Central Nervous System Stimulants MeSH
Drug access to the CNS is hindered by the presence of the blood-brain barrier (BBB), and the intranasal route has risen as a non-invasive route to transport drugs directly from nose-to-brain avoiding the BBB. In addition, nanoparticles (NPs) have been described as efficient shuttles for direct nose-to-brain delivery of drugs. Nevertheless, there are few studies describing NP nose-to-brain transport. Thus, the aim of this work was (i) to develop, characterize and validate in vitro olfactory cell monolayers and (ii) to study the transport of polymeric- and lipid-based NPs across these monolayers in order to estimate NP access into the brain using cell penetrating peptide (CPPs) moieties: Tat and Penetratin (Pen). All tested poly(d,l-lactide-co-glycolide) (PLGA) and nanostructured lipid carrier (NLC) formulations were stable in transport buffer and biocompatible with the olfactory mucosa cells. Nevertheless, 0.7% of PLGA NPs was able to cross the olfactory cell monolayers, whereas 8% and 22% of NLC and chitosan-coated NLC (CS-NLC) were transported across them, respectively. Moreover, the incorporation of CPPs to NLC surface significantly increased their transport, reaching 46% of transported NPs. We conclude that CPP-CS-NLC represent a promising brain shuttle via nose-to-brain for drug delivery.
- Keywords
- CPP, Lipid nanoparticles, NLC, Nanoparticles, Nose-to-brain delivery, Olfactory mucosa,
- MeSH
- Administration, Intranasal MeSH
- Biological Transport MeSH
- Chitosan chemistry MeSH
- Olfactory Mucosa cytology metabolism MeSH
- Chemistry, Pharmaceutical methods MeSH
- Blood-Brain Barrier metabolism MeSH
- Polylactic Acid-Polyglycolic Acid Copolymer MeSH
- Rats MeSH
- Lactic Acid chemistry MeSH
- Polyglycolic Acid chemistry MeSH
- Drug Delivery Systems * MeSH
- Lipids chemistry MeSH
- Brain metabolism MeSH
- Nanoparticles * MeSH
- Nasal Mucosa metabolism MeSH
- Cell-Penetrating Peptides chemistry MeSH
- Polymers chemistry MeSH
- Rats, Wistar MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Validation Study MeSH
- Names of Substances
- Chitosan MeSH
- Polylactic Acid-Polyglycolic Acid Copolymer MeSH
- Lactic Acid MeSH
- Polyglycolic Acid MeSH
- Lipids MeSH
- Cell-Penetrating Peptides MeSH
- Polymers MeSH
OBJECTIVES: The purpose of this study was to classify objectively breathiness in continuous speech according to a subjective evaluation of voice based on the GRBAS scale. STUDY DESIGN: A retrospective, experimental study. METHODS: A total of 593 records with read text were twice evaluated by five experts according to the GRBAS scale within two sessions with a time delay of at least 2 weeks. The records were subsequently subjected to acoustic analysis using parameters which do not rely on the accurate estimation of fundamental frequency: Glottal-to-Noise Excitation ratio, Cepstral Peak Prominence Pearson r at autocorrelation peak, Breathiness Index, and the ratio of high- to mid/low-frequency energy. These parameters were subsequently analyzed and a total of 92 features were created for each record. After feature space reduction based on Correlation Feature Selection and Information Gain, the feature space was reduced to four parameters. These four parameters were used for classification of breathiness. RESULTS: In the final set of four, the acoustic parameters have significantly different mean ranks in every grade of breathiness according to the GRBAS scale (Kruskal-Wallis test [P < 0.001]). The accuracy of classifier for objective evaluation of level of breathiness based on the discrete scale of breathiness reached 77%. Assuming continuous grades of breathiness, the classifier reached ρ = 0.92 (P < 0.001). CONCLUSIONS: The level of breathiness in continuous speech can be effectively described by automatic system-based analysis of acoustic measures. The proposed automatic system is able to determine the level of breathiness in continuous speech with sufficient precision.
- Keywords
- BRI, Breathiness, CPP, Classification, Continuous speech, Dysphonic voice, GNE, GRBAS scale, HLR, RPK,
- MeSH
- Speech Acoustics MeSH
- Respiration * MeSH
- Voice physiology MeSH
- Voice Quality * MeSH
- Humans MeSH
- Speech Production Measurement methods MeSH
- Follow-Up Studies MeSH
- Speech Perception physiology MeSH
- Voice Disorders diagnosis physiopathology MeSH
- Retrospective Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Although the cepstral peak prominence (CPP) and its variant, the cepstral peak prominence smooth (CPPS), are considered to be robust acoustic measures for the evaluation of dysphonia, whether they are sensitive to capture early voice changes in Parkinson's disease (PD) has not yet been explored. This study aimed to investigate the voice changes via the CPP measures in the idiopathic rapid eye movement sleep behavior disorder (iRBD), a special case of prodromal neurodegeneration, and recently diagnosed and advanced-stage Parkinson's disease (AS-PD) patients using different speaking tasks across noise-free and noisy environments. The sustained vowel phonation, reading of passages, and monologues of 60 early stage untreated PD, 30 advanced-stage Parkinson's disease, 60 iRBD, and 60 healthy control (HC) participants were evaluated. Significant differences were found between the PD groups and controls in sustained phonation via the CPP (p < 0.05) and CPPS (p < 0.01) and the monologue via the CPP (p < 0.01), although neither the CPP nor CPPS measures were sufficiently sensitive to capture the possible prodromal dysphonia in the iRBD. The quality of the CPP and CPPS measures was influenced substantially by the addition of ambient noise. It was anticipated that the CPP measures might serve as a promising digital biomarker in assessing the dysphonia from the early stages of PD.
"Candidatus Phytoplasma prunorum" (CPp) is a highly destructive phytopathogenic agent in many stone fruit-growing regions in Europe and the surrounding countries. In this work, we focused on documenting entire bacterial community in the phloem tissues of 60 stone fruit trees. Nested PCR and two real-time PCR assays were used to select CPp-positive (group A) and CPp-negative samples (group B). Afterwards, high-throughput amplicon sequencing was performed to assess bacterial community compositions in phloem tissues. The bacterial composition in phloem tissue consisted of 118 distinct genera, represented mainly by Pseudomonas, Acinetobacter, Methylobacterium, Sphingomonas, and Rhizobium. Statistics showed that CPp influenced the bacterial composition of infected plants (group A) and that the bacterial community depended on the geographical origin of the sample. This is the first work focusing on an analysis of the influence of CPp on the bacteria coexisting in the phloem tissues of stone fruit trees.
- Keywords
- Bacterial composition, High-throughput sequencing, Phloem, Stone Fruit, “Candidatus Phytoplasma prunorum”,
- MeSH
- Bacteria classification genetics isolation & purification MeSH
- Biodiversity MeSH
- Phloem microbiology MeSH
- Plant Diseases microbiology MeSH
- Fruit microbiology MeSH
- Phytoplasma physiology MeSH
- Prunus microbiology MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Publication type
- Journal Article MeSH
Cerebral perfusion pressure (CPP) is the net pressure gradient that drives oxygen delivery to cerebral tissue. It is the difference between the mean arterial pressure (MAP) and the intracranial pressure (ICP). As CPP is a calculated value, MAP and ICP must be measured simultaneously. In research models, anesthetized and acute monitoring is incapable of providing a realistic picture of the relationship between ICP and MAP under physiological and/or pathophysiological conditions. For long-term monitoring of both pressures, the principle of telemetry can be used. The aim of this study was to map changes in CPP and spontaneous behavior using continuous pressure monitoring and video recording for 7 days under physiological conditions (group C - 8 intact rats) and under altered brain microenvironment induced by brain edema (group WI - 8 rats after water intoxication) and neuroprotection with methylprednisolone - MP (group WI+MP - 8 rats with MP 100 mg/kg b.w. applicated intraperitoneally during WI). The mean CPP values in all three groups were in the range of 40-60 mm Hg. For each group of rats, the percentage of time that the rats spent during the 7 days in movement pattern A (standard movement stereotype) or B (atypical movement) was defined. Even at very low CPP values, the standard movement stereotype (A) clearly dominated over the atypical movement (B) in all rats. There was no significant difference between control and experimental groups. Chronic CPP values with correlated behavioral type may possibly answer the question of whether there is a specific, universal, optimal CPP at all.
- MeSH
- Intracranial Pressure * physiology MeSH
- Blood Pressure physiology MeSH
- Rats MeSH
- Monitoring, Physiologic MeSH
- Brain * MeSH
- Cerebrovascular Circulation physiology MeSH
- Telemetry MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH