Clear Speech Variants: An Investigation of Intelligibility and Speaker Effort in Speakers With Parkinson's Disease.

PURPOSE: This study investigated the effects of three clear speech variants on sentence intelligibility and speaking effort for speakers with Parkinson's disease (PD) and age- and sex-matched neurologically healthy controls. METHOD: Fourteen speakers with PD and 14 neurologically healthy speakers participated. Each speaker was recorded reading 18 sentences from the Speech Intelligibility Test in their habitual speaking style and for three clear speech variants: clear (SC; given instructions to speak clearly), hearing impaired (HI; given instructions to speak with someone with a hearing impairment), and overenunciate (OE; given instructions to overenunciate each word). Speakers rated the amount of physical and mental effort exerted during each speaking condition using visual analog scales (averaged to yield a metric of overall speaking effort). Sentence productions were orthographically transcribed by 50 naive listeners. Linear mixed-effects models were used to compare intelligibility and speaking effort across the clear speech variants. RESULTS: Intelligibility was reduced for the PD group in comparison to the control group only in the habitual condition. All clear speech variants significantly improved intelligibility above habitual levels for the PD group, with OE maximizing intelligibility, followed by the SC and HI conditions. Both groups rated speaking effort to be significantly higher for both the OE and HI conditions versus the SC and habitual conditions. DISCUSSION: For speakers with PD, all clear speech variants increased intelligibility to a level comparable to that of healthy controls. All clear speech variants were also associated with higher levels of speaking effort than habitual speech for the speakers with PD. Clinically, findings suggest that clear speech training programs consider using the instruction "overenunciate" for maximizing intelligibility. Future research is needed to identify if high levels of speaking effort elicited by the clear speech variants affect long-term sustainability of the intelligibility benefit.

The early history of the knee-jerk reflex in neurology.

Medical interest in the knee-jerk reflex began in about 1875 with simultaneous and independent publications by Wilhelm Heinrich Erb (1840-1921) and Carl Friedrich Otto Westphal (1833-1890) contending that the knee jerk was absent (and the ankle clonus was present) in all clear cases of locomotor ataxia (tabes dorsalis). Physicians in the medical communities of Europe, Great Britain, and North America responded with case and large group studies that tested this contention. These studies revealed the usefulness of the knee jerk and other myotatic reflexes, but also unexpected characteristics. The knee jerk, apparently so simple, proved to be a complex phenomenon depending the strength of the strike on the patella, induced muscle tension, and inhibition from the brain. Was it a reflex with afferent and efferent nerves and an intervening process in the spinal cord, or was it a local phenomenon confined to the muscle itself? Experimental studies directed at the reflex issue investigated latencies from patella strike to leg extension or muscle contraction and compared them with latencies from direct muscle strikes and theoretical calculations based on reflex components. Such studies were unable to resolve the reflex issue during the nineteenth century. The physicians were shown to be limited, like all scientific explorers of the unknown, by their knowledge, methodology, and technology.

Potential of nafimidone derivatives against co-morbidities of epilepsy: In vitro, in vivo, and in silico investigations.

Nafimidone is known for its clinical antiepileptic effects and alcohol derivatives of nafimidone were reported be potent anticonvulsants. These compounds are structurally similar to miconazole, which is known to inhibit cholinesterases, protect neurons, and ameliorate cognitive decline. Herein, we aimed to reveal the potential of three nafimidone alcohol esters (5 g, 5i, and 5 k), which were previously reported for their anticonvulsant effects, against co-morbidities of epilepsy such as inflammatory and neuropathic pain, cognitive and behavioral deficits, and neuron death, and understand their roles in related pathways such as γ-butyric acid type A (GABAA ) receptor and cholinesterases using in vitro, in vivo and in silico methods. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used for cytotoxicity evaluation, hippocampal slice culture assay for neuroprotection, formalin test for acute and inflammatory pain, sciatic ligation for neuropathic pain, Morris water maze and open field locomotor tasks for cognitive and behavioral deficits, radioligand binding for GABAA receptor affinity, spectrophotometric methods for cholinesterase inhibition in vitro, and molecular docking in silico. The compounds were non-toxic to fibroblast cells. 5 k was neuroprotective against kainic acid-induced neuron death. 5i reduced pain response of mice in both the acute and the inflammatory phases. 5i improved survival upon status epilepticus. The compounds showed no affinity to GABAA receptor but inhibited acetylcholinesterase, 5 k also inhibited butyrylcholinesterase. The compounds were predicted to interact mainly with the peripheric anionic site of cholinesterase enzymes. The title compounds showed neuroprotective, analgesic, and cholinesterase inhibitory effects, thus they bear promise against certain co-morbidities of epilepsy with neurological insults.

Foetal ductus arteriosus constriction unrelated to non-steroidal anti-Inflammatory drugs: a case report and literature review.

Foetal ductus arteriosus (DA) constriction can be found in complex foetal heart malformations, but rarely as an isolated defect. Although many cases of DA constriction are usually related to Non-steroidal Anti-Inflammatory Drugs (NSAIDs) maternal intake, other causes remain without an established aetiology and are referred to as idiopathic. Recently, a wide range of risks factors or substances (polyphenol-rich foods intake, naphazoline, fluoxetine, caffeine and pesticides) showed a definitive effect upon the pathway of inflammation, causing DA constriction. We report a case of a premature DA constriction in a woman whose possible risk factor was identified in her maternal occupational exposure to solvents and a comprehensive literature review of 176 cases of NSAID-unrelated DA constriction. A 30-year-old Asian woman was referred to our institution at 33 gestational weeks and 0 days because of suspicion of premature DA constriction. The woman had no history of medication intake, including NSAIDs, alcohol, tobacco or polyphenol-rich-food consumption during pregnancy. A detailed foetal echocardiography revealed a normal cardiac anatomy with hypertrophic, hypokinetic and a dilated right ventricle due to right pressure overload, holosystolic tricuspid regurgitation, and, at the level of the DA, high systolic and diastolic velocities, indicating premature ductal restriction. The right outflow showed dilatation of the pulmonary artery with narrow DA. An urgent caesarean section was performed at 33 gestational weeks and 4 days due to worsening of DA PI and signs of right pressure overload, despite the interruption of exposure to solvents. We assume a relationship exists between premature DA constriction and a maternal occupational exposure to solvents. This hypothesis is reinforced by the presence of associated foetal malformations in in two of the patient's children. Further research is needed to confirm the role of exposure to solvents and toxic chemicals in the pathogenesis of DA constriction, also with experimental animal models.KEY MESSAGESMany cases of DA constriction are usually related to Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) maternal intake.A wide range of risks factors or substances (polyphenol-rich foods intake, naphazoline, fluoxetine, caffeine and pesticides) can cause foetal DA constriction.Further investigation are needed to confirm the role of maternal exposure to solvents in the pathogenesis of DA constriction.

[Threat of a SARS-CoV-2 endemic in a large hospital specialized in rheumatic diseases-relative all clear through consistent testing]. / Drohende Corona-Endemie in einer rheumatologischen Spezialklinik ­ relative Entwarnung durch konsequente Testung.

The severe acute respiratory coronavirus type 2 (SARS-CoV-2) pandemic is keeping most countries of the world in suspense. In Germany the prevalence of SARS-CoV­2 infections is under 2% but for weeks the numbers in Germany have also been increasing. The care in rheumatology was temporarily impaired by the first wave of the pandemic. This article reports the infection situation in the largest specialized rheumatology clinic in Germany, the Rheumatism Center Ruhrgebiet, because recently during the second wave for the first time several SARS-CoV­2 infections occurred here over one weekend, which led to considerable anxiety in many of those involved. The situation could be clarified by consistent testing of patients and personnel with the rapid antigen test and the situation could be mollified. Ultimately, only a few persons were tested positive and the courses by the patients have so far remained bland. This shows the effectiveness of the protective hygiene measures consistently implemented since April.

Evaluation of Gingival Displacement with Aluminum Chloride and Naphazoline Hydrochloride: A Randomized Controlled Trial.

The objective of this study was to evaluate the use of naphazoline hydrochloride in comparison with aluminum chloride for vertical gingival displacement. The inclusion criteria were: patients with a good general systemic condition; periodontal health; and thick gingival biotype. Moreover, the exclusion criteria were: smoking individuals; canine teeth or central incisors with carious lesions, abrasion, erosion, prosthetic abutments or unsatisfactory restorations; patients with periodontal disease; and users of continuous medication. 72 teeth were included and the Square Block Design was used to randomize the samples. Three measures were obtained from each tooth, and mean vertical gingival displacement was calculated. A descriptive analysis of the average displacement was performed. The normality test used was the Lilliefors' Test and for comparison between treatments, the Kruskal-Wallis Test was used. The Bartlett's Test for homogeneity of variances was used and a 5% (p ⟨ 0.05) significant level was considered. Thus, the Aluminum Chloride and Naphazoline Hydrochloride showed no statistically amount of gingival retraction than the control group (p = 0.3822). The average of gingival vertical displacement in all groups were less than 0,5 mm. The technique used did not allow any amount of horizontal displacement on obtained models.

The Development of Spectrophotometric and Validated Stability- Indicating RP-HPLC Methods for Simultaneous Determination of Ephedrine HCL, Naphazoline HCL, Antazoline HCL, and Chlorobutanol in Pharmaceutical Pomade Form.

BACKGROUND: Allergic rhinitis, acute nasal congestion and sinusitis are one of the most common health problems and have a major effect on the quality of life. Several medications are used to improve the symptoms of such diseases in humans. Pharmaceutical pomade form containing Ephedrine (EPD) HCl, Naphazoline (NPZ) HCl, Antazoline (ANT) HCl, and Chlorobutanol (CLO) is one of them. OBJECTIVE: For these reasons, this study includes the development of spectrophotometric and chromatographic methods for the determination of EPD HCl, NPZ HCl, ANT HCl, and CLO active agents in the pharmaceutical pomade. METHOD: In the spectrophotometric method, third-order derivative of the amplitudes at 218 nm n=5 and the first-order derivative of the amplitudes 254 nm n=13 was selected for the determination of EPD, ANT, respectively while NPZ was determined by the second derivative at 234 nm and n=21. Colorimetric detection was applied for assay analysis of CLO at 540 nm. Furthermore, a reverse phase high performance liquid chromatographic (RP- HPLC) method has been developed and optimized by using Agilent Zorbax Eclipse XDB C18 (75 mm x 3.0 mm, 3.5µm) column. The column temperature was 40°C, binary gradient elution was used and the mobile phase consisted of 15 mM phosphate buffer in distilled water (pH 3.0) and methanol, and the flow rate was 0.6 mL min-1 and the UV detector was detected at 210 nm. The linear operating range was obtained as 11.97-70, 0.59-3, 2.79-30, and 2.92-200 µg mL-1 for EPD HCl, NPZ HCl, ANT HCl, and CLO respectively. RESULTS: The LOD values were found to be 3.95, 0.19, 0.92 and 0.96 µg mL-1 for EPD HCl, NPZ HCl, ANT HCl, and CLO in the spectrophotometric method, respectively. The linear ranges in the RP-HPLC method were 8.2-24.36 µg mL-1, 0.083 - 0.75 µg/mL, 2.01-7.5 µg mL-1 and 2.89-24.4 µg mL-1 for EPD HCl, NPZ HCl, ANT HCl, and CLO, respectively. The LOD values in the validation studies were 2.7, 0.025, 0.66 and 0.86 µg mL-1 for EPD HCl, NPZ HCl, ANT HCl, and CLO in RP-HPLC method respectively. CONCLUSION: The results of the spectrophotometric and chromatographic methods were compared and no differences were found between the two methods.

Non-medical Use of Naphazoline (Naphthyzin): Two Case Reports.

: The paper describes 2 case reports of non-medical use of Naphazoline (Naphthyzin). Both demonstrate that the peripherally acting alpha-adrenergic agonist Naphazoline obtains some addictive potential. The drug produces a feeling of euphoria, which resembles the perceived effects of psychostimulants. Both patients and people who consume Naphazoline for intoxication report increased tolerance after repeated use which indicates the addictive potential of the substance. To the best of our knowledge, this is the first examination of non-medical Naphazoline use and the first attempt to describe its addictive potential. Clinical psychiatrists should be aware of this phenomenon when addressing polysubstance use behavior.

Synthesis, in vivo anticonvulsant testing, and molecular modeling studies of new nafimidone derivatives.

An estimated 50 million people suffer epilepsy worldwide and 30% of the cases do not respond to current antiepileptic drugs (AEDs). Here, we report synthesis and anticonvulsant screening of new derivatives of nafimidone, a well-known member of (arylakyl)azole anticonvulsants. The compounds showed promising protection against maximal electroshock (MES)-induced seizures in mice and rats when administered via intraperitoneal (ip) and oral route. Especially, 5b, 5c, and 5i displayed outstanding activity in rats in MES test when given ip (ED50 : 16.0, 15.8, and 11.8 mg/kg, respectively). Additionally, 5l was active against 6 Hz and corneal-kindled mice models. Behavioral toxicity of the compounds was very low and their therapeutic indexes were high compared to some currently available AEDs. A number of pharmaceutically relevant descriptors and properties were predicted for the compounds in silico in comparison with a set of known drugs. Favorable results were obtained such as good blood-brain barrier permeability and high oral absorption, as well as drug-likeness. 5l was found to show affinity to the benzodiazepine binding site of A-type GABA receptor via molecular docking simulations.

Ophthalmic drug abuse: An observational study from community pharmacies.

BACKGROUND: There has been a trend in the past five years in Jordan for ophthalmic anticholinergic preparations to be misused or abused. This is done mainly to experience mental altering effects such as mood changes, euphoria or hallucinations. Such products are mostly obtained from community pharmacies without a prescription. OBJECTIVES: This study aimed to observe the requests of ophthalmic preparations in community pharmacies in Amman, Jordan, and evaluating the most popular and frequently requested ophthalmic drops suspected of abuse. Also, it aimed to describe the current methods that Jordanian community pharmacists use to manage such requests. METHODS: A prospective cross-sectional observational study was conducted between November 2016 and January 2017 at sixteen different community pharmacies in Amman. All ophthalmic products requested were observed during this period. RESULTS: A total of 140 ophthalmic product requests for 130 customers were observed. Dry eye was the most common complaint for which the customer requested the medication (n = 30, 23.1%) and direct self-medication (ie-requesting the product by name), was the most frequent method of purchase (n = 63, 48.5%). In 19 cases (14.6%), product requests were suspected to be for non-medical (ie-abuse) purposes. Most of the suspected cases were for Pentolate® (n = 11, 57.9%), whereas 7 were for Prisoline® (36.8%) and 1 for Naphcon-A® (5.3%). The majority of observed cases were for products requested without a prescription (n = 16, 84.2%), and in 12 cases out of which, sale was refused (63.2%). CONCLUSION: More effort and enforcement of pharmacy regulation for safe dispensing is needed to reduce the abuse of ophthalmic products. Educating pharmacists and ophthalmologists would help raise awareness and control the type of drug abuse.

Exposure to antazoline-naphazoline eye drops during pregnancy and the risk of congenital malformations: a Danish nationwide cohort study.

PURPOSE: To investigate whether exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy was associated with an increased risk of malformations in humans. METHODS: All women giving live birth between 1997 and 2011 in Denmark were included in this nationwide cohort study. All women redeeming at least one prescription of antazoline-naphazoline eye drops during the first 84 days of pregnancy were identified. Logistic regression was used to estimate the odds ratios of malformations among exposed offspring compared to non-exposed offspring. RESULTS: We identified 977 706 births between 1997 and 2011. A total of 3061 women (0.32%) were exposed to antazoline-naphazoline eye drops in the first trimester of pregnancy. The rate of congenital malformations was 3.0% (n = 93) in exposed offspring and 3.5% (n = 33 594) in unexposed offspring. First-trimester exposure to antazoline-naphazoline was not associated with major congenital malformations overall (odds ratio: 0.88, 95% confidence interval: 0.71-1.09) or with any specific major malformation. The number of redeemed prescriptions was unchanged during all trimesters of pregnancy as compared to before and after pregnancy (p < 0.05). CONCLUSION: Exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy appears not to be associated with increased teratogenic risk.

Intoxicación grave con nafazolina: puesta al día a partir de un error terapéutico / Severe poisoning with naphazoline: update from a therapeutic error

La nafazolina es un fármaco utilizado como descongestivo, generalmente, en pacientes adultos. Su indicación en pediatría no es frecuente; su uso está aprobado a partir de los 12 años por los efectos tóxicos que posee. La intoxicación en niños genera un cuadro clínico potencialmente grave. Se caracteriza por la aparición inmediata de hipotonía, deterioro del sensorio, hipotermia y bradicardia con grado variable de compromiso clínico. Si bien es una intoxicación infrecuente, la anamnesis y el manejo inicial del paciente son la clave en su evolución. Se presenta a un niño de 4 años que, por un error terapéutico, recibió este fármaco y se destaca la instauración rápida y potencialmente grave del cuadro clínico.

Naphazoline is a drug commonly used as a decongestant in adult patients. Its indication in Pediatrics is not frequent, being approved its use from the age of 12 for the toxic effects it possesses. Intoxication in children generates a potentially serious clinical picture. It is characterized by the immediate appearance of hypotonia, deterioration of the sensory, hypothermia and bradycardia of variable degree of clinical compromise. Although it is an infrequent intoxication, the anamnesis and the initial management of the patient are the key in the evolution. We present a 4-year-old boy who, as a therapeutic error, receives this drug, emphasizing the rapid and potentially severe establishment of the clinical picture.

[Severe poisoning with naphazoline: update from a therapeutic error]. / Intoxicación grave con nafazolina: puesta al día a partir de un error terapéutico.

Naphazoline is a drug commonly used as a decongestant in adult patients. Its indication in Pediatrics is not frequent, being approved its use from the age of 12 for the toxic effects it possesses. Intoxication in children generates a potentially serious clinical picture. It is characterized by the immediate appearance of hypotonia, deterioration of the sensory, hypothermia and bradycardia of variable degree of clinical compromise. Although it is an infrequent intoxication, the anamnesis and the initial management of the patient are the key in the evolution. We present a 4-year-old boy who, as a therapeutic error, receives this drug, emphasizing the rapid and potentially severe establishment of the clinical picture.

La nafazolina es un fármaco utilizado como descongestivo, generalmente, en pacientes adultos. Su indicación en pediatría no es frecuente; su uso está aprobado a partir de los 12 años por los efectos tóxicos que posee. La intoxicación en niños genera un cuadro clínico potencialmente grave. Se caracteriza por la aparición inmediata de hipotonía, deterioro del sensorio, hipotermia y bradicardia con grado variable de compromiso clínico. Si bien es una intoxicación infrecuente, la anamnesis y el manejo inicial del paciente son la clave en su evolución. Se presenta a un niño de 4 años que, por un error terapéutico, recibió este fármaco y se destaca la instauración rápida y potencialmente grave del cuadro clínico.

[Experimental study on nasal mucosa injury and repair induced by nasal decongestants in guinea pigs].

Objective: To observe the process of nasal mucosa injury and repair induced by nasal decongestants in guinea pigs Methods: Sixty-five male guinea pigs were randomly divided into 4groups by digital random method.The guinea pigs in Group A (20 guinea pigs)were treated with 2 sprays of 0.1% Naphazoline 6 times a day for 2 weeks; Group B (20 guinea pigs)with 2 drops of 1% Ephedrine 6 times a day for 2 weeks; Group C(20 guinea pigs) with 2 sprays of Naphazolin hydrochloride and Chlorphenamine Maleate Nasal Spray 8 times a day for 2 weeks.Group D (5guinea pigs)did not do any intervention as a control group.At the end of first and second weekend, 6 guinea pigs randomly selected from each group were observed the morphological changes of the nasal cavity with nasal endoscope and pathological microscope.Two weeks after stopping use of decongestant, 24 animals were grouped.Three guinea pigs were selected randomly from each group to form Group E (n=9) and Group F (n=9)respectively. The 6 remaining guinea pigs falled into Group G. Group E received 2 sprays of Mometasone Furoate Nasal Spray once a day for 2 weeks; Group F received 1 ml 2.3% saline to wash the nasal cavities once a day for 2 weeks.Group F was used to show the natural progess without any treatment.At the end of the third and fourth weekend, nasal endoscopic and pathological microscopes were used to observe the nasal cavity structure and the pathological changes of nasal mucosa. Results: Nasal mocusa congestion and edema were observed with nasal endoscopy after 2 weeks of using nasal decongestant. Cell edema, blood vessel expansion, acute and chronic inflammatory cell infiltration, cilium lodging or loss were observed under the pathological microscope in GroupA, B, C. After using MometasoneFuroate Nasal Spray and 2.3% saline for 2 weeks, the above changes were all recovered in Group E and F. No recovery was found in Group G. Conclusions: Short-term and over dose of nasal decongestant can result in the injury of nasal mucosa in guinea pigs, and the injury is much severe as using decongestant last longer.MometasoneFuroate nasal spray and 2.3% saline can repair the injury.

[About the safety of application of nasal decongestants in the practice of pediatricians]. / O bezopasnosti primeneniia nazal'nykh dekongestantov v pediatricheskoi praktike.

Undesirable effects of the application of the intransal vasoconstricting medications are a frequent occurrence in the pediatric practice. The objective of the present study was to evaluate the role of the intranasal vasoconstricting medications in the structure of the means and methods currently available for the treatment of toxicological pathologies based at a multi-field clinical hospital. The retrospective analysis of the medical histories of the patients admitted to the toxicological department and annual reports for the period from 2015 to 2016 was undertaken. The study has demonstrated that intoxication associated with the use of the intranasal vasoconstricting medications was the most common cause of hospitalization of the children in the toxicological departments. Intoxication of this origin accounted for 15-20% of the total number of toxicological pathologies among the children. The cases of intoxication are most frequently documented in the group of children at the age between 1 and 3 years. The risk of the undesirable serious complications is especially high after the application of naphazoline-based intranasal vasoconstricting medications (71.7-77.4% of all the cases of intoxication with these products). It is concluded that the use of intranasal vasoconstricting medications in the pediatric practice should be carried out under the strict control, with the naphazoline-based preparations being totally excluded from the application.