Persistent trigeminal artery as a rare cause of ischaemic lesion and migraine-like headache

The persistent trigeminal artery (PTA) is a rare remnant of the embryonic intracranial circulatory system that forms a carotid-vertebrobasilar anastomosis. In most cases PTA does not have clear clinical implications. However, some authors report the association of PTA occurrence with vertigo, dizziness and nerve palsy, resulting in diplopia, strabismus or trigeminal neuralgia in patients. In rare cases it may also be related to posterior cerebral circulation strokes. This work reports the case of a female patient who presented with migraine-like headache and an ischaemic lesion in the left temporal lobe in association with PTA

To calibrate or not to calibrate? A methodological dilemma in experimental pain research

To calibrate or not to calibrate? This question is raised by almost everyone designing an experimental pain study with supra-threshold stimulation. The dilemma is whether to individualize stimulus intensity to the pain threshold / supra-threshold pain level of each participant or whether to provide the noxious stimulus at a fixed intensity so that everyone receives the identical input. Each approach has unique pros and cons which need to be considered to i) accurately design an experiment, ii) enhance statistical inference in the given data and, iii) reduce bias and the influence of confounding factors in the individual study e.g., body composition, differences in energy absorption and previous experience. Individualization requires calibration, a procedure already irritating the nociceptive system but allowing to match the pain level across individuals. It leads to a higher variability of the stimulus intensity, thereby influencing the encoding of noxiousness by the central nervous system. Results might be less influenced by statistical phenomena such as ceiling/floor effects and the approach does not seem to rise ethical concerns. On the other hand, applying a fixed (standardized) intensity reduces the problem of intensity encoding leading to a large between-subjects variability in pain responses. Fixed stimulation intensities do not require pre-exposure. It can be proposed that one method is not preferable over another, however the choice depends on the study aim and the desired level of external validity. This paper discusses considerations for choosing the optimal approach for experimental pain studies and provides recommendations for different study designs. PERSPECTIVE: To calibrate pain or not? This dilemma is related to almost every experimental pain research. The decision is a trade-off between statistical power and greater control of stimulus encoding. The article decomposes both approaches and presents the pros and cons of either approach supported by data and simulation experiment

Efficacy and safety of trazodone and gabapentin fixed-dose combination in patients affected by painful diabetic neuropathy: randomized, controlled, dose-finding study

Introduction: Up to 50% of diabetic patients with neuropathy suffer from chronic pain, namely painful diabetic neuropathy (PDN), an unmet medical need with significant impact on quality of life. Gabapentin is widely used for PDN, albeit with frequent dose-limiting effects. Trazodone, an antidepressant with multi-modal action, has shown promising results when given at low doses as an add-on to gabapentin. Upon previous clinical trials and experimental evidence, a fixed-dose combination (FDC) of both compounds, at low doses, was developed for neuropathic pain. Methods: This was a phase II, randomized, double-blind, placebo and reference controlled, dose-finding, multicenter, international, prospective study. Male and female diabetic patients aged 18–75 years and affected by PDN were eligible for enrolment. Patients were randomized (1:1:1:1:2 ratio) to trazodone and gabapentin (Trazo/Gaba) 2.5/25 mg t.i.d. for 8 weeks, Trazo/Gaba 5/50 mg t.i.d. for 8 weeks, Trazo/Gaba 10/100 mg t.i.d. for 8 weeks, gabapentin (Gaba), or placebo (PLB). The aim of the study was to collect preliminary information on the effect of the 3 different FDCs of Trazo/Gaba on pain intensity based on the 11-point numeric rating score (NRS) after 8 weeks of treatment. The secondary objectives were the evaluation of the percentage of responders, neuropathic pain symptoms, anxiety, sleep, quality of life, safety, and tolerability. The primary efficacy endpoint was evaluated with last observation carried out forward (LOCF), using an analysis of covariance (ANCOVA), including treatment and centers as factors and baseline as covariate and applying linear contrast test, excluding the active treatment. Only if the linear contrast test was significant (p < 0.05), the step-down Dunnett test would be used to determine the minimum effective dose significantly different from PLB. If linearity was not verified, an adjusted ANCOVA model and comparisons with Dunnett test were performed. Before the application of the ANCOVA model, the non-significance of interaction treatment per baseline was verified. Results: A total of 240 patients were included in the modified intention-to-treat (m-ITT) population: 39 in Trazo/Gaba 2.5/25 mg, 38 in Trazo/Gaba 5/50 mg, 37 in Trazo/Gaba 10/100 mg, 83 in PLB, and 43 in Gaba. After 8 weeks of treatment, changes of the average daily pain score based on the 11-point NRS from baseline were − 2.52 ± 2.31 in Trazo/Gaba 2.5/25 mg group, − 2.24 ± 1.96 in Trazo/Gaba 5/50 mg group, − 2.46 ± 2.12 in Trazo/Gaba 10/100 mg group, − 1.92 ± 2.21 in Gaba group, and − 2.02 ± 1.95 in the PLB group. The linear contrast test did not result in significant differences (p > 0.05) among treatment groups. Consequently, the minimum effective dose against PLB was not determined. The multiple comparison with Dunnett adjustment did not show any statistically significant differences vs. PLB after 8 weeks of treatment: Trazo/Gaba 2.5/25 mg (95% confidence interval (CI) − 1.2739, 0.2026; p = 0.1539); Trazo/Gaba 5/50 mg (95% CI − 0.9401, 0.5390; p = 0.5931); Trazo/Gaba 10/100 mg (95% CI − 1.0342, 0.4582; p = 0.4471). However, patients receiving the lowest dose of Trazo/Gaba 2.5/25 mg showed a statistically significant difference to PLB after 6 weeks of treatment (95% CI − 1.6648, − 0.2126; p = 0.0116). Positive results were also found for responder patients, other items related to the pain, anxiety, depression, sleep, and quality of life, consistently in favor to the lowest Trazo/Gaba FDC. Two serious adverse events (SAEs) occurred but were judged unrelated to the study treatment. Treatment-emergent adverse events (TEAEs) were mainly mild-to-moderate in intensity and involved primarily nervous system, gastrointestinal disorders, and investigations. Conclusions: The primary end point of the study was the change from baseline of the average daily pain score based on the 11-point NRS after 8 weeks of treatment. While the primary endpoint was not reached, patients treated with Trazo/Gaba 2.5/25 mg t.i.d. showed statistically significant improvement of pain and other scores after 6 weeks and reported consistent better results in comparison to PLB on primary and secondary endpoints for the overall study duration. According to these results, the lowest dose of Trazo/Gaba FDC may be the best candidate for further clinical development to confirm the potential benefits of the FDC drug for this condition. Clinical Trial Registration: NCT03749642

Opicapone as adjunct to levodopa in treated Parkinson\u27s disease without motor complications: A randomized clinical trial

\ua9 2024 The Author(s). European Journal of Neurology published by John Wiley &amp; Sons Ltd on behalf of European Academy of Neurology.Background: Catechol-O-methyl transferase (COMT) inhibitors are routinely used to manage motor fluctuations in Parkinson\u27s disease (PD). We assessed the effect of opicapone on motor symptom severity in levodopa-treated patients without motor complications. Methods: This was a randomized, double-blind, 24-week, placebo-controlled study of opicapone 50 mg as adjunct to levodopa (NCT04978597). Levodopa-treated patients without motor complications were randomized to 24 weeks of double-blind treatment with adjunct opicapone 50 mg or matching placebo. The primary efficacy endpoint was the mean change from baseline to week 24 in Movement Disorder Society-Unified Parkinson\u27s Disease Rating Scale Part III (MDS-UPDRS-III) total score. Results: A total of 355 patients were randomized (opicapone 50 mg n = 177, placebo n = 178) and 322 (91%) completed the double-blind period. The adjusted mean [95% CI] change from baseline to week 24 in MDS-UPDRS-III subscore was −6.5 [−7.9, −5.2] in the opicapone group versus −4.3 [−5.7, 3.0] in the placebo group resulting in a significant difference of −2.2 [−3.9, −0.5] favoring opicapone (p = 0.010). There was no difference in the incidence of patients who developed motor complications (5.5% with opicapone vs. 9.8% with placebo) and the incidence of adverse events considered related to study medication was similar between groups (opicapone 10.2% vs. placebo 13.5%). Conclusions: Treatment with once-daily adjunct opicapone was well tolerated, improved motor severity, and did not induce the development of motor complications. These results support the clinical usefulness of opicapone in the management of PD patients without motor complications

Effect of sodium chloride on rheological properties of foams obtained from powdered high whip albumin

Celem pracy było określenie wpływu dodatku chlorku sodu na właściwości reologiczne pian otrzymanych ze sproszkowanej albuminy wysoko pienistej. Z preparatu białkowego użytego do badań przygotowano roztwory o stężeniu białka: 2, 6 i 10 % (m/v). Zastosowano następujące stężenia molowe roztworów soli [mM]: 60, 120, 240 i 480. Piany wytwarzano przez ubijanie 50 ml roztworu w zlewkach wysokościennych o pojemności 600 ml przy użyciu miksera Philips Essence. Czas ubijania każdej próbki roztworu wynosił 2 min. Właściwości reologiczne pian badano przy użyciu reometru oscylacyjnego HAAKE RS 300 (ThermoHaake, Karlsruhe, Niemcy). Pomiary granicy płynięcia (τₒ) wykonywano przy stałej prędkości ścinania wynoszącej 0,01 s-1 zastosowaniem modułu pomiarowego vane oraz układu dwóch płytek równoległych. W teście oscylacyjnym określono liniowy zakres lepkosprężystości badanych pian przy częstotliwości 1 Hz i zakresie odkształcenia 0,002 - 0,05 %. Określono również wartości modułów zachowawczego (G’) i stratności (G”) oraz wielkość kąta przesunięcia fazowego (δ) przy zakresie częstotliwości drgań 0,1 - 10,00 Hz i przy odkształceniu wynoszącym 0,003 %. Pomiary wykonywano w trzech powtórzeniach. Wyznaczono także wydajność pienienia roztworów badanych preparatów. Właściwości reologiczne otrzymanych pian były zależne od stężenia zastosowanego preparatu i stężenia NaCl. Piany otrzymane z roztworów o największym stężeniu białka cechowały się najlepszymi właściwościami reologicznymi. Wzrost stężenia molowego NaCl do wartości 120 mM w badanych roztworach białek prowadził do systematycznego zwiększania się granicy płynięcia i wydajności pienienia. Z kolei dalsze zwiększanie stężenia soli prowadziło do zmniejszenia wartości wyżej wymienionych parametrów, co świadczy o pogorszeniu się właściwości reologicznych badanych pian.The objective of this paper was to determine the effect of sodium chloride addition on rheological properties of foams obtained from powdered high whip albumin. Solutions were made from albumin preparation used in the investigation; their albumin concentration rates were: 2, 6, and 10 %. The following molar concentration rates of NaCl solutions were applied [mM]: 60, 120, 240, and 480. The foams were produced by whipping 50 ml of the solution in lab high-wall beakers of 600 ml volume using a Philips Essence mixer. The whipping time for each solution sample was 2 minutes. The rheological properties of foams were analyzed using an oscillatory ThermoHaake RS 300 rheometer (ThermoHaake, Karlsruhe, Germany). The yield stress (τₒ) measurements were performed at a constant shear velocity of 0.01 s-1 using a vane tool and a system of two plates that were parallel to each other. In the oscillation test, a linear range of viscoelasticity of foams analyzed was determined at a frequency of 1 Hz and for the deformation range between 0.002 and 0.05 %. Furthermore, the storage (G’) and loss (G”) moduli were determined as was the phase angle (δ) value for the oscillation frequency ranging from 0.1 to 10.00 Hz and for the deformation rate of 0.003 %. The measurements were three times repeated. Also, for all the solutions investigated, the values of foam overrun (Φ) were calculated. The rheological properties of the foams produced depended on the concentration rates of the preparation applied and NaCl. The foams produced from the solutions with the highest albumin concentration were characterized by the best rheological properties. The increase in the molar concentration of NaCl to a value of 120 mM in the solutions analyzed caused the yield stress and overrun increase to systematically increase. However, when the sodium chloride concentration continued to increase, the values of the above indicated parameters decreased, thus, proving the deterioration of the rheological properties of foams under analysis

Effect of changing whipping time on rheological properties of foams produced from various whey protein preparations and powdered egg albumin

Celem pracy była ocena właściwości reologicznych pian otrzymanych z trzech rodzajów preparatów białek serwatkowych i sproszkowanej albuminy jaja kurzego, w zależności od czasu ubijania. Właściwości reologiczne pian oceniono za pomocą reometru oscylacyjnego HAAKE RS 300. Wyznaczono wartości granicy płynięcia (τ), modułów zachowawczego (G’) i stratności (G”) oraz wielkości kąta fazowego (E) badanych próbek. Dokonano również wyznaczenia wydajności pienienia roztworów badanych preparatów. Właściwości reologiczne otrzymanych pian były zależne od rodzaju zastosowanego preparatu i czasu ubijania. Piany z albuminy cechowały się lepszymi właściwościami reologicznymi i wymagały krótszego czasu ubijania w porównaniu z pianami otrzymanymi z preparatów białek serwatkowych. W przypadku pian uzyskanych z preparatów białek serwatkowych wzrost czasu ubijania prowadził do systematycznego zwiększania się granicy płynięcia i wydajności pienienia. Z kolei zwiększanie czasu ubijania pian otrzymanych z albuminy prowadziło do zmniejszania wartości granicy płynięcia i wydajności pienienia. W przypadku pian otrzymanych z preparatów białek serwatkowych stwierdzono zależność liniową pomiędzy wartościami granicy płynięcia a czasem ich ubijania. W przypadku pian uzyskanych z izolatu białek serwatkowych (WPI) stwierdzono korelację pomiędzy granicą płynięcia a kątami fazowymi.The objective of this paper was to assess the effect of whipping time on rheological properties of foams produced from various types of whey protein preparations and from egg albumin. Rheological properties of the analyzed foams were assessed using an oscillatory ThermoHaake RS 300 rheometer. The following rheological parameters of the samples studied were determined: yield stress (τ), storage (G’) and loss (G”) moduli, and phase angle (E) values. For each protein solution of the preparations investigated, values of foam overrun (Φ) were also determined. Rheological properties of the analyzed foams depended on the type of preparation used and on the whipping time. The egg albumin foams exhibited better rheological properties and required a shorter whipping time compared to the foams produced from whey protein preparations. As for the foams produced from whey protein preparations, the increase in the whipping time resulted in a systematic increase in both the yield stress and the whipping overrun. As for the egg albumin foams, the increase in their whipping time caused the yield stress and overrun to decrease. In the case of foams produced from whey protein preparations, a linear relationship between the yield stress values and whipping times was found. As for the whey foams (WPI), a correlation was found between the yield stress and the phase angle values

Effect of addition of different of whey protein concentrates [WPC] on rheological properties of set-type yogurt

Celem pracy było określenie wpływu koncentratów białek serwatkowych różniących się składem chemicznym na właściwości reologiczne jogurtów otrzymanych metodą termostatową. Zwiększenie suchej masy mleka przeznaczonego do produkcji jogurtów osiągnięto poprzez dodatek 1, 2 lub 4% WPC 35, WPC 65, WPC 85 i WPC odtłuszczonego (WPCO). Przebieg fermentacji jogurtu monitorowano przy wykorzystaniu reometrii oscylacyjnej oraz oznaczano lepkość, twardość i gumowatość gotowego produktu. W przypadku jogurtu kontrolnego skrzep powstawał po 126 min fermentacji. Dodatek odtłuszczonego mleka w proszku (OMP) spowodował skrócenie czasu do 119 min, natomiast po dodaniu WPC 85 i WPCO zaobserwowano wydłużenie okresu niezbędnego do powstania skrzepu jogurtowego odpowiednio do 148 i 165 min. Największą twardością charakteryzowały się jogurty z 4% dodatkiem WPC 85 i WPCO, jednak miały one zbyt gumowatą teksturę.The aim of this paper was to examine the effect of different types of protein concentrates on rheological properties of set type yogurts. Yogurts were supplemented by addition of 1,2 or 4% of WPC35, 65WPC, WPC 85 and defatted WPC(WPCO). The process of yogurt fermentation was monitored with using of dynamic oscillation rheometry and following parameters such as: viscosity, hardness and gumminess were determined. In case of yogurt where no milk protein powder was added, the curd started to form after 126 minutes of fermentation. The addition of skimmed milk powder (SMP) decreased the curding time and it was 119 minutes. For WPC 85 and WPCO, the increase of curding time was observed and it was 148 and 165 minutes respectively. The hardest yogurts were obtained with 4% of WPC 85 and WPCO addition, but these yogurts characterized with too gummy structure

Effect of some selected prebiotics on rheological properties of set yoghurt

Celem pracy było określenie wpływu dodatku oligofruktozy P95 oraz inuliny GR i HPX na właściwości reologiczne oraz wielkość synerezy jogurtu otrzymanego metodą termostatową. Oznaczano twardość, lepkość pozorną i wielkość synerezy jogurtów stałych. W celu określenia wpływu fruktooligosacharydów na przebieg fermentacji monitorowano ten proces przy użyciu reometru oscylacyjnego. W przypadku jogurtu kontrolnego tworzenie skrzepu rozpoczęło się po ok. 90 min, natomiast tworzenie się skrzepu w przypadku pozostałych jogurtów zaczęło się po ok. 105 min. Najmniejszą twardość miał jogurt kontrolny – 0,23 N. Natomiast największą uzyskał jogurt z dodatkiem inuliny HPX w ilości 3 % – 0,28 N. W przypadku jogurtów z dodatkiem P95 zaobserwowano nieco wyższą twardość w porównaniu z próbą kontrolną. Najmniejszą ilością wydzielanej serwatki charakteryzował się jogurt z dodatkiem 3 % P95. Generalnie wraz ze wzrostem dodatku fruktooligosacharydów malała wielkość synerezy w badanych jogurtach. Zastosowanie fruktooligosacharydów pozwala na otrzymania jogurtów o odpowiednich właściwościach reologicznych i prozdrowotnych.The objective of this paper was to determine the effect of the additions of P95 fructooligosaccharide and GR and HPX inulins on the rheological properties and the syneresis extent of yoghurt produced using a thermostat method. The hardness, apparent viscosity, and syneresis extent of set yoghurts were determined. In order to determine the effect of fructooligosaccharides on the course of fermentation process, this process was monitored using an oscillatory rheometer. In the case of control sample of yoghurt, the curd began to form ca. 90 minutes after the process started whereas, in the case of all other yoghurts, the curd started to form after about 105 min. The control sample of yoghurt had the lowest hardness value of 0.23 N. The yoghurt with the HPX inulin added in the amount of 3 % had the highest hardness: 0.28 N. As for the yoghurts with P95 inulin added, a slightly higher value of hardness was reported compared to the control sample. The lowest amount of whey excreted was found in the case of yoghurt with the added 3 % amount of P95. Generally, for all of the yoghurts examined, the syneresis extent decreased with the increasing amounts of fructooligosaccharides added. The application of fructooligosaccharides allows for manufacturing yoghurts characterized by proper rheological and pro-health properties

The rheological properties of milk desserts obtained from the whey proteins with the addition of different sweeteners

Celem pracy było porównanie wpływu substancji słodzących, takich jak: sacharoza, ksylitol, aspartam i acesulfam-K na właściwości reologiczne deserów mlecznych oraz deserów otrzymanych z izolatu białek serwatkowych (WPI). Badano właściwości reologiczne deserów za pomocą reometru dynamicznego podczas ogrzewania do temp. 85ºC, a następnie chłodzenia do 20ºC i teksturę żeli przechowywanych przez 24 h za pomocą analizatora tekstury TA-XT2i. Najtwardsze desery otrzymano z białek serwatkowych słodzonych sacharozą. Ich twardość wynosiła 212 g. Zastąpienie sacharozy przez inną substancję słodzącą powodowało pogorszenie właściwości reologicznych badanych deserów otrzymanych z izolatu białek serwatkowych. W przypadku deserów otrzymanych z odtłuszczonego mleka w proszku (OMP), nie stwierdzono wyraźnego wpływu stosowanego środka słodzącego na teksturę deserów mlecznych.The purpose of this study was to examine the effect of different sweeteners such as: saccharose, xylitol, aspartame and acesulfame on rheological properties of milk desserts obtained with the addition of whey protein isolate(WPI). The rheological properties of milk desserts were examined using a haake rs 300 rheometer in the temperature range from 85 to 20°C. The dessert texture was determined by TA-XT2i texture analyser. The hardest desserts were obtained from wpi with the saccharose addition. Their hardness was 212 g. The substitution of saccharose by other sweeteners caused general decline of rheological properties of the wpi desserts being examined. In the case of the desserts obtained with the skimmed milk powder, no significant effect of any sweetener applied on the dessert texture was observed