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Background: Prunella vulgaris L., known as self-healing herb, is a widely spread species in the spontaneous flora with beneficial effects on human health, a fact proven in particular by Asian researchers. The aim of this study was to evaluate the antitumor activity and the antibacterial effect on different bacterial strains, including multidrug-resistant ones, depending on the type of solvent used (aqueous, hydroalcoholic), the plant product taken into consideration (spike inflorescence, leaf), its quantity and the concentration of active principles.

A fost validată o metodă simplă şi selectivă de determinare a genisteinei (GNST) din ficat şi rinichi de şobolan în vederea studierii efectului fitoestrogenic al GNST la șobolani Wistar de sex feminin ovariectomizaţi. GNST a fost separată pe o coloană Kromasil 100-RP8, de 150 mm x 4,6 mm, 5 μm prevăzută cu precoloană Kromasil RP 8. Faza mobilă a fost 55:45 (v/v) acid fosforic 15 mmol în apă : metanol la un debit de 1,3 ml/min. Ca standard intern a fost folosită luteolina 20 μg/ml în metanol. Timpul de retenţie al GNST a fost tR = 13,22 min şi tR = 11,60 min pentru standardul intern. Curbele de calibrare pe domeniul 40-400 μg GNST/100g ficat şi 20-200 μg GNST/100g rinichi au prezentat coeficienţi de determinare ˃0,99. Metoda a prezentat o bună precizie şi acurateţe la limita de cuantificare. 10 şobolani albi Wistar de sex feminin, cu vârsta de 8 săptămâni au fost trataţi s.c. cu 10 mg/kg c/zi soluţie GNST timp de 8 săptămâni, în timp ce un lot de 10 animale au folosit ca martor. Valorile obţinute pentru GNST în ficat au fost 192.12 ± 53.46 μg/100g, iar în rinichi 74.51 ± 12.77 μg/100g.

Background: Free valproic acid is shows no characteristic absorption in the ultraviolet region (above 235 nm), therefore its direct quantification and also the quantification of the corresponding metabolites from human plasma has proven to be challenging. Aim: The aim of our study was to develop and validate an effective LC-MS method for the determination of valproic acid in human plasma without using solid phase extraction as sample preparation, with a short analysis time and high sensitivity. Materials and methods: Valproic acid was analyzed on a reversed - phase column (Zorbax SB - C18, 100 mm x 3 mm I.D., 3.5 μm) under isocratic conditions using a mobile phase of a 40:60 (v/v) mixture of acetonitrile and 0.1% (v/v) acetic acid in water. The flow rate was 1 mL/ min and the column temperature 45 °C. In these chromatographic conditions, the retention time was 2.3 minute for valproic acid. The detection of the analyte was in single ion monitoring mode using a triple quadrupole mass spectrometer with electrospray negative ionization. The monitored ion was 143.1 m/z derived from 144.2 m/z valproic acid. The sample preparation was very simple and consisted in plasma protein precipitation from 0.2 mL plasma using 0.6 mL methanol. Results: Calibration curves were generated over the range of 2-200 μg/mL with values for coefficient of determination greater than 0.996 and by using a weighted (1/x) quadratic regression. The values of precision and accuracy for valproic acid at quantification limit were less than 3.3% and 7.2%, for within- and between-run assays, respectively. The mean recovery of the analyte was 104%. Valproic acid samples demonstrated good short-term, post-preparative and freeze-thaw stability. Conclusion: The method is very simple and allows obtaining a very good recovery of the analyte. The validated LC-MS/MS method could be applied to pharmacokinetics and therapeutic drug monitoring study regarding valproic acid in humans. [ABSTRACT FROM AUTHOR]

Introduction/aims: A previous randomized controlled trial showed that guided self-help acceptance and commitment therapy plus standard medical care (ACT+SMC) was superior to standard medical care alone (SMC) for improving quality of life (QoL) and mood at 9-weeks post randomization in a sample of people with muscle disorders (MD). This follow-up study evaluated whether these effects were maintained in the longer term alongside individual patterns of response., Methods: The original study was a two-arm parallel group randomized controlled trial, which compared ACT+SMC to SMC. The primary outcome of QoL was assessed with the Individualized Neuromuscular Quality of Life Questionnaire. We recruited people with different MDs from UK National Health Service clinics and patient registries. In this follow-up study, we re-administered all outcome measures to participants at 6 months post randomization., Results: Questionnaires were completed by 109 participants (70.3% of the original sample). At six months, the adjusted group difference in QoL continued to favor ACT+SMC, which was significant with moderate effect size. Improvements in secondary outcomes of mood and aspects of psychological flexibility also favored ACT+SMC. Reliable improvement was evident in 33.9% of the ACT+SMC group and 5.7% of the SMC group. Reliable deterioration was uncommon following ACT+SMC (1.8% of participants.) DISCUSSION: The beneficial impacts of guided self-help ACT for QoL and mood were maintained in the longer-term. A third of participants showed response to this brief intervention, and negative individual outcomes were very rare. As is common in psychological interventions, there was a considerable group of non-responders., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Introduction Benign prostatic hyperplasia (BPH) is a prevalent condition among aging men that affects their life quality due to urinary symptoms. Current pharmacologic treatments, often lead to sexual dysfunction, so dietary supplements (DS) containing plant-based compounds such as β-sitosterol (SIT) are preferred. DS are highly accessible and widely used, but poorly regulated, so often patients are victims of fraud. The use of DS to treat BPH symptoms is questionable, and this may be due not to the efficacity of the active compound but to the quality of commonly available DS. Aim This study aimed to assess the concentration of SIT in DS available on the market and evaluate whether the concentration of the active compound at the recommended dosage is sufficient to elicit beneficial effects in BPH. Method An HPLC-UV method based on direct saponification and acid hydrolysis was developed for the quantification of free and conjugated SIT in DS. The concentration of SIT in various DS was determined and compared with the one declared on the label. Results The chromatographic analysis confirmed the presence of SIT in all the DS but also showed a considerable variability of SIT content among DS, with only one product meeting the necessary concentration to bring potential benefits in BPH. Conclusion The study highlights inconsistencies in SIT content among DS and the importance of DS containing a standardized extract of SIT. Quality control measures are imperative to ensure that consumers receive effective and safe SIT-based DS to manage BPH symptoms. Further research is needed to establish standardized dosages and to evaluate their long-term efficacy and safety., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mădălina-Georgiana et al.)

Objective: Artificial intelligence (AI) has gradually found its way into healthcare, and its future integration into clinical practice is inevitable. In the present study, we evaluate the accuracy of a novel AI algorithm designed to predict admission based on a triage note after clinical implementation. This is the first of such studies to investigate real-time AI performance in the emergency setting., Methods: The novel AI algorithm that predicts admission using a triage note was translated into clinical practice and integrated within St Vincent's Hospital Melbourne's electronic emergency patient management system. The data were collected from 1 January 2021 to 17 August 2022 to evaluate the diagnostic accuracy of the AI system after implementation., Results: A total of 77 125 ED presentations were included. The live AI algorithm has a sensitivity of 73.1% (95% confidence interval 72.5-73.8), specificity of 74.3% (73.9-74.7), positive predictive value of 50% (49.6-50.4) and negative predictive value of 88.7% (88.5-89) with a total accuracy of 74% (73.7-74.3). The accuracy of the system was at the lowest for admission to psychiatric units (34%) and at the highest for gastroenterology and medical admission (84% and 80%, respectively)., Conclusion: Our study showed the diagnostic evaluation of a real-time AI clinical decision-support tool became less accurate than the original. Although real-time sensitivity and specificity of the AI tool was still acceptable as a decision-support tool in the ED, we propose that continuous training and evaluation of AI-enabled clinical support tools in healthcare are conducted to ensure consistent accuracy and performance to prevent inadvertent consequences., (© 2023 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Introduction: In adults, muscle disease (MD) is typically a chronic long-term condition that can lead to a reduced quality of life (QoL). Previous research suggests that a psychological intervention, in particular Acceptance and Commitment Therapy (ACT), may help improve QoL for individuals living with chronic conditions such as MD., Methods: This nested qualitative study was incorporated within a randomized controlled trial which evaluated a guided self-help ACT intervention for people living with MD to explore their experiences of the intervention. Semi-structured interviews ( n = 20) were conducted with those who had received ACT. Data were analyzed via thematic analysis., Results: There were four overarching themes. (1) Views on whether therapy sessions would help with a medical condition: participants' expectations regarding ACT varied. Some participants were skeptical about mindfulness. (2) I was able to look at things in a different way: participants described increased meaningful activity, greater awareness of thoughts and emotions and acceptance or adaptation to mobility problems. Some described improvement in the quality of relationships and a sense of feeling free. (3) Treating the body and the mind together: following the intervention participants noted that a holistic approach to healthcare is beneficial. (4) Intervention delivery: The remote delivery was generally seen as helpful for practical reasons and allowed participants to speak openly. Participants voiced a need for follow-up sessions., Discussion: Overall, the intervention was experienced as acceptable. Suggested improvements included de-emphasizing the role of mindfulness and adding follow-up sessions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Edwards, Vari, Rose, Graham, O'Connell, Taylor, McCracken, Radunovic, Rakowicz, Norton and Chalder.)

Abstract ., Background: Chronic muscle diseases (MD) are progressive and cause wasting and weakness in muscles and are associated with reduced quality of life (QoL). The ACTMuS trial examined whether Acceptance and Commitment Therapy (ACT) as an adjunct to usual care improved QoL for such patients as compared to usual care alone., Methods: This two-arm, randomised, multicentre, parallel design recruited 155 patients with MD (Hospital and Depression Scale ⩾ 8 for depression or ⩾ 8 for anxiety and Montreal Cognitive Assessment ⩾ 21/30). Participants were randomised, using random block sizes, to one of two groups: standard medical care (SMC) ( n = 78) or to ACT in addition to SMC ( n = 77), and were followed up to 9 weeks. The primary outcome was QoL, assessed by the Individualised Neuromuscular Quality of Life Questionnaire (INQoL), the average of five subscales, at 9-weeks. Trial registration was NCT02810028., Results: 138 people (89.0%) were followed up at 9-weeks. At all three time points, the adjusted group difference favoured the intervention group and was significant with moderate to large effect sizes. Secondary outcomes (mood, functional impairment, aspects of psychological flexibility) also showed significant differences between groups at week 9., Conclusions: ACT in addition to usual care was effective in improving QoL and other psychological and social outcomes in patients with MD. A 6 month follow up will determine the extent to which gains are maintained.

Antihyperglycemic effects of four extracts obtained from leaves and fruits of Vaccinium myrtillus and Vaccinium corymbosum were assessed in diabetic rats. In addition, the effects of extracts on diabetic-related complications such as the development of diabetic cataract and oxidative stress were evaluated. Type 1 diabetes was induced with a single dose of streptozotocin in Wistar rats. The rats were randomly divided into seven equal groups: NC-normal control, DC-diabetic control, PC-positive control treated with metformin, VML-received V. myrtillus leaf extract, VMLF-received VML and fruit extract, VCL-received V. corymbosum leaf extract, and VCLF-received VCL and fruit extract. Body weight and glucose levels were monitored every second week. After 8 weeks of treatment, serum glucose, insulin, and malondialdehyde were measured. Lenses were removed after sacrifice and eight lenses from each group were randomly selected for evaluation of cataract development. A decrease in body weight was observed in all diabetic groups in the first weeks. In the VML group, no significant decrease was observed. Glucose levels during the experiment were high in DC, PC, and VCL groups, with no improvement during the 8 weeks. In VML, VMLF, and VCLF groups, a decrease in blood glucose levels was observed. Similar results regarding serum insulin and glucose levels at the end of the experiment were observed within groups. V. myrtillus extracts prevented the development of cataract compared with the DC group (P < .05).

Introduction: In adults, muscle disease (MD) is often a chronic long-term condition with no definitive cure. It causes wasting and weakness of the muscles resulting in a progressive decline in mobility, alongside other symptoms, and is typically associated with reduced quality of life (QoL). Previous research suggests that a psychological intervention, and in particular Acceptance and Commitment Therapy (ACT), may help improve QoL in MD. ACT is a newer type of cognitive behavioural treatment that aims to improve QoL by virtue of improvement in a process called psychological flexibility. The primary aim of this randomised controlled trial (RCT) is to evaluate the efficacy of a guided self-help ACT programme for improving QoL in people with MD. Main secondary outcomes are mood, symptom impact, work and social adjustment and function at 9-week follow-up., Methods and Analysis: Acceptance and Commitment Therapy for Muscle Disease is an assessor-blind, multicentre, two-armed, parallel-group RCT to assess the efficacy of ACT plus standard medical care (SMC) compared with SMC alone. Individuals with a diagnosis of one of four specific MDs, with a duration of at least 6 months and with mild to moderate anxiety or depression (Hospital Anxiety and Depression Scale score ≥8) will be recruited from UK-based MD clinics and MD patient support organisations. Participants will be randomised to either ACT plus SMC or SMC alone by an independent randomisation service. Participants will be followed up at 3, 6 and 9 weeks. Analysis will be intention to treat, conducted by the trial statistician who will be blinded to treatment allocation., Ethics and Dissemination: The study has received full ethical approval. Study results will be disseminated via peer-reviewed publications, conference presentations and journal articles. Data obtained from the trial will enable clinicians and health service providers to make informed decisions regarding the efficacy of ACT for improving QoL for patients with MD., Trial Registration Number: NCT02810028., Protocol Version: V.11 (4 April 2017)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Affective touch supports affiliative bonds and social cognition. In particular, gentle, stroking touch, which has recently been associated with the C Tactile (CT) system, is typically perceived as pleasant and prosocial. However, it remains unknown whether pre-existing models of social relating influence the perception of CT-optimal touch. In this study (N = 44 adults), we examined how individual differences in attachment styles relate to the perception of CT-optimal touch, as well as to a different modality of interoception, namely heartbeat perception. Using the gold-standard assessment of attachment (Adult Attachment Interview), we found that insecure attachment was associated with reduced pleasantness discrimination between CT-optimal vs. non-CT optimal touch. Acknowledging the different traditions in measuring attachment, we also used a well-validated self-report questionnaire that pertains to explicit representations of current close relationships. Using this measure, we found that higher scores in attachment anxiety (but not attachment avoidance) were associated with reduced pleasantness discrimination between CT-optimal vs. non-CT optimal touch. Attachment patterns (in both measures) were not related to cardiac perception accuracy. These results corroborate and extend previous literature on CT-optimal touch and its relation with affiliative bonds and social cognition. Given that attachment was not related to perceived cardiac accuracy, these findings point to the specificity of the relationship between CT-optimal touch and attachment.

The aim of the present study was to explore the dimensions of alexithymia and attachment styles in a group of disordered gamblers and to evaluate the relationship between alexithymia, attachment styles, and the severity of gambling disorder. Sixty disordered gamblers diagnosed according to the diagnostic and statistical manual-5 filled out the Kurzfragebogen zum Glücksspielverhalten, the 20-Item Toronto Alexithymia Scale, and the Experiences in Close Relationships-Revised. Approximately 70 % of the sample displayed 'intermediate' and 'severe' gambling severity levels on the Kurzfragebogen zum Glücksspielverhalten, and 77 % showed 'high' or 'borderline' levels of alexithymia on the Toronto Alexithymia Scale (mean = 56.40). Regarding attachment styles, 70 % of the sample displayed an 'insecure' attachment, with a particularly high prevalence of the 'fearful' style (26.66 %). A linear regression analysis revealed that only the anxiety dimension of the Experiences in Close Relationships questionnaire predicted the severity of gambling. Our data appear to confirm that gambling disorder is characterised by emotional and relational dysregulation, and that pathological gambling behaviours may serve as external regulators of internal undifferentiated emotional states.

Objectives: There is no gold standard for measuring adherence to prescribed home exercise. Self-report diaries are commonly used however lack of standardisation, inaccurate recall and self-presentation bias limit their validity. A valid and reliable tool to assess exercise adherence behaviour is required. Consequently, this article reports the development and psychometric evaluation of the Exercise Adherence Rating Scale (EARS)., Design: Development of a questionnaire., Setting: Secondary care in physiotherapy departments of three hospitals., Participants: A focus group consisting of 8 patients with chronic low back pain (CLBP) and 2 physiotherapists was conducted to generate qualitative data. Following on from this, a convenience sample of 224 people with CLBP completed the initial 16-item EARS for purposes of subsequent validity and reliability analyses., Methods: Construct validity was explored using exploratory factor analysis and item response theory. Test-retest reliability was assessed 3 weeks later in a sub-sample of patients., Results: An item pool consisting of 6 items was found suitable for factor analysis. Examination of the scale structure of these 6 items revealed a one factor solution explaining a total of 71% of the variance in adherence to exercise. The six items formed a unidimensional scale that showed good measurement properties, including acceptable internal consistency and high test-retest reliability., Conclusions: The EARS enables the measurement of adherence to prescribed home exercise. This may facilitate the evaluation of interventions promoting self-management for both the prevention and treatment of chronic conditions., (Copyright © 2017 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aimed to quantify the cartilage- and subchondral bone-related effects of low-dose and high-dose meloxicam treatment in the late phase of mono-iodoacetate-induced osteoarthritis of the stifle., Methods: Thirty-four male Wistar rats received intra-articular injection of mono-iodoacetate to trigger osteoarthritis; 10 control animals (Grp Co) received saline. The mono-iodoacetate-injected rats were assigned to three groups and treated from week 4 to the end of week 7 with placebo (Grp P, n  = 11), low-dose (GrpM Lo, 0.2 mg/kg, n  = 12) or high-dose (GrpM Hi, 1 mg/kg, n  = 11) meloxicam. After a period of 4 additional weeks (end of week 11) the animals were sacrificed, and the stifle joints were examined histologically and immunohistochemically for cyclooxygenase 2, in conformity with recommendations of the Osteoarthritis Research Society International. Serum cytokines IL-6, TNFα and IL-10 were measured at the end of weeks 3, 7, and 11., Results: Compared with saline-treated controls, animals treated with mono-iodoacetate developed various degrees of osteoarthritis. The cartilage degeneration score and the total cartilage degeneration width were significantly lower in both the low-dose ( p  = 0.012 and p  = 0.014) and high-dose ( p  = 0.003 and p  = 0.006) meloxicam-treated groups than in the placebo group. In the subchondral bone, only high-dose meloxicam exerted a significant protective effect ( p  = 0.011). Low-grade Cox-2 expression observed in placebo-treated animals was abolished in both meloxicam groups. Increase with borderline significance of TNFα in GrpP from week 3 to week 7 ( p  = 0.049) and reduction of IL-6 in GrpM Lo from week 3 to week 11 ( p  = 0.044) were observed., Conclusion: In this rat model of osteoarthritis, both low-dose and high-dose meloxicam had a chondroprotective effect, and the high dose also protected against subchondral bone lesions. The results suggest a superior protection of the high-dose meloxicam arresting the low-grade inflammatory pathway accompanied by chronic cartilage deterioration., Competing Interests: The authors declare there are no competing interests.

Unlabelled: The current trend of replacing conventional pharmaceutical forms is justified because most substances administered in this form give fluctuations of therapeutic concentrations and often outside the therapeutic range. In addition, these formulations offer a reduction in the dose or the number of administrations, thus increasing patient compliance., Aim: In the experiment, we developed an appropriate technology for the preparation of gelatin microspheres containing tramadol hydrochloride by emulsification/cross-linking method., Materials and Methods: The formulated microspheres were characterized by product yield, size distribution, encapsulation efficiency and in vitro release of tramadol hydrochloride. Data obtained from in vitro release studies were fitted to various mathematical models to elucidate the transport mechanisms. The kinetic models used were zero-order, first-order, Higuchi Korsmeyer-Peppas and Hopfenberg., Results: Spherical microspheres were obtained, with free-flowing properties. The entrapment efficiency of tramadol hydrochloride in microparticles was 79.91% and product yield -94.92%. As the microsphere size was increased, the entrapment efficiency increased. This was 67.56, 70.03, 79.91% for formulations MT80-250, MT8-500 and, MT250-500. High entrapment efficiency was observed for MT250-500 formulation. The gelatin microspheres had particle sizes ranging from 80 to 500 microm. The drug was released for a period of 12 hours with a maximum release of 96.02%. Of the three proposed formulations, MT250-500 presented desirable properties and optimal characteristics for the therapy of pain. Release of tramadol hydrochloridi was best fitted to Korsmeyer-Peppas equation because the Akaike Information Criterion had the lowest values for this kinetic model., Conclusions: These results suggest the opportunity to influence the therapeutic characteristics of gelatin microspheres to obtain a suitable drug delivery system for the oral administration of tramadol hydrochloride.

The optimized method for HPLC determination of tramadol and its metabolite O-desmethyl tramadol in human plasma using sotalol as internal standard has been developed and validated by a new approach. The determination by fluorescence detection was performed on re-eluted solution, obtained after liquid-liquid extraction with ethyl acetate of the three analytes from plasma. The chromatographic separation of tramadol under a gradient elution was achieved at a temperature of 15 degrees C with a RP-18 column, guarded by a C18 precolumn. The mobile phase was a mixed aqueous solution containing ortho-phosphoric acid, triethylamine, acetonitrile and methanol in a complex gradient mode. The quantitative determination of tramadol was performed at different successive pairs of excitation/emission wavelengths (200/300 nm, 200/295 nm, 212/305 nm) with lower limits of quantification: LLOQ=4.078 ng/ml for tramadol, respectively LLOQ=3.271 ng/ml for O-desmethyl tramadol. For the LLOQ limits, were calculated the values of the coefficient of variation and difference between mean and the nominal concentration. For tramadol analyte they were CV%=5.147% and bias%=-7.273% in the intra-days and CV%=4.894% and bias%=0.836% in the between-days assay, respectively for the metabolite O-desmethyl tramadol they were CV%=11.517% and bias%=0.337% in the intra-days and CV%=6.41% and bias%=3.259% in the between-days assay. In addition, the stabilities of the analytes were verified in different conditions. Both, tramadol and its metabolite proved to be stable in plasma for four weeks, frozen at -20 degrees C, but also for 48 h at 15 degrees C in the re-eluted solution after liquid-liquid extraction.

Unlabelled: The aim of flavonols complexation is to improve their specific activity., Material and Method: The flavonols sources were Morus alba L. and Morus nigra L., zinc being the biological active ion. Physico-chemical characterization was made by thin-layer chromatography, UV-VIS spectrophotometry, IR spectrometry and polarography., Results: The complexes results were within acceptability limits, but their obtaining is economically inefficient.

Indigene Stachys species have a high content in interesting compounds as iridoids, but also high quantities of flavonoids and phenol-carboxylic acids. These compounds present vasorelaxing effect on smooth vascular muscle interfering with metabolic degradation of nitric oxide pathways (inhibition of peroxynitrites formation) and by inhibition of phosphodiesterase. This work shows flavonoids spectrum of 3 Stachys species using HPLC methods. We identified quercetol, rutoside, miricetin and phenol-carboxylic acids (chlorogenic, caffeic and ferulic acids).