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BACKGROUND: Mild depression lacks a consistent definition across diagnostic criteria and rating scales, posing challenges to standardizing treatment strategies. International guidelines predominantly recommend psychotherapy as the first-line treatment for mild depression, while the use of antidepressants remains contentious. Supplements such as omega-3 fatty acids, St. John's Wort, and magnesium have garnered attention as alternative therapeutic options for depression. This systematic review aims to assess the efficacy of pharmacological interventions, including supplements, in the treatment of mild depression. METHODS: Comprehensive searches were performed in PubMed and Embase through November 2024 to identify randomized controlled trials (RCTs) investigating pharmacotherapy or supplements for mild depression diagnosed using standardized criteria. Eligible studies underwent screening and risk of bias assessment utilizing the ROB2 tool. Data on remission rates, symptom improvement, dropout rates, and adverse events were extracted, with meta-analyses conducted where applicable. RESULTS: Eight RCTs comprising 1049 participants met inclusion criteria. Among the agents studied, St. John's Wort was analyzed in two trials, both comparing it to fluoxetine. A meta-analysis found no significant difference in response rates between the two treatments (risk ratio [RR] = 0.96, 95% CI: 0.78-1.18) or dropout rates (RR = 1.08, 95% CI: 0.62-1.88). For other agents, single studies evaluated their effects. Eicosapentaenoic acid and Rhodiola rosea demonstrated significant improvements in depressive symptoms compared to placebo. In non-blinded trials, magnesium chloride showed efficacy in alleviating depressive symptoms. Other interventions, such as lavender, lemon balm, and transcranial electroacupuncture stimulation, were as effective as antidepressants. Conversely, S-adenosylmethionine did not produce significant improvements relative to placebo. CONCLUSION: This review demonstrates that certain supplements, such as eicosapentaenoic acids and Rhodiola rosea, are therapeutic options for mild depression. However, no RCTs compared antidepressants directly to placebo for mild depres

OBJECTIVES: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations. METHODS: The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence - meta-analysis or two or more RCTs - due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the 'level of evidence' (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was 'Recommended' (+++), 'Provisionally Recommended' (++), 'Weakly Recommended' (+), 'Not Currently Recommended' (+/-), or 'Not Recommended' (-) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed. RESULTS: Amongst nutraceuticals with Grade A evidence,

BACKGROUND: Lavender (Lavandula angustifolia) is often recommended for stress/anxiety relief and believed to possess anxiolytic effects. AIM: To critically evaluate the efficacy/effectiveness of lavender for the reduction of stress/anxiety. METHODS: Seven electronic databases were searched to identify all relevant studies. All methods of lavender administration were included. Data extraction and the assessment of the methodological quality of all included trials were conducted by two independent reviewers. RESULTS: Fifteen RCTs met the inclusion criteria. Two trials scored 4 points on the 5-point Jadad scale, the remaining 13 scored two or less. Results from seven trials appeared to favour lavender over controls for at least one relevant outcome. CONCLUSION: Methodological issues limit the extent to which any conclusions can be drawn regarding the efficacy/effectiveness of lavender. The best evidence suggests that oral lavender supplements may have some therapeutic effects. However, further independent replications are needed before firm conclusions can be drawn.

IMPORTANCE: Intradetrusor chemodenervation with onabotulinumtoxinA (BOTOX) injections, a common office-based procedure for overactive bladder (OAB), is associated with patient anxiety and discomfort. Aromatherapy and music have been shown to decrease procedure-related anxiety and pain with improved satisfaction. OBJECTIVES: The objectives of this study were to determine whether a relaxing environment consisting of lavender aromatherapy, calming music, and dim lighting compared with a typical office environment decreases patients' anxiety level before undergoing intradetrusor chemodenervation. We hypothesized that a relaxing environment would decrease patients' anxiety level before the procedure as measured by the Visual Analog Scale (VAS). Secondary outcomes included the VAS for pain, satisfaction, and staff energy level. STUDY DESIGN: This was a single-center randomized trial of women receiving office intradetrusor chemodenervation for overactive bladder. Participants were randomized to receive their procedures in a relaxing versus typical office environment. Eighty patients were needed to detect a clinically significant 12 mm difference on the anxiety VAS. Staff completed a preclinic and postclinic Burnout Battery VAS to measure change in their energy level during the day. RESULTS: Patients in the relaxing environment reported a clinically significant reduction in anxiety (-13.8 ± 18.1 vs -4.7 ± 14.7, P = 0.015). Pain was lower for the relaxing environment group, although it did not reach statistical significance (21.9 vs 28.9, P = 0.261). Satisfaction scores were high in both groups (91.4 vs 89.3, P = 0.599) and not significantly different. The procedure room environment did not affect staff energy levels. CONCLUSIONS: A relaxing environment of lavender aromatherapy, calming music, and dim lighting is a noninvasive, easily implemented technique to decrease patients' anxiety before office intradetrusor chemodenervation.

Misophonia is a disorder characterized by heightened sensitivity to certain sounds, triggering symptoms such as sympathetic nervous system activation, anger, anxiety, and depression. This study aimed to evaluate the potential role of lavender tea in alleviating these symptoms due to its anxiolytic and antidepressant properties. A single-center, single-blind, randomized clinical trial was conducted with 60 participants aged 18 and over, diagnosed with misophonia. Participants were divided equally into experimental and control groups using block randomization. The experimental group consumed 2 g of lavender tea twice daily for 14 days, while the control group received no intervention. Data were collected using the Misophonia Scale, Beck Depression Inventory II, Anxiety Rating Scale, and Trait Anger Scale and analyzed with SPSS 25.0. Baseline characteristics, including age, gender, marital status, education level, income level, and scores for misophonia, anxiety, depression, and anger, were comparable between groups. The mixed ANOVA results suggested that positive changes were observed in misophonia and related psychological symptoms in the lavender tea group, and that these changes may have been more pronounced compared to the control group. The results suggest that the intervention may correlate with enhancements in misophonia, quality of life, and coping strategies. Lavender tea consumption may have helped alleviate symptoms of misophonia, anxiety, depression, and anger. However, due to the lack of participant blinding and the use of self-report measures, the findings should be interpreted cautiously in terms of placebo effects and expectancy bias. REGISTRATION: ClinicalTrials.gov Number (NCT06785649).

BACKGROUND: Anxiety resulting from dental treatment often leads to avoidance of dental appointments and consequently has a negative impact on oral health. Non-pharmacological approaches have been identified as suitable alternatives for the management of dental anxiety. In this context, lavender oil has traditionally been used in aromatherapy (AT) due to its sedative, carminative, antidepressive, antiinflammatory, and antimicrobial properties. OBJECTIVES: The aim of the study was to perform a triple-blind randomized clinical trial to address the effectiveness of AT with lavender essential oil (ATL) on the dental anxiety of patients undergoing mandibular third molar surgery. MATERIAL AND METHODS: Participants scheduled to undergo mandibular third molar surgery were enrolled in the study and randomly assigned to either the ATL group or the control group. Dental anxiety was assessed using the preoperative Modified Dental Anxiety Scale (MDAS). Vital signs were evaluated before and after the intervention. Cortisol levels were measured by enzyme-linked immunosorbent assay (ELISA). Additionally, a visual analog scale (VAS) was used, and the requirements for anesthesia were determined. RESULTS: A comparison of the pre-operative MDAS scores between the ATL and control groups revealed no statistically significant differences (p = 0.268). The levels of respiratory rate (RR) (p = 0.011) and heart rate (HR) (p = 0.021) significantly decreased in the ATL group after the intervention. Also, the number of local anesthetic cartridges needed (p = 0.030) and cortisol levels (p < 0.0001) were significantly lower in the ATL group. CONCLUSIONS: The evidence suggests that ATL could be helpful in the management of dental anxiety.

BACKGROUND: Reduced quality in patient care is associated with impaired mental health among healthcare professionals. Hospital staff experience intense stress and are at high risk of burnout. AIMS: The study aimed to demonstrate whether inhaling essential oils using sticks improved the well-being of healthcare professionals working in the emergency, intensive care, anaesthesia and operating theatre departments of our hospital. The effects of aromatherapy on stress and anxiety were also studied. STUDY DESIGN: This randomised, single-centre, crossover study was open-label. Healthcare professionals were given a mixture of essential oils to inhale in stick form (sweet orange, lavender, marjoram and ylang ylang) for 2 months, starting either immediately or after a 2-month control period without essential oils. The order was determined by randomisation. The primary outcome was the WHO-5 well-being index, ranging from 0 to 100. RESULTS: A total of 51 participants were randomised, 49 of whom were retained for analysis. Twenty-six professionals received aromatherapy for 2 months immediately after randomisation, followed by a 2-month period without essential oils, while the remaining 23 participants started with a 2-month control period with no intervention. The WHO-5 well-being score, expressed as the least-square mean ± standard error, was significantly increased after the aromatherapy period compared to the control period (65.9 ± 1.8 vs. 60.4 ± 1.8, p-value = 0.0142). There was also a significant reduction in the general anxiety and perceived stress scores. CONCLUSIONS: Aromatherapy could be an interesting way of improving the well-being of healthcare professionals, reducing their anxiety and perceived stress levels. RELEVANCE TO CLINICAL PRACTICE: The complementary use of aromatherapy, an inexpensive method, seems promising but needs to be confirmed by larger scale studies with a robust methodology. TRIAL REGISTRATION: The protocol was registered on ClinicalTrials.gov (NCT05373849) on 4 May 2022. © 2025 British Association of Critical Care Nurses.

OBJECTIVE: Schema modes have been theorized and tested as mechanisms of change in the treatment of personality disorders. We investigated whether schema modes also function as mechanisms of change in borderline personality disorder (BPD) treatment. METHOD: Data from 494 patients (N = 68 male, N = 426 female) with borderline PD who participated in an international randomized clinical trial on effectiveness of two group schema therapy formats vs treatment as usual were analyzed. Granger Causality was tested partially replicating the model predicting PD severity as derived in Yakın et al. (2020) with generalized linear mixed models, testing within-person relationships over time. RESULTS: The effect of the Healthy Adult, the Vulnerable Child and Detached Self-Soother as an Avoidant Coping mode on PD severity, and the reciprocal relationship between the Healthy Adult and the Vulnerable Child were replicated. Unlike previous findings, the Avoidant Coping mode is not predicted by the Healthy Adult. Moreover, the relationship between Impulsive Child and PD severity was unidirectional. The relationships between Healthy Adult, Self-Aggrandizer, and functioning over time were also replicated, but unlike earlier results, Self-Aggrandizer did not influence later scores of the Healthy Adult. CONCLUSIONS: Central relationships in the model were replicated. The centrality of the Healthy Adult and the Vulnerable Child for the treatment of PDs was also applicable to BPD. It appears that these two modes should be primary treatment targets compared to the other modes, unless the avoidant modes block access to the more vulnerable parts of the personality.

BACKGROUND: Hypertension commonly manifests with anxiety, fatigue, and sleep disturbances that negatively impact quality of life. Lavender essential oil is widely used in complementary therapies for its anxiolytic, hypotensive, and sedative properties. This study aimed to investigate the short- and long-term effects of inhaled lavender essential oil, delivered via a magnetic face mask clip, on psychological and physiological outcomes in middle-aged adults with hypertension. METHODS: Fifty-eight hypertensive adults aged 40-60 years were randomly assigned to either an intervention group (lavender essential oil, n = 30) or a placebo group (sweet almond oil, n = 28). Assessments were conducted at baseline, immediately after a single 15-minute inhalation session, and following daily 15-minute sessions over seven consecutive days. Outcome measures included the State-Trait Anxiety Inventory (STAI), Chalder Fatigue Questionnaire (CFQ), systolic (SBP) and diastolic blood pressure (DBP), and the Verran and Snyder-Halpern Sleep Scale (VHS). RESULTS: At baseline, both groups were demographically comparable. Immediately post-intervention, the aroma group showed significantly greater reductions in anxiety (STAI: -15.7 vs. -0.9, p < .001) and SBP (p = .025). After seven days, the intervention group demonstrated significant improvements across all measures: STAI (-15.6 vs. -0.6, p < .001), fatigue (CFQ: -4.8 vs. -0.9, p = .011), SBP (p = .002) and DBP (p = .033), and sleep quality (VHS: +165.0 vs. +4.7, p < .001). CONCLUSION: Inhalation of lavender essential oil via a mask clip may serve as an effective complementary approach for improving emotional and physiological outcomes in hypertensive adults.

INTRODUCTION: Cataract is one of the most common causes of visual impairment globally, often treated with surgery. Patients undergoing cataract surgery frequently experience anxiety and pain, which can adversely affect their physiological and psychological well-being. This randomized controlled trial aimed to compare the effects of lavender aromatherapy and nature sounds on anxiety and pain in patients undergoing cataract surgery with regional anesthesia. METHODS: A total of 120 patients were randomly assigned to three groups: lavender aromatherapy, nature sounds, and control. The experimental groups received their respective interventions for 15 min preoperatively, while the control group received standard care. Anxiety and pain were measured using the Spielberger State-Trait Anxiety Inventory and Visual Analog Scale. Data were analyzed using ANOVA and chi-square tests to compare the groups; statistical significance was set at p < 0.05. RESULTS: Post-intervention, mean anxiety scores were significantly lower in the lavender (34.85 ± 4.77) and nature sounds (31.95 ± 5.87) groups compared to the control group (49.62 ± 8.70) (P < 0.001). Pain scores following the intervention were reduced in both intervention groups (lavender and nature sounds) compared with the control group. No adverse events were observed in either intervention group. Both lavender aromatherapy (mean difference versus control: -14.8, p < 0.001) and nature sounds (mean difference versus control: -17.7, p < 0.001) significantly reduced anxiety compared to the control group. Results indicated that no adverse events were reported in any group. CONCLUSION: Lavender aromatherapy and nature sounds effectively reduced anxiety and pain in cataract surgery patients, suggesting their potential as non-pharmacological complementary therapies.

In DESTINY-Breast04 ( NCT03734029 ), trastuzumab deruxtecan (T-DXd) significantly improved overall survival (OS) and progression-free survival compared with treatment of physician's choice of chemotherapy (TPC) for patients with human epidermal growth factor receptor 2-low (HER2-low) (immunohistochemistry (IHC) 1+ or IHC 2+/in situ hybridization-negative) metastatic breast cancer. After an extended median follow-up of 32.0 months, median OS in the overall cohort was 22.9 months for T-DXd and 16.8 months for TPC (hazard ratio 0.69; 95% confidence interval 0.55-0.86). For the hormone receptor-positive cohort, median OS was 23.9 and 17.6 months for T-DXd and TPC, respectively (hazard ratio 0.69; 95% confidence interval 0.55-0.87). Median OS also favored T-DXd in exploratory analyses of hormone receptor-negative, estrogen receptor IHC 1%-10% and estrogen receptor IHC >10% cohorts. The overall safety profile of T-DXd was acceptable and generally manageable. Results confirm T-DXd as standard of care after prior chemotherapy in patients with HER2-low metastatic breast cancer. ClinicalTrials.gov identifier: NCT03734029 . © 2025. The Author(s).

BACKGROUND: Sotatercept, an activin-signaling inhibitor, reduces morbidity and mortality among patients with long-standing pulmonary arterial hypertension. Its effects in patients with pulmonary arterial hypertension within the first year after diagnosis are unclear. METHODS: In this phase 3 trial, we enrolled adult patients with World Health Organization functional class II or III pulmonary arterial hypertension who had received the diagnosis less than 1 year earlier, had an intermediate or high risk of death, and were receiving double or triple background therapy. Patients were randomly assigned to receive add-on therapy with subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; escalated to target dose, 0.7 mg per kilogram) or placebo every 21 days. The primary end point was clinical worsening, a composite of death from any cause, unplanned hospitalization lasting at least 24 hours for worsening of pulmonary arterial hypertension, atrial septostomy, lung transplantation, or deterioration in performance in exercise testing due to pulmonary arterial hypertension, assessed in a time-to-first-event analysis. RESULTS: The trial was stopped early owing to loss of clinical equipoise after the reporting of positive results from previous sotatercept trials. A total of 320 patients were included (160 each in the sotatercept and placebo groups). The median duration of follow-up was 13.2 months. At least one primary end-point event occurred in 17 patients (10.6%) in the sotatercept group and in 59 patients (36.9%) in the placebo group (hazard ratio, 0.24; 95% confidence interval, 0.14 to 0.41; P<0.001). Deterioration in performance in exercise testing due to pulmonary arterial hypertension occurred in 8 patients (5.0%) in the sotatercept group and in 46 patients (28.8%) in the placebo group; unplanned hospitalization for worsening of pulmonary arterial hypertension occurred in 3 patients (1.9%) and 14 patients (8.8%), respectively; and death from any cause occurred in 7 patients (4.4%) and 6 patients (3.8%). No cases of atrial septostomy or lung transplantation occurred. The most common adverse events with sotatercept were epistaxis (31.9%) and tel

13. Med Sci (Basel). 2025 Sep 1;13(3):166. doi: 10.3390/medsci13030166. Lavender-Neroli Aromatherapy for Reducing Dental Anxiety and Pain in Children During Anesthesia: A Two-Arm Randomized Controlled Trial. Abdalhai R(1), Tolibah YA(1), Alkhatib R(2), Kouchaji C(1), Baghdadi ZD(3)(4). Author in

INTRODUCTION: Antimicrobial resistance is recognized as one of the major health challenges. Thus, urgent therapeutic solutions are needed. This study aims to test the activity of plant extracts against multi-resistant bacteria, as well as the synergistic effect of these extracts with some antibiotics. METHODOLOGY: The evaluation of the antibacterial effect of eight medicinal extract plants (G. alypum, R. graveolens, U. dioica, P. lentiscus, A. vulgaris, L. angustifolia, T. vulgaris, and J. phoenicea) against 10 bacterial strains (K. pneumoniae, E. coli, C. freundii, S. haemolyticus, S. epidermidis, S. saprophyticus) has been performed using both wells and disks diffusion methods (DDM/WDM). The evaluation of the synergistic effect of some of the natural extracts with some antibiotics has been performed using the disk diffusion method (DDM). RESULTS: A significant difference resulting from the effect of various plant extracts on different bacterial species has been observed. Interestingly, an important inhibition zone related to the effect of the essential oil of T. vulgaris and L. angustifolia was observed in all bacterial strains. The combination of plants/antibiotics does not always give a more effective effect than the antibiotic /or the plant extract alone. The lavender oil seems to be able to enhance the activity of ertapenem on C. freundii, while the combination of A. vulgaris/ertapenem induced the reduction of the inhibition zone on the same species. CONCLUSIONS: These results are of great importance; regarding the valorization of natural resources for the creation of solutions to urgent health problems while taking advantage of existing pharmaceutical resources. Copyright (c) 2025 Raoudha Dziri, Imen hammadi, Eya Agreby, Mayssa Trabelsi, Abderrazak Maaroufi.

BACKGROUND: This short communication presents an analytical approach to evaluate the synergistic anticonvulsant effects of an herbal combination containing hydroalcoholic extracts of Origanum vulgare (oregano), Matricaria chamomilla (chamomile), and Lavandula angustifolia (lavender). OBJECTIVE: The study aimed to apply linear dose-response modeling to seizure score data to predict the expected outcomes of combination therapy and quantify synergy by comparing predicted and observed effects. METHODS: The herbal extracts were obtained through maceration with 70% ethanol. The animal study was performed using 2 different doses of each herb, involving 36 rats in 6 groups. Building on previous in vivo findings, the study utilized linear dose-response modeling to analyze the effects of the combination therapy on seizure scores and to determine the synergistic performance at combination doses of 17mg/kg, 34mg/kg, and 68mg/kg. RESULTS: The results highlighted the synergistic performance of the herbal combination, particularly at the dose of 34mg/kg, demonstrating the pharmacodynamic advantages of combination therapy and confirming the enhanced antiseizure effect of the herbal combination. CONCLUSIONS: This study confirms the synergistic anticonvulsant effects of the herbal combination and demonstrates its potential as a new supplementary treatment for seizures via a non-invasive intranasal administration method.

Avian pathogenic Escherichia coli (APEC) causes a variety of infections outside the intestine. The treatment of these infections is becoming increasingly difficult due to the emergence of multi-drug resistant (MDR) strains, which can also be a direct or indirect threat to humans as consumers of poultry products. Therefore, alternative antimicrobial agents are being sought, which could be essential oils, either administered individually or in interaction with antibiotics. Sixteen field isolates of E. coli (originating from 1-day-old broilers) and the ATCC 25922 reference strain were tested. Commercial cinnamon bark, clove bud, lavender flower essential oils (EOs) and enrofloxacin were selected to assess the sensitivity of the selected E. coli strains to antimicrobial agents. The checkerboard method was used to estimate the individual minimum inhibitory concentration (MIC) for each antimicrobial agent as well as to determine the interactions between the selected essential oil and enrofloxacin. In the case of enrofloxacin, ten isolates were resistant at MIC ≥ 2 μg/mL, three were classified as intermediate (0.5-1 μg/mL) and three as sensitive at ≤0.25 μg/mL. Regardless of the sensitivity to enrofloxacin, the MIC for cinnamon EO was 0.25% v/v and for clove EO was 0.125% v/v. All MDR strains had MIC values for lavender EO of 1% v/v, while drug-sensitive isolates had MIC of 0.5% v/v. Synergism between enrofloxacin and EO was noted more frequently in lavender EO (82.35%), followed by cinnamon EO (64.7%), than in clove EO (47.1%). The remaining cases exhibited additive effects. Owing to synergy, the isolates became susceptible to enrofloxacin at an MIC of ≤8 µg/mL. A time-kill study supports these observations. Cinnamon and clove EOs required for up to 1 h and lavender EO for up to 4 h to completely kill a multidrug-resistant strain as well as the ATCC 25922 reference strain of E. coli. Through synergistic or additive effects, blends with a lower than MIC concentration of enrofloxacin mixed with a lower EO content required 6 ± 2 h to achieve a similar effect.

The emergence of antimicrobial resistance (AMR) has urged researchers to explore therapeutic alternatives, one of which includes the use of natural plant products such as essential oils (EO). In fact, EO obtained from clove, oregano, thymus, cinnamon bark, rosemary, eucalyptus, and lavender have been shown to present significant inhibitory effects on bacteria, fungi, and viruses; many studies have been done to measure EO efficacy against microorganisms. The strategy of combinatory effects via conventional and non-conventional methods revealed that the combined effects of EO-EO or EO-antibiotic exhibit enhanced efficacy. This paper aims to review the antimicrobial effects of EO, modes of EO action (membrane disruption, efflux inhibition, increase membrane permeability, and decrease in intracellular ATP), and their compounds' potential as effective agents against bacteria, fungi, and viruses. It is hoped that the integration of EO applications in this work can be used to consider EO for future clinical applications.

Misuse of antibiotics in the clinical and agricultural sectors has caused the emergence of multidrug-resistant (MDR) Klebsiella pneumoniae which contributes a threat to human health. In this study, we assessed the feasibility of lavender essential oil (LVO) as an antimicrobial agent in combinatory therapy with meropenem in suppressing the growth of carbapenemase-producing K. pneumoniae (KPC-KP). Synergistic interactions between LVO and meropenem were detected, which significantly reduce the inhibitory concentration of both LVO and meropenem by 15 and 4-fold respectively. Comparative proteomic profiling identified a disruption in the bacterial membrane via oxidative stress that was indicated by loss of membrane and cytoplasmic proteins and the upregulation of oxidative regulators. As a proof of concept, zeta potential measurements showed a change in cell surface charge while outer membrane permeability measurement indicated an increase in membrane permeability following exposure to LVO. This was indicative of a disrupted outer membrane. Ethidium bromide influx/efflux assays demonstrated no significant efflux pump inhibition by LVO, and scanning electron microscopy revealed irregularities on the cell surface after exposure to LVO. Oxidative stress was also detected with increased level of ROS and lipid peroxidation in LVO-treated cells. In conclusion, our data suggest that LVO induced oxidative stress in K. pneumoniae which oxidizes the outer membrane, enabling the influx of generated ROS, LVO and meropenem into the bacterial cells, causing damage to the cells and eventually death.

In the post-antibiotic era the issue of bacterial resistance refers not only to antibiotics themselves but also to common antiseptics like octenidine dihydrochloride (OCT). This appears as an emerging challenge in terms of preventing staphylococcal infections, which are both potentially severe and easy to transfer horizontally. Essential oils have shown synergisms both with antibiotics and antiseptics. Therefore the aim of this study was to investigate the impact of lavender essential oil (LEO) on OCT efficiency towards methicillin-resistant S. aureus strains (MRSA). The LEO analyzed in this study increased the OCT's susceptibility against MRSA strains. Subsequent FTIR analysis revealed cellular wall modifications in MRSA strain cultured in media supplemented with OCT or LEO/OCT. In conclusion, LEO appears to be a promising candidate for an efficient enhancer of conventional antiseptics.

PURPOSE: Silexan is an oral Lavender oil preparation with proven anxiolytic efficacy. Given the high prevalence of anxiety and restlessness in younger women, oral contraceptives and Silexan will likely be co-administered. METHODS: A double-blind, randomised, 2-period crossover study was performed to investigate the effects of Silexan on the pharmacokinetics and pharmacodynamics of Microgynon(®), a combination oral contraceptive containing ethinyl estradiol 0.03 mg (EE) and levonorgestrel 0.15 mg (LNG) in healthy, fertile, adult females. During 2 consecutive cycles of 28 days, oral contraception was given for 21 days combined with 1 × 160 mg/day Silexan or placebo. Plasma concentration-time profiles of EE and LNG were obtained on day 18 ± 1 up to 24 h after dosing. The primary outcome measure was the area under the concentration-time curve over a dosing interval of τ = 24 h (AUCτ) for EE and LNG plasma levels. An interaction with Silexan was formally excluded if the 90 % confidence interval for the AUCτ ratio during co-administration with Silexan or placebo was included within the range of 0.80-1.25. Secondary outcomes included EE and LNG peak concentration (C max) and time to C max (t max), follicle size, endometrial thickness, the Hoogland score, and serum levels of estradiol, progesterone, and sex hormone-binding globulin. RESULTS: A total of 24 women (mean age 27.3 years; mean body mass index 22.2 kg/m(2)) participated. The confidence intervals for the EE and LNG AUCτ and C max ratios fell within the pre-specified limits, indicating no interaction (point estimates [Silexan/placebo] AUCτ EE 0.97, LNG 0.94; C max EE 0.99, LNG 0.96). For LNG, t max was slightly delayed. No secondary outcome indicated any impairment of contraceptive efficacy. CONCLUSIONS: Co-administration of Silexan did not affect the efficacy of a combination oral contraceptive containing EE and LNG and was well tolerated.

AIM: The aim of this study was to investigate the mode of action of the lavender essential oil (LV) on antimicrobial activity against multi-drug-resistant Escherichia coli J53 R1 when used singly and in combination with piperacillin. METHOD AND RESULTS: In the time-kill analysis, a complete killing of bacteria was observed based on colony counts within 4 h when LV was combined with piperacillin during exposure at determined FIC concentrations. Analysis of the membrane permeabilizing effects of LV on treated cultures through their stability against sodium dodecyl sulphate revealed that the LV played a role in disrupting the bacterial cell membrane. The finding is further supported by scanning electron microscopy analysis and zeta potential measurement. In addition, reduction in light production expression of E. coli [pSB1075] by the LV showed the presence of potential quorum sensing (QS) inhibitors. CONCLUSIONS: These results indicated that the LV has the potential to reverse bacterial resistance to piperacillin in E. coli J53 R1. It may operate via two mechanisms: alteration of outer membrane permeability and inhibition of bacterial QS. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings offer a novel approach to develop a new option of phytopharmaceuticals against multi-drug-resistant E. coli. © 2014 The Society for Applied Microbiology.

In this study we investigated the relationship between several selected commercially available essential oils and beta-lactam antibiotics on their antibacterial effect against multidrug resistant bacteria. The antibacterial activity of essential oils and antibiotics was assessed using broth microdilution. The combined effects between essential oils of cinnamon bark, lavender, marjoram, tea tree, peppermint and ampicillin, piperacillin, cefazolin, cefuroxime, carbenicillin, ceftazidime, meropenem, were evaluated by means of the checkerboard method against beta-lactamase-producing Escherichia coli. In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interaction between the combinations. Substantial susceptibility of the bacteria toward natural antibiotics and a considerable reduction in the minimum inhibitory concentrations (MIC) of the antibiotics were noted in some paired combinations of antibiotics and essential oils. Out of 35 antibiotic-essential oil pairs tested, four of them showed synergistic effect (FIC≤0.5) and 31 pairs showed no interaction (FIC>0.5-4.0). The preliminary results obtained highlighted the occurrence of a pronounced synergistic relationship between piperacillin/cinnamon bark oil, piperacillin/lavender oil, piperacillin/peppermint oil as well as meropenem/peppermint oil against two of the three bacteria under study with a FIC index in the range 0.26-0.5. The finding highlighted the potential of peppermint, cinnamon bark and lavender essential oils being as antibiotic resistance modifying agent. Reduced usage of antibiotics could be employed as a treatment strategy to decrease the adverse effects and possibly to reverse the beta-lactam antibiotic resistance.

This cocktail study evaluated the interaction potential of the oral lavender oil preparation silexan with major P450 (cytochrome P450) enzymes. SUBJECTS AND METHODS: Sixteen healthy male or female Caucasians completed this double-blind, randomized, 2-fold crossover study. Silexan (160 mg) or placebo were administered once daily for 11 days. Additionally, on day 11 of both study periods, 150 mg caffeine (CYP1A2), 125 mg tolbutamide (CYP2C9), 20 mg omeprazole (CYP2C19), 30 mg dextromethorphan-HBr (CYP2D6), and 2 mg midazolam (CYP3A4) were administered orally. Formal interaction was excluded if the 90% confidence interval (CI) for the silexan over placebo ratios for phenotyping metrics (primary: AUC(0-t)) was within a 0.70-1.43 range. RESULTS: According to the AUC(0-t) comparisons, silexan had no relevant effect on CYP1A2, 2C9, 2D6, and 3A4 activity. Secondary phenotyping metrics confirmed this result. Mean ratios for all omeprazole-derived metrics were close to unity. The 90% CI for the AUC(0-t) ratio of omeprazole but not for omeprazole/5-OH-omeprazole plasma ratio 3 hours post-dose or omeprazole/5-OH-omeprazole AUC(0-t) ratio (secondary CYP2C19 metrics) was above the predefined threshold of 1.43, probably caused by the inherent high variability of omeprazole pharmacokinetics. Silexan and the phenotyping drugs were well tolerated. Repeated silexan (160 mg/day) administration has no clinically relevant inhibitory or inducing effects on the CYP1A2, 2C9, 2C19, 2D6, and 3A4 enzymes in vivo.

BACKGROUND: Palliative care is the active holistic treatment of people of all ages who have serious health-related suffering as a result of severe illness, and especially of those who are close to the end of life. Palliative care is provided to cancer patients who experience serious suffering that cannot be relieved without professional intervention and that compromises physical, social, spiritual, and emotional functioning. A straightforward, low-risk, and affordable palliative care approach may be provided through aromatherapy, a type of complementary and alternative medicine. The study objective is to assess the comparative effectiveness of massage, aromatherapy massage, and massage combined with aromatherapy inhalation on cancer patients receiving palliative care. METHODS: A total of 100 participants who were divided into four groups at random. The first group, designated as the control group, received standard hospital nursing care, the second group received massage only (using the odorless almond carrier oil), the third group received massage with lavender oil, and the fourth group received combined (inhalation and massage) aromatherapy. The Rotterdam Symptom Checklist (RSCL), given two weeks after aromatherapy, was used to examine participants' perspectives of care. RESULTS: On the RSCL, combined aromatherapy performed best. In terms of reported physical symptoms, psychological symptoms, and activities, there were statistically significant differences between the scores of the control group and each of the experimental groups. Nonetheless, the total quality of life score showed no significant difference between the control group and the massage only group (t = 0.529, p = 0.60). CONCLUSIONS: When paired with aromatherapy inhalation, massage has a positive effect on physical, psychological symptoms, activities, and overall quality of life for cancer patients receiving early palliative care. Nurses and other healthcare providers are recommended to support programs that provide message therapy to reduce reported bodily symptoms, psychological problems, and limited activities among cancer patients.

Loss of control (LOC)-eating, excess weight, and anxiety are robustly linked, and are independently associated with markers of poorer cardiometabolic health, including hypertension. However, no study has examined whether frequency of LOC-eating episodes among youth with anxiety symptoms and elevated weight status may confer increased risk for hypertension. We examined the relationship between LOC-eating frequency and blood pressure among 39 adolescent girls (14.9 ± 1.8 years; body mass index [BMI] = 29.9 ± 5.6; 61.5 % White; 20.5 % African American/Black; 5 % Multiple Races; 2.5 % Asian; 12.8 % Hispanic/Latino; 30.8 % with reported LOC-eating) with elevated anxiety and above average BMI who enrolled in a clinical trial aimed at preventing excess weight gain. LOC-eating over the past three months was assessed via clinical interview, and blood pressure (systolic and diastolic) was measured with an automatic blood pressure monitor. Adjusting for age, fat mass, and height, LOC-eating episode frequency was significantly, positively associated with diastolic blood pressure (β = 0.38, p = 0.02), but not with systolic blood pressure (β = 0.13, p = 0.41). Replication studies, with larger sample sizes, participants of varying weight-strata, and prospective data are required to elucidate the relationship between LOC-eating and cardiovascular functioning in youth with elevated anxiety. Published by Elsevier Ltd.

Background: Aromatherapy is widely used in women's health as a complementary therapy. Objective: This review aimed to critically evaluate clinical evidence of the effectiveness of aromatherapy in managing menopausal symptoms. Design: A systematic review and meta-analysis. Methods: A total of 11 electronic databases were searched up to November 5, 2020. Randomized controlled trials (RCTs) evaluating any type of aromatherapy against placebo in menopausal individuals were eligible. Two authors independently assessed the study eligibility and risk of bias as well as extracted the data for each study. Cochrane risk of bias tool was used to evaluate the methodological quality of each included studies. No ethical approval was required for this manuscript as this study did not involve human subjects or laboratory animals. Results: Seven RCTs met our inclusion criteria and were analyzed. Most of the included RCTs had low risk of bias in most domains except for blinding. Four studies tested the efficacy of aromatherapy for menopausal symptoms. The results showed that aromatherapy (lavender or low dose of neroli) inhalation had superior effects on reducing the total menopausal symptom score compared with the placebo. One study presented that aromatherapy massage with mixed oils reduced menopausal symptoms. Three studies investigated the effects of aromatherapy inhalation on sexual desire, and all of the studies showed that aromatherapy inhalation (lavender or low dose of neroli or mixed oils) had superior effects compared with the placebo. Conclusion: This review indicates limited evidence of the benefit of aromatherapy (lavender or low dose of neroli) in improving total menopausal symptoms and sexual desire. Further studies are highly warranted to validate the findings.

BACKGROUND: This systematic review investigated the clinical effects of inhalation aromatherapy for the treatment of sleep problems such as insomnia. METHODS: Studies on sleep problems and inhalation aromatherapy, published in Korean and international journals, were included in the meta-analysis. Five domestic and international databases, respectively each, were used for the literature search. Keywords included sleep disorder, sleep problems, insomnia, and aroma inhalation, and the related literature was further searched. After the screening, selected articles were assessed for their quality and conducted the risk of bias using RevMan 5.0, a systematic literature review was then conducted. A meta-analysis comparing the averages was conducted on studies that reported numerical values. Additionally, meta-analysis of variance and meta-regression analyses were performed. RESULTS: Meta-analysis of the 34 studies using the random-effects model revealed that the use of aromatherapy was highly effective in improving sleep problems such as insomnia, including quantitative and qualitative sleep effects (95% confidence interval [CI], effect sizes = 0.6491). Subgroup analysis revealed that the secondary outcomes including stress, depression, anxiety, and fatigue were significantly effective. The single aroma inhalation method was more effective than the mixed aroma inhalation method. Among the single inhalation methods, the lavender inhalation effect was the greatest. CONCLUSION: Inhalation aromatherapy is effective in improving sleep problems such as insomnia. Therefore, it is essential to develop specific guidelines for the efficient inhalation of aromatherapy. ETHICS AND DISSEMINATION: Ethical approval is not required because individual patient data are not included. The findings of this systematic review were disseminated through peer-reviewed publications or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42020142120.

INTRODUCTION: Bone marrow biopsy is a common procedure for the diagnosis and treatment of hematologic diseases and tumors, which are associated with anxiety. The purpose of this study was to examine the effect of lavender aroma on anxiety of patients having bone marrow biopsy. MATERIALS AND METHODS: This study was performed on 80 patients referred to Vali-e-Asr Hospital for bone marrow biopsy. Samples were selected by convenience method and were assigned into intervention and control groups using randomized blocks of 4. Random sequence was generated by RAS software. Several drops of distilled water on a cotton ball was used in the control group and same amount of lavender essential oil on a cotton ball was used in the intervention group. Then, participants in both groups were asked to smell the cotton ball for 15 minutes and then, their anxiety level was measured immediately. The results were analyzed by SPSS software version 25 using covariance analysis and rank regression. RESULTS: The results showed that, the mean scores of anxiety in the control and intervention groups were 6.3 ± 1.92 and 3.75 ± 1.05, respectively. There was a significant difference (p <0.05) between the two groups in terms of anxiety score.The results showed that there was a significant difference in anxiety score between two groups in terms of variables such as age, gender, physician experience, biopsy history and biopsy site (P <0.05). The results also showed no significant difference between the (p >0.05). CONCLUSION: The results of this study showed that bone marrow biopsy is associated with anxiety, and smelling of lavender aroma is effective in reducing anxiety in patients undergoing this procedure. This fragrance can be used by treatment team in hematology and oncology clinics to reduce anxiety caused by bone marrow biopsy.<br />.

PURPOSE: The purpose of this study was to investigate the effects of aromatherapy on sleep quality. METHODS: This is a systematic review of randomized controlled trial studies (PROSPERO registration number CRD42017064519). In this study, the PICO were adults and the elderly, aromatherapy intervention, a comparative intervention with the control and placebo oil groups, and sleep. The selected articles were in English, Korean, and Chinese. RESULTS: The results of the meta-analysis showed that the effect sizes of the experimental group were 1.03 (n=763, SMD=1.03, 95% CI 0.66 to 1.39) (Z=5.47, p<.001). In the aromatherapy intervention group, the effect size of sleep was statistically significant (QB=9.39, df=2, p=.009), with a difference of 0.77 for inhalation, 1.12 for oral intake and 2.05 for massage. A post-analysis showed that the effect of massage on sleep was significantly greater than the inhalation method. The regression coefficient of the intervention period, B=0.01 (Z=1.43, p=.154), also showed that the longer the intervention period, the larger the effect size; however, it was not statistically significant. CONCLUSION: A total of 23 literature analyses showed that aromatherapy is effective in improving quality of sleep, and the massage method is more effective in improving quality of sleep than the inhalation method. A meta-ANOVA showed that the aromatherapy intervention affected the high heterogeneity of the effect size. Thus, future research with stricter control in methods and experimental procedures is necessary. © 2019 Korean Society of Nursing Science.

PURPOSE: Although lavender is purported to possess anxiolytic and sedative properties and is often recommended for relieving anxiety, the efficacy of lavender has not been well established. Thus, this review aimed to evaluate the anxiolytic effects of lavender aromatherapy. METHODS: Ten data bases were searched for studies published between 2000 and 2018. Randomized controlled trials investigating the anxiolytic effects of lavender aromatherapy with any type of application for persons with or without clinical anxiety were included. The outcome variables included self-rated anxiety, vital signs, and salivary cortisol and chromogranin A (CgA) levels. In the meta-analysis, standardized mean difference and 95% confidence interval were calculated as effect measures by applying the random effect model and inverse variance method. RESULTS: Twenty-two trials met our inclusion criteria. Lavender aromatherapy was found to have favorable effects in relieving anxiety (Hedges' ĝ = -0.65; 95% CI, -0.84 to -0.46) and decreasing systolic blood pressure (ĝ = -0.22; 95% CI, -0.43 to -0.02), heart rate (ĝ = -0.53; 95% CI, -0.74 to -0.32), and salivary cortisol (ĝ = -1.29; 95% CI, -2.23 to -0.35) and CgA (ĝ = -2.29; 95% CI, -3.24 to -1.34) levels. However, the meta-analysis did not reveal any significant effects of lavender on diastolic blood pressure (effect size: -0.17; 95% CI, -0.37-0.04). CONCLUSION: Aromatherapy using lavender oil might have favorable effects on anxiety and its physiological manifestations. Future studies are recommended with an emphasis on methodological quality. In nursing practice, it is suggested that lavender aromatherapy be included in programs intended to manage anxiety in patients across diverse healthcare settings.