Search Results (937)

Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative agents of endometriosis, and highlight implications in the general population and clinical work. A thorough review of experimental, epidemiologic, and mechanistic research studies was conducted to explain the association between EDCs and endometriosis. Among the primary EDCs under investigation are polychlorinated biphenyls, dioxins, phthalates, and bisphenol A (BPA). Despite methodological heterogeneity and some discrepancies, epidemiologic evidence supports a positive association between some increased levels of BPA, phthalates, and dioxins in urine or in blood, and endometriosis. Experiments support some effect of EDCs on endometrial cells and causing endometriosis. EDCs function as xenoestrogens, alter immune function, induce oxidative stress, and disrupt progesterone signaling. Epigenetic reprogramming may play a role in mediating EDC-induced endometriosis. Endocrine, immunological, and epigenetic pathways link EDCs and endometriosis. Prevention techniques require deeper comprehension of those factors. Causal linkages and possible treatment targets should be based on longitudinal studies and multi-omics techniques. Restriction of EDCs could be beneficial for endometriosis prevalence limitation. Full article

Background: Pain is a problem faced by critically ill surgical patients and has a major impact on their outcomes. Pain assessment is therefore essential for effective pain management, with a combination of pharmacological and non-pharmacological treatment. Clinical supervision, supported by models such as SafeCare, can improve professional development, safety and the quality of care in intensive care units. Objectives: This study aimed to: (1) assess current pain assessment practices in a polyvalent Intensive Care Unit (ICU) in the Porto district; (2) identify nurses’ training needs regarding the Clinical Supervision-Sensitive Indicator—Pain; and (3) evaluate the impact of clinical supervision sessions on pain assessment practices. Methods: A quantitative, quasi-experimental, cross-sectional study with a pre- and post-intervention design was conducted. Based on the SafeCare model, it included a situational diagnosis, 6 clinical supervision sessions (February 2023), and outcome evaluation via nursing record audits (November 2022 and May 2023) in 31 total critical ill patients. Pain was assessed using standardised tools, in line with institutional protocols. Data was analysed using Software Statistical Package for the Social Sciences v25.0. Results: Pain was highly prevalent in the first 24 h, decreasing during hospitalisation. Generalised acute abdominal pain predominated, with mild to moderate intensity, and was exacerbated by wound care and mobilisation/positioning. Pain management combined pharmacological and non-pharmacological treatment. There was an improvement in all the parameters of the pain indicator post-intervention. Conclusions: Despite routine assessments, gaps remained in reassessing pain post-analgesia and during invasive procedures. Targeted clinical supervision and ongoing training proved effective in improving compliance with protocols and supporting safer, more consistent pain management. Full article

Pain following orthodontic treatment is the chief complaint of patients undergoing this form of treatment. Although the use of diode lasers has been suggested for pain reduction, the mechanism of laser-induced analgesic effects remains unclear. Neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), contribute to the transmission and maintenance of inflammatory pain. Heat shock protein (HSP) 70 plays a protective role against various stresses, including orthodontic forces. This study aimed to examine the effects of diode laser irradiation on neuropeptides and HSP 70 expression in periodontal tissues induced by experimental tooth movement (ETM). For inducing ETM for 24 h, 50 g of orthodontic force was applied using a nickel–titanium closed-coil spring to the upper left first molar and the incisors of 20 male Sprague Dawley rats (7 weeks old). The right side without ETM treatment was considered the untreated control group. In 10 rats, diode laser irradiation was performed on the buccal and palatal sides of the first molar for 90 s with a total energy of 100.8 J/cm². A near-infrared (NIR) laser with a 808 nm wavelength, 7 W peak power, 560 W average power, and 20 ms pulse width was used for the experiment. We measured the number of facial groomings and vacuous chewing movements (VCMs) in the ETM and ETM + laser groups. Immunohistochemical staining of the periodontal tissue with SP, CGRP, and HSP 70 was performed. The number of facial grooming and VCM periods significantly decreased in the ETM + laser group compared to the ETM group. Moreover, the ETM + laser group demonstrated significant suppression of SP, CGRP, and HSP 70 expression. These results suggest that the diode laser demonstrated analgesic effects on ETM-induced pain by inhibiting SP and CGRP expression, and decreased HSP 70 expression shows alleviation of cell damage. Thus, although further validation is warranted for human applications, an NIR diode laser can be used for reducing pain and neuropeptide markers during orthodontic tooth movement. Full article

There is limited knowledge about the benefits of functional textile in arthritis management. This study aimed to evaluate the effect of wearing functional socks in patients with rheumatoid or psoriatic arthritis. Patients were randomized into an experimental group (n = 23) and control group (n = 18). The intervention involved wearing functional textile socks for 12 weeks. Sock composition was analyzed using X-ray fluorescence spectrometry and scanning electron microscopy. Outcome measures included the Numeric Rating Scale, Health Assessment Questionnaire–Disability Index (HAQ-DI), and RAND-36 (Estonian version). At week 12, the experimental group showed significantly lower metatarsophalangeal and toe joint pain (p = 0.001), stiffness (p = 0.005), and ankle stiffness (p = 0.017) scores than the control group. Improvements were also observed in HAQ-DI reaching (p = 0.035) and activity (p = 0.028) scores. RAND-36 scores were higher in physical functioning (p = 0.013), social functioning (p = 0.024), and bodily pain (p = 0.006). Role limitations due to physical problems improved in the experimental group but worsened in the control group (p = 0.029). In conclusion, wearing functional socks led to some statistically significant improvements in foot and ankle pain and stiffness, physical function, and health-related quality of life. However, the effect sizes were small, and the clinical relevance of these findings should be interpreted with caution. Full article

The objective of this study was to determine the pharmacological interaction of some common NSAIDs in the presence of quercetin (QUER). Indomethacin (IND), ketorolac (KET), or celecoxib (CEL) were assessed alone and in combination with QUER using experimental gout-arthritic pain and the carrageenan-induced edema test in rats to evaluate their antinociceptive and anti-inflammatory effects, respectively. The antinociceptive effect of each NSAID was also analyzed after the repeated administration of QUER for 10 days. Molecular docking analysis on COX-1/COX-2 with each drug was explored to analyze the pharmacological interaction. QUER produced minimal antinociceptive or anti-inflammatory effects on experimental gout-arthritic pain or on the carrageenan-induced edema in rats. Additionally, QUER reduced the antinociceptive effect of NSAIDs, mainly those COX-1 inhibitors (IND and KET), when they were combined. However, QUER did not modify the anti-inflammatory effect of these COX-1 inhibitors and slightly improved the anti-inflammatory effect of the COX-2 inhibitor (CEL). According to the docking analysis, COX-1 and COX-2 are likely implicated in these pharmacological interactions. In conclusion, QUER, a known bioactive natural product, may alter the antinociceptive efficacy of NSAIDs commonly used to relieve gout-like pain and suggests not using them together to prevent a negative therapeutic interaction in this effect. Full article

Background: Emerging evidence indicates that some individuals recovering from COVID-19 develop persistent symptoms, including fatigue, pain, cognitive difficulties, and psychological distress, commonly known as Long COVID. These symptoms often overlap with those seen in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), underscoring the need for integrative, non-pharmacological interventions. This Phase II controlled trial aimed to evaluate the feasibility and preliminary efficacy of Heart Rate Variability Biofeedback (HRV-BF) in individuals with Long COVID who meet the diagnostic criteria for CFS/ME. Specific objectives included assessing feasibility indicators (drop-out rates, side effects, participant satisfaction) and changes in fatigue, depression, anxiety, pain, and health-related quality of life. Methods: Participants were assigned alternately and consecutively to the HRV-BF intervention or Treatment-as-usual (TAU), in a predefined 1:1 sequence (quasirandom assignment). The intervention consisted of 10 HRV-BF sessions, held twice weekly over 5 weeks, with each session including a 10 min respiratory preparation and 40 min of active training. Results: The overall drop-out rate was low (5.56%), and participants reported a generally high level of satisfaction. Regarding side effects, the mean total Simulator Sickness Questionnaire score was 24.31 (SD = 35.42), decreasing to 12.82 (SD = 15.24) after excluding an outlier. A significantly greater improvement in severe fatigue was observed in the experimental group (H = 4.083, p = 0.043). When considering all outcomes collectively, a tendency toward improvement was detected in the experimental group (binomial test, p < 0.0001). Conclusions: HRV-BF appears feasible and well tolerated. Findings support the need for Phase III trials to confirm its potential in mitigating fatigue in Long COVID. Full article

Introduction: Deep dry needling (DDN) is commonly applied in physiotherapy to treat musculoskeletal pain. The quadratus femoris (QF) muscle, located in the ischiofemoral space (IFS), represents a clinically relevant yet anatomically complex target. However, limited evidence exists on the safety, accuracy, and reliability of non-ultrasound-guided DDN in this region. Aims: To assess the safety and accuracy of a standardized, non-ultrasound-guided DDN approach to the QF muscle, and to evaluate the intra- and inter-rater reliability of key procedural outcomes. Additionally, to determine the agreement between ultrasound imaging and anatomical dissection as validation methods for needle placement. Methods: An experimental cross-sectional study was conducted on five fresh cadavers (n = 24 approaches) by two physiotherapists with different DN experience. A standardized dry needling protocol was executed without ultrasound guidance, and anatomical and procedural variables were documented. Reliability (intra/inter-rater) was assessed for needle size, sciatic nerve (SN) puncture, IFS targeting, and overall success. In a subset, needle placement was validated through ultrasound and subsequent dissection. Results: The IFS was reached in 70.8% of procedures, and the SN was punctured in 16.7%. Inter-rater reliability for needle size was poor (κ = 0.04). Agreement between ultrasound and dissection was excellent for the ischiofemoral location and success (100%) and moderate for non SN puncture (90%; κ = 0.62). Conclusions: The standardized protocol demonstrated moderate accuracy and revealed a relevant clinical risk when targeting the quadratus femoris muscle. While inter-rater reliability was limited, agreement between ultrasound and dissection methods was high, supporting their complementary use for validating needle placement in anatomically complex procedures. Full article

Background/Objectives: Neonatal pain must be treated due to its potential short- and long-term adverse effects. A frenotomy is a painful procedure where common strategies to relieve pain (oral sucrose solutions and sucking) cannot be used because the technique is performed on the tongue. Lavender essential oil (LEO) is useful in treating pain during blood sampling, heel punctures, vaccination, and frenotomies. We aimed to determine whether smelling colostrum had similar effects as inhaled LEO during frenotomies. Methods: A prospective, randomized clinical trial was carried out with neonates who underwent a frenotomy for ankyloglossia between September 2023 and June 2024. We assessed pain using the NIPS score, heart rate, oxygen saturation, and crying time. After obtaining parental informed consent, we randomized patients into experimental and control groups. In both groups, we performed swaddling, administered 1 mL of oral sucrose, and let the newborn suck for 2 min. In the experimental group, we placed a gauze pad with two drops of colostrum, whereas in the control group, we used one drop of LEO 2 cm under the neonate’s nose prior to and during the frenotomy. Results: We enrolled 142 patients (71 experimental cases and 71 controls). The experimental group showed lower crying times (28.0 vs. 40.2 s, p = 0.03). Both groups showed similar NIPS scores (1.4 vs. 1.5, p = 0.28). We observed no side effects in either of the groups. Conclusions: Inhaled colostrum and LEO help relieve pain in neonates who undergo a frenotomy for ankyloglossia and have no side effects. Aromatherapy with colostrum may decrease crying time during the frenotomy. Full article

Background/Objectives: A randomized controlled trial (RCT) was designed to test the emerging role of respiratory mechanics as part of physiotherapy in patients with non-specific chronic neck pain (NSCNP). Methods: Ninety patients with NSCNP and symptom duration >3 months were randomly allocated to three intervention groups of equal size, receiving either cervical spine (according to the Mulligan Concept) and diaphragm manual therapy plus breathing reeducation exercises (experimental group—EG1), cervical spine manual therapy plus sham diaphragmatic manual techniques (EG2), or conventional physiotherapy (control group—CG). The treatment period lasted one month (10 sessions) for all groups. The effect on the cervical spine range of motion (CS-ROM) and on the craniovertebral angle (CVA) was examined. Outcomes were collected before treatment (0/12), after treatment (1/12), and three months after the end of treatment (4/12). The main analysis comprised a two-way mixed ANOVA with a repeated measures factor (time) and a between-groups factor (group). Post hoc tests assessed the source of significant interactions detected. The significance level was set at p = 0.05. Results: No significant between-group baseline differences were identified. Increases in CS-ROM and in CVA were registered mainly post-treatment, with improvements maintained at follow-up for CS-ROM. EG1 significantly improved over CG in all movement directions except for flexion and over EG2 for extension only, at 1/12 and 4/12. All groups improved by the same amount for CVA. Conclusions: EG1, which included diaphragm manual therapy and breathing re-education exercises, registered the largest overall improvement over CG (except for flexion and CVA), and for extension over EG2. The interaction between respiratory mechanics and neck mobility may provide new therapeutic and assessment insights of patients with NSCNP. Full article

Background: The Nerve Growth Factor (NGF) is essential for neuronal survival and function and represents a key therapeutic target for pain and inflammation-related disorders, as well as for neurodegenerative diseases. Small-molecule antagonists of human NGF (hNGF) offer advantages over monoclonal antibodies, including oral availability and reduced immunogenicity. However, their development is often hindered by solubility challenges, necessitating the use of solvents like dimethyl sulfoxide (DMSO). This study investigates whether DMSO directly interacts with hNGF and affects its receptor-binding properties. Methods: Integrative/hybrid computational and experimental biophysical approaches were used to assess DMSO-NGF interaction by combining machine-learning tools and Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared (FT-IR) spectroscopy, Differential Scanning Fluorimetry (DSF) and Grating-Coupled Interferometry (GCI). These techniques evaluated binding affinity, conformational stability, and receptor-binding dynamics. Results: Our findings demonstrate that DMSO binds hNGF with low affinity in a specific yet non-disruptive manner. Importantly, DMSO does not induce significant conformational changes in hNGF nor affect its interactions with its receptors. Conclusions: These results highlight the importance of considering solvent–protein interactions in drug discovery, as these low-affinity yet specific interactions can affect experimental outcomes and potentially alter the small molecules binding to the target proteins. By characterizing DMSO-NGF interactions, this study provides valuable insights for the development of NGF-targeting small molecules, supporting their potential as effective alternatives to monoclonal antibodies for treating pain, inflammation, and neurodegenerative diseases. Full article

Despite the benefits of resistance training in mitigating sarcopenia, adherence among frail older adults is often limited by osteoarticular pain, comorbidities, and logistical barriers. Pulsed electromagnetic field (PEMF) therapy has emerged as a potential alternative. However, evidence regarding its effects on functional and psychological parameters remains scarce. Objectives: To assess the effects of 12 PEMF therapy sessions on knee extensor strength and functional performance (Timed Up and Go test—TUG) in older adults with sarcopenia. Secondary outcomes included changes in calf circumference (CC), SARC-F + CC scores, and depressive symptoms. Methods: A controlled, non-randomized experimental design was employed, with a pre-intervention control group serving as a baseline reference (PEMF group: n = 25; control group: n = 16). Participants received 12 PEMF therapy sessions (three times per week) targeting the quadriceps and gastrocnemius muscles. Outcomes were measured using knee-extension dynamometry, TUG, CC, SARC-F + CC, and the Yesavage Geriatric Depression Scale. Statistical analyses included ANCOVA, with baseline values as covariates. Results: Significant improvements were observed in knee-extension strength, which increased from 13.05 ± 4.8 kgf to 18.56 ± 8 kgf (p < 0.001); TUG test time improved from 23.1 ± 14.4 to 18.7 ± 10 s (p = 0.048); SARC-F + CC scores decreased from 11.6 ± 8.2 to 6.5 ± 7.6 (p < 0.001), though the interaction effect with time was not significant (p = 0.252). No statistically significant changes were observed in CC, which increased from 34.0 ± 4.0 cm to 36.0 ± 3.9 cm following the intervention (p = 0.548). Yesavage Geriatric Depression Scale scores improved significantly (7.9 ± 2.4 to 5.4 ± 1.7, p = 0.0013). Conclusions: PEMF therapy significantly improved lower-limb muscle strength and functional mobility in elderly individuals with sarcopenia. Additionally, depressive symptoms were significantly reduced. However, no significant changes were observed in CC or SARC-F + CC. Full article

According to our research, the flowers from Citrus grandis ‘Tomentosa’ contain rich biologically active essential oil components, but the chemical components and relative pharmacological properties have not been systematically studied. Therefore, the study aimed to identify the essential oil components by GC-MS/MS and explore the pharmacological activity and mechanism of these essential oil components by a network pharmacology approach. Finally, GC-MS/MS analysis identified 43 essential oil components, which corresponded to 739 potential targets. GO analysis results showed that 12, 18, and 12 entries were related to biological processes, cellular components, and molecular functions, respectively. A total of 120 pathways were obtained based on KEGG analysis, of which the most important was the adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway. The “active component–target–disease” network further demonstrated these essential oil components’ potential efficacy against pain, tumors, neuropsychiatric diseases, eye diseases, and respiratory diseases, which were highly related to PPARA, GABRA1, PTGS2, and SLC6A2. Experimental validation confirmed that β-caryophyllene, a major constituent, dose-dependently inhibited the proliferation of HT29 and MCF-7 cells (0–320 μM). This study provides a reliable basis for elucidating the pharmacological activity of the essential oil components and related mechanisms, which is beneficial to the comprehensive utilization and development of Citrus grandis ‘Tomentosa’. Full article

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. CIPN can lead to a dose reduction and/or the interruption of chemotherapy, limiting its effectiveness, while chronic CIPN decreases patients’ quality of life. Improvements in cancer treatment and patients’ survival have increased the number of patients living with CIPN. The only evidence-based treatment for CIPN-related pain, duloxetine, provides only modest clinical benefit, and there is no effective clinical management option for numbness and tingling. Several experimental studies and clinical reports suggest that adjuvant ozone treatment may be beneficial in managing CIPN. Methods: This narrative review aims to provide an overview of current knowledge regarding CIPN and ozone therapy. Specifically, it summarizes experimental studies (18) and clinical reports (27) published between 1995 and 2025 that offer preliminary evidence supporting the potential role of ozone treatment in managing CIPN, highlighting the need for ongoing randomized clinical trials to establish its efficacy. Additionally, this review highlights existing gaps in the literature and proposes directions for future research. Results: The hypothesized mechanisms of action and experimental findings suggest that ozone therapy may be a valuable intervention for CIPN, a concept supported by preliminary clinical observations. Conclusions: Clinically relevant approaches for established CIPN are currently unavailable. While preliminary data suggest a potential role of ozone therapy, clinical evidence remains limited. Further high-quality randomized controlled trials are needed to confirm its efficacy and safety in this context; several trials are currently ongoing. Full article

Objectives: This study aims to identify the effectiveness of exercise in chronic tension-type headache and chronic migraine. Methods: The PICOS (Population, Intervention, Comparator, Outcomes, Study design) strategy was followed, where P—patients with chronic tension-type headache or chronic migraine; I—exercise; C—conventional treatment; O—pain reduction; and S—RCTs (randomized controlled trials) and quasi-experimental trials. Studies with a high risk of bias according to the RoB 2 (Risk of Bias) scale and with a score < 6 according to the PEDro (Physiotherapy Evidence Database) scale were excluded. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was followed. The databases Pubmed, Web of Science, and Scopus were searched in November 2024. The PEDro and RoB2 scales were used to assess the risk of bias and internal validity of the studies. The results were synthesized qualitatively. Results: Ten studies with a total sample of 848 subjects were analyzed, comparing therapeutic interventions with an exercise versus conventional treatment. In most of the studies, the exercise group significantly outperformed the control group in pain reduction. Discussion: The findings suggest that exercise improves central pain modulation and reinforces the potential of body strategies such as postural integration. The main limitations found were the limited evidence on exercise’s role in chronic tension-type headache or migraine and the risk of bias due to the difficulty of blinding patients, therapists, and evaluators. Conclusions: The studies analyzed have shown that exercise could be an effective strategy to support the management of chronic tension-type headache and migraine. Full article

Objectives: The aim of this study was to investigate the potential anatomical and physiological interconnections between the visual system and the cervical muscular system, as well as to examine the role of the visual system in the etiology and manifestation of cervical musculoskeletal pain or discomfort. Methods: A systematic review was conducted following the PRISMA guidelines, using databases such as PubMed, Scopus, Web of Science, CINAHL, and PEDro. The protocol was registered in PROSPERO. The included study designs comprised experimental studies, randomized controlled trials (RCTs), and pilot RCTs. Results: The literature search was conducted between January and May 2025 and yielded 51 studies across all databases. Seven experimental studies were finally included, all of which met the inclusion criteria and presented a mean methodological quality score of 5 on the PEDro methodological quality scale. The studies included data from a total of 308 participants (n = 261; 84.74% females). Subjects in the intervention group reported cervical pain or visual fatigue. Conclusions: Our results indicated a relationship between visual accommodation and increased electromyographic activity of the trapezius muscle, suggesting that accommodative stress may induce cervical muscle fatigue and pain. Full article