Search Results (51)

Background and Objectives: Acceptance and commitment therapy (ACT) enhances psychological flexibility by fostering acceptance of thoughts and emotions, promoting mindfulness practices, and encouraging engagement in value-based actions. These processes have been associated with improvements in mental health and social functioning, with accumulating evidence supporting ACT’s efficacy across various psychiatric disorders. This systematic review aimed to evaluate current evidence on ACT interventions for reducing psychiatric symptoms and enhancing social functioning and interpersonal relationships in adults with psychiatric conditions. Materials and Methods: A comprehensive search was conducted across PubMed, Web of Science, the Cochrane Library, and Embase for studies published between 2014 and 2024. The review protocol was registered on the Open Science Framework (OSF; registration ID: 2ZAGT). Results: Seventeen studies met the inclusion criteria; however, the evidence base remained fragmented, with most psychiatric diagnoses represented by only one or two studies. The reviewed studies exhibited several methodological limitations, including small sample sizes, lack of randomization and blinding, high risk of bias, reliance on subjective outcome measures, and inadequately designed or absent control groups. Despite these limitations, ACT was associated with beneficial effects in conditions such as post-traumatic stress disorder (PTSD), insomnia, psychosis, and autism spectrum disorder, particularly in reducing experiential avoidance, enhancing mindfulness, and promoting long-term improvements in emotional regulation and life satisfaction. Conclusions: Due to the limited number of studies per diagnosis, significant methodological weaknesses, and the lack of high-quality controlled trials, this review cannot provide strong evidence for the efficacy of ACT in improving social functioning among adults with psychiatric disorders. The heterogeneity and overall low quality of the available literature highlight the urgent need for further large-scale well-controlled studies. Full article

Botulinum toxin is a neurotoxin that is used in the treatments for several medical conditions, such as dystonia, spasticity, hemifacial spasm, overactive bladder, and hyperhidrosis. This toxin can potentially treat several pain disorders through botulinum toxin’s ability to inhibit the release of pro-nociceptive neurotransmitters into the synaptic cleft and its possible action on the central nervous system. This narrative review addresses the use of botulinum toxin in treating primary and secondary headaches and facial pain disorders. The highest level of evidence supporting its use varies among the headache and facial pain disorders: chronic migraine (multicenter, double-blind, placebo-controlled studies), trigeminal neuralgia (double-blind, placebo-controlled studies), post-traumatic headache (double-blind, placebo-controlled study), cluster headache (open-label clinical trials), nummular headache (open-label clinical trial), headache attributed to craniocervical dystonia (prospective cohort study), new daily persistent headache (retrospective cohort study), hemicrania continua, and SUNCT and SUNA (case reports). The site of toxin application and the doses used vary among the studies and depending on headache type. Botulinum toxin has been shown to be safe in different studies, with generally mild adverse reactions. Full article

Traumatic brain injury (TBI) induces complex molecular and cellular responses, often leading to vision deterioration and potential mortality. Current objective diagnostic methods are limited, necessitating the development of novel tools to assess disease severity. This review focuses on the retina, a readily approachable part of the central nervous system (CNS), as a potential indicator of TBI. We conduct a targeted database search and employ a blinded scoring system, incorporating both human and artificial intelligence (AI) assessments, to identify relevant articles. We then perform a detailed analysis to elucidate the molecular pathways and cellular changes in the retina following TBI. Recent findings highlight the involvement of key molecular markers, such as ionized calcium-binding adapter molecule 1 (IBA1), phosphorylated tau, glial fibrillary acidic protein (GFAP), and various cytokines (IL-1β, IL-6, and TNF). Additionally, the roles of oxidative stress, reactive oxygen species (ROS), and blood–retina barrier (BRB) disruption are explored. Based on these findings, we hypothesize that alterations in these molecular pathways and cellular components, particularly microglia, can serve as direct indicators of brain health and TBI severity. Recent technological advancements in retinal imaging now allow for a direct assessment of retinal cells, including microglia, and related inflammatory processes, facilitating the translation of these molecular findings into clinical practice. This review underscores the retina’s potential as a non-invasive window into the molecular pathophysiology of TBI. Full article

Background/Objectives: Distal radius fractures (DRFs) are among the most common fractures in the elderly, with increasing incidence due to population aging. Recent evidence questions the benefits of operative treatment, particularly in elderly patients. The present study aimed to assess post-traumatic osteoarthritis (OA) and patient-reported outcome measures (PROMs) after a minimum of two years of follow-up of the previously published VOLCON randomized controlled trial (RCT), which compared operative and non-operative treatments of unstable DRFs in patients aged ≥ 65 years. Methods: This study presents a minimum two-year follow-up of a single-center, assessor-blinded RCT. A total of 100 patients with unstable DRFs were randomized to either operative treatment with volar locking plating or non-operative treatment with cast immobilization. The primary outcome was post-traumatic OA, assessed using the Knirk and Jupiter classification. Secondary outcomes included PROMs (Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH)) and Patient-Rated Wrist/Hand Evaluation (PRWHE), complications, pain, grip strength, and range of motion (ROM). Statistical analyses were performed using two-way ANOVA. Results: After a median follow-up of 3.0 years, 60 patients (28 non-operative and 32 operative) were available for analysis. There was no significant difference in OA between the groups (p = 0.57). PROMs (Quick-DASH, PRWHE), pain, grip strength, and ROM were time-dependent (p < 0.001) but not treatment-dependent. Complications were more frequent in the operative group, including hardware-related issues requiring reoperation. Conclusions: At a minimum of two years of follow-up, no correlation was found between treatment choice and post-traumatic OA. Functional outcomes were similar between groups, suggesting that non-operative treatment remains a viable option for elderly patients with unstable DRFs. Full article

Background/Objectives: Two of the microvascular complications in type 2 diabetes (T2D) are diabetic retinopathy (DR), which is the most common cause of non-traumatic blindness, and diabetic kidney disease (DKD); the latter generally requires renal replacement therapy. The aim of the present study was to determine the frequency of polymorphisms of Tumor Necrosis Factor-α, interleukin-6, and interleukin-10 (TNF-α, IL-10, and IL-6), as well as to describe the clinical and laboratory characteristics of T2D association with these microvascular complications. Methods: This study included 203 patients with T2D, of which 102 had microvascular complications: 95 with DR, 50 with DKD, and 15 with diabetic neuropathy (the latter were not included in the statistical analysis); those with T2D without confirmed microvascular complications were considered as controls. Clinical and laboratory data were collected from the patient’s medical records. Polymorphism typing of TNF-α rs361525 and rs1800629 and IL-10 rs1800872 and rs1800871 were obtained using MALDI-TOF MS. IL-10 rs1800896 and IL-6 rs1800795 were typed using a quantitative real-time polymerase chain reaction. Results: The results of age, HbA1c, fasting glucose, and arterial hypertension are significantly associated in every group. The TNF-α rs1800629A allele and TNF-α rs1800629G/A genotype were associated with microvascular complications and DR. For IL-10-rs1800896, all the models were associated in DKD. The TNF-α rs361525-rs1800629GA haplotype was associated with microvascular complications and DR, while the IL-10 haplotype, rs1800872-rs1800871-rs1800896 GGC, showed susceptibility in every group. Conclusions: Our results show the contributions of the variants of these cytokines to these microvascular complications, but more studies are required to reach relevant conclusions. Full article

Background/Objectives: Blast-induced traumatic ocular injuries (bTOI) pose a significant risk to military and civilian populations, often leading to visual impairment or blindness. Retina, the innermost layer of ocular tissue consisting of photoreceptor and glial cells, is highly susceptible to blast injuries. Despite its prevalence, the molecular mechanisms underlying retinal damage following bTOI remain poorly understood, hindering the development of targeted therapies. Melatonin, a neuroprotective indoleamine with antioxidant, anti-inflammatory, and circadian regulatory properties, is synthesized in the retina and plays a crucial role in retinal health. Similarly, retina-specific genes, such as Rhodopsin, Melanopsin, and RPE65, are essential for photoreceptor function, visual signaling, and the visual cycle. However, their responses to blast exposure have not been thoroughly investigated. Methods: In this study, we utilized a ferret model of bTOI to evaluate the temporal expression of melatonin-synthesizing enzymes, such as tryptophan hydroxylase 1 and 2 (TPH1 and TPH2), Aralkylamine N-acetyltransferase (AANAT), and Acetylserotonin-O-methyltransferase (ASMT), and retina-specific genes (Rhodopsin, Melanopsin) and retinal pigment epithelium-specific 65 kDa protein (RPE65) at 4 h, 24 h, 7 days, and 28 days post-blast. Ferrets were exposed to tightly coupled blast overpressure waves using an advanced blast simulator, and retinal tissues were collected for quantitative polymerase chain reaction (qPCR) analysis. Results: The results revealed dynamic and multiphasic transcriptional responses. TPH1 and TPH2 exhibited significant upregulation at 24 h, followed by downregulation at 28 days, indicating blast-induced dysregulation of tryptophan metabolism, including melatonin synthesis. Similarly, AANAT and ASMT showed acute downregulation post-blast, with late-phase disruptions. Rhodopsin expression increased at 24 h but declined at 28 days, while Melanopsin and RPE65 demonstrated early upregulation followed by downregulation, reflecting potential disruptions in circadian regulation and the visual cycle. Conclusions: These findings highlight the complex regulatory mechanisms underlying retinal responses to bTOI, involving neuroinflammation, oxidative stress, and disruptions in melatonin synthesis and photoreceptor cell functions. The results emphasize the therapeutic potential of melatonin in mitigating retinal damage and preserving visual function. Full article

Background: The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses atypical nevi (AN) and early-stage melanomas (EN) displaying overlapping clinical and dermoscopic features. This often generates unnecessary excisions or delayed diagnosis. Investigations to date were mostly carried out in specific populations, focusing either on acrolentiginous melanomas or morphologically typical acquired nevi. Aims: To investigate the dermoscopic features of atypical melanocytic palmoplantar skin lesions (aMPPLs) as evaluated by variously skilled dermatologists and assess their concordance; to investigate the variations in dermoscopic appearance according to precise location on palms and soles; to detect the features with the strongest association with malignancy/benignity in each specific site. Methods: A dataset of 471 aMPPLs—excised in the suspect of malignancy—was collected from 10 European Centers, including a standardized dermoscopic picture (17×) and lesion/patient metadata. An anatomical classification into 17 subareas was considered, along with an anatomo-functional classification considering pressure/friction, (4 macroareas). A total of 156 participants (95 with less than 5 years of experience in dermoscopy and 61 with ≥than 5 years) from 17 countries performed a blinded tele-dermoscopic pattern analysis over 20 cases through a specifically realized web platform. Results: A total of 37,440 dermoscopic evaluations were obtained over 94 (20%) EM and 377 (80%) AN. The areas with the highest density of EM compared to AN were the heel (40.3% EM/aMPPLs) of the sole and the “fingers area” (33%EM/aMPPLs) of the palm, both characterized by intense/chronic traumatism/friction. Globally, the recognition rates of 12 dermoscopic patterns were non statistically different between 95 dermatology residents and 61 specialists: aMPPLs in the plantar arch appeared to be the most “difficult” to diagnose, the parallel ridge pattern was poorly recognized and irregular/regular fibrillar patterns often misinterpreted. Regarding the aMPPL of the “heel area”, the parallel furrow pattern (p = 0.014) and lattice-like pattern (p = 0.001) significantly discriminated benign cases, while asymmetry of colors (p = 0.002) and regression structures (p = 0.025) malignant ones. In aMPPLs of the “plantar arch”, the lattice-like pattern (p = 0.012) was significant for benignity and asymmetry of structures, asymmetry of colors, regression structures, or blue-white veil for malignancy. In palmar lesions, no data were significant in the discrimination between malignant and benign aMPPLs. Conclusions: This study highlights that (i) the pattern analysis of aMPPLs is challenging for both experienced and novice dermoscopists; (ii) the histological distribution varies according to the anatomo-functional classification; and (iii) different dermoscopic patterns are able to discriminate malignant from benign aMPPLs within specific plantar and palmar areas. Full article

Background: Anterior cruciate ligament (ACL) tears account for 40% to 50% of all ligamentous knee injuries. Most patients with ACL ruptures undergo surgical treatment. There is currently no objective, well-documented, repeatable, and standardized nonsurgical method for ACL tear treatment. This study aimed to investigate ACL outcomes in patients who underwent a novel nanosurgery and bioengineering treatment (NSBT) for an ACL tear. Methods: This was a double-blind randomized trial including 44 patients with a history of traumatic knee injury and a confirmed ACL tear. The final sample comprised 40 patients who met all the eligibility criteria. The patients were divided into two groups: the treatment group (n = 30) and the control group (n = 10). The treatment group underwent nanosurgery with an ultrasound-guided injection of modified platelet-rich plasma (PRP) using human cell memory (RP-hCM). The control group was treated with an ultrasound-guided PRP injection into the joint capsule. At baseline and post-treatment, all patients underwent both ultrasonography and magnetic resonance imaging (MRI), and the following clinical variables were assessed: the WOMAC score, the Lysholm knee score, the visual analog scale score, and knee instability. In most patients, the clinical outcome was verified using nanoscopy. Results: The median WOMAC, VAS, and LKS scores, as well as knee instability, improved significantly 12 weeks after the procedure in the treatment group (p < 0.001). We found a significantly larger improvement in the assessed parameters in the treatment group compared to the control group (p < 0.001). In the treatment group, all the patients had good and very good clinical outcomes, while 90% of the patients had a normal ACL signal in a follow-up MRI scan. In the control group, a physical examination revealed no changes in knee stability after treatment. Conclusions: This study showed that there is a significant difference in patient experience and the duration of recovery for patients with ACL tears treated with NSBT. The novel nonsurgical method was shown to be repeatable, objective, well documented, standardized, and highly effective. Full article

In a completely locked-in state (CLIS), often resulting from traumatic brain injury or neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), patients lose voluntary muscle control, including eye movement, making communication impossible. Brain-computer interfaces (BCIs) offer hope for restoring communication, but achieving reliable communication with these patients remains a challenge. This study details the design, testing, and comparison of nine visuo-auditory P300-based BCIs (combining different visual and auditory stimuli and different visual layouts) with a CLIS patient over ten months. The aim was to evaluate the impact of these stimuli in achieving effective communication. While some interfaces showed promising progress, achieving up to 90% online accuracy in one session, replicating this success in subsequent sessions proved challenging, with the average online accuracy across all sessions being 56.4 ± 15.2%. The intertrial variability in EEG signals and the low discrimination between target and non-target events were the main challenge. Moreover, the lack of communication with the patient made BCI design a challenging blind trial-and-error process. Despite the inconsistency of the results, it was possible to infer that the combination of visual and auditory stimuli had a positive impact, and that there was an improvement over time. Full article

(1) Background: Traumatic brain injury (TBI) often results in cognitive impairments, including in visuospatial planning and executive function. Methylphenidate (MPh) demonstrates potential improvements in several cognitive domains in patients with TBI. The Tower of London (TOL) is a visuospatial planning task used to assess executive function. (2) Methods: Volunteers with a history of TBI (n = 16) participated in a randomised, double-blinded, placebo-controlled, fMRI study to investigate the neurobiological correlates of visuospatial planning and executive function, on and off MPh. (3) Results: Healthy controls (HCs) (n = 18) and patients on placebo (TBI-placebo) differed significantly in reaction time (p < 0.0005) and accuracy (p < 0.0001) when considering all task loads, but especially for high cognitive loads for reaction time (p < 0.001) and accuracy (p < 0.005). Across all task loads, TBI-MPh were more accurate than TBI-placebo (p < 0.05) but remained less accurate than HCs (p < 0.005). TBI-placebo substantially improved in accuracy with MPh administration (TBI-MPh) to a level statistically comparable to HCs at low (p = 0.443) and high (p = 0.175) cognitive loads. Further, individual patients that performed slower on placebo at low cognitive loads were faster with MPh (p < 0.05), while individual patients that performed less accurately on placebo were more accurate with MPh at both high and low cognitive loads (p < 0.005). TBI-placebo showed reduced activity in the bilateral inferior frontal gyri (IFG) and insulae versus HCs. MPh normalised these regional differences. MPh enhanced within-network connectivity (between parietal, striatal, insula, and cerebellar regions) and enhanced beyond-network connectivity (between parietal, thalamic, and cerebellar regions). Finally, individual changes in cerebellar-thalamic (p < 0.005) and cerebellar-parietal (p < 0.05) connectivity with MPh related to individual changes in accuracy with MPh. (4) Conclusions: This work highlights behavioural and neurofunctional differences between HCs and patients with chronic TBI, and that adverse differences may benefit from MPh treatment. Full article

Background: Traffic injuries include acute low back pain (LBP) needing active treatment to prevent chronicity. This two-armed, parallel, assessor-blinded, randomized controlled trial evaluated the effectiveness and safety of progressive loading–motion style acupuncture treatment (PL-MSAT) for acute LBP following traffic accidents. Methods: Based on an effect size of 1.03, 104 participants were recruited and divided in a 1:1 ratio into PL-MAST and control groups using block randomization. Both groups underwent integrative Korean medicine treatment (IKMT) daily; only the PL-MSAT group underwent three PL-MSAT sessions. The outcomes were assessed before and after the treatment sessions and at 1 and 3 months post-discharge. The primary outcome was the difference in the numeric rating scale (NRS) for LBP. The secondary outcomes included a visual analog scale for LBP, leg pain status, the Oswestry disability index, lumbar active range of motion (ROM), quality of life, Patient Global Impression of Change, and Post-Traumatic Stress Disorder Checklist adverse events. Results: In the modified intention-to-treat analysis, 50 and 51 participants were included in the PL-MSAT and control groups. On Day 4, the mean LBP NRS score was 3.67 (3.44–3.90) in the PL-MSAT group, indicating a significantly lower NRS 0.77 (0.44–1.11) compared to 4.44 (4.20–4.68) for the control group (p < 0.001). The PL-MSAT group exhibited greater ROM flexion (−5.31; −8.15 to −2.48) and extension (−2.09; −3.39 to −0.80). No significant differences were found for the secondary outcomes and follow-ups. Conclusions: Compared with IKMT alone, PL-MSAT plus IKMT showed significantly better outcomes for reducing pain and increasing the ROM in acute LBP. Full article

Glaucoma is a chronic neurodegenerative disorder affecting the visual system which can result in vision loss and blindness. The pathogenetic mechanisms underlying glaucomatous optic neuropathy are ultimately enigmatic, prompting ongoing investigations into its potential shared pathogenesis with other neurodegenerative neurological disorders. Tauopathies represent a subclass of neurodegenerative diseases characterized by the abnormal deposition of tau protein within the brain and consequent microtubule destabilization. The extended spectrum of tauopathies includes conditions such as frontotemporal dementias, progressive supranuclear palsy, chronic traumatic encephalopathy, and Alzheimer’s disease. Notably, recent decades have witnessed emerging documentation of tau inclusion among glaucoma patients, providing substantiation that this ocular disease may similarly manifest features of tauopathies. These studies found that: (i) aggregated tau inclusions are present in the somatodendritic compartment of RGCs in glaucoma patients; (ii) the etiology of the disease may affect tau splicing, phosphorylation, oligomerization, and subcellular localization; and (iii) short interfering RNA against tau, administered intraocularly, significantly decreased retinal tau accumulation and enhanced RGC somas and axon survival, demonstrating a crucial role for tau modifications in ocular hypertension-induced neuronal injury. Here, we examine the most recent evidence surrounding the interplay between tau protein dysregulation and glaucomatous neurodegeneration. We explore the novel perspective of glaucoma as a tau-associated disorder and open avenues for cross-disciplinary collaboration and new treatment strategies. Full article

“Nonspecific shoulder pain” encompasses various non-traumatic musculoskeletal shoulder disorders, diverging from diagnostic terminologies that refer to precise tissue-oriented clinical diagnosis. Blood flow restriction (BFR) training, involving partial arterial inflow and complete venous outflow restriction, has exhibited acute hypoalgesic effects primarily in healthy populations by increasing their pain thresholds. This study aims to examine whether a single BFR session with low-load exercises can alleviate pain perception among nonspecific shoulder pain patients. Conducted as a single-blind crossover randomised clinical trial, 48 adults (age range: 18 to 40) presenting with nonspecific shoulder pain will partake in two trial sessions. Random assignment will place participants into BFR or sham BFR groups and ask them to perform one exercise with BFR. Subsequently, participants will complete a shoulder girdle loading regimen comprising six exercises. The second session will involve participants switching treatment groups. Pain pressure thresholds (PPTs), shoulder pain and disability via the shoulder pain and disability index (SPADI), maximal voluntary isometric contraction (MVIC) of shoulder external rotators, pain during active abduction, and peak pain during shoulder external rotation will be evaluated using the numeric pain rating scale (NPRS). Immediate post-exercise assessments will include patient-perceived pain changes using the global rating of change scale (GROC) and participant-rated perceived exertion (RPE), employing a modified Borg’s scale (Borg CR10) post-BFR or sham BFR exercise session. Each session will encompass three assessment periods, and a combination of mixed-effect models and descriptive statistics will underpin the analysis. This protocol was approved by Cyprus National Bioethics Committee (ΕΕΒΚ/2023/48), and was registered in ClinicalTrials.gov (Registration number: NCT05956288). Conclusion: The anticipated outcomes of this study illuminated the acute effects of BFR training on pain perception within the context of nonspecific shoulder pain, potentially advancing strategies for managing pain intensity using BFR techniques. Full article

The use of high-frequency Transcranial Magnetic Stimulation (HF-rTMS) of the right dorsolateral prefrontal cortex (DLPFC) in treating Post-traumatic Stress Disorder (PTSD) is currently regarded as a level B intervention (probable effectiveness). HF-rTMS has attracted interest as a neuromodulation therapeutic method for PTSD. Prolonged exposure and reactivation therapy are also regarded as first-line treatments for PTSD. Randomized controlled clinical studies examining the effectiveness of several HF-rTMS sessions coupled with psychotherapy have not yet been completed. In total, 102 patients with refractory PTSD will be randomly assigned (1:1) to reactivation therapy, in addition to either active HF-rTMS (20 Hz) or sham HF-rTMS, for 12 sessions in a nationwide, multicenter, double-blind controlled trial. The impact on PTSD symptoms and neurocognitive functioning will be assessed. The primary outcome is the PTSD severity score measured based on the Clinician-Administered PTSD Scale (CAPS-5) at one month. If this additional therapy is successful, it may strengthen the case for regulatory authorities to approve this additional technique of treating PTSD. Additionally, it expands the field of neurostimulation-assisted psychotherapy. Full article

Mild traumatic brain injury (mTBI) represents a significant burden for individuals, economies, and healthcare systems worldwide. Recovery protocols focus on medication and physiotherapy-based interventions. Animal studies have shown that antioxidants, branched-chain amino acids and omega-3 fatty acids may improve neurophysiological outcomes after TBI. However, there appears to be a paucity of nutritional interventions in humans with chronic (≥1 month) symptomology post-mTBI. This systematic literature review aimed to consolidate evidence for nutrition and dietary-related interventions in humans with chronic mTBI. The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021277780) and conducted following the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three reviewers searched five databases (PubMed/MEDLINE, Web of Science, SPORTDiscus, CINAHL Complete and Cochrane), which yielded 6164 studies. Nine studies met the inclusion criteria. The main finding was the lack of interventions conducted to date, and a quality assessment of the included studies was found to be fair to good. Due to heterogeneity, a meta-analysis was not feasible. The six nutrition areas identified (omega-3 fatty acids, melatonin, Enzogenol^®, MLC901, ketogenic diet and phytocannabinoids) were safe and well-tolerated. It was found that these nutritional interventions may improve cognitive failures, sleep disturbances, anxiety, physical disability, systolic blood pressure volume and sport concussion assessment tool scores following mTBI. Potential areas of improvement identified for future studies included blinding, reporting compliance, and controlling for confounders. In conclusion, further research of higher quality is needed to investigate the role of nutrition in recovery from mTBI to reduce the burden of chronic outcomes following mTBI. Full article