Search Results (38)

Genetic variability in terrestrial mammals is essential for understanding population and evolutionary dynamics, as well as for establishing effective strategies in conservation biology. This comprehensive review aimed to critically analyze invasive and non-invasive techniques used to assess genetic variability in wild terrestrial mammals. Using the PICO (Population, Intervention, Comparison, Outcome) format and following PRISMA guidelines, a comprehensive literature search was conducted in Web of Science, Scopus and Science Direct databases, including articles published in English from January 2015 to April 2025. Thirty-one experimental studies were selected that met specific criteria related to genetic evaluation using invasive (direct blood or tissue collection) and non-invasive (stool, hair and saliva collection) techniques. The results indicate that invasive techniques provide samples of high genetic quality, albeit with important ethical and animal welfare considerations. In contrast, non-invasive techniques offer less disruptive methods, although they present significant challenges in terms of quantity and purity of DNA obtained, potentially affecting the accuracy and confidence of genetic analysis. Detailed analysis of selected studies showed diverse patterns of heterozygosity and inbreeding coefficients between different taxonomic orders (Carnivora, Artiodactyla, Proboscidea, Primates and Rodentia). In addition, the main anthropogenic threats and current conservation strategies implemented in different species were identified. An overall genetic variability ranging from high to moderate was observed, with large species being more vulnerable to genetic reduction due to changes in habitat and human activities. Rather than a static comparison, our synthesis traces a clear methodological arc from small short tandem repeats (STR, or microsatellites) panels towards SNP-based approaches enabled by next-generation sequencing, including reduced representation (ddRAD), amplicon panels (GT-seq), and hybridisation capture tailored to degraded DNA from hair, faeces, and environmental substrates. Over 2015–2025, study designs shifted from presence/absence and coarse diversity estimates to robust inference of relatedness, assignment, effective population size, and gene flow using hundreds–thousands of SNPs and genotype-likelihood frameworks tolerant of allelic dropout and low coverage. Laboratory practice converged on multi-tube replication, synthetic blocking oligos, and capture-based enrichment; bioinformatics adopted probabilistic genotype calling, error-aware filtering, and replication-based consensus. This review provides a solid basis for optimizing genetic sampling methods, allowing for more ethical and efficient studies. Furthermore, it contributes to strengthening conservation strategies by underlining the importance of adapting the sampling method to the biological and ecological particularities of each species studied. Ultimately, these findings can significantly improve genetic conservation decision-making, benefiting the sustainability and resilience of wild land mammal populations. Full article

Background/Objectives: Dysregulated gamma oscillations are associated with cognitive dysfunction. Auditory stimulation at 40 Hz enhances neural activity in brain regions associated with learning, attention, and memory. This study assessed the safety and acceptability of 40 Hz amplitude-modulated auditory stimulation in healthy older people. Auditory stimuli were created using popular songs, where vocals and background music were separated and independently amplitude-modulated at 40 Hz with different modulation depths to generate periodic 40 Hz gamma waveforms. Methods: In this open-label, single-arm study, healthy participants aged ≥65 years received 40 Hz amplitude-modulated auditory stimulation daily via a smartphone for 28 days through earphones/headphones. Safety was assessed through adverse event (AE) monitoring and changes in clinical scores for depression, cognitive function, and hearing thresholds. Acceptability was evaluated by adherence rates, listening time, dropout reasons, volume levels, intent for future use, and subjective impressions of the sound source on a 7-point Likert scale. Results: Among 28 participants (mean age 69.1 years, 53.6% female), six reported 12 AEs, with six considered device-related (e.g., ear discomfort, jaw pain, musculoskeletal stiffness). The AEs observed were mild or moderate. Scores for cognitive function, depression, and hearing thresholds did not worsen during the study period. Adherence was observed in 96.4%, with 85.7% expressing interest in continuing. Most participants rated the sounds’ unnaturalness between 2 and 3 and discomfort between 1 and 3 on the 7-point Likert scale. Conclusions: The intervention was well tolerated and acceptable in study participants, with no major safety concerns identified. Auditory stimulation did not cause severe discomfort or reduce acceptability. Further studies should explore the long-term effects and broader clinical applications. Full article

Background/Objectives: Psychogenic non-epileptic seizures (PNES) are seizure-like episodes not caused by abnormal brain activity, often linked to emotional dysregulation, dissociation, and altered interoceptive awareness. Standardized treatments are limited. This study aimed to explore the feasibility and preliminary psychological effects of a group-based mindfulness-based intervention (MBI) in individuals with PNES. Methods: This single-arm, pre–post pilot study (no control group) enrolled fifteen participants in two cycles of an 8-week MBI delivered either in-person or online. Twelve participants completed pre/post self-report assessments of depression (BDI-II), anxiety (STAI-Y1), perceived stress (PSS-10), sleep quality (PSQI), dissociation (DES-II), meteoropathy (METEO-Q), mindfulness (FFMQ), and interoceptive awareness (MAIA). Results: The intervention was well tolerated (dropout rate: 20%). Trend-level, non-significant improvements emerged for depressive symptoms (p = 0.092, r = 0.564) and sleep quality (p = 0.078, r = 0.591). A significant reduction was observed in the FFMQ Describing subscale (p = 0.045, r = 0.697). No significant changes were found in anxiety, perceived stress, or interoceptive awareness, although certain MAIA subscales indicated small, non-significant increases. Conclusions: Despite the limited sample size and absence of a control group, these preliminary findings support the feasibility and acceptability of MBIs for PNES, warranting further controlled investigations. Full article

Recent progress in computer vision and embedded systems has facilitated real-time monitoring of bioprocesses; however, lightweight and scalable solutions for resource-constrained settings remain limited. This work presents a modular framework for monitoring Chlorella vulgaris growth by integrating RGB image processing with multimodal sensor fusion. The system incorporates a Logitech C920 camera and low-cost pH and temperature sensors within a compact photobioreactor. It extracts RGB channel statistics, luminance, and environmental data to generate a 10-dimensional feature vector. A feedforward artificial neural network (ANN) with ReLU activations, dropout layers, and SMOTE-based data balancing was trained to classify growth phases: lag, exponential, and stationary. The optimized model, quantized to 8 bits, was deployed on an ESP32 microcontroller, achieving 98.62% accuracy with 4.8 ms inference time and a 13.48 kB memory footprint. Robustness analysis confirmed tolerance to geometric transformations, though variable lighting reduced performance. Principal component analysis (PCA) retained 95% variance, supporting the discriminative power of the features. The proposed system outperformed previous vision-only methods, demonstrating the advantages of multimodal fusion for early detection. Limitations include sensitivity to lighting and validation limited to a single species. Future directions include incorporating active lighting control and extending the model to multi-species classification for broader applicability. Full article

We investigate the stability of linear discrete-time control systems with a fuzzy logic feedback under sporadic sensor data loss. In our framework, each state measurement is a fuzzy number, and occasional “packet dropouts” are modeled by a lacunary subsequence of missing readings. We introduce a novel mathematical approach using lacunary statistical convergence in fuzzy paranormed spaces to analyze such systems. Specifically, we treat the sequence of fuzzy measurements as a double sequence (indexed by time and state component) and consider an admissible ideal of “negligible” index sets that includes the missing–data pattern. Using the concept of ideal fuzzy—paranorm convergence (I-fp convergence), we formalize a lacunary statistical consistency condition on the fuzzy measurements. We prove that if the closed-loop matrix $A-BK$ is Schur stable (i.e., $\parallel A-BK\parallel <1$) in the absence of dropouts, then under the lacunary statistical consistency condition, the controlled system is practically stable despite intermittent measurement losses. In other words, for any desired tolerance, the state eventually remains within that bound (though not necessarily converging to zero). Our result yields an explicit, non-probabilistic (distribution-free) analytical criterion for robustness to sensor dropouts, without requiring packet-loss probabilities or Markov transition parameters. This work merges abstract convergence theory with control application: it extends statistical and ideal convergence to double sequences in fuzzy normed spaces and applies it to ensure stability of a networked fuzzy control system. 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: Limited access to pulmonary rehabilitation (PR) has contributed to the rise of telerehabilitation (TPR) for COPD patients. Positive comparable effects are observed in exercise tolerance, quality of life (QoL), and dyspnoea with TPR. However, patient adherence to TPR is an outcome that has not been sufficiently analysed. Objective: To analyse adherence, satisfaction, and quality-of-life improvements in COPD patients following the TPR program to determine whether telerehabilitation is comparable to conventional therapy or usual care. Methods: A systematic search was conducted using four electronic databases, retrieving 392 articles. Two independent researchers selected and evaluated these articles based on predefined eligibility criteria. A third researcher was consulted in the event of disagreements. Results: Primary outcomes: Adherence to PR and/or usual care showed a minimum reported value of 62% and a maximum reported value of 91%, while TPR adherence had the lowest reported value of 21% and the highest reported value of 93.5%. Five articles compared TPR to PR and/or usual care, showing that TPR adherence is higher or similar to other interventions, whereas only one article found lower TPR adherence compared to PR. Secondary outcomes: A higher number of dropouts were reported for PR and usual care compared to TPR. Three publications analysed satisfaction and demonstrated that patients are satisfied across groups. Tertiary outcomes: Comparable improvements in QoL were found for TPR and PR, both being superior to usual care. Conclusions: This systematic review reveals heterogeneity in classifying adherence for pulmonary rehabilitation and telerehabilitation. Adherence classification may be standardised in future studies for consistent analysis. Full article

Background: Alcohol use disorder in the context of heroin addiction presents a significant challenge for clinicians, particularly in selecting the most appropriate pharmacological treatment. Methods: The present study aimed to retrospectively evaluate the efficacy of a six-month methadone maintenance (MM)/sodium oxybate (SMO) combination treatment in reducing ethanol intake among chronic alcohol-dependent patients with heroin use disorder (HUD). Specifically, we compared outcomes between those who continued SMO treatment after alcohol detoxification (MM/SMO-Maintained) and those who discontinued it (MM/SMO-Detoxified). Data were recruited using the ‘Pisa Addiction Database’ through a retrospective, naturalistic, cross-sectional comparative design involving a single patient assessment. Results: Our results indicate that treatment retention was higher in the MM/SMO-Maintained group. Conversely, discontinuing SMO treatment after alcohol detoxification was associated with a higher likelihood of dropout. At the endpoint, the MM/SMO-Maintained group showed significant improvement and was considered less severely ill. Conclusions: Long-term SMO treatment has proven to be well tolerated and effective in preventing relapse in individuals with both alcohol and HUD undergoing agonist opioid treatment. SMO may be considered the closest pharmacological option to substitution therapy for alcohol use disorder, and ongoing agonist opioid treatment should not preclude its co-administration. Full article

Background: Borderline Personality Disorder (BPD) is a severe psychiatric condition characterized by pervasive emotional dysregulation, impulsivity, and unstable interpersonal relationships. Affecting over 1% of the general population, BPD carries significant morbidity, frequent hospitalizations, and an increased risk of suicide. Although specialized psychotherapeutic approaches have shown efficacy, their impact is often constrained by availability, lengthy treatment durations, moderate effect sizes, and high dropout rates. Pharmacological treatments for BPD remain inadequate and are usually accompanied by adverse side effects. Objective: This narrative review seeks to explore the potential of transcranial direct current stimulation (tDCS) as a safe, cost-effective, and accessible neuromodulation intervention aimed at alleviating core BPD symptoms—namely, emotional dysregulation and impulsivity—while also addressing common comorbidities and opportunities for integration with existing therapeutic modalities. Methods: We conducted a narrative literature synthesis in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines. A PubMed/MEDLINE search was performed using keywords related to transcranial direct current stimulation (tDCS) and BPD, identifying five published randomized controlled trials on the topic. To provide a broader perspective, we also included studies from related fields examining mechanisms of action, safety and tolerability, cost-effectiveness, stimulation parameters, and clinical outcomes relevant to BPD. Results: Conventional tDCS protocols—typically involving 1–2 mA currents for 20–30 min—have demonstrated an excellent safety profile, resulting in only minimal and transient side effects without any risk of overdose or misuse, which is a key advantage for populations at high risk of suicidality. With moderately priced devices and the feasibility of home-based administration, tDCS provides a substantially more affordable alternative to both long-term pharmacotherapy and intensive psychotherapy. Neurobiologically, tDCS modulates the excitability of the dorsolateral and ventrolateral prefrontal cortex and enhances fronto-limbic connectivity, thereby strengthening top-down regulatory control over emotion and behavior. Pilot randomized controlled trials report moderate effect sizes for improvements in emotional regulation, inhibitory control, and rejection sensitivity, along with ancillary gains in executive functioning and reductions in depressive and substance-use symptoms when stimulating the left dorsolateral prefrontal cortex. Conclusions: tDCS stimulation emerges as a safe and scalable adjunctive treatment for BPD, leveraging targeted neuromodulation to address core features and common comorbidities like depression. However, variability in current protocols and the scarcity of well-powered randomized trials underscore the pressing need for standardized methodologies, longer-term follow-up, and individualized stimulation strategies to establish enduring clinical benefits. Full article

Background: Youth (ages 16–25) is a key window for mental health interventions, as depression rates significantly increase during this developmental stage. However, transcranial direct current stimulation (tDCS) application in youth depression remains underexplored. To reduce the uncertainty of a future trial, we conducted a review and a pilot randomised controlled trial (RCT) of tDCS for youth depression. Methods: Following the PRISMA guidelines, the first part of this study was a review across databases including PubMed, MEDLINE, PsychInfo, CINAHL, Open Access Theses and Dissertations (OATD), WanFang Data, Chinese Medical Journal, and clinical trial registries up to 20 November 2024, on tDCS treatment for youth depression. The second part of this study was a double-blind pilot RCT assessing feasibility, by comparing active tDCS (five daily 30 min 2 mA anodal tDCS applications over the left dorsolateral–pre-frontal-cortex (DLPFC) with sham tDCS. Feasibility outcomes included recruitment, data collection, attendance, retention and randomisation. Outcomes also included depression severity using the Hamilton Depression Rating Scale (HDRS), safety, tolerability, acceptability, and adequacy of blinding. Mann–Whitney U tests were used for between-group comparison. Results: Fourteen eligible studies were identified, with a pooled HDRS reduction of −9.6 (95% CI: −11.2 to −8.1, p < 0.001), though high risks of bias indicated a research gap. Using parameters derived from the review, we conducted a pilot RCT in which 20 youths were screened and 8 were randomised (aged 16–24; 3 females, 5 males). All randomised participants completed their assigned sessions without dropout or protocol discontinuations. Blinding was adequate, and participants’ willingness to engage improved over time. Both groups showed reductions in HDRS, with a greater mean reduction in the active group (−4.75 ± 2.96) compared to the sham group (−3.75 ± 3.78). No serious adverse events occurred, with only mild headaches and tingling reported. The tolerability profile was comparable. However, the decentralised administration of sessions may have introduced inconsistent tDCS applications. Conclusions: This review highlights a lack of RCTs on tDCS for youth depression. Our pilot trial demonstrates the feasibility of a sham-controlled design in youth depression, justifying larger-scale trials to evaluate the efficacy of tDCS in this population. Full article

Objective: To assess the effects of a two-week course of intensive impairment-oriented arm rehabilitation for chronic stroke survivors on motor function. Methods: An observational cohort study that enrolled chronic stroke survivors (≥6 months after stroke) with mild to severe arm paresis, who received a two-week course of impairment-oriented and technology-supported arm rehabilitation (1:1 participant–therapist setting), which was carried out daily (five days a week) for four hours. The outcome measures were as follows: the primary outcome was the arm motor function of the affected arm (mild paresis: BBT, NHPT; severe paresis: Fugl-Meyer arm motor score). The secondary outcomes were measures of finger strength, active ROM, spasticity, joint mobility/pain, somatosensation, emotional distress, quality of life, acceptability, and adverse events. Results: One hundred chronic stroke survivors (≥6 months after stroke) with mild to severe arm paresis were recruited. The training was acceptable (drop-out rate 3%; 3/100). The clinical assessment indicated improved motor function (SMD 0.42, 95% CI 0.36–0.49; n = 97), reduced spasticity/resistance to passive movement, and slightly improved joint mobility/pain and somatosensation. The technology-based objective measures corroborated the improved active range of motion for arm and finger joints, reduced finger spasticity/resistance to passive movement, and the increased amount of use in daily life, but there was no effect on finger strength. The patient’s emotional well-being and quality of life were positively influenced. Adverse events were reported by the majority of participants (51%, 49/97) and were mild. Conclusions: Structured intensive impairment-oriented and technology-supported arm rehabilitation can promote motor function among chronic stroke survivors with mild to severe arm paresis and is an acceptable and tolerable form of treatment when supervised and adjusted by therapists. Full article

Background/Objectives: As long-term prescription opioid use is associated with increased morbidity and mortality, timely dose reduction of prescription opioids should be considered. However, most research has been conducted on patients using heroin. Given the differences between prescription and illicit opioid use, the aim of this review was to provide an overview of pharmacological strategies to reduce prescription opioid use or improve clinical outcomes for people who experience long-term prescription opioid use, including those with opioid use disorder. Methods: We conducted a systematic database search of PubMed, Embase, CINAHL, and the Cochrane Library. Outcomes included dose reduction, treatment dropout, pain, addiction, and outcomes relating to quality of life (depression, functioning, quality of life). Results: We identified thirteen studies (eight randomized controlled trials and five observational studies). Pharmacological strategies were categorized into two categories: (1) deprescribing (tapering) opioids or (2) opioid agonist treatment (OAT) with long-acting opioids. Tapering strategies decreased opioid dosage and had mixed effects on pain and addiction. OAT with buprenorphine or methadone led to improvements in pain relief and quality of life, with a slight (non-significant) preference for methadone in terms of treatment retention (RR = 1.10 [CI: 0.89–1.37]) but not for other outcomes. Most studies had high dropout rates and a serious risk of bias. Conclusions: Tapering reduced prescription opioid doses had mixed effects on pain. OAT improved clinical outcomes without dose reduction. Based on our review findings, there is no clear preference for either tapering or OAT. Tapering may be considered first as it reduces dependency, tolerance, and side effects, but is associated with adverse events and not always feasible. OAT can be a suitable alternative. Non-pharmacological interventions may facilitate tapering. Further research is needed to identify novel pharmacological strategies to facilitate opioid tapering. Registration: PROSPERO 2022 CRD42022323468. Full article

Obstructive sleep apnea (OSA) is a sleep disorder characterized by repetitive episodes of partial or complete obstruction of the upper airway during sleep. Continuous positive airway pressure (CPAP) is a method used as a first-line treatment for obstructive sleep apnea (OSA). However, intolerance and resistance to CPAP can limit its long-term effectiveness. Alternative treatments are available, such as Mandibular Advancement Devices (MADs), positional therapy, upper airway surgery, and maxillomandibular osteotomy. However, often less efficient in reducing the apnea-hypopnea index, the higher tolerance of and compliance to alternative treatment has resulted in the adequate treatment of OSA in CPAP-intolerant patients. This paper describes the protocol of a prospective single-center cohort study including adult patients with moderate to severe OSA (15 events/h ≤ apnea-hypopnea index (AHI) < 65 events/h) that failed to comply with CPAP therapy. Selected patients will be invited to the clinic to explore alternative treatment options where DISE will be a first step in further identifying upper airway collapse during sleep. By exploring alternative treatment options in CPAP-intolerant patients and systematically documenting their treatment paths, an algorithm can be defined to better guide patients towards personalized treatment for OSA. The follow-up is aimed at 5 years with an inclusion of 170 patients per year, including a drop-out rate of 15%. By leveraging a real-world database, this study aims to bridge the gap between research and clinical practice, facilitating the development of evidence-based guidelines and personalized treatment algorithms for CPAP-intolerant patients. Full article

Background: A drug repositioning effort supported the possible use of the anti-HIV drug etravirine as a disease-modifying drug for Friedreich ataxia (FRDA). Etravirine increases frataxin protein and corrects the biochemical defects in cells derived from FRDA patients. Because of these findings, and since etravirine displays a favorable safety profile, we conducted a pilot open-label phase 2 clinical trial assessing the safety and potential efficacy of etravirine in FRDA patients. Methods: Thirty-five patients were stratified into three severity groups and randomized to etravirine 200 mg/day or 400 mg/day. They were treated for 4 months. Safety endpoints were the number and type of adverse events and number of dropouts. Efficacy endpoints were represented by changes in peak oxygen uptake and workload as measured by incremental exercise test, SARA score, cardiac measures, measures of QoL and disability. Data were collected 4 months before the start of the treatment (T − 4), at the start (T0), at the end (T4) and 4 months after the termination of the treatment (T + 4). Results: Etravirine was reasonably tolerated, and adverse events were generally mild. Four months of etravirine treatment did not significantly increase the peak oxygen uptake but was associated with a change in the progression of the SARA score (p value < 0.001), compared to the 4 months pre- and post-treatment. It also significantly increased peak workload (p value = 0.021). No changes in the cardiac measures were observed. Health and QoL measures showed a worsening at the suspension of the drug. Conclusions: In this open trial etravirine treatment was safe, reasonably well tolerated and appreciably improved neurological function and exercise performance. Even though a placebo effect cannot be ruled out, these results suggest that etravirine may represent a potential therapeutic agent in FRDA deserving testing in a randomized placebo-controlled clinical trial. Full article

There are varying data concerning the effect of prior anti-vector immunity on the T-cell response induced by immunisation with an identical vectored vaccine containing a heterologous antigen insert. To determine whether prior exposure to ChAdOx1-SARS-CoV2 immunisation (Vaxzevria^®) impacts magnitudes of antigen-specific T-cell responses elicited by subsequent administration of the same viral vector (encoding HBV antigens, ChAdOx1-HBV), healthy volunteers that had received Vaxzevria^® (n = 15) or the Pfizer or Moderna mRNA COVID-19 vaccine (n = 11) between 10 and 18 weeks prior were recruited to receive a single intramuscular injection of ChAdOx1-HBV. Anti-ChAdOx1-neutralising antibody titers were determined, and vector or insert-specific T-cell responses were measured by a gamma-interferon ELISpot and intracellular cytokine staining (ICS) assay using multiparameter flow cytometry. Participants were followed for three months after the ChAdOx1-HBV injection, which was well-tolerated, and no dropouts occurred. The baseline ChAdOx1 neutralisation titers were higher in the Vaxzevria^® cohort (median of 848) than in the mRNA cohort (median of 25). T-cell responses to HBV antigens, measured by ELISpot, were higher on day 28 in the mRNA group (p = 0.013) but were similar between groups on day 84 (p = 0.441). By ICS, these differences persisted at the last time point. There was no clear correlation between the baseline responses to the adenoviral hexon and the subsequent ELISpot responses. As vaccination within 3 months using the same viral vector backbone affected the insert-specific T-cell responses, a greater interval after prior adenoviral immunisation using heterologous antigens may be warranted in settings in which these cells play critical roles. Full article