Search Results (284)

Dysfunctions and disorders of the craniomandibular system are accompanied by pathophysiological changes of muscle groups in the throat/neck and facial area, e.g., pain in the jaw and muscles of mastication and disturbance of occlusion, leading to teeth injury (loss of dental hard tissue, fractures/sensibility disorders, etc.). For muscular dysfunctions, even in the context of psychosomatic disorders and chronic stress, hippotherapy is particularly suitable, since it helps actively to relieve muscle tensions. In the current project we combined hippotherapy with progressive muscle relaxation (PMR) to achieve a synergistic effect. The horses used for therapy (two mares and five geldings between seven and twenty-one years old) were especially suitable because of their calm temperament. In two cases, trained therapy horses were used; in five other cases, the patients used their own horses, which were not specially trained. Right from the beginning, the project was accompanied by veterinary support. Conditions of horse keeping (active stable, same-sex groups, no boxes) were assessed as well as the horses themselves prior to, during, and after each therapy unit. In patients, cortisol, as a quantifiable parameter for stress, was measured before and after each therapy unit. From before the start until the end of each therapy unit of 15 min, the heart rate variability (HRV) of both patients and horses was registered continuously and synchronously. In addition, the behavior of the horses was monitored and recorded on video by an experienced coach and a veterinarian. The stress load during the tension phases in the therapy units was low, perceivable in the horses lifting their heads and a slightly shortened stride length. Likewise, the horses reflected the patients’ relaxation phases, so that at the end of the units the horses were physically and psychically relaxed, too, noticeable by lowering their necks, free ear movement, and a decreasing heart frequency (HF). Altogether, the horses benefited from the treatment, too. Obvious stress signs like unrest, head tossing, tail swishing, or tense facial expressions were not noticed at any time. Twenty jumpers served as a control group in different situations (training, tournament, and leisure riding). Full article

Background/Objectives: Polymyalgia rheumatica (PMR) is a relatively common inflammatory rheumatic disease of the elderly. The role of vitamin D remains unclear in this condition. The endpoints of this study were to assess 25-hydroxyvitamin D [25(OH)D] serum concentrations in PMR patients with active disease compared to elderly controls and to determine if baseline levels or changes following supplementation [delta 25-hydroxyvitamin D, Δ25(OH)D] were associated with improved clinical outcomes. Methods: In this retrospective, case–control study, 29 PMR patients (55% males, 75.24 ± 9.6 years old, disease duration of 3.8 ± 3 months) were included, meeting the 2012 EULAR/ACR classification criteria, with 29 age- and sex-matched controls without systemic inflammatory rheumatic diseases. We assessed demographic, clinical and laboratory features for PMR patients, including baseline 25(OH)D serum concentrations, disease activity (polymyalgia rheumatica activity score), and serum inflammatory biomarkers. A subgroup of them (n = 25) was followed longitudinally, for an average period of 21.1 ± 17.7 months, to evaluate the association between Δ25(OH)D and clinical outcomes at follow-up using multivariate logistic regression. Results: Although lower than the normal reference values, baseline 25(OH)D concentrations did not differ significantly between PMR patients and controls (21.6 ± 9.2 vs. 22.7 ± 11.3 ng/mL, p = 0.66) and did not predict long-term clinical outcomes. However, after only 3 months of supplementation, the increase in 25(OH)D concentrations was significantly associated with a remission status, and patients in remission showed a significant increase in 25(OH)D compared to those with persistent disease activity (+22.02 vs. +1.33 ng/mL, respectively; p = 0.044). Notably, in the multivariate model, this Δ25(OH)D was the strongest independent predictor of remission (OR = 2.89; 95% CI [1.60–4.11]), an effect independent of prednisone dosage prescribed at first visit (p = 0.32) and glucocorticoid exposure at third month (p = 0.12). Conclusions: Individual’s response of PMR patients to supplementation of vitamin D seems to be a robust independent predictor of early clinical remission achievement. Interestingly, optimizing vitamin D supplementation based on individual responsiveness may represent a valuable adjunctive strategy in PMR management. Full article

The global emergence of multidrug- and pandrug-resistant Klebsiella pneumoniae poses a critical threat to public health, particularly in hospital settings. This study describes a nosocomial outbreak caused by K. pneumoniae in a tertiary-care hospital in Mexico and provides a comprehensive genomic analysis of six clinical isolates. All isolates exhibited pandrug resistance, including carbapenems and colistin. Whole-genome sequencing identified 37 antimicrobial resistance genes, including blaNDM-1, blaOXA-1, blaCTX-M-15, and a pmrB R256G mutation associated with colistin resistance. Two conjugative plasmids (pAA046 and pAA276) carried multiple resistance genes and mobile genetic elements. Although all isolates harbored CRISPR-Cas type I-E systems, no spacers matched resistance plasmids, suggesting functional inactivity. Capsular typing identified the KL27 locus with the wzi187 allele. Phylogenetic and cgMLST analyses confirmed clonal dissemination and close genetic relatedness to strains from Europe and the USA. Despite the absence of classical hypervirulence markers, the presence of kfu, fimH, and mrkD genes indicates adaptation to the hospital environment. These findings confirm the clonal spread of pandrug-resistant K. pneumoniae ST392-KL27 in a Mexican hospital, underscoring the role of plasmid-mediated resistance and the potential for global dissemination. Full article

Background: Immune checkpoint inhibitors (ICIs) transformed cancer treatment, producing significant survival benefits. However, ICIs can trigger toxicities called immune-related adverse events (irAEs), including inflammatory arthritis (IA) and polymyalgia rheumatica (PMR)-like syndromes. Our study aimed to systematically further characterize musculoskeletal ultrasound (MSKUS) findings in patients with ICI-IA and ICI-PMR, collectively referred to as “MSK-irAEs”, and explore the role of US in guiding treatment. Methods: The authors conducted a comprehensive chart review for patients receiving ICIs undergoing MSKUS at our center’s rheumatology clinics. US examinations were performed and reviewed by two MSKUS-certified rheumatologists. Descriptive statistics were performed to summarize demographic, clinical, and treatment-related variables. US findings were categorized with a novel scoring system: 0—no signs of inflammatory arthropathy or tendinopathy, 1—potential signs of inflammation (grayscale ≥ 2, effusion without power Doppler, synovial hypertrophy in the joint), and 2—active inflammation in joints and/or tendons (characterized by power Doppler) and signs of inflammation. Results: Twenty-three patients were included. The median age was 63 years, 52% were male, and 87% were White. Melanoma was the most common cancer (48%). MSK-irAEs were diagnosed in nineteen (83%), with MSKUS showing inflammation in seventeen (74%). Sixteen (70%) received escalation in MSK-irAE treatment after MSKUS. Four (17%) had erosive disease due to MSK-irAEs, while one had erosive osteoarthritis. Individuals with inflammatory erosive changes experienced prolonged intervals between symptom onset and MSKUS, ranging from 17 to 82 months, suggesting that erosions may reflect chronic, under-recognized inflammation. On MSK-irAE therapy, nine (47%) experienced symptomatic improvement, five (26%) achieved resolution, and in four (21%) cases, it was too early to assess the response. MSKUS detected other causes of MSK symptoms besides MSK-irAEs in several patients, allowing ICI resumption in one. Conclusions: Our study highlights the clinical utility of MSKUS not only as a diagnostic tool but also to guide therapeutic decision-making. Full article

Background: Considering that the prevalence of obesity has risen rapidly in recent decades, the aim of this study was to investigate the effects of a carbohydrate mouth rinse (CMR) on the outcomes of aerobic training among adult men with obesity, focusing particularly on the effects of repeated use on body composition and exercise performance. Methods: The intervention targeted 20 men with obesity in their 20s and 30s randomly assigned to either a CMR group (n = 10) or a placebo mouth rinse (PMR) group (n = 10). Both groups completed treadmill-based aerobic training three times per week for eight weeks. Prior to each session, participants used a mouth rinse at 60, 40, and 20 s before the start of each exercise, holding either a 6% maltodextrin solution (CMR) or purified water (PMR) in their mouths for 5 to 10 s before expectorating. Pre- and post-intervention assessments included body composition (body weight and body fat percentage), resting metabolic rate (RMR), maximal oxygen uptake (VO₂max), and exercise performance (rate of perceived exertion [RPE], exercise distance, speed, and time). Data were analyzed using 2 × 2 repeated measures analysis of variance. Results: Following the intervention, the CMR group showed significantly greater improvements than the PMR group did in body fat percentage, RMR, VO₂max, exercise distance, speed, and time (p < 0.01). However, the interaction effect for RPE was not statistically significant between the groups (p = 0.175). Overall, the repeated use of the CMR during aerobic training contributed to enhanced exercise performance and favorable physiological changes without additional caloric intake. Conclusions: A CMR may be a practical and non-caloric ergogenic aid to support exercise performance and metabolic function in individuals with obesity. Its repeated use during aerobic training appears to be effective and safe, especially when fasting while exercising, when improving endurance without compromising fat loss is essential. Full article

Diarrhea in alpaca crias significantly impacts livestock health in high-altitude regions, with Escherichia coli as a common pathogen. This study analyzed 10 E. coli isolates from diarrheic and healthy alpacas using whole-genome sequencing to assess genetic diversity, virulence factors, and antibiotic resistance. Predominant sequence types (ST73, ST29), serotypes (O22:H1, O109:H11), and phylogroups (B2, B1, A) were identified. Virulence profiling revealed ExPEC-like and EPEC pathotypes, while resistance genes for β-lactams (blaEC-15), fosfomycin (glpT_E448K), and colistin (pmrB) were prevalent. These findings highlight the need for genomic surveillance and antimicrobial stewardship to manage E. coli infections in alpacas and reduce public health risks. Full article

Migraine is a common disabling primary headache disorder with significant personal and socio-economic impacts. A combination of medication and non-pharmacological therapies is essential for migraine management. Outpatient multidisciplinary headache therapy has not yet been evaluated in Switzerland. This study evaluates the effectiveness of the headache management program at Inselspital, Bern University Hospital, in improving headache-related disability in migraine patients. This open-label pilot study used prospectively assessed routine data from our headache registry. Participants aged 18 years or older with a diagnosis of migraine, confirmed by a headache specialist, were included. The program consisted of seven weekly sessions, each with a 50 min educational lecture and a 30 min progressive muscle relaxation (PMR) exercise. Primary outcomes were headache-related impact and disability, measured by the Headache Impact Test 6 (HIT-6) and Migraine Disability Assessment (MIDAS). Secondary outcomes included symptoms of anxiety, measured by the Generalized Anxiety Disorder 7-item scale (GAD-7), and symptoms of depression, assessed using the eight-item Patient Health Questionnaire depression scale (PHQ-8). Data were analysed using paired t-test and Wilcoxon signed rank tests. Significant improvements were observed in HIT-6 scores (pre-program: 65.2; post-program: 61.9; p = 0.012) and MIDAS scores (pre-program: 38; post-program: 27; p = 0.011), while PHQ-8 also showed a statistically significant reduction. Although the GAD-7 scores improved numerically, this change was not statistically significant. These findings suggest that the headache management program may reduce headache burden and disability; however, further research with larger samples is needed to confirm these preliminary results. Full article

Background/Objectives: Endoscopic lumbar sympathectomy (ELS) is the definitive treatment for primary plantar hyperhidrosis (PPLH). This study analyzed the mid-term clinical outcomes and technical factors related to ELS. Methods: Retrospective reviews of patients who had ELS for PPLH between July 2019 and May 2023 were analyzed. The study period was categorized into three eras based on the timing when laser Doppler flowmetry (LDF) and PMR (psoas muscle relaxation) were applied; period A represented the initial surgical approach, period B included LDF, and period C included LDF and PMR during surgery. The impacts of these techniques on operative and short-term outcomes were assessed. Additionally, risk factor analysis was performed to find relevant factors related to the reappearance of plantar sweating in long-term follow up. As most patients underwent endoscopic thoracic sympathectomy (ETS) as well, risk assessment for compensatory hyperhidrosis was also investigated. Results: A total of 474 patients were included, and the numbers of patients by periods were as follows: n = 28 in period A, n = 198 in period B, and n = 248 in period C. Operating times were significantly different, with proportional decreases seen with the introduction of LDF and PMR (p < 0.001). In the long-term, reappearance of plantar sweating was noted in 21 patients (4.4%). Risk factors for the reappearance of plantar sweating included an age over 35 years [odds ratio {OR} (95% confidence interval {CI}) 4.57 (1.56–13.40), p = 0.006] and a history of lumbar sympathetic ganglion block (LSGB) prior to ELS [OR (95% CI), 269 (29.30–2460), p < 0.001]. Of 474 patients, 390 (82.3%) patients underwent both ETS and ELS. Risk factors for compensatory hyperhidrosis were age >25 years [OR (95% CI) 0.60 (0.40–0.90), p = 0.014] and concomitant ETS [OR (95% CI) 5.63 (1.88–16.90), p = 0.002]. Compensatory hyperhidrosis among patients who only had ELS was less observed (4/24, 16.7%). Conclusions: ELS is highly effective in treating plantar hyperhidrosis, and LDF and PMR improved perioperative outcomes. Age over 35 and a prior history of LSGB were found to be related to worse long-term outcomes of ELS. Our findings suggest that ELS with additional LDF and PMR could improve outcomes for patients with PPLH. Full article

Background/Objectives: Colistin is a last-resort treatment for Pseudomonas aeruginosa multidrug-resistant infections, but resistance to it is emerging. While colistin resistance in P. aeruginosa is typically associated with chromosomal mutations inducing lipopolysaccharide (LPS) aminoarabinosylation, other mutations unrelated to LPS modifications have been proposed to influence the extent of colistin resistance. Here, we examined whether the genetic background and culture conditions affect the evolution of high-level colistin resistance in this bacterium. Methods: We performed in vitro evolution experiments in the presence or absence of increasing colistin concentrations with two phylogenetically distant reference strains in a standard laboratory medium and in two media mimicking P. aeruginosa growth during lung or systemic infections. Resistance-associated mutations were identified by comparative genomics, and the role of selected mutated genes was validated by allele replacement, deletion, or conditional mutagenesis. Results: Most colistin-resistant mutants carried mutations in genes belonging to four functional groups: two-component systems controlling LPS aminoarabinosylation (PmrAB, PhoPQ), LPS biosynthesis, the production of the polyamine norspermidine, and fatty acid metabolism. No mutation was exclusively and invariably associated with a specific strain or medium. We demonstrated that norspermidine is detrimental to the acquisition of colistin resistance upon PmrAB activation and that impaired fatty acid biosynthesis can promote colistin resistance, even if it increases susceptibility to other antibiotics. Conclusions: The evolution of colistin resistance in P. aeruginosa appeared to be only marginally affected by the genetic background and culture conditions. Notably, mutations in fatty acid biosynthetic genes represent a newly identified genetic determinant of P. aeruginosa colistin resistance, warranting further investigation in clinical isolates. Full article

Background and Objectives: Chronic respiratory diseases, such as COPD, cystic fibrosis, and post-COVID-19, are frequently accompanied by psychological distress and physical impairment. As a non-pharmacological intervention, progressive muscle relaxation (PMR) may benefit these patients psychologically and physiologically. This systematic review aimed to evaluate the effects of PMR on anxiety, depression, fatigue, sleep quality, dyspnea, and pulmonary function in patients with COPD, CF, and COVID-19. Materials and Methods: Following PRISMA guidelines, a comprehensive search was conducted across PubMed, Scopus, Web of Science, MEDLINE, Cochrane, SpringerLink, and ClinicalTrials.gov. Eligible studies assessed PMR in adult patients with COPD, CF, or COVID-19. Psychological and physical outcomes were extracted, and methodological quality and risk of bias were evaluated using standardized tools. Results: A total of 32 studies were included in the analysis. PMR was consistently associated with reductions in anxiety, depression, fatigue, and sleep-related distress, particularly in patients with COPD and COVID-19. Some also reported improvements in dyspnea and mild pulmonary function tests, but these were more variable. Only one study evaluated PMR in patients with cystic fibrosis, providing the first clinical data for this group. Interventions were predominantly short-term, with significant variation in design, duration, and methodology, and the risk of bias was often moderate or high. Conclusions: PMR is a helpful strategy in treating chronic respiratory diseases, particularly for reducing psychological distress and improving sleep. However, the evidence is limited by methodological variations and lack of long-term follow-up. Rigorous research is needed to support clinical application, particularly in cystic fibrosis. Full article

Background/Objectives: We reviewed Post-Marketing Requirements (PMRs) under the Pediatric Research Equity Act (PREA) for antibiotics approved in adults from 2009 to 2024 to better understand factors associated with PMR study completion. Methods: Initial PMRs, including study design and completion timelines were extracted from Food and Drug Administration (FDA) approval letters. Studies were cross-referenced at clinicaltrials.gov, with follow-up from adult approval to study completion or through 31 December 2024. Results: Eighteen antibiotics were approved in adults from 2009 to 2024, with 53 associated PREA PMRs. A total of nine PMRs were excluded from analysis (six exclusions for projected study completion dates on or after 12/31/2024, one exclusion due to lack of information, and two exclusions because the study type was not categorizable as Phase 1 or Phase 2). Of the 44 remaining PMRs in the analysis set, the median pediatric study follow-up time from adult approval was 5.3 years (range 0.94 to 11.5 years), with a study completion rate of 54.5% (N = 24). Small- and medium-sized companies had a study completion rate of 10% (N = 2/20) over a median of 6.44 years of follow-up, with no pediatric approvals. Large pharmaceutical corporations had a significantly higher study completion rate of 91.6% (N = 22/24; adjusted hazard ratio 20.3 95%CI, 5.02 to 82.4) over a median follow-up time of 4.7 years and achieved pediatric approval with labelling updates for 75% of antibiotics (N = 6/8). Conclusions: Compared to larger organizations, smaller pharmaceutical companies have experienced difficulty in PREA PMR antibiotic study completion, which may be related to financial difficulties in the challenging market for antibiotics. To improve PMR study completion, smaller companies require continued financial support and innovation in study design. For pediatric antibiotic development, the FDA accepts the extrapolation of efficacy from well-conducted randomized adult trials (i.e., pharmacokinetics (PK) and the safety approach). Therefore, sponsors should consider the use of single-arm, non-comparative PK and safety study designs to reduce the size and scope of trials. Sponsors should also assess whether the evaluation of an antibiotic is necessary in adolescents, or if data in a surrogate population of adults (e.g., low-weight adults) may serve as adequate evidence for adolescent approval. Full article

Background: Polymyalgia rheumatica (PMR) has a multifaceted onset and course, and making a distinction between true PMR and so-called “polymyalgic syndrome” (that is, similar manifestations caused by different conditions) is far from easy in clinical practice. The existence of subsets within true PMR may further complicate the diagnostic question. Distinguishing PMR subsets from PMR-mimicking conditions does not just carry nomenclature value and speculative significance. Indeed, the correct diagnosis influences treatment, prognosis, epidemiological assessments, and health policies. Objectives: We aimed to (1) ascertain the presence of a definite and peculiar subset/subgroup/cluster of PMR in the scientific literature; (2) describe any possible subset/cluster/subgroup of PMR identified in at least two different studies. Methods: We performed a non-systematic (PRISMA protocol not followed) literature search on Embase and Medline (OVID interface). The following search terms were used: polymyalgia rheumatica, subset, cluster, subgroup, subclinical giant cell arteritis, mimicking conditions, polymyalgia rheumatica-like conditions, immunotherapy, checkpoint inhibitor, acute-phase reactants or acute-phase proteins, vaccination, infection, and calcium pyrophosphate deposition disease or chondrocalcinosis. Each paper’s reference list was scanned for additional publications meeting this study’s aim. Abstracts submitted at conferences or from non-peer-reviewed sources were not included. Results: The initial search yielded 2492 papers, of which 2389 articles were excluded based on title and abstract screening. A total of 103 articles underwent a full-length review, and 84 of them were finally assessed for eligibility. A total of seven large subsets of PMR could be identified: (1) PMR with normal acute-phase reactants; (2) PMR with an infection trigger; (3) PMR with a vaccination trigger; (4) PMR with subclinical giant cell arteritis (GCA); (5) PMR and calcium pyrophosphate deposition disease (CPPD); (6) PMR following immune checkpoint inhibitor (ICI) therapy; (7) PMR with peculiar clinical clusters (based on clinical or statistic clustering methods). Conclusions: PMR with normal baseline acute-phase reactants and PMR with an infection or a vaccination trigger could be categorized as subsets of disease. PMR with subclinical GCA and most cases of PMR/CPPD should be categorized as mimickers. Finally, further studies are required to better categorize some peculiar clinical subsets emerging from cluster analyses, and ICI-induced PMR. Full article

The integration of intermittent Distributed Generations (DGs) like solar photovoltaics into Radial Distribution Systems (RDSs) reduces system losses but causes voltage and power instability issues. It has also been observed that seasonal variations affect the performance of such DGs. These issues can be resolved by placing optimum-sized Battery Energy Storage (BES) Systems into RDSs. This work proposes a new approach to the placement of optimally sized BESSs considering multiple objectives, Active Power Losses, the Power Stability Index, and the Voltage Stability Index, which are prioritized using the Weighted Sum Method. The proposed multi-objectives are investigated using the probabilistic and Polynomial Multiple Regression (PMR) approaches to account for the randomness in solar irradiance and its effect on BESS sizing and placements. To analyze system behavior, simultaneous and sequential strategies considering aggregated and distributed BESS placement are executed on IEEE 33-bus and 94-bus Portuguese RDSs by applying the Improved Grey Wolf Optimization and TOPSIS techniques. Significant loss reduction is observed in distributed BESS placement compared to aggregated BESSs. Also, the sequentially distributed BESS stabilized the RDS to a greater extent than the simultaneously distributed BESS. In view of the uncertainty, the probabilistic and PMR approaches require a larger optimal BESS size than the deterministic approach, representing practical systems. Additionally, the results are validated using Improved Particle Swarm Optimization–TOPSIS techniques. Full article

This study examines how research and development (R&D) expenditures, temperature fluctuations, and rainfall variability influenced wheat productivity in China, India, and Pakistan from 1996 to 2018. Drawing on data from FAOSTAT, the Pakistan Economic Survey, and World Development Indicators, we employ Pooled Mean Group (PMG) and Autoregressive Distributed Lag (ARDL) models to explore short- and long-run dynamics. Our findings indicate that R&D investments do not exert a significant short-run effect but play a pivotal role in boosting wheat yields over the long run. Specifically, a 1% increase in R&D expenditure correlates with a 10% rise in wheat productivity across the three countries, although the returns vary—6% in China, 17% in India, and 12% in Pakistan—due in part to differences in innovation adoption and infrastructure. Additionally, a 1% temperature rise is associated with a 4% decrease in long-run yield, while variability in rainfall disrupts sowing schedules and reduces water availability during critical growth stages, further constraining productivity. These findings underscore that while climate factors pose significant risks to wheat yields, sustained investments in agricultural R&D and improved resource management are essential for enhancing food security in South Asia. Full article

Background/Objective: Cystic fibrosis (CF) is a chronic genetic disease affecting multiple body systems and having a significant impact on mental health and sleep. Patients with CF frequently suffer from anxiety, depression, and sleep disturbances, but non-pharmacological strategies are understudied. Although progressive muscle relaxation (PMR) has recognized benefits, its impact on CF remains insufficiently explored. The study aimed to analyze the effect of integrating PMR into a standard pulmonary rehabilitation (PR) program on mental health, sleep quality, and quality of life in adults with CF. Methods: A total of 22 adult patients with CF were randomly assigned to either the intervention group (PR + PMR) or the control group (PR only). Assessments were performed at baseline, after 21 days of intervention, and at the 48-day follow-up. Outcome measures included the CFQ-R for quality of life, the HADS for mental health, and the PSQI for sleep. Results: Compared to the control group, participants who practiced PMR experienced significant reductions in anxiety (p = 0.05) and depression (p = 0.02) at the final assessment. A significant improvement in sleep quality was also observed (p < 0.01). No relevant differences were found in pulmonary function or performance on the six-minute walk test. Conclusions: Integrating PMR into pulmonary rehabilitation programs may be an effective strategy for improving mental health and sleep in patients with CF. Due to its accessibility and ease of implementation, PMR could be adopted as a complementary method in the holistic care of these patients. Full article