Search Results (442)

Background and Objectives: Acute pulmonary thromboembolism (PTE) is one of the leading causes of cardiovascular mortality. Recent insights into PTE pathophysiology emphasize the complex interplay of multiple mechanisms, particularly the roles of thrombosis and inflammation. Methods: This retrospective, single-center observational study included 138 participants: 69 adult patients diagnosed with PTE via computed tomography pulmonary angiography (CTPA) and 69 matched healthy controls. Upon admission, a standard 12-lead electrocardiogram (ECG) was performed, and Daniel’s score was calculated. Peripheral blood samples were collected to assess inflammatory biomarkers and hemogram-derived ratios (SII, NLR, dNLR, NPR, PLR, LMR). CTPA scans were analyzed not only for diagnostic purposes and PTE localization but also for inflammatory changes. PTE severity was classified according to the 2019 ESC guidelines. Results: Patients with PTE had significantly higher Daniel’s ECG scores, initial values of inflammatory biomarkers (WBC, neutrophils, IL-6, CRP) and hemogram-derived ratios (SII, NLR, dNLR, NPR) compared to controls. In multivariate analysis, older age (OR = 1.05; p = 0.038), higher Daniel’s ECG score (OR = 1.24; p < 0.001), and higher dNLR (OR = 1.40; p = 0.001) were found as an independent predictors of PTE severity. Ground-glass opacity (GGO) was the most common parenchymal and pleural inflammatory finding relating to CTPA (48.4%), but these findings did not show significant predictive value for PTE severity. Conclusions: Daniel’s ECG score and dNLR, both readily available and cost-effective biomarkers demonstrated independent predictive value for assessing PTE severity. Full article

Background: Musculoskeletal (MSK) pain is a frequent but under-addressed concern during pregnancy. In Bangladesh, challenges such as limited antenatal care (ANC) access and heavy maternal workloads make this issue particularly urgent for maternal health. This study aimed to determine the prevalence and predictors of MSK pain among pregnant women attending government ANC clinics in Bangladesh. Methods: A facility-based cross-sectional study was conducted among 300 pregnant women recruited from two government hospitals in Dhaka Division. Data were collected using structured interviewer-administered questionnaires covering patient characteristics, pain-related characteristics, and pregnancy-related characteristics. Pain was measured using the Numeric Pain Rating Scale (NPRS; mild <4, moderate 4–7, severe >7), and body mass index (BMI) was calculated based on self-reported height and weight. Descriptive statistics, chi-square tests, and multivariable logistic regression were employed to identify factors independently associated with MSK pain. Results: Overall, 67% of women reported MSK pain, most frequently in the lower back and lower abdomen. Women in later trimesters had about twice the odds of experiencing pain, while those with obesity had nearly six times higher odds compared to women with normal body mass index (BMI). Conclusions: MSK pain is common among pregnant women in Bangladesh and shows associations with later gestational stages and obesity. These findings suggest that integrating routine screening and non-pharmacological management into ANC may help support maternal health and reduce preventable complications in resource-limited settings. Full article

Fusarium wilt disease, caused by Fusarium oxysporum f. sp. cucumerinum (FOC), leads to widespread yield losses and quality deterioration in cucumber. Endophytes, as environmentally friendly control agents that enhance pathogen resistance in their host plants, may mitigate these problems. In this study, we isolated 14 endophytic bacteria from invasive Ambrosia artemisiifolia and screened the strain Bacillus subtilis TCX1, which exhibited significant antagonistic activity against FOC (inhibitory rate of 86.0%). TCX1 killed Fusarium oxysporum by being highly likely to produce lipopeptide and producing wall hydrolytic enzymes including protease, cellulase, and β-glucanase, thereby inhibiting mycelial growth and spore germination and causing peroxidation of FOC’s cytoplasmic membrane. In addition to its direct effects, TCX1 exerts indirect effects by inducing cucumber resistance to FOC. When cucumber seedlings were inoculated with TCX1, antioxidant enzymes related to disease resistance, including Superoxide dismutase (SOD), Peroxidase (POD), Polyphenol oxidase (PPO) and Phenylalanine ammonialyase (PAL) in cucumber, were significantly increased. The marker genes involved in induced systemic resistance and the salicylic acid signaling pathway, such as npr1, pr1a, pr2, pr9, lox1, and ctr1, were also dramatically upregulated, indicating these pathways played an important role in improving cucumber resistance. Notably, TCX1 can also promote cucumber growth through producing indole-3-acetic acid, solubilizing phosphate, and secreting siderophores. Given that TCX1 has dual functions as both a biological control agent and a biofertilizer, it offers an effective strategy for managing cucumber seedling blight while enhancing plant productivity. Full article

We report the simultaneous generation of conventional solitons (CSs) and dissipative solitons (DSs) in an erbium-doped mode-locked fiber laser with a dual-branch cavity configuration based on the nonlinear polarization rotation (NPR) technique. By incorporating fibers with different dispersion properties in two propagation branches, the laser can establish simultaneous operation in the normal and anomalous dispersion regimes within the respective loops, enabling the generation of two distinct soliton types. The CSs exhibit a 3 dB spectral bandwidth of 9.7750 nm and a pulse duration of 273 fs, while the DSs have a quasi-rectangular spectrum spanning 18.7074 nm and a pulse duration of 2.2 ps, which can be externally compressed to 384 fs. The fundamental repetition rate is approximately 21 MHz, with a repetition rate difference of 216 Hz for the two pulse trains. Stable second-order, third-order, and fourth-order harmonic mode-locking (HML) can be achieved through optimization of pump power and intracavity polarization states. The laser we build in this work has significant potential for applications in high-precision spectroscopy and asynchronous optical sampling. Full article

The cores of honeycomb panels are usually made of hexagonal cells. Due to their structure, they create anticlastic surfaces that are difficult to use in furniture design. Synclastic surfaces in lightweight sandwich panels are typically associated with auxetic cores characterized by a negative Poisson’s ratio. This study aimed to transform the hexagonal cell cores into cells with a negative or positive Poisson’s ratio (NPR, PPR), enabling these cores to form synclastic surfaces. New core structures for synclastic furniture sandwich honeycomb panels were modeled numerically and experimentally. It has been demonstrated that reentrant cells with NPR create synclastic surfaces, and new shapes of core cells, created by transforming hexagonal cells with PPR, also enable the formation of synclastic surfaces. Cores’ synclasticity was assessed in two orthogonal planes using physical models and Finite Element Analysis (FEA). A new and original discovery is the demonstration that not only auxetic but also modified hexagonal cells with Poisson’s ratios of ${\nu }_{xy}$ = 0.545 and ${\nu }_{yx}$ = 0.512, respectively, exhibit excellent synclastic properties. The agreement between FEA and experiment was very high. The results show that not only NPR but also cell topology provides a practical route to the synclastic formation of cores without the use of auxetic materials. Full article

Introduction: Posterior tibial tendon dysfunction (PTTD) is a progressive degenerative tendinopathy often unresponsive to conservative care, necessitating surgical interventions with significant postoperative risks. Wharton’s jelly (WJ) tissue allograft from the human umbilical cord, with its collagen-rich matrix homologous to tendon tissue, presents a potential alternative intervention. This study aims to report preliminary findings on the safety and efficacy of WJ allografts for the supplementation of degenerated tissue in patients with PTTD. Material and Methods: Twenty-six patients from the observational repository were identified with PTTD (Stages II-IV) and failed at least three months of conservative care. Patients received one or two ultrasound-guided percutaneous applications of the WJ allograft. Outcomes were tracked using the Numeric Pain Rating Scale (NPRS), the Western Ontario and McMaster University Arthritis Index (WOMAC), and the Quality-of-Life Scale (QOLS) at the initial, 30, 90, and 120-day follow-ups. Results: The cohort was 62% male (n = 16) and 38% female (n = 10), with a mean age predominantly in the 70–89 range. From the initial to final visit (90 days for single applications, 120 days for double applications), the single-application group (n = 22) showed a 48.32% improvement in NPRS and a 22.73% improvement in total WOMAC. The double-application group (n = 8) showed a 50% improvement in NPRS and a 27.86% improvement in total WOMAC. A statistically significant improvement in NPRS was observed in the single-application group (p = 0.042). No adverse events were reported. Discussion: This study provides preliminary evidence that WJ tissue allografts may be a safe and effective minimally invasive application for degeneration of the PTT, which is associated with improvements in pain, function, and quality of life. Key limitations include a lack of a control group and a small cohort size. Conclusions: The positive findings of this study warrant further research through randomized controlled trials to confirm efficacy, establish optimal dosage, and compare WJ to other conservative interventions. Full article

Background/Objectives: Our objective was to evaluate the clinical feasibility and sustainability of an awake breast conserving surgery (BCS) protocol integrating opioid-free anesthesia, telemedicine, and environmental sustainability compared to standard care. Methods: A prospective, monocentric, non-inferiority randomized controlled trial (133.24 CET2 ptv; NCT06624917) named Breast Green Surgery (BuGS) was planned. Women aged 18–75 years eligible for level I BCS were randomized to either the BuGS group—comprising opioid-free monitored anesthesia care (MAC), a telehealth follow-up, and intraoperative waste reduction—or the control. The primary endpoint was postoperative pain at rest (PPR) and during movement (PPD) both at 24 h, measured with the Numeric Pain Rating Scale (NPRS). Secondary exploratory endpoints included SF-36, PSQ-18, TSQ test, LOS, and KgCO₂ equivalent (KgCO₂e) from surgical waste, patient transport, and complications. The interim analysis included patients completing a 30-day follow-up by 31 December 2024. Results: A total of 45 patients were enrolled (BuGS n = 18, control n = 27). While disproportionate, no significant differences were observed in PPR/PPD at 24 h (4.75 (3.725–5.875) vs. 4.5 (4.15–5.35); p = 0.626; 4 (3.10–4.75) vs. 4.6 (3.90–5.2); p = 0.130), confirmed using group ANOVA analysis (p = 0.515; p = 0.779, respectively). The BuGS group reported a reduced surgical room occupation (80.03 (64.84–101.87) vs. 133.23 (95.47–144.25) min; p = 0.002) and length of stay (0 (0–1) vs. 1 (1–2); p = 0.0001), without hospital unplanned admissions. Reduced KgCO₂e emissions from waste disposal were reported, with no difference in SF-36, PSQ-18, and complication rates. Conclusions: If confirmed after complete accrual, BuGS could potentially promote a clinically equivalent, environmentally sustainable, and hospital efficient surgery without affecting the QoL of our patients. Further multicentric validation is warranted. Full article

(1) Objective: The biosynthesis of medicinal secondary metabolites in Dendrobium nobile Lindl. is regulated by complex environmental, hormonal, and microbial interactions. However, the mechanisms by which subtle variations in plant elevation shape metabolite accumulation through plant–microbe–hormone networks remain largely unexplored. (2) Methods: We conducted a multi-omics investigation of D. nobile cultivated under simulated wild conditions at four elevation gradients (347–730 m) in Chishui, China. High-throughput transcriptome sequencing and ITS-based fungal community profiling were combined with hormone quantification and functional prediction (FUNGuild), enabling integrated analysis of hormone pathway activation, microbial structure–function dynamics, and dendrobine levels. (3) Reults: This study systematically investigated D. nobile cultivated under simulated wild conditions across four elevation gradients (347–730 m) in the Danxia region of Chishui, China. We identified a dual regulatory mechanism underlying the elevation-dependent accumulation of dendrobine alkaloids, involving both plant hormone signaling and endophytic fungal communities. Transcriptomic analyses revealed coordinated upregulation of key hormone pathway genes, including DELLA, PYR/PYL, SnRK2, COI1-JAZ-MYC2, and NPR1-TGA, particularly in CY01Y samples at 670 m elevation from ChiYan base in Chishui city, which corresponded to the highest dendrobine content. Concurrently, functional prediction of the ITS-based fungal sequencing data revealed that CY01Y harbored a stable, functionally enriched fungal community dominated by saprotrophs, fungal parasites, and plant pathogens. (4) Conclusions: Through integrative hormone profiling, gene expression, and microbial function analysis, we propose that elevation-induced environmental cues reshape hormone pathways both directly and indirectly via microbial feedback. Specific microbial taxa were identified as potential modulators of hormone signaling and secondary metabolism. The coordinated interaction between plant hormones and endophytic fungi supports a hormone–microbiome–metabolite network that dynamically regulates dendrobine biosynthesis in response to micro-elevation variation. Full article

Introduction: Plantar fasciitis (PF), or more recently plantar fasciopathy due to its degenerative nature, is the most common cause of heel pain in adults and is often refractory to conservative care. One alternative conservative intervention involves replacing damaged fascia with homologous tissue, such as Wharton’s jelly (WJ) connective tissue allografts. The purpose of this observational study is to evaluate the efficacy and safety of collagen-rich Wharton’s jelly (WJ) when applied to defects in the plantar fascia. Materials and Methods: From the observational repository, nine patients who had plantar fasciopathy and received a single application of WJ were observed over 90 days. Outcomes were tracked using the Numeric Pain Rating Scale (NPRS), the Western Ontario and McMaster University Arthritis Index (WOMAC), and the Quality-of-Life Scale (QOLS) with no adverse reactions reported. Results: The cohort was 56% male (n = 5) and 44% female (n = 4), with a mean age of 73. From the initial to final visit, patients reported an overall trend of improvement in all scales. Statistically significant Bonferroni-adjusted differences were observed in the WOMAC scale. Age was a significant predictor of the total WOMAC score change from the initial to the final visit. Discussion: Although only a small cohort was observed, the preliminary evidence suggests the safety and efficacy of WJ allografts for plantar fascia degeneration. Key limitations of this study included a small cohort size and a lack of a comparison group with other alternative methods. Conclusions: The favorable results in this study could encourage future research to validate the clinical potential, safety, and dosing protocols of Wharton’s jelly as a primary conservative care method for patients suffering from plantar fasciopathy. Full article

Child growth in South America results from a complex interplay of genetic, environmental, and socioeconomic factors. The region’s high ancestral diversity—stemming from Native American, European, and African admixture—shapes growth patterns in ways not fully captured by international standard curves such as World Health Organization (WHO) charts, which are primarily based on European population. This mismatch may cause misclassification, especially among Native American and other underrepresented groups, and reduce the effectiveness of interventions like growth hormone (GH) therapy. Evidence from national surveys, cohort studies, and genetic analyses reveals persistent ethnic and socioeconomic disparities, with Native American children showing higher stunting prevalence even after adjusting for wealth and residence. Differences between WHO and national growth curves further contribute to inconsistent prevalence estimates due to methodological and contextual variants. Regional genomic studies, although limited, have identified population-specific variants, such as FBN1 (E1297G) in Peru, and modulators of GH therapy response, including GHR exon 3 deletion, ACAN, and NPR2, highlighting the role of genetic background, treatment timing, and adherence in height outcomes. These findings underscore the need to move toward precision growth medicine, integrating anthropometry, genetic, environmental, and socioeconomic data to design population-specific growth references, optimize pharmacogenetic approaches, and reduce inequities in pediatric growth care. Full article

Background/Objectives: While some dietary indices have been developed to assess diet quality and chronic disease risk, their comparative effectiveness within the same population remains unclear due to methodological limitations in observational studies. This study employs a causal inference framework to compare nine dietary indices for reducing all-cause and cardiovascular mortality, while investigating inflammatory pathways through multiple mediation analysis. Methods: Using dietary data from 33,881 adults (aged ≥ 20 years, median follow-up 92 months), we applied a causal directed acyclic graph to identify the minimum sufficient adjustment set and implemented generalized propensity score matching to address confounding. Robust Cox proportional hazards regression assessed associations between nine dietary indices—Dietary Inflammatory Index (DII), Composite Dietary Antioxidant Index (CDAI), Healthy Eating Index 2015/2020 (HEI-2015/2020), Alternate Healthy Eating Index (AHEI), Alternate Mediterranean Diet (aMED), Mediterranean Diet Index (MEDI), and Dietary Approaches to Stop Hypertension (DASH/DASHI)—and mortality outcomes. Multiple additive regression trees (MART) algorithm was used for multiple mediation analysis to examine inflammatory markers (PAR, SII, NPR, TyG, LMR, PLR, ELR, CRP) as mechanistic mediators. Results: Among 33,881 participants (mean age 47.07 years, 51.34% women), 4,230 deaths occurred, including 827 cardiovascular deaths. Under the causal inference framework, higher DII scores increased both all-cause (HR: 1.07; 95% CI: 1.02–1.12) and cardiovascular mortality risk (HR: 1.07; 95% CI: 1.04–1.10) by 7%. The aMED demonstrated the strongest protective association, reducing all-cause mortality by 12% (HR: 0.88; 95% CI: 0.80–0.97) and cardiovascular mortality by 11% (HR: 0.89; 95% CI: 0.80–0.98), followed by MEDI with similar magnitude effects. Other healthy dietary indices showed modest 1–3% risk reductions. Multiple mediation analysis revealed that inflammatory markers, particularly neutrophil-to-platelet ratio (NPR) and systemic immune-inflammation index (SII), significantly mediated diet–mortality associations across all indices, with C-reactive protein (CRP) serving as the most frequent mediator. Conclusions: Using causal inference methodology, the Mediterranean dietary pattern (aMED) shows the strongest causal association with reduced mortality risk, with inflammatory pathways serving as key mediating mechanisms. These findings provide robust evidence for prioritizing Mediterranean dietary patterns in public health interventions and clinical practice, while highlighting inflammation as a critical therapeutic target for dietary interventions aimed at reducing mortality risk. Full article

Background: Chronic pain represents a major therapeutic challenge due to the limited efficacy and tolerability of conventional pharmacological treatments. Equisetum arvense L., a medicinal plant with potent antioxidant properties, and palmitoylethanolamide (PEA), an endogenous fatty acid amide with well-established anti-inflammatory and analgesic effects, are increasingly recognised as promising nutraceutical agents. Methods: This prospective, single-centre clinical trial aimed to evaluate the efficacy and safety of a novel oral supplement (Assonal^®PEA) combining 600 mg of PEA and 300 mg of Equisetum arvense L. in improving the reduction of pain and quality of life in patients with chronic pain, also obtaining information on the patient’s state of satisfaction after the treatment. Fifty patients suffering from chronic pain (low back pain and radiculopathy) for two months were enrolled and received the supplement over eight weeks in a tapered regimen (two tablets daily for two weeks, followed by one tablet daily). Results: Clinical outcomes were evaluated using validated instruments, including the Numeric Pain Rating Scale (NPRS), Verbal Rating Scale (VRS), Short-Form McGill Pain Questionnaire (SF-MPQ), Global Perceived Effect (GPE), and EuroQol-5D-5L. Results showed a significant decrease in pain intensity (NPRS: −3.8 points; VRS: −2.1 points; p < 0.0001), along with meaningful improvements in patient-perceived benefit, pain descriptors, and quality of life (EQ-5D-5L: +35%; p < 0.0001). Conclusions: These findings endorse the use of this novel PEA–Equisetum arvense formulation as a safe, well-tolerated, and potentially effective supplementary intervention for managing chronic pain. No adverse events were reported, and the overall response rate reached 94%. Full article

Background/Objectives: The static in vitro permeability assay based on cell monolayers has been widely used in the pharmaceutical industry and recognized by regulatory agencies as a surrogate method for BCS classification. However, the application of such an experiment to study the effects of formulations is limited by the oversensitivity to the excipient effect on drug permeability. In this article, we studied the effects of common excipients on the permeability of moderately and poorly absorbed model compounds across cell monolayers, using two approaches to control said oversensitivity. Methods: Drug permeability across MDCK-wt was assessed in the absence (control) or presence (treatment) of excipients, using minoxidil as a high-permeability marker. The effects of excipients were parameterized as a permeability ratio (PR = treatment/control) without or with normalization (nPR) by minoxidil permeability. Metrics were compared by either ANOVA (p < 0.01) or confidence intervals (CI90, as per bioequivalence metrics) to identify excipient effects. Results: Acyclovir and hydrochlorothiazide showed the highest and lowest number of interactions, respectively. The most impactful excipients were sodium lauryl sulfate, microcrystalline cellulose, and sodium starch glycolate. Unexpectedly, nPR increased the number of excipient effects across model drugs (19 vs. 21). Alternatively, the CI90 approach was more sensitive than ANOVA in identifying excipient effects (41 vs. 32). Conclusions: Minoxidil was not able to control the anticipated oversensitivity of cell-based permeability experiments. Meanwhile, ANOVA was overall able to reduce oversensitivity to excipient effects on drug permeability compared to CI90. Nonetheless, there might be a niche for CI90 analysis when comparing the performance of two formulations on the permeability of moderately and poorly absorbed drugs. Full article

Background and Clinical Significance: Non-palpable migrated contraceptive implants pose significant challenges for removal and are associated with neurovascular complications. Traditional open surgery near nerves is associated with postoperative morbidity. Migrated or deeply embedded implants near critical structures can result in severe complications, such as neuropathy, and their removal typically requires open surgical intervention. Case Presentation: We report a novel, minimally invasive, ultrasound (US)-guided technique for removing a migrated etonogestrel Implanon^® implant that caused ulnar neuropathy. A 38-year-old woman presented with severe neuropathic pain and paresthesia (NPRS 10/10; QuickDASH 55) along her left ulnar nerve following multiple failed removal attempts that induced deep migration. US confirmed the proximity of the implant to the ulnar nerve. Initial US-guided removal exacerbated her symptoms. Hydrodissection (HD) with 50 mL of 5% dextrose in water (D5W) without local anesthetic (LA) was performed to reduce inflammation and achieve separation. The implant migrated proximally during extraction. An additional HD with 50 mL of D5W without LA distally repositioned the implant. Percutaneous stabilization using a 25-gauge needle enabled secure removal. The intact 4 cm implant was extracted under real-time US guidance without open surgery. The patient experienced immediate symptom relief (NPRS 2/10; QuickDASH 4.5 at one month) and full resolution (NPRS 0/10; QuickDASH 0) with no motor deficits at one year. Conclusions: This case represents the first documented percutaneous removal of a nerve-adherent implant using combined US-guided D5W HD and needle stabilization, marking a paradigm shift in the management of such cases. This approach confirms the safety of US-guided foreign body removal using HD for nerve-adjacent implants and demonstrates the efficacy of combining D5W HD with needle stabilization. Surgical morbidity was avoided, while excellent long-term outcomes were achieved. Full article

Structures that possess negative Poisson’s ratio are termed “Auxetic” structures. They elongate laterally on longitudinal–tensile loading and compress laterally on longitudinal–compressive loading. Auxetic structures are a composition of unit cells that are available in various geometries, which include triangular, hexa-triangular, re-entrant, chiral, star, arrowhead, etc. Due to their unique shape, these structures possess remarkably good mechanical properties such as shear resistance, indentation resistance, fracture resistance, synclastic behavior, energy absorption capacity, etc. However, they have poor load-bearing capacity. To improve the load bearing strength of these structures, this paper presents a numerical analysis of oriented re-entrant structured (ORS) beams with auxetic clusters aligned at various angles (0°, 45° and 90°), using Finite Element Methods. Oriented re-entrant unit cell clusters enclosed by a bounded frame were modeled and a three-point bending test was conducted to perform a comparison study on deformation mechanisms of the different oriented re-entrant honeycomb structures with honeycomb beams. The computational analysis of ORS beams revealed that the directional deformation and normal strain along the x-axis were the lowest in ORS45, followed by ORS90, ORS0, and honeycomb. Among all the beams, ORS45 displayed the best load-bearing capacity with comparably low mass density. Full article