Search Results (665)

Soybean root rot, caused by diverse soil-borne pathogens, is a major constraint on production worldwide, with yield losses ranging from 10 to 60% under epidemic conditions. Symptomatic plants were collected from three locations in Harbin, Heilongjiang Province, China, and 23 fungal isolates were recovered using standard tissue isolation procedures. Integrated morphological characterization and rDNA-ITS sequencing identified these isolates as three Fusarium species: F. oxysporum (18 isolates, 78%), F. equiseti (3 isolates, 13%), and F. brachygibbosum (2 isolates, 9%). Pathogenicity assays following Koch’s postulates confirmed F. oxysporum as the predominant and most aggressive pathogen in this region. To identify resistance resources, 200 soybean germplasm accessions adapted to Northeast China were screened using an etiolated seedling hypocotyl inoculation method with Fusarium oxysporum isolate A3 (DSI = 68.5) as the test pathogen. Disease severity indices exhibited a continuous distribution (mean = 52.84, range = 0–100), suggesting quantitative inheritance. Accessions were classified as highly resistant (13, 6.5%), resistant (40, 20%), moderately susceptible (67, 33.5%), susceptible (43, 21.5%), or highly susceptible (37, 18.5%). To explore potential molecular mechanisms underlying resistance, RT-qPCR analysis was performed on two extreme genotypes—a highly resistant line (H9477F5, DSI = 15.3) and a highly susceptible line (HN91, DSI = 88.7) at 1, 3, and 5 days post-inoculation. The resistant line maintained consistently higher expression of positive regulators GmFER and GmSOD1, with GmFER reaching 15.89-fold induction at day 3. Conversely, expression of negative regulators GmJAZ1 and GmTAP1 remained lower in the resistant line, with susceptible plants showing 5.62-fold higher GmJAZ1 expression at day 3. These findings provide characterized pathogen isolates, resistant germplasm resources (53 accessions with HR or R classifications), and preliminary molecular insights that may inform breeding strategies for improving root rot resistance in Northeast China. Full article

Background: Patients who undergo pelvic lymphadenectomy for gynecologic or genitourinary cancers have an increased risk of developing lower extremity lymphedema. Although total lymphadenectomy is performed, bilateral lower extremity lymphedema is rare. A state-of-the-art radiologic technique, single-photon emission computed tomography (SPECT) with radioisotope injection, was used to establish lymph flow physiology and identify retrograde lymphatic flow in patients with lower extremity lymphedema after lymphadenectomy. Methods: Data from patients who underwent treatment for lower extremity lymphedema were collected from January 2017 to December 2018. These patients had gynecological or genitourinary cancers and had undergone pelvic lymphadenectomy. Among them, 10 were evaluated for reverse lymph flow using SPECT. The radioisotope was injected solely into the subdermal area of the healthy foot, not the affected foot, in contrast to other studies. Four hours later, SPECT images were obtained and analyzed. The radiologic results were correlated with clinical observations. Results: Most patients had undergone surgery for gynecological cancers. The mean disease duration was 9.4 ± 8.1 years. Retention in the pelvis and hip was confirmed in seven out of ten patients; six patients showed reverse lymphatic flow in the affected limb. Conclusions: SPECT-CT imaging after tracer injection into the unaffected limb revealed retrograde lymphatic flow toward the clinically affected side in a substantial proportion of patients with unilateral lower-extremity lymphedema. Full article

Background: Conservative treatment of chronic musculoskeletal pain includes exercise, manual therapy, medications, physical agents/modalities, and Therapeutic Patient Education (TPE). Research on TPE has predominantly focused on spinal pain, so we do not know the extent and scope of clinical research in other areas, particularly lower extremities. This review aimed to map current research on this topic. Methods: We searched PubMed, PEDro, CINAHL, PsycINFO, and Cochrane Library up to 1 April 2024. We included RCTs on adults with chronic lower limb musculoskeletal pain, written in English, French, Spanish, or Italian. Results: Fifty-two records concerning knee osteoarthritis (n.33), hip and knee osteoarthritis (n.8), hip osteoarthritis (n.3), chronic knee pain (n.3), patellofemoral pain (n.3), and gluteal tendinopathy (n.2) were included. TPE was delivered through self-management, disease-specific information, pain education, and the management of physical activity, load, diet, stress, and sleep. Interventions were both individual- and group-based; delivery methods included in-person intervention, telephone/video calls, and web tools/apps. TPE combined with exercise seemed to be more effective than exercise alone, information/little education, or usual care. The effects of TPE as a stand-alone intervention appeared uncertain. Conclusions: There is considerable variability in TPE in terms of teaching topics, providers, administration methods, and dosage of interventions. Future studies should investigate the effects of TPE in young adult populations and in ankle conditions. They should also investigate the effects of TPE on pain intensity versus pain interference with activities, by deepening TPE effects on disability and quality of life. Full article

Background/Objectives: Targeted muscle reinnervation and regenerative peripheral nerve interface procedures have emerged as effective techniques for reducing post-amputation pain and preventing symptomatic neuroma formation. However, the optimal timing of these procedures remains debated. This study aims to compare complication and reoperation rates between acute and delayed advanced nerve interface procedures in lower-extremity amputees. Methods: A retrospective cohort study was conducted including 74 patients who underwent acute or delayed targeted muscle reinnervation and/or regenerative peripheral nerve interface procedures between 2019 and 2025 at a tertiary academic medical center. Procedures performed concurrently with amputation or during early-stage reconstruction were classified as acute, whereas procedures performed more than one month after amputation were classified as delayed interventions. The primary outcome was postoperative surgical complications occurring within one year. Mann–Whitney U and chi-square tests were used for group comparisons. Univariable and multivariable logistic regression analyses were performed to identify factors associated with surgical complications, adjusting for potential confounders. A p-value < 0.05 was considered statistically significant. Results: Of 80 limbs, 47 (58.8%) underwent acute and 33 (41.3%) underwent delayed procedures. One-year complication rates were 23.4% in the acute group, and 12.1% in the delayed group, with wound-related complications predominantly occurring in patients undergoing amputation for infection or vascular disease. Unexpected reoperation rates were 19.1% for acute and 12.1% for delayed interventions. On univariable and multivariable analyses, early procedures demonstrated higher odds of surgical complications. However, these associations did not reach statistical significance and were limited by baseline differences in patient comorbidity and etiology. Conclusions: Early advanced nerve interface procedures were performed in more medically complex patients and were associated with higher observed rates of surgical complications, whereas delayed procedures were associated with a higher incidence of recurrent symptomatic neuromas. These findings underscore the importance of patient selection, etiology of amputation, and surgical context, rather than timing alone, when determining the optimal approach to nerve interface reconstruction following lower-extremity amputation. Full article

Tick-borne diseases are rising across Europe, yet human-biting tick data from the central Balkans remain limited. We analysed ticks removed from patients seeking care after tick bites at centers in Skopje (North Macedonia) and Novi Sad (Serbia) between January 2022 and December 2024, recording species, developmental stage, month of removal, and anatomical attachment site. A total of 1641 ticks were collected (North Macedonia, n = 157; Serbia, n = 1484) and identified morphologically. Six tick species were detected in North Macedonia and eight in Serbia. Ixodes ricinus was dominant in both countries, comprising ~69% of ticks in North Macedonia and >90% in Serbia, while Hyalomma marginatum was found in North Macedonia. Adult females predominated among ticks in North Macedonia (75.8%), whereas nymphs were most frequent among ticks in Serbia (55.6%); between-center comparisons of developmental stage should be interpreted cautiously given the marked sampling imbalance. In both settings, collections peaked in May–June (~64% of annual ticks), indicating highest bite pressure in late spring/early summer. Attachment sites were most commonly the torso and lower extremities, with significant between-country differences and species-/stage-specific patterns most evident in Serbia. These data refine the epidemiology of human tick exposure in two Balkan countries and support targeted seasonal prevention messaging and strengthened regional surveillance. Full article

Background: High residual platelet reactivity (HRPR) and persistent dyslipidemia remain important unmet needs in cardiovascular risk management, particularly in patients undergoing coronary revascularization. Despite intensive lipid-lowering and antiplatelet therapy, a substantial proportion of patients fail to reach recommended low-density lipoprotein cholesterol (LDL-C) targets or exhibit inadequate platelet inhibition. Inclisiran, a PCSK9-targeting small interfering RNA, represents an emerging approach for long-term LDL-C reduction. Methods: A narrative review of the literature published between 2009 and 2025 was performed using PubMed, Scopus, Web of Science, and MEDLINE. Studies evaluating the addition of inclisiran to standard lipid-lowering therapy in patients with dyslipidemia and HRPR, assessed using the VerifyNow assay, were included. Illustrative clinical cases from Kazakhstan were analyzed to demonstrate real-world changes in LDL-C levels and platelet reactivity following insufficient response to conventional treatment. The review had a descriptive design. Results: Available evidence indicates that a significant proportion of high- and very-high-risk patients do not achieve LDL-C targets or are unable to tolerate high-intensity statin therapy. Inclisiran consistently induces sustained reductions in LDL-C and circulating PCSK9 levels. Emerging data suggest a potential indirect modulation of platelet reactivity associated with intensive lipid lowering. In patients at extreme cardiovascular risk—including those after coronary artery bypass grafting (CABG) and with long-standing multivessel coronary artery disease—inclisiran therapy was associated with marked LDL-C reduction and a trend toward normalization of platelet reactivity. Conclusions: Assessment of platelet function using the VerifyNow assay may improve identification of residual thrombotic risk in patients with advanced atherosclerotic disease. Inclisiran appears to be a promising adjunctive therapy for dyslipidemic patients with persistently elevated cardiovascular risk and HRPR despite standard treatment. Further prospective studies are warranted to clarify the relationship between intensive LDL-C lowering, platelet reactivity, and clinical outcomes, and to optimize integrated lipid-lowering and antiplatelet strategies. Full article

Intermittent claudication (IC) is the most frequent symptomatic manifestation of lower-extremity peripheral artery disease (PAD). Supervised exercise therapy (SET) and endovascular revascularization (ER) are established treatments, but their relative and combined effects on health-related quality of life (HRQoL) remain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing SET, ER, and ER+SET, with HRQoL as the primary outcome. Methods: Following PRISMA 2020, PubMed, Embase, and CENTRAL were used in December 2024. Eligible RCTs enrolled with IC (excluding critical limb-threatening ischemia) and reported validated HRQoL outcomes at ≥3 months. Two reviewers independently extracted data and assessed risk of bias using the Cochrane RoB 2.0 tool. Random-effects meta-analyses pooled standardized mean differences (SMDs) for HRQoL and mean differences (MDs) for walking distance. Results: Five RCTs (n = 728) were included. Compared with optimal medical therapy, both SET and ER improved HRQoL and walking distance. At 12 months, no significant effect was observed between SET and ER (SMD 0.02; 95% CI: −0.18 to 0.22). ER+SET was superior to SET alone (SMD 0.35; 95% CI: 0.12–0.57). Beyond 24 months, improvements were sustained with SET but attenuated with ER, accompanied by higher reintervention rates in ER-containing arms (approximately 20–30% by 2 years). Adverse events were rare (<1%). Conclusions: Given moderate-certainty evidence (GRADE), SET should remain the first-line therapy for intermittent claudication because it provides durable improvements in patient-centered outcomes with minimal harm. Endovascular revascularization (ER) can provide faster symptom relief, but its long-term benefits are constrained by restenosis and repeat procedures, particularly in femoropopliteal disease. Full article

Background: Sinonasal neuroendocrine carcinoma (SNEC) is an extremely rare malignancy, and, to date, no clinical reports have detailed the use of proton beam therapy (PBT) for this disease. The present study describes the clinical courses of patients with SNEC treated with PBT and highlights the advantages of PBT. Methods: In this retrospective study, we included patients with pathologically confirmed SNEC without distant metastasis who underwent PBT at our institution between 2006 and 2021. To evaluate the dosimetric advantages of PBT, comparative treatment plans using VMAT were created. Result: Six patients with pathologically diagnosed SNEC without distant metastasis were treated with PBT. Multimodal treatment was applied in five patients, including chemotherapy in four cases and surgery in two cases. The median follow-up period was 37.4 months (range: 6.9 to 108.9 months). At the end of the follow-up, three patients were alive without recurrence, while three had died due to the disease. Recurrence occurred in three cases: one local recurrence, one in cervical lymph nodes, and two distant metastases. A late adverse event of Grade 4 vision decrease was observed in one patient on the ipsilateral side. Compared with VMAT, PBT lowered the average brain dose (median 3.3 Gy (RBE) vs. 12.6 Gy), brainstem D2 cc (10.7 Gy (RBE) vs. 34.9 Gy) and contralateral optic nerve D0.1 cc (47.6 Gy (RBE) vs. 63.3 Gy), while doses to the ipsilateral optic pathway were comparable. Conclusions: PBT in multimodal treatment achieved feasible local control for SNEC. The dose-sparing effect of PBT was more evident in organs distant from the target, although careful consideration is required for adjacent structures. Full article

Background and Clinical Significance: Paroxysmal extreme pain disorder (PEPD) is an extremely rare autosomal dominant sodium channelopathy caused by SCN9A gain-of-function variants. It is characterized by infantile-onset excruciating paroxysmal pain, typically in rectal, ocular, or mandibular regions, triggered by innocuous stimuli and accompanied by autonomic flares. Carbamazepine is dramatically effective in most reported cases. To date, only two genetically confirmed cases have been documented in Chinese patients, and fewer than 20 disease-causing variants are reported worldwide. We report the third Chinese case harboring a novel likely pathogenic SCN9A variant (p.Leu1623Gln), notable for its unusually severe, progressive, and carbamazepine-refractory phenotype, as well as life-threatening psychiatric sequelae, highlighting phenotypic heterogeneity and the devastating impact when standard therapy fails. Case Presentation: A Chinese male proband with positive family history presented with lifelong trigger-induced catastrophic burning and tearing pain in the perineum and lower limbs, associated with erythema, swelling, and occasional non-epileptic seizures. Attacks worsened with age despite escalating polypharmacy, including high-dose opioids, benzodiazepines, topical lidocaine and carbamazepine. Both the proband and his father developed profound psychosocial sequelae including severe depression and suicidal attempts. Next-generation sequencing in the proband revealed a novel heterozygous likely pathogenic variant NM_001365536.1 (SCN9A): c.4868T>A p.(Leu1623Gln). Conclusions: This third reported ethnic Chinese PEPD case expands the genotypic and phenotypic spectrum of SCN9A-related channelopathies, demonstrating that some variants can produce carbamazepine-refractory, progressive, and profoundly disabling disease with high suicidality risk. Early genetic diagnosis is critical in family planning and cascade testing, and has the potential in guiding targeted therapy that is under active research. Full article

Acute myocardial infarction (AMI) is a significant factor leading to the death of patients with coronary heart disease. Both AMI and reperfusion therapy after AMI cause myocardial cell death, which plays a significant role in heart failure. Following the restoration of blood flow during reperfusion, myocardial cells generate a large amount of oxygen free radicals, causing various forms of myocardial ischemia–reperfusion (IR) injury (IRI), ultimately leading to multiple types of myocardial cell death, among which apoptosis and necroptosis are the two major types. Given the extremely limited regenerative capacity of myocardium, inhibiting myocardial cell apoptosis and necroptosis is a key strategy for reducing mortality in patients with AMI. Both apoptosis and necroptosis are regulated by the BCL2 family of proteins, which were modulated by multiple signaling pathways, converging at BAK/BAX-mediated mitochondrial outer membrane permeabilization (MOMP), as well as mitochondrial inner membrane permeabilization (MIMP). BAK/BAX double knock out (DKO) mice showed reduced cell apoptosis, necroptosis, and infarct size in AMI animal models compared to wild type. This review describes the role of BCL2 family proteins in regulating apoptotic and necroptotic myocardial cell death during AMI and IR, explores the upstream pathways modulating apoptosis and necroptosis, and summarizes the recent advances in targeting BAK and/or BAX for cardiac protection. In addition, targeted delivery of BAK/BAX inhibitors to cardiomyocytes during AMI or myocardial IR has the potential to reduce myocardial cell death and therefore lower the mortality and enhance long-term prognosis for myocardial infarction patients. Full article

Coarctation of the aorta is a localized narrowing of the aortic lumen. This pathology leads to hypertension in upper extremity vessels, left ventricular hypertrophy and to impaired perfusion of the abdominal cavity and lower extremities. Along with traditional diagnostic methods, mathematical modeling is used for risk assessment and the prediction of disease outcomes. However, when applying numerical models to describe hemodynamic parameters, the choice of turbulence model to describe swirling flow occurring in the aorta in this pathology must be justified. Thus, three turbulence models, namely k-ε, k-ω, and SST were analyzed for the description of swirling flows in the study of coarctation’s effect on hemodynamic parameters and analysis of the mechanisms leading to various cardiovascular diseases caused by altered hemodynamics. The results revealed significant differences in swirling flow patterns between the k-ε and k-ω models, while the k-ω and SST models showed consistent results over the cardiac cycle. In the peak systolic phase, average velocity rises to 1.07–1.98 m·s⁻¹ for the k-ε model, 0.82–2.12 m·s⁻¹ for the k-ω model, 1.22–2.12 m·s⁻¹ for the SST model and 0.8–2.12 m·s⁻¹ for laminar flow. WSS values increase rapidly to 11–22 Pa in k-ε, 25–50 Pa in k-ω and SST models of turbulence, and 30–55 Pa for laminar flow. Significant differences were also evident in the prediction of wall shear stress, with the k-ε model giving values more than twice as high as the k-ω and SST models. The data obtained confirm the necessity of careful model selection for accurate hemodynamic parameter estimation, especially in coarctation. The findings of this study can be used for further physics-informed neural network analysis of evaluation of treatment evaluations for congenital heart disease patients. Full article

Background and Objectives: Sarcopenia and muscle wasting contribute significantly to functional decline in older adults, but differences in lower extremity muscle stiffness and gait variability between these groups are not yet fully understood. This study aimed to compare gait variability, and lower extremity muscle stiffness during contraction and relaxation in community-dwelling older adults classified as non-diseased, sarcopenic, and dynapenic. Materials and Methods: This cross-sectional study included 164 community-dwelling older adults classified as non-diseased, dynapenic, or sarcopenic, based on handgrip strength, 5-time sit-to-stand test, and skeletal muscle index. Spatiotemporal gait variability was measured at the participants’ preferred speed. Moreover, muscle thickness, as well as the contractile and relaxed stiffness, were measured for the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), gastrocnemius medialis (GAmed), and lateralis (GAlat). Results: In dynapenic and sarcopenic groups, gait variability increased across most parameters, but only the step width coefficient of variation differed significantly between the dynapenic and sarcopenic groups. Contractile stiffness of the RF, BF, and GAlat was lower in both groups, with additional GAmed stiffness reduction in the sarcopenic group. Relaxed stiffness of the BF and GAmed was significantly higher in the sarcopenic group than in the dynapenic group. Conclusions: This study identified differences in muscle thickness, stiffness, and gait variability among non-diseased, dynapenic, and sarcopenic older adults. Step width variability, GAmed contractile stiffness, and BF and GAmed relaxed stiffness emerged as potential early indicators for distinguishing dynapenia from sarcopenia. These findings highlight the importance of assessing muscle quality—including both mass and stiffness characteristics—to better characterize early stages of age-related muscle decline and to inform targeted intervention strategies. Full article

Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome (HPS) present two vascular complications of portal hypertension, which make opposite extremes occur against the same pathophysiological background. In PoPH, vasoconstriction predominates, along with gradual remodeling of pulmonary arteries, while HPS develops due to pathological vasodilation and creation of intrapulmonary shunts. Even though they come about by different mechanisms, both disorders significantly affect quality of life, survival, and the possibility of liver transplant. In the early phases, in clinical practice, symptoms are mainly mild and nonspecific, and overlapping with symptoms of advanced liver disease often delays forming a diagnosis. In PoPH, elevated pressures in pulmonary arteries and increased vascular resistance are observed, while HPS exhibits arterial hypoxemia with normal or lowered pulmonary pressure. Standard diagnostic workup includes echocardiography, right-heart catheterization, and analysis of the arterial gases. In patients with severe PoPH, pronounced pulmonary hypertension can represent absolute contraindication for liver transplantation due to risk of acute right heart failure during operation. Conversely, HPS usually resolves itself after a successful transplant, which confirms that the transplant is an indication of being potentially curative. Therapeutic possibilities for both states are still limited. In PoPH, specific vasodilators and supportive measures are applied, while HPS treatment is mostly supportive, directed at maintaining oxygenation until the transplant. Future research should be focused on the development of targeted therapies that address vascular remodeling, angiogenesis, and oxidative stress, as well as on the standardization of diagnostic criteria and multicentric cooperation. This approach would facilitate earlier recognition, a precise assessment of transplantability, and a better long-term outcome for patients with portal hypertension and lung vascular complications. Key Points: Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome (HPS) represent two opposite vascular complications of portal hypertension, posing distinct challenges for liver transplantation. This review summarizes their pathophysiology, diagnostic pathways, and therapeutic strategies, emphasizing the importance of hemodynamic profiling and multidisciplinary management to optimize transplant outcomes. Full article

Background and Purpose: Surgical treatment of lower-extremity fractures can result in postoperative complications. Irrespective of specific surgical procedures, postoperative outcomes may be influenced by pre-existing comorbidities, as well as by the severity of the injury. This study investigates whether (I) internal factors and (II) external factors are associated with (III) postoperative complication rates. Material and Methods: A prospective study was conducted at a Level I trauma center between 2014 and 2018. A cohort of 416 patients with surgical treatment after traumatic long bone fractures of the lower extremities was assessed, with comorbidities along with factors such as age, malnutrition, and impaired mobility systematically evaluated. Injury severity was classified using the Abbreviated Injury Scale; fracture type and location using the AO/OTA classification; and postoperative complications using the Clavien–Dindo system. Results: Across the cohort, internal factors such as immobility and malnutrition were associated with an increased complication rate. Age showed a weak correlation. Obesity demonstrated a trend toward a protective effect. Patients with femoral fractures exhibited a higher prevalence of cardiovascular comorbidities, with heart failure representing the most pronounced risk factor. In the subgroup with lower leg fractures, chronic heart disease also remained a significant predictor of complications. Correlation analysis further revealed a significant positive association between injury severity and the occurrence of complications across the overall cohort. Conclusions: This study provides valuable insights into risk factors for complicated postoperative courses. Injury severity appears to be a promising predictor of complication risk in patients with leg fractures. Reduced mobility and malnutrition, likewise, were significantly associated with increased complication rates; these may represent the most readily addressable modifiable risk factors. All data were collected using validated, user-friendly classification systems that may be suitable for predictive modeling. Full article

Background/Objectives: Endovascular therapy (EVT) is the treatment of choice for femoropopliteal artery (FPA) disease manifesting as critical limb-threatening ischemia (CLTI) or intermittent claudication (IC). This study aimed to compare the clinical outcomes of patients with CLTI with those of patients with IC after EVT in a real-world setting. Methods: In total, 1924 patients with FPA disease (CLTI: n = 812, IC: n = 1112) from the K-VIS ELLA (Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases) registry who underwent EVT between 2006 and 2021 were analyzed. The primary endpoint was defined as target limb amputation or clinically driven (CD) target extremity revascularization (TER) 2 years after the procedure. Results: The incidence of the primary endpoint after inverse probability of treatment weighting (IPTW) was significantly higher in the CLTI group (hazard ratio [HR], 1.314; 95% confidence interval [CI], 1.105–1.561; p = 0.002). The incidences of loss of clinical patency, major adverse limb events (MALEs), and all-cause mortality were also higher in the CLTI group (hazard ratio [HR], 1.312; 95% confidence interval [CI], 1.157–1.488; p < 0.001). However, the risk of repeat percutaneous transluminal angioplasty (PTA) was similar between the groups (HR, 1.014; 95% CI, 0.833–1.234; p = 0.920). The use of drug-coated balloons (DCBs) was associated with favorable primary outcomes in both groups, particularly in patients with IC (HR: 0.429, 95% CI: 0.25–0.734; p = 0.002). Conclusions: Patients with CLTI undergoing EVT for FPA disease experienced worse clinical outcomes than those with IC, although the repeat PTA rates were similar. The use of DCBs showed promising results in both groups. Full article