Clinical relevance and druggability of sole reciprocal kinase fusions: A large-scale study.

BACKGROUND: Building on our prior work that RNA alternative splicing modulates the druggability of kinase fusions, this study probes the clinical significance of sole reciprocal fusions. These rare genomic arrangements, despite lacking kinase domains at the DNA level, demonstrated potential RNA-level druggability in sporadic cases from our prior research. METHODS: Utilizing the large-scale multicenter approach, we performed RNA sequencing and clinical follow-up to evaluate a broad spectrum of kinase fusions, including ALK, ROS1, RET, BRAF, NTRK, MET, NRG1, and EGFR, in 1943 patients. RESULTS: Our findings revealed 51 instances (2.57%) of sole reciprocal fusions, predominantly in lung (57%), colorectal (14%), and glioma (10%) cancers. Comparative analysis with an MSKCC cohort confirmed the prevalence in diverse cancer types and identified unique fusion partners and chromosomal locales. Cross-validation through RNA-NGS and FISH authenticated the existence of functional kinase domains in subsets including ALK, ROS1, RET, and BRAF, which correlated with positive clinical responses to targeted kinase inhibitors (KIs). Conversely, fusions involving EGFR, NRG1, and NTRK1/2/3 generated nonfunctional transcripts, suggesting the need for alternative therapeutic interventions. CONCLUSION: This inaugural multicenter study introduces a novel algorithm for detecting and treating sole reciprocal fusions in advanced cancers, expanding the patient population potentially amenable to KIs.

Comprehensive lipidomics study of basa catfish and sole fish using ultra-performance liquid chromatography Q-extractive orbitrap mass spectrometry for fish authenticity.

The authenticity of fish products has become a widespread issue in markets due to substitution and false labeling. Lipidomics combined with chemometrics enables the fraudulence identification of food through the analysis of a large amount of data. This study utilized ultra-high-performance liquid chromatography (UHPLC)-QE Orbitrap MS technology to comprehensively analyze the lipidomics of commercially available basa catfish and sole fish. In positive and negative ion modes, a total of 779 lipid molecules from 21 lipid subclasses were detected, with phospholipid molecules being the most abundant, followed by glycerides molecules. Significant differences in the lipidome fingerprinting between the two fish species were observed. A total of 165 lipid molecules were screened out as discriminative features to distinguish between basa catfish and sole fish, such as TAG(16:0/16:0/18:1), PC(14:0/22:3), and TAG(16:1/18:1/18:1), etc. This study could provide valuable insights into authenticating aquatic products through comprehensive lipidomics analysis, contributing to quality control and consumer protection in the food industry.

The Role of Sole Lift in Treating Pediatric Idiopathic Scoliosis with Mild Thoracolumbar/Lumbar Curve.

OBJECTIVE: Lower limb discrepancy (LLD) was frequently observed in patients with idiopathic scoliosis (IS), potentially associated with etiopathogenesis. Although sole lifts had been proposed as a conservative treatment for IS, evidence supporting their efficacy was limited. This study aimed to assess the effects of sole lift intervention on pediatric patients with mild IS, specifically focusing on thoracolumbar/lumbar (TL/L) curvature. METHODS: Twenty patients, with an average age of 12.3 ± 3.1 years and presenting mild TL/L curve (15.6° ± 6.2°), were selected from a pool of 267 pediatric IS patients in the outpatient of our spine center from February 2023 to August 2023. Inclusion criteria comprised a main TL/L curve ranging between 10° and 40°, the lower limb positioned at the convexity of the main curve, and LLD of less than 2 cm; individuals requiring bracing or surgical intervention were excluded. Custom sole lifts were used to address the shorter lower limb with the objective of leveling the pelvis. Radiographic evaluations were conducted both before and after intervention using standing full spine posteroanterior radiographs and full leg length radiographs. Statistical analysis was undertaken to evaluate curve correction and its associations with other influencing factors. RESULTS: The mean structural and functional LLD were 7.1 ± 4.5 mm and 7.1 ± 4.1 mm, respectively. Among the 20 patients, four exhibited structural LLD greater than 10 mm. The average follow-up duration was 6.4 ± 1.9 months (range: 3-8 months). Following sole lift intervention (7.0 ± 3.0 mm), a significant reduction was observed in the TL/L curve compared to the pre-sole lifting measurements (15.6° ± 6.2° vs. 12.1° ± 7.2°, p < 0.001), as well as a notable decrease in the thoracic curve (12.2° ± 4.0° vs. 8.6° ± 6.3°, p = 0.064). Nine patients experienced a significant curve reduction of ≥5°, while eight showed a reduction between 0° and 5°; however, two patients exhibited no change in curve magnitude. Furthermore, the correction rate of the TL/L curve correlated significantly with functional LLD (r = -0.484, p = 0.030) and pelvic obliquity (r = -0.556, p = 0.011), highlighting the active pelvic compensation in maintaining balance between the spine and lower limbs. Conversely, no significant correlation was observed between curve correction and structural LLD (p > 0.05). Additionally, even after adjusting for other influencing factors, the TL/L Cobb angle remained significantly different between pre- and post-sole lifting (p = 0.037). CONCLUSION: This study confirmed the effectiveness of sole lift intervention in correcting TL/L and thoracic curves among the mild IS children with a main TL/L curve, providing a supplementary conservative treatment option for patients with the lower limb at the convexity of the main curve. Moreover, our findings underscored the active compensation of the lower limbs and the pelvis in the etiopathogenesis of IS, highlighting the importance of considering their influence in treatment strategies.

Leptins regulate the migration, proliferation, apoptosis, and synthesis of sexual steroid in tongue sole (Cynoglossus semilaevis) ovarian cells.

Leptin is an important hormone in mammals, which plays a key role in regulating reproduction and energy metabolism. However, there are few studies on the function of leptin in reproductive regulation in fish, especially on tongue sole (Cynoglossus semilaevis). Thus, in this study, we firstly exploited the basic function of tongue sole leptins, the migration and growth rate of ovarian cells were reduced after knocking down lepA and lepB in ovarian cells, while increasing the apoptosis rate. Then both rlepA and rlepB were proved to be combined with lepR to further exert functions by dual luciferase assay. Transcriptome sequencing showed that differentially expressed genes (DEGs) were mainly enriched in KEGG pathways related to membrane receptors, fatty acid synthesis, growth, etc. when lepA and lepB were knocked down or additionally added in vitro. Additionally, the estradiol (E2) hormone was increased significantly after knocking down lepB. Finally, based on DEGs and the signaling pathways they participated in, we proposed a hypothesis about the signaling pathways in which leptin may be involved in ovarian cells. Taken together, these results provide new insights into the role of leptin in the regulation of physiological functions such as ovarian growth and development.

Efficacy of auxetic lattice structured shoe sole in advancing footwear comfort-From the perspective of plantar pressure and contact area.

Introduction: Designing footwear for comfort is vital for preventing foot injuries and promoting foot health. This study explores the impact of auxetic structured shoe soles on plantar biomechanics and comfort, motivated by the integration of 3D printing in footwear production and the superior mechanical properties of auxetic designs. The shoe sole designs proposed in this study are based on a three-dimensional re-entrant auxetic lattice structure, orthogonally composed of re-entrant hexagonal honeycombs with internal angles less than 90 degrees. Materials fabricated using this lattice structure exhibit the characteristic of a negative Poisson's ratio, displaying lateral expansion under tension and densification under compression. Methods: The study conducted a comparative experiment among three different lattice structured (auxetic 60°, auxetic 75° and non-auxetic 90°) thermoplastic polyurethane (TPU) shoe soles and conventional polyurethane (PU) shoe sole through pedobarographic measurements and comfort rating under walking and running conditions. The study obtained peak plantar pressures (PPPs) and contact area across seven plantar regions of each shoe sole and analyzed the correlation between these biomechanical parameters and subjective comfort. Results: Compared to non-auxetic shoe soles, auxetic structured shoe soles reduced PPPs across various foot regions and increased contact area. The Auxetic 60°, which had the highest comfort ratings, significantly lowered peak pressures and increased contact area compared to PU shoe sole. Correlation analysis showed that peak pressures in specific foot regions (hallux, second metatarsal head, and hindfoot when walking; second metatarsal head, third to fifth metatarsal head, midfoot, and hindfoot when running) were related to comfort. Furthermore, the contact area in all foot regions was significantly associated with comfort, regardless of the motion states. Conclusion: The pressure-relief performance and conformability of the auxetic lattice structure in the shoe sole contribute to enhancing footwear comfort. The insights provided guide designers in developing footwear focused on foot health and comfort using auxetic structures.

The genome sequence of the thickback sole, Microchirus variegatus (Donovan, 1808).

We present a genome assembly from an individual female Microchirus variegatus (the thickback sole; Chordata; Actinopteri; Pleuronectiformes; Soleidae). The genome sequence is 724.7 megabases in span. Most of the assembly is scaffolded into 23 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 17.42 kilobases in length.

Transcriptional responses consistent with perturbation in dermo-epidermal homeostasis in septic sole ulceration.

The aim of this study was to evaluate transcriptional changes in sole epidermis and dermis of bovine claws with septic sole ulceration of the lateral claw. Assessment included changes in transcripts orchestrating epidermal homeostatic processes including epidermal proliferation, differentiation, inflammation, and cell signaling. Sole epidermis and dermis was removed from region 4 of lesion-bearing lateral and lesion-free medial claws of pelvic limbs in multiparous, lactating Holstein cows. Control sole epidermis and dermis was obtained from region 4 of lateral claws of normal pelvic limbs. Transcript abundances were evaluated by real-time QPCR and relative expression analyzed by ANOVA. Relative to normal lateral claws, sole epidermis and dermis in ulcer-bearing claws exhibited downregulation of genes associated with growth factors, growth factor receptors, activator protein 1 (AP-1) and proto-oncogene (CMYC) transcription components, cell cycle elements, lateral cell-to-cell signaling elements and structures of early and late keratinocyte differentiation. These changes were accompanied by upregulation of pro-inflammatory transcripts interleukin 1 α (IL1A), interleukin1 ß (IL1B), interleukin 1 receptor 1 (IL1R1), inducible nitric oxide synthase (NOS2), the inflammasome components NOD like receptor protein 3 (NLRP3), pyrin and caspase recruitment domain (PYCARD), and caspase-1 interleukin converting enzyme (CASPASE), the matrix metalloproteinases (MMP2 and MMP9), and anti-inflammatory genes interleukin 1 receptor antagonist (IL1RN) and interleukin1 receptor 2 (IL1R2). Transcript abundance varied across epidermis and dermis from the ulcer center, margin and epidermis and dermis adjacent to the lesion. Sole epidermis and dermis of lesion-free medial claws exhibited changes paralleling those in the adjacent lateral claws in an environment lacking inflammatory transcripts and downregulated IL1A, interleukin 18 (IL18), tumor necrosis factor α (TNFA) and NOS2. These data imply perturbations in signal pathways driving epidermal proliferation and differentiation are associated with, but not inevitably linked to epidermis and dermis inflammation. Further work is warranted to better define the role of crushing tissue injury, sepsis, metalloproteinase activity, and inflammation in sole ulceration.

Molecular evidence sterile tissue damage during pathogenesis of pododermatitis aseptica hemorrhagica circumscripta is associated with disturbed epidermal-dermal homeostasis.

Podermatitis aseptica hemorrhagica circumscripta is associated with metalloproteinase 2 weakening of distal phalangeal suspensory structures and sinkage of the distal phalanx in the claw capsule. Pressure from the tuberculum flexorium on the sole epidermis and dermis produces hemorrhagic tissue injury and defective horn production appearing as yellow-red, softened claw horn in region 4 of the sole. A model of the MAPK/ERK signal cascade orchestrating epidermal-dermal homeostasis was employed to determine if sterile inflammatory responses are linked to disturbed signal transduction for epidermal homeostasis in sole epidermis and dermis. The objective was to assess shifts in target genes of inflammation, up- and downstream MAPK/ERK signal elements, and targeted genes supporting epidermal proliferation and differentiation. Sole epidermis and dermis was removed from lateral claws bearing lesions of podermatitis aseptica hemorrhagica circumscripta, medial claws from the same limb and lateral claws from completely normal limbs of multiparous, lactating Holstein cows. The abundance levels of targeted transcripts were evaluated by real-time QPCR. Lesion effects were assessed by ANOVA, and mean comparisons were performed with t-tests to assess variations between mean expression in ulcer-bearing or medial claw dermis and epidermis and completely normal lateral claw dermis and epidermis or between ulcer-bearing dermis and epidermis and medial claw dermis and epidermis. The lesions were sterile and showed losses across multiple growth factors, their receptors, several downstream AP1 transcription components, CMYC, multiple cell cycle and terminal differentiation elements conducted by MAPK/ERK signals and ß 4, α 6 and collagen 17A hemidesmosome components. These losses coincided with increased cytokeratin 6, ß 1 integrin, proinflammatory metalloproteinases 2 and 9, IL1B and physiologic inhibitors of IL1B, the decoy receptor and receptor antagonist. Medial claw epidermis and dermis from limbs with lateral claws bearing podermatitis aseptica hemorrhagica circumscripta showed reductions in upstream MAPK/ERK signal elements and downstream targets that paralleled those in hemorrhagic lesions. Inhibitors of IL1B increased in the absence of real increases in inflammatory targets in the medial claw dermis and epidermis. Losses across multiple signal path elements and downstream targets were associated with negative effects on targeted transcripts supporting claw horn production and wound repair across lesion-bearing lateral claws and lesion-free medial claw dermis and epidermis. It was unclear if the sterile inflammation was causative or a consequence of these perturbations.

Association between hoof trimming frequency in primiparous cows and hoof health and survival in second lactation.

Lameness, mostly resulting from claw lesions, causes major welfare problems in the dairy industry. One way to prevent claw lesions is hoof trimming, but the overall effect and the optimal hoof trimming frequency are unknown. In a retrospective cohort study, we investigated the association between hoof trimming frequency in primiparous cows and hoof health and culling in second lactation. We based our analysis on breed, calving and culling data in the period 2015-2018 for 30,613 primiparous cows in 202 Swedish dairy herds. Of the cows enrolled, 20% were not hoof-trimmed, 30% were trimmed once, 34% were trimmed twice, 13% were trimmed 3 times, and 2% were trimmed ≥ 4 times. We used multivariable mixed-effect logistic and multivariable multinomial logistic regression models to investigate the association between trimming frequency and 2 outcomes: hoof lesions at first trimming occasion within 90 d from second calving and culling in second lactation within 300 d after second calving. In general, cows trimmed 2 or 3 times during first lactation were at lower odds of having claw lesions compared with cows that were not trimmed (Odds Ratio (OR) = 0.66, 95% CI = 0.62-0.71 and 0.60, 95% CI = 0.55-0.66, respectively) or cows trimmed once (OR = 0.80, 95% CI = 0.75-0.85 and OR = 0.72, 95% CI = 0.66-0.79, respectively), and this beneficial effect was observed for most types of claw lesions. Moreover, cows trimmed 2, 3, or ≥ 4 times were at lower odds of being culled compared with cows that were not trimmed (OR = 0.71, 95% CI = 0.65-0.77, 0.68, 95% CI = 0.61-0.76 and 0.70, 95% CI = 0.54-0.90, respectively) or trimmed once (OR = 0.77, 95% CI = 0.71-0.83, OR = 0.74, 95% CI = 0.66-0.82 and OR = 0.75, 95% CI = 0.59-0.97, respectively). In particular, 2 trimmings, compared with 1 or no trimming, lowered the relative risk-ratio of dying or being euthanized on-farm, or being culled due to claw and leg disorders. More than 1 hoof trimming in first lactation also reduced the relative-risk ratio of being culled for other reasons. In conclusion, 2 or 3 hoof trimmings during first lactation were generally beneficial for hoof health in early second lactation and survival in second lactation. These findings can help improve animal welfare and production by reducing claw lesions, and thereby lameness among dairy cows, which would increase the longevity of dairy cows and the sustainability of the dairy industry.

The Impacts of Planting Patterns Combined with Irrigation Management Practices on Watermelon Growth, Photosynthesis, and Yield.

(1) Background: Crop yields in China's arid and semi-arid regions are limited by water shortages. Exploring the interactions and resource utilization among agroforestry species is key to maintaining diversified agricultural production. (2) Objective: An apple-watermelon agroforestry system and watermelon sole-cropping system were compared to quantify how resource availability (light, water) and watermelon performance (leaf photosynthetic rate, growth, and yield) change with irrigation strategies. (3) Methods: A three-year apple and watermelon field experiment was conducted in a young apple orchard in the arid area of central Ningxia to test the effect of light competition and irrigation systems on light environment, leaf photosynthetic rate, plant growth, and yield in watermelon. The experiment encompassed two planting patterns: (i) apple-watermelon agroforestry (AF) and watermelon sole-cropping (SC) and (ii) three irrigation quotas (W1: 105 mm, W2: 210 mm, and W3: 315 mm). (4) Results: The results show that the agroforestry planting pattern extended the growth period of watermelon and increased the leaf area index. Mean daily shade intensity increased by 16.02% from 2020 to 2022. The land equivalent ratio (LER) was >1 in 2021 and 2022. The SWC, leaf photosynthetic rate, LAI, and yield of watermelon in an agroforestry planting pattern were lower than when in a sole-cropping planting pattern. However, under the W1 irrigation strategy, the total soluble solids of the agroforestry planting pattern were 2.27% higher than those of the sole-cropping pattern, and the yield of the agroforestry planting pattern was 2.59% higher than that of the sole-cropping pattern. Under the W3 irrigation strategy, the average watermelon weight in the agroforestry planting pattern was 2.85% higher than that of the sole-cropping pattern. A path analysis showed that the agroforestry planting pattern can increase the yield by increasing soil water content, which is different from the sole-cropping pattern. (5) Conclusions: The results confirm that the apple-watermelon agroforestry planting pattern reduced watermelon yields. However, the LER of the agroforestry system was greater than 1.0. It is reasonable to plant watermelons in young apple forests.

miR-144 affects the immune response and activation of inflammatory responses in Cynoglossus semilaevis by regulating the expression of CsMAPK6.

MicroRNAs are increasingly recognized for their pivotal role in the immune system, yet the specific regulatory functions of fish-derived microRNAs remain largely unexplored. In this research, we discovered a novel miRNA, Cse-miR-144, in the Chinese tongue sole (Cynoglossus semilaevis), characterized by a 73-base pair precursor and a 21-nucleotide mature sequence. Our findings revealed that the expression of Cse-miR-144 was notably inhibited by various Vibrio species. Utilizing bioinformatics and dual-luciferase assay techniques, we established that the pro-inflammatory cytokine gene CsMAPK6 is a direct target of Cse-miR-144. Subsequent in vitro and in vivo western blotting analyses confirmed that Cse-miR-144 can effectively reduce the protein levels of CsMAPK6 post-transcriptionally. Moreover, CsMAPK6 is known to be involved in the activation of the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB). Additional investigations using qPCR and ELISA demonstrated that suppression of Cse-miR-144 leads to an upsurge in the liver mRNA levels of various immune genes (including MYD88, TRAF6, NF-κB, TRAF2, TRAF3, and TNF), alongside a marked increase in the production and secretion of pro-inflammatory cytokines (IL-1ß, IL-6, and IL-8) in the bloodstream of C. semilaevis. These findings collectively underscore the potential of Cse-miR-144 as a key inhibitor of CsMAPK and its crucial role in modulating the immune and inflammatory responses in teleost fish. Compared to the siRNA, miRNA is a better tool in controlling the expression of target gene with a lower cost.

Mechanoreceptor sensory feedback is impaired by pressure induced cutaneous ischemia on the human foot sole and can predict cutaneous microvascular reactivity.

Introduction: The foot sole endures high magnitudes of pressure for sustained periods which results in transient but habitual cutaneous ischemia. Upon unloading, microvascular reactivity in cutaneous capillaries generates an influx of blood flow (PORH: post-occlusive reactive hyperemia). Whether pressure induced cutaneous ischemia from loading the foot sole impacts mechanoreceptor sensitivity remains unknown. Methods: Pressure induced ischemia was attained using a custom-built-loading device that applied load to the whole right foot sole at 2 magnitudes (15 or 50% body weight), for 2 durations (2 or 10 minutes) in thirteen seated participants. Mechanoreceptor sensitivity was assessed using Semmes-Weinstein monofilaments over the third metatarsal (3MT), medial arch (MA), and heel. Perceptual thresholds (PT) were determined for each site prior to loading and then applied repeatedly to a metronome to establish the time course to return to PT upon unload, defined as PT recovery time. Microvascular flux was recorded from an in-line laser speckle contrast imager (FLPI-2, Moor Instruments Inc.) to establish PORH peak and recovery rates at each site. Results: PT recovery and PORH recovery rate were most influenced at the heel and by load duration rather than load magnitude. PT recovery time at the heel was significantly longer with 10 minutes of loading, regardless of magnitude. Heel PORH recovery rate was significantly slower with 10minutes of loading. The 3MT PT recovery time was only longer after 10 minutes of loading at 50% body weight. Microvascular reactivity or sensitivity was not influenced with loading at the MA. A simple linear regression found that PORH recovery rate could predict PT recovery time at the heel (R2=0.184, p<0.001). Conclusion: In populations with degraded sensory feedback, such as diabetic neuropathy, the risk for ulcer development is heightened. Our work demonstrated that prolonged loading in healthy individuals can impair skin sensitivity, which highlights the risks of prolonged loading and is likely exacerbated in diabetes. Understanding the direct association between sensory function and microvascular reactivity in age and diabetes related nerve damage, could help detect early progressions of neuropathy and mitigate ulcer development.

'We no longer experience the same pain': a cross-sectional study assessing the impact of Heart and Sole Africa's podoconiosis prevention education program.

BACKGROUND: Podoconiosis is a non-infectious neglected tropical disease caused by long-term exposure to irritant volcanic soils. It results in severe physical, psychological and financial consequences. Heart and Sole Africa (HASA) is a non-governmental, community-based organization providing management to podoconiosis patients in Rwanda. We sought to analyze the impact of their program on the lives of patients. METHODS: Quantitative surveys recorded the participants' demographics, adherence to HASA's management recommendations and changes in quality of life (QOL). Qualitative questions were used to gather respondent perspectives on HASA programming. RESULTS: We interviewed 127 patients from HASA's Musanze (n=47) and Burera (n=80) clinics. Almost all participants (98.4%) reported statistically significant (p<0.01) improvements in their QOL, and more than one-half (51.2%) had a favorable adherence score of >80%. Qualitative feedback identified specific challenges to adherence and recognition of program success in symptom management. CONCLUSIONS: Our study demonstrated the value of community-based podoconiosis programming in improving the lives of patients. Practices such as regular feet washing, emollient application, shoe wearing and limb raising can result in a marked reduction of morbidity. Our findings support the argument for scaling up these management practices across Rwanda.

Water-in-oil adjuvant challenges in fish vaccination: An experimental inactivated adjuvanted vaccine against betanodavirus infection in Senegalese sole.

The extensive growth of intensive fish farming has led to a massive spread of infectious diseases. Nervous necrosis virus (NNV) is the causative agent of the viral encephalo- and retinopathy disease which has become a major threat for fish farming all over the globe. The devastating mortality rates recorded in disease outbreaks, especially when infected specimens are at early stages of development, have a high economic impact on the sector. Currently, vaccines are the most cost-effective preventing tool in the fight against viruses. Inactivated vaccines have the advantage of simplicity in their development at the same time as present the antigen in a similar manner than the natural infection in the host. Nevertheless, they usually trigger weaker immune responses needing adjuvants to boost their effectiveness. In this work, we have intraperitoneally vaccinated Senegalese sole juveniles (Solea senegalensis) with a previously designed inactivated vaccine against NNV based on binary ethylenimine (BEI), mixed or not with an oil-adjuvant. Our results demonstrated the potential activation of different immune pathways when the vaccine was administered alone compared to the oil-adjuvanted vaccine, both resulting in an equivalent partial improvement in survival following a NNV challenge. However, whilst the vaccine alone led to a significant increase in specific antibodies, in the adjuvanted version those antibodies were kept basal although with a slight improvement in their neutralization capacity. At transcriptional level, neither vaccine (adjuvanted or not) triggered the immune system activation during the vaccination period. However, after NNV infection, the BEI-inactivated vaccines alone and oil-adjuvanted both elicited the stimulation of antiviral responsive genes (rtp3, herc4), antigen presentation molecules (mhcii) and T-cell markers (cd8a) in the head-kidney. Additionally, the oil-adjuvanted vaccine appears to stimulate mediator cytokines (il6) and B-cell markers (ight and ighm). Surprisingly, when the adjuvant was administered alone, fish showed the highest survival rates concomitantly with a lack of NNV-IgM production, pointing to the possible induction of different immune pathways than the B-cell responses via antibodies by the adjuvant. Since this combined vaccine did not succeed in the full extension of protection against the pathogen, further studies should be performed focusing on unravelling the molecular mechanisms through which adjuvants trigger the immune response, both independently and when added to a vaccine antigen.

Interactive impacts of CO2-induced seawater acidification and cadmium exposure on antioxidant defenses of juvenile tongue sole Cynoglossus semilaevis.

Antioxidant responses of juvenile sole exposed to seawater acidification (SA) and Cd were investigated. SA increased lipid peroxidation (LPO) in the fish, independent of Cd concentrations. Cd at medium and high levels inflated LPO under no or moderate SA conditions. This effect was absent under high SA levels, due to SA effect exceeding and obscuring Cd effect. SA and Cd collaborated to provoke LPO, with SOD and CAT being stimulated to defend against oxidative stress, while those related to GSH redox cycle were inhibited under SA exposure. Responses of GSH-related antioxidants to Cd impact varied contingent on their interactions with SA. This defensive strategy was insufficient to protect fish from increased LPO. Antioxidants responded more sensitively to SA than Cd exposure. GSH, GR, SOD and CAT are sensitive biomarkers for SA conditions. The findings offer insights into assessing fish's antioxidant defense strategy under Cd and SA circumstances in natural habitats.

Effectiveness of gait plate insole and lateral sole wedged shoes on foot progression angle in children with in-toeing gait: A prospective randomized control trial.

BACKGROUND: In-toeing gait is defined as the internal rotation of the long axis of the foot to the line of progression. Although most of the time it is corrected spontaneously but sometimes causes torsional misalignment syndrome and maybe patellofemoral instability and arthritis of the knee. RESEARCH QUESTION: What is the effect of gait plate insoles and lateral sole wedged shoes on foot progression angle (FPA) in children with in-toeing? METHOD: In this study, a randomized control trial was conducted with 11 participants (18 feet) who were girls aged between seven and ten years old. They were randomly assigned to either the gait plate group (6 girls, 11 feet) or the lateral sole wedge group (5 girls, 11 feet). The foot progression angle was measured using the RS scanner pressure platform before and after four weeks of intervention, both with and without interventions. The interaction effects of time and group on outcomes were analyzed using Mixed ANOVA and post-hoc complementary tests with a confidence interval of 95%. RESULTS: It was observed that none of the interventions had an immediate impact on the FPA (P > 0.05). However, after four weeks, the FPA increased by 9.96 degrees with the lateral sole wedge and by 3.51 degrees with the gate plate insole. During the immediate and short-term evaluation, no significant difference was noticed between the two groups (P > 0.05). However, there was a large effect size (eta square = 0.269) observed in the time group interaction between the two groups (P = 0.028). SIGNIFICANCE: Conservative methods like using a gait plate insole or modifying shoes with a lateral sole wedge can improve the foot progression angle in children with in-toeing gait. However, longer studies with larger sample sizes are needed to reach a conclusion.

Effect of dietary l-glutamine supplementation on the intestinal physiology and growth during Solea senegalensis larval development.

The maturation of the intestinal digestive and absorptive functions might limit the amount of absorbed nutrients to fulfil the high requirements of the fast-growing marine fish larva. Glutamine (Gln) has been described to improve intestinal epithelium functions, due to its involvement in energy metabolism and protein synthesis. The purpose of this study was to evaluate dietary 0.2% Gln supplementation on aspects of intestinal physiology, protein metabolism and growth-related genes expression in Senegalese sole larvae. Experiment was carried out between 12 and 33 days post hatching (DPH) and fish were divided into two experimental groups, one fed Artemia spp. (CTRL) and the other fed Artemia spp. supplemented with Gln (GLN). GLN diet had two times more Gln than the CTRL diet. Samples were collected at 15, 19, 26 and 33 DPH for biometry, histology, and digestive enzymes activity, and at 33 DPH for gene expression, protein metabolism and AA content determination. Growth was significantly higher for Senegalese sole fed GLN diet, supported by differences on protein metabolism and growth-related gene expression. Slight differences were observed between treatments regarding the intestinal physiology. Overall, GLN diet seems to be directed to enhance protein metabolism leading to higher larval growth.

A 20-year misdiagnosis: a rare presentation of a basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common form of skin cancer. BCCs are seldom reported on the sole of the foot due to a lack of exposure to UV radiation which is the main risk factor. We present a brief literature review and case report of a 42-year-old female with a non-resolving lesion on the mid-arch of her left foot over a 20-year period. Tissue diagnosis identified the lesion as a BCC. Disease-free control was achieved but the patient experienced significant morbidity resulting in three separate procedures to diagnose, excise and reconstruct the defect. When evaluating lesions on the sole clinicians should consider BCC as a differential, particularly in those which do not respond to initial treatment.

Sustainable Composites: Analysis of Filler-Rubber Interaction in Natural Rubber-Styrene-Butadiene Rubber/Polyurethane Composites Using the Lorenz-Park Method and Scanning Electron Microscopy.

This study examined micronized polyurethane residues as a reinforcing filler in elastomeric composites made from natural rubber (NR) and styrene-butadiene rubber (SBR). Due to growing environmental concerns, this research aimed to find sustainable alternatives to synthetic materials. The results indicated that adding micronized polyurethane improved the mechanical properties of the composites, reinforcing the polymer matrix and increasing the cross-link density as a barrier against solvents. The composites met the requirements for industrial applications, though; at 40 phr of polyurethane filler, material deformation was reduced, indicating saturation. FTIR analysis confirmed the homogeneity of the materials without chemical reactions, while electron microscopy revealed an increase in the number of particles and irregularities with the filler. The composite with 10 phr showed a lower volume loss in abrasion resistance, meeting the standards for soles. The composite with 30 phr of polyurethane achieved the best results without the filler's saturation and met the footwear industry's requirements. The results show the potential for sustainable practices in industry using this elastomeric blend.

Elucidating sole application of farmyard manure and blended NPSB fertilizer effects on soil properties at Bench Shako and West Omo zone, South West Ethiopia.

Soil nutrient depletion is the main problem in Ethiopia for agriculture sector. Comparison of organic and inorganic source of fertilizer is needed for soil physicochemical properties improvement. Hence, the current study was investigated to investigate the sole application of farmyard manure and blended NPSB fertilizer on soil properties. For this investigation, farm yard manure at three level (0,5, and 10 t ha-1) and NPSB at four level (0, 50, 100, and 150 kg ha-1). All collected data were analysed by GenStat software. Sole application of farm yard manure significantly improves soil bulk density ((1.23 gcm3 to 1.11 gcm3 at kuja Guraferda, and 2.22 gcm3 to 1.12 g/cm3 deka Maenit-Goldia) and soil moisture content from 12.14 % to 33.79 % at kuja, and 11.88 % to 36.01%at deka). More over application of farm yard manure improve soil pH (6.15) organic carbon (6.20 mg/kg) available phosphorus (18.94 mg/kg, total nitrogen (0.32), sulfur (18.27), boron, exchangeable base, cation exchange capacity, micronutrients (copper, manganese & zinc). Application of NPSB fertilizer improves only, total nitrogen, available phosphorus, sulfur and boron. Application of Farm yard manure significantly improve soil physicochemical properties than NPSB mineral fertilizer in comparison. Therefore, application of farm yard manure is more important than mineral NPSB fertilizer for sustainable soil physical and chemical properties improvement from soil management aspect. Thus, application farmyard manure at 10 t/ha is recommended for the studied soil at West Omo zone Maenit-Goldia district, Deka kebele, and Bench-Skako zone, Guraferda district at Koyi kebele, south west people regional state, South West Ethiopia.