Search Results (537)

Background: Transcription factors have been linked to changes in various physiological processes, such as attractive and rewarding phenotypes during plant–pollinator interactions. In the genus Petunia, most species are pollinated by bees, but hawkmoth- and bird pollination are also observed. Here, we aimed to test the hypothesis that species with the same pollination syndrome evolved through convergence, while differences in pollinators indicate divergence. We selected six genes (MYB-FL, DFR, EOBII, ODO1, BPBT, and NEC1) involved in establishing pollination syndromes to explore the potential role of cis-regulatory elements in shifts among pollination syndromes, attracting and rewarding pollinators. Methods: We retrieved the genomic sequences of genes from the genomes of four Petunia species, which exhibit distinct pollination syndromes. We analyzed the cis-regulatory elements, focusing on the structure and composition of motifs, and inferred the functions of these transcription factors using Gene Ontology analysis. Results: All sequences were highly conserved among species, with variations in promoter motif structure and TF binding sites. The evolutionary relationships among the genes closely reflected the species’ phylogeny. Likewise, regulatory elements and gene structure mostly followed the species’ evolutionary history. However, different pollination syndromes are present, and there is an unexpected lack of convergence between the two bee-pollinated species. Conclusions: Our findings showed that the most recent common ancestor of these species better predicts relationships among gene regulatory elements than does the pollination syndrome. To fully understand the evolution of pollination syndromes in Petunia, additional studies are needed to analyze entire pathways and compare genomes and transcriptomes. Full article

Background: While most Escherichia coli strains are harmless members of the gastrointestinal microbiota, certain pathogenic variants can cause severe intestinal and extraintestinal diseases. A notable outbreak of E. coli O104:H4, involving both enteroaggregative (EAEC) and enterohemorrhagic (EHEC) strains, occurred in Europe, resulting in symptoms ranging from bloody diarrhea to life-threatening colitis and hemolytic uremic syndrome (HUS). Since treatment options remain limited and have changed little over the past 40 years, there is an urgent need for an effective vaccine. Such a vaccine would offer major public health and economic benefits by preventing severe infections and reducing outbreak-related costs. A multiepitope vaccine approach, enabled by advances in immunoinformatics, offers a promising strategy for targeting HUS-causing E. coli (O104:H4 and O157:H7 serotypes) with minimal disruption to normal microbiota. This study aimed to design an immunogenic multiepitope vaccine (MEV) construct using bioinformatics and immunoinformatic tools. Methods and Results: Comparative proteomic analysis identified 672 proteins unique to E. coli O104:H4, excluding proteins shared with the nonpathogenic E. coli K-12-MG1655 strain and those shorter than 100 amino acids. Subcellular localization (P-SORTb) identified 17 extracellular or outer membrane proteins. Four proteins were selected as vaccine candidates based on transmembrane domains (TMHMM), antigenicity (VaxiJen), and conservation among EHEC strains. Epitope prediction revealed ten B-cell, four cytotoxic T-cell, and three helper T-cell epitopes. Four MEVs with different adjuvants were designed and assessed for solubility, stability, and antigenicity. Structural refinement (GALAXY) and docking studies confirmed strong interaction with Toll-Like Receptor 4 (TLR4). In silico immune simulations (C-ImmSim) indicated robust humoral and cellular immune responses. In Conclusions, the proposed MEV construct demonstrated promising immunogenicity and warrants further validation in experimental models. Full article

Background: Midportion Achilles tendinopathy (Mid-AT) is a complex condition that may be exacerbated by anatomical variations of the plantaris tendon. Recent anatomical studies, particularly the classification proposed by Olewnik et al., have enhanced the understanding of plantaris–Achilles interactions and their clinical implications. Objective: This review aims to assess the anatomical types of the plantaris tendon, their imaging correlates, and the impact of the Olewnik classification on diagnosis, treatment planning, and surgical outcomes in patients with Mid-AT. Methods: We present an evidence-based analysis of the six anatomical types of the plantaris tendon and their relevance to Achilles tendinopathy, with emphasis on MRI and ultrasound (USG) evaluation. A diagnostic and therapeutic algorithm is proposed, and clinical outcomes of both conservative and operative management are compared across tendon types. Results: Types I and V were most strongly associated with symptomatic conflict and showed the highest benefit from surgical resection. Endoscopic approaches were effective in Types II and III, while Type IV typically responded to conservative treatment. Type VI, often misdiagnosed as tarsal tunnel syndrome, required combined neurolysis. The classification significantly improves surgical decision-making, reduces overtreatment, and enhances diagnostic precision. Conclusions: The Olewnik classification provides a reproducible, clinically relevant framework for individualized management of Mid-AT. Its integration into imaging protocols and treatment algorithms may improve therapeutic outcomes and guide future research in orthopaedic tendon pathology. Full article

Background and Clinical Significance: Serratus Anterior Muscle Pain Syndrome (SAMPS) is an underdiagnosed cause of anterior chest wall pain, often attributed to myofascial trigger points of the serratus anterior muscle (SAM) or dysfunction of the Long Thoracic Nerve (LTN), leading to significant disability and affecting ipsilateral upper limb movement and quality of life. Current diagnosis relies on exclusion and physical examination, with limited treatment options beyond conservative approaches. This case report presents a novel approach to chronic SAMPS, successfully diagnosed using Sonoguided Digital Palpation (SDP) and treated with ultrasound-guided hydrodissection of the LTN using 5% dextrose in water (D5W) without local anesthetic (LA), in a patient where conventional treatments had failed. Case Presentation: A 72-year-old male presented with a three-year history of persistent left chest pain radiating to the upper back, exacerbated by activity and mimicking cardiac pain. His medical history included two percutaneous coronary interventions. Physical examination revealed tenderness along the anterior axillary line and a positive hyperirritable spot at the mid axillary line at the 5th rib level. SDP was used to visualize the serratus anterior fascia (SAF) and LTN, and to reproduce the patient’s concordant pain by palpating the LTN. Ultrasound-guided hydrodissection of the LTN was then performed using 20–30cc of D5W without LA to separate the nerve from the surrounding tissues, employing a “fascial unzipping” technique. The patient reported immediate pain relief post-procedure, with the pain reducing from 9/10 to 1/10 on the Numeric Rating Scale (NRS), and sustained relief and functional improvement at the 12-month follow-up. Conclusions: Sonoguided Digital Palpation (SDP) of the LTN can serve as a valuable diagnostic adjunct for visualizing and diagnosing SAMPS. Ultrasound-guided hydrodissection of the LTN with D5W without LA may provide a promising and safe treatment option for patients with chronic SAMPS refractory to conservative management, resulting in rapid and sustained pain relief. Further research, including controlled trials, is warranted to evaluate the long-term efficacy and generalizability of these findings and to compare D5W to other injectates. Full article

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized, non-atherosclerotic cause of acute coronary syndrome (ACS), particularly in younger women. This comprehensive review outlines SCAD’s unique pathophysiology, which is linked to underlying arteriopathies like fibromuscular dysplasia, and highlights the critical role of advanced intravascular imaging for accurate diagnosis. A fundamental shift in management is detailed, with evidence favoring a conservative strategy for stable patients due to high rates of spontaneous vessel healing, reserving technically challenging invasive interventions for high-risk cases. Importantly, this review also addresses long-term outcomes, noting significant rates of recurrence and Major Adverse Cardiac Events (MACE), a high prevalence of persistent chest pain, and the central role of beta-blocker therapy in secondary prevention. Ultimately, SCAD requires a departure from standard ACS protocols towards a personalized approach that emphasizes accurate diagnosis, cautious initial management, and vigilant long-term follow-up. Full article

Background and Clinical Significance: Spontaneous renal hematoma, also known as Wunderlich syndrome (WS), is a rare disease characterized by the acute onset of spontaneous renal hemorrhage into the subcapsular, perirenal, and/or pararenal spaces without a history of prior trauma. WS can be a life-threatening condition due to hemorrhagic shock; consequently, prompt diagnosis and a therapeutic approach are essential for favorable outcomes. Treatment ranges from conservative management to surgical intervention. The most common etiologies are neoplasms and vascular diseases, but WS can also be observed in patients undergoing hemodialysis. In patients with end-stage renal disease (ESRD), especially those on hemodialysis, acquired cystic kidney disease and renal cell carcinoma are among the primary causes of WS. Although less common, WS can develop in dialysis patients even in the absence of traditional (primary) risk factors. In general, patients with chronic kidney disease (CKD) have a paradoxical hemostatic profile, likely explaining their higher tendency to bleed, so WS can occur without existing predisposing factors. The multifactorial pathogenesis in these patients includes functional platelet abnormalities, intimal arterial fibrosis, chronic inflammation, and oxidative stress associated with ESRD. The use of hemodialysis-related antithrombotic medications could serve as another contributing factor increasing the risk of bleeding. Case Presentation: We present a case report of a 62-year-old male on chronic dialysis who developed sudden right-sided lumbar pain and hematuria during dialysis without evidence of prior trauma. Imaging revealed a large subcapsular hematoma of the right kidney. Further investigations did not reveal additional risk factors in this instance; however, his routinely used hemodialysis-related antithrombotic medications were potentially a contributing factor. Despite conservative treatment, his condition worsened, and the hematoma enlarged, requiring emergency nephrectomy. Postoperatively, his condition gradually improved. Conclusions: This case highlights the importance of considering WS in hemodialysis patients, even without the presence of traditional risk factors, as well as including WS in the differential diagnosis of acute abdominal pain. Full article

Biallelic pathogenic variants in DHCR7 result in decreased activity of 7-dehydrocholesterol (7-DHC) reductase, which converts 7-DHC to cholesterol, and causes Smith–Lemli–Opitz syndrome (SLOS). Elevated serum 7-DHC levels are indicative of SLOS as are intellectual disability (ID), growth retardation, microcephaly, craniofacial anomalies, and 2–3 toe syndactyly. Additional congenital malformations may be present in SLOS, and broad clinical variability has been recognized in SLOS. Rarely, biallelic pathogenic DHCR7 variants were reported with low-normal and normal intelligence quotient (IQ) and development. We report here a pair of siblings with mild global developmental delay, infrequent epileptic seizures, and elevated serum 7-DHC levels, associated with the homozygous DHCR7 variant c.988G>A (p.Val330Met). Remarkably, neither sibling displayed congenital anomalies nor dysmorphisms. Quattro-exome sequencing performed for global delay and mild ID in both siblings did not identify other ID causes. c.988G>A affects a highly conserved amino acid and displays a relatively high global population allele frequency of 0.04%, with absence of homozygotes from the population database gnomADv4.1.0. Our observation leads us to suggest that DHCR7 variant c.988G>A and other DHCR7 variants might be generally considered as underlying non-syndromic ID. Full article

Guillain-Barre syndrome is an autoimmune disease that provokes neural illness causing acute paralysis neuropathy. This syndrome appears after some bacterial infections produced by Campylobacter jejuni, Streptococcus pyogenes, S. pneumoniae, Haemophilus influenciae, E. coli and current studies showed the appears of this syndrome after SARS-CoV-2 infection. In this study, a in silico analysis was carry out in which to determinate bacterial epitopes than produce the molecule mimicry phenomena and that can produce the immune system activation against this epitope. A conserved amino acid sequence has been encountered with the highest probability to activate the immune system against this bacterial epitope, human gliomedin and ryanodine 3 type receptor. More studies needed to demonstrate in vivo the molecular mimicry in Guillain-Barre syndrome patients. Full article

Background: Bertolotti syndrome describes a painful lumbosacral transitional vertebra (LSTV) with a pseudoarticulation between an enlarged lateral process of the caudal lumbar vertebra (L5) and ilium or sacrum. It often presents with chronic lower back pain with or without radiculopathy. The current literature emphasizes Bertolotti as a differential diagnosis in young adults. However, it is presumably underdiagnosed in middle-aged and older patients. Treatment ranges from conservative treatment with physiotherapy, infiltration, and radiofrequency ablation to surgical interventions. Case Description: In this case illustration, we present the diagnostic and therapeutic challenges in a 48-year-old female triathlete with persistent left gluteal pain caused by Bertolotti syndrome. When conservative treatment with physiotherapy, infiltrations, thermocoagulation, and radiofrequency ablation of the pseudoarticulation failed, microsurgical reduction of the hypertrophic transverse process was performed. This minimally invasive intervention achieved satisfactory pain relief of at least 70% one year after surgery, allowing the patient to resume her athletic activities. Conclusions: Bertolotti syndrome should be considered a potential differential diagnosis in patients of all ages. Since many patients endure years of misdiagnosis, adequate treatment is crucial upon diagnosis. If conservative measures fail, surgical treatment such as “processectomy” or spinal fusion should be evaluated. This case follows the CARE reporting guidelines. Full article

Background/Objectives: The co-existence of multiple compression sites on the same nerve can pose a clinical and diagnostic challenge, warranting a different treatment strategy. This so-called double crush syndrome (DCS) has mainly been investigated in the upper limb. Only a few studies have investigated DCS for the lower limb. In this article, a single-center illustrative clinical case series is presented, and current literature on L5 nerve root (NR) and concomitant common peroneal nerve (CPN) is reviewed. Methods: All patients presenting between 2019 and 2022 with L5 nerve root (NR) compression and, along their clinical courses, concomitant compression of the common peroneal nerve (CPN) at the fibular head were included. Information on clinical features, diagnostics and surgeries was obtained. The outcome was assessed at the last outpatient follow-up appointment. In addition, an extensive literature review has been conducted. Results: Fourteen patients were included with a mean follow-up of 6.8 months. The majority had pain (71%) or motor deficits (71%). Seven patients were referred for clinical and radiological L5 NR compression but were also found to have CPN compression; the other seven patients had persisting or recurrent symptoms after surgically or conservatively treated L5 NR compression, suggestive of additional peroneal neuropathy. All patients had CPN decompression at the fibular head, with successful results obtained in 93% of the patients. Pain of the lower leg improved in all patients, and dorsiflexion function improved in 78%. Conclusions: Concomitant L5 NR and CPN appear to occur more frequently than expected. Peroneal neuropathy can present simultaneously with L5 nerve radiculopathy or after surgically or conservatively treated L5 NR compression. Overlapping symptoms and variation in clinical presentations make it difficult to diagnose and, therefore, underrecognized. More awareness among treating physicians of this specific double crush syndrome is important to prevent any delay in treatment, in this case, a less invasive common peroneal nerve release at the fibular head, and to avoid unnecessary (additional) spinal surgery. Full article

Hyperekplexia (OMIM 149400), a sensorimotor syndrome of perinatal clinical relevance, causes newborns to display an energic startle reflex in response to certain trivial stimuli. This condition can be lethal due to apnea episodes. The disease is caused by a blockade of glycinergic neurotransmission. Glycinergic interneurons preserve their identity by the activity of the surface glycine transporter GlyT2, which supplies glycine to presynaptic terminals to maintain glycine content in synaptic vesicles. Loss-of-function mutations in the GlyT2 gene (SLC6A5) cause a presynaptic form of human hyperekplexia. Here, we describe a new GlyT2 variant found in an infantile patient diagnosed with hyperekplexia. A missense mutation in the open reading frame of the GlyT2 gene inherited in homozygosity caused the substitution G449E in a residue highly conserved across the phylogenetic scale. The sequences of the glycine receptor genes GLRA1 and GLRB did not show abnormalities. We expressed the recombinant GlyT2 variant in heterologous cells and analyzed its pathogenic mechanism. The transporter was totally inactive, behaving as a bona fide loss-of-function mutant. Furthermore, the mutation promoted the abnormal insertion of the protein into the membrane, leading to its large incorporation into lipid rafts. However, there was no apparent alteration of wild-type trafficking upon mutant coexpression, as the mutant was prematurely degraded from the endoplasmic reticulum. Rescue with chemical chaperones was not possible for this mutant. Proteomics demonstrated that the expression of the mutant induced the unfolded protein response and interfered with raft-dependent processes. Therefore, the new variant causes a loss of function regarding GlyT2 activity but a gain of function as a cell proteostasis disturber. Full article

Background: Klippel–Trenaunay syndrome (KTS) is a congenital vascular malformation syndrome characterized by low-flow vascular anomalies, including venous malformation (VM) and lymphatic involvement. These anomalies may lead to limb asymmetry due to soft tissue and/or bone overgrowth. Compression therapy using elastic garments is considered a conservative and minimally invasive first-line treatment option for KTS. However, the benefits of compression therapy for low-flow vascular malformations, particularly limb VMs, have not been sufficiently evaluated. This prospective, multi-center study assessed the efficacy and safety of compression therapy for KTS with VM. Methods: After measuring the affected limb, a custom-made elastic garment providing 30 mmHg of compression was manufactured (THUASNE, France). A total of 20 patients (7 male, 13 female; mean age: 10.9 years) underwent compression therapy for 26 weeks at four nationwide institutions in Japan. The primary outcome was the change in lower limb circumference. Secondary outcomes included pain, modified Rankin Scale (mRS) score, body water content, vital signs, changes in garment elasticity, and adverse events. Results: All 20 patients completed the study. At the study endpoint, the circumference ratio of the affected to unaffected limbs was significantly reduced at the superior end of the tibial tuberosity (p = 0.02) and the thinnest part of the ankle (p < 0.001). The elastic force of the garment declined by approximately 50% over 26 weeks. No serious adverse events related to the intervention were reported. Conclusions: Compression therapy using a custom-made elastic garment appears to be a safe and effective approach for managing limb overgrowth in patients with KTS and VM. To maintain the therapeutic effect, garment replacement is recommended at least every six months. Full article

Since its emergence in China in 2018, African swine fever virus (ASFV) has posed a severe threat to the pig farming industry due to its high transmissibility and mortality rate. The clinical signs of ASFV infection often overlap with those caused by other swine viruses such as classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), pseudorabies virus (PRV), and porcine circovirus type 2 (PCV2), making timely and precise diagnosis a considerable challenge. To address this, we established a TaqMan-based multiplex real-time quantitative PCR (qPCR) assay capable of simultaneously detecting ASFV, CSFV, PRRSV, PRV, and PCV2. Specific primer-probe sets were developed targeting conserved genomic regions: the ASFV P72 gene, CSFV 5’UTR region, PRRSV ORF6, PCV2 cap gene, and PRV gB gene. After thorough optimization, the assay demonstrated robust analytical performance, exhibiting strong target specificity with no cross-detection of non-target pathogens. The detection threshold was determined to be 10 copies/μL per virus, indicating high assay sensitivity. Repeatability analysis revealed low variability, with intra- and inter-assay coefficient of variation values remaining below 2.3%. When applied to 95 clinical samples, the multiplex assay yielded results that were fully consistent with those obtained using commercially available singleplex qPCR kits. In conclusion, the multiplex TaqMan qPCR method developed in this study is characterized by high specificity, sensitivity, and reproducibility. It provides a reliable and efficient diagnostic tool for the simultaneous detection and differential diagnosis of ASFV and other clinically similar viral infections in swine, thereby offering robust technical support for swine disease surveillance and control. Full article

The aim of this study was to evaluate the efficacy of manual therapy based on neurodynamic techniques and electrophysical modalities in the conservative treatment of cubital tunnel syndrome (CuTS). A total of 128 upper limbs affected by CuTS were initially enrolled in this study, with 82 completing the full treatment protocol. The participants were divided into the following two intervention arms: the first arm (MT) (42 arms) received therapy based on sliding and tensioning neurodynamic techniques, while the second arm (EM) (40 arms) underwent physiotherapy based on electrophysical modalities, specifically low-level laser therapy (LLLT) and ultrasound therapy (US). Chi² and Student’s t-test were used to compare the intervention arms, and no statistically significant differences were found. The evaluated outcomes included nerve conduction testing, ultrasound assessments (measuring cross-sectional area and shear modulus), pain levels, two-point discrimination, thresholds for cutaneous sensory perception, symptom severity, functional ability in specific tasks, and overall post-treatment improvement. Baseline comparisons indicated no statistically significant differences in any measured variables between the intervention groups (p > 0.05). Following treatment, each group exhibited significant improvements in their respective parameters (p < 0.01). Comparisons between groups post-intervention revealed statistically significant differences in nerve conduction results, ultrasound measurements (cross-sectional area and shear modulus), two-point discrimination, and sensory perception thresholds. These parameters improved more in the MT intervention arm. The use of neurodynamic techniques, ultrasound, and low-level laser therapy in the conservative treatment of mild to moderate forms of CuTS has a beneficial therapeutic effect. Full article

Hearing impairments (HIs) are clinically and genetically very heterogeneous. Finding the causative mutations in patients is frequently a challenge. We investigated two brothers affected by a sensorineural, moderate non-syndromic HI. Exome sequencing revealed that they carried the heterozygous c.812C>T (p.Ser271Leu) variant in GATA3. This gene encodes a transcription factor involved in embryonic development, its mutations causing the autosomal dominant HDR (hypoparathyroidism, deafness, and renal disease) syndrome. The variant affects a conserved residue within the proximal zinc-finger motif of GATA3. Sanger sequencing confirmed the presence of the variant in the two brothers, but it showed that surprisingly it was not carried by any of the parents. Segregation studies on 20 fully informative microsatellite markers in the family confirmed that the variant arose de novo. A benign SNP in the mother, close to the position of the variant, allowed us to determine that this was inherited from the father. Gene reporter functional assays supported the pathogenicity of the variant. Clinical reassessment of the two brothers did not disclose any additional abnormality. We conclude that mosaicism for this de novo mutation in the father’s germ line explains the pattern of inheritance in this family and that p.Ser271Leu is causing this unexpected phenotype of non-syndromic HI. Full article