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mation, irrespective of gender.Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a rare and heterogeneous subgroup of tumors with a challenging management because of their extremely variable biological and clinical behaviors. Due to their different prognosis, there is an urgent need to identify molecular markers which would enable to discriminate between grade 3 neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), despite both being diagnosed mainly on the basis of proliferation index and cell differentiation. DLL3, a negative Notch regulator, is a promising molecular target highly expressed in several tumors with neuroendocrine features. We conducted a retrospective analysis of DLL3, RB1, and PD-L1 expression by immunohistochemistry (IHC), in formalin-fixed, paraffin-embedded (FFPE) samples from 47 patients with GEP-NENs. Then, we correlated the results with patients' clinical features and outcome. The absence of DLL3 expression in 5 well-differentiated GEP-NETs with high-grade features (G3 NET), and the presence of DLL3 in 76.9% of poorly-differentiated NECs (G3 NEC), highlights DLL3 expression as a marker of G3 NECs (p = 0.007). DLL3 expression was correlated with RB1-loss (p less then 0.001), negative 68 Ga-PET/CT scan (p = 0.001), and an unfavorable clinical outcome, with important implications for treatment response and patient's follow-up. Median progression-free survival (PFS) and overall survival (OS) were 22.7 months (95% CI 6.1-68.8) and 68.8 months (95% CI 26.0-78.1), respectively, in patients with DLL3-negative tumor compared with 5.2 months (95% CI 2.5-18.5) and 9.5 months (95% CI 2.5-25.2), respectively, in patients with DLL3-positive tumor (PFS p = 0.0083, OS p = 0.0071). Therefore, combined with morphological cell analysis, DLL3 could represent a valuable histological marker, for the diagnosis of poorly differentiated NECs. The high percentage of DLL3 expression in NEC patients also highlights a potential opportunity for a DLL3 targeted therapy in this tumor subset.Loss of mitosis regulation is a common feature of malignant cells that leads to aberrant cell division with inaccurate chromosome segregation. The mitotic checkpoint is responsible for faithful transmission of genetic material to the progeny. Defects in this checkpoint, such as mutations and changes in gene expression, lead to abnormal chromosome content or aneuploidy that may facilitate cancer development. Furthermore, a defective checkpoint response is indicated in the development of drug resistance to microtubule poisons that are used in treatment of various blood and solid cancers for several decades. Mitotic slippage and senescence are important cell fates that occur even with an active mitotic checkpoint and are held responsible for the resistance. read more However, contradictory findings in both the scenarios of carcinogenesis and drug resistance have aroused questions on whether mitotic checkpoint defects are truly responsible for these dismal outcomes. Here, we discuss the possible contribution of the faulty checkpoint signaling in cancer development and drug resistance, followed by the latest research on this pathway for better outcomes in cancer treatment.
Barley (Hordeum vulgare L.) is one of the most important cereals worldwide. Although this crop is drought-tolerant, water deficiency negatively affects its growth and production. To detect key genes involved in drought tolerance in barley, a reconstruction of the related gene network and discovery of the hub genes would help. Here, drought-responsive genes in barley were collected through analysis of the available microarray datasets (- 5 ≥ Fold change ≥ 5, adjusted p value ≤ 0.05). Protein-protein interaction (PPI) networks were reconstructed.
The hub genes were identified by Cytoscape software using three Cyto-hubba algorithms (Degree, Closeness, and MNC), leading to the identification of 17 and 16 non-redundant genes at vegetative and reproductive stages, respectively. These genes consist of some transcription factors such as HvVp1, HvERF4, HvFUS3, HvCBF6, DRF1.3, HvNAC6, HvCO5, and HvWRKY42, which belong to AP2, NAC, Zinc-finger, and WRKY families. In addition, the expression pattern of four hub genes was compared between the two studied cultivars, i.e., "Yousef" (drought-tolerant) and "Morocco" (susceptible). The results of real-time PCR revealed that the expression patterns corresponded well with those determined by the microarray. Also, promoter analysis revealed that some TF families, including AP2, NAC, Trihelix, MYB, and one modular (composed of two HD-ZIP TFs), had a binding site in 85% of promoters of the drought-responsive genes and of the hub genes in barley.
The identified hub genes, especially those from AP2 and NAC families, might be among key TFs that regulate drought-stress response in barley and are suggested as promising candidate genes for further functional analysis.
The identified hub genes, especially those from AP2 and NAC families, might be among key TFs that regulate drought-stress response in barley and are suggested as promising candidate genes for further functional analysis.
Sports-related sudden cardiac death (Sr-SCD) is a leading natural cause of death in young athletes. To prevent Sr-SCD in athletes, it is important to identify individuals at risk. This review sought to summarize the current knowledge of symptoms prior to Sr-SCD in athletes aged 1-49years.
Cardiovascular screening of athletes is a subject of interest. However, the cost of ECG screening in a young population is relatively high compared to potential benefits, and systematic screening of athletes is heavily debated. In the background population, both cardiac and non-specific symptoms are often present prior to SCD. Both cardiac and non-specific symptoms are present in up to 74% prior to Sr-SCD. The main symptoms are syncope, chest pain, palpitations and dizziness. Knowledge of symptoms could potentially be used in combination with non-invasive prediction models to prevent Sr-SCD and treat athletes at risk.
Cardiovascular screening of athletes is a subject of interest. However, the cost of ECG screening in a young population is relatively high compared to potential benefits, and systematic screening of athletes is heavily debated. In the background population, both cardiac and non-specific symptoms are often present prior to SCD. Both cardiac and non-specific symptoms are present in up to 74% prior to Sr-SCD. The main symptoms are syncope, chest pain, palpitations and dizziness. Knowledge of symptoms could potentially be used in combination with non-invasive prediction models to prevent Sr-SCD and treat athletes at risk.
Wave surfing will debut in the next Olympic Games and is increasingly popular as a sport. Chronic shoulder complaints are frequently reported amongst surfers, though literature researching its pathophysiology and prevention is scarce. This article provides an overview of the current literature, proposes a potential pathogenesis and a potential physiotherapeutic prevention program for surf-induced shoulder complaints.
A systematic review was performed considering the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for articles regarding kinematic analysis of the surf paddling movement. Data sources were Embase, MEDLINE (PubMed) and Research gate. We included case series and cohort studies that originally studied or described the paddle movement made by wave surfers, studies that reported on kinesiologic analysis with nerve conduction studies and studies on 3D motion analysis of the shoulder while paddling.
Eight original articles were included that analysed the shouand hence increase the risk of impingement around the shoulder joint. A potential physiotherapeutic prevention programme should address all these aspects, with the main goal being to increase external rotator strength and to stretch the internal rotators.
There is a high incidence of chronic surf-induced shoulder complaints in surfers. Symptoms may arise due to imbalanced training or scapular dyskinesis, which may subsequently trigger subacromial pain. Physiotherapeutic prevention should include stretching of the internal rotators, external rotator training and optimisation of thoracic extension and scapulothoracic movement.
There is a high incidence of chronic surf-induced shoulder complaints in surfers. Symptoms may arise due to imbalanced training or scapular dyskinesis, which may subsequently trigger subacromial pain. Physiotherapeutic prevention should include stretching of the internal rotators, external rotator training and optimisation of thoracic extension and scapulothoracic movement.
This review surveys our current understanding of the impact of parental migraine on children. Understanding the impact of migraine on others in a family unit is critical to describing the full burden of migraine and to developing psychosocial supportive interventions for patients and their families.
Having a parent with migraine is associated with several early developmental features including infant colic. Adolescent children of parents with migraine self-report their parent's migraine interferes with school and activities and events. Further, migraine is perceived to impact the relationship between the parent and child. Having a parent with migraine increases a child's risk of having migraine, and having more severe migraine disease. However, children with migraine whose parent also has migraine appear to receive more early and aggressive treatment. The impact of migraine extends beyond the parent with migraine and influences children across biological, psychological, and social domains.
Having a parent with migraine is associated with several early developmental features including infant colic. Adolescent children of parents with migraine self-report their parent's migraine interferes with school and activities and events. Further, migraine is perceived to impact the relationship between the parent and child. Having a parent with migraine increases a child's risk of having migraine, and having more severe migraine disease. However, children with migraine whose parent also has migraine appear to receive more early and aggressive treatment. The impact of migraine extends beyond the parent with migraine and influences children across biological, psychological, and social domains.Lake Van is the largest lake in Turkey. It is one of the few soda lakes in the world. Its water is brackish and soda. The lake water has a salinity rate of 19‰ and a pH of 9.8. The salty-soda content of the lake greatly limits biodiversity. Since the Lake Van fish is anadromous, it migrates from the extreme conditions of Lake Van to the freshwater pouring into the lake to spawn. In the same way, once they have emerged from the eggs, the newly hatched fish return to the lake environment to feed again. In this study, the changes in Lake Van fish gill mucus cell histochemistry were examined using different histological stains. The area and density of the mucus cells were observed to have changed in the aquatic areas of different physicochemical properties due to reproductive migration. The intensity of the mucus staining was also found to vary in different aquatic locations and gill regions. As a result, it was clearly demonstrated that mucus cell glycoprotein contents and levels found in Lake Van fish gills varied in different lake freshwater and aquatic environments.
