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While the International Classification of Functioning, Disability, and Health (ICF) has significantly contributed to educational research supporting inclusive initiatives worldwide, its application in special education contexts across the African continent remains unclear. This study aims to explore how the ICF is currently used in the field of education in Africa, with an emphasis on children with disabilities, although not restricted to this group. The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) diagram shows that the 11 African-specific databases that were searched yielded 256 records. These records were uploaded to Rayyan, an online collaborative review platform. First, 158 duplicates were removed. Following title and abstract level screening, six records were eligible at full-text level, of which four were excluded, as they focused on the health context. The findings from the remaining two studies were compared and discussed in terms of similarities and differences. Both articles addressed the interactive nature between an individual's activities and participation and environmental factors, agreeing on the importance of addressing societal barriers to inclusion. The use of the ICF in educational settings across Africa is still scarce, thus requiring strategies that could drive inclusive education for children with disabilities on the African continent. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive and invasive type of pancreatic cancer and is expected to soon become the second leading cause of cancer-associated death. The high mortality rate is due to the clinical features that allow asymptomatic progression to advanced stages, a period when current therapeutic treatments have limited efficacy. To address these challenges, researchers are focused on identifying new molecular and circulating markers for early PDAC detection and precision medicine. In this mini-review, we report the most well-known and recently identified molecular and circulating biomarkers. This study aimed to emphasize the need for continued innovative research to develop diagnostic algorithms and therapies to improve the management of patients with PDAC. [ABSTRACT FROM AUTHOR]

Simple Summary: Protein Induced by Vitamin K Absence (PIVKA II), also known as Des-γ-Carboxy prothrombin (DCP), is an established tumor marker for hepatocellular carcinoma (HCC) and a good diagnostic performance has also been demonstrated for Pancreatic Ductal Adenocarcinoma (PDAC). Circulating PIVKA II has been recently associated in vitro with epithelial-to-mesenchymal transition (EMT) activation in pancreatic origin cells PANC-1. The aim of this manuscript is to investigate whether this association is also detectable in vivo. The matter of this research lies in the fact that the diagnostic performance of PIVKA II in PDAC, along with its association with the EMT program, suggests that this molecule could be considered an indirect indicator of EMT and, therefore, a marker of the acquisition of an aggressive phenotype. "Background/Aim": the current inability to diagnose Pancreatic Cancer Adenocarcinoma (PDAC) at an early stage strongly influences therapeutic strategies. Protein Induced by Vitamin K Absence (PIVKA II) showed an accurate diagnostic performance for PDAC. Since circulating PIVKA II has been recently associated with pancreatic origin cells with Vimentin, an epithelial-to-mesenchymal transition (EMT) early activation marker, the aim of this study was to investigate in vivo the combination between the two proteins. "Materials and Methods": we assayed the presence of PIVKA II and Vimentin proteins by using different diagnostic methods. A total of 20 PDAC patients and 10 healthy donors were tested by Western Blot analysis; 74 PDAC patient and 46 healthy donors were assayed by ECLIA and Elisa. "Results": Western Blot analysis showed the concomitant expression of PIVKA II and Vimentin in PDAC patient sera. Immunometric assay performed on a larger cohort of patients demonstrated that 72% of PIVKA II-positive PDAC patients were Vimentin-positive. Additionally, in a group of PDAC patients with PIVKA II levels ≥2070 ng/mL, the percentage of Vimentin-positive subjects reached 84%. "Conclusion": the association between PIVKA II protein and the EMT suggests that this molecule could be considered a marker of the acquisition of an aggressive phenotype. [ABSTRACT FROM AUTHOR]

Aims: Inherited or somatic mutations in the MRE11, RAD50 and NBN genes increase the incidence of tumours, including medulloblastoma (MB). On the other hand, MRE11, RAD50 and NBS1 protein components of the MRN complex are often overexpressed and sometimes essential in cancer. In order to solve the apparent conundrum about the oncosuppressive or oncopromoting role of the MRN complex, we explored the functions of NBS1 in an MB‐prone animal model. Materials and methods: We generated and analysed the monoallelic or biallelic deletion of the Nbn gene in the context of the SmoA1 transgenic mouse, a Sonic Hedgehog (SHH)‐dependent MB‐prone animal model. We used normal and tumour tissues from these animal models, primary granule cell progenitors (GCPs) from genetically modified animals and NBS1‐depleted primary MB cells, to uncover the effects of NBS1 depletion by RNA‐Seq, by biochemical characterisation of the SHH pathway and the DNA damage response (DDR) as well as on the growth and clonogenic properties of GCPs. Results: We found that monoallelic Nbn deletion increases SmoA1‐dependent MB incidence. In addition to a defective DDR, Nbn+/− GCPs show increased clonogenicity compared to Nbn+/+ GCPs, dependent on an enhanced Notch signalling. In contrast, full NbnKO impairs MB development both in SmoA1 mice and in an SHH‐driven tumour allograft. Conclusions: Our study indicates that Nbn is haploinsufficient for SHH‐MB development whereas full NbnKO is epistatic on SHH‐driven MB development, thus revealing a gene dosage‐dependent effect of Nbn inactivation on SHH‐MB development. [ABSTRACT FROM AUTHOR]

The human family of Potassium (K+) Channel Tetramerization Domain (KCTD) proteins counts 25 members, and a significant number of them are still only partially characterized. While some of the KCTDs have been linked to neurological disorders or obesity, a growing tally of KCTDs are being associated with cancer hallmarks or involved in the modulation of specific oncogenic pathways. Indeed, the potential relevance of the variegate KCTD family in cancer warrants an updated picture of the current knowledge and highlights the need for further research on KCTD members as either putative therapeutic targets, or diagnostic/prognostic markers. Homology between family members, capability to participate in ubiquitination and degradation of different protein targets, ability to heterodimerize between members, role played in the main signalling pathways involved in development and cancer, are all factors that need to be considered in the search for new key players in tumorigenesis. In this review we summarize the recent published evidence on KCTD members' involvement in cancer. Furthermore, by integrating this information with data extrapolated from public databases that suggest new potential associations with cancers, we hypothesize that the number of KCTD family members involved in tumorigenesis (either as positive or negative modulator) may be bigger than so far demonstrated. -fFEfNtUXdeWcKncW3NUpD Video abstract [ABSTRACT FROM AUTHOR]

Purpose of Review: This review was designed to revaluate the androgen role on the mechanisms of hypertension and cardiovascular risks in both men and women. Sex steroids are involved in the regulation of blood pressure, but pathophysiological mechanism is not well understood. Androgens have an important effect on metabolism, adipose and endothelial cell function, and cardiovascular risk in both men and women. A focal point in this contest is represented by the possible gender-specific regulation of different tissues and in particular of the adipose cell. Available data confirm that androgen deficiency is linked to increased prevalence of hypertension and cardiovascular diseases. Adipocyte dysfunction seems to be the main involved mechanism. Androgen replacement reduces inflammation state in man, protecting by metabolic syndrome progression. In women, androgen excess has been considered as promoting factor of cardiovascular risk. However, recent data suggest that excessive androgen production has little effect per se in inducing hypertension in young women of reproductive age. Also in postmenopausal women, data on relative androgen excess and hypertension are missing, while adrenal androgen deficiency has been associated to increased mortality. Recent Findings: Molecular mechanisms linking androgen dysregulation to hypertension are almost Unknown, but they seem to be related to increased visceral fat, promoting a chronic inflammatory state through different mechanisms. One of these may involve the recruitment and over-activation of NF-kB, a ubiquitous transcription factor also expressed in adipose cells, where it may cause the production of cytokines and other immune factors. The NF-kB signalling pathway may also influence brown adipogenesis leading to the preferential enlargement of visceral adipocytes. Chronic inflammation and adipocyte dysfunction may alter endothelial function leading to hypertension. Summary: Both in men and in women, particularly in the post-menopausal period, hypoandrogenism seems to be a major determinant of the increased prevalence of hypertension. The relationship between androgen signalling and NF-kB might explain the pathophysiological mechanism leading to the development of endothelium dysfunction and hypertension. [ABSTRACT FROM AUTHOR]

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Individual educational planning (IEP) in inclusive settings in mainstream schools is a challenging task that needs the multi-professional cooperation of teachers, parents and specialists for special educational needs (SEN). This article describes ongoing research and the concepts and tools developed so far for multi-professional IEP on the basis of the international classification of functioning, disability and health (ICF) in inclusive settings in Switzerland. The aim of the research reported in this overview is to describe and analyse the process of IEP on both theoretical and practical levels, to understand its impacts on inclusive special education and to develop useful instruments and tools to support the professionals involved in IEP. As current findings, the importance and role of useful diagnostic information and meaningful goal setting in IEP is emphasised and tools supporting a multi-professional IEP-process are presented. [ABSTRACT FROM AUTHOR]

Cell proliferation is a metabolically demanding process. It requires active reprogramming of cellular bioenergetic pathways towards glucose metabolism to support anabolic growth. NF-?B/Rel transcription factors coordinate many of the signals that drive proliferation during immunity, inflammation and oncogenesis, but whether NF-?B regulates the metabolic reprogramming required for cell division during these processes is unknown. Here, we report that NF-?B organizes energy metabolism networks by controlling the balance between the utilization of glycolysis and mitochondrial respiration. NF-?B inhibition causes cellular reprogramming to aerobic glycolysis under basal conditions and induces necrosis on glucose starvation. The metabolic reorganization that results from NF-?B inhibition overcomes the requirement for tumour suppressor mutation in oncogenic transformation and impairs metabolic adaptation in cancer in vivo. This NF-?B-dependent metabolic pathway involves stimulation of oxidative phosphorylation through upregulation of mitochondrial synthesis of cytochrome c oxidase 2 (SCO2; ref. ). Our findings identify NF-?B as a physiological regulator of mitochondrial respiration and establish a role for NF-?B in metabolic adaptation in normal cells and cancer. [ABSTRACT FROM AUTHOR]

There is a lack of knowledge on the possible influence of systemic conditions on peri-implantitis. The aim of this case-control study is to evaluate the difference in terms of oral pathogens' concentrations in the peri-implant sulcus of a group of patients affected by metabolic syndrome (Mets) compared to healthy subjects. For each patient, peri-implant sulcular biofilm samples were obtained by inserting two sterile endodontic paper points in the deepest aspect of the peri-implant sulcus for 30 s. The quantitative real-time polymerase chain reaction was performed to evaluate total bacterial counts of six pathogens. Patients were screened for peri-implant diseases and clinical and radiographic parameters were recorded. A total of 50 patients was enrolled in the study, 25 affected by Mets and 25 healthy. Significantly higher bacterial counts were discovered for Aggregatibacter actinomycetemcomitans (p = 0.0008), Prevotella intermedia (p = 0.0477) and Staphylococcus aureus (p = 0.034) in MetS patients compared to healthy subjects. Performing a sub-group analysis, considering peri-implant status and dividing patients by MetS diagnosis, no statistically significant (p < 0.05) differences were found. For the first time, a correlation between MetS presence and a greater prevalence of some bacterial species in the peri-implant sulcus was reported, irrespectively from peri-implant status (health vs. disease). [ABSTRACT FROM AUTHOR]

Pharmacological Hedgehog (Hh) pathway inhibition has emerged as a valuable anticancer strategy. A number of small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector glioma-associated oncogene 1 (Gli1) has been designed and developed. In a recent study, we exploited the high versatility of the natural isoflavone scaffold for targeting the Hh signaling pathway at multiple levels showing that the simultaneous targeting of Smo and Gli1 provided synergistic Hh pathway inhibition stronger than single administration. This approach seems to effectively overcome the drug resistance, particularly at the level of Smo. Here, we combined the pharmacophores targeting Smo and Gli1 into a single and individual isoflavone, compound 22, which inhibits the Hh pathway at both upstream and downstream level. We demonstrate that this multitarget agent suppresses medulloblastoma growth in vitro and in vivo through antagonism of Smo and Gli1, which is a novel mechanism of action in Hh inhibition. [ABSTRACT FROM AUTHOR]