Development and Validation of a UHPLC-MS/MS Method for the Simultaneous Quantification of Candesartan and Bisoprolol Together with Other 16 Antihypertensive Drugs in Plasma Samples.

Antihypertensive pharmacological therapy is often characterized by a coadministration of different classes of drugs. Therefore, analytical methods allowing the simultaneous quantification of many drugs are needed for therapeutic drug monitoring (TDM) purposes in this context. In particular, TDM represents a useful tool to discriminate poor adherence from real cases of resistant hypertension.

DNA damage and cell death in human oral squamous cell carcinoma cells: The potential biological effects of cannabidiol.

Objective: The present study examined the in vitro effects on oral squamous cell carcinoma cells (HSC-3) of cannabidiol (CBD), the main chemical component of Cannabis, proposed as a novel adjuvant therapy in the treatment of cancers.

Design: Cell viability (MTT assay), morphology (SEM), apoptosis and cell cycle (flow cytometry), and DNA damage (phospho-γ-H2AX immunofluorescence) were evaluated. Cytotoxicity was evaluated with concentrations between 100 µM and 1 µM, and two concentrations were selected for subsequent analysis: 25 µM, as toxic dose, and 6.

Transition in action: toward a social theory of the governance of transitions.

This article explores how a re-interpretation of the socio-technical, socio-ecological and transition design approaches to transition from the point of view of Niklas Luhmann's general systems theory of society. The need to understand and promote changes that include a technological and ecological dimension has led to different approaches, such as socio-technical or socio-environmental approaches, to incorporate links with society. While these approaches often include sociological insights, they rarely offer a general understanding of how these are embedded into society.

Nuclear miRNAs: Gene Regulation Activities.

MicroRNAs (miRNAs) are small non-coding RNAs which contribute to the regulation of many physiological and pathological processes. Conventionally, miRNAs perform their activity in the cytoplasm where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus.

Cannabinoid levels description in a cohort of patients with chronic and neuropathic pain treated with Cannabis decoction: A possible role of TDM.

The phytocomplex of Cannabis is made up of approximately 500 substances: terpeno-phenols metabolites, including Δ-9-tetrahydrocannabinol and cannabidiol, exhibit pharmacological activity. Medical Cannabis has several pharmacological potential applications, in particular in the management of chronic and neuropathic pain. In the literature, a few data are available concerning cannabis pharmacokinetics, efficacy and safety.

Acute and chronic cannabidiol treatment: In vitro toxicological aspects on human oral cells.

Cannabidiol is gaining increasing interest for its potential anti-inflammatory, immunomodulatory, and antineoplastic effects. The purpose of this study is to investigate the biological effects of acute and chronic CBD administration on gingival fibroblasts and oral keratinocytes. Viability, morphology, migration, apoptosis and cell cycle, and expression of related genes (p53, BCL2, p21, and BAX) and of endocannabinoid system receptors (CB1, CB2 and GPR55) with real-time PCR and DNA damage with phospho-γ-H2AX immunofluorescence detection were analyzed.

Protecting environmental flows to achieve long-term water security.

In this work, we propose a new approach to diagnose if a water allocation scheme is compatible with long-term water security at the catchment scale, and suggest steps to achieve such compatibility. We argue that when the remaining flow of a river after upstream withdrawals is not sufficient to safeguarding ecological river functions, the basin is at extreme risk of water scarcity, which indicates that the water management is failing. To test this, we analysed the water scarcity risks and the safeguarded environmental flows (e-flows) in 277 basins across a wide range of hydro-climatic conditions in Chile (17-55°S).

In Vitro effects of alternative smoking devices on oral cells: Electronic cigarette and heated tobacco product versus tobacco smoke.

Objective: To investigate the biological effects of electronic cigarette (e-cigarette) and heated tobacco product extracts respect to tobacco smoke extract on human gingival fibroblasts and human oral keratinocytes analysing cell viability, morphology, migration, apoptosis, cell cycle and epithelial-mesenchymal transition (EMT).

Design: Human gingival fibroblasts and human oral keratinocytes viability was analysed by MTT assay, cell morphology using scanning electron microscope (SEM) and cell migration by Scratch assay, a method that mimics the cell migration during wound healing in vivo. Apoptosis and cell cycle were analysed with flow cytometry and the related-gene expression of TP53, BCL2, CDKN2A and CDKN1A was indagated using real-time polymerase chain reaction.

Biological effects of cannabidiol on human cancer cells: Systematic review of the literature.

This systematic review examine the biological effects of CBD, a major component of therapeutic Cannabis, on human pathological and cancer cell populations of integumentary, gastro-intestinal, genital and breast, respiratory, nervous, haematopoietic and skeletal districts in terms of cell viability, proliferation, migration, apoptosis, inflammation, metastasis, and CBD receptor expression. The included studies were in English, on human cell lines and primary culture from non-healthy donors with CBD exposure as variable and no CBD exposure as control. Quality assessment was based on ToxRtool with a reliability score ranging from 15 to 18.

Pain Management through Neurocognitive Therapeutic Exercises in Hypermobile Ehlers-Danlos Syndrome Patients with Chronic Low Back Pain.

Background: The hypermobile type of Ehlers-Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue mainly characterized by joint hypermobility. Patients with hEDS suffer joint pain, in particular low back pain, commonly resistant to drug therapy. The aim of this research was to evaluate a neurocognitive rehabilitation approach based not only on the motion and function recovery but also on the pain management.

Heat-not-burn tobacco (IQOS), oral fibroblasts and keratinocytes: cytotoxicity, morphological analysis, apoptosis and cellular cycle. An in vitro study.

Objectives: The aim of this work is to investigate the biological effects of IQOS smoking on human gingival fibroblasts and human keratinocytes analysing cell viability, morphology, migration, apoptosis and cell cycle.

Background: Electronic cigarettes and tobacco heating systems have been marketed to reduce smoking damages caused by combustion.

Methods: Human gingival fibroblasts and human keratinocytes viability was determined by a colorimetric assay measuring mitochondrial dehydrogenase activity (MTT assay); after an in vitro exposure of 24 h, cell morphology was analysed with scanning electron microscope and cell migration was tested by Scratch assay, a method to mimic the migration of the cells during wound healing in vivo.

Prognostic Role of Circulating miRNAs in Early-Stage Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is the primary cause of cancer-related death worldwide, with a low 5-year survival rate even in fully resected early-stage disease. Novel biomarkers to identify patients at higher risk of relapse are needed. We studied the prognostic value of 84 circulating microRNAs (miRNAs) in 182 patients with resected early-stage NSCLC (99 adenocarcinoma (ADC), 83 squamous cell carcinoma (SCC)) from whom peripheral blood samples were collected pre-surgery.

Eicosapentaenoic acid induces DNA demethylation in carcinoma cells through a TET1-dependent mechanism.

In cancer cells, global genomic hypomethylation is found together with localized hypermethylation of CpG islands within the promoters and regulatory regions of silenced tumor suppressor genes. Demethylating agents may reverse hypermethylation, thus promoting gene re-expression. Unfortunately, demethylating strategies are not efficient in solid tumor cells.

The functional manual therapy intervention in infants with non-synostotic plagiocephaly: a pilot study.

Background: The aim of this study was to document the evolution of cranial asymmetries in infants with signs of nonsynostotic occipital plagiocephaly (NSOP) who underwent to many functional manual therapy treatments (in addition to the standard positioning recommendations); as well as to determine the feasibility of this methodology to conduct outcome research investigating the impact of this intervention for infants with NSOP.

Methods: This is a pilot clinical standardization project using pre-post design in which 10 infants participated. Nine infants presented an initial Oblique Diameter Difference Index (ODDI) (over 104%), three an initial Ear Deviation Index (EDI) (over 4%), and three a Cranial Proportional Index (CPI) (over 90%).

Eicosapentaenoic acid activates RAS/ERK/C/EBPβ pathway through H-Ras intron 1 CpG island demethylation in U937 leukemia cells.

Epigenetic alterations, including aberrant DNA methylation, contribute to tumor development and progression. Silencing of tumor suppressor genes may be ascribed to promoter DNA hypermethylation, a reversible phenomenon intensely investigated as potential therapeutic target. Previously, we demonstrated that eicosapentaenoic acid (EPA) exhibits a DNA demethylating action that promotes the re-expression of the tumor suppressor gene CCAAT/enhancer-binding protein δ (C/EBPδ).

The impact of a multidisciplinary approach on response rate of mandibular advancing device therapy in patients with obstructive sleep apnoea syndrome.

The aim of the present study was to evaluate the importance of a multidisciplinary approach on increasing the response ratio expectation to mandibular advancing device (MAD) therapy in patients with obstructive sleep apnoea syndrome, especially in severe cases. Forty-two mild-to-severe OSAS patients were selected, after comprehensive evaluation by neurologists, otorhinolaryngologists and orthodontists, and treated with a Somnodent® device. Six months later, a polysomnographic exam with the MAD in situ was performed.

Transcriptional fine-tuning of microRNA-223 levels directs lineage choice of human hematopoietic progenitors.

MicroRNAs (miRNAs) regulate cell proliferation, differentiation and death during development and postnatal life. The expression level of mature miRNAs results from complex molecular mechanisms, including the transcriptional regulation of their genes. MiR-223 is a hematopoietic-specific miRNA participating in regulatory signaling networks involving lineage-specific transcription factors (TFs).

Evaluation of an in-clinic assay for the diagnosis of canine parvovirus.

The results of a study designed to evaluate the performance of an in-clinic test for the detection of canine parvovirus (CPV) are reported. A total of 150 faecal samples collected from dogs with acute diarrhoea were tested using the in-clinic test, a haemagglutination assay (HA) and a real-time PCR assay for CPV detection, quantification and characterisation. CPV was detected in 66, 73, and 101 faecal samples by in-clinic, HA and PCR testing, respectively.

Factors associated with the efficacy of mandibular advancing device treatment in adult OSA patients.

The aim of this study was to evaluate the anthropometric, demographic, occlusal and cephalometric characteristics of a group of adult obstructive sleep apnea (OSA) patients treated with mandibular advancement devices (MADs) and to determine the factors associated with treatment efficacy. Twenty-three consecutive patients with mild to severe OSA (polysomnographically diagnosed [T0]) were recruited for this prospective study; they were treated with a Silensor(®) appliance, and a polysomnographic exam with the MAD in situ was performed 2 to 3 months later (T1) to evaluate MAD's efficacy. Based on apnea-hypopnea index (AHI) differences between the T0 and T1 values, patients were classified into two groups: completely recovered and not completely recovered patients.

Transcriptional targeting by microRNA-polycomb complexes: a novel route in cell fate determination.

Advances in the understanding of the epigenetic events underlying the regulation of developmental genes expression and cell lineage commitment are revealing novel regulatory networks. These also involve distinct components of the epigenetic pathways, including chromatin histone modification, DNA methylation, repression by polycomb complexes and microRNAs. Changes in chromatin structure, DNA methylation status and microRNA expression levels represent flexible, reversible and heritable mechanisms for the maintenance of stem cell states and cell fate decisions.

Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression.

Epigenetic modifications regulate developmental genes involved in stem cell identity and lineage choice. NFI-A is a posttranscriptional microRNA-223 (miR-223) target directing human hematopoietic progenitor lineage decision: NFI-A induction or silencing boosts erythropoiesis or granulopoiesis, respectively. Here we show that NFI-A promoter silencing, which allows granulopoiesis, is guaranteed by epigenetic events, including the resolution of opposing chromatin "bivalent domains," hypermethylation, recruitment of polycomb (PcG)-RNAi complexes, and miR-223 promoter targeting activity.

Clinical evaluation of immediate loading of electroeroded screw-retained titanium fixed prostheses supported by tilted implant: a multicenter retrospective study.

Statement Of Problem: Immediate occlusal loading of dental implants in the edentulous mandible has proven to be an effective, reliable, and predictable treatment protocol. However, there is limited long-term data available in the literature, when an electroeroded definitive cast-titanium fixed prosthesis is used for this treatment protocol.

Purpose: The aim of this study was to evaluate the clinical effectiveness of dental implants (Astra Tech Dental, Mölndal, Sweden) in the edentulous mandible immediately loaded with an electroeroded cast-titanium screw-retained fixed prosthesis.