Thermoresponsive Hydrogel Containing Viscum album Extract for Topic and Transdermal Use: Development, Stability and Cytotoxicity Activity

Viscum album L. (Santalaceae), also known as European mistletoe, is a semi-parasitic plant that grows on different host trees. Our group recently demonstrated the antitumoral activity of ethanolic V. album extracts in vitro, depending on the dose and the host tree, V. album ssp abietis from Abies alba being the most active extract. The goal of this work focused on the development of a new topical formulation containing V. album extracts, evaluation of in vitro toxicity and ex vivo skin permeation assays. The Poloxamer 407 hydrogel containing 5% of dry (VA_DEH) or aqueous (VA_AEH) extract presented dermal compatible pH and microbiological stability for 180 days. The hydrogels flow curve presented a non-linear relation, characteristic of non-Newtonian fluids, and the mean viscosity for the VA_DEH and VA_AEH was 372.5 ± 7.78 and 331.0 ± 2.83 Pa.s, respectively, being statistically different (Welch’s t test; p < 0.01). Additionally, WST-1 in vitro assays revealed a dose-dependent toxicity for both formulations and VA_DEH presented a higher activity than the VA_AEH. The promising cytotoxic potential of VA_DEH lead to the ex vivo skin permeation assay with 2.73 ± 0.19 µg/cm2 of chlorogenic acid, which permeated at 8 h, showing a transdermal potential. These in vitro results support the idea that VA_DEH is a novel promising candidate for mistletoe therapy. Therefore, further in vivo and pre-clinical experiments should be performed to evaluate the safety and efficacy of this new dermic delivery system.

Characterization and Critical Appraisal of Physiotherapy Intervention Research in Nigeria: A Systematic Review

Objectives Clinical research is the bedrock of clinical innovation, education and practice. We characterized and critically appraised physiotherapy clinical research to avoid implementing misleading research findings into practice and to task the Nigerian physiotherapy societies on responsible conduct of clinical research. Methods This is a systematic review of articles published in English between 2009 and 2021. We searched Pubmed, Medline, Cumulative Index to Nursing and Allied Health Literature, Academic Search Complete, PsycINFO and African Journal Online, and reference lists of relevant articles. Data were selected and extracted according to predesigned eligibility criteria and using a standardized data extraction table. Where appropriate, the Pedro and Cochrane ROBINS1 were used to examine the risk of bias. Results Of the clinical experiments, the randomized controlled trial (RCT) was the most common design (87.5%). Musculoskeletal conditions (39.3%) were the most studied disorder. Most of the studies (76.8%) were of suboptimal quality. Interventions constituted exercise therapy (76.3%), manual therapy (8.5%) and electrotherapy (8.5%). More than half (67.8%) of the studies recorded medium to large effect sizes. A fair proportion (48.2%) of the studies had a confounding-by-indication bias. A few studies conducted normality tests (10.9%) and intention-to-treat analysis (37.5%). Discussion Of the clinical research, the volume of clinical experiments in the Nigeria Physiotherapy research community is small; notwithstanding, RCT is the most frequent clinical experiment. Physiotherapy interventions especially exercise appears effective, although incongruence between effect size and study quality limits inference. Sources of bias include absent/inadequate covariate analysis, blinding and intention-to-treat analysis approach. Registration: We registered the protocol with PROSPERO. The registration number: CRD42021228514.

Treatment of Pregnant Women with Ivermectin during Mass Drug Distribution: Time to Investigate Its Safety and Potential Benefits

To date, pregnant women are excluded from programmes delivering community-directed treatment of ivermectin (CDTI) for onchocerciasis and preventive chemotherapy of other helminthiases because of concerns over ivermectin safety during pregnancy. This systematic exclusion sustains an infection reservoir at the community level and deprives a vulnerable population from known benefits—there are indications that treating O. volvulus infected women may improve pregnancy outcomes and reduce the risk that their children develop onchocerciasis-associated morbidities. Furthermore, teratogenic effects are seen in non-clinical experiments at doses that far exceed those used in CDTI. Lastly, early, undetected and undeclared pregnancies are being systematically exposed to ivermectin in practice. Treatment of this population requires appropriate supporting evidence, for which we propose a three-pronged approach. First, to develop a roadmap defining the key steps needed to obtain regulatory clearance for the safe and effective use of ivermectin in all pregnant women who need it. Second, to conduct a randomised placebo-controlled double-blind clinical trial to evaluate the safety and benefits of ivermectin treatment in O. volvulus infected pregnant women. Such a trial should evaluate the possible effects of ivermectin in reducing adverse pregnancy outcomes and neonatal mortality, as well as in reducing the incidence of onchocerciasis-associated epilepsy. Third, to establish a pregnancy registry for women who inadvertently received ivermectin during pregnancy. This situation is not unique to ivermectin. Access to valuable therapies is often limited, delayed, or denied to pregnant women due to a lack of evidence. Concerns over protecting vulnerable people may result in harming them. We need to find acceptable ways to build robust evidence towards providing essential interventions during pregnancy.

Observation on the effect of high-quality nursing intervention in gadolinium-based sodium material adjuvant radiotherapy for non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a common malignant tumor. Because of the concealment of its early clinical symptoms, most of the patients are diagnosed at the middle and advanced stages. Nowadays, the NSCLC has become one of the critical factors affecting the quality of life of Chinese residents. Traditional radiotherapy cannot meet the clinical treatment needs of NSCLC patients. Here, we used gadolinium oxide (Gd2O3) as a new radiosensitizer matrix and introduced paclitaxel (PTX), with excellent anticancer cell migration function to construct paclitaxel-gadolinium oxide nanoparticles (PTX-Gd2O3 NPs). The clinical experiments show the unique nanometer radiation dose enhancement effect and radiosensitive function of PTX-Gd2O3 NPs. The new nanodrug can successfully exert the secretion of thrombin-sensitive protein-1 of PTX, thereby inhibiting the proliferation and migration of tumor cells, which is expected to provide a new direction for treating long-term NSCLC.

Inverse effect and receptor dynamics – Coffee, Opium and Wine's secondary pharmacology

A homeopathic widespread belief is that the inversion of effect of the drugs in homeopathic medical practice is due to dilution or very low doses, but there are many homeopathic incoherencies. For example the first conception of the similia principle was obtained through planned, small sample, clinical experiments with ponderal/pharmacological doses in healthy and diseased subjects1. Furthermore the classical foundations of the similia principle in Organon2, the primary and secondary actions of drugs, were thought to be connected with opposite, time-dependent reactions of the body to high doses and the inversion of effect was seen in temporal sequence after a strong dose and not after changes of doses, so the idea that dilutions are responsible for inversion of effects is not suitable to the classical theory. And lastly homeopathic provings or pathogenetic trials have frequently mixed, unregarded to the doses, occasional toxicological symptoms and symptoms obtained through diluted substances3, reinforcing the idea that, on healthy subjects, in several cases many substances produce the same symptoms in pharmacological or infinitesimal doses. So at least the dose-dependent inversion of effect is not generalized in a great part of the collected symptoms. Biological foundations to similia principle have to be searched in other directions4, as in different sensitivity to drugs between health and disease, or in different time-dependent effect of drugs on specific, but different, cell sensitivity set point. In the vision described here both these possibilities represent the same phenomenon of altered cell sensitivity. It is aim of this article to show that the original hahnemannian idea to explain homeopathic similia principle starting from a pharmacological and biological point of view with ponderal doses, seems correct, rationally comprehensible and based on modern knowledges. The three pharmacologic examples that best illustrate this reasoning, coffe, opium and wine, will be discussed.

Potential Imaging Capability of Optical Coherence Tomography as Dental Optical Probe: A Mini-Review

Optical coherence tomography (OCT) has been emerging in the dental field as an alternative diagnostic imaging for “optical probes” owing to its micro-meter resolution and non-invasiveness. This review aims to answer the following question: what is the imaging capability of OCT to visualize the subgingival area? Online searches were performed on PubMed and SPIE digital library databases, followed by a manual screening of references listed in relevant studies. The feasibility and imaging performance of OCT to visualize the subgingival area, including the periodontal, peri-implant, and crown margins, are discussed. All of the literature reviewed in this study demonstrated that OCT has the ability to visualize periodontal, including hard and soft tissues, and peri-implant conditions with high resolution. Gingival sulcus depth, periodontal pocket, and calculus deposition can also be depicted. However, clinical evidence that support the imaging capability of OCT as a dental optical probe to visualize subgingival area is lacking. Limited availability, portability, and usability of OCT for clinical experiments in dentistry, particularly for the subgingival area, might be contributed to its limitations. Hence, further development of handheld OCT systems and controlled clinical trials are needed to confirm the imaging capability of OCT reported in this review.

Integration of Gene Expression Profile Data of Human Epicardial Adipose Tissue From Postoperative Atrial Fibrillation to Verification of Hub Genes

Background: The occurrence of post-operative atrial fibrillation (POAF) can significantly reduce the prognosis of patients and increase the mortality of cardiovascular diseases. Meanwhile, epicardial adipose tissue (EAT), plays a crucial role in the occurrence and development of a variety of cardiovascular diseases.Methods: To link EAT with POAF and explore biomarkers with predictive value or therapeutic intervention significance for POAF in EAT.Through the Gene Expression Omnibus (GEO) database, gene expression profiles were collected while GSE 143924 contained EAT from POAF patients and sinus rhythm (SR) patients. And the R package "ClusterProfiler" as well as genetic ontology (GO) and The Kyoto Genomic Encyclopedia (KEGG) were utilized to annotate differential genes and to assess relevant functional categories. Cytoscape was used for protein interaction network (PPI) analysis of the differentially expressed genes. In the end, specimens from clinical patients were collected to further verify the selected genes.Results: The screened differentially expressed genes includes 53 up-regulated genes and 95 down-regulated genes. According to the results obtained by analyzing KEGG, GO enrichment analysis and PPI were made to identify the five genes with the highest degree of connectivity, which includes TNF-α, TLR2, CCL4, TIMP1 and CDH2. Therefore, in peripheral blood samples of clinical POAF patients, CCL4 showed significantly high expression while TIMP1 and CDH2 showed low expression, which was consistent with the results of data screening. But the expression of TLR2 is higher in the POAF group, which is inconsistent with the results of data screening.Conclusion: TNF-α and CCL4 were up-regulated and TIMP1 and CDH2 were down-regulated in EAT with POAF through data analysis and clinical experiments, which features great clinical value for the prevention, diagnosis and treatment of POAF.

Therapy for Pulmonary Arterial Hypertension: Glance on Nitric Oxide Pathway

Pulmonary arterial hypertension (PAH) is a severe disease with a resultant increase of the mean pulmonary arterial pressure, right ventricular hypertrophy and eventual death. Research in recent years has produced various therapeutic options for its clinical management but the high mortality even under treatment remains a big challenge attributed to the complex pathophysiology. Studies from clinical and non-clinical experiments have revealed that the nitric oxide (NO) pathway is one of the key pathways underlying the pathophysiology of PAH. Many of the essential drugs used in the management of PAH act on this pathway highlighting its significant role in PAH. Meanwhile, several novel compounds targeting on NO pathway exhibits great potential to become future therapy medications. Furthermore, the NO pathway is found to interact with other crucial pathways. Understanding such interactions could be helpful in the discovery of new drug that provide better clinical outcomes.

Medicinal Herbs with Anti-Inflammatory Activities for Natural and Organic Healing

: One of the principal causes of different disorders is an uncontrolled inflammatory response. Alkaloids, flavonoids, polyphenolic, proanthocyanidin, terpenoid, and steroid compounds are the main reasons for the anti-inflammatory activities of medicinal herbs and plants. The current manuscript introduces a series of potential anti-inflammatory plants, particularly those which are routines in Iranian and Chinese traditional herbal medicine, and simplifies the function and mechanisms of natural constituents for the prevention and treatment of inflammatory disorders. PubMed, Science Direct, Google Scholar, Wiley Online Library, Springer, Taylor, Francis, etc., have been used to search for collecting of scientific publications for a full evaluation of current documentation in the literature showing the importance of medicinal plants with anti-inflammatory characteristics and natural medicines. The most notable medicinal plants with anti-inflammatory activities are Baccharis dracunculifolia, Aconitum bulleyanum, Crateya adansonii, Alliums spp., Centella asiatica, Flos lonicerae, Corydalis dubia, Syringae folium, Coptis chinensis, Casearia decandra, Nigella sativa, Cannabis sativa, Tamarindus indica L., Glycyrrhiza glabra, Panax ginseng, Panax notoginseng, Pistacia vera, Smilax china, Scutellaria baicalensis, Rosemarinus officinalis, Moringa olifera, Pulsatilla radix, Pistacia atlantica, Rullia tuberose, Canarium album, Dodonaea polyandra, Forsythia suspense, Polygala tenuifolia, Radiz Isatidis, Hypericum sampsonii, Geranium koreanum, Typha capensis, Isatidis folium, Ginkgo biloba, Houttuynia cordata, snow lotus, etc. Herbal medicine mainly uses numerous parts of plants or combinations of them to prevent and remedy diseases and promote health. More investigations and clinical experiments are needed to provide more information on the importance of medicinal plants as well as their roles in the treatment and prevention of inflammatory diseases.

A Novel Development of TRIZ-Analogic Construction Interface Problem Identification and Solutions Framework

One of the critical factors of project success is the interface management. Past project interface management mainly relies on knowledge and experience of the project managers. The existing studies of project interface management also mainly focused on the definition and the classification of project interfaces. There is no workable and flexible framework for construction interface problem identification and solutions. This study conducted an analogic study of contradiction matrix at Theory of Inventive Problem Solving (TRIZ) to develop such a framework. This research collected around six hundred interface management cases from civil works and building projects. For comparison, this research defined an experimental group (TRIZ case) and a control group (experience-oriented solution case) based on the concept of clinical experiments in medical science to evaluate and improve the rationality of the matrix. Subsequently, based upon the theory of information retrieval (IR), this research conducted statistical evaluation and TRIZ features remedies to develop generalized construction interface problem identification and solutions. For solving project management interface problems, the TRIZ-analogic construction interface problem identification and solutions framework provides a systematic approach to develop more robust solutions for interface problems in construction engineering rather than just simply relying on intuitive experience.