Polyamidoamine Dendrimers Decorated Multifunctional Polydopamine Nanoparticles for Targeted Chemo- and Photothermal Therapy of Liver Cancer Model.

The development of multifunctional drug delivery systems combining two or more nanoparticle-mediated therapies for efficient cancer treatment is highly desired. To face this challenge, a photothermally active polydopamine (PDA) nanoparticle-based platform was designed for the loading of chemotherapeutic drug and targeting of cancer cells. PDA spheres were first functionalized with polyamidoamine (PAMAM) dendrimers followed by the conjugation with polyethylene glycol (PEG) moieties and folic acid (FA) targeting ligand. The anticancer drug doxorubicin (DOX) was then absorbed on the particle surface. We performed the physico-chemical characterization of this versatile material and we assessed further its possible application in chemo- and photothermal therapy using liver cancer cell model. These nanoparticles exhibited high near-infrared photothermal conversion efficacy and allowed for loading of the drug, which upon release in specifically targeted cancer cells suppressed their growth. Using cell proliferation, membrane damage, apoptosis, and oxidative stress assays we demonstrated high performance of this nanosystem in cancer cell death induction, providing a novel promising approach for cancer therapy.

Legal regulations, ethical guidelines and recent policies to increase transparency of clinical trials.

Timely and accurate dissemination of outcomes is essential to accomplish main benefits of scientific research including clinical trials. Clinical trial results can be disseminated in two main ways: by publication in a peer-reviewed journal and by posting on a publicly available clinical trial register. The credibility of the literature on clinical trials is significantly diminished because a high percentage of trials is not published. While current legal regulations both in the European Union (EU) and the USA impose a duty to submit summary results of clinical trials to a respective register (EU Clinical Trial Register and ClinicalTrials.gov, respectively), the compliance with this requirement has been generally inadequate. Trial outcomes can be also made accessible by data sharing. However, in spite of the wide promotion of this idea, the access of investigators to participant-level datasets remains limited. The main objective of this review is to discuss current legal regulations, international standards, ethical guidelines and recent policies pertaining to dissemination of clinical trial results.

The effects of 3-year growth hormone treatment and body composition in Polish patients with Silver-Russell syndrome.

INTRODUCTION: Silver-Russell syndrome (SRS) is characterized by clinical and genetic heterogeneity. SRS is the only disease entity associated with (epi)genetic abnormalities of 2 different chromosomes: 7 and 11. In SRS, the 2 most frequent molecular abnormalities are hypomethylation (loss of methylation) of region H19/IGF2:IG-DMR on chromosome 11p15.5 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (upd(7)mat). Therapy with recombinant human growth hormone (rhGH) is implemented to increase body height in children with SRS. The effect of the administered rhGH on height, weight, body mass index (BMI), body composition, and height velocity in patients with SRS during 3 years of rhGH therapy was analysed. MATERIAL AND METHODS: 31 SRS patients (23 with 11p15 LOM, 8 with upd(7)mat) and 16 patients small for gestational age (SGA) as a control group were diagnosed and followed up in The Children's Memorial Health Institute. Patients were eligible for the 2 Polish rhGH treatment programmes [for patients with SGA or with growth hormone deficiency (GHD)]. Anthropometric parameters were collected in all patients. Body composition using bioelectrical impedance was measured in 13 SRS and 14 SGA patients. RESULTS: Height, weight, and weight for height (SDS) at baseline of rhGH therapy were lower in SRS patients than in the SGA control group: -3.3 ± 1.2 vs. -2.6 ± 06 (p = 0.012), -2.5 vs. -1.9 (p = 0.037), -1.7 vs. -1.1 (p = 0.038), respectively. Height SDS was increased from -3.3 ± 1.2 to -1.8 ± 1.0 and from -2.6 ± 0.6 to -1.3 ± 0.7 in the SRS and SGA groups, respectively. Patients with 11p15 LOM and upd(7) mat achieved similar height, 127.0 ± 15.7 vs. 128.9 ± 21.6 cm, and -2.0 ± 1.3 vs. -1.7 ± 1.0 SDS, respectively. Fat mass percentage decreased in SRS patients from 4.2% to 3.0% (p < 0.05) and in SGA patients from 7.6% to 6.6% (p < 0.05). CONCLUSIONS: Growth hormone therapy has a positive influence on the growth of SRS patients. Regardless of molecular abnormality type (11p15 LOM vs. upd(7)mat), height velocity was similar in SRS patients during 3 years of rhGH therapy.

Endocrine disorders in a patient with a suspicion of a mitochondrial disease, MELAS syndrome - a case report and literature review.

MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) is a genetically determined disease caused by mutations in mitochondrial DNA. We present a girl who was suspected of MELAS syndrome during the diagnostic evaluation of short stature. The patient suffered from symptoms potentially indicating mitochondrial disease, such as muscular weakness, cranial nerve VI palsy, headaches, retinitis pigmentosa, sensory-neural hearing loss, and elevated lactic acid. T2-weighted brain MRI showed hyperintense lesions in the white matter. Muscular biopsy revealed ragged red fibres. Genetic evaluation did not detect the most common mutations in the MT-TL1 gene and MT-ND5 gene. Endocrine tests led to the confirmation of growth hormone deficiency, and so replacement treatment was started. After 1 year of recombinant growth hormone therapy the patient was diagnosed with diabetes. At the age of 14 years the LH-RH test showed prepubertal values. Endocrine disorders may be one of the first manifestations of MELAS syndrome. In differential diagnosis of short stature, less common causes, such as mitochondrial diseases, should be taken into consideration.

Legal and ethical aspects of ghostwriting in medicine.

Ghostwriting in medicine represents a highly significant problem in both legal and ethical terms, and particularly in recent years owing to a sudden increase in the practice. The main goal in this paper is to present the legal and ethical rules connected with the ghostwriting phenomenon. The problem is presented in the context of international, European and Polish law. From a legal perspective the issues bound up with ghostwriting are those of the notion and authorship of a work, authors' rights (both moral rights and copyright), the content of these rights and their nature, as well as the question of the transfer of such rights. From the point of view of ethics there arises a need for reflection on honesty, accuracy and credibility as defined both generally and scientifically.

The admissibility of research in emergency medicine.

The main goal in this paper is to present the legal rules connected with medical experiment on human beings in emergency medicine and to explain the scope, significance, and meaning of these rules, especially with regard to their interpretation. As the provisions about medical experiments truly make sense only if they can be observed by the whole "civilised" international community, they are presented in the context of international law with reference to Polish law. By considering the appropriate regulations of research contained in legal documents, it is possible to formulate a catalogue of doctors' duties and patients' rights. This general catalogue refers to all kinds of medical research involving human beings. In the field of emergency medicine, general provisions are sometimes involved, and they are sometimes limited. The main and most important conclusion is that a medical experiment in emergency medicine is admissible only if previously indicated conditions based on general rules of conducting research are fulfilled.