A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models.

Inherited retinopathies are devastating diseases that in most cases lack treatment options. Disease-modifying therapies that mitigate pathophysiology regardless of the underlying genetic lesion are desirable due to the diversity of mutations found in such diseases. We tested a systems pharmacology-based strategy that suppresses intracellular cAMP and Ca2+ activity via G protein-coupled receptor (GPCR) modulation using tamsulosin, metoprolol, and bromocriptine coadministration. The treatment improves cone photoreceptor function and slows degeneration in Pde6ßrd10 and RhoP23H/WT retinitis pigmentosa mice. Cone degeneration is modestly mitigated after a 7-month-long drug infusion in PDE6A-/- dogs. The treatment also improves rod pathway function in an Rpe65-/- mouse model of Leber congenital amaurosis but does not protect from cone degeneration. RNA-sequencing analyses indicate improved metabolic function in drug-treated Rpe65-/- and rd10 mice. Our data show that catecholaminergic GPCR drug combinations that modify second messenger levels via multiple receptor actions provide a potential disease-modifying therapy against retinal degeneration.

Mechanical Joining of Fibre Reinforced Polymer Composites to Metals-A Review. Part I: Bolted Joining.

As the fibre reinforced plastic composites gain larger and larger share in industry, the problem of joining them with metal elements becomes significant. The current paper is the first part of the literature review, which gathers and evaluates knowledge about methods suitable for mechanical joining of composite and metal elements. This paper concerns bolted joining, because this method of mechanical joining is widely used for joining composite materials. The paper describes failure modes of bolted joints in composite materials, the influence of the bolt clamping torque, the clearance between the bolt and the hole and aging on the performance of the joint, drilling techniques used in composite materials in order to minimize damages, different fastener types, inspection techniques, and finally, the techniques that have been developed in order to improve the strength of the bolted joints in composites. Since the hole drilled in a composite material in order to perform bolted joining is a weak point of the structure, those techniques: bonded inserts, titanium foil internal inserts, fibre steering, additional reinforcement, and moulded holes, mainly aim to improve the strength of the hole in the composite. The techniques have been discussed in details and compared with each other in the summary section.

Mechanical Joining of Fibre Reinforced Polymer Composites to Metals-A Review. Part II: Riveting, Clinching, Non-Adhesive Form-Locked Joints, Pin and Loop Joining.

As fiber reinforced plastic composites gain an increasingly larger share in aerospace structures, the problem of joining them with metal elements becomes significant. The current paper is the second part of the literature review, which gathers and evaluates knowledge about methods suitable for the mechanical joining of composite and metal elements. This paper reviews the joining methods other than bolted joining, which are discussed in the first part of the review, namely self-piercing riveting, friction riveting, clinching, non-adhesive form-locked joints, pin joints, and loop joints. Some of those methods are full-fledged and employed in commercial applications, whereas others are merely ideas tested at the level of specimens. The current review describes the ideas and the qualities of the joining methods as well as the experimental work carried out so far. The summary section of this paper contains a comparison of those methods with the reference to their qualities, which is important from the point of view of a composite structure designer: possibility of the joint disassembly, damages induced in composite, complication level, weight penalty, range of possible materials to be joined, and the joint strength.

[Blood culture analysis in children with central venous catheter]. / Analiza wyników posiewów krwi u dzieci z zalozonym cewnikiem centralnym.

We analyzed 99 blood cultures taken from 28 children with central venous catheter. Children were hospitalized in pediatric, pediatric surgery and pediatric intensive care department. All samples were collected from peripherial vein. Positive blood cultures were obtained more frequently from children with central venous catheter than from children without central venous catheter (57.5% vs. 7.4%). Staphylococcus epidermidis was the most frequently obtained bacteria. The other bacterial species were obtained less frequently. The highest percentage of multi resistant straines was isolated from blood samples collected from intensive care department patients. In each departments in which coagulase-negative Staphylococci were isolated, metycillin-resistant straines dominated.

[Evaluation of selected immunocompetent cells expression in gastric mucosa in children with Helicobacter pylori infection before and after eradication treatment--a preliminary study]. / Ocena ekspresji wybranych komórek immunokompetentnych w blonie sluzowej zoladka u dzieci zakazonych Helicobacter pylori przed i po eradykacji zakazenia--doniesienie wstepne.

INTRODUCTION: Helicobacter pylori infection activates local immunological response and causes mononuclear cells infiltration in the gastric mucosa. On this account the studies on lymphocyte subpopulations in the gastric mucosa in children during Helicobacter pylori infections are inconsistent. It has been shown that the morphological status of gastric mucosa in children with Helicobacter pylori infection is different than in adult patients. THE AIM OF THE STUDY was the evaluation of chosen immunocompetent cells expression in gastric mucosa in children before and after eradication treatment. MATERIAL AND METHODS: Forty-nine children with chronic abdominal pain was enrolled in the study. They were divided into the following groups: 22 children without infection (negative urease test and absence of Helicobacter pylori antigen assessed by immunoenzymatic and immunofluorescent methods) and 27 with Helicobacter pylori infection. Part of the children (11) from the second group had a follow-up endoscopy after eradication therapy. The tissue samples from the gastric antrum and fundus were obtained for morphological and immunohistochemistry assays by direct immunofluorescent and immunoenzymatic methods. RESULTS: There were negative Helicobacter pylori tests in group I. In the group of infected children superficial colonisation of pathogen dominated In analysed groups percentage of patients with superficial antigens and cytokines (CD3, CD4, CD8, CD20, IL-4, IL-6, INF-gamma) characteristic for each lymphocytes subpopulations were established. In infammatory infiltrations T lymphocytes CD4 and B lymphocytes CD20 dominated localised mainly in the lamina propria of the gastric mucosa. Expression of above lymphocytes subpopulations diminished after eradication treatment. After treatment the total eradication of Helicobacter pylori was observed in 5 children and in 6 patients the pathogen persisted. CONCLUSIONS: The dominant role in local response during Helicobacter pylori infection in children is played by T CD4 and B CD20 lymphocytes localised mainly in lamina propria of gastric mucosa. Degree of T cells CD4 and CD20 expression decreases after eradication treatment.

[Serum neopterin level in children with lower respiratory tract infections]. / Stezenie neopteryny w surowicy u dzieci z infekcjami dolnych dróg oddechowych.

THE AIM OF THE STUDY: was to determinate the serum neopterin concentration in children with lower respiratory tract infections. MATERIAL AND METHODS: eighty-seven children with lower respiratory tract infections, aged from 1 month to 8 years, were analyzed. The control group consisted of 105 children without infection. The serum C-reactive protein level and whole blood count with differential white blood count were estimated The serum neopterin concentration was evaluated using the immunoenzyme assay (ELISA). RESULTS: statistically significantly higher serum neopterin concentration was observed in the studied than in the control group. The sensitivity of serum neopterin concentration evaluation in children with lower respiratory tract infection was 90.5% and specificity 55.2%. No correlation was found between serum neopterin concentrations and commonly evaluated inflammatory markers. CONCLUSIONS: serum neopterin concentration is elevated in children with lower respiratory tract infections and may be of clinical value as the marker of a viral infection.

[The case of gastric and ileal bezoar in a 3 year old boy]. / Przypadek bezouaru zoladka i jelita cienkiego u 3-lentniego chlopca.

The authors report a case of a 3-year-old boy with a gastric and ileal bezoar, in whom severe anaemia and tumor in the epigastrium were the main symptoms. Bezoars are rare foreign bodies of the gut. They contain swallowed hair, different fibres, seeds, nutshells, sweets or drugs. The group of risk factors for bezoar formation includes anatomical defects, motoric disorders of the digestive tract, type of prescribed drugs and other coexisting chronic diseases. Most cases need surgical treatment.

[Prevalence of ESBL strains in urinary tract infections in children in 1996 and 2004]. / Wystepowanie szczepów ESBL w zakazeniach ukladu moczowego u dzieci w latach 1996 i 2004.

Ethiological agents in urinary tract infections and prevalence of bacterial strains producing extended spectrum of beta-lactamases isolated from urine of children with urinary tract infections were compared. Patients were hospitalized in Department of Pediatry, Pediatric Gastroenterology and Oncology of Medical University of Gdansk in 1996 and 2004. Seventy bacterial strains isolated from urine in 1996 and 113 strains isolated in 2004 were analyzed. In both years Enterobacteriaceae were the most frequently encountered with Escherichia coli predominance. Proteus spp. (10.9%), Enterobacter spp. (7.1%), Klebsiella spp. (4.4%), and Enterococcus spp. (9.3%) were isolated rarely. Among bacteria isolated in 1996 there were no ESBL strains while in 2004 ESBL strains accounted for 11.5% of all urinary bacteria. Klebsiella oxytoca (25%) and Klebsiella pneumaniae (20%) produced ESBL most frequently. ESBL production was less frequent in Escherichia coli (13.2%) and Proteus mirablilis (10%). In conclusion, among bacteria isolated from urine of children with urinary tract infections G(-) strains producing ESBL were encountered only in recent years.

[Antibiotics in lower respiratory tract infection]. / Anybiotykoterapia w zakazeniach dolnych dróg oddechowych u dzieci.

THE AIM OF THE STUDY: Comparison of clinical outcome of lower respiratory tract infections in small children treated or not treated with antibiotics. MATERIAL AND METHODS: Eighty seven children aged from 2 months to 5 years admitted to hospital with mild to moderate bronchitis and/or pneumonia were randomly allocated to one of two groups: group A children were treated with antibiotics and group B patients were not. The children remained under close clinical observation. The clinical outcome was considered good if symptoms of the disease decreased after 72 hours. In case of no clinical improvement or worsening, the children from group B received antibiotics and in children from group A antibiotic therapy was changed. RESULTS AND CONCLUSIONS: There were no significant differences between the two groups in the course of the disease, the frequency of pulmonary complications and recurrence during one month of follow-up.

[Erythema nodosum of tuberculous etiology in a 18 months old girl]. / Rumien guzowaty o etiologii gruzliczej u 18-miesiecznej dziewczynki.

The authors report a case of an 18-months old girl with primary tuberculosis, where erythema nodosum was the main symptom. She received BCG vaccination on the first day of life according to the Polish vaccination programme. Although there was no postvaccinal scar when she was 12 months old, she was not revaccinated. On hospitalisation, the tuberculin skin test was strongly positive. The girl had a confirmed contact with tuberculosis. On the base of the anamnestic data and the clinical course, Erythema nodosum of tuberculous etiology was diagnosed and treatment was introduced. Erythema nodosum is not specific for tuberculosis but in the differential diagnosis tuberculosis should be taken into consideration.