Amblyopia-A novel virtual round table to explore the caregiver perspective.

Purpose: A survey aimed to capture the caregiver's perspective on the impact of amblyopia and its treatment on the child and family, as well as caregivers' views on the design and feasibility of clinical trials investigating dichoptic binocular therapies for amblyopia.

Methods: Parents of amblyopic children, patient advocates and healthcare professionals took part in a moderated, structured discussion on a novel virtual advisory-board platform.

Results: Seven parents of children with amblyopia, two patient organisation representatives, one ophthalmologist and one optometrist participated in the survey.

HAWK Extension Study: Safety and Efficacy of Intravitreal Brolucizumab in Neovascular Age-related Macular Degeneration.

To collect data on efficacy and safety of brolucizumab 6 mg drug product intended for commercialization in patients with neovascular age-related macular degeneration to support comparability to brolucizumab product used in the Phase III HAWK and HARRIER studies. The HAWK extension study was a 24-week, double-masked, multicenter study of patients with neovascular age-related macular degeneration who completed the 96-week HAWK core study. All patients were planned to receive three intravitreal injections of either brolucizumab 6 mg or aflibercept 2 mg.

Metabolic Acidosis Alters Expression of Slc22 Transporters in Mouse Kidney.

Introduction: The kidneys play a central role in eliminating metabolic waste products and drugs through transporter-mediated excretion along the proximal tubule. This task is mostly achieved through a variety of transporters from the solute carrier family 22 (SLC22) family of organic cation and anion transporters. Metabolic acidosis modulates metabolic and renal functions and also affects the clearance of metabolites and drugs from the body.

Disease-modifying Antirheumatic Drugs (DMARD) and Combination Therapy of Conventional DMARD in Patients with Spondyloarthritis and Psoriatic Arthritis with Axial Involvement.

Treatment with nonsteroidal antiinflammatory drugs (NSAID) is the recommended first-line therapy in patients with axial spondyloarthritis (axSpA); and for those patients who have persistently active disease, the introduction of tumor necrosis factor-α (TNF-α) inhibitors is indicated. Conventional nonbiological disease-modifying antirheumatic drugs (DMARD), although effective and used in clinical practice for peripheral arthritis, are not recommended. Few studies have been conducted with the aim of evaluating the effect of conventional DMARD, either alone or in combination, in axSpA.

Body weight, gender and response to TNF-α blockers in axial spondyloarthritis.

Objective: The objective of this study was to determine whether BMI and gender could lead to a different response rate to anti-TNF agents in patients affected by axial SpA.

Methods: One hundred and seventy patients with active axial SpA (defined as a BASDAI ≥ 4) treated with an anti-TNF agent [adalimumab (ADA), etanercept (ETA), infliximab (IFX)] were retrospectively evaluated. Patients were divided according to the baseline BMI as normal weight (BMI < 25), overweight (BMI 25-30) and obese (BMI ≥ 30).

Assessment of two-dimensional separative systems using nearest-neighbor distances approach. Part 1: orthogonality aspects.

We propose here a new approach to the evaluation of two-dimensional and, more generally, multidimensional separations based on topological methods. We consider the apex plot as a graph, which could further be treated using a topological tool: the measure of distances between the nearest neighbors (NND). Orthogonality can be thus defined as the quality of peak dispersion in normalized separation space, which is characterized by two factors describing the population of distances between nearest neighbors: the lengths (di(o)) of distances and the degree of similarity of all lengths.

Assessment of two-dimensional separative systems using the nearest neighbor distances approach. Part 2: separation quality aspects.

In this paper we propose a method for the evaluation of real separation quality in multidimensional separations based on the nearest neighbor distances (NND). This approach allows us to overcome the principal drawback of the orthogonality measurement which does not evaluate how good the real separation obtained with one system is, especially when compared to another one. Separation quality evaluation takes into account the distances (di(s)) between peaks in whole separation space.

Apoptosis-, proliferation, immune function-, and drug resistance- related genes in ER positive, HER2 positive and triple negative breast cancer.

The aim of our study was to examine an association between gene expression assessed using a 23-gene microarray and receptor status of breast cancer samples categorized as ER positive, HER2 positive and triple negative subtypes. The ER positive cohort was subsequently divided into Luminal A, Luminal B HER2 negative and Luminal B HER2 positive subtypes. Core- needle biopsies were collected from 78 female patients with inoperable locally advanced breast cancer or resectable tumors suitable for downstaging, before any treatment.

Gene expression and pathologic response to neoadjuvant chemotherapy in breast cancer.

Pathologic complete response after neoadjuvant systemic treatment appears to be a valid surrogate for better overall survival in breast cancer patients. Currently, together with standard clinicopathologic assessment, novel molecular biomarkers are being exhaustively tested in order to look into the heterogeneity of breast cancer. The aim of our study was to examine an association between 23-gene real-time-PCR expression assay including ABCB1, ABCC1, BAX, BBC3, BCL2, CASP3, CYP2D6, ERCC1, FOXC1, GAPDH, IGF1R, IRF1, MAP2, MAPK 8, MAPK9, MKI67, MMP9, NCOA3, PARP1, PIK3CA, TGFB3, TOP2A, and YWHAZ receptor status of breast cancer core biopsies sampled before neoadjuvant chemotherapy (anthracycline and taxanes) and pathologic response.

Polymorphisms of the IgH enhancer HS1.2 and risk of systemic lupus erythematosus.

Objective: To determine whether the allelic frequency variation of the HS1.2 enhancer of the immunoglobulin heavy chain (IgH) 3' regulatory region (3'RR-1) locus represents a risk factor for systemic lupus erythematosus (SLE) and to identify a possible functional difference in the two most frequent alleles (*1 and *2) in binding nuclear factor- κB (NF-κB) and Sp1.

Methods: The frequency of the enhancer HS1.

Fatty acid profile and influence of oxythiamine on fatty acid content in Malassezia pachydermatis, Candida albicans and Saccharomyces cerevisiae.

Malassezia pachydermatis and Candida albicans are fungi involved in the skin diseases and systemic infections. The therapy of such infections is difficult due to relapses and problems with pathogen identification. In our study, we compare the fatty acids profile of M.

Proliferation of acid-secretory cells in the kidney during adaptive remodelling of the collecting duct.

The renal collecting duct adapts to changes in acid-base metabolism by remodelling and altering the relative number of acid or alkali secreting cells, a phenomenon termed plasticity. Acid secretory A intercalated cells (A-IC) express apical H(+)-ATPases and basolateral bicarbonate exchanger AE1 whereas bicarbonate secretory B intercalated cells (B-IC) express basolateral (and apical) H(+)-ATPases and the apical bicarbonate exchanger pendrin. Intercalated cells were thought to be terminally differentiated and unable to proliferate.

Induction of metabolic acidosis with ammonium chloride (NH4Cl) in mice and rats--species differences and technical considerations.

Ammonium chloride addition to drinking water is often used to induce metabolic acidosis (MA) in rodents but may also cause mild dehydration. Previous microarray screening of acidotic mouse kidneys showed upregulation of genes involved in renal water handling. Thus, we compared two protocols to induce metabolic acidosis in mice and rats: standard 0.

The calcium-sensing receptor promotes urinary acidification to prevent nephrolithiasis.

Hypercalciuria increases the risk for urolithiasis, but renal adaptive mechanisms reduce this risk. For example, transient receptor potential vanilloid 5 knockout (TPRV5(-/-)) mice lack kidney stones despite urinary calcium (Ca(2+)) wasting and hyperphosphaturia, perhaps as a result of their significant polyuria and urinary acidification. Here, we investigated the mechanisms linking hypercalciuria with these adaptive mechanisms.

Clinical evidence that very small embryonic-like stem cells are mobilized into peripheral blood in patients after stroke.

Background And Purpose: In a murine model of stroke, we identified a population of very small embryonic-like (VSEL) stem cells (SCs) in adult murine bone marrow that could be mobilized into peripheral blood (PB). This raised the question of whether a similar population of cells is mobilized in human stroke patients.

Methods: We evaluated a number of cells that corresponded to VSEL SCs in the PB of 44 stroke patients and 22 age-matched controls.

A role for Rhesus factor Rhcg in renal ammonium excretion and male fertility.

The kidney has an important role in the regulation of acid-base homeostasis. Renal ammonium production and excretion are essential for net acid excretion under basal conditions and during metabolic acidosis. Ammonium is secreted into the urine by the collecting duct, a distal nephron segment where ammonium transport is believed to occur by non-ionic NH(3) diffusion coupled to H(+) secretion.

Renal phosphaturia during metabolic acidosis revisited: molecular mechanisms for decreased renal phosphate reabsorption.

During metabolic acidosis (MA), urinary phosphate excretion increases and contributes to acid removal. Two Na(+)-dependent phosphate transporters, NaPi-IIa (Slc34a1) and NaPi-IIc (Slc34a3), are located in the brush border membrane (BBM) of the proximal tubule and mediate renal phosphate reabsorption. Transcriptome analysis of kidneys from acid-loaded mice revealed a large decrease in NaPi-IIc messenger RNA (mRNA) and a smaller reduction in NaPi-IIa mRNA abundance.

Hemodynamic blood flow disturbances in the middle cerebral arteries in patients with atrial fibrillation during acute ischemic stroke.

Objectives: The purpose of the present study was to evaluate whether blood flow in the middle cerebral arteries (MCAs) in patients with atrial fibrillation (AF) during acute ischemic stroke is disturbed, as well as to assess if potential disturbances result from arrhythmia rather than a consequence of an embolus within the cerebral circulation.

Patients And Methods: A total of 180 subjects were included in the study; 90 consecutive patients with AF and 90 consecutive patients in sinus rhythm who were admitted to the Stroke Unit of the Department of Neurology at Pomeranian Medical University Hospital in Szczecin, Poland within 24h of the onset of ischemic stroke symptoms. During the acute phase of the stroke (24h), all patients underwent transcranial Doppler ultrasonography (TCD) with assessment of mean blood flow velocity (MV) in the MCAs.

Genome-wide gene expression profiling reveals renal genes regulated during metabolic acidosis.

Production and excretion of acids are balanced to maintain systemic acid-base homeostasis. During metabolic acidosis (MA) excess acid accumulates and is removed from the body, a process achieved, at least in part, by increasing renal acid excretion. This acid-secretory process requires the concerted regulation of metabolic and transport pathways, which are only partially understood.

Patients' and bystanders' awareness of stroke and pre-hospital delay after stroke onset: perspectives for thrombolysis in West Pomerania Province, Poland.

Objective: Thrombolysis is a time-dependent therapy. It is therefore very important how fast stroke patients can reach hospital. The present study was designed to assess which proportion of patients with stroke (from the population of Szczecin, the capital of West Pomerania Province, Poland) reaches hospital within the recommended time from the thrombolytic therapy point of view.

Can we talk about CD4+CD28- lymphocytes as a risk factor for ischemic stroke?

Background: CD4+CD28- lymphocytes are implicated in the destabilization of atheromatous plaque, leading to acute coronary episodes. One may ask whether these cells play a similar role in ischemic stroke pathogenesis with an atherosclerotic background.

Methods: Flow cytometry was applied to determine the percentage of CD4+CD28- lymphocytes in the peripheral blood of patients during the acute phase of their first ischemic stroke (group I) and in patients without a history of stroke but with two of the most important risk factors (hypertension, diabetes) for atherosclerosis-related ischemic stroke (group II).

Thyroid hormone deficiency alters expression of acid-base transporters in rat kidney.

Hypothyroidism in humans is associated with incomplete distal renal tubular acidosis, presenting as the inability to respond appropriately to an acid challenge by excreting less acid. Here, we induced hypothyroidism in rats with methimazole (HYPO) and in one group substituted with l-thyroxine (EU). After 4 wk, acid-base status was similar in both groups.

Stimulatory effect of LH, PGE2 and progesterone on StAR protein, cytochrome P450 cholesterol side chain cleavage and 3beta hydroxysteroid dehydrogenase gene expression in bovine luteal cells.

The aim of these studies was to investigate the effect of LH, progesterone (P4), PGE, noradrenaline (NA) and a nitric oxide donor, S-nitroso-N-acetylpenicillamine (S-NAP), on steroid acute regulatory protein (StAR), 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and cytochrome P450 side chain cleavage (P450scc) gene expression and on the synthesis of their protein products. Bovine luteal cells were collected and prepared on days 6-10 of the estrous cycle and preincubated in vitro for 24 h. Thereafter, medium was changed and supplemented with one of six treatments: control medium, LH (100 ng/ml), P4 (10(-5)M), PGE2 (10(-6)M), NA (10(-5)M) or S-NAP (10(-4)M).

Intraoperative monitoring of the biliary tracts as a means of preventing choledocholithiasis oversight.

The aim of the work is to assess the performance and effectiveness of intraoperative cholangiography or choledochoscopy in the prevention of choledocholithiasis oversight. The effectiveness of choledochoscopy was assessed in 50 patients during the years 2001-2002. Since 2000 intraoperative cholangiography has been performed on all patients after classic cholecystostomy in the absence of indications to choledochotomy.

The use of modern techniques of biliary tract monitoring in percutaneous drainage.

The aim of this work is to assess the usefulness of current imaging techniques of biliary tracts in percutaneous transhepatic biliary drainage (PTBD). In the period from January 1996 to March 2003 44 cases of PTBD were carried out under ultrasonographic and X-ray control in 34 patients who could not have a bypass or endoscopic prothesis of the bile duct. The effectiveness of the method was evaluated in relation to the extent of the intra-hepatic bile ducts, the usefulness of simultaneous monitoring (ultrasonography and X-ray) and the possibility of preoperative contrasting of the bile ducts.