The role of shear forces in primary and secondary nucleation of amyloid fibrils.

Shear forces affect self-assembly processes ranging from crystallization to fiber formation. Here, the effect of mild agitation on amyloid fibril formation was explored for four peptides and investigated in detail for A[Formula: see text]42, which is associated with Alzheimer's disease. To gain mechanistic insights into the effect of mild agitation, nonseeded and seeded aggregation reactions were set up at various peptide concentrations with and without an inhibitor. First, an effect on fibril fragmentation was excluded by comparing the monomer-concentration dependence of aggregation kinetics under idle and agitated conditions. Second, using a secondary nucleation inhibitor, Brichos, the agitation effect on primary nucleation was decoupled from secondary nucleation. Third, an effect on secondary nucleation was established in the absence of inhibitor. Fourth, an effect on elongation was excluded by comparing the seeding potency of fibrils formed under idle or agitated conditions. We find that both primary and secondary nucleation steps are accelerated by gentle agitation. The increased shear forces facilitate both the detachment of newly formed aggregates from catalytic surfaces and the rate at which molecules are transported in the bulk solution to encounter nucleation sites on the fibril and other surfaces. Ultrastructural evidence obtained with cryogenic transmission electron microscopy and free-flow electrophoresis in microfluidics devices imply that agitation speeds up the detachment of nucleated species from the fibril surface. Our findings shed light on the aggregation mechanism and the role of detachment for efficient secondary nucleation. The results inform on how to modulate the relative importance of different microscopic steps in drug discovery and investigations.

Discovery of potent inhibitors of α-synuclein aggregation using structure-based iterative learning.

Machine learning methods hold the promise to reduce the costs and the failure rates of conventional drug discovery pipelines. This issue is especially pressing for neurodegenerative diseases, where the development of disease-modifying drugs has been particularly challenging. To address this problem, we describe here a machine learning approach to identify small molecule inhibitors of α-synuclein aggregation, a process implicated in Parkinson's disease and other synucleinopathies. Because the proliferation of α-synuclein aggregates takes place through autocatalytic secondary nucleation, we aim to identify compounds that bind the catalytic sites on the surface of the aggregates. To achieve this goal, we use structure-based machine learning in an iterative manner to first identify and then progressively optimize secondary nucleation inhibitors. Our results demonstrate that this approach leads to the facile identification of compounds two orders of magnitude more potent than previously reported ones.

Design of amyloidogenic peptide traps.

Segments of proteins with high ß-strand propensity can self-associate to form amyloid fibrils implicated in many diseases. We describe a general approach to bind such segments in ß-strand and ß-hairpin conformations using de novo designed scaffolds that contain deep peptide-binding clefts. The designs bind their cognate peptides in vitro with nanomolar affinities. The crystal structure of a designed protein-peptide complex is close to the design model, and NMR characterization reveals how the peptide-binding cleft is protected in the apo state. We use the approach to design binders to the amyloid-forming proteins transthyretin, tau, serum amyloid A1 and amyloid ß1-42 (Aß42). The Aß binders block the assembly of Aß fibrils as effectively as the most potent of the clinically tested antibodies to date and protect cells from toxic Aß42 species.

Evaluation of potential prognostic value of Bmi-1 gene product and selected markers of proliferation (Ki-67) and apoptosis (p53) in the neuroblastoma group of tumors.

INTRODUCTION: Cancer in children is a very important issue in pediatrics. The least satisfactory treatment outcome occurs among patients with clinically advanced neuroblastomas. Despite much research, the biology of this tumor still remains unclear, and new prognostic factors are sought. The Bmi-1 gene product is a currently highly investigated protein which belongs to the Polycomb group (PcG) and has been identified as a regulator of primary neural crest cells. It is believed that Bmi­1 and N-myc act together and are both involved in the pathogenesis of neuroblastoma. The aim of the study was to assess the potential prognostic value of Bmi-1 protein and its relations with mechanisms of proliferation and apoptosis in the neuroblastoma group of tumors. MATERIAL/METHODS: 29 formalin-fixed and paraffin-embedded neuroblastoma tissue sections were examined using mouse monoclonal antibodies anti-Bmi-1, anti-p53 and anti-Ki-67 according to the manufacturer's instructions. RESULTS: There were found statistically significant correlations between Bmi-1 expression and tumor histology and age of patients. CONCLUSIONS: Bmi-1 seems to be a promising marker in the neuroblastoma group of tumors whose expression correlates with widely accepted prognostic parameters. The pattern of BMI-1 expression may indicate that the examined protein is also involved in maturation processes in tumor tissue.

Prognostic significance of MCM 2 and Ki-67 in neuroblastic tumors in children.

INTRODUCTION: Neuroblastic tumors can be characterized by three features: spontaneous regression, maturation and aggressive proliferation. The most common and routinely used method of assessing tumor cell proliferation is to determine the Ki-67 index in the tumor tissue. Despite numerous studies, neuroblastoma biology is not fully understood, which makes treatment results unsatisfactory. MCM 2 is a potential prognostic factor in the neuroblastoma group. MATERIAL/METHODS: The study is based on retrospective analysis of 35 patients treated for neuroblastic tumors in the Department of Pediatric Surgery and Oncology of the Medical University of Lodz, during the period 2001-2011. The material comprised tissues of 16 tumors excised during the operation and 19 biopsy specimens. Immunohistochemical examinations were performed with immunoperoxidase using mouse monoclonal anti-MCM 2 and anti-Ki-67 antibodies. RESULTS: We observed that MCM 2 expression ranged from 2% to 98% and the Ki-67 index ranged from 0 to 95%. There was a statistically significant correlation between expression of MCM 2 and the value of the Ki-67 index and a correlation close to statistical significance between expression of MCM 2 and unfavorable histopathology. There was no statistical relationship between expression of MCM 2 and age over 1 year and N-myc amplification. DISCUSSION: The presented research shows that MCM 2 may have prognostic significance in neuroblastic pediatric tumors and as a potential prognostic factor could be the starting point of new individualized therapy.

The Role of Ultrasound Imaging of Callus Formation in the Treatment of Long Bone Fractures in Children.

BACKGROUND: In the process of diagnosis and treatment of fractures, an X-ray study is typically performed. In modern medicine very important is the development of new diagnostic methods without adverse effects on the body. One of such techniques is ultrasound imaging. It has a high value in imaging most areas of the body, including the musculoskeletal system. Reports on the use of ultrasound in the evaluation of the callus are rare and this could be a method equivalent to or even better than standard radiographs. The aim of the study was to analyze the correlation of ultrasound with radiographs in imaging of callus formation after fractures of long bones in children and to analyze the correlation of vascular resistance index (RI) and the degree of vascularization of the callus with a subjective radiological assessment of the bone union quality. MATERIAL/METHODS: The prospective study was planned to qualify 50 children treated for long bones fractures of the arm, forearm, thigh and lower leg. Ultrasound diagnosis was carried out using a Philips iU22 camera equipped with a linear probe with 17-5-MHz resolution and MSK Superficial program. During ultrasound examination measurements of the callus were performed. Using the Power Doppler callus vascularity was visualized and vascular resistance index (RI) was measured. The same measurements were made within the corresponding area of the healthy limb. The results obtained by ultrasound were compared with radiograph measurements and with the subjective assessment of the callus quality. RESULTS: Preliminary results were developed on a group of 24 patients, where 28 fractured bones and 28 corresponding healthy bones were examined. Fifteen boys and 9 girls participated in the study. The average age at injury was, respectively, 11 and 9 years. In both groups fractures without displacement were the most frequent. A similar frequency was observed in fractures requiring reposition and subperiosteal fractures. In contrast, fractures with a slight displacement of the fragments, were 3 times more common in girls. Statistical analysis of the measurements of length and width of the callus demonstrated that the differences between results obtained in the ultrasound in comparison with X-rays were not statistically significant. Moreover, preliminary results showed a significantly higher degree of vascularization of the callus than of the healthy periosteum. CONCLUSIONS: Preliminary results indicate the high efficacy of ultrasound in the evaluation of callus formation after fractures of long bones in children and the possibility of its alternative use to X-ray examinations.

Aß Oligomer Dissociation Is Catalyzed by Fibril Surfaces.

Oligomeric assemblies consisting of only a few protein subunits are key species in the cytotoxicity of neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. Their lifetime in solution and abundance, governed by the balance of their sources and sinks, are thus important determinants of disease. While significant advances have been made in elucidating the processes that govern oligomer production, the mechanisms behind their dissociation are still poorly understood. Here, we use chemical kinetic modeling to determine the fate of oligomers formed in vitro and discuss the implications for their abundance in vivo. We discover that oligomeric species formed predominantly on fibril surfaces, a broad class which includes the bulk of oligomers formed by the key Alzheimer's disease-associated Aß peptides, also dissociate overwhelmingly on fibril surfaces, not in solution as had previously been assumed. We monitor this "secondary nucleation in reverse" by measuring the dissociation of Aß42 oligomers in the presence and absence of fibrils via two distinct experimental methods. Our findings imply that drugs that bind fibril surfaces to inhibit oligomer formation may also inhibit their dissociation, with important implications for rational design of therapeutic strategies for Alzheimer's and other amyloid diseases.

[Evaluation of COX-2 protein expression in melanocytic nevi in children]. / Ocena odczynów z COX-2 w znamionach melanocytarnych u dzieci.

UNLABELLED: Melanocytic skin tumors can be divided into benign nevi and malignant which take the form of melanoma. Melanocytic nevi are common in both adults and children. It is widely acknowledged that they are one of the risk factors of the formation of melanoma. However, melanoma among children is rare. In addition, differentiation of benign and malignant melanocytic tumors is often challenging. Recent studies suggest that COX-2 protein maybe useful in excluding malignant transformation of melanocytic lesion. The aim of the study was to evaluate the occurrence and differences of reactions with COX-2 in groups of nevi in children and melanoma adults. MATERIAL AND METHODS: The study included 75 common nevi and 43 atypical nevi incised in children and 15 cases of melanoma removed in adults. Paraffin blocks were used to make a preparations with routine hematoxylin and eosin staining (H + E) and immunohistochemistry. The results were statistically analyzed. RESULTS: Positive reactions were observed in both melanocytic nevi and melanoma. Differences between benign and malignant melanocytic tumors were statistically significant. Differences within melanocytic nevi were not statistically significant. CONCLUSIONS: The reactions of COX-2 are present in all nevi and do not allow to differentiate between their various types. COX-2 has potential utility in the differentiation of benign and malignant melanocytic tumors.

Improving community-based COPD care in general practice in Poland - a cluster randomized controlled trial.

INTRODUCTION AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. The aim of the study was to evaluate the impact of intervention on exacerbations of COPD in elderly patients compared to those receiving usual care. MATERIAL AND METHODS: A 12 month, multicentre, three-arm, pragmatic, cluster randomized controlled trial was performed (CRCT). The 97 largest PHC clinics with at least 46 COPD registered patients in the Lódz Province, in central Poland. In total, 27,534 COPD patients aged 65 and over were identified from the National Health Fund (NFZ) electronic health records. A checklist of selected, recommended COPD interventions sent to GPs once or twice by post and shown on their desk in their clinics, in the intervention arms. RESULTS: A primary outcome was the difference in exacerbations or deaths between the 3 arms at 12 months. The amounts of specific short- and long-acting drugs purchased by patients were also assessed as secondary outcomes. Only 0.44% (122 of 27 534) COPD patients demonstrated exacerbations after the one-year study period. No statistically significant associations were found between interventions and exacerbations (p=0.1568, Chi-Square) or deaths (p=0.8128, Chi-Square) at 12 months. CONCLUSIONS: As this study coincided with the pandemic period, the results should be interpreted with care. The intervention had no association with exacerbations. Future research on interventions aimed at improving chronic illness care are needed.

Minichromosome maintenance 2 (MCM2) is a new prognostic proliferative marker in Wilms tumour.

OBJECTIVE: We examined expression of minichromosome maintenance 2 (MCM2) by immunohistochemistry in nephrectomy specimens of children with nephroblastoma treated according to the Society International d'Oncologie Pediatrique (SIOP) scheme to determine its potential prognostic significance. MATERIAL AND METHODS: 18 children with nephroblastoma, 9 females and 9 males, 2 months to 7 years of age, treated in the Department of Oncology and Paediatric Surgery, Medical University of Lodz, during the period 1994-2006 were analysed. Children were treated by neoadjuvant chemotherapy and subsequent nephrectomy according to SIOP protocols -93 and 2001 and followed up from 2 to 11 years. The tumour stage and classification in nephrectomy specimens were established according to the revised 2001 SIOP working classification of renal tumours of childhood. RESULTS: In low risk nephroblastoma MCM2 expression was low, ranging from 0% in two cases of completely necrotic nephroblastoma to 5% in one child with cystic partially differentiated nephroblastoma. In mesoblastic nephroma, which is a distinct type of neoplasm with a low malignant potential and the most common congenital renal neoplasm, MCM2 expression was variable ranging from 2-5% in 2 children with stage I disease to 70% in one child with stage III disease In intermediate risk nephroblastoma MCM2 expression was low (10%) in one case of regressive type nephroblastoma and stage II disease and intermediate to high in children with epithelial type nephroblastoma, ranging from 40-50% in one case with stage I disease to 70% and 70-100% in 2 children with stage I and stage IV disease, respectively. In high risk nephroblastoma (7 children with nephroblastoma blastemal type) MCM2 expression was intermediate to high, ranging from 40 to 90%. MCM2 expression tends to be lower in children with less advanced stage of disease (stage II) and higher in more advanced disease (stage III and IV). Two children with blastemal type and high (> 60% MCM2) died of disease within 2-4 years from diagnosis and one child was lost to follow-up. Both children who died were older 8.5 yo M and 7 yo M and presented with advanced disease stage IV or III with anaplasia. CONCLUSION: MCM2 is a promising prognostic factor in WT treated according to the SIOP scheme.

A checklist-based method for improving COPD care for the elderly in general practice: study protocol for a cluster randomized controlled trial using electronic health records.

BACKGROUND: The third most frequent chronic condition, and the fourth most common cause of death, in Poland is chronic obstructive pulmonary disease (COPD). The diagnosis and treatment of COPD is the responsibility of the general practitioner (GP); the GP also serves as gatekeeper, referring patients to the other levels of public health care system when necessary. Undertreatment of COPD can result in a greater frequency of exacerbations and hospitalizations. Elderly patients require special attention due to the increased prevalence of COPD and systemic comorbidities. However, both the occurrence of exacerbations and the quality of life of the patients may be improved by developing and implementing guidelines for practice and ensuring their adherence. This proposal concerns the development of a checklist-based educational program to assist general practitioners in managing COPD patients. METHODS: No less than eighty-four general clinics in the Lodz region, Poland (28 clusters in each of three study arms), will be identified, randomized, and included in the trial. The trial will be based on anonymized data in electronic health records within the national public health care system. The educational intervention program will consist of GPs in two intervention arms being provided with a COPD management checklist: those in the first intervention arm with receive the checklist once at the beginning, while those in the second with receive it twice. The third (control) arm receives standard care without the checklist. The study used the International Code of Diseases (ICD)-10 for COPD. The primary aim is to determine the effect of interventions delivered to general practitioners (GPs) in primary health care. These interventions are aimed at decreasing the hospitalization of elderly patients with medical code J-44 (COPD) as the main reason for hospital admission. DISCUSSION: The results of this trial will be directly applicable to primary care in Poland and add new data to the growing body of evidence regarding interventions aimed at improving chronic illness care. TRIAL REGISTRATION: This trial has been registered with the Clinical Trials Protocol Registration System. Please see in ClinicalTrial.gov identifier (NCT Number): NCT04301505 . Registered on 10 March 2020.

The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends.

Molecular chaperones contribute to the maintenance of cellular protein homoeostasis through assisting de novo protein folding and preventing amyloid formation. Chaperones of the Hsp70 family can further disaggregate otherwise irreversible aggregate species such as α-synuclein fibrils, which accumulate in Parkinson's disease. However, the mechanisms and kinetics of this key functionality are only partially understood. Here, we combine microfluidic measurements with chemical kinetics to study α-synuclein disaggregation. We show that Hsc70 together with its co-chaperones DnaJB1 and Apg2 can completely reverse α-synuclein aggregation back to its soluble monomeric state. This reaction proceeds through first-order kinetics where monomer units are removed directly from the fibril ends with little contribution from intermediate fibril fragmentation steps. These findings extend our mechanistic understanding of the role of chaperones in the suppression of amyloid proliferation and in aggregate clearance, and inform on possibilities and limitations of this strategy in the development of therapeutics against synucleinopathies.

Soluble receptors for vascular endothelial growth factor (sVEGFR1/sVEGFR2) in infantile hemangioma.

UNLABELLED: Vascular endothelial growth factor (VEGF) and its receptors were postulated to be involved in pathogenesis of infantile hemangioma. The aim of this study was to determine the serum levels of VEGF and soluble VEGF receptors (sVEGFR1/sVEGFR2) in children with hemangiomas. MATERIALS AND METHODS: Thirty-eight children with infantile hemangiomas (25 proliferating, 13 involuting) and 34 healthy children were included in the study. sVEGFR1 and sVEGFR2 serum levels in peripheral blood and in vascular tumors were determined with ELISA test. RESULTS: sVEGFR1 serum levels were slightly lower in hemangioma patients (p = 0.049). No significant differences in sVEGFR2 levels were observed in any study group. VEGF levels did differ significantly, with median level being 364.05 pg/ml in hemangioma patients and 107.40 pg/ml in the control group (p < 0.0001). CONCLUSIONS: The obtained results suggest that VEGF is involved in hemangioma angiogenesis but that soluble VEGFRs marginally influence this process. Lower serum levels of sVEGFR1 in hemangioma patients indicate the possible dysregulation between VEGFR1 and VEGFR2 receptors.

Local serum levels of vascular endothelial growth factor in infantile hemangioma: intriguing mechanism of endothelial growth.

UNLABELLED: The pathogenesis of hemangiomas still remains poorly understood. Dysregulation of angiogenesis has been proposed to play a central role in hemangioma pathogenesis. The aim of our study was to determine the peripheral and local serum levels of VEGF in patients with hemangiomas and vascular malformations. MATERIAL AND METHODS: The study group consisted of 52 children with infantile hemangioma (33 with proliferative lesions, 19 with involuting lesions), 14 children with vascular malformations and 36 healthy children. VEGF serum levels were analyzed by an ELISA assay and the values between the groups were compared. RESULTS: The serum peripheral VEGF concentrations in children with proliferative hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and controls. There was no correlation between the measured cytokine level, hemangioma size, and the age of the patients. The local serum VEGF levels in 29 children with hemangiomas were distinctly lower than in the peripheral blood, both in 20 proliferating hemangiomas (p<0.0001) and 9 involuting ones (p=0.007); and the difference between females and males was non-significant (NS p=0.06). CONCLUSIONS: (1) VEGF serum levels vary in the different phases of hemangioma growth and may help to distinguish hemangiomas from vascular malformations; (2) obtained local results may support the intrinsic theory of endothelial cell proliferation in hemangiomas.

Natural killer cell cytotoxicity and immunosuppressive cytokines (IL-10, TGF-beta1) in patients with gastric cancer.

Cytotoxic activity of NK cells was estimated as related to IL-10 and TGF-beta1 serum levels and Helicobacter pylori infection in gastric cancer patients. Moreover, we sought to determine whether human gastric adenocarcinoma cells in vitro release IL-10, TGF-beta1 or factor(s) affecting NK cytotoxicity. The studies were conducted on 42 patients with gastric cancer (14 with I-II stage-group 1; 28 with III-IV stage-group 2) and on 20 healthy volunteers. The cytotoxicity was tested on NK cells isolated from peripheral blood. IL-10 and TGF-beta1 levels were determined by ELISA. H. pylori was detected in cultures of gastric mucosa biopsies and in direct preparations. In 71.4% patients of group 1 NK cytotoxicity and IL-10 serum levels remained within a normal range while in 68% patients of group 2 a marked decrease was noted in cytotoxic function of NK cells, accompanied by increased levels of IL-10 in serum. In turn, in most patients of either group, independently of NK cytotoxicity and stage grouping in the patients, elevated serum levels of TGF-beta1 were detected. Presence of H. pylori infection manifested no relationship with NK cytotoxicity, IL-10, or the TGF-beta1 serum levels. In cultures of tumour cells presence of IL-10 and TGF-beta1 was demonstrated. Nevertheless, supernatants of the cultures did not change cytotoxic activity of NK cells. Development of gastric carcinoma is accompanied by markedly decreased cytotoxic function of NK cells and by elevated IL-10 and TGF-beta1 serum levels. Gastric carcinoma cells may release IL-10, the suppressive activity of which may in a secondary manner decrease NK cytotoxicity.

Soluble cytokine receptors sTNFR I and sTNFR II, receptor antagonist IL-1ra, and anti-inflammatory cytokines IL-10 and IL-13 in the pathogenesis of systemic inflammatory response syndrome in the course of burns in children.

BACKGROUND: This is a prospective clinical study focusing on cytokine inhibitors (sTNFR I, sTNFR II, IL-1ra) and anti-inflammatory cytokines (IL-10, IL-13) following burn injury in children. The aim of the study was to evaluate the prognostic values of the selected cytokine-related molecules. MATERIAL/METHODS: Fifty-one patients (29 burned children and 22 controls) admitted to the Department of Pediatric Surgery and Oncology were included in this study. Serum sTNFR I, sTNFR II, IL-1ra, IL-10, IL-13, and CRP concentrations were evaluated twice using ELISA, the first determination being performed within 6-24 hrs after the burn and the second following completion of treatment and normalization of the CRP level. RESULTS: With the exception of IL-13, significantly higher cytokine and cytokine inhibitor levels were observed within 6-24 hours after burn compared with controls (p<0.05). Moreover, a significant attenuation of the burn-induced increases in sTNFR I, sTNFR II, IL-1ra, and IL-10 concentrations was recorded after burn therapy (p<0.05). TNF-alpha soluble receptor levels correlated significantly with serum CRP concentrations. Similarly, the levels of sTNFR I, sTNFR II, and IL-1ra significantly correlated with TBSA of the burned children. CONCLUSIONS: The results confirm the involvement of these markers in the pathogenesis of SIRS in this clinical entity. Their monitoring simultaneously with CRP level allows evaluating the generalized inflammatory response and may clinically support diagnostic and prognostic methods.

Serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in children with hemangiomas and vascular malformations--preliminary report.

Impaired balance between proangiogenic and antiangiogenic factors has been implicated in the development of hemangiomas. Elevated vascular endothelial growth factor serum levels and basic fibroblastic growth factor urine levels in patients with proliferating hemangiomas were reported. However, whether these growth factors can be used for the differential diagnosis of vascular anomalies or assessment of the clinical course of hemangiomas has yet to be determined. We report here our preliminary results of serum vascular endothelial growth factor and basic fibroblastic growth factor levels as an aid in the diagnosis of hemangiomas and in the follow up of patients with this lesion. Twenty two children with infantile hemangioma (13 with proliferating hemangiomas, nine with involuting lesions), five children with vascular malformations, and 25 healthy children study group. Vascular endothelial growth factor and basic fibroblastic growth factor serum levels were analyzed by an ELISA assay. The serum vascular endothelial growth factor concentrations in children with proliferating hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and healthy patients. The serum basic fibroblastic growth factor concentrations were low and similar in all patients with no statistical correlation between study groups. We concluded that (i) ELISA can easily determine vascular endothelial growth factor concentrations in different phases of hemangioma growth and help distinguishing them from vascular malformations. (ii) A potential role for vascular endothelial growth factor in the pathophysiology of hemangiomas is probable.

Antimicrobial resistance of Helicobacter pylori clinical strains in the last 10 years.

In the present work primary antimicrobial resistance was analyzed in clinical H. pylori strain isolates from adult patients from Polish Wielkopolska region within the last 10 years. Drug sensitivity was evaluated in a total of 142 H. pylori isolates, with 66 strains originating from years 1997/1998 forming group 1 and 76 strains isolated in 2007/2008 forming group 2. Sensitivity to amoxicillin, tetracycline, metronidazole and clarithromycin was determined by E-test. All strains were susceptible to amoxicillin and tetracycline. On the other hand, a high proportion of strains resistant to metronidazole was determined (36.4% in group 1 and 44.7% in group 2). In parallel, a growing tendency was discovered for resistance to clarithromycin (9.1% strains resistant in group 1 and 18.4% isolates resistant in group 2). The studies confirm the need for monitoring the drug resistance of Helicobacter pylori strains.

Anchor Effect in Polymerization Kinetics: Case of Monofunctionalized POSS.

The effect of the anchoring group on the detailed polymerization kinetics was investigated using monomethacryloxy-heptaisobutyl POSS (1M-POSS). This compound was copolymerized with lauryl methacrylate (LM) as the base monomer, at various molar ratios. The process was initiated photochemically. The polymerization kinetics were followed by photo-DSC and photorheology while the polymers were characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). For comparison, a methacrylate containing the branched siloxy-silane group (TSM) was also studied. It was found that the modifiers with a bulky substituent have a dual effect on the termination process: (i) At low concentrations, they increase the molecular mobility by increasing the free volume fraction, which leads to an acceleration of the termination and slows the polymerization; while (ii) at higher concentrations, they retard molecular motions due to the "anchor effect" that suppresses the termination, leading to acceleration of the polymerization. The anchor effect can also be considered from a different point of view: The possibility of anchoring a monomer with a long substituent (LM) around the POSS cage, which can further enhance propagation. These conclusions were derived based on kinetic results, determination of polymerization rate coefficients, and copolymer analysis.

[Adverse events following BCG vaccination in infants and children up to 36 months of age]. / Niepozadane odczyny po szczepieniu przeciw gruzlicy u niemowlat i dzieci do trzeciego roku zycia.

The aim of the study is to evaluate frequency, treatment and clinical type of adverse reaction (AEFI) after BCG vaccination. Between January 2003 and December 2006, 64 children with AEFI after BCG vaccination were registered in the Pediatric Vaccination Centre in Lódz. Different types of AEFI were distinguished on the basis of Lotte's classification (1977). On the basis of 265 registered cases of adverse events after compulsory vaccination, 41.1% (109/265) of them appeared as a result of BCG vaccination. The AEFI clinical analysis showed that in children aged up to 36 months the most frequent symptoms were auxiliary lymphadenitis 67.2% (43/64) or local subcutaneous abscess. In 43.8% (28/64) of cases after BCG vaccination surgical treatment was needed, including 17.2% (11/64) of children who had lymphadenectomy. The majority of AEFI cases after BCG vaccination were observed in children up to 36 months. The AEFI clinical analysis showed that in children aged up to 36 months the most frequent symptoms were regional lymphadenopathy and local subcutaneous abscess. The second most important strategy in AEFI treatment is the cooperation with surgeons. Higher rates of local reaction may result from incorrect methods of BCG vaccine administration.