Value of short exercise and short exercise with cooling tests in the diagnosis of myotonic dystrophies (DM1 AND DM2)

Introduction: Standard electromyography (EMG) is useful in the diagnosis of myotonic dystrophy type 1 (DM1) and type 2 (DM2), but it does not differentiate between them. The aim of this study was to estimate the utility of the short exercise test (SET) and short exercise test with cooling (SETC) in differentiating between DM1 and DM2. Methods: SET and SETC were performed in 32 patients with DM1 (mean age 35.8 ± 12.7 years) and 28 patients with DM2 (mean age 44.5 ± 12.5 years). Results: We observed a significant decline in compound motor action potential (CMAP) amplitude in DM1 with both SET and SETC immediately after effort. In DM2, there was no marked change in CMAP amplitude with either SET or SETC. Conclusions: SET and SETC may serve as useful tools for clinical differentiation between DM1 and DM2, and they may be used as a guide for molecular testing. Muscle Nerve 49 : 277–283, 2014     

Usefulness of Reynolds Risk Score in men with stable angina

Introduction

Recently several risk scores have been proposed that, beyond traditional risk factors, also include additional inflammatory biomarkers underlying atherothrombosis. The Reynolds Risk Score (RRS) is a point scale assessing the risk of cardiovascular events over 10 years, which takes into account for the first time high-sensitivity C-reactive protein. The aim of this study was to establish clinical usefulness of RRS in men with stable coronary artery disease and preserved left ventricular systolic function.

Material and Methods

In total, 119 symptomatic non-diabetic man (mean age 63.9±9.23) who were directed for an elective coronary arteriography were enrolled in the study. Clinical data were collected including the elevated heart rate ≥70 bpm/min, basic laboratory results, placental growth factor and results of coronary angiography. Patients were analyzed related to RRS: low risk <10% (n=50), moderate risk 10-19% (n=46) and high risk >20% (n=23).

Results

Opposite to high RRS patients, in the low risk group more often occurred marginal or none atherosclerotic coronary arteries (13% vs. 44%, P=0.0214). The findings have revealed the relationship between the higher risk score and the lower frequency of marginal or no atherosclerotic coronary arteries (OR=0.19, 95%CI 0.05–0.67).

Conclusions

The Reynolds Risk Score appears to be useful in men with stable coronary artery disease and preserved left ventricular systolic function in stratifying the severity of coronary atherosclerosis.     

The heterogeneous immune microenvironment in breast cancer is affected by hypoxia-related genes

The immune system constitutes an important first-line defence against malignant transformation. However, cancer mediated immunosuppression inactivates the mechanisms of host immune surveillance. Cancer cells shut down anti-cancer immunity through direct cell–cell interactions with leukocytes and through soluble factors, establishing an immunosuppressive environment for unimpeded cancer growth. The composition of the immunosuppressive microenvironment in breast tumours is not well documented. To address this question, selected immunosuppressive factors were analyzed in tumour specimens from 33 breast cancer patients after surgery. The mRNA expression of selected genes was quantified in fresh tumour samples. Tumour infiltrating leukocytes were characterized by flow cytometry to identify regulatory T cells, myeloid derived suppressor cells, and type 2 macrophages. Statistical analysis revealed several interesting correlations between the studied parameters and clinical features. Overall, a surprisingly high degree of heterogeneity in the composition of the immunosuppressive environment was found across all breast cancer samples which adds to the complexity of this disease. The influence of the hypoxia inducible factors (HIFs) on the immune microenvironment was also addressed. The level of HIFs correlated with hormone receptor status and the expression of several immunosuppressive molecules. Targeting HIFs might not only sensitize breast tumours for radiation and chemotherapies but also interfere with cancer immunosuppression.     

Thermophilic potentially pathogenic amoebae isolated from natural water bodies in Poland and their molecular characterization

The free-living amoebae (FLA) may live in the environment and also within other organisms as parasites and then they are called amphizoic. They are potentially pathogenic for humans and animals and are found in water that is a source of infection. The aim of this study was molecular detection and identification of these FLA in natural water bodies in North-Western Poland to evaluate the risk of the pathogenic amoebae infections. We examined surface water samples collected from 50 sites and first, the tolerance thermic test was performed in order to select thermophilic, potentially pathogenic strains. For molecular identification of FLA, regions of 18S rDNA, 16S rDNA and intergenic spacers were amplified. Acanthamoeba T4 and T16 genotypes of 18S rDNA gene and 18S rDNA of H. vermiformis were detected. We identified two variants of Acanthamoeba T4 genotype, two variants of Acanthamoeba T16 genotype and one variant of H. vermiformis. Identification of the T16 genotype and H. vermiformis in water was for the first time in Poland. Additionally, we made attempts to adapt the RLB method for detection and differentiation of FLA species and strains. PCR seems to be more sensitive than RLB hybridization, though.     

The Assessment of Eating Behaviour in Children Who Are Obese: A Psychological Approach. A Position Paper from the European Childhood Obesity Group

ObjectiveThis paper introduces health professionals to the different psychological models thought to influence eating behaviour in the absence of hunger in children who are obese and to propose a method of assessing these behaviours in practice.MethodsClinical researchers from the European Childhood Obesity Group (ECOG) adopted an evidence-based approach to examine the literature concerning the assessment of eating behaviour in children who are obese. Studies published in English were filtered out of the medical and psychological literature from 1960 to the present, and the resulting bibliography was searched for relevant articles. Key themes from the current evidence were compiled and classified according to the underpinning psychological models. Based on the current evidence and the authors'' combined clinical experience, a three-staged approach to assessment was agreed by consensus.ResultsValid and reliable tools for assessing and monitoring each of the three identified models (Dietary Restraint Theory, Emotional Eating and the Diathesis-Stress Model) are suggested for use in clinical practice, and the ECOG three-staged approach to assessing eating behaviours in the absence of hunger is described.ConclusionsThis paper presents practical guidance on how to assess eating behaviour in the absence of hunger in children who are clinically obese and suggests a focus for future research.Key Words: Children, Obesity, Psychological assessment, Eating behaviour     

Elevated hemoglobin concentration in 3 children with HFE mutation

Aim

The aim of the study was to analyse the reason of elevated hemoglobin concentration in childhood.

Background

Elevated hemoglobin concentration is a rare abnormality during childhood. There are disorders of hereditary or acquired hyperproliferations of red cells or pseudo high hemoglobin conditions.

Materials and methods

We present 3 asymptomatic children in whom high hemoglobin concentration was diagnosed by a family doctor.

Results

Given that the iron concentration was elevated, genetic testing for HFE mutation was carried out.

Conclusion

Patients presented with HFE mutation might have an increased hemoglobin production.     

Six-month results following treatment of aggressive periodontitis with antimicrobial photodynamic therapy or amoxicillin and metronidazole

Objective

The use of antibacterial photodynamic therapy (aPDT) additionally to scaling and root planing (SRP) has been shown to positively influence the clinical outcomes. However, at present, it is unknown to what extent aPDT may represent a potential alternative to the use of systemic antibiotics in nonsurgical periodontal therapy in patients with aggressive periodontitis (AP). The aim of this study was to evaluate the outcomes following nonsurgical periodontal therapy and additional use of either aPDT or amoxicillin and metronidazole (AB) in patients with AP.

Material and methods

Thirty-six patients with AP displaying at least three sites with pocket depth (PD) ≥6 mm were treated with SRP and either systemic administration of AB for 7 days or with two episodes of aPDT. The following clinical parameters were evaluated at baseline and at 6 months: plaque index (PI), bleeding on probing (BOP), PD, gingival recession (GR) and clinical attachment level (CAL).

Results

Thirty-five patients have completed the 6-month evaluation. At 6 months, mean PD was statistically significantly reduced in both groups (from 5.0?±?0.8 to 3.0?±?0.6 mm with AB and from 5.1?±?0.5 to 3.9?±?0.8 mm with aPDT (p?p?p?p?=?0.03). Both therapies resulted in statistically significant reductions in all parameters compared to baseline.

Conclusion

While both treatments resulted in statistically significant clinical improvements, AB showed statistically significantly higher PD reduction and lower number of pockets ≥7 mm compared to aPDT.

Clinical relevance

In patients with AP, the two times application of aPDT in conjunction with nonsurgical periodontal therapy cannot be considered an alternative to the systemic use of amoxicillin and metronidazole.     

Spatio-temporal pattern of N-methyl-D-aspartate receptor NR1 mRNA expression during postnatal development of visual structures of the rat brain

N-methyl-D -aspartate (NMDA) excitatory amino acid receptors (NMDAR) play a pivotal role in various physiological and pathological responses of the central nervous system (CNS), including such phenomena of neuronal plasticity as cortical development. Hence, it could be suggested that expression of genes coding for NMDAR components can be differentially regulated throughout the development. To test this notion we analyzed with in situ hybridization mRNA levels of NMDAR subunit designated as NR1, during time of development (1–6 weeks postnatally) spanning the critical period of functional formation of major visual structures of the rat brain, namely visual cortex (VC), superior colliculus (SC), and lateral geniculate nucleus (LGN). The highest levels of NR1 mRNA were found in the VC and SC at the onset of the critical period, i.e., 21 days postnatally, whereas in the LGN a tendency toward a similar pattern of expression was observed. Analysis of spatial distribution of NR1 mRNA in the SC and VC revealed that an adult-like laminar pattern of expression was also achieved between 14 and 21 days postnatally. This pattern of expression corroborates with developmentally regulated changes in an overall density of cell bodies in these areas. © 1996 Wiley-Liss, Inc.     

Novel engineered TRAIL-based chimeric protein strongly inhibits tumor growth and bypasses TRAIL resistance

Targeting of the TRAIL-DR4/5 pathway was proposed as a promising approach for specific induction of apoptosis in cancer cells. Clinical trials, however, showed inadequate efficiency of TRAIL as a monotherapy. It is a widely held view that the application of multifunctional molecules or combination therapy may lead to substantial improvement. Here, we demonstrate the effectiveness and safety of a novel chimeric protein, AD-O51.4, which is a TRAIL equipped with positively charged VEGFA-derived effector peptides. The study was performed in multiple cancer cell line- and patient-derived xenografts. A pharmacokinetic profile was established in monkeys. AD-O51.4 strongly inhibits tumor growth, even leading to complete long-term tumor remission. Neither mice nor monkeys treated with AD-O51.4 demonstrate symptoms of drug toxicity. AD-O51.4 exhibits a satisfactory half-life in plasma and accumulates preferentially in tumors. The cellular mechanism of AD-O51.4 activity involves both cytotoxic effects in tumor cells and antiangiogenic effects on the endothelium. The presence of DRs in cancer cells is crucial for AD-O51.4-driven apoptosis execution. The TRAIL component of the fusion molecule serves as an apoptosis inducer and a cellular anchor for the effector peptides in TRAIL-sensitive and TRAIL-resistant cancer cells, respectively. The FADD-dependent pathway, however, seems to be not indispensable in death signal transduction; thus, AD-O51.4 is capable of bypassing the refractoriness of TRAIL. AD-O51.4-driven cell death, which exceeds TRAIL activity, is achieved due to the N-terminally fused polypeptide, containing VEGFA-derived effector peptides. The high anticancer efficiency of AD-O51.4 combined with its safety has led to the entry of AD-O51.4 into toxicological studies.