Axillary Lymph Node Status and Prognosis in Multifocal and Multicentric Breast Carcinoma

According to tumor‐node‐metastasis classification, tumor size should be based only on the largest tumor for multifocal and multicentric (MFMC) carcinomas. We estimated tumor size of MFMC carcinoma using either largest dimension of the largest tumor (dominant tumor size) or sum of the largest dimension of all tumors (aggregate tumor size), and compared the risk of axillary lymph node metastasis and prognosis between MFMC and unifocal carcinoma. We retrospectively reviewed the file records of 3,616 patients with MFMC (258 patients, 7.1%) and unifocal (3,358 patients) carcinoma. In T1 and T2 tumor subgroups, using dominant (p = 0.001 and p < 0.001) and aggregate (p = 0.017 and p = 0.004) tumor size axilla‐positivity ratio was significantly higher in MFMC carcinoma compared with unifocal carcinoma. In stage I and II disease classified according to either dominant or aggregate tumor size, there was no significant survival difference between MFMC and unifocal carcinoma patients. In patients with stage III disease by dominant and aggregate tumor size disease‐free survival was significantly worse in MFMC carcinoma compared with unifocal carcinoma (p = 0.036 and p = 0.041); multifocality and multicentricity had no independent prognostic significance (p = 0.074 and p = 0.079). The risk of axillary metastasis in MFMC carcinoma was higher than unifocal carcinoma, regardless of the method employed for tumor size estimation. MFMC carcinoma staged according to either dominant or aggregate tumor size had similar survival with unifocal carcinoma. We recommend using the largest dimension of the largest tumor in estimation of tumor size for MFMC carcinoma.     

Severe renal failure and hyperammonemia in a newborn with propionic acidemia: effects of treatment on the clinical course

Neonatal-onset propionic acidemia (PA), the most common form, is characterized by poor feeding, vomiting, and somnolence in the first days of life in a previously healthy infant, followed by lethargy, seizures, and can progress to coma if not identified and treated appropriately. It is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. PA is caused by deficiency of propionyl-CoA carboxylase (PCC), the enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA. Herein, we report a case of 3-day-old neonate with PA presented with acute renal failure and metabolic acidosis was effectively treated by peritoneal dialysis and conventional methods.     

Comparison of quality of life in patients with peripheral arterial disease caused by atherosclerosis obliterans or Buerger’s disease

Vascular diseases are well studied today because of the relationship between arterial age and human age, the close connection between aging and arterial diseases, and the fact that the majority of deaths result from diseases of the vascular system. Among vascular diseases, chronic occlusive arterial disease of the lower extremities is of great importance in terms of mortality and morbidity. An increase in the incidence of peripheral arterial diseases is also a consequence of the gradually increasing size of the elderly population.1The treatment strategy for patients should not be intended only for the prevention of extremity loss in peripheral arterial diseases (PAD), but also for the determination and treatment of risk factors, thus resulting in increased quality of life. Nowadays, the objective determination of quality of life, and evaluation of the association between quality of life and treatment methods in PAD is of great importance.1-3Buerger’s disease is a PAD that is frequently encountered and causes significant loss of the extremities. Generally, although its pathological characteristics are well described, there is inadequate information about its impact on daily life and general health levels of patients, and about the difference in terms of quality of life between patients with Buerger’s disease and atherosclerosis obliterans (ASO), which are the most significant causes of PAD.These two types of PAD show different aetiology, age of appearance and co-morbidity. These differences may influence the patient’s quality of life differently. Based on our clinical observations, we assumed the quality of life in patients with Buerger’s disease may be worse than that of patients with ASO.Although studies evaluating quality of life in PAD have been carried out, there is, to our knowledge, no study that evaluates quality of life in patients with Buerger’s disease, or a comparison of quality of life in patients with ASO and Buerger’s disease, which are the most significant chronic occlusive arterial diseases. The objective of our study was to compare the quality of life in patients with ASO and Buerger’s disease.     

Syndromic Disorders with Short Stature

Short stature is one of the major components of many dysmorphic syndromes. Growth failure may be due to a wide variety of mechanisms, either related to the growth hormone (GH)/insulin-like growth factor axis or to underlying unknown pathologies. In this review, the relatively more frequently seen syndromes with short stature (Noonan syndrome, Prader-Willi syndrome, Silver-Russell syndrome and Aarskog-Scott syndrome) were discussed. These disorders are associated with a number of endocrinopathies, as well as with developmental, systemic and behavioral issues. At present, GH therapy is used in most syndromic disorders, although long-term studies evaluating this treatment are insufficient and some controversies exist with regard to GH dose, optimal age to begin therapy and adverse effects. Before starting GH treatment, patients with syndromic disorders should be evaluated extensively.     

Predicting the virulence of MRSA from its genome sequence

Microbial virulence is a complex and often multifactorial phenotype, intricately linked to a pathogen’s evolutionary trajectory. Toxicity, the ability to destroy host cell membranes, and adhesion, the ability to adhere to human tissues, are the major virulence factors of many bacterial pathogens, including Staphylococcus aureus. Here, we assayed the toxicity and adhesiveness of 90 MRSA (methicillin resistant S. aureus) isolates and found that while there was remarkably little variation in adhesion, toxicity varied by over an order of magnitude between isolates, suggesting different evolutionary selection pressures acting on these two traits. We performed a genome-wide association study (GWAS) and identified a large number of loci, as well as a putative network of epistatically interacting loci, that significantly associated with toxicity. Despite this apparent complexity in toxicity regulation, a predictive model based on a set of significant single nucleotide polymorphisms (SNPs) and insertion and deletions events (indels) showed a high degree of accuracy in predicting an isolate’s toxicity solely from the genetic signature at these sites. Our results thus highlight the potential of using sequence data to determine clinically relevant parameters and have further implications for understanding the microbial virulence of this opportunistic pathogen.A key factor affecting the severity and outcome of any infection is the virulence potential of the infecting organism. If the virulence phenotype could be determined directly from its genome sequence, next generation sequencing technology would provide for the first time an opportunity to make predictions of virulence at an early stage of infection. Since the first whole-genome sequence of a free-living organism, Haemophilus influenzae, was published (Fleischmann et al. 1995), sequencing technology has advanced to a stage where a bacterial genome can be sequenced in a matter of hours (Parkhill and Wren 2011; Didelot et al. 2012a; Eyre et al. 2012; Köser et al. 2012a). This has led to an explosion of genomic data that has allowed us to monitor outbreaks in hospitals (Köser et al. 2012b; Young et al. 2012; Harris et al. 2013; Sherry et al. 2013; Walker et al. 2013), track strains transitioning from carrier to invasive status (Young et al. 2012), and perform detailed epidemiological studies to understand aspects of pathogen biology (Castillo-Ramírez et al. 2011, 2012; Didelot et al. 2012b; McAdam et al. 2012; Holden et al. 2013). While some success has also been made in predicting phenotype from genotype, such as the antimicrobial resistance (Farhat et al. 2013; Holden et al. 2013), for more complex phenotypes, such as virulence, involving the contribution of several genes, this has not yet been possible. Furthermore, complex interactions between genes (epistasis) are not apparent from genome sequences alone, nor is the effect of epigenetics (Borrell and Gagneux 2011; Jelier et al. 2011; Beltrao et al. 2012; Bierne et al. 2012).Staphylococcus aureus is a major human pathogen, the treatment of which has been complicated by the worldwide emergence of multiple lineages that have acquired resistance to methicillin (methicillin resistant S. aureus, MRSA) (Lowy 1998; Gordon and Lowy 2008; Otto 2010). Its virulence is conferred by the activity of many effector molecules which can be broadly grouped into being either toxins (Lowy 1998; Gordon and Lowy 2008; Otto 2010)—factors that cause specific tissue damage in the host, or adhesins—factors that facilitate adherence to and invasion of host tissues (Foster et al. 2014). The ability of toxins to lyse human cells causes local tissue damage, facilitating immune evasion, release of nutrients, dissemination within a host, and transmission to others (Lowy 1998; Gordon and Lowy 2008; Otto 2010). A complex network of regulatory proteins controls the expression of many individual toxins (Priest et al. 2012), such that various sites on the S. aureus chromosome contribute to the overall toxicity of an individual isolate. The ability of S. aureus cells to bind human glycoproteins, such as fibrinogen and fibronectin, is another critical determinant in disease outcome. It facilitates attachment to and damage of host tissues, host cell invasion, and systemic dissemination (Foster et al. 2014). Several genes encode fibronectin- and fibrinogen-binding proteins (e.g., fnbA, fnbB, clfA, clfB, eap, isdA, emp, ebh, etc.), whose expression is again controlled by a complex regulatory network (Priest et al. 2012). Similar to toxicity, many sites on the chromosome can therefore contribute to the overall adhesiveness of S. aureus, with many regulators common to both adhesion and toxicity (Priest et al. 2012).The success of epidemic MRSA clones such as USA300 and sequence type (ST) 239 is attributed to a variation in their expression of either toxins or adhesins (Li et al. 2010; Otto 2010; Li et al. 2012). In response to the prevalence of the highly toxic USA300 clone, guidelines exist that recommend treating suspected infections with vancomycin and a second antibiotic such as clindamycin or linezolid to reduce toxin expression and the associated disease severity (http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1242630044068). It is therefore clear that the ability to predict whether an infecting isolate is either highly adhesive or highly toxic could allow clinicians to adapt treatment approaches and increase their index of suspicion for disease complications for infected individuals.To address this, we adopted a genome-wide association study (GWAS) and a machine learning approach to determine the feasibility of predicting virulence from the genome sequences of 90 MRSA isolates. Our findings demonstrate that using whole-genome sequence data for large collections of isolates to identify genetic signature associated with a specific trait can be used to infer complex phenotypes from genotype.     

Regulation of oxidative stress and somatostatin,cholecystokinin, apelin gene expressions by ghrelin in stomach of newborn diabetic rats

The aim of the study was to determine whether ghrelin treatment has a protective effect on gene expression and biochemical changes in the stomach of newborn streptozotocin (STZ) induced diabetic rats. In this study, four groups of Wistar rats were used: control, ghrelin control, diabetic and diabetic + ghrelin. The rats were sacrificed after four weeks of treatment for diabetes. The gene expressions of: somatostatin, cholecystokinin, apelin and the altered active caspase-3, active caspase-8, proliferating cell nuclear antigen, were investigated in the pyloric region of the stomach and antioxidant parameters were measured in all the stomach. Although ghrelin treatment to diabetic rats lowered the stomach lipid peroxidation levels, the stomach glutathione levels were increased. Exogenous ghrelin caused an increased activities of stomach catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase in diabetic rats. Numbers of somatostatin, cholecystokinin and proliferating cell nuclear antigen immunoreactive cells decreased in the diabetic + ghrelin group compared to the diabetic group. Apelin mRNA expressions were remarkably less in the diabetic + ghrelin rats than in diabetic rats. The results may indicate that ghrelin treatment has a protective effect to some extent on the diabetic rats. This protection is possibly accomplished through the antioxidant activity of ghrelin observed in type 2 diabetes. Consequently exogenous ghrelin may be a candidate for therapeutic treatment of diabetes.