Obesity and high risk pathological features of papillary thyroid carcinoma: A retrospective analysis of a university hospital in Pakistan

BACKGROUND: Incidence of papillary thyroid carcinoma (PTC) and the frequency of obesity is increasing globally. In literature, relationship between excessive body weight and bad prognostic features of PTC is still debatable. In this study, we aimed to explore the association of obesity with high risk pathological features of PTC in a population treated by total thyroidectomy +/- neck dissection. MATERIALS AND METHODS: Retrospective analysis of patients at Aga Khan University Hospital from January 2013 to December 2014, who underwent total thyroidectomy +/- neck dissection due to PTC. Patients were grouped according to World Health Organization (WHO) classification of BMI. They were categorized into two groups, i.e. normal (BMI= 18.5 - 24.9 kg/m2) and obese (BMI = 30 kg/m2) as none of our patients lie in underweight and overweight category. Pathological features i.e. T-stage, multifocality, bilaterality, extrathyroidal extension, vascular invasion and N-stage were assessed. All tumors were staged according to TNM staging system proposed by 2010 American Joint Committee on Cancer (AJCC). Odds ratio (OR) with 95% confidence interval was used to examine the association between BMI ∧ pathological characteristics of PTC. RESULTS: A total of 53 patients were treated for PTC in two-years period. There were 38 female and 15 male patients. Twenty-eight patients had BMI in normal while twenty-five in obese category. Patients who were in obese category had a significantly greater risk of having a multifocal tumor (OR=5.55, p-value=0.02) and bilaterality (OR=6.54, p-value=0.01) compared to normal weight patients. No positive associations were identified between BMI and extrathyroidal extension, high T-stage, vascular invasion and N-stage. CONCLUSION: Obesity is not associated with high risk pathological features such as extrathyroidal extention, high T-stage, vascular invasion and N-stage in PTC. Although it has been correlated with multifocal and bilateral tumors in this retrospective study, the presence of these factors alone is not adequate to support the association conclusively

Does the information in the phase of low frequency LFP reflect the low frequency envelope of local spike rates?

Recently, it has been shown that when the timing of spikes is measured relative to the phase of the cortical local field potentials (LFP), spikes can carry substantial more information about an external stimulus [1]. Experimental studies in sensory cortices of macaque have shown that the extra information obtained with such phase-of-firing codes above that in the firing rate alone ranges from 55 in primary visual cortex [1] to more than 100 in primary auditory cortex [2]. Here, we use a mathematical model that relates local spike trains and the resulting LFP, to explain the emergence of the phase-of-firing codes in cortex. The model is based on the one proposed in [3] and incorporates two types of integration over the spiking activity: i) a time convolution that results from the filtering properties of neural structures [4], which embeds history effects in LFP from past spiking activity, and ii) an integration step over the activity of neurons in the neighbourhood of the measuring electrode. When the spikes recorded from macaque primary visual cortex were used to synthesize the LFP, the model could reproduce the phase-of-firing information found using the real LFP, as shown in Figure 1. This suggests that an important component of phase-of-firing information originates from the surrounding neural population and past spiking activity. The next question that arises is what is the relative contribution of the neuron population size and the length of the firing rate history embedded in the LFP. We are currently investigating this question by parametrically varying both the population size and time integration ranges in generating the synthetic LFP

Effect of &#946-Glucuronidase on Extraction Efficiency of Silymarin from Human Plasma Samples Using Validated HPLC-UV Analysis

Purpose: To investigate the effect of β-glucuronidase on the extraction efficiency of silymarin (mainly as silybin) from spiked human plasma using a sensitive and reproducible high performance liquid chromatography (HPLC) method.Methods: The importance of β-glucuronidase was evaluated by comparing the extraction efficiency of silymarin in β-glucuronidase-treated and untreated plasma samples. Isocratic HPLC with simple UV detection (288 nm) was applied to analyze the major silymarin components using Thermo-Electron C18 column (200 mm, 4.6 mm I.D., 5μm particle size). The mobile phase, consisting of methanol and 20 mM potassium dihydrogen phosphate buffer (50:50 v/v pH 2.8), was pumped at 1 ml/min.Results: The mean extraction efficiency was 98.97 % (CV = 1.69 %) for treated and 40.88 % (CV = 2.77 %) for untreated plasma samples, compared with nominal concentrations.Conclusion: The studied method showed 60 % reduced extraction efficiency of untreated samples compared to treated samples.Keywords: Silymarin, Silybin, Extraction Efficiency, β-glucuronidase, HPL

Inguinal lymph node metastases from a testicular seminoma: a case report and a review of the literature

<p>Abstract</p> <p>Introduction</p> <p>We report the case of a true hermaphrodite with testicular seminoma with resulting metastases to the inguinal lymph nodes eight months after radical orchidectomy. This is an unusual presentation of testicular cancer and, to the best of our knowledge, the first report of this kind in the literature.</p> <p>Case presentation</p> <p>A 45-year-old Caucasian true hermaphrodite, raised as a male, developed a testicular seminoma. He had undergone a left orchidopexy at the age of 10 for undescended testes. Metastases from testicular tumors to inguinal lymph nodes are a rare occurrence. It has been suggested that previous inguinal or scrotal surgery may alter the pattern of nodal metastasis of testicular cancer. We review the literature to evaluate the incidence of inguinal lymph node involvement in early stage testicular cancer and discuss possible routes of metastases to this unusual site. We also discuss the management of the inguinal lymph nodes in patients with testicular tumors and a previous history of inguinal or scrotal surgery, as this remains controversial.</p> <p>Conclusion</p> <p>Inguinal lymph node metastases from testicular cancer are rare. A history of inguinal or scrotal surgery may predispose involvement of the inguinal nodes. During radical inguinal orchidectomy, the surgeon should be careful to minimize the handling of the testis and ensure high ligation of the spermatic cord up to the internal inguinal ring to reduce the risk of inguinal lymph node metastasis.</p

Crystal Structure of the RNA Recognition Motif of Yeast Translation Initiation Factor eIF3b Reveals Differences to Human eIF3b

BACKGROUND: The multi-subunit eukaryotic initiation factor3 (eIF3) plays a central role in the initiation step of protein synthesis in eukaryotes. One of its large subunits, eIF3b, serves as a scaffold within eIF3 as it interacts with several other subunits. It harbors an RNA Recognition Motif (RRM), which is shown to be a non-canonical RRM in human as it is not capable to interact with oligonucleotides, but rather interacts with eIF3j, a sub-stoichiometric subunit of eIF3. PRINCIPAL FINDING: We have analyzed the high-resolution crystal structure of the eIF3b RRM domain from yeast. It exhibits the same fold as its human ortholog, with similar charge distribution on the surface interacting with the eIF3j in human. Thermodynamic analysis of the interaction between yeast eIF3b-RRM and eIF3j revealed the same range of enthalpy change and dissociation constant as for the human proteins, providing another line of evidence for the same mode of interaction between eIF3b and eIF3j in both organisms. However, analysis of the surface charge distribution of the putative RNA-binding β-sheet suggested that in contrast to its human ortholog, it potentially could bind oligonucleotides. Three-dimensional positioning of the so called "RNP1" motif in this domain is similar to other canonical RRMs, suggesting that this domain might indeed be a canonical RRM, conferring oligonucleotide binding capability to eIF3 in yeast. Interaction studies with yeast total RNA extract confirmed the proposed RNA binding activity of yeast eIF3b-RRM. CONCLUSION: We showed that yeast eIF3b-RRM interacts with eIF3j in a manner similar to its human ortholog. However, it shows similarities in the oligonucleotide binding surface to canonical RRMs and interacts with yeast total RNA. The proposed RNA binding activity of eIF3b-RRM may help eIF3 to either bind to the ribosome or recruit the mRNA to the 43S pre-initiation complex

Osmotin-loaded magnetic nanoparticles with electromagnetic guidance for the treatment of Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain.</p

Inhibition of Endothelin-1-Mediated Contraction of Hepatic Stellate Cells by FXR Ligand

Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen and the enhanced contractile response to vasoactive mediators such as endothelin-1 (ET-1). The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidneys, adrenals, and intestine. FXR is also expressed in HSCs and activation of FXR in HSCs is associated with significant decreases in collagen production. However, little is known about the roles of FXR in the regulation of contraction of HSCs. We report in this study that treatment of quiescent HSCs with GW4064, a synthetic FXR agonist, significantly inhibited the HSC transdifferentiation, which was associated with an inhibition of the upregulation of ET-1 expression. These GW4064-treated cells also showed reduced contractile response to ET-1 in comparison to HSCs without GW4064 treatment. We have further shown that GW4064 treatment inhibited the ET-1-mediated contraction in fully activated HSCs. To elucidate the potential mechanism we showed that GW4064 inhibited ET-1-mediated activation of Rho/ROCK pathway in activated HSCs. Our studies unveiled a new mechanism that might contribute to the anti-cirrhotic effects of FXR ligands