Unusual presentation of metastatic adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>The most common tumours of the adrenal gland are adenoma, pheochromocytoma, adrenocortical carcinoma, and metastases. Although the imaging features of these tumours are established, the imaging characteristics of uncommon adrenal masses are less well known. In patients with extradrenal tumour, incidental discovery of an adrenal mass necessitates excluding the possibility of metastatic malignancy.</p> <p>Case presentation</p> <p>A 52 year-old female was diagnosed with oesophageal adenocarcinoma and treated with oesophagectomy and adjuvant chemotherapy. Sixteen months later on staging CT scan a 2 × 2 cm adrenal mass was detected, which increased in size over a period of time to 3 × 3 cm in size. Adrenalectomy was performed and histological examination revealed metastatic adenocarcinoma within an adrenal adenoma.</p> <p>Conclusion</p> <p>The present case highlights the unusual behaviour of an oesophageal adenocarcinoma causing metastasis to an adrenocortical adenoma.</p

Schistosomiasis and Urinary Bladder Cancer in North Western Tanzania: A Retrospective Review of 185 Patients.

Worldwide, cancers of the urinary bladder are well known to be associated with environmental chemical carcinogens such as smoking and occupational exposure to polycyclic aromatic hydrocarbons. These cancers are typically transitional cell carcinoma (urothelial carcinoma). In areas where schistosomiasis is endemic there is a high incidence of squamous cell carcinoma of the urinary bladder. Schistosomiasis causes chronic granulomatous cystitis leading to squamous metaplasia of transitional epithelium, and subsequently development of squamous cell carcinoma. The western part of Tanzania on the shores of Lake Victoria is such an endemic area. This study was done to document the burden of urinary bladder cancer associated with schistosomiasis in this region. This was a descriptive retrospective study of histologically confirmed cases of urinary bladder cancer seen at the Department of Pathology Bugando Medical Centre (BMC) over a period of 10 years. Data were retrieved from the records of the Departments of Pathology, Medical Records and Surgery. Data were analyzed by the use of contingency tables. A total of 185 patients were diagnosed with cancer of the urinary bladder during the study period, where as 90 (48.6%) were males and 95 (51.4) were females. The mean age at diagnosis was 54.3 years. Squamous cell carcinoma was the most frequent histological type (55.1%), followed by conventional transitional cell carcinoma (40.5%). Eighty three of all cancer cases (44.9%) were found to have schistosomal eggs. Schistosomiasis was commonly associated with squamous cancers compared to non squamous cancers. Most of the cancers associated with schistosomiasis had invaded the muscularis propria of the urinary bladder at the time of diagnosis (p<0.001) and such cancers were frequent below 50 years of age with a significant statistical difference (p<0.001). Poorly differentiated tumors were more frequent in females than males with a significant statistical difference (p=0.006). The majority of urinary bladder cancers seen in the Lake Region were squamous cell carcinoma associated with schistosomiasis. These cancers showed an aggressive behavior and were commonly seen in the younger age groups. Effective control of schistosomiasis in this region should significantly reduce the burden of urinary bladder cancer

The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers

Introduction: We examined if a combination of proliferation markers and estrogen receptor (ER) activity could predict early versus late relapses in ER-positive breast cancer and inform the choice and length of adjuvant endocrine therapy. Methods: Baseline affymetrix gene-expression profiles from ER-positive patients who received no systemic therapy (n = 559), adjuvant tamoxifen for 5 years (cohort-1: n = 683, cohort-2: n = 282) and from 58 patients treated with neoadjuvant letrozole for 3 months (gene-expression available at baseline, 14 and 90 days) were analyzed. A proliferation score based on the expression of mitotic kinases (MKS) and an ER-related score (ERS) adopted from Oncotype DX® were calculated. The same analysis was performed using the Genomic Grade Index as proliferation marker and the luminal gene score from the PAM50 classifier as measure of estrogen-related genes. Median values were used to define low and high marker groups and four combinations were created. Relapses were grouped into time cohorts of 0-2.5, 0-5, 5-10 years. Results: In the overall 10 years period, the proportional hazards assumption was violated for several biomarker groups indicating time-dependent effects. In tamoxifen-treated patients Low-MKS/Low-ERS cancers had continuously increasing risk of relapse that was higher after 5 years than Low-MKS/High-ERS cancers [0 to 10 year, HR 3.36; p = 0.013]. High-MKS/High-ERS cancers had low risk of early relapse [0-2.5 years HR 0.13; p = 0.0006], but high risk of late relapse which was higher than in the High-MKS/Low-ERS group [after 5 years HR 3.86; p = 0.007]. The High-MKS/Low-ERS subset had most of the early relapses [0 to 2.5 years, HR 6.53; p < 0.0001] especially in node negative tumors and showed minimal response to neoadjuvant letrozole. These findings were qualitatively confirmed in a smaller independent cohort of tamoxifen-treated patients. Using different biomarkers provided similar results. Conclusions: Early relapses are highest in highly proliferative/low-ERS cancers, in particular in node negative tumors. Relapses occurring after 5 years of adjuvant tamoxifen are highest among the highly-proliferative/high-ERS tumors although their risk of recurrence is modest in the first 5 years on tamoxifen. These tumors could be the best candidates for extended endocrine therapy

Performance Comparisons of Jet and Mesh Nebulizers Using Different Interfaces in Simulated Spontaneously Breathing Adults and Children

Background: Different types of nebulizers and interfaces are used for the treatment of adults and children with pulmonary diseases. The purpose of this study was to determine the efficiency of a mesh nebulizer (MN) with a proprietary adapter and a jet nebulizer (JN) under different configurations in adult and pediatric models of spontaneous breathing. We hypothesize that delivery efficiency of JN and MN will differ depending on the interface used during aerosol therapy in simulated spontaneously breathing adult and pediatric models. While we expect that aerosol delivery with JN will be less efficient than MN, we also hypothesize that lung deposition obtained with the adult lung model will be more than that with the pediatric lung model in all conditions tested in this study. Methods: A lung model using a teaching manikin connected to a sinusoidal pump via a collecting filter at the level of the bronchi simulating a spontaneously breathing adult (Vt 500 mL, RR 15 bpm, I:E ratio 1:2) or pediatric patient (Vt 150 mL, RR 25 bpm, I:E ratio 1:2). Albuterol sulfate (2.5 mg/3 mL) was aerosolized with JN (Mistymax 10, Airlife) or MN (Aerogen Solo®, Aerogen) with the Adapter (Aerogen Solo® Adapter, Aerogen Ltd, Galway, Ireland) using mouthpiece, aerosol mask, and valved-mask in adults and the dragon mask, aerosol mask, and valved-mask in pediatrics (n=3). The Adapter, specifically designed for MN, was attached to all the interfaces used in this study with supplemental oxygen of 2 lpm, and in addition, the MP was tested with no additional flow in the adult model. The JN was driven with 10 lpm based on the manufacturer\u27s label. Drug was eluted from the filter and analyzed via spectrophotometry. Descriptive statistics, dependent t-test and one-way analysis of variance were used for data analysis. Significant level was set at 0.05. Results: In adults, delivery efficiency of JN with the valved mask was significantly greater than that with the aerosol mask (p=0.01). Aerosol delivery of JN with the mouthpiece was not statistically significant from the valved mask (p=0.123) and the aerosol mask (p=0.193). Drug delivery with MN with mouthpiece (15.42±1.4%) and valved-mask (15.15±1.1%) was greater than the open aerosol mask (7.54±0.39%; p=0.0001) in the adult lung model. With no flow mouthpiece delivery increased\u3e2 fold (34.9±3.1%; p=.0001) compared to use of 2 lpm of flow. Using the JN with the pediatric model deposition with valved-mask (5.3±0.8%), dragon mask (4.7±0.9%), and aerosol mask (4.1±0.3%) were similar (p\u3e0.05); while drug delivery with MN via valved-mask (11.1±0.7%) was greater than the dragon mask (6.44±0.3%; p=0.002) and aerosol mask (4.6±0.4%; p=0.002), and the dragon mask was more efficient than the open aerosol mask (p=0.009) Conclusion: The type of nebulizer and interface used for aerosol therapy affects delivery efficiency in these simulated spontaneously breathing adult and pediatric models. Drug delivery was greatest with the valved-mouthpiece and mask with JN and MN, while the standard aerosol mask was least efficient in these simulated spontaneously breathing adult and pediatric lung models. Delivery efficiency of JN was less than MN in all conditions tested in this study except in the aerosol mask. Lung deposition obtained with the adult lung model was more than that with the pediatric lung model

The Dynamical Mechanism of Auto-Inhibition of AMP-Activated Protein Kinase

We use a novel normal mode analysis of an elastic network model drawn from configurations generated during microsecond all-atom molecular dynamics simulations to analyze the mechanism of auto-inhibition of AMP-activated protein kinase (AMPK). A recent X-ray and mutagenesis experiment (Chen, et al Nature 2009, 459, 1146) of the AMPK homolog S. Pombe sucrose non-fermenting 1 (SNF1) has proposed a new conformational switch model involving the movement of the kinase domain (KD) between an inactive unphosphorylated open state and an active or semi-active phosphorylated closed state, mediated by the autoinhibitory domain (AID), and a similar mutagenesis study showed that rat AMPK has the same auto-inhibition mechanism. However, there is no direct dynamical evidence to support this model and it is not clear whether other functionally important local structural components are equally inhibited. By using the same SNF1 KD-AID fragment as that used in experiment, we show that AID inhibits the catalytic function by restraining the KD into an unproductive open conformation, thereby limiting local structural rearrangements, while mutations that disrupt the interactions between the KD and AID allow for both the local structural rearrangement and global interlobe conformational transition. Our calculations further show that the AID also greatly impacts the structuring and mobility of the activation loop

Estimating prognosis and palliation based on tumour marker CA 19-9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy

To investigate the prognostic value of quality of life (QOL) relative to tumour marker carbohydrate antigen (CA) 19-9, and the role of CA 19-9 in estimating palliation in patients with advanced pancreatic cancer receiving chemotherapy

Complete chloroplast genome sequence of Holoparasite Cistanche Deserticola (Orobanchaceae) reveals gene loss and horizontal gene transfer from Its host Haloxylon Ammodendron (Chenopodiaceae)

The central function of chloroplasts is to carry out photosynthesis, and its gene content and structure are highly conserved across land plants. Parasitic plants, which have reduced photosynthetic ability, suffer gene losses from the chloroplast (cp) genome accompanied by the relaxation of selective constraints. Compared with the rapid rise in the number of cp genome sequences of photosynthetic organisms, there are limited data sets from parasitic plants. The authors report the complete sequence of the cp genome of Cistanche deserticola, a holoparasitic desert species belonging to the family Orobanchaceae

Weapons Make the Man (Larger): Formidability Is Represented as Size and Strength in Humans

In order to determine how to act in situations of potential agonistic conflict, individuals must assess multiple features of a prospective foe that contribute to the foe's resource-holding potential, or formidability. Across diverse species, physical size and strength are key determinants of formidability, and the same is often true for humans. However, in many species, formidability is also influenced by other factors, such as sex, coalitional size, and, in humans, access to weaponry. Decision-making involving assessments of multiple features is enhanced by the use of a single summary variable that encapsulates the contributions of these features. Given both a) the phylogenetic antiquity of the importance of size and strength as determinants of formidability, and b) redundant experiences during development that underscore the contributions of size and strength to formidability, we hypothesize that size and strength constitute the conceptual dimensions of a representation used to summarize multiple diverse determinants of a prospective foe's formidability. Here, we test this hypothesis in humans by examining the effects of a potential foe's access to weaponry on estimations of that individual's size and strength. We demonstrate that knowing that an individual possesses a gun or a large kitchen knife leads observers to conceptualize him as taller, and generally larger and more muscular, than individuals who possess only tools or similarly mundane objects. We also document that such patterns are not explicable in terms of any actual correlation between gun ownership and physical size, nor can they be explained in terms of cultural schemas or other background knowledge linking particular objects to individuals of particular size and strength. These findings pave the way for a fuller understanding of the evolution of the cognitive systems whereby humans – and likely many other social vertebrates – navigate social hierarchies

Test-retest variability of left ventricular 4D flow cardiovascular magnetic resonance measurements in healthy subjects

Background: Quantification and visualisation of left ventricular (LV) blood flow is afforded by three-dimensional, time resolved phase contrast cardiovascular magnetic resonance (CMR 4D flow). However, few data exist upon the repeatability and variability of these parameters in a healthy population. We aimed to assess the repeatability and variability over time of LV 4D CMR flow measurements. Methods: Forty five controls underwent CMR 4D flow data acquisition. Of these, 10 underwent a second scan within the same visit (scan-rescan), 25 returned for a second visit (interval scan; median interval 52 days, IQR 28–57 days). The LV-end diastolic volume (EDV) was divided into four flow components: 1) Direct flow: inflow that passes directly to ejection; 2) Retained inflow: inflow that enters and resides within the LV; 3) Delayed ejection flow: starts within the LV and is ejected and 4) Residual volume: blood that resides within the LV for > 2 cardiac cycles. Each flow components’ volume was related to the EDV (volume-ratio). The kinetic energy at end-diastole (ED) was measured and divided by the components’ volume. Results: The dominant flow component in all 45 controls was the direct flow (volume ratio 38 ± 4%) followed by the residual volume (30 ± 4%), then delayed ejection flow (16 ± 3%) and retained inflow (16 ± 4%). The kinetic energy at ED for each component was direct flow (7.8 ± 3.0 microJ/ml), retained inflow (4.1 ± 2.0 microJ/ml), delayed ejection flow (6.3 ± 2.3 microJ/ml) and the residual volume (1.2 ± 0.5 microJ/ml). The coefficients of variation for the scan-rescan ranged from 2.5%–9.2% for the flow components’ volume ratio and between 13.5%–17.7% for the kinetic energy. The interval scan results showed higher coefficients of variation with values from 6.2–16.1% for the flow components’ volume ratio and 16.9–29.0% for the kinetic energy of the flow components. Conclusion: LV flow components’ volume and their associated kinetic energy values are repeatable and stable within a population over time. However, the variability of these measurements in individuals over time is greater than can be attributed to sources of error in the data acquisition and analysis, suggesting that additional physiological factors may influence LV flow measurements