Iso-conversional study of crystallization activation energy of amorphous-crystallization transformation for Se79Te20Pb1 glass using non-isothermal differential scanning calorimetry technique

The ternary Se79Te20Pb1 chalcogenide glass is prepared using melt quenching technique. Differential scanning calorimetry technique (DSC) is used to investigate the kinetics of crystallization of amorphous-crystallization (a-c) phase transformation under non-isothermal conditions at three different heating rates; 5, 10 and 15° C min-1. The variation of crystallized activation energy (Ec) with crystallized fraction (ϰ) and hence, with temperature (T) is investigated using five iso-conversional methods namely KAS, OFW, Friedman, Tang and Chen and Starink. It is found that Ec is not constant but vary with ϰ as well as T. Thus, the iso-conversional analysis of investigated glass indicates that the assumption of constant Ec is not appropriat

How safe are clinical systems?

Th is study was commissioned by the Health Foundation to examine the extent, type and causes of failures in reliability in different healthcare systems: failures which have the potential to create risk or cause patient harm

Molecular Changes in Pre-Metastatic Lymph Nodes of Esophageal Cancer Patients

Lymph node metastasis indicates poor prognosis in esophageal cancer. To understand the underlying mechanisms, most studies so far focused on investigating the tumors themselves and/or invaded lymph nodes. However they neglected the potential events within the metastatic niche, which precede invasion. Here we report the first description of these regulations in patients on transcription level. We determined transcriptomic profiles of still metastasis-free regional lymph nodes for two patient groups: patients classified as pN1 (n = 9, metastatic nodes exist) or pN0 (n = 5, no metastatic nodes exist). All investigated lymph nodes, also those from pN1 patients, were still metastasis-free. The results show that regional lymph nodes of pN1 patients differ decisively from those of pN0 patients--even before metastasis has taken place. In the pN0 group distinct immune response patterns were observed. In contrast, lymph nodes of the pN1 group exhibited a clear profile of reduced immune response and reduced proliferation, but increased apoptosis, enhanced hypoplasia and morphological conversion processes. DKK1 was the most significant gene associated with the molecular mechanisms taking place in lymph nodes of patients suffering from metastasis (pN1). We assume that the two molecular profiles observed constitute different stages of a progressive disease. Finally we suggest that DKK1 might play an important role within the mechanisms leading to lymph node metastasis

Rescue bedside laparotomy in the intensive care unit in patients too unstable for transport to the operating room

INTRODUCTION: The prognoses of critically ill patients with a requirement for emergency laparotomy and severe respiratory and/or hemodynamic instability precluding transport to the operating room (OR) are often fatal without surgery. Attempting emergency surgery at the bedside might equally result in an adverse outcome. However, risk factors and predictors that could support clinical decision making have not been identified so far. This study describes the clinical characteristics, indicative pathophysiology and outcomes in patients undergoing resuscitative laparotomy in the intensive care unit (ICU). METHODS: This was a retrospective observational study of all critically ill adult patients undergoing resuscitative laparotomy in the ICUs of a German university hospital from January 2005 to July 2013. Clinical characteristics, risk factors, and treatments were compared between survivors and non-survivors. The primary endpoint was 28-day survival. RESULTS: A total of 41 patients with a median age of 64 (21 to 83) were included. The most frequent reasons for ICU admission were sepsis, pneumonia, and pancreatic surgery. All patients were mechanically ventilated, receiving vasopressors, and were in multiple organ failure. Twenty-nine patients (70.7%) were on renal replacement therapy and two patients (4.9%) on extracorporeal membrane oxygenation. The main reasons for surgery were suspected intra-abdominal bleeding (39.0%), suspected intestinal ischemia (24.4%) or abdominal compartment syndrome (24.4%). Twenty-eight-day, ICU and hospital mortalities were 75.6%, 80.5%, and 82.9%, respectively. In six out of ten patients (60%) who survived surgery for more than 28 days, bedside laparotomy was rated as a life-saving procedure by an interdisciplinary group of the investigators. CONCLUSIONS: These findings suggest that in selected critically ill patients with a vital indication for emergency laparotomy and severe cardiopulmonary instability precluding transport to the OR, a bedside resuscitative laparotomy in the ICU can be considered as a rescue procedure, even though very high mortality is to be expected

The role of CDC48 in the retro-translocation of non-ubiquitinated toxin substrates in plant cells

When the catalytic A subunits of the castor bean toxins ricin and Ricinus communis agglutinin (denoted as RTA and RCA A, respectively) are delivered into the endoplasmic reticulum (ER) of tobacco protoplasts, they become substrates for ER-associated protein degradation (ERAD). As such, these orphan polypeptides are retro-translocated to the cytosol, where a significant proportion of each protein is degraded by proteasomes. Here we begin to characterise the ERAD pathway in plant cells, showing that retro-translocation of these lysine-deficient glycoproteins requires the ATPase activity of cytosolic CDC48. Lysine polyubiquitination is not obligatory for this step. We also show that while RCA A is found in a mannose-untrimmed form prior to its retro-translocation, a significant proportion of newly synthesised RTA cycles via the Golgi and becomes modified by downstream glycosylation enzymes. Despite these differences, both proteins are similarly retro-translocated

A living cell quartz crystal microbalance biosensor for continuous monitoring of cytotoxic responses of macrophages to single-walled carbon nanotubes

<p>Abstract</p> <p>Background</p> <p>Numerous engineered nanomaterials (ENMs) exist and new ENMs are being developed. A challenge to nanotoxicology and environmental health and safety is evaluating toxicity of ENMs before they become widely utilized. Cellular assays remain the predominant test platform yet these methods are limited by using discrete time endpoints and reliance on organic dyes, vulnerable to interference from ENMs. Label-free, continuous, rapid response systems with biologically meaningful endpoints are needed. We have developed a device to detect and monitor in real time responses of living cells to ENMs. The device, a living cell quartz crystal microbalance biosensor (QCMB), uses macrophages adherent to a quartz crystal. The communal response of macrophages to treatments is monitored continuously as changes in crystal oscillation frequency (Δf). We report the ability of this QCMB to distinguish benign from toxic exposures and reveal unique kinetic information about cellular responses to varying doses of single-walled carbon nanotubes (SWCNTs).</p> <p>Results</p> <p>We analyzed macrophage responses to additions of Zymosan A, polystyrene beads (PBs) (benign substances) or SWCNT (3-150 μg/ml) in the QCMB over 18 hrs. In parallel, toxicity was monitored over 24/48 hrs using conventional viability assays and histological stains to detect apoptosis. In the QCMB, a stable unchanging oscillation frequency occurred when cells alone, Zymosan A alone, PBs alone or SWCNTs without cells at the highest dose alone were used. With living cells in the QCMB, when Zymosan A, PBs or SWCNTs were added, a significant decrease in frequency occurred from 1-6 hrs. For SWCNTs, this Δf was dose-dependent. From 6-18 hrs, benign substances or low dose SWCNT (3-30 μg/ml) treatments showed a reversal of the decrease of oscillation frequency, returning to or exceeding pre-treatment levels. Cell recovery was confirmed in conventional assays. The lag time to see the Δf reversal in QCMB plots was linearly SWCNT-dose dependent. Lastly, the frequency never reversed at high dose SWCNT (100-150 μg/ml), and apoptosis/necrosis was documented in conventional 24 and 48 hr-assays.</p> <p>Conclusion</p> <p>These data suggest that the new QCMB detects and provides unique information about peak, sub-lethal and toxic exposures of living cells to ENMs before they are detected using conventional cell assays.</p

EPHA2 Polymorphisms and Age-Related Cataract in India

Objective: We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India. Methods: We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear >= 4, cortical >= 3, posterior sub-capsular (PSC) >= 2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location. Results: 7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p > 0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract. Conclusions: Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians

Adoption of resource conservation technologies in indo-gangetic plains of India: scouting for profitability and efficiency

This study has evaluated the superiority of resource conservation technologies (RCTs) over conventional methods of cultivation and has identified the factors influencing adoption of these technologies. It has provided succinct evidences from four states — Bihar, Haryana, Punjab and Uttar Pradesh — by comparing the adopters and non-adopters of RCTs in the rice-wheat cropping system of the Indo-Gangetic Plains of India. The study has highlighted superiority of RCTs over the conventional practices in terms of cost saving and efficient inputs-use. However, there is a need to internalize the RCTs in their totality by applying plans and strategies based on local dynamics. The study has suggested the need of policy formulations for dissemination and wider adoption of these technologie

The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders