Evidence of Association of CYP1A1 Expression in Blood Lymphocytes and Clinicopathological Variables in Oral Cancer.

Association of smokeless tobacco (SLT) with oral cancer is well documented. The nitrosamines of SLT are metabolically bioactivated by CYP1A1. Therefore, in this pilot study, we investigated association of CYP1A1 expression with polymorphism, clinicopathological variables and outcome in exclusive SLT chewers. Semiquantitative RT-PCR analysis on RNA isolated from peripheral blood lymphocytes of 65 histopathologically confirmed cases revealed increased CYP1A1 mRNA expression in Msp I (CYP1A1*2A) and Ile/Val (CYP1A1*2C) polymorphic variants. A higher trend of CYP1A1 mRNA levels in invasive and recurrent tumors which also associated with shorter disease free and overall survival was seen. Odds ratio analysis indicated the association of higher CYP1A1 mRNA levels with disease aggressiveness i.e. metastasis and invasion. Study revealed wider oncogenic role of CYP1A1 in oral cancer patients and justifies further studies and analysis in a large cohort.

Testing the photon-number statistics of a quantum key distribution light source.

A commonly held tenet is that lasers well above threshold emit photons in a coherent state, which follow Poissonian statistics when measured in photon number. This feature is often exploited to build quantum-based random number generators or to derive the secure key rate of quantum key distribution systems. Hence the photon number distribution of the light source can directly impact the randomness and the security distilled from such devices. Here, we propose a method based on measuring correlation functions to experimentally characterize a light source's photon statistics and use it in the estimation of a quantum key distribution system's key rate. This promises to be a useful tool for the certification of quantum-related technologies.

Hyperglycaemia-related complications at the time of diagnosis can cause permanent neurological disability in children with neonatal diabetes.

BACKGROUND: Children with neonatal diabetes often present with diabetic ketoacidosis and hence are at risk of cerebral oedema and subsequent long-term neurological deficits. These complications are difficult to identify because neurological features can also occur as a result of the specific genetic aetiology causing neonatal diabetes. CASE REPORTS: We report two cases of neonatal diabetes where ketoacidosis-related cerebral oedema was the major cause of their permanent neurological disability. Case 1 (male, 18 years, compound heterozygous ABCC8 mutation) and case 2 (female, 29 years, heterozygous KCNJ11 mutation) presented with severe diabetic ketoacidosis at 6 and 16 weeks of age. Both had reduced consciousness, seizures and required intensive care for cerebral oedema. They subsequently developed spastic tetraplegia. Neurological examination in adulthood confirmed spastic tetraplegia and severe disability. Case 1 is wheelchair-bound and needs assistance for transfers, washing and dressing, whereas case 2 requires institutional care for all activities of daily living. Both cases have first-degree relatives with the same mutation with diabetes, who did not have ketoacidosis at diagnosis and do not have neurological disability. DISCUSSION: Ketoacidosis-related cerebral oedema at diagnosis in neonatal diabetes can cause long-term severe neurological disability. This will give additional neurological features to those directly caused by the genetic aetiology of the neonatal diabetes. Our cases highlight the need for increased awareness of neonatal diabetes and earlier and better initial treatment of the severe hyperglycaemia and ketoacidosis often seen at diagnosis of these children.

Floc Formation Reduces the pH Stress Experienced by Microorganisms Living in Alkaline Environments.

The survival of microorganisms within a cementitious geological disposal facility for radioactive wastes heavily depends on their ability to survive the calcium-dominated, hyperalkaline conditions resulting from the dissolution of the cementitious materials. The results from this study show that the formation of flocs, composed of a complex mixture of extracellular polymeric substances (EPS), provides protection against alkaline pH values up to 13.0. The flocs were dominated by Alishewanella and Dietzia spp., producing a mannose-rich carbohydrate fraction incorporating extracellular DNA, resulting in Ca2+ sequestration. EPS provided a ∼10-µm thick layer around the cells within the center of the flocs, which were capable of growth at pH values of 11.0 and 11.5, maintaining internal pH values of 10.4 and 10.7, respectively. Microorganisms survived at a pH of 12.0, where an internal floc pH of 11.6 was observed, as was a reduced associated biomass. We observed limited floc survival (<2 weeks) at a pH of 13.0. This study demonstrates that flocs maintain lower internal pHs in response to the hyperalkaline conditions expected to occur within a cementitious geological disposal facility for radioactive wastes and indicates that floc communities within such a facility can survive at pHs up to 12.0.IMPORTANCE The role of extracellular polymeric substances (EPS) in the survival of microorganisms in hyperalkaline conditions is poorly understood. Here, we present the taxonomy, morphology, and chemical characteristics of an EPS-based microbial floc, formed by a consortium isolated from an anthropogenic hyperalkaline site. Short-term (<2 weeks) survival of the flocs at a pH of 13 was observed, with indefinite survival observed at a pH of 12.0. Measurements from micro-pH electrodes (10-µm-diameter tip) demonstrated that flocs maintain lower internal pHs in response to hyperalkaline conditions (pH 11.0, 11.5, and 12.0), demonstrating that floc formation and EPS production are survival strategies under hyperalkaline conditions. The results indicate how microbial communities may survive and propagate within the hyperalkaline environment that is expected to prevail in a cementitious geological disposal facility for radioactive wastes; the results are also relevant to the wider extremophile community.

Type 1 Diabetes Genetic Risk Score: A Novel Tool to Discriminate Monogenic and Type 1 Diabetes.

Distinguishing patients with monogenic diabetes from those with type 1 diabetes (T1D) is important for correct diagnosis, treatment, and selection of patients for gene discovery studies. We assessed whether a T1D genetic risk score (T1D-GRS) generated from T1D-associated common genetic variants provides a novel way to discriminate monogenic diabetes from T1D. The T1D-GRS was highly discriminative of proven maturity-onset diabetes of young (MODY) (n = 805) and T1D (n = 1,963) (receiver operating characteristic area under the curve 0.87). A T1D-GRS of >0.280 (>50th T1D centile) was indicative of T1D (94% specificity, 50% sensitivity). We then analyzed the T1D-GRS of 242 white European patients with neonatal diabetes (NDM) who had been tested for all known NDM genes. Monogenic NDM was confirmed in 90, 59, and 8% of patients with GRS <5th T1D centile, 50-75th T1D centile, and >75th T1D centile, respectively. Applying a GRS 50th T1D centile cutoff in 48 NDM patients with no known genetic cause identified those most likely to have a novel monogenic etiology by highlighting patients with probable early-onset T1D (GRS >50th T1D centile) who were diagnosed later and had less syndromic presentation but additional autoimmune features compared with those with proven monogenic NDM. The T1D-GRS is a novel tool to improve the use of biomarkers in the discrimination of monogenic diabetes from T1D.

Efficient decoy-state quantum key distribution with quantified security.

We analyse the finite-size security of the efficient Bennett-Brassard 1984 protocol implemented with decoy states and apply the results to a gigahertz-clocked quantum key distribution system. Despite the enhanced security level, the obtained secure key rates are the highest reported so far at all fibre distances.

TCL1 shows a regulated expression pattern in chronic lymphocytic leukemia that correlates with molecular subtypes and proliferative state.

Expression of the human oncogene TCL1 in transgenic mice produces B-cell tumors that resemble chronic lymphocytic leukemia (CLL) suggesting its role in B-cell tumorigenesis. To clarify the expression pattern and regulation of TCL1 in CLL, we assessed 213 primary tumors by immunohistochemistry (IHC), flow-cytometry and/or Western blot, using a new monoclonal antibody. TCL1 protein was detectable in the majority of CLL (90% by IHC) but showed marked variations across cases with virtual absence in approximately 10% of tumors. Higher TCL1 levels correlated with markers of the 'pre-germinal center' CLL subtype including unmutated VH status (P=0.005), ZAP70 expression (P=0.007), and presence of chromosome 11q22-23 deletions (P=0.04). Intratumoral heterogeneity in TCL1 levels was also prominent and explained in part by markedly lower TCL1 expression in proliferating tumor cells. In vitro exposure of CLL cells to interleukin-4 (but not other growth factors) produced progressive and irreversible decrease in TCL1 protein levels in association with the onset of proliferation. TCL1 expression patterns in CLL are complex and highly dynamic and appear to reflect both the histogenetic subtypes of the disease and the growth parameters of individual tumors. The observed regulation pattern suggests that TCL1 may exert its effects predominantly in the unmutated/ZAP70-positive tumor subset.

Increased sural nerve epineurial blood flow in human subjects with painful diabetic neuropathy.

AIMS/HYPOTHESIS: The pathogenesis of painful diabetic neuropathy remains unknown. As a consequence we still do not have any effective, rational treatments and a greater understanding of the mechanisms is urgently required. Previous studies have shown no consistent morphological differences in the nerves of patients with and without painful neuropathy. The aim of this study was to compare epineurial haemodynamics in patients with chronic painful and painless neuropathy. METHODS: The techniques of microlightguide spectrophotometry and fluorescein angiography were used to measure epineurial intravascular oxygen saturation and blood flow respectively. Eleven patients with painful and eight with painless neuropathy were studied, with the groups matched carefully in terms of severity of neuropathy and diabetes control. RESULTS: Intravascular oxygen saturation was higher in the painful neuropathy group compared to those without pain (median 73.8% vs 67.7%, respectively; p=0.021). Fluorescein rise time was also faster in those with painful symptoms (median 18.3 s vs 53.6 s; p=0.046) indicating higher epineurial blood flow in these subjects. CONCLUSION/INTERPRETATION: These results indicate that there are distinct differences in haemodynamics within the epineurium of the sural nerve in subjects with painful and painless neuropathy. Haemodynamic factors could therefore have an important role in the pathogenesis of neuropathic pain and might offer further insight into potential treatments for this distressing condition.

Prediction of prognosis in patients with uveal melanoma using fluorescence in situ hybridisation.

BACKGROUND/AIMS: Uveal melanoma is the commonest malignancy of the eye, with a high proportion of patients dying of metastatic disease. Tumours showing a loss of chromosome 3 and gains of chromosome 8 are associated with a worse prognosis. The efficiency of fluorescence in situ hybridisation (FISH) in determining copy numbers of these chromosomes was assessed in individual tumours and related to patient survival. METHODS: 33 fresh frozen samples were analysed with centromeric probes for chromosomes 3 and 8. Patient outcomes were divided into two groups: (1) absence of genetic abnormalities (no genetic imbalance) and (2) presence of genetic abnormalities (genetic imbalance). The log rank test was used to compare survival, which was represented by Kaplan-Meier survival curves. RESULTS: Of the 33 tumours analysed, 16 showed evidence of genetic imbalances. Of these 16 tumours, 14 patients had died by the end of the study, with 10 having died of liver metastases. Of the tumours without evidence of genetic imbalances, five patients had died by the end of the study, although none had died as a result of either liver metastases or from the primary uveal melanoma. The difference in survival between the two groups was highly significant (p<0.0001). CONCLUSION: The authors have shown that FISH analysis for chromosome 3 and 8 is a reliable and efficient technique in the analysis of fresh frozen tumour specimens and is valuable in the prediction of prognosis in individuals with uveal melanomas.

Impact of moods and social context on eating behavior.

The relationship of moods and social context to energy and nutrient intakes was examined to ascertain if these variables interact or function independently. The subjects were 78 predominantly white, obese women participating in weight-loss studies. Mean age was 36.7 (SD=7.6) and mean Body Mass Index was 32.1 (SD=3.6). Subjects completed 2-week baseline food diaries recording everything they ate, including moods and people present during the meals. Meals eaten in positive and negative moods were significantly larger than meals eaten in a neutral mood. Meals eaten with other people were significantly larger than meals eaten alone. There were no significant moods by social context interactions for total energy intake. Moods and social context functioned additively to increase the risk of over-eating. Macro nutrient analysis revealed only a main effect for social context. Percentage of calories from fat and protein were greater, whereas the percentage of carbohydrate was less in social context meals compared to meals eaten alone. Clinicians should conduct a functional analysis to assess exposure to the frequency and types of risky situations. Teaching people to cope more effectively with social situations and moods may increase the efficacy of weight loss and maintenance programs.

Preoperative localization of a parathyroid adenoma with Tc-99m sestamibi imaging in a patient with concomitant nontoxic multinodular goiter.

Preoperative localization of parathyroid adenomas is useful in patients undergoing parathyroidectomy. The authors report a patient with hyperparathyroidism and an associated nontoxic nodular goiter. Technetium-99m sestamibi scintigraphy localized and differentiated the parathyroid adenoma from the multinodular goiter. Excellent correlation was found between preoperative radionuclide imaging and surgical pathology. Technetium-99m sestamibi parathyroid imaging may be a simple and helpful test in the surgical management of parathyroid adenomas, particularly in patients with nontoxic multinodular goiter.

Caprolactam waste liquor degradation by various yeasts.

Waste liquor from caprolactam manufacture contains many mono- and di-carboxylic acids. Of four yeasts tested, Yarrowia lipolytica DS-1 was the best at decreasing Chemical Oxygen Demand values, by up to 60% with 50 and 100 g waste liquor/after 48 h. Caproic, butyric and valeric acids were utilized most easily. Adipic acid was not decreased below 13% (w/v).

The hot clot sign. A new finding in deep venous thrombosis on bone scintigraphy.

Focal Tc-99m MDP uptake on bone scanning in regions of deep venous thrombosis (DVT) is reported in two patients with documented DVT. It is speculated that this uptake may be related to localized calcification or ossification, which is occasionally observed on radiographs of patients with chronic DVT.

Purification and properties of the inhibitory protein isolated from Lactobacillus acidophilus AC1.

Lactobacillus acidophilus AC1 was found to produce a proteinic inhibitor having a molecular weight of 5.4 kd, active against both Gram-positive and Gram-negative bacteria. Some of the sensitive bacteria were found to be resistant to most of the commonly employed drugs and antibiotics. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of the purified inhibitor showed the presence of a single polypeptide. The inhibitor was active over a wide pH range from 4.0 to 7.5. It was heat sensitive, and complete inactivation occurred within 20 min at 50 degrees C. The purified inhibitor lost 50% of its activity within 24 h at room temperature and after 5 days at 4 degrees-8 degrees C. The inhibitory protein was readily distinguished from other inhibitors in lactic cultures by its immunological cross-reactivity.

Prodigiosin, a component of kappa phage receptor complex in Serratia marcescens.

Studies on kappa phage inactivation with isolated pigments from Serratia marcescens were carried out. Kappa phage is sensitive to inactivation with diethyl ether, petroleum ether, acetone and methanol, but is quite stable in chloroform and dimethyl sulphoxide. The pigment extract dissolved in chloroform inactivates about 50% of the total suspended phages. The pigment dissolved in acetone and dimethyl sulphoxide inactivates about 96.50% and 64.10% of the phages, respectively. High inactivation values with acetone were partially due to direct inactivation rather than the pigment itself.