Antibody Conjugated, Raman Tagged Hollow Gold-Silver Nanospheres for Specific Targeting and Multimodal Dark-Field/SERS/Two Photon-FLIM Imaging of CD19(+) B Lymphoblasts.
In this Research Article, we propose a new class of contrast agents for the detection and multimodal imaging of CD19(+) cancer lymphoblasts. The agents are based on NIR responsive hollow gold-silver nanospheres conjugated with antiCD19 monoclonal antibodies and marked with Nile Blue (NB) SERS active molecules (HNS-NB-PEG-antiCD19). Proof of concept experiments on specificity of the complex for the investigated cells was achieved by transmission electron microscopy (TEM). The microspectroscopic investigations via dark field (DF), surface-enhanced Raman spectroscopy (SERS), and two-photon excited fluorescence lifetime imaging microscopy (TPE-FLIM) corroborate with TEM and demonstrate successful and preferential internalization of the antibody-nanocomplex. The combination of the microspectroscopic techniques enables contrast and sensitivity that competes with more invasive and time demanding cell imaging modalities, while depth sectioning images provide real time localization of the nanoparticles in the whole cytoplasm at the entire depth of the cells. Our findings prove that HNS-NB-PEG-antiCD19 represent a promising type of new contrast agents with great possibility of being detected by multiple, non invasive, rapid and accessible microspectroscopic techniques and real applicability for specific targeting of CD19(+) cancer cells. Such versatile nanocomplexes combine in one single platform the detection and imaging of cancer lymphoblasts by DF, SERS, and TPE-FLIM microspectroscopy.


Sawtooth waves during REM sleep after administration of haloperidol combined with total sleep deprivation in healthy young subjects.
We sought to examine the possible participation of dopaminergic receptors in the phasic events that occur during rapid eye movement (REM) sleep, known as sawtooth waves (STW). These phasic phenomena of REM sleep exhibit a unique morphology and, although they represent a characteristic feature of REM sleep, little is known about the mechanisms which generate them and which are apparently different from rapid eye movements. STW behavior was studied in 10 male volunteers aged 20 to 35 years, who were submitted to polysomnographic monitoring (PSG). On the adaptation night they were submitted to the first PSG and on the second night, to the basal PSG. On the third night the volunteers received placebo or haloperidol and spent the whole night awake. On the fourth night they were submitted to the third PSG. After a 15-day rest period, the volunteers returned to the sleep laboratory and, according to a double-blind crossover randomized design, received haloperidol or placebo and spent the whole night awake, after which they were submitted to the fourth PSG. The volunteers who were given haloperidol combined with sleep deprivation exhibited an elevation of the duration and density of the STW, without significant alterations of the other REM sleep phasic phenomena such as rapid eye movement. These findings suggest that sawtooth waves must have their own generating mechanisms and that the dopaminergic receptors must exert a modulating role since REM sleep deprivation, as well as administration of neuroleptics, produces supersensitivity of dopaminergic receptors.


Association Studies of the GPR103 and BCL2L15 Genes in Autoimmune Thyroid Disease in the Japanese Population.
While the past genome-wide association study (GWAS) for autoimmune thyroid diseases (AITDs) was done in Caucasians, a recent GWAS in Caucasian patients with both AITD and type 1 diabetes [a variant of autoimmune polyglandular syndrome type 3 (APS3v)] identified five non-HLA genes: BCL2L15, MAGI3, PHTF1, PTPN22, and GPR103. The aim of our study was to replicate these associations with AITD in a Japanese population. Since analyzing the rs2476601 single-nucleotide polymorphism (SNP) within the PTPN22 gene revealed no polymorphism in the Japanese, we analyzed four SNPs, rs2358994 (in BCL2L15), rs2153977 (in MAGI3), rs1111695 (in PHTF1), and rs7679475 (in GPR103) genotypes in a case-control study based on 447 Japanese AITD patients [277 Graves' disease (GD) and 170 Hashimoto's thyroiditis (HT) patients] and 225 matched Japanese controls using the high-resolution melting and unlabeled probe methods. Case-control association studies were performed using the χ(2) and Fisher's exact tests with Yates correction. The G allele of rs7679475 (A/G) was associated with HT compared with controls [P = 0.022, odds ratio (OR) = 0.69]. GD showed no significant associations with any SNPs. However, when patients with GD were stratified according to Graves' ophthalmopathy (GO), the G allele of rs2358994 (A/G) was associated with GO vs. controls (P = 0.018, OR = 1.52). These findings suggest that in the Japanese population the GPR103 gene may contribute to the pathogenesis of HT. Moreover, this study demonstrated that the SNP rs2358994 within BCL2L15 gene is associated with GO in the Japanese population.


External time-varying fields and electron coherence.
The effect of time-varying electromagnetic fields on electron coherence is investigated. A sinusoidal electromagnetic field produces a time-varying Aharonov-Bohm phase. In a measurement of the interference pattern which averages over this phase, the effect is a loss of contrast. This is effectively a form of decoherence. We calculate the magnitude of this effect for various electromagnetic field configurations. The result seems to be sufficiently large to be observable.


Suppression of the contact hypersensitivity response following topical exposure to 2-butoxyethanol in female BALB/c mice.
The effects of route of exposure, time of exposure and metabolism of 2-butoxyethanol (BE) on the contact hypersensitivity response (CHR) were evaluated in female BALB/c mice. Mice were either orally exposed to 50, 150 or 400 mg BE/kg or topically exposed to 0.25, 1.0, 4.0 or 16.0 mg BE on the ear and the oxazolone (OXA)-induced CHR evaluated by measuring ear thickness before and after OXA challenge. While no modulation was observed following oral exposure to BE, topical exposure resulted in a significant decrease in the CHR. Application of 4.0 mg BE in 4:1 acetone and olive oil (AOO) vehicle at the time of sensitization, challenge or both, decreased the CHR by 18%, 18% and 22%, respectively. A time course study of the effects of topical exposure to 4.0 mg BE/ear during the challenge phase of the CHR revealed that BE must be applied at the time of OXA challenge to significantly reduce the ear swelling response. In order to determine if metabolism of topically applied BE was required for suppression of the CHR, butoxyacetic acid (BAA), the primary metabolite of BE, was applied to the ear immediately following OXA challenge. No topical dose of BAA (2.0,4.0 and 8.0 mg BAA/ear) administered in this study altered the CHR. Blocking the metabolism of BE by oral administration of 4-methylpyrazole (MP), further reduced OXA-induced ear swelling when compared to mice exposed to BE without MP treatment. Taken together, these studies indicated that suppression of the CHR in mice following topical exposure to this glycol ether was due to the activity of BE itself and was not dependent on metabolic activation of the compound. Further studies were undertaken to identify a potential mechanism of BE-induced reduction of the CHR. Epidermal cells from untreated BALB/c mice were isolated and exposed to BE in vitro (10(-12), 10(-10), 10(-8), 10(-6) and l0(-4) M BE). In vitro exposure to BE at these concentrations did not significantly affect expression of MHC class II surface protein or protein synthesis in epidermal Langerhans cells, failing to provide in vitro evidence that BE-associated suppression of the CHR is associated with a reduction in MHC class II expression.


Ultrasonographic examination for inversion ankle sprains associated with osseous injuries.
The study attempted to evaluate the value of ultrasonography in determining the therapeutic strategy for patients with osseous injuries caused by ankle sprains. A 10-MHz compact linear-array ultrasound transducer was used to assess patients with inversion ankle sprains. Eleven female and 12 male patients who had fractures detected by sonograms were included in the study. All 23 patients underwent radiographic examination for identification of fractures. Bone scintigraphy was performed for those who had negative x-ray findings. Eighteen patients had distal fibular tip fractures, three patients had the fifth metatarsal base fractures, one patient had a talar neck fracture, and one patient had a navicular fracture. These fractures were all detected by ultrasonography and then proved even by radiography or by bone scans. All the 23 patients had anterior talofibular ligament injuries. Among these patients, 11 had anterior ankle-joint recess effusion, and two had additional anterioinferior tibiofibular ligament injuries. Six weeks of immobilization with the ankle fracture brace was prescribed for all the patients after the identification of fractures. Their ankle pain symptoms soon improved. Ultrasonography is valuable in evaluating tiny foot and ankle fractures and coexistent soft tissue injuries. It can guide the treatment for patients with osseous injuries caused by ankle sprains.


Outbreak of Listeria Monocytogenes in Pheasants.
Listeria monocytogenes is capable of infecting almost all animals. However, outbreaks of listeriosis are infrequent in birds. This report describes an outbreak of listeriosis in a small pheasant (Phasianus colchicus) breeder farm with more than 2,000 pheasants from Hubei province of the People's Republic of China. The affected flock consisted of adult and young birds. Approximately 300 young birds and a few adult birds were found dead within a few days of the onset of clinical signs. Twenty-five dead birds were collected for further examination. Histopathological lesions in the visceral organs were characterized by monocyte infiltration and proliferation. Localized encephalitis and meningitis were detected in the brains of dead birds. Gram-positive organisms were observed in heart blood smear, liver, and brain impression smears. The organisms were isolated from fresh liver and were identified as L. monocytogenes serotype 4b based on multiplex polymerase chain reaction (PCR) and hlyA gene sequence analysis. This is the first report describing outbreak of listeriosis in pheasant flock.


Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism.
The mammalian gut is colonized by numerous microorganisms collectively termed the microbiota, which have a mutually beneficial relationship with their host. Normally, the gut microbiota matures during ontogeny to a state of balanced commensalism marked by the absence of adverse inflammation. Subsets of innate lymphoid cells (ILCs) and conventional T cells are considered to have redundant functions in containment and clearance of microbial pathogens, but how these two major lymphoid-cell populations each contribute to shaping the mature commensal microbiome and help to maintain tissue homeostasis has not been determined. Here we identify, using advanced multiplex quantitative imaging methods, an extensive and persistent phosphorylated-STAT3 signature in group 3 ILCs and intestinal epithelial cells that is induced by interleukin (IL)-23 and IL-22 in mice that lack CD4+ T cells. By contrast, in immune-competent mice, phosphorylated-STAT3 activation is induced only transiently by microbial colonization at weaning. This early signature is extinguished as CD4+ T cell immunity develops in response to the expanding commensal burden. Physiologically, the persistent IL-22 production from group 3 ILCs that occurs in the absence of adaptive CD4+ T-cell activity results in impaired host lipid metabolism by decreasing lipid transporter expression in the small bowel. These findings provide new insights into how innate and adaptive lymphocytes operate sequentially and in distinct ways during normal development to establish steady-state commensalism and tissue metabolic homeostasis.


Multiphasic denaturation of glutathione transferase B1-1 by guanidinium chloride. Role of the dimeric structure on the flexibility of the active site.
The unfolding and refolding mechanisms of dimeric glutathione transferase GSTB1-1 from Proteus mirabilis, using guanidinium chloride as a denaturant, have been investigated. The protein transitions were monitored by enzyme activity, intrinsic fluorescence, far ultraviolet circular dichroism and gel-filtration chromatography. The non coincidence of denaturation curves at equilibrium indicates that the unfolding of GSTB1-1 is a multistep process, i. e. inactivation of the structured dimer, dissociation into partially structured monomers followed by complete unfolding. In the 50% inactivated enzyme the Km for glutathione increases threefold, while the kcat appears almost the same, indicating that the initial phase of the denaturation involves the binding site of glutathione. The rapid recovery of the folded dimer precedes the complete enzyme reactivation. This indicates that the reconstitution of the native structure of GSTB1-1 is the result of folding and association of compact monomers followed by subtle rearrangements of assembled monomers that build up the active site.


Aflibercept and navigated versus conventional laser in diabetic macular oedema: a 12-month randomized clinical trial.
To examine the efficacy of intravitreal aflibercept and navigated laser as compared to intravitreal aflibercept and conventional laser in diabetic macular oedema (DME) treatment. In 12-month randomized clinical trial, 48 eyes of 37 patients with centre-involved DME at Odense University Hospital were randomized 1:1 to receive three monthly injections of aflibercept followed by navigated (group A) or conventional (group B) focal/grid laser. From month four through twelve, patients were examined monthly, and additional injections were given pro re nata (PRN) (central retinal thickness [CRT]>20% from lowest measurement or loss in visual acuity [VA]>5 Early Treatment Diabetic Retinopathy Study [ETDRS] letters compared with baseline). Outcome measures; (1) percentage of eyes that needed additional injections after laser in group A and B, (2) mean number of injections in group A and B, and (3) mean change in VA and CRT in group A and B. In the PRN phase, 60.5% of patients needed additional injections without differences between groups A and B (58.3 versus 63.2%, p > 0.99). The mean number of injections between baseline and month 12 was 4.4 (4.2 versus 4.6, p = 0.41). From baseline to month 12, VA improved by 8.4 ETDRS letters, and CRT was reduced by 97.4 μm (+9.4 versus +7.1 letters, p = 0.17, and -83.2 versus -115.4 μm, p = 0.21). No difference in need for retreatment was detected between treatment arms of aflibercept and navigated versus conventional laser.


Techniques for Repair of Obstetric Anal Sphincter Injuries.
Obstetric anal sphincter injuries (OASISs) complicate up to 11% of vaginal deliveries; obstetricians must be able to recognize and manage these technically challenging injuries. The aim of this study was to share our approach for management of these challenging complications of childbirth based on a multidisciplinary collaboration between general obstetrician-gynecologists, maternal fetal medicine specialists, and female pelvic medicine and reconstructive surgeons established at our institution. A systematic literature search was performed in 3 search engines: PubMed 1946-, EMBASE 1947-, and the Cochrane Database of Systematic Reviews using keywords obstetric anal sphincter injuries and episiotomy repair. Identification should begin with an assessment of risk factors, notably nulliparity and operative vaginal delivery, consistently associated with the highest risk of OASISs, and proceed with a thorough examination to grade the degree of laceration. Repair should be performed or supervised by an experienced clinician in an operating room with either regional or general anesthesia. The external anal sphincter may be repaired using either an overlapping or end-to-end anastomosis. Providers should be comfortable with both approaches as the degree of laceration may necessitate one approach over the other. We advocate for use of monofilament suture on all layers to decrease risk of bacterial seeding, as well as preoperative antibiotics and postoperative bowel regimen, which are associated with improved outcomes. Long-term sequelae, including pain, dyspareunia, and fecal incontinence, significantly impact quality of life for many patients who suffer OASISs and may be avoided if evidence-based guidelines for recognition and repair are utilized.


Gluconeogenesis in the kidney and liver slices of a lizard, Uromastix hardwickii.
1. The liver and kidney of the lizard Uromastix hardwickii have much higher contents of carbohydrate than have been reported for the corresponding rat tissues. Most of this carbohydrate still remains in the tissue even after a long preincubation. 2. Kidney slices of this lizard release both glucose and other carbohydrates into the medium. Hence glucose release alone, as demonstrated for rats, cannot be used as a good criterion of gluconeogenesis in this lizard. Moreover, the results obtained by glucose release did not agree with those in which the total carbohydrate was estimated in the slice and medium. 3. l-Glutamate, l-aspartate, dl-valine, l-proline, l-cysteine, l-lactate and succinate stimulated gluconeogenesis in the kidney slices, whereas citrate, l-alanine, l-serine, glycine, l-arginine and l-leucine did not. In liver slices only l-glutamate increased gluconeogenesis. 4. New carbohydrate formation in the kidney and liver slices after incubation with various substrates indicated that gluconeogenesis as well as the amino acid metabolism in this animal may be somewhat different from that of mammals.


miR-675 promotes disease progression of non-small cell lung cancer via activating NF-κB signaling pathway.
Non-small cell lung cancer (NSCLC) is a major type of lung cancer significantly affected human life. Current studies have revealed potential role of miR-675 in the etiology of lung cancer. Therefore, in this study, we aimed to investigate the role of miR-675 in NSCLC cell line. We recruited 92 cases of NSCLC patients from July 2009 to February 2011 in the oncology department. Tumor and peripheral tissue was collected for miR-675 expression. NSCLC cell lines with either miR-675 over-expression or low-expression were established. Western blotting and immunofluorescence staining were used for detecting P65 and pP65 expression and translocation in the nuclei. MiR-675 expression was significantly higher in the lung cancer tissue than the peripheral normal tissue (P < 0.001). The gene expression of pP65 was also increased and decreased in cells with over-expression or low-expression of miR-675, respectively (both P < 0.05). Whereas the trend of P65 expression was on the opposite (both P < 0.05), indicating the NF-κB signaling pathway was activated when miR-675 was expressed and vice versa. Immunofluorescence staining showed that more pP65 expression was clustered in the nuclei in miR-675 over-expressed cells, which further demonstrated NF-κB signaling pathway activation. Increased miR-675 expression is associated with NSCLC progression through activation of NF-κB signaling pathway.


Preparation and evaluation of Tc-99m hydroxyethyl starch as a potential radiopharmaceutical for lymphoscintigraphy: comparison with Tc-99m human serum albumin, Tc-99m dextran, and Tc-99m sulfur microcolloid.
Tc-99m hydroxyethyl starch (Tc-99m HES) prepared with a labeling efficiency greater than 95% was evaluated in rabbits for visualization of lymphatic channels and lymph nodes, and the findings compared with Tc-99m human serum albumin (Tc-99m HSA), Tc-99m dextran (Tc-99m DXT), and Tc-99m sulfur microcolloid (Tc-99m SMC). Tc-99m HES showed good visualization of lymphatic channels and regional nodes and it had the highest clearance rate from the injection site (p less than 0.01). Tc-99m HES showed greater uptake by the nodes than Tc-99m DXT (p less than 0.001) at 90 minutes post-injection. The concentration of Tc-99m HES in the lymphatic channels was higher than that of Tc-99m SMC at 90 minutes post-injection (p less than 0.001). Preliminary clinical studies of Tc-99m HES yielded high quality lymphoscintigrams of the leg, and the pelvic and para-aortic lymph nodes in less than 10 minutes post-injection. In addition, partially and completed obstructed lymphatics could be differentiated from normal lymphatic pathways. In conclusion, Tc-99m HES is a promising radiopharmaceutical for imaging of lymphatic channels and nodes.


An Improvement Effort to Optimize Electronically Generated Hospital Discharge Instructions.
The purpose of hospital discharge instructions (HDIs) is to facilitate safe patient transitions home, but electronic health records can generate lengthy documents filled with irrelevant information. When our institution changed electronic health records, a cumbersome electronic discharge workflow produced low-value HDI and contributed to a spike in discharge delays. Our aim was to decrease these delays while improving family and provider satisfaction with HDI. We used quality improvement methodology to redesign the electronic discharge navigator and HDI to address the following issues: (1) difficulty preparing discharge instructions before time of discharge, (2) suboptimal formatting of HDI, (3) lack of standard templates and language within HDI, and (4) difficulties translating HDI into non-English languages. Discharge delays due to HDI were tracked before and after the launch of our new discharge workflow. Parents and providers evaluated HDI and the electronic discharge workflow, respectively, before and after our intervention. Providers audited HDI for content. Discharge delays due to HDI errors decreased from a mean of 3.4 to 0.5 per month after our intervention. Parents' ratings of how understandable our HDIs were improved from 2.35 to 2.74 postintervention (P = .05). Pediatric resident agreement that the electronic discharge process was easy to use increased from 9% to 67% after the intervention (P < .001). Through multidisciplinary collaboration we facilitated advance preparation of more standardized HDI and decreased related discharge delays from the acute care units at a large tertiary care hospital.


Cyclooxygenase-2 directly regulates gene expression of P450 Cyp19 aromatase promoter regions pII, pI.3 and pI.7 and estradiol production in human breast tumor cells.
The present studies evaluated the direct effects of the presence of human cyclooxygenase-2 (Cox-2) on gene expression of specific promoter regions of the P450 Cyp19 enzyme aromatase enzyme and its product, estradiol, in Cox-2 null estrogen-dependent MCF-7 breast tumor cells and in a stable clone of MCF-7 cells containing transfected Cox-2 cDNA, designated as MCF-7/Cox-2 Clone 10. Clone 10 human breast tumor cells have significantly increased gene expression of total mRNA of the P450 Cyp19 enzyme aromatase, with high levels of gene expression of specific aromatase promoter (p) regions pII, pI.3, and p1.7, with no significant change in mRNA levels of p1.4. Clone 10 human breast tumor cells produced significantly increased amounts of both prostaglandin E2 (PGE2) derived from Cox-2 enzyme activity and estradiol derived from aromatase enzyme activity (p<0.01), compared to MCF-7/vector control cells. The greatest inhibition of PGE2 or estradiol production was observed by the combination of the selective Cox-2 inhibitor celecoxib (25 microM) and the aromatase inhibitor, formestane (10nM) (p<0.01). The greatest anti-proliferative effect in Cox-2 null MCF-7/vector control cells was observed with the combination of 25 microM celecoxib and 10nM formestane but not with 10 microM celecoxib, suggesting that there are Cox-2-independent mechanisms involved in the anti-proliferative effect of this agent at doses greater than 10 microM. Celecoxib (25 microM) also significantly inhibited proliferation of MCF-7/Cox-2 Clone 10 human breast tumor cells, with no further anti-proliferative activity with the addition of 10 nM formestane observed at either 24 or 48 h of treatment. These studies demonstrate that Cox-2 directly regulates gene expression of specific aromatase promoter regions and regulates aromatase enzyme activity. Agents that inhibit Cox-2 or block the biological effects of PGE2 may be useful in significantly limiting aromatase activity and proliferation of human breast tumor cells regardless of the presence of Cox-2. In addition, the unique human breast tumor cell model used in these studies may be a useful tool in identifying the spectrum of activities of agents that block the biological effects of PGE2 and estradiol.


Acquired savolitinib resistance in non-small cell lung cancer arises via multiple mechanisms that converge on MET-independent mTOR and MYC activation.
Lung cancer is the most common cause of cancer death globally with a significant, unmet need for more efficacious treatments. The receptor tyrosine kinase MET has been implicated as an oncogene in numerous cancer subtypes, including non-small cell lung cancer (NSCLC). Here we explore the therapeutic potential of savolitinib (volitinib, AZD6094, HMPL-504), a potent and selective MET inhibitor, in NSCLC. In vitro, savolitinib inhibits MET phosphorylation with nanomolar potency, which correlates with blockade of PI3K/AKT and MAPK signaling as well as MYC down-regulation. In vivo, savolitinib causes inhibition of these pathways and significantly decreases growth of MET-dependent xenografts. To understand resistance mechanisms, we generated savolitinib resistance in MET-amplified NSCLC cell lines and analyzed individual clones. We found that upregulation of MYC and constitutive mTOR pathway activation is a conserved feature of resistant clones that can be overcome by knockdown of MYC or dual mTORC1/2 inhibition. Lastly, we demonstrate that mechanisms of resistance are heterogeneous, arising via a switch to EGFR dependence or by a requirement for PIM signaling. This work demonstrates the efficacy of savolitinib in NSCLC and characterizes acquired resistance, identifying both known and novel mechanisms that may inform combination strategies in the clinic.


Plaster cast burns: the reality.
An in vivo experimental study was performed of the temperatures produced by a setting plaster cast using hot and cold water. The results confirmed a statistical difference in the temperatures reached using hot and cold water. Forearm and below knee plasters did not represent a burn risk. Lower limb cylinder casts reached sufficient temperatures to cause burns with hot water but did not remain at these temperatures long enough to pose a clinical risk.


Neoadjuvant chemoradiation treatment followed by surgery for esophageal cancer: there is much more than the mandard tumor regression score.
Tumor regression grading (TRG) systems categorize residual tumor volume on the primary tumor after neoadjuvant treatment. Aim was to evaluate the impact of Mandard TRG, residual tumor depth (ypT) and residual lymph node status (ypN) and extent (ELNI) i.e. intracapsular versus extracapsular involvement on overall (OS) and disease-free survival (DFS) in esophageal carcinoma. Between 2005 and 2014, 344 patients receiving R0-esophagectomy after neoadjuvant chemoradiation therapy (nCRT) were selected. Mandard TRG, ypTN and ELNI were prospectively recorded. Mandard TRG1 was found in 110 (32%); TRG2 in 120 (35%); TRG3 in 53 (15%); TRG4 in 54 (16%) and TRG5 in 7 (2%) patients. Both OS and DFS showed no significant difference between TRG1 and 2 (p = 0.059 and 0.105, respectively). Therefore, TRG1/2 was classified together as 'major response', TRG3/4 as 'minor response' and TRG5 as 'no response'. Multivariate analysis showed two independent prognosticators for OS (tumor regression response (TRR) and number of positive lymph nodes) and three independent prognosticators for DFS (TRR, ypT and ELNI). After nCRT followed by surgery for esophageal carcinoma, number of residual positive lymph nodes as well as TRR are prognosticators for OS. Minor TRR, ypT and extracapsular lymph node invasion are prognosticators for recurrence.


Barriers to physical activity participation in colorectal cancer survivors at high risk of cardiovascular disease.
Lifestyle factors including inadequate physical activity may contribute to increased risk of developing cardiovascular disease in colorectal cancer survivors. Identification of the barriers to physical activity is important for forming an evidence base of factors to target in future physical activity programs aimed at improving cardiovascular health in this population. Colorectal cancer survivors (N = 24) from St. John of God Subiaco Hospital participated in semi-structured interviews about their current physical activity behaviors and perceived barriers to physical activity. Inductive thematic analysis of interviews revealed 5 overarching themes relating to barriers to physical activity: psychological barriers, environmental barriers, knowledge of guidelines, lack of practitioner support, and energy/age barriers. Novel findings revealed participants' dependence on practitioner support, including a reliance on practitioners to recommend lifestyle change. Survivors also revealed that regular checkups to monitor cardiovascular risk replaced the need for healthy lifestyle changes. With survivors holding the advice of clinicians in high regard, an opportunity exists for clinicians to facilitate lifestyle change. Health care professionals such as nurses can implement motivational strategies and provide additional health information during follow-up visits, to ensure long-term adherence. Individuals who reported psychological, motivational, and environmental barriers may benefit from interventions to improve self-regulation, planning, and problem-solving skills.


Identification of A Protein Interacting with Type 2 Methionine Aminopeptidase by Yeast Two-hybrid System.
Type 2 methionine aminopeptidase (MetAP2) is the molecular target for the fumagillin inhibitors against angiogenesis. Making use of the yeast two-hybrid system with GAL4 DBD-fused MetAP2 as a bait, a human brain cDNA library was screened to isolate protein factors that might interact with MetAP2. Among the 2x10(6) transformants obtained, five positive clones were picked out. Sequence analysis revealed that three of them contained cDNA fragments from flotillin and encode a carboxy terminus (starting from amino acids 145--233, respectively) of flotillin protein. The interaction between MetAP2 and flotillin detected by yeast two-hybrid system suggests that MetAP2 might play a role in some biological processes where flotillin is involved.


Acute pancreatitis: a review of pathophysiology and nutrition management.
Acute pancreatitis (AP) is an acute inflammatory process of the pancreas that may involve peripancreatic tissue or remote organs. In its more severe forms, it is a significantly catabolic illness for which specialized nutrition support is required. This review summarizes the pathophysiology of AP, the severity grading systems used in its evaluation, and general treatment strategies, and reviews the value of enteral tube feeding and parenteral nutrition in supporting the patient with this common disease.


[Profile and sensitivity to antibiotics of 2063 uropathogenic bacteria isolated in the center of Tunisia].
Current bacteriological data are very useful when making therapeutic decisions in cases of non complicated urinary tract infection. In this article, we present the data gathered by a university hospital laboratory in mid-Tunisia as well as the results of 17,829 urinary cytobacteriological examinations conducted in a multidisciplinary hospital during the year 2000. Urine was sowed on usual agar. All bacterium cultivating at least 10(5) bacteria reported to ml and at 37 degrees C in a normal atmosphere was retained; identification and sensitivity to antibiotics of the bacterium followed the recommendations of the French Society of Microbiology. We collected 2063 non-redundant bacteria of which 82.3% came from female samples. Gram negative rods were distinctly predominant with 92% of the whole bacterium and Escherichia coli represented 67% of the whole of the germs; Staphylococcus saprophyticus with 4.8% and Streptococcus agalactiae with 1% dominated Gram positive bacteria. The susceptibility of bacteria to the principal antibiotics used for the treatment of the urinary tract infection was characterised by the low percentage of sensitivity of the Gram negative rods to amoxicillin (41.2% of sensitivity for Escherichia coli and 22% for the Proteus sp), and by cotrimoxazole which preserved an activity between 63.8% for Escherichia coli and 94.7% for Staphylococcus saprophyticus. The highest percentage of sensitivity was achieved by gentamicine (99.4% of Escherichia coli and 98.9% of Staphylococcus saprophyticus) and fluoroquinolons (97.8% of Escherichia coli and 100% of Staphylococcus saprophyticus are sensible); furadoin was active on almost all Escherichia coli and Staphylococcus saprophyticus. Apart from natural resistance, colistin was constantly active. Escherichia coli and Staphylococcus saprophyticus were the major agents of the urinary tract infection. Gentamicin and fluoroquinolons showed themselves to be constantly active antibiotics. Nitrofurans and colistin deserve a better place in therapeutic choice.


Temperature dependence of inhomogeneous broadening: on the meaning of isosbestic points.
An isosbestic point in the temperature dependence of an absorption spectrum is commonly viewed as a sign of interconverting chemical or structural species. Here I explore an alternative microscopic origin of temperature-independent absorbance in inhomogeneously broadened spectra: While the equilibrium probability of observing a particular frequency generally changes with the magnitude of thermal fluctuations, the weight of at least one frequency is insensitive to small changes in temperature. The range of temperature accessible to aqueous solutions at ambient pressure is sufficiently small that such insensitivity would appear in experiments as an isosbestic point. This mechanism depends only on the continuity of equilibrium distributions, not on the presence of multiple components. Even the simplest model of a single solute species in a fluctuating environment exhibits isosbestic points, van't Hoff behavior, and, with appropriate dependence of transition frequency on configuration, multiple absorption peaks.


Stem cell derived phenotypic human neuromuscular junction model for dose response evaluation of therapeutics.
There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units. A system was developed in which human myotubes and motoneurons derived from stem cells were cultured in a serum-free medium in a BioMEMS construct. The system is composed of two chambers linked by microtunnels to enable axonal outgrowth to the muscle chamber that allows separate stimulation of each component and physiological NMJ function and MN stimulated tetanus. The muscle's contractions, induced by motoneuron activation or direct electrical stimulation, were monitored by image subtraction video recording for both frequency and amplitude. Bungarotoxin, BOTOX® and curare dose response curves were generated to demonstrate pharmacological relevance of the phenotypic screening device. This quantifiable functional hNMJ system establishes a platform for generating patient-specific NMJ models by including patient-derived iPSCs.


Higher liver stiffness in patients with chronic congestive heart failure: data from NHANES with liver ultrasound transient elastography.
Liver stiffness in patients with chronic congestive heart failure (CCHF) is poorly understood and liver ultrasound transient elastography (LUTE) is a new non-invasive method to detect this condition. In this cross-sectional study we explored liver stiffness and secondary congestive hepatopathy in patients with CCHF detected by LUTE. Data from the National Health and Nutrition Examination Survey (NHANES 2017-2018) were analyzed. All participants undergoing LUTE and without liver disease were included, among whom, 110 participants were diagnosed with CCHF. The cut-off values of stiffness for fibrosis and cirrhosis were above 7.65 and 13.01 kPa, respectively. Data regarding liver stiffness were compared between the participants with and without CCHF. Among patients with CCHF, the median liver stiffness was 6.0 kPa, above 7.65 kPa in 32.7% of patients, and above 13.01 kPa in 14.6% of patients. The mean liver stiffness was 5.0 kPa in the control group and was significantly lower than that of patients with CCHF (P<0.001). The ratio of serum albumin/globulin (A/G) gradually decreased according to the liver stiffness of patients with CCHF (P=0.03). Patients with CCHF had higher liver stiffness values than controls, nearly one-third had substantial fibrosis, and more than one in seven patients progressed to cirrhosis. The A/G ratio may be a potential biomarker for liver stiffness caused by CCHF.


Increased interleukin-4 and decreased interferon gamma production in children with asthma: function of atopy or asthma?
Both atopy and asthma are claimed to be associated with a Th-2 cytokine pattern. We sought to determine the contribution of atopy and asthma to the observed Th-2/Th-1 imbalance in these conditions. Of 60 children aged 6-16 years that were included in the study, 13 were nonatopic nonasthmatic, 15 atopic nonasthmatic, 14 nonatopic asthmatic, and 18 atopic asthmatic. Atopic children had positive skin prick tests to grass pollens only. All children were studied after an asymptomatic and drug-free period of at least three months. Total IgE was measured in serum. Peripheral blood mononuclear cells were cultured and stimulated in vitro with phytohemagglutinin and interferongamma (IFN-gamma) and interleukin-4 (IL-4) measured in the supernatants. Total IgE was significantly higher in atopic asthmatics compared to nonatopic asthmatics (p = 0.004), and nonatopic nonasthmatics (p = 0.001), but was not different from atopic nonasthmatics (p >0.05). On the other hand, IL-4 was significantly elevated in atopic asthmatics and in nonatopic asthmatics compared to nonatopic nonasthmatics (p = 0.037 and p = 0.009, respectively). Although atopic asthmatics had lower IFN-gamma values than nonatopic asthmatics, the difference did not reach statistical significance. No correlation was detected between any two parameters. Our results suggest that both atopy and asthma contribute to the increased levels of IL-4 and that, whereas nonatopic asthma is associated with increases in both IL-4 and IFN-gamma release by mononuclear cells, only atopic asthma is characterized by a Th-2 type cytokine dominance.


Organization of Chemically Activated Food Search Behavior in Procambarus clarkii Girard and Orconectes rusticus Girard Crayfishes.
The feeding responses of decapod crustaceans to chemical stimuli have most often been evaluated in terms of one defining act, ignoring the organization of the behavior. To gain greater insight into foraging behavior, we considered the organization of food-search behavior in evaluating the responses of two species of crayfishes to a feeding stimulant. We also examined the effects of food deprivation on the behavioral organization and whether a behavioral dichotomy exists between food search and feeding behavior in these species. Individual crayfish of the species Procambarus clarkii and Orconectes rusticus were presented with infusions of a feeding stimulant consisting of a supernatant leachate of 100 ml water and 1 g of fish flakes. The stimulant was injected with a syringe and small-bore plastic infusion tubing into the center of a behavioral arena 25 cm square and 15 cm deep. Total injection time was 20 s. Experimental groups were presented with either the full-strength leachate (100%) or one of five dilutions: 75%, 50%, 25%, 10%, or 0% (controls) of full-strength. The feeding stimulant was presented either the day after the crayfish were fed or after one week of food deprivation. We analyzed three components of food-search behavior--detection, probing (near-field search), and locomotion (far-field, or distant, search)--recording the order of occurrence and the latency time to initiation for each behavior. When presented with the stimulus following regular feeding, both species responded to concentrations {ge}50% full-strength with probing behavior (near-field search) prior to locomotion, and to concentrations <50% full-strength with locomotion prior to, or even in the absence of, probing. Detection always occurred first. These results indicate that chemical stimuli preferentially activate distant food search in both species and that a behavioral dichotomy exists between food search and feeding behavior. One week of food deprivation had no effect on the organization of food-search behavior in P. clarkii; however, groups of unfed O. rusticus presented with 25% and 10% full-strength concentrations probed prior to locomotion, indicating a change in behavioral organization.


Myocarditis requiring extracorporeal membrane oxygenation support following Influenza B infection: a case report and literature review.
Seasonal influenza A (IA) and B (IB) viruses co-circulate every year, causing respiratory tract infections in individuals of all ages. Recently, the association between laboratory-confirmed influenza infection and acute myocardial infarction has been clearly demonstrated. However, most of the reported cases of fulminant myocarditis had been associated with influenza virus type A infection. Here we report the case of a 44 y/o man who experienced myocarditis with cardiogenic shock [requiring percutaneous extracorporeal membrane oxygenation (ECMO) support], following influenza B virus infection, which circulated widely in Italy in 2017-18.


Host plant use by competing acacia-ants: mutualists monopolize while parasites share hosts.
Protective ant-plant mutualisms that are exploited by non-defending parasitic ants represent prominent model systems for ecology and evolutionary biology. The mutualist Pseudomyrmex ferrugineus is an obligate plant-ant and fully depends on acacias for nesting space and food. The parasite Pseudomyrmex gracilis facultatively nests on acacias and uses host-derived food rewards but also external food sources. Integrative analyses of genetic microsatellite data, cuticular hydrocarbons and behavioral assays showed that an individual acacia might be inhabited by the workers of several P. gracilis queens, whereas one P. ferrugineus colony monopolizes one or more host trees. Despite these differences in social organization, neither of the species exhibited aggressive behavior among conspecific workers sharing a tree regardless of their relatedness. This lack of aggression corresponds to the high similarity of cuticular hydrocarbon profiles among ants living on the same tree. Host sharing by unrelated colonies, or the presence of several queens in a single colony are discussed as strategies by which parasite colonies could achieve the observed social organization. We argue that in ecological terms, the non-aggressive behavior of non-sibling P. gracilis workers--regardless of the route to achieve this social structure--enables this species to efficiently occupy and exploit a host plant. By contrast, single large and long-lived colonies of the mutualist P. ferrugineus monopolize individual host plants and defend them aggressively against invaders from other trees. Our findings highlight the necessity for using several methods in combination to fully understand how differing life history strategies affect social organization in ants.


Evaluating the efficacy of hydrogen peroxide vapour against foot-and-mouth disease virus within a BSL4 biosafety facility.
An evaluation was made of the efficacy of 35% hydrogen peroxide vapour (HPV) against foot-and-mouth disease virus (FMDV) in a biosafety facility. Biological indicators (BIs) were produced using three serotypes of FMDV, all with a titre of ≥106 TCID50 per ml. Fifteen BIs of each serotype were distributed across five locations, throughout a 30-m3 airlock chamber, producing a total of 45 BIs. Thirty-five percent HPV was generated and applied using a Bioquell vaporization module located in the centre of the chamber. After a dwell period of 40 min, the HPV was removed via the enclosures air handling system and the BIs were collected. The surfaces of the BIs were recovered into Glasgow's modified Eagle's medium (GMEM), cultivated in BHK21 Cl13 cell culture and analysed for evidence of cytopathic effect (CPE). No CPE was detected in any BI sample. Positive controls showed CPE. The experimentation shows that FMDV is susceptible to HPV decontamination and presents a potential alternative to formaldehyde. Foot-and-mouth disease virus (FMDV) is an important pathogen in terms of biosafety due to its infectious nature and wide range of host animals, such as cattle, sheep, goats and pigs. Outbreaks of FMDV can have a severe impact on livestock production, causing morbidity, mortality, reduced yields and trade embargoes. Laboratories studying FMDV must possess BSL4 robust bio-decontamination methods to prevent inadvertent release. Formaldehyde has been the primary agent for environmental decontamination, but its designation as a human carcinogen has led to a search for alternatives. This study shows 35% hydrogen peroxide vapour has the potential to be a rapid, effective, residue-free alternative.


Desmoid-type infantile fibromatosis of the mandible: case report with long-term follow-up.
A 6-year-old girl was referred to Eppendorf University Hospital because of a suspected malignant mandibular tumour. An osteolytic lesion was depicted on panoramic radiograph in the premolar region. The tumour was resected with covering skin and the defect was closed by primary intention. Histological investigation revealed fibromatosis. No local recurrence of infantile fibromatosis occurred during seven years of follow-up. The differential diagnosis of fibro-osseous lesion of the facial region is challenging. Especially in children, caution should be exercised in the treatment of benign lesions that resemble malignant conditions derived from connective tissue, with special reference to long-term follow-up.


Hepatitis C in organ transplantation: its significance and influence on transplantation policies.
Posttransplantation liver disease due to non-A, non-B hepatitis (NANBH) is an important cause of morbidity and mortality in renal transplant recipients. The cloning of the hepatitis C virus (HCV), which is the major cause of parenterally transmitted NANBH, and the development of tests to detect HCV infection have shed light on the prevalence, transmission, and natural course of HCV infection. This review discusses the influence of this information on transplantation policies.


Properties of C84 and C24H12 molecular ion sources for routine TOF-SIMS analysis.
C84+ and coronene (C24H12+) have been studied as primary ions for use in secondary ion mass spectrometry. A representative range of samples has been used to compare the effectiveness of each primary ion with the existing C60+, Au+, and Au3+ primary ions. It was found that C84 is the most effective primary ion providing higher secondary ion yields and a high molecular to fragment ion ratio. Coronene had a performance similar to C60. Coronene and C60 primary ions were also used to extend a previous study of matrix suppression/enhancement effects. The C60 was found to ameliorate this effect, possibly due to the increase in protonation in polyatomic sputtering, and coronene was found to further reduce suppression showing evidence of a chemical effect.


Echocardiographic diagnosis of pseudoaneurysm of the left ventricle.
The echocardiographic features of postinfarction pseudoaneurysm of the left ventricle are described for the first time. Because ultrasound allows the detection of soft-tissue structures in a manner not possible with other diagnostic techniques, the left ventricular wall can be visualized separating the left ventricular cavity from the saccular aneurysm which is delineated by pericardium and/or extracardiac tissue. In addition to these anatomic findings, relevant qualitative hemodynamic data can also be obtained. Echocardiography seems to be a safe and specific method for the diagnosis of left ventricular pseudoaneurysm. It is suggested that echocardiography should be used in the incipeint phase of pseudoaneurysm formation to detect subacute cardiac rupture.


Chronic maternal dietary iodine deficiency but not thiocyanate feeding affects maternal reproduction and postnatal performance of the rat.
Iodine deficiency disorders affect reproductive performance in the afflicted populations. Environmental iodine deficiency (ID) and goitrogens are important in their aetiology. We observed earlier that chronic maternal dietary ID but not goitrogen feeding altered the blood-brain barrier nutrient transport in adult rats. Whether similar differences exist in their effects on reproduction of dams and postnatal performance of the offspring has been assessed. Inbred, female, weaning WNIN rats were rendered hypothyroid by feeding for 8-12 weeks, a low iodine test diet or a control diet with added potassium thiocyanate (KSCN) (@ 25 mg/rat/day). Following mating with control males, they continued on their respective diets till their pups were weaned. Indices of reproductive performance such as percentage of conception, mortality of dams during pregnancy and parturition, litter size, and survival of pups till weaning were affected markedly by ID but not thiocyanate feeding. Neither ID nor thiocyanate feeding from conception or parturition affected their reproductive performance. Nevertheless, postnatal weight gain of pups was less in all the three ID groups but not thiocyanate fed dams. Rehabilitation of chronically ID pregnant dams from conception or parturition did not improve their pregnancy weight gain, litter size or birth weight of pups but decreased abortion and mortality of mothers during pregnancy and parturition. Rehabilitation improved the pups' postnatal weight gain but the effect was only moderate. Based on the results of the present study it may be suggested that maternal ID but not thiocyanate feeding affects reproductive performance and postnatal performance of their offspring.


Effects of percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy on renal function and prostaglandin excretion.
The aim of the study was to investigate the effects of percutaneous nephrolithotomy (PCN) and extracorporeal shock wave lithotripsy (ESWL) on renal function and urinary prostaglandin excretion. Twenty/ESWL patients and 20 PCN patients were studied pre-, 24 h and two weeks after treatment. Twenty-four hours after treatment PCN resulted in a fall in serum potassium, sodium and calcium. There was a small rise in urinary prostaglandin excretion. All results had returned to normal by two weeks. ESWL caused a rise in serum creatinine with a fall in calculated glomerular filtration rate (GFR). This was coupled with a fall in urinary excretion of sodium, potassium, and calcium. There was a rise in urinary prostaglandin excretion. Serum calcium and LDH levels also rose. All results had returned to normal by two weeks except urinary calcium excretion, and serum albumin had now fallen. ESWL had more effect on renal function in the acute phase of treatment than PCN.


Roles of glutathione (GSH) in dopamine (DA) oxidation studied by improved tandem HPLC plus ESI-MS.
In this study, new procedure with improved tandem HPLC plus ESI-MS was utilized to decipher the protective role of glutathione (GSH) against dopamine (DA) oxidation. We demonstrated that auto-oxidation of DA could produce aminochrome (AM, a cyclized DA quinone), which could be effectively abrogated by reductants, especially by GSH. Furthermore GSH was demonstrated to be able to conjugate with AM to form various conjugates via condensation reactions without enzymatic catalysis. The GSH-AM conjugates tend to aggregate, possibly mediated by conjugated AM structures, but could be inhibited by GSH. We hypothesized that proteins conjugated by AM might facilitate Lewy body formation of Parkinson's disease (PD) in dopaminergic neurons via similar polymerization. We proposed that GSH could protect dopaminergic neurons against DA-induced toxicity via various mechanisms. The imbalance between DA oxidation and GSH protective capacity could be a key factor contributing to PD. Strategies to use GSH analogues, GSH inducers or to control DA oxidation might work to control PD onset and development.


Treatment of restless legs syndrome and periodic movements during sleep with L-dopa: a double-blind, controlled study.
Six patients with restless legs syndrome (RLS) and periodic movements during sleep (PMS) received placebo or L-dopa in a double-blind study. We recorded patients for 36 consecutive hours in the sleep laboratory during a baseline investigation and at the end of each treatment period. Daily evening questionnaires and a suggested immobilization test (SIT) performed at bedtime on each recording night documented the effect of L-dopa in RLS. A nocturnal EMG recording of the anterior tibialis muscles revealed the effect of L-dopa on PMS. L-Dopa proved effective in treating both RLS and PMS. Although not present in every patient, leg movements recorded during the SIT exhibited a clear periodicity. These observations support the hypothesis that RLS and PMS are two manifestations of the same central sensorimotor disorder.


Mucinous Cell Clusters in Infantile Congenital Pulmonary Airway Malformations Mimic Adult Mucinous Adenocarcinoma But Are Not Associated With Poor Outcomes When Appropriately Resected.
Congenital pulmonary airway malformations (CPAMs) are abnormalities of the lung arising during development. At our institution the majority of type I infantile CPAMs contain mucinous cell clusters (MCCs). The overlapping histology of MCCs and adult in situ mucinous adenocarcinomas, as well as reports of metastatic mucinous adenocarcinoma arising in CPAMs resected later in childhood raise concerns about the malignant potential of these cells. However, after adequate surgical resection, malignant recurrence has not been reported in infants with CPAMs. Despite benign behavior, MCCs often have histologic features that, in an adult, would be consistent with a diagnosis of adenocarcinoma. Therefore, to assess the spectrum of features that may be seen in these presumed precursor lesions, we characterized the histology of 671 MCCs spread across 44 infantile CPAMs and compared them to 10 adult mucinous adenocarcinomas. MCCs in CPAMS were often numerous, widespread, and located outside of the large cysts. Mucinous and nonmucinous epithelium within CPAMs showed complex architecture, making application of adult adenocarcinoma architectural patterns difficult. The MCCs within CPAMs displayed nuclear features similar to adult mucinous adenocarcinomas. The proliferative index in infantile MCCs was higher than in adult mucinous adenocarcinomas but was also higher in uninvolved infantile lung tissue. This work illustrates that histologic features typically associated with adenocarcinoma frequently occur within CPAMs; however, this does not alter their benign behavior. Therefore, extreme caution should be used if adult lung cancer terminology is applied to avoid significant potential psychological and physical harms associated with the label of adenocarcinoma.


Adsorption kinetics and isotherm of vanadium with melamine.
Melamine, possessing three free amino groups and three aromatic nitrogen atoms in its molecule, has great potential as an adsorbent for metal ions. We investigated three impact factors of the adsorption process: the initial pH of the vanadium solution, contact time and reaction temperature. The adsorption kinetics could be accurately described by the pseudo-second-order kinetic model. Langmuir and Freundlich models fitted well with the experimental equilibrium data, and the maximal adsorption capacity was found to be 1,428.57 mg vanadium/g melamine, and the Freundlich model showed the adsorption is privilege type.


A synthesis of L-vancosamine derivatives from non-carbohydrate precursors by a short sequence based on the Marshall, McDonald, and Du Bois reactions.
[reaction: see text] The carbamate-protected l-vancosamine glycal, viewed as a universal precursor for vancosamine derivatives, was prepared by a short scheme based on diastereoselective addition of an allenyl stannane to a lactaldehyde ether, the tungsten-catalyzed alkynol cycloisomerization, and the rhodium-catalyzed C-H insertion of a carbamate nitrogen. This sequence is a prototype for a new and efficient strategy for the synthesis of 3-amino sugar derivatives. The key intermediate was elaborated to the silyl ether of N,N-dimethyl vancosamine glycal.


Poloidal mode analysis of magnetic probe data in a spherical tokamak configuration.
A method to determine the poloidal mode number m in a spherical tokamak based on magnetic probe data was developed. Perturbed magnetic fields at Mirnov coils are calculated for distributed helical filamentary currents on rational surfaces assuming the maximum current amplitude, m and n (toroidal mode number), and the toroidal location of the filaments. These free parameters were determined from the best fit to the measured signals. The residual error was reduced by a factor of 2 by introducing helical filaments instead of toroidal filaments. Using this method, m/n=2/1 and 3/2 modes were identified in Mega-Ampere Spherical Tokamak discharges, and the time evolution of the tearing modes was derived.


Supramolecular assembly of DNA-constructed vesicles.
The self-assembly of DNA hybrids possessing tetraphenylethylene sticky ends at both sides into vesicular architectures in aqueous medium is demonstrated. Cryo-electron microscopy reveals the formation of different types of morphologies from the amphiphilic DNA-hybrids. Depending on the conditions, either an extended (sheet-like) or a compact (columnar) alignment of the DNA hybrids is observed. The different modes of DNA arrangement lead to the formation of vesicles appearing either as prolate ellipsoids (type I) or as spheres (type II). The type of packing has a significant effect on the accessibility of the DNA, as evidenced by intercalation and light-harvesting experiments. Only the vesicles exhibiting the sheet-like DNA alignment are accessible for intercalation by ethidium bromide or for the integration of chromophore-labelled DNA via a strand exchange process. The dynamic nature of type I vesicles enables their elaboration into artificial light-harvesting complexes by DNA-guided introduction of Cy3-acceptor chromophores. DNA-constructed vesicles of the kind shown here represent versatile intermediates that are amenable to further modification for tailored nanotechnology applications.


A strategy for improving health disparities education in medicine.
A health disparities curriculum that uses evidence-based knowledge rooted in pedagogic theory is needed to educate health care providers to meet the needs of an increasingly diverse U.S. population. The Health Disparities Education: Beyond Cultural Competency Precourse, along with its accompanying Train the Trainer Guide: Health Disparities Education (2008), developed by the Society of General Internal Medicine (SGIM) Disparities Task Force (DTF), is a comprehensive tool to facilitate developing, implementing and evaluating health disparities education. The curriculum includes five modules highlighting several fundamental concepts in health disparities, suggestions for teaching about health disparities in a wide range of settings and strategies for curriculum evaluation. The modules are Disparities Foundations, Teaching Disparities in the Clinical Setting, Disparities Beyond the Clinical Setting, Teaching about Disparities Through Community Involvement, and Curriculum Evaluation. All five modules were delivered as a precourse at the 31st Annual SGIM Annual Meeting in Pittsburgh, PA and received the "Best Precourse Award". This award is given to the most highly rated precourse based on participant evaluations. The modules have also been adapted into a web-based guide that has been downloaded at least 59 times. Ultimately, the modules are designed to develop a professional commitment to eliminating racial and ethnic disparities in health care quality, promote an understanding of the role of health care providers in reducing health care disparities through comprehensive education and training, and provide a framework with which providers can address the causes of disparities in various educational settings.


The role of C-peptide levels in screening for latent autoimmune diabetes in adults.
Early detection of latent autoimmune diabetes in adults (LADA) is important in that the earlier insulin therapy is initiated, the greater the preservation of pancreatic beta cells. This study assessed whether a random C-peptide level is an effective screening test for LADA. Random C-peptide levels were measured in 39 subjects with LADA and 39 subjects with type 2 diabetes who were matched for age, race, gender, and duration of diabetes. LADA was definitively diagnosed by the presence of antiglutamic acid decarboxylase antibodies. The mean C-peptide level in the LADA group was 1.0 +/- 0.2 ng/mL and 5.1 +/- 0.4 ng/mL in the group with type 2 diabetes. Only 1 LADA subject had a C-peptide level above the normal range, and all subjects with type 2 diabetes had a C-peptide level within or above the normal range. LADA can be ruled out in adult-onset diabetes by the presence of elevated C-peptide. The more expensive testing for anti-GAD antibodies to definitively diagnose LADA should be reserved for patients who on screening have a low or normal random C-peptide level.


Specificity of the synergistic anion for iron binding by ferric binding protein from Neisseria gonorrhoeae.
Ferric binding protein in Neisseria gonorrhoeae (nFbpA) transports iron from outer membrane receptors for host proteins across the periplasm to a permease in an alternative pathway to the use of siderophores in some pathogenic bacteria. Phosphate and nitrilotriacetate, both at pH 8, and vanadate at pH 9 are shown to be synergistic in promoting ferric binding to nFbpA, in contrast to carbonate and sulfate. Interestingly, only phosphate produces the fully closed conformation of nFbpA as defined by native electrophoresis. The role of phosphate was probed by constructing three mutants: Q58E, Q58R, and G140H. The anion and iron binding properties of the Q58E mutant are similar to the wild-type protein, implying that one phosphate oxygen is a hydrogen bond donor and may in part define the specificity of nFbpA for phosphate over sulfate. Phosphate is a weakly synergistic anion in the Q58R and G140H mutants, and these mutants do not form completely closed structures. Ferric binding was investigated by both isothermal titration and differential scanning calorimetry. The apparent affinity of nFbpA for iron in a solution of 30 mM citrate is 1 order of magnitude larger in the presence (K(app)= 1.7 x 10(5) M(-1)) of phosphate than in its absence (K(app) = 1.6 x 10(4) M(-1)) at pH 7. Similar results were obtained at pH 8. This increase in affinity with phosphate as well as the formation of closed structure allows nFbpA to compete for free ferric ions in solution and suggests that ferric binding to nFbpA is regulated by the synergistic phosphate anion at sites of iron uptake.


[Leukocyte adhesion defect--a rare form of congenital immune deficiency].
Leukocyte adhesion defect (LAD) is an inherited defect of phagocytic function. This disorder is characterised by delayed separation of the umbilical cord, severe recurrent bacterial infections, impaired formation of pus, and high leukocyte counts. The granulocytes have severe defect in their chemotactic mobility and endocytosis. The disease is attributed to the absence of the leukocyte adhesion molecules. (CD11/CD18), which can be verified with monoclonal antibodies. The authors describe the disease-process of the first patient diagnosed in Hungary. Perinatally the omphalitis, periumbilical abscess and periproctal abscess leading to rectovaginal fistula, in the first months the otitis, mastoiditis, and expressed leukocytosis referred to the impaired function of phagocytic cells, which was verified by laboratory tests as well. The decreased inflammation and cicatrization were also striking. This severe form of LAD can be cured only by bone marrow transplantation with preliminary sanitation of the foci of infection. It took about six months. Unfortunately, the patient died of sepsis immediately before transplantation.


Differential expression of endogenous ferritin genes and iron homeostasis alteration in transgenic tobacco overexpressing soybean ferritin gene.
For studying the effects of endogenous ferritin gene expressions (NtFer1, GenBank accession number AY083924; and NtFer2, GenBank accession number AY141105) on the iron homeostasis in transgenic tobacco (Nicotiana tabacum L.) plants expressing soybean (Glycine max Merr) ferritin gene (SoyFer1, GenBank accession number M64337), the transgenic tobacco has been produced by placing soybean ferritin cDNA cassette under the control of the CaMV 35S promoter. The exogenous gene expression was examined by both Northern- and Western-blot analyses. Comparison of endogenous ferritin gene expressions between nontransformant and transgenic tobacco plants showed that the expression of NtFer1 was increased in the leaves of transgenic tobacco plants, whereas the NtFer2 expression was unchanged. The iron concentration in the leaves of transgenic tobacco plants was about 1.5-folds higher than that in nontransformant. Enhanced growth of transgenic tobacco was observed at the early development stages, resulting in plant height and fresh weights significantly greater than those in the nontransformant. These results demonstrated that exogenous ferritin expression induced increased expression of at least one of the endogenous ferritin genes in transgenic tobacco plants by enhancing the ferric chelate reductase activity and iron transport ability of the root, and improved the rate of photosynthesis.


Brachytherapy for localized prostate cancer in the modern era: a comparison of patient-reported quality of life outcomes among different techniques.
To report our institutional quality of life (QOL) data for low-dose-rate (LDR) monotherapy (LDR mono), high-dose-rate (HDR) monotherapy (HDR mono), and EBRT with an HDR brachytherapy boost (HDR boost). The charts of 165 patients with localized adenocarcinoma of the prostate treated with LDR monotherapy (LDR mono), HDR monotherapy (HDR mono), and EBRT with an HDR brachytherapy boost (HDR boost) at a single institution between 2012 and 2015 were reviewed. All patients completed the American Urological Association symptom score (AUASS) and Expanded Prostate Index for Prostate Cancer - Clinical Practice (EPIC-CP) quality of life assessments prior to treatment and at least one follow-up survey. Time points included baseline, ≤ 2 months, 2-≤ 6 months, 6-≤ 12 months, 12-≤ 18 months, 18-≤ 24 months, 24-≤ 30 months, and > 30 months. Linear mixed models were performed to test for significant changes and differences in each outcome over time. Mean follow-up was 19.5 months. All major functional QOL domains were affected after treatment with brachytherapy for localized prostate cancer. All domains improved over time, with the exception of sexual function scores for all groups and urinary incontinence scores for the HDR mono group. Patients treated with LDR did have higher AUA, irritability/obstructive symptoms, incontinence, bowel, and QOL scores acutely compared to the HDR and HDR + boost groups. Vitality scores were significantly worse in the HDR boost group both acutely and at the > 30-month time point. Patients receiving HDR brachytherapy had lower acute urinary and rectal toxicity compared to the patients receiving LDR, even when combined with EBRT. However, long-term toxicity was similar.


Hemodialysis immediately after cardiac catheterization is a risk factor for intradialytic hypotension.
Many hemodialysis clinicians have noticed that patients frequently develop intradialytic hypotension (IDH) immediately after cardiac catheterization (CC). However, precise data about the incidence of IDH immediately after CC are scarce. This study involved a single-center, retrospective, cross-sectional design. We reviewed the medical records of all HD patients who underwent CC between January 2009 and March 2012 at Hiroshima Prefectural Hospital. IDH was defined as a fall of systolic blood pressure of more than 20 mm Hg or a fall of mean blood pressure of more than 10 mm Hg, with symptoms according to the K/DOQI criteria. Data on a total of 112 patients were obtained: 64 patients commenced HD immediately after CC (IA group) and 48 patients underwent HD on the day after CC (ND group). The overall incidence of IDH was 34% (38/112). The incidence of IDH was significantly higher in the IA group than in the ND group (27/64, 42% vs. 11/48, 23%; P < 0.05). Multivariate logistic regression analysis showed that IA (odds ratio, 5.39; 95% confidence interval, 1.76 to 16.49; P < 0.01), coronary stenosis (odds ratio, 4.16; 95% confidence interval, 1.49 to 11.64; P < 0.05) were independently associated with IDH. This study revealed that HD immediately after CC is associated with a higher incidence of IDH. Clinicians should consider that HD following CC be scheduled for the next day, especially in patients with coronary stenosis.


Mechanism of a lymphocyte abnormality associated with HLA-B8/DR3 in clinically healthy individuals.
An important unanswered question in clinical immunology is why the histocompatibility antigens HLA-B8/DR3 should be associated with at least nine quite different immune-mediated diseases. The purpose of this study was to examine the mechanism of an immunologic abnormality, commonly found in healthy individuals with HLA-DR3, that may reflect an immune defect predisposing to autoimmunity. Fourteen healthy subjects with HLA-DR3 had a proliferative response to a suboptimal concentration of PHA nearly eight-fold lower than that observed in 10 individuals without this HLA antigen. Impaired responsiveness to PHA was more strongly associated with HLA-DR3 than with HLA-B8. The IL-2 concentration in mitogen-stimulated cultures was similarly decreased in subjects with HLA-DR3 and was highly predictive of the proliferative response 24 h later (r = 0.82, P less than 0.0001). Inhibition of IL-2 utilization by anti-IL-2 receptor antibody indicated that the reduced IL-2 concentration reflects impaired lymphokine production rather than increased utilization. Expression of IL-2 receptors is decreased in these subjects, although the magnitude of their proliferative response is appropriate for the available lymphokine. These results indicate that impaired lymphocyte activation associated with HLA-DR3 reflects impaired IL-2 production and an abnormality of activation events preceding the production of this lymphokine.


Spontaneous Leydig cell tumors in inbred laboratory mice.
Six Leydig cell tumors were identified in 6,500 male mice necropsied over a period of 8.5 years. All tumors developed spontaneously in BALB/cJ and BALB/cByJ inbred mice. When submitted for necropsy, affected mice were 8 to 9 months old. The incidence was calculated to be 5.5 per 100,000 males retained as breeders. Tumors were unilateral, with no predilection for right or left testis, Histologically all Leydig cell tumors were well differentiated and of the solid, diffuse type.


Work capacity after myocardial revascularization: factors related to work resumption.
For patients with coronary artery disease the ability to retain or resume a normal occupation must be one of the goals of myocardial revascularization procedures. Provided myocardial revascularization is sufficiently complete and left ventricular function is not severely impaired, this goal should be achieved in virtually all cases. The rates of return to work after coronary surgery, however, are often lower than what could be expected. Analysis of the factors related to work resumption after coronary surgery shows that non-medical preoperative parameters (age, educational level, type of occupation, and, most of all, length of preoperative unemployment) are major predictors of subsequent re-employment, whereas medical preoperative factors have little or no influence on return to work. In contrast, re-employment following coronary surgery is strongly influenced by the success of the revascularization procedure, with much fewer patients resuming work in case of poor exercise capacity or persisting angina after surgery. Percutaneous transluminal coronary angioplasty is usually given to patients with less extensive coronary artery disease, and rates of return to work higher than after surgery are observed; re-employment after PTCA is also influenced by the initial result of the procedure. Recognition of the factors negatively influencing return to work after myocardial revascularization is important in an attempt to improve work resumption by appropriate medical, psychological and social measures.


Osteonecrosis of the jaws in periodontal patients with a history of bisphosphonates treatment.
Osteonecrosis of the jaws is being increasingly reported in patients with bone metastasis from a variety of solid tumours and disseminated multiple myeloma receiving intra-venous bisphosphonates. The signs and symptoms that may occur before the appearance of clinical evident osteonecrosis include changes in the health of periodontal tissues, non-healing mucosal ulcers, loose teeth and unexplained soft-tissue infection. A series of nine periodontally involving patients showing osteonecrosis of the jaws that appeared following the intra-venous use of bisphosphonates is reported. Nine consecutive patients with osteonecrosis of the jaws were prospectically studied. Patients' past medical histories and the drugs that they had received for their malignant disease were systematically documented. Clinical, histopathological and radiographic features and proposal for treatment modalities of osteonecrosis are also reported. Of the nine patients (six women and three men) observed, all had osteonecrosis in the mandible; two had maxillary involvement as well. All nine patients had a history of extraction of periodontally hopeless teeth preceding the onset of osteonecrosis. In two patients, the lesions also appeared in edentulous areas spontaneously. All the patients had received intra-venous bisphosphonates as treatment for their disseminated haematological neoplasms or metastatic bone disease. The duration of bisphosphonate therapy at presentation ranged from 10 to 70 months (median: 33 months). Jaw osteonecrosis appears to be associated with the intra-venous use of bisphosphonates. Dental professionals should be aware of this potentially serious complication in periodontal patients receiving long-term treatment with bisphosphonates.


The Prescription of the Morning-After Pill in a Berlin Emergency Department Over a Four-Year Period - User Profiles and Reasons for Use.
Questions: There are no current health care studies from Germany regarding the "morning-after pill". This paper will use routine data to analyse details regarding the users' profiles, reasons for using it and the utilisation of hospital outpatient facilities. Patient Collective and Methods: Retrospective analysis of all triage sheets in the emergency department of the Virchow Hospital Campus/Charité University Hospital, Berlin, over a four-year period from 2007 to 2010 that were coded with the ICD diagnosis Z30 (= contraception advice) and statistical processing of the associated administrative data. Results: 860 triage sheets were included in the analysis. The emergency department is used most frequently for the prescription of the "morning-after pill" at the weekend. The average age of the users was 25.1 years. The most common reason cited for needing emergency contraception was unprotected sexual intercourse, with the second-most common being "condom failure". Around half of the women attended the department within 12 hours of having unprotected sex. Less than 2 % (n = 14) of all women decided against a prescription of emergency contraceptive after counselling. Conclusions: The user profile and reasons for using emergency oral contraception correlate largely with the information contained in international literature. Although the "morning-after pill" is probably prescribed mainly in general practices in Germany, and despite the availability of new drugs with a permitted post-exposure interval of up to 120 hours after unprotected sex, there appears to still be a high demand for counselling and prescriptions of the "morning-after pill" in the context of the emergency department.


Cytomegalovirus in liver transplant recipients.
Cytomegalovirus (CMV) is the most common opportunistic infection following solid-organ transplant and remains a cause of life-threatening disease and allograft rejection in liver transplant recipients. The purpose of this review is to highlight the current strategies in diagnosis and management of this disease in this vulnerable population. Identification of high-risk individuals and aggressive treatment with antiviral agents, either via prophylaxis or by early initiation during active disease, has become the standard of care. Despite this, CMV continues to exert a significant effect, remaining a major cause of morbidity and mortality. Given these findings, continuing efforts are underway to determine whether further therapy, vaccination, or alternative management strategies may improve outcomes in solid-organ transplant recipients. Until that time, however, aggressive monitoring of post-transplant patients for signs and symptoms of CMV infection is the best strategy to prevent solid-organ loss and death.


Health outcomes for HIV-infected persons released from the New York City jail system with a transitional care-coordination plan.
We sought to assess 6-month outcomes for HIV-infected people released from New York City jails with a transitional care plan. Jail detainees in New York City living with HIV who accepted a transitional care plan during incarceration were asked to participate in a multi-site evaluation aimed at improving linkages to community-based care. The evaluation included a 6-month follow-up; HIV surveillance data were used to assess outcomes for those considered lost to follow-up. Participants (n=434) completed baseline surveys during incarceration in a jail in New York City. Of those seen at 6 months (n=243), a greater number were taking antiretroviral medications (92.6% vs 55.6%), had improved antiretroviral therapy adherence (93.2% vs 80.7%), and reported significant reductions in emergency department visits (0.20 vs 0.60 visits), unstable housing (4.15% vs 22.4%), and food insecurity (1.67% vs 20.7%) compared with baseline. Transitional care coordination services facilitate continuity of care and improved health outcomes for HIV-positive people released from jail.


Patent Foramen Ovale and Stroke-Current Status.
Patent foramen ovale (PFO) is growing in clinical interest because of a renewed focus on embolic stroke of undetermined source (ESUS), the PFO attributable fraction (the 10-point Risk of Paradoxical Embolism score), technical advances in PFO diagnosis, and the emergence of endovascular device closure as a treatment option. However, recent randomized controlled trials of the management of patients with ESUS and PFO failed to demonstrate the superiority of closure over medical treatment. The mechanisms of stroke other than paradoxical embolism may be important in patients with ESUS and PFO. This paper reviews the current understanding of the pathophysiology of stroke and therapeutic options in patients with PFO and ESUS.


Pond use by captive African penguins (Spheniscus demersus) in an immersive exhibit adjacent to human bathers.
Nonhuman animals in zoos are exposed to a continuous human presence, which affects their behaviors and welfare. However, little is known about what role the "visitor effect" has on penguins in captivity. The African penguin (Spheniscus demersus) is an endangered species commonly housed in zoos worldwide. The aim of this study was to evaluate whether the abundance of human bathers could reduce the average time spent in the water of a colony of African penguins housed in an exhibit where their pond habitat was adjacent to a swimming pool. Observations were carried out on 7 penguins in the summer of 2009. Data were collected during 3 time periods (Time 1 [T1] = opening of the swimming season, Time 2 [T2] = core of the season, Time 3 [T3] = late season) of 14 days each. The human disturbance caused by bathers strongly reduced the pond use by penguins at T1 and T2, especially when there were large numbers of visitors. However, at T3, we observed that the overall use of the pond by penguins increased, and the average duration of their diving was no longer dependent on the number of visitors.


Dietary Inflammatory Index and Type 2 Diabetes Mellitus in Adults: The Diabetes Mellitus Survey of Mexico City.
Diet and inflammation are both associated with type 2 diabetes mellitus (T2DM). In the present study, we aimed to assess the relation between the dietary inflammatory index (DII) and the presence of T2DM in Mexican adults participating in the Diabetes Mellitus Survey administered in Mexico City (DMS-MC). The study involved 1174 subjects (48.5% men) between 20-69 years of age. A validated semi-quantitative food frequency questionnaire was employed to evaluate dietary intake and to compute DII. The DII is based on scientific evidence about the association between dietary compounds and six established inflammatory biomarkers. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of DII in relation to T2DM. Our results suggest that subjects in the highest quintile of the DII had higher odds of T2DM (OR = 3.02; 95% CI: 1.39, 6.58; p = 0.005) compared to subjects in the lowest quintile of DII scores. Assessing possible effect modification, an association with T2DM was evident when comparing DII quintile 5 to quintile 1 for participants aged ≥ 55 years (OR = 9.77; 95% CI: 3.78, 25.50; p = 0.001). These results suggest that a pro-inflammatory diet is associated with significantly higher odds of T2DM among adult Mexicans.


Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life-Threatening Arrhythmias.
Patients with dilated cardiomyopathy (DCM) may present with ventricular arrhythmias early in the disease course, unrelated to the severity of left ventricular dysfunction. These patients may be classified as having an arrhythmogenic DCM (AR-DCM). We investigated the phenotype and natural history of patients with AR-DCM. Two hundred eighty-five patients with a recent diagnosis of DCM (median duration of the disease 1 month, range 0 to 7 months) and who had Holter monitoring at baseline were comprehensively evaluated and followed for 107 months (range 29 to 170 months). AR-DCM was defined by the presence of ≥1 of the following: unexplained syncope, rapid nonsustained ventricular tachycardia (≥5 beats, ≥150 bpm), ≥1000 premature ventricular contractions/24 hours, and ≥50 ventricular couplets/24 hours, in the absence of overt heart failure. The primary end points were sudden cardiac death (SCD), sustained ventricular tachycardia (SVT), or ventricular fibrillation (VF). The secondary end points were death from congestive heart failure or heart transplantation. Of the 285 patients, 109 (38.2%) met criteria for AR-DCM phenotype. AR-DCM subjects had a higher incidence of SCD/SVT/VF compared with non-AR-DCM patients (30.3% vs 17.6%, P=0.022), with no difference in the secondary end points. A family history of SCD/SVT/VF and the AR-DCM phenotype were statistically significant and cumulative predictors of SCD/SVT/VF. One-third of DCM patients may have an arrhythmogenic phenotype associated with increased risk of arrhythmias during follow-up. A family history of ventricular arrhythmias in DCM predicts a poor prognosis and increased risk of SCD.


Starter strain related effects on the biochemical and sensory properties of Cheddar cheese.
A detailed investigation was undertaken to determine the effects of four single starter strains, Lactococcus lactis subsp. lactis 303, Lc. lactis subsp. cremoris HP, Lc. lactis subsp. cremoris AM2, and Lactobacillus helveticus DPC4571 on the proteolytic, lipolytic and sensory characteristics of Cheddar cheese. Cheeses produced using the highly autolytic starters 4571 and AM2 positively impacted on flavour development, whereas cheeses produced from the poorly autolytic starters 303 and HP developed off-flavours. Starter selection impacted significantly on the proteolytic and sensory characteristics of the resulting Cheddar cheeses. It appeared that the autolytic and/or lipolytic properties of starter strains also influenced lipolysis, however lipolysis appeared to be limited due to a possible lack of availability or access to suitable milk fat substrates over ripening. The impact of lipolysis on the sensory characteristics of Cheddar cheese was unclear, possibly due to minimal differences in the extent of lipolysis between the cheeses at the end of ripening. As anticipated seasonal milk supply influenced both proteolysis and lipolysis in Cheddar cheese. The contribution of non-starter lactic acid bacteria towards proteolysis and lipolysis over the first 8 months of Cheddar cheese ripening was negligible.


Alterations in local stability and dynamics of A4V SOD1 in the presence of trifluoroethanol.
Alterations in the local dynamics of Cu/Zn Superoxide dismutase (SOD1) due to mutations affect the protein folding, stability, and function leading to misfolding and aggregation seen in amyotrophic lateral sclerosis (ALS). Here, we study the structure and dynamics of the most devastating ALS mutation, A4V SOD1 in aqueous trifluoroethanol (TFE) through experiments and simulation. Far-UV circular dichroism (CD) studies shows that TFE at intermediate concentrations (∼15% - 30%) induce partially unfolded β-sheet-rich extended conformations in A4V SOD1 which subsequently aggregates. Molecular dynamics (MD) simulation results shows that A4V SOD1 increases local dynamics in the active site loops that leads to the destabilization of the β-barrel and loss of hydrophobic contacts, thus stipulating a basis for aggregation. Free energy landscape (FEL) and essential dynamics (ED) analysis demonstrates the conformational heterogeneity in A4V SOD1. Our results thus shed light on the role of local unfolding and conformational dynamics in aggregation of SOD1.


1H-2H cross-polarization NMR in fast spinning solids by adiabatic sweeps.
Cross-polarization (CP) experiments employing frequency-swept radiofrequency (rf) pulses have been successfully used in static spin systems for obtaining broadband signal enhancements. These experiments have been recently extended to heteronuclear I, S = spin-1/2 nuclides under magic-angle spinning (MAS), by applying adiabatic inversion pulses along the S (low-γ) channel while simultaneously applying a conventional spin-locking pulse on the I-channel (1H). This study explores an extension of this adiabatic frequency sweep concept to quadrupolar nuclei, focusing on CP from 1H (I = 1/2) to 2H spins (S = 1) undergoing fast MAS (νr = 60 kHz). A number of new features emerge, including zero- and double-quantum polarization transfer phenomena that depend on the frequency offsets of the swept pulses, the rf pulse powers, and the MAS spinning rate. An additional mechanism found operational in the 1H-2H CP case that was absent in the spin-1/2 counterpart, concerns the onset of a pseudo-static zero-quantum CP mode, driven by a quadrupole-modulated rf/dipolar recoupling term arising under the action of MAS. The best CP conditions found at these fast spinning rates correspond to double-quantum transfers, involving weak 2H rf field strengths. At these easily attainable (ca. 10 kHz) rf field conditions, adiabatic level-crossings among the {|1⟩,|0⟩,|-1⟩} mS energy levels, which are known to complicate the CP MAS of quadrupolar nuclei, are avoided. Moreover, the CP line shapes generated in this manner are very close to the ideal 2H MAS spectral line shapes, facilitating the extraction of quadrupolar coupling parameters. All these features were corroborated with experiments on model compounds and justified using numerical simulations and average Hamiltonian theory models. Potential applications of these new phenomena, as well as extensions to higher spins S, are briefly discussed.


Use of operating telescopes with multifocal corrective lenses.
Many older practitioners who wear spectacles with multifocal lenses for surgery work have been told that they cannot use flip-up magnifying telescopes with these owing to the difficulty of positioning them over the appropriate part of the lens and therefore must resort to normal bifocals. They thereby lose the advantages of clear vision at all distances which multifocals give. This article describes a way of overcoming this problem.


Ultrastructural effects of oritavancin on methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus.
The ultrastructural effects of the lipoglycopeptide oritavancin on methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) were examined by transmission electron microscopy. Oritavancin but not vancomycin induced aberrant septum formation and loss of staining of nascent septal cross walls in MRSA. Septal distortions were also observed in VRE exposed to oritavancin.


A double blind, randomized, controlled trial to study the effect of dexmedetomidine on hemodynamic and recovery responses during tracheal extubation.
The α2-adrenoreceptor agonist, dexmedetomidine, provides excellent sedation with minimal cardiovascular instability or respiratory depression and may be a useful adjunct to facilitate smooth tracheal extubation. Fifty American Society of Anesthesiologists grade I-II patients, aged 20-45 years, scheduled for elective general surgical, urological and gynecological surgeries were studied after randomization into two groups. Group A and B, received an intravenous infusion of dexmedetomidine 0.75 mcg/kg or placebo respectively, over 15 minutes before anticipated time of end of surgery, in a double blind manner. Anesthesia techniques were standardized. Heart rate, systolic, diastolic, mean arterial pressures were recorded while starting injection, at 1, 3, 5, 10, 15 minutes after starting injection, during extubation, at 1, 3, 5 minutes after extubation, and thereafter every 5 minutes for 30 minutes. Quality of extubation was evaluated on a 5 point scale and postoperative sedation on a 6 point scale. Any event of laryngospasm, bronchospasm, desaturation, respiratory depression, vomiting, hypotension, undue sedation was noted. Heart rate, systolic, diastolic, mean arterial pressures were significantly higher in group B (P < 0.05). Extubation quality score of majority of patients was 2 in group A and 3 in group B. Sedation score of most patients was 3 in group A and 2 in group B. Bradycardia and hypotension incidences were higher in group A. One patient in group A, two patients in group B had vomiting. No patient had any other side effects. Dexmedetomidine 0.75 mcg/kg administered 15 minutes before extubation, stabilizes hemodynamics and facilitates smooth extubation.


[Further analysis of location of the gene for inborn dominant Nochurli cataract].
The study of location of the gene for inborn dominant nokhur kataracta is going on. No linkage of this gene with the locus of alpha-globin gene (16p13.3) and the locus (7q36-qter) was revealed. Additional evidence was obtained for a possible location of the gene for inborn dominant nokhur kataracta on the 14 chromosome. The maximal lod value equaled to 1.089 at theta = 0.20 in the analysis of kataracta genes and alpha-1-antitrypsin (14q32.1), and 0.846 at theta = 0.30 for the kataracta gene and D14S13 (14q32.1-q32.32). For the alpha-1-antitrypsin gene the maximal lod value was 2.24 at theta = 0.05.


Altered expressions of circulating microRNAs 122 and 192 during antitubercular drug induced liver injury indicating their role as potential biomarkers.
Drug induced liver toxicity is a serious health complication leading to high mortality rates and post marketing withdrawal of drugs. Although considered to be the gold standard biomarkers; aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase have been found to have specificities beyond liver, therefore more specific and predictive markers for the detection of antitubercular drug mediated liver damage are required. Unfortunately, the effectiveness of currently used first line antitubercular drugs namely isoniazid, rifampicin, pyrazinamide is often accompanied with liver injury, impeding the cure of patients. Keeping in view, the prognostic and diagnostic applications of microRNAs in various diseases, we tried to assess the importance of microRNAs 122 and 192 in antitubercular drug associated liver injuries. The study included subjects having tuberculosis of any type with antitubercular drug induced liver injury; naïve or newly diagnosed tuberculosis patients, tuberculosis patients on drugs not having toxicity and healthy controls. Observations from this study revealed that expression levels of miR-122 and miR-192 were significantly decreased in the serum of antitubercular drug induced liver injury patients only. Therefore, these microRNAs or the pathways associated with them can be used as a tool to predict or cure antitubercular drug associated liver injury in future.


Baseline risk of gastrointestinal disorders among new users of meloxicam, ibuprofen, diclofenac, naproxen and indomethacin.
Meloxicam (Mobic((R))) was introduced in the UK in 1996 as a nonsteroidal anti-inflammatory drug (NSAID). To help evaluate the postmarketing experience with meloxicam in the UK, we used the General Practitioners Research Database (GPRD) to characterize the baseline risk of an upper gastrointestinal (GI) event among new users of meloxicam, ibuprofen, diclofenac, naproxen and indomethacin. We selected for analysis a random sample of 5000 meloxicam users, and 5000 users of each of the comparator NSAIDS except indomethacin, for which we selected 2500 subjects. Comparators were matched to meloxicam subjects on age and sex. We examined for each subject history of certain GI diagnoses and recent use of anti-inflammatory drugs and acid-suppressing drugs. We found that patients receiving meloxicam were at least twice as likely as patients receiving other NSAIDs to have a recent history of GI diagnoses or treatment. We conclude that in the UK meloxicam was used more often than other popular NSAIDs among patients who were at increased baseline risk of GI events. The occurrence of GI events among users of meloxicam, even at a relatively high frequency, therefore, would be expected based solely on this increased baseline risk. Copyright (c) 2000 John Wiley & Sons, Ltd.


Radiation detriment: its quantification and use in setting standards.
At the end of 1990 the International Commission on Radiological Protection adopted new recommendations for the control of exposure to ionizing radiation. The main reasons for the revision of existing standards were first, the new estimates of the risks associated with exposure and second, the need to develop a conceptual framework that covered not only occupational exposures but also radon in homes and the consequences of accidents. This paper addresses these issues and shows how the definition of radiation detriment is used to set new standards in a System of Radiological Protection.


Efficacy and safety assessment of ERCP in patients with malignant biliary obstruction.
To assess the efficacy and safety of Endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary obstruction (MBO). A review of all ERCP-procedures performed at Akershus University Hospital during the six year period between 2009-2014 was analysed. Data for the period 2009- 2013 were obtained retrospectively and prospectively for 2014. Patients with jaundice due to MBO were selected for the present study. A total of 210 patients (51% females), median age of 70 years (range 33-96) were included. The total number of procedures were 314, whereof 218 (69%) were successful and 96 (31%) were failures. 292 procedures were palliative and 22 procedures were intended as 'bridge to surgery' whereof 15 patients underwent surgery. Pancreatic carcinoma occurred in 105 (50%) patients and was the most common reason for MBO. Straight plastic stents (I-stents) were applied in 145 (74%), double-pigtail stents (JJ-stents) in 29 (15%), self-expanding metal stent (SEMS) in 18 (9%) procedures and in 3 procedures (1.5%) an I-stent was inserted through an indwelling SEMS. Median duration of stentpatency in months was 2 (range 0-74) for I-stent, 1 (range 0-29) for JJ-stent and 4 (range 0-29) for SEMS. The rates of complication and mortality due to complication were 8.9% and 1.3% per procedure. Adequate drainage of MBO by ERCP was obtained in 69%. The rates of complication and procedure related mortality were at acceptable levels.