Tacrolimus- (FK 506) based immunosuppression in severe systemic lupus erythematosus.
In a 30-year-old male patient systemic lupus erythematosus was diagnosed based on the presence of 8 out of 11 ARA criteria. Disease onset was acute and included renal function impairment with biopsy-proven lupus nephritis (WHO class IV) requiring renal replacement therapy. Although conventional immunosuppressive therapy regimens proved effective in controlling disease activity, all of the administered drugs were accompanied by serious side effects: bilateral femur head necrosis with corticosteroids, allergic skin reaction in response to azathioprine, nephrotoxicity with cyclosporine, nausea and abdominal pain with mycophenolate mofetil and life-threatening septicemia with cyclophosphamide treatment. In search for alternative treatment options, tacrolimus (FK506, trough serum levels 3-6 ng/ml) was started. FK506 was well-tolerated and lupus activity completely resolved within 7 months after initiation of therapy. During 36 months of follow-up no arthritic complaints occurred and renal function stabilized at a serum creatinine of 2.1 mg/dl with negative anti-ds-DNA antibodies and ANA titers. In conclusion, FK506 may be considered as alternative immunosuppressive for maintenance treatment in patients with severe lupus erythematosus and side effects to conventional regimens.


TLR4 Deficiency Impairs Oligodendrocyte Formation in the Injured Spinal Cord.
Acute oligodendrocyte (OL) death after traumatic spinal cord injury (SCI) is followed by robust neuron-glial antigen 2 (NG2)-positive OL progenitor proliferation and differentiation into new OLs. Inflammatory mediators are prevalent during both phases and can influence the fate of NG2 cells and OLs. Specifically, toll-like receptor (TLR) 4 signaling induces OL genesis in the naive spinal cord, and lack of TLR4 signaling impairs white matter sparing and functional recovery after SCI. Therefore, we hypothesized that TLR4 signaling may regulate oligodendrogenesis after SCI. C3H/HeJ (TLR4-deficient) and control (C3H/HeOuJ) mice received a moderate midthoracic spinal contusion. TLR4-deficient mice showed worse functional recovery and reduced OL numbers compared with controls at 24 h after injury through chronic time points. Acute OL loss was accompanied by reduced ferritin expression, which is regulated by TLR4 and needed for effective iron storage. TLR4-deficient injured spinal cords also displayed features consistent with reduced OL genesis, including reduced NG2 expression, fewer BrdU-positive OLs, altered BMP4 signaling and inhibitor of differentiation 4 (ID4) expression, and delayed myelin phagocytosis. Expression of several factors, including IGF-1, FGF2, IL-1β, and PDGF-A, was altered in TLR4-deficient injured spinal cords compared with wild types. Together, these data show that TLR4 signaling after SCI is important for OL lineage cell sparing and replacement, as well as in regulating cytokine and growth factor expression. These results highlight new roles for TLR4 in endogenous SCI repair and emphasize that altering the function of a single immune-related receptor can dramatically change the reparative responses of multiple cellular constituents in the injured CNS milieu. Myelinating cells of the CNS [oligodendrocytes (OLs)] are killed for several weeks after traumatic spinal cord injury (SCI), but they are replaced by resident progenitor cells. How the concurrent inflammatory signaling affects this endogenous reparative response is unclear. Here, we provide evidence that immune receptor toll-like receptor 4 (TLR4) supports OL lineage cell sparing, long-term OL and OL progenitor replacement, and chronic functional recovery. We show that TLR4 signaling is essential for acute iron storage, regulating cytokine and growth factor expression, and efficient myelin debris clearance, all of which influence OL replacement. Importantly, the current study reveals that a single immune receptor is essential for repair responses after SCI, and the potential mechanisms of this beneficial effect likely change over time after injury.


Xenograft technology: a new frontier in medicine.
The era of xenotransplantation is here and will certainly impact nursing. It is a 21st century answer to curing fatal diseases and prolonging life. Our society can no longer deny life-saving treatment to individuals simply because there are not enough human organs available. Xenotransplantation is a viable, exciting, and preferable option. The public will accept xenotransplantation better than the "presumed consent" system. Xenotransplantation may not fully replace human organs and tissue transplantation even with the recent successes of animal cloning. It can, however, serve as a back-up system for human graft donors. As nurses, we must be open to xenotransplantation as an alternative method that can eliminate the current human organ supply and demand problem.


Neutropenia in kidney and liver transplant recipients: Risk factors and outcomes.
No studies have directly compared the key characteristics and outcomes of kidney (KTx) and liver transplantation (LTx) recipients with neutropenia. In this single-center, retrospective, cohort study, we enrolled all adult patients who received a KTx or LTx between 2000 and 2011. Neutropenia was defined as 2 consecutive absolute neutrophil count (ANC) values <1500/mm3 in patients without preexisting neutropenia. The first neutropenia episode occurring during the first year post-transplantation was analyzed. A total of 663 patients with KTx and 354 patients with LTx met the inclusion criteria. Incidence of neutropenia was 20% in KTx and 38% in LTx, respectively. High-risk CMV status and valganciclovir (VGCV) use were significant predictors of neutropenia for KTx recipients, but only VGCV use vs nonuse in LTx recipients. Neutropenia was associated with worse survival in KTx recipients (adjusted HR 1.95, 95% CI 1.18-3.22, P<.01), but not in LTx recipients (adjusted HR 0.75, 95% CI 0.52-1.10, P=.15). Sixteen acute rejection episodes were associated with preceding neutropenia in KTx recipients (HR 1.77, 95% CI 1.16-2.68, P=.007) and 24 acute rejection episodes in LTx recipients (HR 1.41, 95% CI 0.97-2.04, P=.07). Incidence of infection was similar in patients with and without neutropenia among KTx and LTx recipients.


Characterization of additives in plastics: From MS to MS10 multistep mass analysis and theoretical calculations of tris(2,4-di-tert-butylphenyl)phosphate.
In the analysis by electrospray (+) of an extract of hemp sprouts put in a polypropylene vial, we found a large contamination of a plastic additive. It was characterized by multiple-stage MSn experiments (MS ÷ MS10 ) and identified as tris(2,4-di-tert-butylphenyl)phosphate, also known with the synonyms F32IRS6B46, oxidized Naugard 524, and others. The MS2 ÷ MS7 spectra are characterized by consecutive eliminations of six isobutene molecules from the tert-butyl moieties, some of them also occurring in the ion source. The first three are calculated to occur preferentially from the ortho positions, whereas eliminations from the para positions are estimated to be less favored at about 5-6 kcal/mol in each step. Once the first three isobutene molecules are eliminated, the remaining three are lost from the tert-butyl moieties in para positions (MS5 ÷ MS7 ), yielding protonated triphenylphosphate, whose structure has been confirmed by the MS2 spectrum of triphenylphosphate standard: the latter spectrum is almost superimposable with the MS8 spectrum of the analyte under investigation. MS8 and MS9 spectra show main losses of water and C6 H4 molecules. The MS10 spectrum of precursor ions at m/z 215 shows the gas-phase addition of water and methanol and ions at m/z 168, attributable to the loss of a phosphorus oxide radical. Density functional theory (DFT) calculations (Becke 3LYP [B3LYP] 6-311+G(2d,2p)) have been used to evaluate structure and stability of different ionic and neutral species involved in the decomposition pathways and to calculate thermochemical data of the decomposition reactions. This multistep mass analysis combined with theoretical calculations resulted to be particularly useful and effective, yielding chemical, thermochemical, and mechanistic data of significant utility in the structural characterization and identification of the unknown analyte as well as to define its gas-phase reactivity under a multistep low-energy collision-induced dissociation regime.


Identification of the amino acid residues and domains in the cysteine-rich protein of Chinese wheat mosaic virus that are important for RNA silencing suppression and subcellular localization.
Cysteine-rich proteins (CRPs) encoded by some plant viruses in diverse genera function as RNA silencing suppressors. Within the N-terminal portion of CRPs encoded by furoviruses, there are six conserved cysteine residues and a Cys-Gly-X-X-His motif (Cys, cysteine; Gly, glycine; His, histidine; X, any amino acid residue) with unknown function. The central domains contain coiled-coil heptad amino acid repeats that usually mediate protein dimerization. Here, we present evidence that the conserved cysteine residues and Cys-Gly-X-X-His motif in the CRP of Chinese wheat mosaic virus (CWMV) are critical for protein stability and silencing suppression activity. Mutation of a leucine residue in the third coiled-coil heptad impaired CWMV CRP activity for suppression of local silencing, but not for the promotion of cell-to-cell movement of Potato virus X (PVX). In planta and in vitro analysis of wild-type and mutant proteins indicated that the ability of the CRP to self-interact was correlated with its suppression activity. Deletion of up to 40 amino acids at the C-terminus did not abolish suppression activity, but disrupted the association of CRP with endoplasmic reticulum (ER), and reduced its activity in the enhancement of PVX symptom severity. Interestingly, a short region in the C-terminal domain, predicted to form an amphipathic α-helical structure, was responsible for the association of CWMV CRP with ER. Overall, our results demonstrate that the N-terminal and central regions are the functional domains for suppression activity, whereas the C-terminal region primarily functions to target CWMV CRP to the ER.


Systemic treatment for severe atopic dermatitis in children: a case series.
Atopic dermatitis (AD) is children's most frequent chronic inflammatory skin disease. In most patients, this condition is controlled with topical treatments; however, some patients with severe AD do not respond to these treatments, requiring systemic therapy. There is insufficient information about the ideal dose, time of use, clinical response, and safety of systemic therapy in children with severe AD. This study described the clinical characteristics of patients with severe AD who required systemic treatment, drugs used, their clinical course, adverse effects, and associated complications. We conducted a retrospective review of the records of pediatric patients with severe AD treated in the Dermatology Clinic, Instituto Nacional de Pediatría (2000 to 2018), who required systemic treatment for more than 3 months. We included 21 patients. The mean age at disease onset was 3.31 years. The drugs used were methotrexate (57.1%), thalidomide (38%), prednisone (42.8%), azathioprine (19%), mycophenolate mofetil (9.5%), cyclosporine (4.7%), and systemic steroids as bridging therapy (42.8%). Adverse effects were mild and were observed in two patients (9.5%) treated with methotrexate and mycophenolate mofetil. Methotrexate was the most frequently used drug in > 50% of the patients, and most patients attained remission. Cyclosporine, azathioprine, and mycophenolate mofetil were also effective. Side effects were mild and infrequent. Comparative studies of systemic treatments for severe AD in the pediatric population are necessary.


Design and Implementation of a Smart Home System Using Multisensor Data Fusion Technology.
This paper aims to develop a multisensor data fusion technology-based smart home system by integrating wearable intelligent technology, artificial intelligence, and sensor fusion technology. We have developed the following three systems to create an intelligent smart home environment: (1) a wearable motion sensing device to be placed on residents' wrists and its corresponding 3D gesture recognition algorithm to implement a convenient automated household appliance control system; (2) a wearable motion sensing device mounted on a resident's feet and its indoor positioning algorithm to realize an effective indoor pedestrian navigation system for smart energy management; (3) a multisensor circuit module and an intelligent fire detection and alarm algorithm to realize a home safety and fire detection system. In addition, an intelligent monitoring interface is developed to provide in real-time information about the smart home system, such as environmental temperatures, CO concentrations, communicative environmental alarms, household appliance status, human motion signals, and the results of gesture recognition and indoor positioning. Furthermore, an experimental testbed for validating the effectiveness and feasibility of the smart home system was built and verified experimentally. The results showed that the 3D gesture recognition algorithm could achieve recognition rates for automated household appliance control of 92.0%, 94.8%, 95.3%, and 87.7% by the 2-fold cross-validation, 5-fold cross-validation, 10-fold cross-validation, and leave-one-subject-out cross-validation strategies. For indoor positioning and smart energy management, the distance accuracy and positioning accuracy were around 0.22% and 3.36% of the total traveled distance in the indoor environment. For home safety and fire detection, the classification rate achieved 98.81% accuracy for determining the conditions of the indoor living environment.


Imaging evaluation of demyelinating processes of the central nervous system.
Demyelinating processes involving the central nervous system have a variety of aetiologies and can be separated into primary and secondary demyelinating processes. The classic example of primary demyelination is multiple sclerosis. Secondary demyelination, where the aetiology is known, includes infectious, metabolic and toxic disease processes. The underlying component of all demyelinating disorders is damage to the myelin sheath and/or the oligodendrocyte, the cell forming the myelin sheath. These processes often have similar imaging findings, making knowledge of the patient's history, physical examination and laboratory evaluation imperative for developing a differential diagnosis. This pictorial essay provides a review of the imaging of these diverse disorders.


Quantitative T2 Mapping to Discriminate Mucinous from Nonmucinous Adenocarcinoma in Rectal Cancer: Comparison with Diffusion-weighted Imaging.
Mucinous adenocarcinoma (MA) is associated with worse clinicopathological characteristics and a poorer prognosis than non-MA. Moreover, MA is related to worse tumor regression grade and tumor downstaging than non-MA. This study investigated whether lesions in MA and non-MA can be quantitatively assessed by T2 mapping technique and compared with the diffusion-weighted imaging (DWI). High-resolution MRI, DWI, and T2 mapping were performed on 81 patients diagnosed with rectal cancer via biopsy. Afterward, T2 and apparent diffusion coefficient (ADC) values were manually measured by a senior and a junior radiologist independently. By examining surgical specimens, the patients with MA and non-MA were identified. Inter-observer reproducibility was tested, and T2 and ADC values were compared using Mann-Whitney U test. Finally, receiver operating characteristic (ROC) curves were drawn to determine the cut-off value. Of the 81 patients, 11 patients with MA were confirmed by pathology. The inter-observer reproducibility of T2 and ADC values showed an excellent intraclass correlation coefficient (ICC) of 0.993 and 0.913, respectively. MA had higher T2 (87.9 ± 5.11 ms) (P = 0.000) and ADC (2.03 × 10-3 mm2/s) (P = 0.000) values than non-MA (66.6 ± 6.86 ms and 1.17 × 10-3 mm2/s, respectively). The area under the ROC curves (AUC) of the T2 and ADC values were 0.999 (95% confidence interval [CI]: 0.953-1) and 0.979 (95% CI: 0.920-0.998), respectively. When the cutoff value in T2 mapping was 80 ms, the Youden index was the largest, sensitivity was 100%, and specificity was 97%. As a stable quantitative sequence, T2 mapping of MRI is useful in differentiating MA from non-MA. Compared to ADC values, T2 values are also diagnostically effective and non-inferior to ADC values.


The interstitial atom of the nitrogenase FeMo-cofactor: ENDOR and ESEEM evidence that it is not a nitrogen.
X-ray crystallographic study of the nitrogenase MoFe protein revealed electron density from an atom (denoted X) inside the active-site metal cluster, the [MoFe7S9:homocitrate] FeMo-cofactor. The electron density associated with X is consistent with a single N, O, or C atom. We now have tested whether X is an N or not by comparing the Q-band ENDOR and ESEEM signals from resting-state (S = 3/2) MoFe protein and NMF-extracted FeMo-co from bacteria grown with either 14N or 15N as the exclusive N source. All of the 14N or 15N signals associated with the protein are lost upon extraction of the FeMo-co. We interpret this as strong evidence that X is not an N.


Prescription drug use during pregnancy in Southern Tigray region, North Ethiopia.
Judicious utilization of drugs rescues the fetus from the harmful effects while treating the health problems of the pregnant women. This study aimed at evaluating drug utilization pattern and its associated factors among pregnant women in Southern Tigray, Ethiopia. Institution based cross-sectional study was conducted among 647 pregnant women who had been attending obstetrics-gynecology and antenatal care units in different health facilities of Southern Tigray region. The study participants were selected using multistage sampling technique. Data collection was done using pre-tested semi-structured questionnaires and by reviewing antenatal follow-up cards. Descriptive and inferential statistics were analyzed, to assess drug utilization pattern and its associated factors among pregnant women, using SPSS version 20 software. Of 647 pregnant women, 87.5% were prescribed with at least one medication. As per the United States Food and Drug Administration (US-FDA) risk classification system, 87.7, 7.9, 3.9, and 0.5% of the prescribed drug were from category A, B, C and D, respectively. Prescription drug use was more likely among gynecology ward visitors [AOR = 8.97, 95% Cl (2.69-29.88)] and among those who visited health facilities for the first time during their first [AOR =2.65, 95% Cl (1.44-4.84)] and second [AOR = 2.50, 95% Cl (1.36-4.61)] trimesters. Majority of the study population used safe and appropriate medications according to US-FDA risk classification system, with the exception of low proportion (0.5%) of medication with potential risk for the fetus. The average number of drug prescribed per pregnant women was in the recommended range of WHO drug use indicators guideline.


A weighted negative binomial Lindley distribution with applications to dispersed data.
A new discrete distribution is introduced. The distribution involves the negative binomial and size biased negative binomial distributions as sub-models among others and it is a weighted version of the two parameter discrete Lindley distribution. The distribution has various interesting properties, such as bathtub shape hazard function along with increasing/decreasing hazard rate, positive skewness, symmetric behavior, and over- and under-dispersion. Moreover, it is self decomposable and infinitely divisible, which makes the proposed distribution well suited for count data modeling. Other properties are investigated, including probability generating function, ordinary moments, factorial moments, negative moments and characterization. Estimation of the model parameters is investigated by the methods of moments and maximum likelihood, and a performance of the estimators is assessed by a simulation study. The credibility of the proposed distribution over the negative binomial, Poisson and generalized Poisson distributions is discussed based on some test statistics and four real data sets.


[Thrombopenia and disseminated intravascular coagulation during treatment with heparin: 2 cases with neurological complications].
We report two cases of heparin-induced thrombocytopenia (H.T.) associated with a disseminated intravascular coagulopathy (DIC). Heparin was prescribed after a cerebral infarct in the first case and after an orthopedic surgical procedure in the second case. The DIC induced neurological complications and the death of both patients. Heparin-induced thrombocytopenia is common but is exceptionally associated with neurological symptoms. Heparin-induced DIC is quite uncommon, since only 20 cases have been reported but neurological complications (focal deficits or disturbances of consciousness) are noted in about one third of the cases and the outcome is fatal in 60 percent of the cases. The treatment of heparin-induced DIC and thrombocytopenia is disappointing. Monitoring of the platelets count is warranted during heparin treatment to prevent this severe complication.


Assessment of therapy with continuous subcutaneous insulin infusion in an academic diabetes clinic.
To assess the results of continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus, especially relative to glycemic control and rate of discontinuation of insulin pump therapy. A retrospective review of the medical records of 107 patients with type 1 diabetes who were receiving CSII at the Diabetes Care Center at the University of Washington Medical Center was performed to evaluate clinical outcomes. All patients considering CSII therapy participated in a class to learn the details of insulin pump treatment. The mean age of our patient population was 36.0 +/- 10.4 years (mean value +/- standard deviation). The mean duration of diabetes at the initiation of insulin pump therapy was 17.0 +/- 9.1 years. The mean duration of CSII use was 36.1 +/- 25.5 months (median, 26.2 months). Insulin lispro was used by 89.7% of the patients. Six patients (5.6%) discontinued CSII therapy after a mean of 19.1 +/- 14.7 months for a variety of reasons. Despite no significant difference in home blood glucose monitoring (number of tests per day) before initiation of CSII, mean hemoglobin A1c levels decreased from 7.6% to 7.1% (P<0.0001), and the occurrence of severe hypoglycemic episodes decreased 73.8% (P = 0.0003). In our academic diabetes clinic with a formal insulin pump program, we noted a significant improvement in hemoglobin A1c values, a significant reduction in the frequency of severe hypoglycemic episodes, and a low rate of discontinuation of CSII. CSII therapy, when provided in conjunction with a standard educational program, should continue to be an important treatment option in appropriately selected patients with type 1 diabetes.


Barrier function and natural moisturizing factor levels after cumulative exposure to a fruit-derived organic acid and a detergent: different outcomes in atopic and healthy skin and relevance for occupational contact dermatitis in the food industry.
Fruit-derived organic compounds and detergents are relevant exposure factors for occupational contact dermatitis in the food industry. Although individuals with atopic dermatitis (AD) are at risk for development of occupational contact dermatitis, there have been no controlled studies on the effects of repeated exposure to multiple irritants, relevant for the food industry, in atopic skin. The aim of the study was to investigate the outcomes of repeated exposure to a fruit-derived organic acid and a detergent in AD compared to healthy volunteers. The volunteers were exposed to 2.0% acetic acid (AcA) and/or 0.5% sodium lauryl sulfate (SLS) in controlled tandem repeated irritation test. The outcomes were assessed by measurements of erythema, transepidermal water loss (TEWL) and natural moisturizing factor (NMF) levels. In the AD volunteers, repeated AcA exposure led to barrier disruption and significant TEWL increase; no significant differences after the same exposure in the healthy controls were found. Repeated exposure to SLS and the irritant tandems enhanced the reactions and resulted in a significantly higher increase in TEWL in the AD compared to the control group. Cumulative irritant exposure reduced the NMF levels in both groups. Differences in the severity of irritant-induced barrier impairment in atopic individuals contribute to the risk for occupational contact dermatitis in result of multiple exposures to food-derived irritants and detergents.


Neuroendocrine hormones as prognostic biomarkers in the setting of acute stroke: overcoming the major hurdles.
Stroke represents one of the major causes of disability and mortality worldwide and prediction of outcome represents a challenge for both clinicians and researchers. In the past years, many blood markers have been associated with stroke outcome but despite this evidence, no biomarker is routinely used in stroke management. In this review, we focus on markers of the neuroendocrine system, which represent potential candidates to be implemented in clinical practice. Moreover, we present a systematic review and literature-based meta-analysis for copeptin, a new biomarker of the hypothalamo-pituitary-adrenal axis that has shown additional predictive value over clinical information in a large prospective study. The meta-analysis of the included 7 studies, with more than 2000 patients, reinforced its association with poor outcome (pooled odds ratio: 2.474 [1.678-3.268]) and mortality (pooled OR: 2.569 [1.642-3.495]). We further review the current situation of the topic and next steps to implement these tools by clinicians.


Calculating pressure in polymer lattice simulations.
We propose several novel methods for calculating the bulk pressure in polymer lattice simulations. Our first method combines chain insertion/deletion with Wang-Landau--Optimized Ensemble sampling in the space of number of chains n, which is very efficient and accurate at low to intermediate polymer volume fractions ϕ (e.g., ≲ 0.7). We then propose two methods in canonical-ensemble simulations to efficiently and accurately calculate the bulk pressure at high ϕ where chain insertion/deletion becomes inefficient. Finally, combining these methods leads to complete thermodynamics over the entire range of continuous and exact ϕ-values with negligible finite-size effects. We also analyze in detail the error caused by the cut-off in n-space.


Effect of plasminogen activator inhibitor-1 4G/5G polymorphism in Turkish deep vein thromboembolic patients with and without prothrombin 20210 G-A.
Prothrombin 20210 G-A mutation is a common factor that predispose to thrombosis. The effect of the mutations in PAI-1 gene on the risk of thrombosis is controversial. We aimed to evaluate the role of these two polymorphisms in Turkish patients with deep vein thrombosis. Although there was no statistically significant difference in patient and control group for the distribution of PAI-1 4G/5G polymorphism in the present study, the risk of thrombosis increased from 3.4 fold to 8.4 in patients carrying PT20210 A and PAI-1 4G.


[Criteria valued in the nurse selection process in the health area of Lleida (Spain)].
To determine the factors valued by persons taking part in the process of selecting and hiring university nursing graduates. An additional aim was to identify how the need for new specialties is evaluated. A cross-sectional study was carried out. From April 2005 to April 2006 we contacted all persons involved in the selection and hiring of nursing graduates in the health area of Lleida (Spain) and gave them a self-administered questionnaire. The questionnaire included items on training, other aspects unrelated to training and issues related to the activation of new specialties. Thirty-four persons involved in the selection and hiring process (89.5%) believed that the most important factor was the training profile. High scores were assigned to attitudes (6/6), competence in drug administration (5.8/6), and consideration of emotional, physical and personal care (5.7/6). Ninety percent of those interviewed agreed on the current need for the new law on specialties. All the specialties obtained a high score based on current need. The 2 most highly scored specialties were those already developed (mental health and midwifery). The most highly valued aspect of training was attitudes. This finding should be kept in mind in the training of university nursing graduates. Competencies such as participation in teaching and directing or coordinating groups are insufficiently valued. The need to activate all the specialties is positively valued.


Harnessing the Versatility of Optical Biosensors for Target-Based Small-Molecule Drug Discovery.
Optical biosensors entered target-based small-molecule drug discovery more than two decades ago and have since transformed into a value-adding component in the decision-making process. Here, we briefly highlight the major application areas of optical biosensors and focus on desirable profiles of such platforms in order to ensure their effective use in small molecule drug discovery. Furthermore, we will emphasize current technology-based constraints and discuss experimental strategies to address these limitations as well as provide a view of necessary technology improvements for next generation platforms.


A localized primary sclerosing cholangitis preoperatively diagnosed as hilar cholangiocarcinoma; report of a case.
The authors report herein a case of primary sclerosing cholangitis localized to the hepatic hilum which occurred in a 67-year-old male. The direct cholangiography revealed bile duct stenosis from the common hepatic duct to bilateral hepatic ducts. We could not confirm bile duct malignancy, however, hilar cholangiocarcinoma was most suspicious. We performed right trisegmentectomy of the liver with caudate lobectomy and lymph node dissection 3 weeks after right portal embolization. Pathological findings confirmed localized primary sclerosing cholangitis. Surgical resection of the affected bile duct is most effective in localized primary sclerosing cholangitis, because the prognosis of the disease is poor and secondary carcinogenesis in primary sclerosing cholangitis has high incidence.


A preliminary study on the consistency between the non-surgical staging and the surgical-pathological staging in oesophageal carcinoma.
OBJECTIVES To evaluate the consistency between the clinical staging of non-surgically treated oesophageal carcinoma (preliminary draft) and the surgical-pathological staging of the oesophageal carcinoma. METHODS Comprehensive clinical data from 112 patients with oesophageal cancer were collected from January 2009 to June 2010. Based on the clinical staging standard for oesophageal carcinomas treated with non-surgical methods, the preoperative TNM staging was performed and the results were compared with pTNM. The Kappa statistic was used to analyse the degree of consistency. RESULTS The Kappa values from the T staging, N staging and TNM staging of surgical-pathological results were 0.545, 0.615 and -0.090, respectively. CONCLUSIONS Consistency was observed between the non-surgical T staging and N staging and the postoperative pathological T staging and N staging, but the degree of consistency was only moderate. Additionally, no consistency was observed between the TNM staging results from the two staging systems. Whether the non-surgical staging system can replace the pathological staging system and its significance in evaluating the prognosis remain to be determined.


GABAB Receptors Regulate Extrasynaptic GABAA Receptors.
Tonic inhibitory GABA(A) receptor-mediated currents are observed in numerous cell types in the CNS, including thalamocortical neurons of the ventrobasal thalamus, dentate gyrus granule cells, and cerebellar granule cells. Here we show that in rat brain slices, activation of postsynaptic GABA(B) receptors enhances the magnitude of the tonic GABA(A) current recorded in these cell types via a pathway involving G G proteins, adenylate cyclase, and cAMP-dependent protein kinase. Using a combination of pharmacology and knockout mice, we show that this pathway is independent of potassium channels or GABA transporters. Furthermore, the enhancement in tonic current is sufficient to significantly alter the excitability of thalamocortical neurons. These results demonstrate for the first time a postsynaptic crosstalk between GABA(B) and GABA(A) receptors.


ALDH2 polymorphism and biological monitoring of toluene.
In this study, we evaluated the effects of the genetic polymorphism of ALDH2 (low Km aldehyde dehydrogenase) on toluene metabolism and determined biological exposure indices (BEIs) of the genotypes of ALDH2. The study subjects included 45 toluene workers and 122 nonexposed students. The genotype of ALDH2 was classified into the homozygous genotype of normal ALDH2 (NN), the homozygous genotype of an inactive one (DD), and the heterozygous genotype of normal and inactive ones (ND) by means of artificial-RFLP. The personal exposure levels to toluene were monitored, using diffusion type samplers and urinary hippuric acid (HA) and creatine concentrations were determined. The urinary HA levels of the three genotypes of ALDH2 of nonexposed students did not differ. In the toluene workers, positive correlations between the personal exposure to toluene and urinary HA levels were observed in the NN, ND, and DD groups. The urinary HA level of the DD group was significantly lower than that of the NN or ND group. Regression lines were used to estimate the BEIs of the NN, ND, and DD groups, which were approximately 2.9 g/g creatinine, 3.3 g/g creatinine, and 1.9 g/g creatinine, respectively.


[Comparison of PCDD/Fs content and profile in fish between marine and fresh water in a typical Chinese area].
To study the dioxins (polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans, PCDD/Fs) content and profile in fish from marine and fresh water in a certain water area, and to assess the dioxins intake from fish in the local people. Samples were prepared using advanced technique, confirmation and quantitative analysis of Dibenzo-p-Dioxins and Dibenzo-Furans was performed by isotope dilution HRGC/HRMS using multiple ion detection mode (MID). The average concentration of fish from marine and fresh water was 1.43pg/g wet weight and 3.43pg/g wet weight respectively, and WHO-TEQ concentration was 0.28 and 0.43pg/g wet weight respectively. The congener-specific profile dominated by OCDD and 2,3,7,8-TCDF, and the main contributor of toxicity was 1,2,3,7,8-PeCDD, 2,3,4,7,8-PeCDF, 2,3,7,8-TCDD. The exposure from fish for local people was estimated as 0.63 pg WHO-TEQ/kg bw x day. The level of PCDD/Fs in fresh water fish was higher than that of marine fish with one fold. The average PCDD/Fs concentration was lower than 1.0 pg WHO-TEQ/kg, which is the maximum limit (ML) set up by European Union.


Dopamine modulates the kinetics of ion channels gated by excitatory amino acids in retinal horizontal cells.
Upon exposure to dopamine, cultured teleost retinal horizontal cells become more responsive to the putative photoreceptor neurotransmitter L-glutamate and to its analog kainate. We have recorded unitary and whole-cell currents to determine the mechanism by which dopamine enhances ion channels activated by these agents. In single-channel recordings from cell-attached patches with agonist in the patch pipette, the frequency of 5- to 10-pS unitary events, but not their amplitude, increased by as much as 150% after application of dopamine to the rest of the cell. The duration of channel openings also increased somewhat, by 20-30%. In whole-cell experiments, agonists with and without dopamine were applied to voltage-clamped horizontal cells by slow superfusion. Analysis of whole-cell current variance as a function of mean current indicated that dopamine increased the probability of channel opening for a give agonist concentration without changing the amount of current passed by an individual channel. For kainate, noise analysis additionally demonstrated that dopamine did not alter the number of functional channels. Dopamine also increased a slow spectral component of whole-cell currents elicited by kainate or glutamate, suggesting a change in the open-time kinetics of the channels. This effect was more pronounced for currents induced by glutamate than for those induced by kainate. We conclude that dopamine potentiates the activity of horizontal cell glutamate receptors by altering the kinetics of the ion channel to favor the open state.


Angiotensin II inhibition attenuates postexercise proteinuria in rats.
An important explanatory theory for the mechanism of postexercise proteinuria is that angiotensin II could be inhibited by angiotensin converting enzyme inhibitors. Because of the kininase effect of the angiotensin converting enzyme, it is unclear whether the kallikrein-kinin system contributes to the effect of angiotensin converting enzyme inhibitors on postexercise proteinuria. The aim of this study was to evaluate any possible involvement of the kallikrein-kinin system in the therapeutic effect of angiotensin converting enzyme inhibitors on postexercise proteinuria. We evaluated urinary protein levels in exhausted rats receiving an angiotensin converting enzyme inhibitor (enalapril) or an angiotensin II type I receptor antagonist (losartan). Enalapril (30 mg/kg/day, two days) or losartan (20 mg/kg/day, two days) were given to animals using an intragastric catheter. Urinary protein levels increased (41 %) in rats which were exhausted via treadmill running (p < 0.05). In animals that received drug treatment (enalapril or losartan), but did not exercise to exhaustion, urinary protein levels were not different from the control group. Urinary protein levels were found to be significantly lower (p < 0.05) in animals which performed acute exhaustive exercise after enalapril or losartan administration, compared to rats which were exhausted without drug administration. Inhibition of postexercise proteinuria by either enalapril or losartan suggested that angiotensin II plays an important role in postexercise proteinuria, however, it appears the kallikrein-kinin system is not involved in angiotensin converting enzyme inhibitors effect.


Effect of Blade Geometry on γ' Lattice Parameter and Primary Orientation of SX Cored Turbine Blades (II).
The distributions of the lattice parameter of the γ'-phase (aγ') and angular components of the primary crystal orientation along the lines parallel to the main axis of the single-crystalline CMSX 4-cored turbine blades were studied. The studies were carried out on the regions of the blades located far from the selector and its continuer extension (CE), positioned asymmetrically relative to the blade's axis. It was found that, similarly to the regions of the blade located close to the CE (studied in part I), at the level of the blade related to the change of its cross-section, there were correlated local changes in aγ' and the angular components of the primary crystal orientation representing the bending of the dendrites. However, the correlation was less clear due to the presence of low-angle boundaries (LABs) and the intensification of the consequences of the "fanning effect" in the regions far from the CE. It was found that the range of local changes in aγ' and the angular components of the primary crystal orientation of the blade regions were influenced by both the distance from the CE and the separation of these regions from the CE by surfaces of the cooling bores. It was found that the deviation angle in the [001] direction from the blade axis increased with an increase in the distance from the CE. Based on the aγ' changes, differences in the alloying element concentration near the cooling bores were discussed.


Astrocytic inclusions in epilepsy: expanding the spectrum of filaminopathies.
We report the finding of unique astrocytic inclusions in a series of pediatric epilepsy patients, all of whom presented with seizures in their first year of life and had mild-to-moderate developmental delay. All eventually underwent surgical treatment for refractory epilepsy and, on pathological examination, were found to have distinctive, eosinophilic, globular cytoplasmic inclusions confined to cortical astrocytes. These inclusions were almost exclusively juxtanuclear, highly refractile, spared distal subpial, or perivascular astrocytic processes and were strongly and exclusively immunopositive for filamin A, an actin binding protein involved in neuronal migration. Identical inclusions have been identified and characterized in cases of Aicardi syndrome, a rare neurodevelopmental disease. The presence of the same inclusions in the cortex of epilepsy patients, some of whom had concomitant brain anomalies related to migrational problems, prompted us to consider that these patients may lie within a spectrum of disease involving dysfunction of filamin or filamin-interacting proteins. The term "filaminopathy" is tentatively proposed as a distinct pathological entity for this condition in which clinical manifestations range from epilepsy in mildly neurologically impaired patients to severe mental and physical handicap in the Aicardi syndrome. Future studies will be necessary to unravel the exact nature of the filamin A protein or gene aberrations in these patients.


Cyclodeviation in skew deviation.
We examined four patients with dorsolateral pontomedullary lesions and skew deviation, with ocular torsion of varying symmetry. In three patients, the hypotropic eye was excyclodeviated relative to the fellow eye. Observations of these patients, combined with recent evidence, suggest that cyclodeviation is a frequent component of skew deviation and may result from variable involvement of utricular, semicircular canal, and cerebelloocular pathways. Although cyclodeviation is a feature of trochlear-nerve palsies, its presence does not exclude skew deviation and underlying brainstem lesions.


Quantitative tritium autoradiography of mammalian chromosomes. I. The basic method.
A technique has been developed that allows repeated autoradiographs to be made of the isotope distribution in the chromosomes of a single cell. A series of 10 separate autoradiographs were made of a Chinese hamster diploid male metaphase cell which had been labeled with tritiated thymidine during the first 15 minutes of its DNA synthesis period in the previous interphase. Each autoradiograph had low grain densities above the chromosomes so that quantitation was feasible. The separate autoradiographs were photographically combined into a single composite in which grain images were converted to lines oriented at right angles to the chromosome axis. The line densities were then measured with a recording microdensitometer to yield graphs reflecting the isotope distribution along each chromosome. The area under each graph was directly proportional to the total number of grains counted above the corresponding chromosome in the 10 separate autoradiographs. The distribution of isotope along the chromosomes was different for each chromosome, and in some cases homologs also differed in their early labeling patterns.


Reliability of cone beam computed tomography as a biopsy-independent tool in differential diagnosis of periapical cysts and granulomas: An In vivo Study.
Differential diagnosis of periapical cysts and granulomas is required as their treatment modalities are different. The aim of this study was to evaluate the efficacy of cone beam computed tomography (CBCT) in the differential diagnosis of periapical cysts from granulomas. A single-centered observational study was carried out in the Department of Conservative Dentistry and Endodontics, Dr. R. Ahmed Dental College and Hospital, using CBCT and dental operating microscope. Forty-five lesions were analyzed using CBCT scans. One evaluator analyzed each CBCT scan for the presence of the following six characteristic radiological features: cyst like-location, shape, periphery, internal structure, effect on the surrounding structures, and cortical plate perforation. Another independent evaluator analyzed the CBCT scans. This process was repeated after 6 months, and inter- and intrarater reliability of CBCT diagnoses was evaluated. Periapical surgeries were performed and tissue samples were obtained for histopathological analysis. To evaluate the efficacy, CBCT diagnoses were compared with histopathological diagnoses, and six receiver operating characteristic (ROC) curve analyses were conducted. ROC curve, Cronbach's alpha (α) test, and Cohen Kappa (κ) test were used for statistical analysis. Both inter- and intrarater reliability were excellent (α = 0.94, κ = 0.75 and 0.77, respectively). ROC curve with regard to ≥4 positive findings revealed the highest area under curve (0.66). CBCT is moderately accurate in the differential diagnosis of periapical cysts and granulomas.


Effect of thimerosal on arrhythmia induced by coronary ligation: the involvement of ATP-dependent potassium channels.
Thiol-modifying agents induce the release of nitric oxide (NO) from endothelial epithelium and the release of reactive oxygen free radicals in the vascular system. Moreover, thiol groups are essential for the functioning of the ATP dependent potassium channel (K-ATP). The effects of thiol-modifying agents and their molecular mechanisms on arrhythmia have not been widely studied. In this study, we investigated the effect of the hydrophilic SH-group-oxidizing substance thimerosal on the arrhythmia induced by reperfusion/ischemia after coronary artery ligation in rats. We studied the possible involvement of the K-ATP and NOS on the effect of thimerosal. Thimerosal pretreatment (3, 30 mg/kg dose iv. 10 minutes before coronary occlusion) significantly decreased the length of total arrhythmia, ventricular tachycardia, and the arrhythmia score. This effect of thimerosal was reversed by the K-ATP opener pinacidil but not by the K-ATP blocker glibenclamide. The inhibition of iNOS by L-NAME did not alter the antiarrhythmic effect of thimerosal. These data clearly suggest that the antiarrhythmic effect of thimerosal is dependent upon the blockage of K-ATP.


If the pay banding system is broke, let's fix it.
The way nurses are placed in pay bands has always been contentious. Some of you will remember the introduction of the old clinical grades, which over time fell into disrepute and had to be replaced. Inevitably, a similar problem has afflicted the band 1-9 system introduced 12 years ago under the banner Agenda for Change.


How Does the Encapsulation of Porphyrinic Photosensitizers into Polymer Matrices Affect Their Self-Association and Dynamic Properties?
Photodynamic therapy (PDT) with porphyrinic photosensitizers largely relies on efficient drug formulations to prevent porphyrin aggregation and to enhance water solubility and stability in physiologic environments. In this study, we compare two polymeric carrier systems, polyvinylpyrrolidone (PVP) and block copolymer micelles (BCMs) formed by the poloxamer Kolliphor P188 (KP), for their encapsulation efficiencies of porphyrin (xPP) and chlorin e6 (xCE) derivatives. Monomerization, loading efficiency, and dynamic properties were examined by 1 H NMR spectroscopy chemical shift titration, DOSY, and T2 relaxation time measurements. Binding affinity was determined by UV/Vis spectroscopy. Both PVP and KP-BCMs were well suited to disaggregate and encapsulate amphiphilic xCE, whereas they were less efficient for the xPP compounds. PVP exhibited higher monomerization efficiency than KP-BCMs. Significant differences were found in the dynamic behavior of the carriers. PVP formed rather stable complexes with the porphyrinic compounds, whereas a dynamic equilibrium between free and bound porphyrins was found to exist in the presence of KP-BCMs. This may have a considerable impact on the pharmacokinetic properties of the corresponding delivery systems.


Role of STAT3 as a negative regulator in Mac2- binding protein expression.
Mac-2 binding protein (Mac-2BP) is a secreted glycoprotein from the culture fluid of several human cancer cells, especially breast, lung, and gastric cells. Mac-2BP plays a role in immune response and cell adhesion activity in patients with various cancer and infectious diseases. In this study, we attempted to identify the regulators of Mac-2BP expression at the transcriptional level. To determine the effect of epidermal growth factor (EGF) to Mac-2BP expression in gastric cancers, we constructed the different lengths of Mac-2BP promoter plasmids and measured the promoter activity and Mac-2BP expression. In addition to investigating the role of signal transducer and activator of transcription3 (STAT3) or human telomerase reverse transcriptase (hTERT) as a regulator of Mac-2BP, we transfected the small interfering RNA (siRNA) specific for STAT3 or hTERT, and Mac-2BP level was observed by a quantitative ELISA. EGF treatment could suppress the Mac-2BP transcription in HEK293 or gastric cancer cell lines (SNU-638 or AGS). In 5'-deleted promoter experiment, pGL3-Mac Pro-2377 transfected cells showed a decreased luciferase activity compared to pGL3-Mac Pro-2277. We also identified that (-2,366/-2,356) on Mac-2BP promoter is a putative STAT3 binding site and suppression of STAT3 with STAT3 specific siRNA increased the Mac-2BP level, suggesting the role of STAT3 as a negative regulator, in contrast to hTERT, which is known as a positive regulator. EGF signal is critical for the Mac-2BP expression, and more importantly, STAT3 could work as a negative regulator, while hTERT as a positive regulator in Mac-2BP transcription.


Preneoplastic and neoplastic changes in colonic mucosa in Crohn's disease.
In order to further substantiate the associated risk of colonic adenocarcinoma in cases of Crohn's disease, colonic mucosa from 12 patients with documented Crohn's disease was studied. All of the cases exhibited a wide spectrum of mucosal changes. These changes included the following: dilation and distortion of the crypts, cellular basophilia with decreased mucus, Paneth's cell metaplasia, variable degrees of atypia, and carcinoma in situ. These findings are consistent with the increased incidence of carcinoma of the colon in cases of Crohn's disease.


[The transporters of intestinal tract and their study methods].
The absorption of oral drug in the intestine is an important factor to determine the drug bioavailability. There are many intestinal transporters mediating drug absorption, distribution, excretion and drug-drug interaction. Understanding the transport mechanism can improve the effectiveness and safety of drug and guide clinical rational use of drugs. The in vivo and in vitro methods are used to predict the transport mechanism of drugs by intestinal transporters in the intestine. The purposes of this article are to introduce the main transporters in the intestinal tract, to explain the transport mechanism and to summarize the advantages and disadvantages of the research methods of them.


Assessment of enamel hypoplasia in a high status burial site.
Social differentiation is a characteristic of all societies, and higher social status is often associated with better nutrition and good health. Traditional archeologically inferred social status has been linked with biological evidence such as skeletal robusticity and the incidence of disease. In this regard, linear enamel hypoplasia (LEH) is considered a good indicator of health, and individuals with a high status should, at least in theory, not suffer from severe defects. In order to test this hypothesis, the prevalence and occurrence of LEH were assessed in a skeletal sample at the Fort Center, Florida, site. Located near Lake Okeechobee, this site was occupied from about A.D. 200-800, and was considered a mortuary ceremonial center. These archeological findings suggested that individuals buried there belonged to a high class and merited special mortuary rituals. Although 1,835 teeth were found, only 679 maxillary and 393 mandibular teeth were analyzed. The upper I1 and lower C are reported to be most representative for LEH, and were thus selected for further analysis. There were 45 left incisors and 48 left canines. Results indicated that about 95% of incisors and 98% of canines were affected. The occurrence of severe hypoplastic lines was much lower (between 30% and 40%). The minimum number of defects affecting the canine surpassed three, thus showing evidence of repeated stress during childhood. Hypoplasia was first observed between the ages of 1.0 and 1.5 years for incisors and between 2.0 and 2.5 years for canines. Severe defects were first noted to occur at 2.5-3.0 years of age for incisors and 3.0-3.5 years for canines. In conclusion, the high frequency of LEH in this socially elite population seems to prove that in prehistory even privileged classes were severely subjected to stress and the social stratification alone was not sufficient to buffer them from rigorous environments. Am. J. Hum. Biol. 9:213-222, 1997. © 1997 Wiley-Liss, Inc.


Angiogenesis as a target for tumor treatment.
Angiogenesis is a key step in tumor growth, invasion and metastasis. Thus, antiangiogenic therapy was postulated to be an attractive approach for antitumor treatment. Based on today's knowledge, at least three strategies for inhibition of angiogenesis are feasible: (1) inhibition of release of angiogenic factors from tumor cells and/or neutralization of angiogenic molecules that have already been released: (2) inhibition of vascular endothelial cell proliferation and migration, and (3) inhibition of the synthesis and turnover of vessel basement membrane. To date, a number of antiangiogenic agents have been identified. In animal models, treatment with angiogenesis inhibitors has proven antitumor effects. Early clinical experience with angiogenic inhibitors indicates that optimal antiangiogenic therapy in the future is likely to be based on the long-term administration to cancer patients in adjunct to surgery, radiotherapy and conventional chemotherapy.


A virtual reality simulation of a novel way to illuminate the surgical field - A feasibility study on the use of automated lighting systems in the operating theatre.
Surgical lighting systems have to be re-adjusted manually during surgery by the medical personnel. While some authors suggest that interaction with a surgical lighting system in the operating room might be a distractor, others support the idea that manual interaction with the surgical lighting system is a hygiene problem as pathogens might be present on the handle. In any case, it seems desirable to develop a novel approach to surgical lighting that minimizes the need for manual interaction during a surgical procedure. We investigated the effect of manual interaction with a classical surgical lighting system and simulated a proposed novel design of a surgical lighting system in a virtual reality environment with respect to performance accuracy as well as cognitive load (measured by electroencephalographical recordings). We found that manual interaction with the surgical lights has no effect on the quality of performance, yet for the price of a higher mental effort, possibly leading to faster fatigue of the medical personnel in the long run. Our proposed novel surgical lighting system negates the need for manual interaction and leads to a performance quality comparable to the classical lighting system, yet with less mental load for the surgical personnel.


Mortality salience and morality: thinking about death makes people less utilitarian.
According to the dual-process model of moral judgment, utilitarian responses to moral conflict draw on limited cognitive resources. Terror Management Theory, in parallel, postulates that mortality salience mobilizes these resources to suppress thoughts of death out of focal attention. Consequently, we predicted that individuals under mortality salience would be less likely to give utilitarian responses to moral conflicts. Two experiments corroborated this hypothesis. Experiment 1 showed that utilitarian responses to non-lethal harm conflicts were less frequent when participants were reminded of their mortality. Experiment 2 showed that the detrimental effect of mortality salience on utilitarian conflict judgments was comparable to that of an extreme concurrent cognitive load. These findings raise the question of whether private judgment and public debate about controversial moral issues might be shaped by mortality salience effects, since these issues (e.g., assisted suicide) often involve matters of life and death.


SLX4 Prevents GEN1-Dependent DSBs During DNA Replication Arrest Under Pathological Conditions in Human Cells.
SLX4 is a versatile protein serving as docking for multiple structure-specific endonucleases during DNA repair, however, little is known about its function at demised replication forks. Using RNAi or FA-P cells complemented with SLX4 mutants that abrogate interaction with MUS81 or SLX1, we show that SLX4 cooperates with MUS81 to introduce DSBs after replication stress but also counteracts pathological targeting of demised forks by GEN1. Such unexpected function of SLX4 is unrelated to interaction with endonucleases, but concerns the physical presence of the protein. Strikingly, ectopic expression of the Holliday junction-binding protein RuvA inhibits DSBs in SLX4-deficient cells by preventing GEN1 chromatin-association, and rescues proliferation and genome integrity upon replication stress. Altogether, our results indicate that SLX4 is crucial to prevent accidental processing of Holliday junction-like intermediates at demised forks also suggesting that spontaneous genome instability in FA-P cells may derive, at least partially, from unscheduled action of GEN1 in S-phase.


Expression of the metabotropic glutamate receptor, mGluR4a, in the taste hairs of taste buds in rat gustatory papillae.
Taste-mGluR4, cloned from taste tissues, is a truncated variant of brain-expressed mGluR4a (brain-mGluR4), and is known to be a candidate for the receptor involved in the umami taste sense. Although the expression patterns of taste- and brain-mGluR4 mRNAs have been demonstrated, no mention has so far been made of the expression of these two mGluR4 proteins in taste tissues. The present study examined the expression of taste-mGluR4 and brain-mGluR4 proteins in rat taste tissues by using a specific antibody for mGluR4a which shared a C-terminus of both taste- and brain-mGluR4, for immunoblot analysis and immunohistochemistry. Immunoblot analysis showed that both brain-mGluR4 and taste-mGluR4 were expressed in the taste tissues. Taste-mGluR4 was not detected in the cerebellum. The immunoreactive band for brain-mGluR4 protein was much stronger than that for taste-mGluR4 protein. In the cryosections of fungiform, foliate and circumvallate papillae, the antibody against taste-mGluR4 exhibited intense labeling of the taste pores and taste hairs in all the taste buds of gustatory papillae examined; the immunoreaction to the antibody against brain-mGluR4 was more intense at the same sites of the taste buds. The portions of the taste bud cells below the taste pore and surrounding keratinocytes did not show any immunoreactivities. The results of the present study strongly suggest that, in addition to taste-mGluR4, brain-mGluR4 may function even more importantly than the former as a receptor for glutamate, i.e. the umami taste sensation.


Secular Trends of Overweight and Obesity in Young Southern Californians 2008-2013.
To investigate secular trends in pediatric obesity in Southern California between 2008 and 2013. In a population-based cohort study, measured weight and height were extracted from electronic health records of 1,331,931 patients aged 2-19 years who were enrolled in an integrated prepaid health plan between 2008 and 2013. Outcomes were the prevalence of overweight and obesity (body mass index-for-age ≥85th percentile). The prevalence of obesity was 19.1% in 2008 and decreased by 1.6% (95% CI, 1.7%-1.5%) by 2013, corresponding to a relative decline of 8.4%. A significant decline was observed across all ages, sexes, races, and socioeconomic groups, but the magnitude of the decrease varied. The relative decline in obesity was stronger in boys (-9.3%) than in girls (-7.2%), in children aged 2-5 years (-15.4%) and 6-11 years (-11.8%) than in adolescents aged 12-19 years (-4.5%), and in whites (-12.6%) and Asians (-12.2%) than in Hispanics (-6.9%) and African Americans (-7.5%). Secular trends from this large population-based cohort suggest that overweight and obesity in boys and girls are declining across age and racial/ethnic groups. However, the declines are less pronounced in adolescents compared with children, in girls, and in some minority groups. Programs addressing childhood obesity may need to be targeted.


Bias correction for estimates from linear excess relative risk models in small case-control studies.
Epidemiologic studies conducted to quantify the impact of radiation dose d on an outcome typically model the hazard ratio (HR) for association using a linear term, HR(d)=1+βd , via a linear excess relative risk (ERR) model, based on biological considerations. To study associations of risk of a second cancer with radiation treatment for a first cancer, several nested case-control designs to estimate β have been proposed that use refined doses received by different locations in the organ of interest. Here we first evaluated the small sample bias in maximum likelihood estimates of β for the linear ERR model using location-specific radiation doses in simulations. As we found substantial upward bias for studies of realistic sample sizes (more than 50% relative bias for studies with 75 cases), we also proposed and investigated several approaches to correct this bias. We studied first and second order jackknife bias corrections and we derived a modified set of score functions under retrospective case-control sampling, from which we directly obtained bias-corrected estimates. In simulations based on doses from a study of stomach cancer among testicular cancer survivors and synthetically generated data, neither the first nor second order jackknife bias correction performed well. Estimates based on the modified score equations corrected the bias much better, albeit not completely, and were numerically much more stable.


Legionella pneumophila 6S RNA optimizes intracellular multiplication.
Legionella pneumophila is a Gram-negative opportunistic human pathogen that infects and multiplies in a broad range of phagocytic protozoan and mammalian phagocytes. Based on the observation that small regulatory RNAs (sRNAs) play an important role in controlling virulence-related genes in several pathogenic bacteria, we attempted to identify sRNAs expressed by L. pneumophila. We used computational prediction followed by experimental verification to identify and characterize sRNAs encoded in the L. pneumophila genome. A 50-mer probe microarray was constructed to test the expression of predicted sRNAs in bacteria grown under a variety of conditions. This strategy successfully identified 22 expressed RNAs, out of which 6 were confirmed by northern blot and RACE. One of the identified sRNAs is highly expressed in postexponential phase, and computational prediction of its secondary structure reveals a striking similarity to the structure of 6S RNA, a widely distributed prokaryotic sRNA, known to regulate the activity of sigma(70)-containing RNA polymerase. A 70-mer probe microarray was used to identify genes affected by L. pneumophila 6S RNA in stationary phase. The 6S RNA positively regulates expression of genes encoding type IVB secretion system effectors, stress response genes such as groES and recA, as well as many genes involved in acquisition of nutrients and genes with unknown or hypothetical functions. Deletion of 6S RNA significantly reduced L. pneumophila intracellular multiplication in both protist and mammalian host cells, but had no detectable effect on growth in rich media.


[Effect of Fitofron on the persistence factors of opportunistic pathogens in urine isolated from patients with urinary tract infections].
To perform an experimental evaluation of the effect of Phytofron, used for the treatment of urinary tract infections, on the ability of opportunistic pathogens to inactivate innate immunity factors (lysozyme, pro- and anti-inflammatory cytokines) and form biofilms. In vitro experiments were carried out on clinical isolates from urine of patients with pyelonephritis and cystitis: Escherichia coli, Staphylococcus aureus, S. haemolyticus, S. epidermidis, Enterococcus faecalis. The effect of Fitofron NPO FarmVILAR (Russia) on the anticytokine activity of bacteria against regulatory cytokines (IL4, IL6, IL8, TNF and IL17A) was determined by enzyme immunoassay, while anti-lysozyme trait and the ability to form biofilms was evaluated by the photometric method. The inhibitory effect of Fitofron on the ability of opportunistic microorganisms to inactivate innate immunity factors (lysozyme) and form biofilms, as well as the predominant inhibition of the studied cytokines, was experimentally established. Inhibition of the persistence factors of opportunistic pathogens by Fitofron, documented in vitro, can be considered as one of the possible mechanisms of its biological activity in vivo.


A systematic review of methodologies, endpoints, and outcome measures in randomized trials of radiation therapy-induced nausea and vomiting.
Clinical trials in radiation therapy-induced nausea and vomiting (RINV) appear to have varied methodologies, endpoints, and outcome measures. This complicates trial comparisons, weakens practice guideline recommendations, and contributes to variability in supportive care patterns of practice. We systematically reviewed RINV trials to describe and compare their pertinent design features. Ovid versions of the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, EMBASE, and MEDLINE to January/February 2017 were searched for adult phase III trials of RINV management strategies. Key abstracted data included trial interventions and eligibility criteria, standard radiation therapy (RT) metrics, symptom assessment procedures, symptom definitions and grading systems, pre-specified and reported endpoints, and other outcome measures. From 1166 references identified in the initial database search, we selected 34 trials for analysis that collectively randomized 4529 patients (median 61, range 11-1492). Twenty-eight trials (82%) were published prior to the year 2000. Twenty-seven trials (79%) involved multiple fraction RT and 7 (21%) single fraction RT. Twenty-four trials (71%) evaluated prophylactic interventions, 9 (26%) rescue interventions, and 1 trial did not specify. Thirty-three trials (97%) evaluated pharmacologic interventions. Twenty trials (59%) had patient report symptoms, 5 (15%) healthcare professionals or researchers, and 10 (29%) did not specify. Nausea was not defined in any trial but was reported as a stand-alone symptom in 26 trials (76%) and was graded in 20 (59%), with categorical qualitative scales being the most common method. Vomiting was defined in 3 trials (9%), was reported as a stand-alone symptom in 17 (47%), and was graded in 7 (21%), with continuous numerical scales being the most common method. Retching was defined in 3 trials, was not reported as a stand-alone symptom in any trial, and was graded in 1 (3%). Twenty-one trials (62%) created compound symptom measures that combined individual symptoms. Fifteen trials (44%) reported "emetic episode/event" measures but only 9 defined them. Seventeen trials (50%) reported complicated endpoints (e.g., "response," "control," "success") that combined multiple symptom or compound symptom measures, but 7 did not define them comprehensively. Ten trials (29%) defined a primary endpoint a priori. Methodologies, endpoints, and outcome measures varied considerably among 34 randomized trials in RINV.


Physical activity and lipids and lipoproteins in American Indians ages 45-74.
The Strong Heart Study is a study of cardiovascular disease and its risk factors among American Indian men and women aged 45-74 yr representative of 13 communities from Arizona (AZ), Oklahoma (OK), and North/South Dakota (N/SD). This investigation sought to characterize the amount and type of physical activity and to determine the association between activity and lipids in this population. Total physical activity (occupational plus leisure) was assessed with a validated questionnaire. Men and women from OK (21 +/- 19 and 16 +/- 15 h.wk-1; respectively) and N/SD (23 +/- 21 and 17 +/- 17 h.wk-1; respectively) had activity levels that were similar if not lower than the U.S. population with the AZ communities (17 +/- 21 and 10 +/- 14 h.wk-1; respectively) being substantially lower than the other two communities. Total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), and low density lipoprotein cholesterol (LDL-c) levels were lower than the U.S. population. For most of the population (diabetic men and nondiabetic men and women), activity was significantly associated (P < 0.05) with apolipoprotein (apo) AI after controlling for covariates. With levels of activity as low if not lower than the general U.S. population coupled with high prevalence of obesity and diabetes, efforts to increase physical activity in American Indians are warranted. Hopefully these increases in activity will result in favorable lipid changes as well as decreasing the risk of diabetes which is epidemic in these populations.


Intraoperative neuromonitoring of hypogastric plexus branches during surgery for rectal cancer - preliminary report.
The aim of this study was to present our preliminary experience with intraoperative neuromonitoring during rectal resection. We qualified 4 patients (2 women, 2 men; age 42 - 53 years) with rectal cancer for surgery with intraoperative neuromonitoring. In all patients, functional tests of the anorectal area were performed before surgery. Action potentials from the sphincter complex in response to nerve fiber stimulation were recorded with electrodes implanted before surgery. Moreover, we inserted a standard, 18FR Foley's urinary catheter to which a T-tube was connected to allow urine outflow and measurement of pressure changes in the bladder induced by detrusor contractions during stimulation. Setting up neuromonitoring prolonged surgery time by 30 to 40 minutes, or even by 60 to 80 minutes in the case of the first two patients. Neuromonitoring itself took additional 20 to 30 minutes during surgery. In all patients, we stimulated branches of the inferior hypogastric plexus in their anatomical position during dissection. In three patients, we evoked responses both from the bladder and the sphincter in all planes of stimulation. In one patient, there was no response from the left side of the bladder, and in the same patient, we observed symptoms of neurogenic bladder. Based on the available literature and our own experience, we state that monitoring of bladder pressure and electromyographic signals from rectal sphincters enables visualization and preservation of autonomic nervous system structures, both sympathetic and parasympathetic. Intraoperative signals seem to be correlated with clinical presentation and functional examinations after surgery. In order to objectify our results, it is necessary to perform functional examinations before and after surgery in a larger group of patients.


Macrophage Activation Marker Soluble CD163 Associated with Fatal and Severe Ebola Virus Disease in Humans1.
Ebola virus disease (EVD) is associated with elevated cytokine levels, and hypercytokinemia is more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of 2 rheumatologic disorders known as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, which are characterized by macrophage and T-cell activation. An evaluation of 2 cohorts of patients with EVD revealed that a marker of macrophage activation (sCD163) but not T-cell activation (sCD25) was associated with severe and fatal EVD. Furthermore, substantial immunoreactivity of host tissues to a CD163-specific antibody, predominantly in areas of extensive immunostaining for Ebola virus antigens, was observed in fatal cases. These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed antiinflammatory therapies could be beneficial in the treatment of EVD.


Fusobacterium nucleatum Aggravates the Progression of Colitis by Regulating M1 Macrophage Polarization via AKT2 Pathway.
Disordered intestinal flora and discordant immune response are associated with the development of ulcerative colitis (UC). Recent work has described the ability of macrophages to undergo repolarization toward a proinflammatory M1 or anti-inflammatory M2 phenotype in response to particular bacterium-derived signals. Fusobacterium nucleatum (F. nucleatum, Fn) is a species of intestinal commensal bacteria with potential pathogenicity, but its association with UC and how it may contribute to progression of UC is largely unknown. In this study, we provide new evidence that F. nucleatum accumulated heavily in the intestine of UC patients and was accompanied by the secretion of IFN-γ and the skewing of M1 macrophages. Mechanistically, our data showed that F. nucleatum aggravated dextran sodium sulfate (DSS)-induced colitis in the production of Th1-related cytokines IFN-γ through the AKT2 signaling pathway in vitro and in vivo. To further confirm the disease-relevance of these shifts in macrophage repolarization in response to F. nucleatum, stimulated bone marrow-derived macrophages (BMDMs) were transferred into recipient mice with DSS colitis. This transfer resulted in increased disease activity and inflammatory cytokine production. Taken together, we show clearly that F. nucleatum can promote the progression of UC via proinflammatory M1 macrophage skewing, and targeting F. nucleatum or AKT2 signaling may be a viable means of blocking development of UC.


Recognition of variant HIV-1 epitopes from diverse viral subtypes by vaccine-induced CTL.
Recognition by CD8(+) T lymphocytes (CTL) of epitopes that are derived from conserved gene products, such as Gag and Pol, is well documented and conceptually supports the development of epitope-based vaccines for use against diverse HIV-1 subtypes. However, many CTL epitopes from highly conserved regions within the HIV-1 genome are highly variable, when assessed by comparison of amino acid sequences. The TCR is somewhat promiscuous with respect to peptide binding, and, as such, CTL can often recognize related epitopes. In these studies, we evaluated CTL recognition of five sets of variant HIV-1 epitopes restricted to HLA-A*0201 and HLA-A*1101 using HLA transgenic mice. We found that numerous different amino acid substitutions can be introduced into epitopes without abrogating their recognition by CTL. Based on our findings, we constructed an algorithm to predict those CTL epitopes capable of inducing responses in the HLA transgenic mice to the greatest numbers of variant epitopes. Similarity of CTL specificity for variant epitopes was demonstrated for humans using PBMC from HIV-1-infected individuals and CTL lines produced in vitro using PBMC from HIV-1-uninfected donors. We believe the ability to predict CTL epitope immunogenicity and recognition patterns of variant epitopes can be useful for designing vaccines against multiple subtypes and circulating recombinant forms of HIV-1.


[Vasodilator drugs that act by stimulating guanylate cyclase in vascular smooth muscle].
Many exogenous and endogenous vasodilator substances produce their effects by stimulation of guanylate cyclase in vascular smooth muscle and increasing cyclic 3',5'-guanosine monophosphate (cGMP) levels. Activation of such enzyme leads to vasodilatation. Possibly as a consequence of a change in the pattern of protein phosphorylation, including dephosphorylation of the light chain myosin and of a decrease in the bioavailability of free calcium. Guanylate cyclase exists in two different forms in the vascular smooth muscle cells: a cytosolic (soluble) and the other associated to membranes (particulate). The nitro vasodilators and vasodilators with endothelium-dependent activity, act by main stimulation of the soluble guanylate cyclase, while the atrial natriuretic factor acts specifically on the particulate form of the enzyme. Guanylate cyclase represents the final path in the vasodilatation induced by diverse endogenous and exogenous substances, an aspect that has created a great interest among investigators due to its possible physiological, physiopathological and therapeutic implications. The more relevant aspects related with the mechanism of action of this numerous group of drugs are deeply analyzed in the present review.


Circadian neuron feedback controls the Drosophila sleep--activity profile.
Little is known about the ability of Drosophila circadian neurons to promote sleep. Here we show, using optogenetic manipulation and video recording, that a subset of dorsal clock neurons (DN1s) are potent sleep-promoting cells that release glutamate to directly inhibit key pacemaker neurons. The pacemakers promote morning arousal by activating these DN1s, implying that a late-day feedback circuit drives midday siesta and night-time sleep. To investigate more plastic aspects of the sleep program, we used a calcium assay to monitor and compare the real-time activity of DN1 neurons in freely behaving males and females. Our results revealed that DN1 neurons were more active in males than in females, consistent with the finding that male flies sleep more during the day. DN1 activity is also enhanced by elevated temperature, consistent with the ability of higher temperatures to increase sleep. These new approaches indicate that DN1s have a major effect on the fly sleep-wake profile and integrate environmental information with the circadian molecular program.


From laboratory bench to benchmark: technology transfer in laboratory medicine.
Life Sciences research, enhancing the occurrence of innovation, is able to impact clinical decision-making, both at diagnosis and therapy. Indeed, starting from the knowledge of specific needs and of technical-scientific demands, researchers can conceive and experiment innovative solutions. Despite these strengths, transferring research to the market in Life Sciences shows considerable criticalities. The aim of this paper is to provide concrete evidences on the processes of technology transfer based on the exploitation of the results obtained by KronosDNAsrl, an academic spin-off focused on reproductive medicine. Different tools were used to evaluate the technical feasibility (validation of the results obtained with the prototype) and to manage the technology transfer process of One4Two®. The different analyses we carried out showed the feasibility of the proposed solution. As a result, the One4Two® prototype has been developed and validated. Here, we provide a strength of evidences on how knowledge obtained by translational research on "bench" can be used to be transferred to the market on "benchmark" enabling innovation in Laboratory Medicine. In addition, the model described for One4Two® can be easily transferred to other products.


Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma.
Hemangioma (HA) is one of the most common benign vascular tumors among children. Propranolol is used as the first-line treatment for hemangioma and is a non-selective blocker of the β-adrenergic receptor. β-elemene is a compound extracted from Rhizoma zedoariae and has been approved for the treatment of tumors in clinical practice. However, the combinatorial effects of β-elemene and propranolol in the treatment of HA remains unclear. This study explored the combinative effects and mechanisms of β-elemene and propranolol using hemangioma-derived endothelial cells (HemECs). Cytotoxic assays showed that the combinatorial treatment of β-elemene and propranolol did not increase the cytotoxic effects of HemECs. Furthermore, functional analysis showed that the combinatorial treatment with β-elemene and propranolol significantly inhibited the proliferation, migration, and tube formation of the HemECs compared to the single treatment regimens. Mechanistic analysis showed that combinative treatment with β-elemene and propranolol synergistically down-regulated the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor-A (HIF-1-α/VEGFA) signaling pathway. Additionally, in a xenograft tumor model, angiogenesis in the combinatorial treatment group was significantly lower than in the control, propranolol, and β-elemene treatment alone groups. Our results suggest that β-elemene combined with propranolol can significantly inhibit the proliferation, migration, and tube formation of HemECs via synergistically down-regulating the HIF-1-α/VEGFA signaling pathway without increasing any cytotoxic side effects.


Nodular type and older age as the most significant associations of thick melanoma in Victoria, Australia.
To explore the clinical associations of thick melanoma and to compare the clinicopathological variables of nodular and superficial spreading types. Cross-sectional study of all invasive primary melanomas recorded by the Victorian Cancer Registry for 1998 and those reviewed by the Victorian Melanoma Service between October 1, 1994, and April 31, 1999. Population-based cancer registry and public hospital-based multidisciplinary melanoma clinic. This study included 1422 patients recorded by the Victorian Cancer Registry and 674 patients who had attended the Victorian Melanoma Service; unclassifiable tumor types were excluded, leaving 1144 and 645 patients, respectively, eligible for analysis. Melanomas were categorized by thickness into thin (< or =1 mm), intermediate (>1-3 mm), and thick (>3 mm) and compared according to patient age, sex, and tumor type and site. Superficial spreading and nodular types were also compared in this manner. Use of the Victorian Melanoma Service database enabled a more comprehensive analysis of historical and phenotypic characteristics. Thick melanoma was predominantly nodular, occurring in older men, mostly on the head and neck and associated with fewer nevi. Nodular melanoma was thicker and found mostly on the lower limbs or head and neck; it had a greater association with a history of solar keratoses than did superficial spreading melanoma. Nodular type and older age are the most significant associations of thick melanoma.


Exosomal mRNAs for Angiogenic-Osteogenic Coupled Bone Repair.
Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone regeneration in rats with challenging femur critical-size defects are introduced. Abundant t-sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track-etched membrane (TM-nanoEP) to deliver plasmid DNAs to human adipose-derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t-sEVs for enhanced angiogenic-osteogenic regeneration. Localized and controlled release of t-sEVs within the PEGS-A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs.


Concurrent Dual-Contrast Enhancement Using Fe3O4 Nanoparticles to Achieve a CEST Signal Controllability.
Traditional T2 magnetic resonance imaging (MRI) contrast agents have defects inherent to negative contrast agents, while chemical exchange saturation transfer (CEST) contrast agents can quantify substances at trace concentrations. After reaching a certain concentration, iron-based contrast agents can "shut down" CEST signals. The application range of T2 contrast agents can be widened through a combination of CEST and T2 contrast agents, which has promising application prospects. The purpose of this study is to develop a T2 MRI negative contrast agent with a controllable size and to explore the feasibility of dual contrast enhancement by combining T2 with CEST contrast agents. The study was carried out in vitro with HCT-116 human colon cancer cells. A GE SIGNA Pioneer 3.0 T medical MRI scanner was used to acquire CEST images with different saturation radio-frequency powers (1.25/2.5/3.75/5 μT) by 2D spin echo-echo planar imaging (SE-EPI). Magnetic resonance image compilation (MAGiC) was acquired by a multidynamic multiecho 2D fast spin-echo sequence. The feasibility of this dual-contrast enhancement method was assessed by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, dynamic light scattering, ζ potential analysis, inductively coupled plasma, X-ray photoelectron spectroscopy, X-ray powder diffraction, vibrating-sample magnetometry, MRI, and a Cell Counting Kit-8 assay. The association between the transverse relaxation rate r2 and the pH of the iron-based contrast agents was analyzed by linear fitting, and the linear relationship between the CEST effect in different B1 fields and pH was analyzed by the ratio method. Fe3O4 nanoparticles (NPs) with a mean particle size of 82.6 ± 22.4 nm were prepared by a classical process, and their surface was successfully modified with -OH active functional groups. They exhibited self-aggregation in an acidic environment. The CEST effect was enhanced as the B1 field increased, and an in vitro pH map was successfully plotted using the ratio method. Fe3O4 NPs could stably serve as reference agents at different pH values. At a concentration of 30 μg/mL, Fe3O4 NPs "shut down" the CEST signals, but when the concentration of Fe3O4 NPs was less than 10 μg/mL, the two contrast agents coexisted. The prepared Fe3O4 NPs had almost no toxicity, and when their concentration rose to 200 μg/mL at pH 6.5 or 7.4, they did not reach the half-maximum inhibitory concentration (IC50). Fe3O4 magnetic NPs with a controllable size and no toxicity were successfully synthesized. By combining Fe3O4 NPs with a CEST contrast agent, the two contrast agents could be imaged simultaneously; at higher concentrations, the iron-based contrast agent "shut down" the CEST signal. An in vitro pH map was successfully plotted by the ratio method. CEST signal inhibition can be used to realize the pH mapping of solid tumors and the identification of tumor active components, thus providing a new imaging method for tumor efficacy evaluation.


Draft Genome Sequence of Corynebacterium pseudotuberculosis Strain PA06 Isolated from a Subauricular Abscess in an Ovine Host.
We report here the draft genome sequence of Corynebacterium pseudotuberculosis PA06, isolated from a subauricular abscess in an ovine host. C. pseudotuberculosis is a worldwide pathogen of small and large ruminants. The genome comprises 2,320,074 bp, with a G+C content of 52.2%, 2,195 coding sequences, 48 tRNAs, and three rRNAs.


Effect of nimodipine on the cognitive dysfunction induced by phenytoin and valproate in rats.
Anticonvulsant effects of phenytoin (PHT) and valproate (VPA) were studied alone and in combination with nimodipine (NMD) against maximal electroshock (MES)-induced seizures in rats. PHT and VPA induce cognitive deficit in terms of long-term memory loss. The effect of NMD on the cognitive deficit induced by PHT and VPA was studied through the step-through passive avoidance test (PAT). It was seen that there was a potentiation of antielectroshock effect of PHT and VPA when NMD at a dose of 4 mg/kg was combined with PHT or VPA. NMD reversed the long-term memory loss induced by PHT and VPA in the PAT.


A heuristic multi-criteria classification approach incorporating data quality information for choropleth mapping.
Despite conceptual and technology advancements in cartography over the decades, choropleth map design and classification fail to address a fundamental issue: estimates that are statistically indifferent may be assigned to different classes on maps or vice versa. Recently, the class separability concept was introduced as a map classification criterion to evaluate the likelihood that estimates in two classes are statistical different. Unfortunately, choropleth maps created according to the separability criterion usually have highly unbalanced classes. To produce reasonably separable but more balanced classes, we propose a heuristic classification approach to consider not just the class separability criterion but also other classification criteria such as evenness and intra-class variability. A geovisual-analytic package was developed to support the heuristic mapping process to evaluate the trade-off between relevant criteria and to select the most preferable classification. Class break values can be adjusted to improve the performance of a classification.


DNA/Ag Nanoparticles as Antibacterial Agents against Gram-Negative Bacteria.
Silver (Ag) nanoparticles were produced using DNA extracted from salmon milt as templates. Particles spherical in shape with an average diameter smaller than 10 nm were obtained. The nanoparticles consisted of Ag as the core with an outermost thin layer of DNA. The DNA/Ag hybrid nanoparticles were immobilized over the surface of cotton based fabrics and their antibacterial efficiency was evaluated using E. coli as the typical Gram-negative bacteria. The antibacterial experiments were performed according to the Antibacterial Standard of Japanese Association for the Functional Evaluation of Textiles. The fabrics modified with DNA/Ag nanoparticles showed a high enough inhibitory and killing efficiency against E. coli at a concentration of Ag ≥ 10 ppm.


Obesity and high blood pressure of 12-hour night shift female clean-room workers.
The 12 h shift schedule is widely used in clean rooms for electronic semiconductor production in Taiwan. This study investigated the associations of obesity and metabolic syndrome (MetS) components among women working in a semiconductor manufacturing factory in North Taiwan. Workers were divided into four groups according to their work schedules and duties (i.e., office workers, day workers, fixed 12 h day shift, and fixed 12 h night shiftworkers). The subjects comprised 1838 women who voluntarily attended a health examination between August 2006 and November 2006. Their mean (+/-SD) age was 33.6 (+/-7.1) yrs and their mean duration of work was 7.4 (+/-5.2) yrs. Each subject's health-related behaviors, body mass index, and MetS components were measured and analyzed using multivariate logistic regression. Obesity and MetS were defined according to World Health Organization criteria for Asian populations and the National Cholesterol Educational Program and Adult Treatment Panel III Guidelines, respectively. The results showed that women working in the clean room on fixed 12 h night shifts had significantly elevated odds ratios for obesity (OR, 2.7; 95% CI, 1.6-4.5), central obesity (OR, 2.9; 95% CI, 1.7-5.1), and high blood pressure (OR, 2.3; 95% CI, 1.2-4.4) compared to female office workers; these results persisted after adjusting for age, smoking, drinking, education, and duration of work. We did not find any significant differences in triglyceride and high-density lipoprotein cholesterol among women working different schedules. We conclude that working fixed 12 h night shifts was associated with an increased odds ratio for obesity, central obesity, and high blood pressure among clean-room women workers. Weight reduction and blood pressure control programs should be implemented in the workplace for women working fixed 12 h night shifts.


Integration of acoustical information in the perception of impacted sound sources: the role of information accuracy and exploitability.
Sound sources are perceived by integrating information from multiple acoustical features. The factors influencing the integration of information are largely unknown. We measured how the perceptual weighting of different features varies with the accuracy of information and with a listener's ability to exploit it. Participants judged the hardness of two objects whose interaction generates an impact sound: a hammer and a sounding object. In a first discrimination experiment, trained listeners focused on the most accurate information, although with greater difficulty when perceiving the hammer. We inferred a limited exploitability for the most accurate hammer-hardness information. In a second rating experiment, listeners focused on the most accurate information only when estimating sounding-object hardness. In a third rating experiment, we synthesized sounds by independently manipulating source properties that covaried in Experiments 1 and 2: sounding-object hardness and impact properties. Sounding-object hardness perception relied on the most accurate acoustical information, whereas impact-properties influenced more strongly hammer hardness perception. Overall, perceptual weight increased with the accuracy of acoustical information, although information that was not easily exploited was perceptually secondary, even if accurate.


Activatable NIR Fluorescence/MRI Bimodal Probes for in Vivo Imaging by Enzyme-Mediated Fluorogenic Reaction and Self-Assembly.
Stimuli-responsive in situ self-assembly of small molecules to form nanostructures in living subjects has produced promising tools for molecular imaging and tissue engineering. However, controlling the self-assembly process to simultaneously activate multimodality imaging signals in a small-molecule probe is challenging. In this paper, we rationally integrate a fluorogenic reaction into enzyme-responsive in situ self-assembly to design small-molecule-based activatable near-infrared (NIR) fluorescence and magnetic resonance (MR) bimodal probes for molecular imaging. Using alkaline phosphatase (ALP) as a model target, we demonstrate that probe (P-CyFF-Gd) can be activated by endogenous ALP overexpressed on cell membranes, producing membrane-localized assembled nanoparticles (NPs) that can be directly visualized by cryo-SEM. Simultaneous enhancements in NIR fluorescence (>70-fold at 710 nm) and r1 relaxivity (∼2.3-fold) enable real-time, high-sensitivity, high-spatial-resolution imaging and localization of the ALP activity in live tumor cells and mice. P-CyFF-Gd can also delineate orthotopic liver tumor foci, facilitating efficient real-time, image-guided surgical resection of tumor tissues in intraoperative mice. This strategy combines activatable NIR fluorescence via a fluorogenic reaction and activatable MRI via in situ self-assembly to promote ALP activity imaging, which could be applicable to design other activatable bimodal probes for in vivo imaging of enzyme activity and locations in real time.


[Quantitative study of serum protein loss into the alimentary tract in patients with gastric cancer].
Quantitative study of serum protein loss into the alimentary tract from the tumor of gastric cancer using 111Indium-transferrin (111In-Tf) was performed. Gamma counting of 111In-Tf excreted in feces and 111In-Tf scintigram were performed in 24 patients with gastric cancer and 10 controls. Transferrin was labelled by incubating 111MBq (3mCi) of 111In chloride with approximately 13ml of patient plasma in vitro. After intravenous injection of 111In-Tf, an aliquot was weighed and its radioactivity was measured in a gamma-counter. Feces were collected every 24hrs up to 72hrs. Then 111In in the feces was calculated as a percentage of the injection dose. 111In excreted in the feces within 72hrs in patients with gastric cancer was 3.71 +/- 3.87% (mean +/- SD), which was significantly higher than the 0.48 +/- 0.26% in 10 controls. 111In in feces correlated the area of the tumor in the stomach (p < 0.001). In 18 patients positive scan was recognized and was localized the protein loss in the cavity of the stomach within 10 minutes. Positive scan was found to move along the intestine successively. 111In-Tf can be useful in assessing of hypoproteinemia of gastric cancer.


Fluorescence spectrometric study on the interactions of Isoprocarb and sodium 2-isopropylphenate with bovine serum albumin.
The binding interaction of the pesticide Isoprocarb and its degradation product, sodium 2-isopropylphenate, with bovine serum albumin (BSA) was studied by spectrofluorimetry under simulated physiological conditions. Both Isoprocarb and sodium 2-isopropylphenate quenched the intrinsic fluorescence of BSA. This quenching proceeded via a static mechanism. The thermodynamic parameters (DeltaH(o), DeltaS(o) and DeltaG(o)) obtained from the fluorescence data measured at two different temperatures showed that the binding of Isoprocarb to BSA involved hydrogen bonds and that of sodium 2-isopropylphenate to BSA involved hydrophobic and electrostatic interactions. Synchronous fluorescence spectroscopy of the interaction of BSA with either Isoprocarb or sodium 2-isopropylphenate showed that the molecular structure of the BSA was changed significantly, which is consistent with the known toxicity of the pesticide, i.e., the protein is denatured. The sodium 2-isopropylphenate, was estimated to be about 4-5 times more toxic than its parent, Isoprocarb. Synchronous fluorescence spectroscopy and the resolution of the three-way excitation-emission fluorescence spectra by the PARAFAC method extracted the relative concentration profiles of BSA, Isoprocab and sodium 2-isopropylphenate as a function of the added sodium 2-isopropylphenate. These profiles showed that the degradation product, sodium 2-isopropylphenate, displaced the pesticide in a competitive reaction with the BSA protein.