Genetic diversity of the endangered Chinese endemic herb Primulina tabacum (Gesneriaceae) revealed by amplified fragment length polymorphism (AFLP).
Primulina tabacum Hance, is a critically endangered perennial endemic to limestone area in South China. Genetic variability within and among four extant populations of this species was assessed using AFLP markers. We expected a low genetic diversity level of this narrowly distributed species, but our results revealed that a high level of genetic diversity remains, both at population level (55.5% of markers polymorphic, H (E) = 0.220, I (S) = 0.321), and at species level (P = 85.6% of markers polymorphic, H (E) = 0.339, I (S) = 0.495), probably resulting from its refugial history and/or breeding system. High levels of genetic differentiation among populations was apparent based on Nei's genetic diversity analysis (G (st)=0.350). The restricted gene flow between populations is a potential reason for the high genetic differentiation. The population genetic diversity of P. tabacum revealed here has clear implications for conservation and management. To maintain present levels of genetic diversity, in situ conservation of all populations is necessary.


Haemostasis at low heparin dosage during cardiopulmonary bypass with heparin-coated circuits in pigs.
Cardiopulmonary bypass (CPB) causes activation of cascade systems. Although heparin coating of CPB circuits improves biocompatibility, the effects on coagulation remain controversial. Theoretically, heparin coating should permit the reduction of systemic anticoagulation during CPB. We investigated influences on haemostatic variables in animal CPB, comparing heparin-coated circuits and reduced systemic heparinization (group HC) with uncoated circuits and full heparinization (group C). Twenty pigs underwent 2-h CPB. Seven (HC, n = 4; C, n = 3) were weaned from CPB and studied for up to 4 h. Total administered heparin was 470 +/- 6 IU/kg (mean +/- SEM) in group C and 100 +/- 0 IU/kg in group HC. Protamine dosage was significantly reduced in group HC. In group C, levels of prothrombin complex, factor VIII and adhesive platelets were reduced significantly during CPB, and postoperatively there were significantly lower values of prothrombin complex, fibrinogen antithrombin III, factor VIII and adhesive platelets but a significantly increased concentration of von Willebrand factor and cumulative bleeding after 4 h. In conclusion, heparin-coated CPB circuits combined with lowered heparin dosage reduced coagulation factor consumption and preserved platelet function, possibly contributing to improved postoperative haemostasis.


Human African trypanosomiasis in a rural community, Democratic Republic of Congo.
According to the World Health Organization, human African trypanosomiasis (HAT) (sleeping sickness) caused the loss of approximately 1.5 million disability-adjusted life years (DALYs) in 2002. We describe the effect of HAT during 2000-2002 in Buma, a rural community near Kinshasa in the Democratic Republic of Congo. We used retrospective questionnaire surveys to estimate HAT-related household costs and DALYs. The HAT outbreak in Buma involved 57 patients and affected 47 (21%) households. The cost to each household was equivalent to 5 months' income for that household. The total number of HAT-related DALYs was 2,145, and interventions to control HAT averted 1,408 DALYs. The cost per DALY averted was US $17. Because HAT has a serious economic effect on households and control interventions are cost-effective, considering only global burden of disease rankings for resource allocation could lead to misguided priority setting if applied without caution in HAT-affected countries.


Early electronic screen exposure and autistic-like symptoms.
Prevalence autism spectrum disorders (ASD) has been on rise, but many studies suggests over-diagnosed. Currently, children have more access to electronic media on the daily basis than those of previous generation. Some studies suggest that increases screen time is associated with melanopsin-expressing neurons and decreasing gamma-aminobutyric acid (GABA) neurotransmitter, and thus results aberrant behavior, decreased cognitive, and language development. Early exposure of electronic media in early life (< 2 years old) gives an impact on language, but it still inconclusive. We made a study aiming at revealing the impact of early exposure of electronic screen on language development and autistic-like behavior. Results showed that children who spent viewing ≤ 3 hours per day had language delay and short attention span, while children who spent viewing ≥ 3 hours per day had language delay, short attention span, and hyperactivity. While, we found that more than a half of children (66.6%) had no parents-child interaction during the exposure, speech delayed and short attention had been reported in all cases, and hyperactivity was found in 66.6% children.


Invasive behavior of ulcerative colitis-associated carcinoma is related to reduced expression of CD44 extracellular domain: comparison with sporadic colon carcinoma.
To elucidate relations of invasion of ulcerative colitis (UC)-associated carcinoma with its prognosis, the characteristics of invasive fronts were analyzed in comparison with sporadic colonic carcinomas. Prognoses of 15 cases of UC-associated colonic carcinoma were compared with those of sporadic colon carcinoma cases, after which 75 cases of sporadic invasive adenocarcinoma were collected. Tumor budding was examined histologically at invasive fronts using immunohistochemistry (IHC) of pancytokeratin. Expressions of beta-catenin with mutation analysis, CD44 extracellular domain, Zo-1, occludin, matrix matalloproteinase-7, laminin-5γ2, and sialyl Lewis X (LeX) were immunohistochemically evaluated. UC-associated carcinoma showed worse prognosis than sporadic colon carcinoma in all the cases, and exhibited a tendency to become more poorly differentiated when carcinoma invaded the submucosa or deeper layers than sporadic carcinoma. When the lesions were compared with sporadic carcinomas considering differentiation grade, reduced expression of CD44 extracellular domain in UC-associated carcinoma was apparent. Laminin-5γ2 and sialyl-LeX expression showed a lower tendency in UC-associated carcinomas than in their sporadic counterparts. There were no differences in the numbers of tumor budding foci between the two lesion types, with no apparent relation to nuclear beta-catenin levels in IHC. UC-associated carcinoma showed poorer differentiation when the carcinoma invaded submucosa or deeper parts, which may influence the poorer prognosis. The invasive behavior of UC-associated carcinoma is more associated with CD44 cleavage than with basement membrane disruption or sialyl-Lewis-antigen alteration.


Determination of the infectious nature of the agent of acute hepatopancreatic necrosis syndrome affecting penaeid shrimp.
A new emerging disease in shrimp, first reported in 2009, was initially named early mortality syndrome (EMS). In 2011, a more descriptive name for the acute phase of the disease was proposed as acute hepatopancreatic necrosis syndrome (AHPNS). Affecting both Pacific white shrimp Penaeus vannamei and black tiger shrimp P. monodon, the disease has caused significant losses in Southeast Asian shrimp farms. AHPNS was first classified as idiopathic because no specific causative agent had been identified. However, in early 2013, the Aquaculture Pathology Laboratory at the University of Arizona was able to isolate the causative agent of AHPNS in pure culture. Immersion challenge tests were employed for infectivity studies, which induced 100% mortality with typical AHPNS pathology to experimental shrimp exposed to the pathogenic agent. Subsequent histological analyses showed that AHPNS lesions were experimentally induced in the laboratory and were identical to those found in AHPNS-infected shrimp samples collected from the endemic areas. Bacterial isolation from the experimentally infected shrimp enabled recovery of the same bacterial colony type found in field samples. In 3 separate immersion tests, using the recovered isolate from the AHPNS-positive shrimp, the same AHPNS pathology was reproduced in experimental shrimp with consistent results. Hence, AHPNS has a bacterial etiology and Koch's Postulates have been satisfied in laboratory challenge studies with the isolate, which has been identified as a member of the Vibrio harveyi clade, most closely related to V. parahemolyticus.


First Report of Fusarium Wilt of Tobacco Caused by Fusarium kyushuense in China.
Tobacco (Nicotiana tabacum L.) is a leafy, annual, solanaceous plant grown commercially for its leaves. China accounts for more than 39.6% of total global tobacco production (3). In May 2012, seedlings of tobacco cv. Honghuadajinyuan in a Guiyang tobacco commercial field (Guizhou, China, 26.35° N, 106.42° E) developed symptoms of severe wilting, chlorosis, and stunting. The main stem and taproot exhibited reddish to light brown vascular discoloration; further progression of these symptoms eventually caused mortality of infected seedlings. To isolate the causal agent, necrotic tissues from the symptomatic root were placed on potato dextrose agar (PDA) and incubated at 25°C in darkness. Colonies with white to rose mycelia and red-brown colony colors developed on PDA after 5 days of incubation. Microconidia were abundant, straight or slightly curved, clavate, 0- to 3-septate, and 7.5 to 20.0 × 2.5 to 5.0 μm. Macroconidia were straight or slightly curved, slender, 3- to 5-septate, and 25.0 to 45.0 × 3.3 to 5.0 μm. Based on the observed colony attributes, growth patterns, absence of chlamydospores, micro- and macro-spore attributes (1), and PCR amplification (using primers ITS1/4) combined with translation elongation factor primers (EF1/2) (2), the fungus was identified as F. kyushuense O'Donnell & T. Aoki. Sequence of ITS1-5.8s-ITS2 region of rDNA (GenBank Accession No. JX235957) exactly matched the sequences of F. kyushuense accession AB587020.1 (100% similarity). Analysis of the elongation factor (EF-1alpha) gene of the fungus (JX658565) resulted in a 99% match for F. kyushuense accession AB674297.1. Pathogenicity of the fungus was confirmed by performing Koch's postulate as follows. Pure cultures of the fungus F. kyushuense obtained from symptomatic tissues of tobacco seedlings were grown on PDA for 6 days. Tobacco plants to be used in pathogenicity tests were germinated and grown on potting soils in a plastic container. Additional fertilization was supplied by adding 0.2 g/L of 20-20-20 (N-P-K) in the float water. When seedlings got 6-leaf stage, they were ready for pathogenicity tests. Spores harvested from these culture plates were suspended in sterile distilled water, adjusted to a concentration of 1 × 104 conidia/ml, and inoculated by irrigating 10 ml of the conidia suspension onto roots of each of the 12 tobacco seedlings with 6-leaf stage. A group of 12 seedlings of the same age treated with sterile water served as control. Inoculated seedlings were maintained at 25°C, 100 μE m-2.s-1, relative humidity >70%, and 16 h light per day, and monitored for 9 days for symptom development. Seedlings inoculated with conidia developed disease symptoms with roots with vascular discoloration of roots whereas control seedlings remained symptomless. F. kyushuense was reisolated from the symptomatic seedlings 9 days after inoculation. F. kyushuense has also been isolated from rice seeds in China (4), and from diseased wheat in Japan (1). The common tobacco Fusarium disease reported in China was caused by F. oxysporium f. sp. nicotianae. However, to the best of our knowledge, this is the first report of F. kyushuense causing wilt on tobacco in China and the disease must be considered in existing disease management practices. References: (1) T. Aoki and K. O'Donnell. Mycoscience. 39:1, 1998. (2) D. M. Geiser et al. Eur. J. Plant Pathol. 110:473, 2004. (3) US Census Bureau. Foreign Trade Statistics. Washington DC, 2005. (4) Z. H. Zhao and G. Z. Lu. Mycotaxon. 102:119, 2007.


Structural similarities of micelle-bound peptide YY (PYY) and neuropeptide Y (NPY) are related to their affinity profiles at the Y receptors.
Here, we investigate the structure of porcine peptide YY (pPYY) both when unligated in solution at pH 4.2 and when bound to dodecylphosphocholine (DPC) micelles at pH 5.5. pPYY in solution displays the PP-fold, with the N-terminal segment being back-folded onto the C-terminal alpha-helix, which extends from residue 17 to 31. In contrast to the solution structure of Keire et al. published in the year 2000 the C-terminal helix does not display a kink around residue 23-25. The root mean square deviation (RMSD) for backbone atoms of the NMR ensemble of conformers to the mean structure is 0.99(+/-0.35) Angstrom for residues 14-31. The back-fold is supported by values of 0.60+/-0.1 for the (15)N(1)H-NOE and by generalized order parameters S(2) of 0.74+/-0.1 for residues 5-31 which indicate that the peptide is folded in that segment. We have additionally used DPC micelles as a membrane model and determined the structure of pPYY when bound to it. Therein, an alpha-helix occurs in the segment comprising residues 17-31 and the N terminus freely diffuses in solution. The hydrophobic side of the amphipathic helix forms the micelle-binding interface and hydrophobic side-chains extend into the micelle interior. A significant stabilization of helical conformation occurs in the C-terminal pentapeptide, which is important for receptor binding. The latter is supported by positive values of the heteronuclear NOE in that segment (0.52+/-0.1 compared to 0.08+/-0.4 for the unligated form) and by values of S(2) of 0.6+/-0.2 (versus 0.38+/-0.2 for the unligated form). The structures of micelle-bound pPYY and pNPY are much more similar than those of pPYY and bPP with pairwise RMSDs of 1.23(+/-0.21)A or 3.21(+/-0.39) Angstrom, respectively. In contrast to the conformational similarities in the DPC-bound state their structures in solution are very different. In fact pPYY is more similar to bPP, which with its strong preference for the Y(4) receptor displays a completely different binding profile. Considering the high degree of sequence homology of pNPY and pPYY (>80%) and the fact, that their binding affinities at all receptor subtypes are high and, more importantly, rather similar, it is much more likely that PYY and NPY are recognized by the Y receptors from the membrane-bound state. As a consequence of the latter the PP-fold is not important for recognition of PYY or NPY at the Y receptors. To our knowledge this work provides for the first time strong arguments derived from structural data that support a membrane-bound receptor recognition pathway.


Household costs of 'malaria' morbidity: a study in Matale district, Sri Lanka.
Short-run economic consequences of 'malaria' on households were examined in a household survey in Matale, a malaria-endemic district of Sri Lanka. On average a household incurred a total cost of Rs 318 (US$ 7) per patient who fully recovered from 'malaria'. 24% of this was direct cost, 44% indirect cost for the patient and 32% indirect cost for the household. Direct costs were greater for those seeking treatment in the private sector. Notably a large proportion of direct costs was spent on complementary goods such as vitamins and foods considered to be nutritional. Indirect cost was measured and valued on the basis of output/ income losses incurred at the household level rather than using a general indicator such as average wage rate. Loss of output and wages accounted for the highest proportion of the indirect cost of the patients as well as the households. Relative to children, more young adults and middle-aged people had 'malaria' which also caused greater economic loss in these age groups. Women tended to care for patients rather than substitute their labour to cover productive work lost due to illness. We compare the methods used by other researchers for valuing indirect cost, demonstrating the significant impact that methods of measurement and valuation can have on the estimation of indirect cost, and justify the recommendation for methodological research in this area.


Sorafenib induced radiation recall dermatitis after spine radiosurgery.
Radiation recall dermatitis has been documented to occur in previously irradiated skin (within the radiation port) the administration of some chemotherapeutic agents. Clinically, it can occur weeks or months after radiation therapy, and resembles the appearance of acute radiation skin reaction. The patterns of the reaction correspond with radiation fields and skin doses. We report a case of recall dermatitis 8 weeks after of spine radiosurgery initiated by the use of a multi-targeted tyrosine kinase inhibitor, Sorafenib, used for treatment of hepatocellular carcinoma.


Environmental sensitivity of gas exchange in different-sized trees.
The carbon isotope signature (delta13C) of foliar cellulose from sunlit tops of trees typically becomes enriched as trees of the same species in similar environments grow taller, indicative of size-related changes in leaf gas exchange. However, direct measurements of gas exchange in common environmental conditions do not always reveal size-related differences, even when there is a distinct size-related trend in delta13C of the very foliage used for the gas exchange measurements. Since delta13C of foliage predominately reflects gas exchange during spring when carbon is incorporated into leaf cellulose, this implies that gas exchange differences in different-sized trees are most likely to occur in favorable environmental conditions during spring. If gas exchange differs with tree size during wet but not dry conditions, then this further implies that environmental sensitivity of leaf gas exchange varies as a function of tree size. These implications are consistent with theoretical relationships among height, hydraulic conductance and gas exchange. We investigated the environmental sensitivity of gas exchange in different-sized Douglas-fir (Pseudotsuga menziesii) via a detailed process model that specifically incorporates size-related hydraulic conductance [soil-plant-atmosphere (SPA)], and empirical measurements from both wet and dry periods. SPA predicted, and the empirical measurements verified, that differences in gas exchange associated with tree size are greatest in wet and mild environmental conditions and minimal during drought. The results support the hypothesis that annual net carbon assimilation and transpiration of trees are limited by hydraulic capacity as tree size increases, even though at particular points in time there may be no difference in gas exchange between different-sized trees. Maximum net ecosystem exchange occurs in spring in Pacific Northwest forests; therefore, the presence of hydraulic limitations during this period may play a large role in carbon uptake differences with stand-age. The results also imply that the impacts of climate change on the growth and physiology of forest trees will vary depending on the age and size of the forest.


A mechanistic evolutionary model explains the time-dependent pattern of substitution rates in viruses.
Estimating viral timescales is fundamental in understanding the evolutionary biology of viruses. Molecular clocks are widely used to reveal the recent evolutionary histories of viruses but may severely underestimate their longer-term origins because of the inverse correlation between inferred rates of evolution and the timescale of their measurement. Here, we provide a predictive mechanistic model that readily explains the rate decay phenomenon over a wide range of timescales and recapitulates the ubiquitous power-law rate decay with a slope of -0.65. We show that standard substitution models fail to correctly estimate divergence times once the most rapidly evolving sites saturate, typically after hundreds of years in RNA viruses and thousands of years in DNA viruses. Our model successfully recreates the observed pattern of decay and explains the evolutionary processes behind the time-dependent rate phenomenon. We then apply our model to re-estimate the date of diversification of genotypes of hepatitis C virus to 423,000 (95% highest posterior density [HPD]: 394,000-454,000) years before present, a time preceding the dispersal of modern humans out of Africa, and show that the most recent common ancestor of sarbecoviruses dates back to 21,000 (95% HPD: 19,000-22,000) years ago, nearly thirty times older than previous estimates. This creates a new perspective for our understanding of the origins of these viruses and also suggests that a substantial revision of evolutionary timescales of other viruses can be similarly achieved.


The latest in antiretroviral therapy.
The XVI International AIDS Conference (AIDS 2006), organized by the International AIDS Society (IAS), took place August 12-18 in Toronto, Canada. It was attended by over 26,000 participants from more than 170 countries and featured more than 4,500 abstracts as well as an array of community and cultural activities. The theme of the meeting was "Time to deliver", emphasizing the continued need and urgency in bringing effective HIV prevention and treatment strategies to those living with and affected by HIV/AIDS. The meeting's agenda was broad and included policy and programmatic topics as well as scientific research. This report focuses on reports presented at the conference that directly deal with antiretroviral therapy. This is primarily because of the nature of the venue where it is intended to be published (Drug News & Perspectives) as well as the expertise of the author. It is not a lack of recognition of the other equally important topics and discussions that took place at AIDS 2006. The author is solely responsible for the selection of topics and presentations to be included in this report.


Agreement of self-reported use of menopausal hormone replacement therapy with physician reports.
There have been relatively few epidemiological studies to verify the information obtained from study participants on the use of menopausal hormone replacement therapy. We conducted this study as part of a case-control study of diet, hormone use, and endometrial cancer in Toronto, Ontario, Canada, 1994-1998. We compared records from 653 subjects, 30-79 years of age, with reports from their physicians on ever/never use of hormone replacement therapy and duration, type, and dose of hormone replacement therapy. A total of 88% of the interview records were in agreement with physician reports for ever/never use of hormone replacement therapy. The overall kappa value for ever/never use agreement was 0.76 (range = 0.71-0.81), and the intraclass correlation coefficient was 0.64 (range = 0.57-0.70) for duration of hormone replacement therapy use, indicating good agreement; similar correlations were seen among cases and controls for overall use, as well as estrogen- or progestogen-alone use. Concordance for brand codes was observed for about 43% of the subjects. This study suggests that information obtained by interview in case-control studies provides a reasonable measure of ever use of hormone replacement therapy and duration of use. Interviews, however, do not represent a reliable source of information on brands and dosage of hormone replacement therapy preparations.


Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food.
(+)-Methamphetamine (METH) addiction is a chronic disease that interferes with fundamental brain-mediated behaviors and biological functions like eating. These studies present preclinical efficacy and safety profiles for a METH conjugate vaccine (IC(KLH)-SMO9) designed to treat METH abuse. ICKLH-SMO9 efficacy and safety were assessed over a 16-week period by monitoring general health and stability of responding in a food maintained behavioral paradigm. Male Sprague-Dawley rats were trained to lever press for food reinforcers until stable behavior was established. Rats (n=9/group) were then immunized with 100 μg of a control antigenic carrier protein (IC(KLH)-Cys) or IC(KLH)-SMO9 in Alhydrogel adjuvant, with booster immunizations at 4, 8 and 12 weeks. Health, immunization site and behavior were assessed daily. No adverse effects were found. During weeks 14-16, when antibody titers and METH affinity (K(d)=13.9 ± 1.7 nM) were maximal, all rats received progressively higher METH doses (0.3-3.0 mg/kg) every 3-4 days, followed by behavioral testing. Even though the lower METH doses from 0.3 to 1.0 mg/kg produced no impairment in food maintained behavior, 3.0-mg/kg in control rats showed significantly (p<0.05) reduced response rates and number of reinforcers earned, as well as reduced food intake. In sharp contrast, the IC(KLH)-SMO9 group showed no changes in food maintained behavior at any METH dose, even though METH serum concentrations showed profound increases due to anti-METH antibody binding. These findings suggest the IC(KLH)-SMO9 vaccine is effective and safe at reducing adverse METH-induced effects, even at high METH doses.


Differential phosphoproteome regulation of nucleus accumbens in environmentally enriched and isolated rats in response to acute stress.
Increasing evidence shows that stress contributes to the pathogenesis of major depressive disorder which is a severe neuropsychiatric disorder and influences over 10% of the world's population. Our previous studies revealed that rats reared in an enriched environment display less depression-related behavior compared to rats raised in an isolated environment, which implies that environmental enrichment produces an antidepressant-like behavioral phenotype. However, the molecular mechanisms are not fully understood. Protein phosphorylation rapidly changes signaling pathway function and alters the function of proteins associated with the stress-induced depressive disorder. Thus, in this study, a phosphoproteomic approach was used to uncover differential phosphoprotein regulation in rat nucleus accumbens between isolated (IC) and enriched environmental conditions (EC) under basal conditions, and in response to acute stress. We found 23 phosphoproteins were regulated in EC vs. IC rats under basal conditions; 10 phosphoproteins regulated by stress in IC rats; and 15 regulated by stress in EC rats. Among all significantly regulated phosphoproteins, 11 of them were represented in at least two conditions. The regulated phosphoproteins represent signaling pathway proteins (including ERK2), enzymes, transcriptional regulators, protein translation regulators, transporters, chaperones and cytoskeletal proteins. These findings provide a global view for further understanding the contribution of protein phosphorylation in depression pathogenesis and antidepressant action.


Molecular electrostatics for probing lone pair-π interactions.
An electrostatics-based approach has been proposed for probing the weak interactions between lone pair containing molecules and π deficient molecular systems. For electron-rich molecules, the negative minima in molecular electrostatic potential (MESP) topography give the location of electron localization and the MESP value at the minimum (Vmin) quantifies the electron-rich character of that region. Interactive behavior of a lone pair bearing molecule with electron deficient π-systems, such as hexafluorobenzene, 1,3,5-trinitrobenzene, 2,4,6-trifluoro-1,3,5-triazine and 1,2,4,5-tetracyanobenzene explored within DFT brings out good correlation of the lone pair-π interaction energy (E(int)) with the Vmin value of the electron-rich system. Such interaction is found to be portrayed well with the Electrostatic Potential for Intermolecular Complexation (EPIC) model. On the basis of the precise location of MESP minimum, a prediction for the orientation of a lone pair bearing molecule with an electron deficient π-system is possible in the majority of the cases studied.


Low power consumption integrated acousto-optic filter in domain inverted LiNbO3 superlattice.
We report on an integrated acousto-optic filter in domain inverted LiNbO3 using a coplanar electrode configuration, which can achieve complete optical switching at electrical powers as low as 50 mW. These values are more than one order of magnitude lower than previously reported results [Opt. Lett. 34, 3205 (2009)]. In order to design the low power consumption devices, we have calculated surface acoustic wave excitation, propagation and acousto-optic interaction in the domain inverted LiNbO3 superlattice using scalar approximation and FEM analysis. Results from both modeling techniques are in good agreement with the experiments, including direct measurement of the acoustic displacement using laser interferometry and acousto-optic performance.


Prostate cancer: screening, diagnosis, and management.
To provide physicians with a review of diagnosis, screening, staging evaluation, treatment options, prognosis, psychosocial issues, economic considerations, and future research directions in the management of patients with all stages of prostate cancer. A MEDLINE search of articles relating to the diagnosis, staging, screening, surgery, radiation therapy, medical management, and research in prostate cancer. Emphasis on information reported from government- and nongovernment-sponsored large cooperative trials, consensus development conferences, and proceedings of prostate cancer organ site workshops. Results of randomized treatment trials and consensus summary statements are reported where long-term results (> 5 years follow-up) are available for localized prostate cancer treatment and where survival outcomes are available for metastatic disease treatment. Both qualitative and quantitative data are reported. Information on staging, management, and prognosis of localized prostate cancer is based on studies that are predominantly nonrandomized, include heterogeneous patient groups, and often use differing outcome measures. Information on management of metastatic prostate cancer is more quantitative and includes side effects of treatment and survival results obtained from randomized, prospective, multi-institutional studies. Despite the increase in prostate cancer incidence and detection, substantial controversy still exists about the advisability and effectiveness of screening programs, the most appropriate staging evaluation, and the optimal management of patients with all stages of prostate cancer. Although randomized, prospective studies attempt to address some of these issues, physicians must appreciate inherent ambiguities involved in recommending staging and treatment choices.


Design of oxytocin antagonists with prolonged action: potential tocolytic agents for the treatment of preterm labor.
In our continuing effort to produce more potent and specific oxytocin (OT) antagonists that may have value as tocolytic agents, we have synthesized a number of new OT antagonists. Our previous studies have shown that rigid conformational structure and restricted dynamic properties are associated with antagonistic activity of the [1-penicillamine]OT [( Pen1]OT) analogs. We therefore synthesized a series of structural analogs of [Pen1,] OT; [Pen1,Thr4]-OT and [Pen1,Phe2,Thr4]OT with greater restricted conformational features. They are [Pen1,delta 3,4-Pro7]OT; [Pen1,Thr4,delta 3,4-Pro7]OT; [Pen1,Phe2,Thr4,delta 3,4-Pro7]OT; [Pen1, Orn8]OT; [Pen1,Phe2,Thr4,delta 3,4,-Pro7,Orn8]OT; [Pen1, Tyr(OMethyl)2,-Thr4,Orn8]OT; [Pen1,Tyr(OEthyl)2,Thr4,Orn8]OT; [Pen1,Phe(Methyl)2,Thr4,Orn8]OT and [Pen1Phe(Ethyl)2,Thr4, Orn8]OT. As expected, all were found to be potent OT antagonists, with in vitro pA2 values ranging from 5.32 to 7.67. They were also effective OT antagonists in vivo in the term pregnant rats. Structural modifications in the above analogs produced various and interesting effects. Dehydroproline substitution for 7-proline in [Pen1]OT increased antagonistic potency, whereas in [Pen1,Thr4]OT and in [Pen1,Phe2,Thr4]OT decreased antagonistic potency. Most significantly, analogs with O-alkyl-Tyr2, Orn8 and p-alkyl-Phe2,Orn8 substitutions were found to have prolonged action both in the isolated rat uterus assays and in the term pregnant rats. Generally, substitution of the alkyl groups resulted in a reduction in anti-OT potency, and increasing the size of the alkyl substituent from a methylene group to an ethyl group diminished antagonistic potencies markedly.(ABSTRACT TRUNCATED AT 250 WORDS)


Multiporphyrin arrays with π-π interchromophore interactions.
A recently reported synthetic method has been employed to prepare several arrays of free base and zinc porphyrins. In the arrays, the porphyrins are arranged around a central benzene ring. The lack of aryl rings in the linkages to the central benzene ring, coupled with the presence of only one meso-aryl substituent on each porphyrin, allows strong electronic interactions between the porphyrin macrocycles. In arrays containing two or six porphyrins, a variety of evidence indicates that the porphyrins exist as twist-stacked dimers reminiscent of the special pairs of bacteriochlorophylls found in some photosynthetic bacteria. These dimers feature van der Waals contact between the macrocycles, and demonstrate excitonic splitting due to π-π interactions. The excitonic effects split and blue-shift the Soret absorptions, and slightly broaden the Q-band absorptions and shift them to longer wavelengths. The interactions also lower the first oxidation potentials by ca. 100 mV, and the arrays show evidence for delocalization of the radical cation over both porphyrins in the dimer. The arrays demonstrate singlet-singlet energy transfer among the chromophores. Arrays of this type will be good models for some aspects of the interactions of photosynthetic pigments, including those of reaction center special pairs and possibly quantum coherence effects. They can also be useful in artificial photosynthetic constructs.


The maltose permease encoded by the MAL61 gene of Saccharomyces cerevisiae exhibits both sequence and structural homology to other sugar transporters.
The MAL61 gene of Saccharomyces cerevisiae encodes maltose permease, a protein required for the transport of maltose across the plasma membrane. Here we report the nucleotide sequence of the cloned MAL61 gene. A single 1842 bp open reading frame is present within this region encoding the 614 residue putative MAL61 protein. Hydropathy analysis suggests that the secondary structure consists of two blocks of six transmembrane domains separated by an approximately 71 residue intracellular region. The N-terminal and C-terminal domains of 100 and 67 residues in length, respectively, also appear to be intracellular. Significant sequence and structural homology is seen between the MAL61 protein and the Saccharomyces high-affinity glucose transporter encoded by the SNF3 gene, the Kluyveromyces lactis lactose permease encoded by the LAC12 gene, the human HepG2 glucose transporter and the Escherichia coli xylose and arabinose transporters encoded by the xylE and araE genes, indicating that all are members of a family of sugar transporters and are related either functionally or evolutionarily. A mechanism for glucose-induced inactivation of maltose transport activity is discussed.


The feasibility and acceptability of trial procedures for a pragmatic randomised controlled trial of a structured physical activity intervention for people diagnosed with colorectal cancer: findings from a pilot trial of cardiac rehabilitation versus usual care (no rehabilitation) with an embedded qualitative study.
Pilot and feasibility work is conducted to evaluate the operational feasibility and acceptability of the intervention itself and the feasibility and acceptability of a trials' protocol design. The Cardiac Rehabilitation In Bowel cancer (CRIB) study was a pilot randomised controlled trial (RCT) of cardiac rehabilitation versus usual care (no rehabilitation) for post-surgical colorectal cancer patients. A key aim of the pilot trial was to test the feasibility and acceptability of the protocol design. A pilot RCT with embedded qualitative work was conducted in three sites. Participants were randomly allocated to cardiac rehabilitation or usual care groups. Outcomes used to assess the feasibility and acceptability of key trial parameters were screening, eligibility, consent, randomisation, adverse events, retention, completion, missing data, and intervention adherence rates. Colorectal patients' and clinicians' perceptions and experiences of the main trial procedures were explored by interview. Quantitative study. Three sites were involved. Screening, eligibility, consent, and retention rates were 79 % (156/198), 67 % (133/198), 31 % (41/133), and 93 % (38/41), respectively. Questionnaire completion rates were 97.5 % (40/41), 75 % (31/41), and 61 % (25/41) at baseline, follow-up 1, and follow-up 2, respectively. Sixty-nine percent (40) of accelerometer datasets were collected from participants; 31 % (20) were removed for not meeting wear-time validation. Qualitative study: Thirty-eight patients and eight clinicians participated. Key themes were benefits for people with colorectal cancer attending cardiac rehabilitation, barriers for people with colorectal cancer attending cardiac rehabilitation, generic versus disease-specific rehabilitation, key concerns about including people with cancer in cardiac rehabilitation, and barriers to involvement in a study about cardiac rehabilitation. The study highlights where threats to internal and external validity are likely to arise in any future studies of similar structured physical activity interventions for colorectal cancer patients using similar methods being conducted in similar contexts. This study shows that there is likely to be potential recruitment bias and potential imprecision due to sub-optimal completion of outcome measures, missing data, and sub-optimal intervention adherence. Hence, strategies to manage these risks should be developed to stack the odds in favour of conducting successful future trials. ISRCTN63510637.


UVC-induced apoptosis in Dubca cells is independent of JNK activation and p53(Ser-15) phosphorylation.
Ultraviolet C (UVC) irradiation in mammalian cell lines activates a complex signaling network that leads to apoptosis. By using Dubca cells as a model system, we report the presence of a UVC-induced apoptotic pathway that is independent of c-Jun N-terminal kinases (JNKs) activation and p53 phosphorylation at Ser(15). Irradiation of Dubca cells with UVC results in a rapid JNK activation and phosphorylation of its downstream target c-Jun, as well as, phosphorylation of activating transcription factor 2 (ATF2). Pre-treatment with JNK inhibitor, SP600125, inhibited UVC-induced c-Jun phosphorylation without preventing UVC-induced apoptosis. Similarly, inhibition of UVC-induced p53 phosphorylation did not prevent Dubca cell apoptosis, suggesting that p53(Ser-15) phosphorylation is not associated with UVC-induced apoptosis signaling. The pan-caspase inhibitor z-VAD-fmk inhibited UVC-induced PARP cleavage, DNA fragmentation, and ultimately apoptosis of Dubca cells. Altogether, our study clearly indicates that UVC-induced apoptosis is independent of JNK and p53 activation in Dubca cells, rather, it is mediated through a caspase dependent pathway. Our findings are not in line with the ascribed critical role for JNKs activation, and downstream phosphorylation of targets such as c-Jun and ATF2 in UVC-induced apoptosis.


Focused Ultrasound for Essential Tremor: Review of the Evidence and Discussion of Current Hurdles.
While there is no breakthrough progress in the medical treatment of essential tremor (ET), in the past decades several remarkable achievements happened in the surgical field, such as radiofrequency thalamotomy, thalamic deep brain stimulation, and gamma knife thalamotomy. The most recent advance in this area is magnetic resonance-guided focused ultrasound (MRgFUS). The purpose of this review is to discuss the new developments and trials of MRgFUS in the treatment of ET and other tremor disorders. MRgFUS is an incisionless surgery performed without anesthesia and ionizing radiation (no risk of cumulative dose and delayed side effects). Studies have shown the safety and effectiveness of unilateral MRgFUS-thalamotomy in the treatment of ET. It has been successfully used in a few patients with Parkinson's disease-related tremor, and in fewer patients with fragile X-associated tremor/ataxia syndrome. The safety and long-term effects of the procedure are still unclear, as temporary and permanent adverse events have been reported as well as recurrence of tremor. MRgFUS is a promising new surgical approach with a number of unknowns and unsolved issues. It represents a valuable option particularly for patients who refused or could not be candidates for other procedures, deep brain stimulation in particular.


Benzo[a]phenoxazinium chlorides: Synthesis, antifungal activity, in silico studies and evaluation as fluorescent probes.
Four new benzo[a]phenoxazinium chlorides with combinations of chloride, ethyl ester and methyl as terminals of the amino substituents were synthesized. These compounds were characterized and their optical properties were studied in absolute dry ethanol and water. Their antiproliferative activity was tested against Saccharomyces cerevisiae in a broth microdilution assay, along with an array of 36 other benzo[a]phenoxazinium chlorides. Minimum Inhibitory Concentration (MIC) values between 1.56 and >200 µM were observed. Fluorescence microscopy studies, used to assess the intracellular distribution of the dyes, showed that these benzo[a]phenoxazinium chlorides function as efficient and site specific probes for the detection of the vacuole membrane. The added advantage of some of the compounds, that displayed the lower MIC values, was the simultaneous staining of both the vacuole membrane and the perinuclear membrane of endoplasmic reticulum (ER). Molecular docking studies were performed on the human membrane protein oxidosqualene cyclase (OSC), using the crystal structure available on PDB (code 1W6K). The results showed that these most active compounds accommodated better in the active sites of ER enzyme OSC suggesting this enzyme as a potential target. As a whole, the results demonstrate that the benzo[a]phenoxazinium chlorides are interesting alternatives to the available commercial dyes. Changes in the substituents of these compounds can tailor both their staining specificity and antimicrobial activity.


Motion estimation-based image enhancement in ultrasound imaging.
High resolution medical ultrasound (US) imaging is an ongoing challenge in many diagnosis applications and can be achieved either by instrumentation or by post-processing. Though many works have considered the issue of resolution enhancement in optical imaging, very few works have investigated this issue in US imaging. In optics, several algorithms have been proposed to achieve super-resolution (SR) image reconstruction, which consists of merging several low resolution images to create a higher resolution image. However, the straightforward implementation of such techniques for US imaging is unsuccessful, due to the interaction of ultrasound with tissue and speckle. We show how to overcome the limit of SR in this framework by refining the registration part of common multiframe techniques. For this purpose, we investigate motion estimation methods adapted to US imaging. Performance of the proposed technique is evaluated on both realistic simulated US images (providing an estimated best-case performance) and real US sequences of phantom and in-vivo thyroid images. Compared to classical SR methods, our technique brings both quantitative and qualitative improvements. Resolution gain was found to be 1.41 for the phantom sequence and 1.12 for the thyroid sequence and a quantitative study using the phantom further confirmed the spatial resolution enhancement. Furthermore, the contrast-to-noise ratio was increased by 27% and 13% for simulated and experimental US images, respectively.


Smoking Is the Most Significant Modifiable Lung Cancer Risk Factor in Systemic Lupus Erythematosus.
To assess lung cancer risk in systemic lupus erythematosus (SLE), relative to demographics, drug exposures, smoking, and disease activity. We analyzed data from 14 SLE cohorts. We calculated adjusted HR estimates for lung cancer in SLE, relative to demographics, smoking, time-dependent medication exposures, and cumulative disease activity [mean adjusted SLE Disease Activity Index (SLEDAI) scores]. This project was approved by the ethics boards of all participating institutions, including the Institutional Review Board of the McGill University Health Centre. The ethics approval number for the Cancer Risk study is GEN-06-031. Within these 14 SLE cohorts, 49 incident lung cancers occurred. Among lung cancer cases, 59.0% were in the highest SLEDAI quartile at baseline versus 40.8% of lung cancer-free SLE controls. The vast majority (84.2%) of SLE lung cancer cases were ever-smokers at baseline, versus 40.1% of those without lung cancer. In adjusted models, the principal factors associated with lung cancer were ever smoking (at cohort entry) and current age. Estimated adjusted effects of all drugs were relatively imprecise, but did not point toward any drug exposures as strong lung cancer risk factors. We saw no clear evidence for drugs as a trigger for lung cancer risk in SLE, although drug risk estimates were relatively imprecise. Smoking may be the most significant modifiable lung cancer risk factor in SLE.


Sweat gland function as a measure of radiation change.
Radiotherapy may result in dryness of the skin even when no other change can be detected. We describe a system for recording the electrical conductance of skin as a measure of sweat gland function. In 22 normal volunteers close agreement was obtained between measurements obtained from comparable sites on both sides of the chest. Measurements were subsequently made in 38 patients treated by radiotherapy to one side of the chest for tumours of the breast or lung using one of five different fractionation schedules. Simultaneous readings were obtained from both sides of the chest with the non irradiated side acting as a control. A dose response relationship was demonstrated: five patients who received the equivalent total dose of 15 Gy in 2-Gy fractions showed no change in conductance. Sixteen out of 23 who received an equivalent total dose of 42-46 Gy in 2-Gy fractions had a greater than 22% reduction in mean skin conductance compared with that of the control areas despite the skin appearing normal in the large majority. Marked changes in skin conductance were seen after higher total doses. In a prospective study 18 women receiving breast irradiation underwent weekly readings during treatment. A mean reduction of 40% in skin conductance was noted by the end of the second week of treatment prior to any clinical evidence of radiation change. Skin conductance returned to normal in 44% of patients by 6 months. In the remainder, those patients who showed the greatest reduction in skin conductance during treatment demonstrated the least recovery. Changes in sweat gland function can be detected and quantified in skin which may otherwise appear normal. Differences may so be demonstrated between areas treated using different fractionation schedules and the method may be applied to the detection during radiotherapy of unusually sensitive patient.


Effect of taurine and gold nanoparticles on the morphological and molecular characteristics of muscle development during chicken embryogenesis.
The objective of the present investigation was to evaluate the effects of taurine and Au nanoparticles on the expression of genes related to embryonic muscle development and on the morphological characteristics of muscles. Fertilised chicken eggs (n = 160) were randomly divided into four groups: without injection (Control) and with injection of Au nanoparticles (NanoAu), taurine (Tau) or Au nanoparticles with taurine (NanoAu + Tau). The experimental solutions were given in ovo, on the third day of incubation, by injecting 0.3 ml of the experimental solution into the air sack. The embryos were evaluated on the 20th day of incubation. The methods included gene expression at the mRNA and protein levels, immunohistochemistry, histology and microscopy. In groups NanoAu, Tau and NanoAu + Tau, the muscle structure and the number of muscle cells were affected. Furthermore, taurine increased fibre diameter, the total number of nuclei, the proportion of proliferating cell nuclear antigen (PCNA)-positive cells and the total cell number. Also, gene expression of basic fibroblast growth factor-2 and PCNA was downregulated. There were no significant interactions between NanoAu and taurine, indicating that NanoAu did not enhance the effects of taurine. It may be concluded that 20 days after injection, NanoAu affected some parameters of muscle development, but the most profound effects were those of taurine.


Optical response of high-power laser windows-ultrashort pulse regime.
The passage of a high-power laser pulse through a material window can result in optical distortion that significantly reduces the far-field irradiance. Optical distortion due to pulses having durations on the order of the acoustic wave propagation time through the thickness of the window is a result of heating by the absorbed laser energy and thermally induced plane-strain stress waves. For a given laser pulse duration and axially symmetric irradiance distribution, expressions are derived for the evolution of the window's aberation function. It is shown that, in this pulse regime, there is no stress induced birefringence and the evolution of the beam profile is such that the Gaussian focus always propagates towards the window aperture. Expressions are derived for the threshold for fracturing. It is shown that in the case of KBr fracturing occurs before lensing whereas for CdTe, Ge, and TI-1173 glass, lensing occurs before fracturing.


Alpha6-Containing Nicotinic Acetylcholine Receptors Mediate Nicotine-Induced Structural Plasticity in Mouse and Human iPSC-Derived Dopaminergic Neurons.
Midbrain dopamine (DA) neurons are considered a critical substrate for the reinforcing and sensitizing effects of nicotine and tobacco dependence. While the role of the α4 and β2 subunit containing nicotinic acetylcholine receptors (α4β2∗nAChRs) in mediating nicotine effects on DA release and DA neuron activity has been widely explored, less information is available on their role in the morphological adaptation of the DA system to nicotine, eventually leading to dysfunctional behaviors observed in nicotine dependence. In particular, no information is available on the role of α6∗nAChRs in nicotine-induced structural plasticity in rodents and no direct evidence exists regarding the occurrence of structural plasticity in human DA neurons exposed to nicotine. To approach this problem, we used two parallel in vitro systems, mouse primary DA neuron cultures from E12.5 embryos and human DA neurons differentiated from induced pluripotent stem cells (iPSCs) of healthy donors, identified using TH+ immunoreactivity. In both systems, nicotine 1-10 μM produced a dose-dependent increase of maximal dendrite length, number of primary dendrites, and soma size when measured after 3 days in culture. These effects were blocked by pretreatments with the α6∗nAChR antagonists α-conotoxin MII and α-conotoxin PIA, as well as by the α4β2nAChR antagonist dihydro-β-erythroidine (DHβE) in both mouse and human DA neurons. Nicotine was also ineffective when the primary DA neurons were obtained from null mutant mice for either the α6 subunit or both the α4 and α6 subunits of nAChR. When pregnant mice were exposed to nicotine from gestational day 15, structural plasticity was also observed in the midbrain DA neurons of postnatal day 1 offspring only in wild-type mice and not in both null mutant mice. This study confirmed the critical role of α4α6∗nAChRs in mediating nicotine-induced structural plasticity in both mouse and human DA neurons, supporting the translational relevance of neurons differentiated from human iPSCs for pharmacological studies.


Clinical characteristics and comorbidities of elderly asthmatics who attend allergy clinics.
To date, few studies have focused on the clinical and allergic characteristics of asthma in the elderly, defined as asthma in people aged 60 or over. Thus, we propose to identify and study the clinical and allergic characteristics and comorbidities of patients with asthma among the elderly. A retrospective, observational, descriptive study was developed in five clinics and hospitals in Argentina. Allergy Physicians analyzed their patients' medical records in 2014 and included those adults over the age of 60, who had been diagnosed with asthma according to the GINA guidelines. Clinical and allergic characteristics were analyzed. A total of 152 patients diagnosed with asthma, of whom 73% were women and 11% ex-smokers, were included in this study, with a mean age of 66 years. Only 10.5% of the participants had onset asthma past the age of 60. Regarding asthma severity, 74.3% were diagnosed with moderate persistent asthma, and 7.2% with severe persistent asthma. Eighty-four percent of the patients were treated with an inhaled corticosteroid (ICS) along with a long-acting β 2-adrenergic agent (LABA). More than half of the patients had two or more comorbidities simultaneously. Allergic comorbidities were the most frequent comorbidities, followed by arterial hypertension. Among allergic comorbidities, most patients presented allergies at the nasal level. There were no significant differences between the subpopulations of patients with late-onset asthma (LOA) and asthma with onset before the age of 60, i.e. early onset asthma (EOA) in most of their clinical characteristics. However, it was observed that EOA accounted for a higher percentage of patients with nasal allergies as compared to LOA (71% vs 46%, p < 0.05).It is worth mentioning that almost half of the patients with LOA had allergies at the nasal level. These results may provide a better understanding of the clinical characteristics of asthma in the elderly in Argentina, thus, enabling the development of future therapeutic strategies and a better quality of life for our elderly asthma patients.


DNA methylation of PAX1 as a biomarker for oral squamous cell carcinoma.
DNA methylation has been shown to be a promising cancer biomarker. The aim of this study was to evaluate DNA methylation of three transcription factors, sex-determining region Y-box 1 (SOX1), paired box gene 1 (PAX1), and zinc-finger 582 (ZNF582), in detecting oral squamous cell carcinoma (OSCC). A case-control study was conducted at Taipei Medical University Hospital in Taiwan with 31 cases of various oral cavity squamous cell carcinomas and 40 controls. Questionnaire data assessing environmental exposure, such as alcohol consumption, cigarette smoking, and betel nut chewing, were obtained from each participant. DNA from oral swabs were analyzed for methylation using quantitative methylation polymerase chain reaction with TaqMan probes. Methylation status was determined using a methylation index. Methylation levels of SOX1, PAX1, and ZNF582 were significantly higher in cancer patients (p = 0.02, p = 0.02, and p = 0.03, respectively). Patients with highly methylated SOX1, PAX1, and ZNF582 had an increased cancer risk with odds ratios (ORs) of 16.50 (95 % CI = 2.85-96.65), 60.57 (95 % CI = 5.85-629.94), and 5.07 (95 % CI = 1.08-23.76), respectively. Area under the curve (AUC) values were 0.85, 0.78, and 0.78 for PAX1, SOX1, and ZNF582, respectively. When stratified based on environmental exposure, the AUC of PAX1 methylation (PAX1 (m) ) was 0.94 in environmental exposure-naïve subjects and 0.85 for SOX1 methylation in subjects who chewed betel nut. In general, the sensitivity and specificity of PAX1 (m) were 87 and 80 % for OSCC detection. The sensitivity of PAX1 (m) in subjects who chewed betel nut was 83 %, with a specificity of 75 %. Testing PAX1 DNA methylation using oral swabs is a promising method for oral cancer detection. Combined assessments regarding betel nut consumption and DNA methylation can improve OSCC screening. The double E (environmental and epigenetic) assessment is a potential strategy in OSCC screening.


Novel p-n heterojunction BiOI/CeO2 photocatalyst for wider spectrum visible-light photocatalytic degradation of refractory pollutants.
Recently, visible-light-driven photocatalysts have been widely used in environmental pollutant remediation. In the present study, BiOI/CeO2 p-n junction photocatalysts were successfully fabricated using a facile in situ chemical bath method. The BiOI/CeO2 p-n junction photocatalysts exhibited excellent photoactivity for the decomposition of the refractory pollutant bisphenol A (BPA) and methylene orange (MO) under visible light illumination. The sample with a 1 : 1 mole ratio of BiOI : CeO2 possessed the highest photocatalytic performance out of all of the as-obtained catalysts. Mott-Schottky plots indicated that p-n junctions were successfully constructed between BiOI and CeO2. The optical and electrical properties of the materials demonstrate that the introduction of BiOI can broaden the visible-light absorption region of CeO2, and the transfer rate of the electron-hole pairs dramatically improves through forming a p-n junction. Furthermore, the BPA degradation efficiency exhibited excellent photostability after four consecutive cycles. These features show that the BiOI/CeO2 p-n junction has great application potential for refractory pollutant removal from wastewater.


Environmental policies to reduce college drinking: options and research findings.
The goal of this article is to provide an overview of environmental strategies that may reduce college drinking. Drinking behavior is influenced by many environmental factors, including messages in the media, community norms and attitudes, public and institutional policies and practices and economic factors. College student drinking may be influenced by environmental factors on and off campus. A comprehensive search of MEDLINE, ETOH, Current Contents and Social Science Abstracts databases was conducted to identify research studies evaluating effects of environmental strategies on college and general populations. The identified environmental strategies fall into four categories: (1) increasing compliance with minimum legal drinking age laws, (2) reducing consumption and risky alcohol use, (3) decreasing specific types of alcohol-related problems and (4) de-emphasizing the role of alcohol on campus and promoting academics and citizenship. Although the extant research indicates that many environmental strategies are promising for reducing alcohol-related problems among the general population, few of these strategies have been evaluated for effects on the college population. Further research is needed to evaluate effects of alcohol control policies on alcohol consumption and its related problems among college students.


Extrahepatic portal biliopathy: proposed etiology on the basis of anatomic and clinical features.
To compare the anatomic and clinical features in patients with chronic portal vein thrombosis (PVT) to determine why some patients develop portal biliopathy (PB) while most do not and propose an etiology for PB. This project satisfied HIPAA regulations and received institutional review board approval for a retrospective review without the need for consent. From 100 patients with PVT, 60 were extracted who had chronic, nonmalignant PVT, after exclusion of those with sclerosing cholangitis, liver transplants, choledocholithiasis, or portosystemic shunts. Clinical and imaging data from 19 patients with biliary dilatation (PB group) were compared with data from 41 patients without biliary dilatation (no-PB group). Statistical analysis was performed with the Fisher exact test for categorical variables or the Wilcoxon rank-sum test for numerical and ordered categorical variables. P values of .05 or less were considered to indicate a significant difference. The etiology of PVT differed between the groups (P < .001); cirrhosis was infrequently seen in the PB group (two of 19, 11%) but was common in the no-PB group (31 of 41, 76%). Only two of 33 (6%) patients with cirrhosis and PVT had PB. Extension of PVT into the mesenteric veins was significantly more common in the PB group (18 of 19, 95%) than in the no-PB group (one of 41, 2%) (P < .001). Compared with the no-PB group, patients in the PB group had more acute angulation of the bile duct (median, 110° vs 128°; P = .008), less frequent gastroesophageal varices (three of 19 [16%] vs 20 of 41 [49%], P = .021), and a smaller mean coronary vein diameter (median, 5 vs 6 mm; P = .014). Noncirrhotic patients with hypercoagulable states tend to develop PB when PVT extends to the splenomesenteric veins. A possible etiology is the formation of specific peribiliary venous pathways responsible for bile duct compression and tethering.


The Haiti Medical Education Project: development and analysis of a competency based continuing medical education course in Haiti through distance learning.
Recent calls for reform in healthcare training emphasize using competency-based curricula and information technology-empowered learning. Continuing Medical Education programs are essential in maintaining physician accreditation. Haitian physicians have expressed a lack access to these activities. The Haiti Medical Education Project works in alliance with Haitian medical leadership, faculty and students to support the Country's medical education system. We present the creation, delivery and evaluation of a competency-based continuing medical education curriculum for physicians in rural Haiti. Real time lectures from local and international institutions were teleconferenced to physicians in remote Haitian sites using VidyoConferencing™ technology. With American Academy of Family Physicians (AAFP) and College of Family Physicians Canada (CFPC) guidelines as references, a competency-derived syllabus was created for a Haitian continuing medical education program. The resulting educational goals were reviewed by a committee of Haitian and North American physician/medical education practitioners to reflect local needs. All authors reviewed lectures and then conferred to establish agreement on competencies presented for each lecture. Sixty-seven lectures were delivered. Human immunodeficiency virus/Acquired Immunodeficiency Syndrome, ophthalmologic, infectious diseases, renal and endocrine competencies were well-represented, with more than 50 % of the joint AAFP and CFPC recommended competencies outlined. Areas under-represented included allergy and immunology, cardiology, surgery, pain management, gastroenterology, neurology, pulmonology, men's health and rheumatology; these topics accounted for less than 25 % of AAFP/CFPC recommended competencies. Areas not covered included geriatrics, nutrition, occupational health and women's health. Within practice-based lectures, only disaster medicine, health promotion and information management were included, but only partially covered. We identified teaching goals covered and competencies that were missing from a CME program for rural Haitian physicians. We aim to use this analysis to provide a competency-based CME lecture series that proportionally meets local needs while following recommendations of recognized national family medicine organizations.


Diagnosis of breast cancer using diffuse reflectance spectroscopy: Comparison of a Monte Carlo versus partial least squares analysis based feature extraction technique.
We explored the use of diffuse reflectance spectroscopy in the ultraviolet-visible (UV-VIS) spectrum for the diagnosis of breast cancer. A physical model (Monte Carlo inverse model) and an empirical model (partial least squares analysis) based approach, were compared for extracting diagnostic features from the diffuse reflectance spectra. The physical model and the empirical model were employed to extract features from diffuse reflectance spectra measured from freshly excised breast tissues. A subset of extracted features obtained using each method showed statistically significant differences between malignant and non-malignant breast tissues. These features were separately input to a support vector machine (SVM) algorithm to classify each tissue sample as malignant or non-malignant. The features extracted from the Monte Carlo based analysis were hemoglobin saturation, total hemoglobin concentration, beta-carotene concentration and the mean (wavelength averaged) reduced scattering coefficient. Beta-carotene concentration was positively correlated and the mean reduced scattering coefficient was negatively correlated with percent adipose tissue content in normal breast tissues. In addition, there was a statistically significant decrease in the beta-carotene concentration and hemoglobin saturation, and a statistically significant increase in the mean reduced scattering coefficient in malignant tissues compared to non-malignant tissues. The features extracted from the partial least squares analysis were a set of principal components. A subset of principal components showed that the diffuse reflectance spectra of malignant breast tissues displayed an increased intensity over wavelength range of 440-510 nm and a decreased intensity over wavelength range of 510-600 nm, relative to that of non-malignant breast tissues. The diagnostic performance of the classification algorithms based on both feature extraction techniques yielded similar sensitivities and specificities of approximately 80% for discriminating between malignant and non-malignant breast tissues. While both methods yielded similar classification accuracies, the model based approach provided insight into the physiological and structural features that discriminate between malignant and non-malignant breast tissues.


Phyllodes tumours of the breast: a consensus review.
Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours from cellular fibroadenomas is fraught with difficulty, due to overlapping microscopic features. Similarly, separation of the malignant phyllodes tumour from spindle cell metaplastic carcinoma and primary breast sarcoma can be problematic. Phyllodes tumours are treated by surgical excision. However, there is no consensus on the definition of an appropriate surgical margin to ensure completeness of excision and reduction of recurrence risk. Interpretive subjectivity, overlapping histological diagnostic criteria, suboptimal correlation between histological classification and clinical behaviour and the lack of robust molecular predictors of outcome make further investigation of the pathogenesis of these fascinating tumours a matter of active research. This review consolidates the current understanding of their pathobiology and clinical behaviour, and includes proposals for a rational approach to the classification and management of phyllodes tumours.


Three-dimensional director structures of defects in Grandjean-Cano wedges of cholesteric liquid crystals studied by fluorescence confocal polarizing microscopy.
We use a nondestructive technique of fluorescence confocal polarizing microscopy to visualize three-dimensional director patterns of defects in Grandjean-Cano wedges filled with a cholesteric liquid crystal of pitch p=5 microm. Strong surface anchoring of the director causes a stable lattice of dislocations in the bulk. Optical slicing in the vertical cross sections of the wedges allows us to establish the detailed structure of dislocations and their kinks. Dislocations of Burgers vector b=p/2 are located in the thin part of the sample, very close to the bisector plane. Their cores are split into a pair of tau(-1/2) and lambda(+1/2) disclinations. Pairs of lambda(-1/2) and tau(+1/2) disclinations are observed when the b=p/2 dislocation forms a kink. The kinks along the b=p/2 dislocations change the level of dislocations by +/-p/4 and +/-p/2; these kinks are confined to the glide plane and are very long, (5-10) p. Above some critical thickness h(c) of the wedge sample, the dislocations are of Burgers vector b=p. They are often found away from the bisector plane. The core of b=p dislocations is split into a pair of nonsingular lambda(-1/2) and lambda(+1/2) disclinations. The kinks along the b=p dislocation are of a typical size p and form cusps in the direction perpendicular to the glide plane. At the cusp, lambda(-1/2) and lambda(+1/2) disclinations interchange ends. Other defect structures inlude "Lehmann clusters," i.e., dislocations of zero Burgers vector formed by two lambda(-1/2) and two lambda(+1/2) disclinations and dislocations of nonzero Burgers vector with a core split into more than two disclinations. We employ the coarse-grained Lubensky-de Gennes model of the cholesteric phase to describe some of the observed features. We calculate the elastic energy of a dislocation away from the core, estimate the energy of the core split into disclinations of different types, study the effect of finite sample thickness on the dislocations energy, and calculate the Peach-Koehler elastic forces that occur when a dislocation is shifted from its equilibrium position. Balance of the dilation/compression energy in the wedge and the energy of dislocations defines the value of h(c) and allows to estimate the core energy of the dislocations. Finally, we consider the Peierls-Nabarro mechanisms hindering glide of dislocations across the cholesteric layers. Because of the split disclination character of the core, glide is difficult as compared to climb, especially for b=p dislocations.


Is the relationship between mast-seeding and weather in oaks related to their life-history or phylogeny?
Although the functional basis of variable and synchronous seed production (masting behavior) has been extensively investigated, only recently has attention been focused on the proximate mechanisms driving this phenomenon. We analyzed the relationship between weather and acorn production in 15 species of oaks (genus Quercus) from three geographic regions on two continents, with the goals of determining the extent to which similar sets of weather factors affect masting behavior across species and to explore the ecological basis for the similarities detected. Lag-1 temporal autocorrelations were predominantly negative, supporting the hypothesis that stored resources play a role in masting behavior across this genus, and we were able to determine environmental variables correlating with acorn production in all but one of the species. Standard weather variables outperformed "differential-cue" variables based on the difference between successive years in a majority of species, which is consistent with the hypothesis that weather is linked directly to the proximate mechanism driving seed production and that masting in these species is likely to be sensitive to climate change. Based on the correlations between weather variables and acorn production, cluster analysis failed to generate any obvious groups of species corresponding to phylogeny or life-history. Discriminant function analyses, however, were able to identify the phylogenetic section to which the species belonged and, controlling for phylogeny, the length of time species required to mature acorns, whether they were evergreen or deciduous, and, to a lesser extent, the geographic region to which they are endemic. These results indicate that similar proximate mechanisms are driving acorn production in these species of oaks, that the environmental factors driving seed production in oaks are to some extent phylogenetically conserved, and that the shared mechanisms driving acorn production result in some degree of synchrony among coexisting species in a way that potentially enhances predator satiation, at least when they have acorns requiring the same length of time to mature.


Accounting for inertia effects to access the high-frequency microrheology of viscoelastic fluids.
We study the Brownian motion of microbeads immersed in water and in a viscoelastic wormlike micelles solution by optical trapping interferometry and diffusing wave spectroscopy. Through the mean-square displacement obtained from both techniques, we deduce the mechanical properties of the fluids at high frequencies by explicitly accounting for inertia effects of the particle and the surrounding fluid at short time scales. For wormlike micelle solutions, we recover the 3/4 scaling exponent for the loss modulus over two decades in frequency as predicted by the theory for semiflexible polymers.


Digital PCR-based Competitive Index for High-throughput Analysis of Fitness in Salmonella.
A competitive index is a common method used to assess bacterial fitness and/or virulence. The utility of this approach is exemplified by its ease to perform and its ability to standardize the fitness of many strains to a wild-type organism. The technique is limited, however, by available phenotypic markers and the number of strains that can be assessed simultaneously, creating the need for a great number of replicate experiments. Concurrent with large numbers of experiments, the labor and material costs for quantifying bacteria based on phenotypic markers are not insignificant. To overcome these negative aspects while retaining the positive aspects, we have developed a molecular-based approach to directly quantify microorganisms after engineering genetic markers onto bacterial chromosomes. Unique, 25 base pair DNA barcodes were inserted at an innocuous locus on the chromosome of wild-type and mutant strains of Salmonella. In vitro competition experiments were performed using inocula consisting of pooled strains. Following the competition, the absolute numbers of each strain were quantified using digital PCR and the competitive indices for each strain were calculated from those values. Our data indicate that this approach to quantifying Salmonella is extremely sensitive, accurate, and precise for detecting both highly abundant (high fitness) and rare (low fitness) microorganisms. Additionally, this technique is easily adaptable to nearly any organism with chromosomes capable of modification, as well as to various experimental designs that require absolute quantification of microorganisms.


A gravid lizard from the Cretaceous of China and the early history of squamate viviparity.
Although viviparity is most often associated with mammals, roughly one fifth of extant squamate reptiles give birth to live young. Phylogenetic analyses indicate that the trait evolved more than 100 times within Squamata, a frequency greater than that of all other vertebrate clades combined. However, there is debate as to the antiquity of the trait and, until now, the only direct fossil evidence of squamate viviparity was in Late Cretaceous mosasauroids, specialised marine lizards without modern equivalents. Here, we document viviparity in a specimen of a more generalised lizard, Yabeinosaurus, from the Early Cretaceous of China. The gravid female contains more than 15 young at a level of skeletal development corresponding to that of late embryos of living viviparous lizards. This specimen documents the first occurrence of viviparity in a fossil reptile that was largely terrestrial in life, and extends the temporal distribution of the trait in squamates by at least 30 Ma. As Yabeinosaurus occupies a relatively basal position within crown-group squamates, it suggests that the anatomical and physiological preconditions for viviparity arose early within Squamata.


Graft materials provide greater static strength to medial opening wedge high tibial osteotomy than when no graft is included.
The purpose of this study was to compare the stability of medial opening-wedge high tibial osteotomy (MOWHTO) with and without different graft materials. Good clinical and radiological outcomes have been demonstrated when either using or not using graft materials during MOWHTO. Variations in the biomechanical properties of different graft types, regarding the stability they provide a MOWHTO, have not been previously investigated. A 10 mm biplanar MOWHTO was performed on 15 artificial sawbone tibiae, which were fixed using the Activmotion 2 plate. Five bones had OSferion60 wedges (synthetic group), five had allograft bone wedges (allograft group), and five had no wedges (control group) inserted into the osteotomy gap. Static compression was applied axially to each specimen until failure of the osteotomy. Ultimate load, horizontal and vertical displacements were measured and used to calculate construct stiffness and valgus malrotation of the tibial head. The synthetic group failed at 6.3 kN, followed by the allograft group (6 kN), and the control group (4.5 kN). The most valgus malrotation of the tibial head was observed in the allograft group (2.6°). The synthetic group showed the highest stiffness at the medial side of the tibial head (9.54 kN·mm- 1), but the lowest stiffness at the lateral side (1.59 kN·mm-1). The allograft group showed high stiffness on the medial side of the tibial head (7.54 kN·mm- 1) as well as the highest stiffness on the lateral side (2.18 kN·mm- 1). The use of graft materials in MOWHTO results in superior material properties compared to the use of no graft. The static strength of MOWHTO is highest when synthetic grafts are inserted into the osteotomy gap. Allograft wedges provide higher mechanical strength to a MOWHTO than when no graft used. In comparison to the synthetic grafts, allograft wedges result in the stiffness of the osteotomy being more similar at the medial and lateral cortices.


Higher levels of serum lycopene are associated with reduced mortality in individuals with metabolic syndrome.
Metabolic syndrome increases the risk of mortality. Increased oxidative stress and inflammation may play an important role in the high mortality of individuals with metabolic syndrome. Previous studies have suggested that lycopene intake might be related to the reduced oxidative stress and decreased inflammation. Using data from the National Health and Nutrition Examination Survey, we examined the hypothesis that lycopene is associated with mortality among individuals with metabolic syndrome. A total of 2499 participants 20 years and older with metabolic syndrome were divided into 3 groups based on their serum concentration of lycopene using the tertile rank method. The National Health and Nutrition Examination Survey from years 2001 to 2006 was linked to the mortality file for mortality follow-up data through December 31, 2011, to determine the mortality rate and hazard ratios (HR) for the 3 serum lycopene concentration groups. The mean survival time was significantly higher in the group with the highest serum lycopene concentration (120.6 months; 95% confidence interval [CI], 118.8-122.3) and the medium group (116.3 months; 95% CI, 115.2-117.4), compared with the group with lowest serum lycopene concentration (107.4 months; 95% CI, 106.5-108.3). After adjusting for possible confounding factors, participants in the highest (HR, 0.61; P = .0113) and in the second highest (HR, 0.67; P = .0497) serum lycopene concentration groups showed significantly lower HRs of mortality when compared with participants in the lower serum lycopene concentration. The data suggest that higher serum lycopene concentration has a significant association with the reduced risk of mortality among individuals with metabolic syndrome.


Candi(e)d action: biosocialities of Turkish Berliners living with diabetes.
In this article, I explore Turkish migrants' responses to diabetes in Germany. Anthropological studies on health inequalities tend to theorize "social suffering" as passive experiences; those that analyze active social engagement by patient groups as "biosociality" do so solely in the realm of biotechnologies and suggest that social disadvantage prevent active engagement. This article draws on 12 months of ethnographic fieldwork in Berlin from 2006 to 2007. Although Turkish Berliners seem burdened by diabetes, informal diabetes care, for example through a self-help group, is nonetheless collectively negotiated. Increasing incidence and awareness of diabetes in Berlin's Turkish population and their growing political organization and economic entrepreneurship, against the backdrop of experiences of marginality, gives rise to biosociality unanticipated in previous accounts. Addressing the limitations of previous uses of biosociality, this ethnography suggests that social interaction and belonging that formed around altered biologies, here diabetes, are complex and fragmented.


Watt-level blue light for precision spectroscopy, laser cooling and trapping of strontium and cadmium atoms.
High-power and narrow-linewidth laser light is a vital tool for atomic physics, being used for example in laser cooling and trapping and precision spectroscopy. Here we produce Watt-level laser radiation at 457.75 nm and 460.86 nm of respective relevance for the cooling transitions of cadmium and strontium atoms. This is achieved via the frequency doubling of a kHz-linewidth vertical-external-cavity surface-emitting laser (VECSEL), which is based on a novel gain chip design enabling lasing at > 2 W in the 915-928 nm region. Following an additional doubling stage, spectroscopy of the 1S0 → 1P1 cadmium transition at 228.87 nm is performed on an atomic beam, with all the transitions from all eight natural isotopes observed in a single continuous sweep of more than 4 GHz in the deep ultraviolet. The absolute value of the transition frequency of 114Cd and the isotope shifts relative to this transition are determined, with values for some of these shifts provided for the first time.


Impacts of salinity and fish-exuded kairomone on the survival and macromolecular profile of Daphnia pulex.
Global warming is already causing salinization of freshwater ecosystems located in semi-arid regions, including Turkey. Daphnids, which are important grazers on phytoplankton and a major food source for fish and invertebrates, are sensitive to not only changes in salinity levels, but also presence of predators. In this study, the interactive effect of salinity toxicity (abiotic factor) with predation pressure mimicked by the fish-exuded kairomone (biotic factor) and the effect of salt acclimation on daphnids were investigated. Impacts of these stressors on daphnid survival, life history and molecular profile were observed. The presence of the kairomone antagonistically alters the effect of salinity, as observed from the 24- and 48-h LC(50) values and survival results. Molecular findings provided solid evidence to this antagonism at even lower salt concentrations, for which antagonism was not evident with organismal data. Fish predation counterbalances the negative effect of salinity in terms of reserve energy density. Therefore, it is important to investigate multiple stressor effects in ecotoxicological bioassays complemented with molecular techniques. The single effect of increasing salinity resulted in increased mortality, decreased fecundity, and slower somatic growth in Daphnia, despite their acclimation to salinity. This insignificance of acclimation indicates that Daphnia do not have any physiological mechanisms to buffer the adverse effects of salinity, making it a very crucial factor. Salinity-induced reduction in population growth rate of freshwater keystone species Daphnia-despite acclimation-indicates that global warming-induced salinity may cascade through the food web and lead to dramatic environmental consequences in the structure of lake ecosystems.


Burnout and perceptions of conscience among health care personnel: a pilot study.
Although organizational and situational factors have been found to predict burnout, not everyone employed at the same workplace develops it, suggesting that becoming burnt out is a complex, multifaceted phenomenon. The aim of this study was to elucidate perceptions of conscience, stress of conscience, moral sensitivity, social support and resilience among two groups of health care personnel from the same workplaces, one group on sick leave owing to medically assessed burnout (n = 20) and one group who showed no indications of burnout (n = 20). The results showed that higher levels of stress of conscience, a perception of conscience as a burden, having to deaden one's conscience in order to keep working in health care and perceiving a lack of support characterized the burnout group. Lower levels of stress of conscience, looking on life with forbearance, a perception of conscience as an asset and perceiving support from organizations and those around them (social support) characterized the non-burnout group.


The biology of fear.
Each of us has felt afraid, and we can all recognize fear in many animal species. Yet there is no consensus in the scientific study of fear. Some argue that 'fear' is a psychological construct rather than something discoverable through scientific investigation. Others argue that the term 'fear' cannot properly be applied to animals because we cannot know whether they feel afraid. Studies in rodents show that there are highly specific brain circuits for fear, whereas findings from human neuroimaging seem to make the opposite claim. Here, I review the field and urge three approaches that could reconcile the debates. For one, we need a broadly comparative approach that would identify core components of fear conserved across phylogeny. This also pushes us towards the second point of emphasis: an ecological theory of fear that is essentially functional. Finally, we should aim even to incorporate the conscious experience of being afraid, reinvigorating the study of feelings across species.


Adaptive evolution of Escherichia coli K-12 MG1655 during growth on a Nonnative carbon source, L-1,2-propanediol.
Laboratory adaptive evolution studies can provide key information to address a wide range of issues in evolutionary biology. Such studies have been limited thus far by the inability of workers to readily detect mutations in evolved microbial strains on a genome scale. This limitation has now been overcome by recently developed genome sequencing technology that allows workers to identify all accumulated mutations that appear during laboratory adaptive evolution. In this study, we evolved Escherichia coli K-12 MG1655 with a nonnative carbon source, l-1,2-propanediol (l-1,2-PDO), for approximately 700 generations. We found that (i) experimental evolution of E. coli for approximately 700 generations in 1,2-PDO-supplemented minimal medium resulted in acquisition of the ability to use l-1,2-PDO as a sole carbon and energy source so that the organism changed from an organism that did not grow at all initially to an organism that had a growth rate of 0.35 h(-1); (ii) six mutations detected by whole-genome resequencing accumulated in the evolved E. coli mutant over the course of adaptive evolution on l-1,2-PDO; (iii) five of the six mutations were within coding regions, and IS5 was inserted between two fuc regulons; (iv) two major mutations (mutations in fucO and its promoter) involved in l-1,2-PDO catabolism appeared early during adaptive evolution; and (v) multiple defined knock-in mutant strains with all of the mutations had growth rates essentially matching that of the evolved strain. These results provide insight into the genetic basis underlying microbial evolution for growth on a nonnative substrate.


Coordinating end of life care for individuals with a mental illness--A nurse practitioner collaboration.
People with a severe and persistent mental illness (SPMI) who develop a life limiting illness are one of the most vulnerable and marginalised groups of people in society today (Woods, Willison, Kington, & Gavin, 2008). In addition to the effects of mental illness, individuals who also have comorbid life limiting illness frequently suffer the compounding issues of social isolation, declining physical abilities and physical pain. The Integrated Mental Health and Palliative Care Task (IMhPaCT) was an eighteen-month project funded through an Australian Government Department of Health and Ageing Grant. The project included a range of service improvement initiatives to enhance the quality of care for individuals with SPMI who also had a life limiting illness. This paper will report on the collaboration between two nurse practitioners, from the specialities of Mental Health and Palliative Care and their impact on optimising end of life care for this client group. Both specialities are underpinned by similar values including addressing the needs of the whole person and the importance of developing a therapeutic relationship (McGrath & Holewa, 2004). This paper will demonstrate how similarities in philosophy, as well as differences in focus of care, enhanced joint clinical practice at an advanced and extended level.


Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain.
Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthetic drugs trigger apoptotic death of neurons and oligodendrocytes in developing mammalian brains. Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in developing nonhuman primate brains. Fetal macaques (n = 7-8/group), at a neurodevelopmental age comparable to premature human infants, were exposed in utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3 fold for neurons and 3.4 fold for oligodendrocytes compared to control brains. Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to control levels but did not augment oligoapoptosis. Neuronal death was particularly pronounced in the basal ganglia and cerebellum. Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis. Caffeine markedly augments neurotoxicity of isoflurane in the fetal macaque brain and challenges the assumption that caffeine is safe for premature infants.


Gonadotropin alpha-subunit glycoprotein from channel catfish (Ictalurus punctatus) and its expression during hormone-induced ovulation.
Complementary DNA (cDNA) encoding the channel catfish (Ictalurus punctatus) gonadotropin (GTH) alpha-subunit glycoprotein was cloned by polymerase chain reaction (PCR) from a plasmid library made from pituitary RNA. Complete cDNA cloning was achieved by carrying out two PCR reactions: one with an upstream sense primer plus the universal sequencing primer, located downstream of the poly(A) sequence of the cDNA in the plasmid vector, to amplify the downstream portion of the cDNA; the other with a downstream antisense primer plus the reverse-sequencing primer, located upstream of the very 5' end of the cDNA sense strand in the plasmid vector, to amplify the upstream portion of the cDNA. The two amplified fragments overlapping about 70 bp. Nucleotide sequence analysis revealed that the catfish GTH alpha-subunit was 658 bp encoding 116 amino acids and harboring a 5' nontranslated region (NTR) of 42 bp and a 3' NTR of 265 bp. The deduced amino acid sequence of the catfish GTH alpha-subunit is highly conserved with those from other cloned teleost GTH alpha-subunits. The GTH alpha-subunit was highly expressed even before induction for ovulation in females during spawning season. Administration of carp pituitary extract (a spawning-inducing reagent) induced only 1.4-fold higher expression of the GTH alpha-subunit RNA, but included very rapid egg maturation and ovulation. This unexpected result indicated that the GTH alpha-subunit may not be the limiting factor for ovulation and spawning, which may be regulated by the change of proportional coupling of the GTH alpha-subunit with specific beta-subunit during hormone-induced ovulation.


Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.
Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes. We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution. No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined. Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions.


Lightness matching and perceptual similarity.
Lightness constancy is the ability to perceive surface reflectance correctly despite substantial changes in lighting intensity. A classic view is that lightness constancy is the result of a "discounting" of lighting intensity, and this continues to be a prominent view today. Logvinenko and Maloney (2006) have proposed an alternative approach to understanding lightness constancy, in which observers do not make explicit estimates of reflectance, and lightness constancy is instead based on a perceptual similarity metric that depends on both the reflectance and the illuminance of surfaces viewed under different lighting conditions. Here we compare these two views using a novel, free-adjustment reflectance-matching task. We test whether observers can match reflectance in a task where they are free to adjust both the illuminance and the reflectance of the match stimulus over a wide range. We find that observers can match reflectance under these conditions, which supports the view that observers make explicit estimates of reflectance. We also compare performance in this free adjustment task using physical objects and computer-rendered images as stimuli. We find that lightness constancy is good in both cases, but with some evidence of a glow-related artifact with computer-rendered stimuli.


Risk Factors for Spousal Physical Violence Against Women in Saudi Arabia.
This study aimed to explore selected risk factors for spousal physical violence (SPV) in women frequenting primary health care clinics (PHCs) in Saudi Arabia. A cross-sectional study design was conducted in six PHCs, where one-on-one, private interviews with 200 women were conducted using a standardized World Health Organization (WHO) violence against women questionnaire (v.10.0). SPV was reported by 45.5% of women. Husband-specific risk factors including alcohol or drug addiction, unemployment, control of wealth in the family, and physical aggression toward other men were significant predictors for SPV. A multisectoral approach should be implemented with focus on providers' training, women's safety, and involvement of men in violence prevention and intervention programs.


Personal, Family, and Peer Correlates of General and Sport Physical Activity among African American, Latino, and White Girls.
This study examined associations between personal, family, and peer variables on objectively measured physical activity (PA), and sports participation, of African American, Latino, and white girls. Specific variables included barriers efficacy, parent PA, parent support of PA, the home exercise environment, friends' PA, and friends' support of PA. The sample comprised 372 girls (mean age = 12.03 years; SD = 1.81; n = 128 African American, n = 120 Latino, and n = 124 white). Data were analyzed using multiple-sample structural equation models (by ethnicity), controlling for age, household income, body mass index, and physical development. Girls' moderate to vigorous PA (MVPA) was positively related to friends' support for all groups, and to parent PA only for African American girls. For sports, greater parental support related to more participation across ethnic/racial groups, whereas friends' support was important only for African American girls. Age and physical development were negatively related to MVPA, and higher income was associated with greater sports participation. Numerous significant correlations emerged between the independent variables, with some differences across racial/ethnic groups. Findings highlight the role of parent and friends' support for both MVPA and sports participation of early adolescent girls, as well as the importance of determining PA correlates among different ethnic/racial subgroups.