The Role of Physicians During Hunger Strikes of Undocumented Migrant Workers in a Non-Custodial Setting.
Since the beginning of the 21st century, the living conditions of undocumented migrant workers in Belgium have deteriorated drastically. In Brussels, after various social actions, undocumented people began squatting and occupying public buildings to make their struggle visible to society. Desperate, some seized the possibility of a loophole in Belgian law that permits ill persons to have access to a temporary residence permit and started hunger striking. Confronted with consecutive strikes, medical teams of voluntary health professionals faced a big dilemma. A search of the medical literature yielded information about the overall and specific tasks of health professionals during hunger strikes in custodial and hospital settings, but no scientific guidelines were found to address the specific problems the team was confronted with. Information was collected about 15 hunger strikes over a period of seven years, involving the participation of 1,158 strikers. This article describes the medical, organizational, and ethical difficulties encountered in the follow-up of hunger strikes in non-custodial settings, including those associated with the establishment of a health-care structure, operation with very limited resources, and communication with the media and other health professionals.


Transtympanic gentamicin for Meniere's syndrome.
Study the impact of transtympanic gentamicin on patients with unilateral Meniere's syndrome. Partial chemical labyrinthectomy is a relatively recent concept for the treatment of Meniere's syndrome. It uses the ototoxic effect of gentamicin to reduce the symptom of vertigo and maintain cochlear function. A prospective study using transtympanic gentamicin was begun in January 1994. Patients selected had failed medical therapy, but were not incapacitated. Patients had preinjection audiometric and electronystagmography data. Most had an imaging study. All had one injection, about half had more than one. Patients were seen 1 month after therapy and repeat studies were obtained. Repeat injection was performed if indicated. Follow-up from the chart or by telephone was obtained. Data were tabulated using the 1995 American Academy of Otologaryngology-Head and Neck Surgery guidelines. Through December 1996 43 patients with unilateral Meniere's syndrome were treated. The pretherapy function level was 3 through 5. After therapy the function level was 1 or 2. There was almost no change in cochlear function and no patient became deaf. Many patients had mild ataxia or dysequilibrium during the first 2 weeks following therapy. Most patients showed some decrease in labyrinthine function measured on electronystagmography. No attempt was made to ablate labyrinthine function. Seventeen of 18 patients had a vertigo index in the class A or B category after 2 years. Transtympanic gentamicin has become the treatment of choice for patients who fail medical therapy for Meniere's syndrome at the authors' institution.


Gp63 gene polymorphism and population structure of Leishmania donovani complex: influence of the host selection pressure?
The gp63 encoding genes were characterized by PCR-RFLP in 35 isolates representative of the Leishmania donovani complex (L. infantum, L. donovani, L. archibaldi and L. chagasi), with special attention to Mediterranean L. infantum from different geographical origins, and in separate groups from Old World Leishmania (L. major, L. tropica and L. aethiopica). The aim was to evaluate how the possible selective pressure by the host on these important surface proteins would influence structuring of our sample. Comparison was carried out with the structure obtained (i) from reported isoenzyme data, characters supposed to vary neutrally, and (ii) from PCR-RFLP analysis of gp63 inter-genic regions, containing nontranslated spacers and regulatory genes. Polymorphism within the gp63-encoding region, was much higher than in gp63 inter-genic regions. In the gp63 intra-genic dendrogram, the 4 species of L. donovani complex were discriminated and quite distinct from outgroups. Within L. infantum, geographical structuring was observed and did not overlap with the structure built-up from isoenzymes and inter-genic data. These results support the idea of a strong host-selection on gp63, at vector level but most of all at vertebrate (human or dog) immunological level. Furthermore, they illustrate how the nature of genetic characters may influence the perception of population structuring.


Entropy Mapping Approach for Functional Reentry Detection in Atrial Fibrillation: An In-Silico Study.
Catheter ablation of critical electrical propagation sites is a promising tool for reducing the recurrence of atrial fibrillation (AF). The spatial identification of the arrhythmogenic mechanisms sustaining AF requires the evaluation of electrograms (EGMs) recorded over the atrial surface. This work aims to characterize functional reentries using measures of entropy to track and detect a reentry core. To this end, different AF episodes are simulated using a 2D model of atrial tissue. Modified Courtemanche human action potential and Fenton-Karma models are implemented. Action potential propagation is modeled by a fractional diffusion equation, and virtual unipolar EGM are calculated. Episodes with stable and meandering rotors, figure-of-eight reentry, and disorganized propagation with multiple reentries are generated. Shannon entropy ( S h E n ), approximate entropy ( A p E n ), and sample entropy ( S a m p E n ) are computed from the virtual EGM, and entropy maps are built. Phase singularity maps are implemented as references. The results show that A p E n and S a m p E n maps are able to detect and track the reentry core of rotors and figure-of-eight reentry, while the S h E n results are not satisfactory. Moreover, A p E n and S a m p E n consistently highlight a reentry core by high entropy values for all of the studied cases, while the ability of S h E n to characterize the reentry core depends on the propagation dynamics. Such features make the A p E n and S a m p E n maps attractive tools for the study of AF reentries that persist for a period of time that is similar to the length of the observation window, and reentries could be interpreted as AF-sustaining mechanisms. Further research is needed to determine and fully understand the relation of these entropy measures with fibrillation mechanisms other than reentries.


Genetic evidence for the association between COVID-19 epidemic severity and timing of non-pharmaceutical interventions.
Unprecedented public health interventions including travel restrictions and national lockdowns have been implemented to stem the COVID-19 epidemic, but the effectiveness of non-pharmaceutical interventions is still debated. We carried out a phylogenetic analysis of more than 29,000 publicly available whole genome SARS-CoV-2 sequences from 57 locations to estimate the time that the epidemic originated in different places. These estimates were examined in relation to the dates of the most stringent interventions in each location as well as to the number of cumulative COVID-19 deaths and phylodynamic estimates of epidemic size. Here we report that the time elapsed between epidemic origin and maximum intervention is associated with different measures of epidemic severity and explains 11% of the variance in reported deaths one month after the most stringent intervention. Locations where strong non-pharmaceutical interventions were implemented earlier experienced much less severe COVID-19 morbidity and mortality during the period of study.


Chemical-free inactivated whole influenza virus vaccine prepared by ultrashort pulsed laser treatment.
There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques.


Calcium-dependent, swelling-activated K+ conductance in human neuroblastoma cells.
In most mammalian cells, regulatory volume decrease (RVD) is mediated by swelling-activated Cl(-) and K(+) channels. Previous studies in the human neuroblastoma cell line CHP-100 have demonstrated that exposure to hypoosmotic solutions activates Cl(-) channels which are sensitive to Ca(2+). Whether a Ca(2+)-dependent K(+) conductance is activated after cell swelling was investigated in the present studies. Reducing the extracellular osmolarity from 290 to 190 mOsm/kg H(2)O rapidly activated 86Rb effluxes. Hypoosmotic stress also increased cytosolic Ca(2+) in fura-2 loaded cells. Pretreatment with 2.5 mM EGTA and nominally Ca(2+) free extracellular solution significantly decreased the hypoosmotically induced rise in cytosolic Ca(2+) and the swelling-activated 86Rb efflux. In cell-attached patch-clamp studies, decreasing the extracellular osmolarity activated a K(+) conductance that was blocked by Ba(2+). In addition, the swelling-activated K(+) channels were significantly inhibited in the presence of nominally free extracellular Ca(2+) and 2.5mM EGTA. These results suggest that in response to hypoosmotic stress, a Ca(2+)-dependent K(+) conductance is activated in the human neuroblastoma cell line CHP-100.


Detection of extraordinary large bio-magnetic field strength from human hand during external Qi emission.
It is generally accepted that more than 10(-6) gauss order magnetism was not detected in normal human condition. However, we detected 10(-3) gauss (mGauss) order bio-magnetic field strength from the palm in special persons who emitted External Qi ("Chi" or "Ki"). This detection was possible by special arranged magnetic field detection system, consisted of a pair of 2 identical coils with 80,000 turns and a high sensitivity amplifier. Each of the coils were rolled 80,000 turns accurately, and were connected in series in opposite direction, actuating as a gradiometer. We measure bio-magnetic field strength in 37 subjects with this detection system. The only 3 subjects of them exhibited strong bio-magnetic field of 2 to 4 mGauss in frequency range of 4 to 10 Hz. This magnetic field strength was greater than that of normal human bio-magnetism by 1,000 times at least. A simultaneous measurement of bio-magnetic field strength and its corresponding bio-electric current was examined in one subject. During exhibiting such strong bio-magnetism, its corresponding electric current was not detectable. Therefore, the extra-ordinary large bio-magnetic field strength can not derive from internal body current alone, hence the origin of the large bio-magnetism is still unknown. We suppose that the extraordinary large bio-magnetic field strength might be originated from "Qi" energy in the oriental medicine or in the oriental traditional philosophy.


Pretreatment motivation and therapy outcomes in eating disorders: A systematic review and meta-analysis.
Identifying modifiable predictors of outcomes following treatment for eating disorders may help to tailor interventions to patients' individual needs, improve treatment efficacy, and develop new interventions. The goal of this meta-analysis was to quantify the association between pretreatment motivation and posttreatment changes in eating disorder symptomology. We reviewed 196 longitudinal studies reporting on change on indices of overall eating-disorder symptomatology, weight gain, binge-eating, vomiting, anxiety/depression, and treatment adherence. Meta-analyses were performed using two complementary approaches: (a) combined probability analysis using the added Z's method; (b) effect size analyses. Using random-effect models, effect sizes were pooled when there were at least three studies with the same type of statistical design and reporting statistics on the same outcome. Heterogeneity in study outcome was evaluated using Q and I2 statistics. Studies were reviewed qualitatively when the number of studies or reported data were insufficient to perform a meta-analysis. Forty-two articles were included. Although samples and treatments differed substantially across studies, results across studies were remarkably consistent. Both combined-probability and effect-size analyses indicated positive effects of pretreatment motivation on improvement in general eating-disorder symptoms (Cohen's r = .17), and an absence of effects on anxiety/depression symptoms. Remaining outcome indices were subject to selective reporting and/or small sample size bias. Our findings underscore the importance of incorporating treatment engagement approaches in the treatment of eating disorders. Optimal reporting of study findings and improving study quality would improve future efforts to obtain an in-depth understanding of the relationship between motivation and eating disorder symptoms.


Human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis: viral load and muscle tone are correlated.
Human T-lymphotropic virus type 1 (HTLV-1) infections are associated with varying degrees of HTLV-1 viral load and spasticity. Increased viral load is associated with higher risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The authors performed a cross-sectional study of 24 people with HAM/TSP in Lima, Perú, to determine if higher HTLV-1 viral load was correlated with increased muscle tone, measured with a device providing quantitative spasticity assessment (QSA). Median HTLV-1 viral load was 17.0 copies/100 peripheral blood mononuclear cells and QSA value was 39.9 Newton-meters/radian. HTLV-1 viral load was significantly correlated with QSA value (Spearman rho = .48, P = .02), suggesting viral load may play a role in expression of symptomatic neurologic disease. Longitudinal studies are needed to determine if treatments that reduce viral load will reduce muscle tone.


Zodiac: A Comprehensive Depiction of Genetic Interactions in Cancer by Integrating TCGA Data.
Genetic interactions play a critical role in cancer development. Existing knowledge about cancer genetic interactions is incomplete, especially lacking evidences derived from large-scale cancer genomics data. The Cancer Genome Atlas (TCGA) produces multimodal measurements across genomics and features of thousands of tumors, which provide an unprecedented opportunity to investigate the interplays of genes in cancer. We introduce Zodiac, a computational tool and resource to integrate existing knowledge about cancer genetic interactions with new information contained in TCGA data. It is an evolution of existing knowledge by treating it as a prior graph, integrating it with a likelihood model derived by Bayesian graphical model based on TCGA data, and producing a posterior graph as updated and data-enhanced knowledge. In short, Zodiac realizes "Prior interaction map + TCGA data → Posterior interaction map." Zodiac provides molecular interactions for about 200 million pairs of genes. All the results are generated from a big-data analysis and organized into a comprehensive database allowing customized search. In addition, Zodiac provides data processing and analysis tools that allow users to customize the prior networks and update the genetic pathways of their interest. Zodiac is publicly available at www.compgenome.org/ZODIAC. Zodiac recapitulates and extends existing knowledge of molecular interactions in cancer. It can be used to explore novel gene-gene interactions, transcriptional regulation, and other types of molecular interplays in cancer.


Age-specific incidence, risk factors and outcome of acute abdominal aortic aneurysms in a defined population.
Contemporary population-based data on age-specific incidence and outcome from acute abdominal aortic aneurysm (AAA) events are needed to understand the impact of risk factor modification and demographic change, and to inform AAA screening policy. In a prospective population-based study (Oxfordshire, UK, 2002-2014), event rates, incidence, early case fatality and long-term outcome from all acute AAA events were determined, both overall and in relation to the four main risk factors: smoking, hypertension, male sex and age. Over the 12-year interval, 103 incident acute AAA events occurred in the study population of 92,728 (men 72·8 per cent; 59·2 per cent 30-day case fatality rate). The incidence per 100,000 population per year was 55 in men aged 65-74 years, but increased to 112 at age 75-84 years and to 298 at age 85 years or above. Some 66·0 per cent of all events occurred in those aged 75 years or more. The incidence at 65-74 years was highest in male smokers (274 per 100,000 population per year); 27 (96 per cent) of 28 events in men aged less than 75 years occurred in ever-smokers. Mean(s.d.) age at event was lowest in current smokers (72·2(7·2) years), compared with that in ex-smokers (81·2(7·0) years) and never-smokers (83·3(7·9) years) (P < 0·001). Hypertension was the predominant risk factor in women (diagnosed in 93 per cent), with 20 (71 per cent) of all 28 events in women occurring in those aged 75 years or above with hypertension. The 30-day case fatality rate increased from 40 per cent at age below 75 years to 69 per cent at age 75 years or more (P = 0·008). Two-thirds of acute AAA events occurred at age 75 years or above, and more than 25 per cent of events were in women. Taken with the strong associations with smoking and hypertension, these findings could have implications for AAA screening.


Immunosuppressive factors from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10. IV. Lack of strain restrictions among allogeneic, nonresponder donors and recipients.
The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder mice but stimulates development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT plaque-forming cell responses to GAT complexed to methylated bovine serum albumin (MBSA). Extracts from lymphoid cells of GAT-primed but not control, nonresponder (DBA/1) mice contain a T-cell factor (GAT-TsF) that also specifically suppresses responses to GAT-MBSA by normal syngeneic spleen cells. The experiments reported in this communication demonstrate that: (a) extracts from all GAT-primed nonresponder mice tested contain GAT-TsF; (b) non-H-2 genes do not restrict the production of GAT-TsF; (c) all nonresponder strains of mice regardless of their non-H-2 genes are suppressed by GAT-TsF from all other strains bearing the nonresponder H-2p,q,s haplotypes; (d) suppression of GAT-MBSA responses by both syngeneic and allogeneic nonresponder spleen cells is mediated by a molecule encoded by the H-2 gene complex; and (e) both syngeneic and allogeneic nonresponder mice are suppressed by purified GAT-TsF that lacks immunoreactive GAT.


Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.
Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .).


Defining approaches to settlement mapping for public health management in Kenya using medium spatial resolution satellite imagery.
This paper presents an appraisal of satellite imagery types and texture measures for identifying and delineating settlements in four Districts of Kenya chosen to represent the variation in human ecology across the country. Landsat Thematic Mapper (TM) and Japanese Earth Resources Satellite-1 (JERS-1) synthetic aperture radar (SAR) imagery of the four districts were obtained and supervised per-pixel classifications of image combinations tested for their efficacy at settlement delineation. Additional data layers including human population census data, land cover, and locations of medical facilities, villages, schools and market centres were used for training site identification and validation. For each district, the most accurate approach was determined through the best correspondence with known settlement and non-settlement pixels. The resulting settlement maps will be used in combination with census data to produce medium spatial resolution population maps for improved public health planning in Kenya.


The Italian version of the Fear-Avoidance Beliefs Questionnaire (FABQ-I): cross-cultural adaptation, factor analysis, reliability, validity, and sensitivity to change.
Evaluation of the psychometric properties of a translated and culturally adapted questionnaire. Translating, culturally adapting, and validating the Italian version of the Fear-Avoidance Beliefs Questionnaire (FABQ-I) to allow its use with Italian-speaking patients with low-back pain (LBP). Growing attention is being given to standardized outcome measures to improve interventions for LBP. A translated form of the FABQ has never been validated in Italian patients with LBP. The FABQ-I questionnaire was developed by means of forward-backward translation, a final review by an expert committee, and a test of the prefinal version to establish its correspondence with the original English version. The psychometric testing included factor analysis, reliability by internal consistency (Cronbach α) and test-retest reliability (intraclass coefficient correlation), convergent validity by comparing FABQ-I with the Italian version of the Tampa Scale of Kinesiophobia (TSK-I), and discriminant validity by comparing FABQ-I with a visual analogue scale, the Roland Morris Disability Questionnaire, and the Hospital Anxiety and Depression Scale (Pearson correlation). It took 4 months to develop a shared version of the FABQ-I. The questionnaire was administered to 180 subjects and proved to be acceptable. Factor analysis revealed a 2-factor, 12-item solution (57% of explained variance). The questionnaire showed good internal consistency (α = 0.822) and high test-retest reliability (intraclass coefficient correlation = 0.869). Convergent validity showed a moderate correlation with TSK-I (r = 0.440), and discriminant validity showed moderate-poor correlations with a visual analogue scale (r = 0.335), Roland Morris Disability Questionnaire (r = 0.414), and Hospital Anxiety and Depression Scale (r = 0.258 for the Anxiety score and r = 0.246 for the Depression score). The results of the psychometric analyses of the subscales were similar to those of the scale as a whole. The FABQ outcome measure was successfully translated into Italian and proved to have a good factorial structure and psychometric properties that replicated the results of other existing versions. Its use is recommended for research purposes.


Does Climate Change Communication Matter for Individual Engagement with Adaptation? Insights from Forest Owners in Sweden.
Natural resource managers urgently need to adapt to climate change, and extension services are increasingly using targeted communication campaigns to promote individual engagement with adaptation. This study compares two groups of Swedish forest owners: 1493 who participated in two climate communication projects by the Swedish Forest Agency, and 909 who were randomly sampled. The study finds statistically significant differences between the two groups in terms of climate change awareness and concern, belief in the urgency to act and intentions to take adaptive measures. Results suggest that the primary effect of the climate chance communication seems to have been on forest owners' subjective risk perceptions and beliefs in their knowledge and ability, which make it more likely that individuals will take adaptive action in the future. The study also finds that experience with extreme events affects people's intentions to take adaptive measures independently from their beliefs that these extremes were caused by climate change. Furthermore, findings also highlight the need for communication research and practice to recognise the impeding role social norms and economic rationales can play for individual adaptation. Future research should make use of longitudinal and qualitative research to assess the effect of deliberation- and solution-orientated communication on people's intentions and actions to adapt to climate change.


Intravitreal Fluocinolone Acetonide May Decelerate Diabetic Retinal Neurodegeneration.
There is no prevention or treatment for diabetic retinal neurodegeneration (DRN), which is a complication of diabetes that can occur independently of diabetic retinopathy (DR). We hypothesized that an intravitreal fluocinolone acetonide (FAc) implant may affect the rate of DRN when used in patients with diabetic macular edema (DME). In this retrospective analysis, optical coherence tomography with neuroretinal analysis was obtained at 3-month intervals from 130 patients in the USER study both before (mean duration 903 days, range 35-4005 days) and after administration of FAc (mean 408 days, range 7 to 756 days). The rate of DRN was defined as the change over time on inner neuroretinal thickness using logistic regression. A DRN rate was calculated independently for two areas: region 1 located within 1.5 mm of the fovea, and region 2 from 1.5 mm to 3.0 mm from the fovea. In regions of the macula more than 1.5 mm from the central fovea, there was a statistically significant decrease in the rate of DRN in the post-FAc period. The pre-FAc neuroretinal loss in this area occurred at 4.0 μm/y, compared with a post-FAc loss rate of 1.1 μm/y (P = 0.001). This retrospective study suggests that FAc may decelerate the rate of inner retinal thinning in patients with persistent DME. Further prospective studies are necessary to determine the effects of FAc on the rate of DRN in patients with DME.


The Trichoptera barcode initiative: a strategy for generating a species-level Tree of Life.
DNA barcoding was intended as a means to provide species-level identifications through associating DNA sequences from unknown specimens to those from curated reference specimens. Although barcodes were not designed for phylogenetics, they can be beneficial to the completion of the Tree of Life. The barcode database for Trichoptera is relatively comprehensive, with data from every family, approximately two-thirds of the genera, and one-third of the described species. Most Trichoptera, as with most of life's species, have never been subjected to any formal phylogenetic analysis. Here, we present a phylogeny with over 16 000 unique haplotypes as a working hypothesis that can be updated as our estimates improve. We suggest a strategy of implementing constrained tree searches, which allow larger datasets to dictate the backbone phylogeny, while the barcode data fill out the tips of the tree. We also discuss how this phylogeny could be used to focus taxonomic attention on ambiguous species boundaries and hidden biodiversity. We suggest that systematists continue to differentiate between 'Barcode Index Numbers' (BINs) and 'species' that have been formally described. Each has utility, but they are not synonyms. We highlight examples of integrative taxonomy, using both barcodes and morphology for species description.This article is part of the themed issue 'From DNA barcodes to biomes'.


Selective targeting of PARP-1 zinc finger recognition domains with Au(iii) organometallics.
The binding of Au(iii) complexes to the zinc finger domain of the anticancer drug target PARP-1 was studied using a hyphenated mass spectrometry approach combined with quantum mechanics/molecular mechanics (QM/MM) studies. Competition experiments were carried out, whereby each Au complex was exposed to two types of zinc fingers. Notably, the cyclometallated Au-C^N complex was identified as the most selective candidate to disrupt the PARP-1 zinc finger domain, forming distinct adducts compared to the coordination compound Auphen.


Thermal evolution of the crystal structure of proton conducting BaCe0.8Y0.2O3-δ from high-resolution neutron diffraction in dry and humid atmosphere.
The crystal structure of the proton conducting perovskite BaCe(0.8)Y(0.2)O(3-δ) (BCY20) has been studied via high-resolution in situ neutron diffraction performed in controlled dry and humid (heavy water) oxygen flow. Two phase transitions, cubic Pm3[combining macron]m→R3[combining macron]c (775 °C)→Imma (250 °C) were observed on cooling from 1000 °C in dry O(2). A significant shift of the phase stability fields was observed on cooling in wet oxygen (pD(2)O ≈ 0.2 atm) with the R3[combining macron]c structure stabilised at 900 °C, and the R3[combining macron]c→Imma transition occurring at 675 °C. On cooling below 400 °C a monoclinic, I2/m, phase started to appear. The structural dependence on hydration level is primarily due to the de-stabilisation of the correlated, octahedra tilts as a consequence of structural relaxation around the oxygen vacancies present in the non-hydrated phase. The tendency of hydrated BaCe(0.8)Y(0.2)O(3-δ) to show octahedral tilting is also found to be enhanced, indicating that the deuteronic (protonic) defects influence the crystal structure, possibly via hydrogen bonding. Stabilisation of the monoclinic I2/m phase is attributed to the structural effect of deuterons that is inferred to increase on cooling as deuterons localise to a greater extent. Changing from wet oxidising (O(2) + D2O(g)) to wet reducing (5% H2 in Ar + D2O(g)) atmosphere did not influence the structure or the phase stability, indicating that Ce(4+) was not reduced under the present conditions. Based on the observed cell volume expansion protonic defects are present in the material at 900 °C at a D(2)O partial pressure of ∼0.2 atm. The origin of the chemical expansion is explained by the effective size of the oxygen vacancy being significantly smaller than the [OD] defect. Rietveld analysis has been used to locate possible sites for the deuterons in the high temperature, R3[combining macron]c and Imma, phases that are most relevant for proton transport.


Eye tracking, attention, and schizotypal symptoms in nonpsychotic relatives of patients with schizophrenia.
Biological relatives of patients with schizophrenia demonstrate an increased prevalence of schizotypal personality disorder symptoms, eye tracking deficits, and attentional disturbances. We investigated whether these hypothesized components of a schizophrenia-related phenotype are associated with one another or are independent in nonpsychotic relatives of patients with schizophrenia. Eighty-three nonpsychotic first-degree relatives of 38 patients with schizophrenia and 45 control subjects without a psychiatric diagnosis underwent clinical evaluation, eye tracking evaluation, and the Continuous Performance Test (CPT) of visual attention. Eye tracking qualitative rating was more powerful than quantitative eye tracking measures or CPT measures in discriminating relatives of patients with schizophrenia from control subjects. Correlations between neurocognitive variables and DSM-III-R schizotypal personality disorder symptom clusters suggested that CPT errors of omission are associated with positive schizotypal symptoms. Eye tracking measures were not significantly correlated with schizotypal symptoms or CPT errors in relatives of patients with schizophrenia. Eye tracking deficits in the relatives of patients with schizophrenia are unrelated to CPT deficits and schizotypal symptoms. Eye tracking deficits and disturbances in visual attention may be separate components of a schizophrenia-related phenotype and should be considered as independent factors in genetic studies of schizophrenia.


Clinical and prognostic implications of self-rating depression scales and plasma B-type natriuretic peptide in hospitalised patients with chronic heart failure.
Depression is common among patients with chronic heart failure (CHF) and has been independently associated with a poorer prognosis. This study evaluated the clinical and prognostic value of depression scales (Beck Depression Inventory (BDI), Zung Self-rating Depression Scale (Zung SDS)) along with plasma B-type natriuretic peptide (BNP) in CHF. 155 hospitalised CHF patients (ejection fraction 26.9% (SD 6.4%)) were studied by depression (BDI, Zung SDS) and functional questionnaires (Kansas City Cardiomyopathy Questionnaire (KCCQ), Duke Activity Status Index (DASI)), BNP and 6-minute walk test (6MWT). Patients were followed for 6 months for cardiovascular events, including death from any cause or rehospitalisation for CHF decompensation. Seventy-six (49%) patients with depressive symptoms, as estimated by both scales, had significantly lower DASI and KCCQ scores (13.2 (SD 9.9) vs 23.6 (SD 13.0) and 26.6 (SD 15.0) vs 45.0 (SD 17.0), respectively; p<0.001), higher BNP (921 (SD 889) vs 439 (SD 267) pg/ml, p = 0.001) and reduced 6MWT (270 (SD 130) vs 337 (SD 133); p<0.001). According to logistic regression analysis, Zung SDS and BNP were independently associated with adverse clinical outcomes; values of Zung SDS >or=40 and of BNP >or=290 pg/ml predicted future events with a sensitivity of 82% and 94% and a specificity of 45% and 46%, respectively. The combination of Zung SDS plus BNP had an additive prognostic value, predicting events with a sensitivity of 77% and a specificity of 70% (event-free survival: Zung <40 and BNP <290 pg/ml; 170 (SD 9) days; Zung >or=40 and BNP <290 pg/ml, 159 (SD 14) days; Zung <40 and BNP >or=290 pg/ml, 118 (SD 15) days; Zung >or=40 and BNP >or=290 pg/ml, 73 (SD 8) days, p<0.001). CHF patients with depressive symptoms have impaired physical activity, associated with excessive neurohormonal activation. Among the studied scales, Zung SDS seemed to independently predict clinical outcome, especially in patients with increased plasma BNP concentration. Hence, the combination of those two modalities provides a practical means for risk stratification in CHF.


The Diagnostic and Prognostic Value of Neuropsychological Assessment in Memory Clinic Patients.
Neuropsychological testing has long been embedded in daily clinical practice at memory clinics but the added value of a complete neuropsychological assessment (NPA) to standard clinical evaluation is unknown. To evaluate the added diagnostic and prognostic value of NPA to clinical evaluation only in memory clinic patients. In 221 memory clinic patients of a prospective cohort study, clinical experts diagnosed clinical syndrome (subjective cognitive impairment (SCI), mild cognitive impairment (MCI), or dementia) and etiology (Alzheimer's disease (AD) or no AD), and provided a prognosis of disease course (decline or no decline) before and after results of NPA were made available. The reference standard was a panel consensus based on all clinical information at baseline and up to 2 follow-up assessments. With NPA data available, clinicians changed their initial syndromal diagnosis in 22% of patients, and the etiological diagnosis as well as the prognosis in 15%. This led to an increase in correctly classified cases of 18% for syndromal diagnosis, 5% for etiological diagnosis, and 1% for prognosis. NPA data resulted in the largest improvement in patients initially classified as SCI (syndrome: 93.3% (n = 14) correctly reclassified, etiology: net reclassification improvement [NRI] = 0.61, prognosis: NRI = 0.13) or MCI (syndrome: 89.3% (n = 23) correctly reclassified, etiology: NRI = 0.17, prognosis: NRI = 0.14), while there was no improvement in patients with dementia (syndrome: 100% (n = 1) correctly reclassified, etiology: NRI = -0.05, prognosis: NRI = -0.06). Overall, inclusion of NPA in the diagnostic process increased confidence in all diagnoses with 6-7%. Administration of a complete NPA after standard clinical evaluation has added value for diagnosing cognitive syndrome and its underlying etiology in patients regarded as non-demented based on the first clinical impression.


Anti-modified LDL antibodies, LDL-containing immune complexes, and susceptibility of LDL to in vitro oxidation in patients with type 2 diabetes.
We investigated the hypothesis that modified lipoproteins trigger an immune response leading to the production of autoantibodies and subsequently to the formation of atherogenic immune complexes (IC). We recruited 20 type 2 diabetic patients with macrovascular disease, 14 nondiabetic patients with coronary artery disease (CAD), and 34 healthy control subjects matched for age, sex, and race. Serum antibodies to oxidized and glycated LDL did not differ significantly among the 3 groups. Serum IC contained variable, but not statistically different, amounts of IgG, IgM, and IgA. In contrast, the content of cholesterol in IC isolated from diabetic patients was significantly higher than that in IC isolated from control subjects, and the content of apolipoprotein (apo)-B was significantly higher than that in IC isolated from control subjects and patients with CAD. Cholesteryl ester accumulation in human monocyte-derived macrophages incubated with IC, a measure of the atherogenic potential of IC, was significantly higher in macrophages incubated with red blood cell-adsorbed IC isolated from diabetic patients compared with IC isolated from control subjects (P < 0.03) or from patients with CAD (P < 0.04) and was strongly correlated with the content of apoB (r = 0.68, P < 0.001) and cholesterol (r = 0.61, P < 0.001) in IC. LDL from diabetic patients was more susceptible to oxidation in vitro, was significantly smaller, and contained significantly less alpha-tocopherol than LDL isolated from subjects in the other groups. In addition, the n-3 polyunsaturated fatty acid content of phospholipids and cholesteryl esters in LDL isolated from diabetic patients was significantly increased (P < 0.05) compared with that from patients with CAD or from control subjects. We postulate that LDL size, susceptibility to oxidation, and lipid fatty acid composition may play a critical role in the production of antibodies to oxidized LDL and consequently in the formation of LDL-containing IC in patients with type 2 diabetes.


Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses.
Cellular immunity plays a crucial role in cytomegalovirus (CMV) infection and substantial populations of CMV-specific T cells accumulate throughout life. However, although CMV infection occurs during childhood, relatively little is know about the typical quantity and quality of T cell responses in pediatric populations. One thousand and thirty-six people (Male/Female = 594/442, Age: 0-19 yr.; 959 subjects, 20-29 yr.; 77 subjects) were examined for HLA typing. All of 1036 subjects were tested for HLA-A2 antigen. Of 1036 subjects, 887 were also tested for HLA-A23, 24 antigens. In addition, 50 elderly people (Male/Female = 11/39, Age: 60-92 yr.) were also tested for HLA-A2 antigen. We analyzed the CD8+ T cell responses to CMV, comparing these to responses in children and young. The frequencies, phenotype and function CD8+ T cells for two imunodominant epitopes from pp65 were measured. We observed consistently high frequency and phenotypically "mature" (CD27 low, CD28 low, CD45RA+) CMV-specific CD8+ T cell responses in children, including those studied in the first year of life. These CD8+ T cells retained functionality across all age groups, and showed evidence of memory "inflation" only in later adult life. CMV consistently elicits a very strong CD8+ T cell response in infants and large pools of CMV specific CD8+ T cells are maintained throughout childhood. The presence of CMV may considerably mould the CD8+ T cell compartment over time, but the relative frequencies of CMV-specific cells do not show the evidence of a population-level increase during childhood and adulthood. This contrast with the marked expansion ("inflation") of such CD8+ T cells in older adults. This study indicates that large scale analysis of peptide specific T cell responses in infants is readily possible. The robust nature of the responses observed suggests vaccine strategies aimed at priming and boosting CD8+ T cells against major pathogens (including HIV, malaria and CMV itself) could be successful in this age-group.


Applications and limitations of machine learning in radiation oncology.
Machine learning approaches to problem-solving are growing rapidly within healthcare, and radiation oncology is no exception. With the burgeoning interest in machine learning comes the significant risk of misaligned expectations as to what it can and cannot accomplish. This paper evaluates the role of machine learning and the problems it solves within the context of current clinical challenges in radiation oncology. The role of learning algorithms within the workflow for external beam radiation therapy are surveyed, considering simulation imaging, multimodal fusion, image segmentation, treatment planning, quality assurance, and treatment delivery and adaptation. For each aspect, the clinical challenges faced, the learning algorithms proposed, and the successes and limitations of various approaches are analyzed. It is observed that machine learning has largely thrived on reproducibly mimicking conventional human-driven solutions with more efficiency and consistency. On the other hand, since algorithms are generally trained using expert opinion as ground truth, machine learning is of limited utility where problems or ground truths are not well-defined, or if suitable measures of correctness are not available. As a result, machines may excel at replicating, automating and standardizing human behaviour on manual chores, meanwhile the conceptual clinical challenges relating to definition, evaluation, and judgement remain in the realm of human intelligence and insight.


The preparation of frozen-dried tissue for electron microscopy.
A method is described for the preparation of liver by freezing and drying which avoids the formation of ice crystals visible with the electron microscope. Such dried preparations after postfixation may be stained with numerous reagents. They may also be stained for cytochemical study of ribonucleic and desoxyribonucleic acids, and for glycogen. Details of the methods are given, together with a brief justification of them through a summary of the controls employed. Further details, as well as a description of the submicroscopic morphology following the use of the methods, will be described elsewhere.


Thymosin β4 protects against aortic aneurysm via endocytic regulation of growth factor signaling.
Vascular stability and tone are maintained by contractile smooth muscle cells (VSMCs). However, injury-induced growth factors stimulate a contractile-synthetic phenotypic modulation which increases susceptibility to abdominal aortic aneurysm (AAA). As a regulator of embryonic VSMC differentiation, we hypothesized that Thymosin β4 (Tβ4) may function to maintain healthy vasculature throughout postnatal life. This was supported by the identification of an interaction with low density lipoprotein receptor related protein 1 (LRP1), an endocytic regulator of platelet-derived growth factor BB (PDGF-BB) signaling and VSMC proliferation. LRP1 variants have been implicated by genome-wide association studies with risk of AAA and other arterial diseases. Tβ4-null mice displayed aortic VSMC and elastin defects that phenocopy those of LRP1 mutants, and their compromised vascular integrity predisposed them to Angiotensin II-induced aneurysm formation. Aneurysmal vessels were characterized by enhanced VSMC phenotypic modulation and augmented PDGFR-β signaling. In vitro, enhanced sensitivity to PDGF-BB upon loss of Tβ4 was associated with dysregulated endocytosis, with increased recycling and reduced lysosomal targeting of LRP1-PDGFR-β. Accordingly, the exacerbated aneurysmal phenotype in Tβ4-null mice was rescued upon treatment with the PDGFR-β antagonist Imatinib. Our study identifies Tβ4 as a key regulator of LRP1 for maintaining vascular health, and provides insights into the mechanisms of growth factor-controlled VSMC phenotypic modulation underlying aortic disease progression.


Protective effect of magnesium and metformin on endometrium and ovary in experimental diabetes mellitus.
We evaluated the effect of magnesium and metformin on streptozotocin (STZ)-induced diabetes mellitus (DM) in non-pregnant female rats. The study comprised four groups, each consisting of eight, non-pregnant, adult Wistar female rats with a weight range of 170-250 g, maintained under the usual laboratory conditions. One group of female rats was the control group that received no treatment. To induce DM, the other three groups of animals received streptozotocin (STZ), 60 mg/kg i.p. (in a single dose). The first STZ group received no additional treatment. The second group received MgCl2 1 mmol/kg/day i.p. daily, for eight weeks. The third group received daily metformin, 100 mg/kg/day per os (endogastric probe), for eight weeks. Blood glucose, total plasma magnesium concentrations, and oxidative status were determined prior to, 24 hours and eight weeks after administration of the STZ. After eight weeks of treatment, the animals were anesthetized and sacrificed. The uterus and ovaries were removed and examined under optical microscopy. The data obtained were analyzed statistically using the ANOVA test. The results showed that the number of atretic ovarian follicles was 84%higher in the STZ-induced diabetes group compared to the control group (p<0.01). The number of atretic follicles found in the group receiving daily MgCl2 was 32% higher compared to the untreated control group (p<0.05). The number of atretic follicles was increased by only 27% in the metformin-treated group, as compared with the untreated control group.. The STZ-induced diabetes group presented an endometrial epithelial atrophy not seen in the control group. MgCl2 administration attenuated the degree of endometrial atrophy, there being an endometrial epithelial thickness of 19.43 ± 0.51 μm in the STZ+MgCl2 group (p<0.05), as compared to a thickness of 13.51 ± 0.27 μm in the STZ only-treated diabetic group.


Hepatitis B virus mutations potentially conferring adefovir/tenofovir resistance in treatment-naive patients.
Anti-hepatitis B virus (HBV) therapy leads to the emergence of mutant viral strains during the treatment of chronic hepatitis B with nucleos(t)ides analogues. The existence of HBV variants with primary antiviral resistance may be important for treatment choice. We studied two patients with chronic HBV infection by sequencing the HBV polymerase gene. They had adefovir- and tenofovir-related mutations in the viral polymerase, although they had never been treated. These mutations were rtV214A/rtN238T in one patient and rtA194T in the other. Thus, mutations in untreated patients deserve cautious surveillance. These data indicate that mutations that can theoretically confer adefovir or tenofovir resistance may emerge in treatment-naive patients.


Vasculogenesis in the early quail blastodisc as studied with a monoclonal antibody recognizing endothelial cells.
QH1, a monoclonal antibody that recognizes quail endothelial and haemopoietic cells, was applied to quail blastodiscs in toto, in order to analyse by immunofluorescence the emergence of the vascular tree. The first endothelial cells were detected in the area opaca at the headfold stage and in the area pellucida at the 1-somite stage. Single cells then interconnected progressively, especially in the anterior intestinal portal and along the somites building up the linings of the heart and dorsal aortas. This study demonstrates that endothelial cells differentiate as single entities 4 h earlier in development than hitherto detected and that the vascular network forms secondarily. The horseshoe shape of the extraembryonic area vasculosa is also a secondary acquisition. A nonvascularized area persists until later (at least the 14-somite stage) in the region of the regressing primitive streak.


Cytochrome a1 of acetobacter aceti is a cytochrome ba functioning as ubiquinol oxidase.
Cytochrome a1 is a classic cytochrome that in the 1930s had already been detected in Acetobacter strains and in the 1950s was identified as a terminal oxidase. However, recent studies did not substantiate the previous observations. We have detected a cytochrome a1-like chromophore in Acetobacter aceti, which was purified and characterized in this study. The cytochrome was solubilized from membranes of the strain with octyl beta-D-glucopyranoside and was purified by single column chromatography. The purified cytochrome exhibited a broad alpha peak around 600-610 nm, which turned to a sharp peak at 589 nm in the presence of cyanide. Carbon monoxide difference spectra of the cytochrome indicated the presence of an alpha-type cytochrome. The cytochrome contained 1 mol each of hemes b and a and probably one copper ion. These results suggest that the cytochrome purified from A. aceti is the so-called cytochrome a1, and thus the existence of the classic cytochrome has been reconfirmed. The purified enzyme consisted of four polypeptides of 55, 35, 22, and 18 kDa, and it showed a sedimentation coefficient of 6.3 S in the native form. The enzyme had a high ubiquinol oxidase activity (140-160 mumol of ubiquinol-2 oxidized per min per mg of protein). When reconstituted into proteoliposomes, the cytochrome could generate an electrochemical proton gradient during oxidation of ubiquinol. Thus, cytochrome a1 of A. aceti has been shown to be a cytochrome ba terminal oxidase capable of generating an electrochemical proton gradient concomitant with ubiquinol oxidation.


Near-field effect in the infrared range through periodic Germanium subwavelength arrays.
Using finite-difference-time-domain simulation, we have studied the near-field effect of Germanium (Ge) subwavelength arrays designed in-plane with a normal incidence. Spectra of vertical electric field component normal to the surface show pronounced resonance peaks in an infrared range, which can be applied in a quantum well infrared photodetector. Unlike the near-field optics in metallic systems that are commonly related to surface plasmons, the intense vertical field along the surface of the Ge film can be interpreted as a combination of diffraction and waveguide theory. The existence of the enhanced field is confirmed by measuring the Fourier transform infrared spectra of fabricated samples. The positions of the resonant peaks obtained in experiment are in good agreement with our simulations.


A 1-year multicenter randomized double-blind comparison of repaglinide and glyburide for the treatment of type 2 diabetes. Dutch and German Repaglinide Study Group.
Repaglinide is a newly developed oral blood glucose-lowering agent that exerts its effect by stimulating insulin secretion. This multicenter study was designed to compare the efficacy and safety of this drug with glyburide in a 1-year randomized double-blind study of outpatients with type 2 diabetes. A total of 424 subjects (154 women, 270 men) participated and had the following characteristics: age, 61 +/- 9 years; duration of diabetes. 8 years (range 0.5-35); BMI, 28.3 +/- 3.5 kg/m2; HbA1c, 7.1 +/- 1.4%; and fasting plasma glucose, 10.8 +/- 3.1 mmol/l. The majority of the subjects (91%) were previously treated with sulfonylurea, alone or in combination with metformin. The patients were randomized to a 2:1 ratio of repaglinide (0.5-4 mg t.i.d.) or glyburide (1.75-10.5 mg daily) treatment. The study protocol included a screening visit to assess patient eligibility; a titration period of 6-8 weeks, during which the dosages of repaglinide and glyburide were optimized; and a subsequent 12-month treatment period on fixed, optimal dosages. The trial was completed by 320 subjects, 211 (74%) in the repaglinide and 109 (78%) in the glyburide group. HbA1c initially decreased in both groups and then increased during the second half-year of the maintenance period to a similar extent in the repaglinide and glyburide subjects (0.58 and 0.45% vs. at screening, respectively). In the small group of subjects who previously controlled their condition with diet only (n = 37), a sustained improvement of metabolic control could be observed with both drugs, which was slightly better with glyburide than with repaglinide (theta HbA1c -2.4 vs. -1.0%; P < 0.05). The same trends were seen with fasting plasma glucose. There were no changes in serum lipids. Over the course of the study, 15% of the repaglinide-treated and 13% of glyburide-treated subjects withdrew due to adverse events, mostly hyperglycemia. No differences in adverse events between both drugs were reported. There were no differences in incidences of hypoglycemia. Repaglinide is a safe and efficacious oral blood glucose-lowering agent, with a potency similar to that of glyburide. Its rapid onset of action and hepatic clearance allows meal-related administration, including in subjects with impaired kidney function.


Grain accumulation of selenium species in rice (Oryza sativa L.).
Efficient Se biofortification programs require a thorough understanding of the accumulation and distribution of Se species within the rice grain. Therefore, the translocation of Se species to the filling grain and their spatial unloading were investigated. Se species were supplied via cut flag leaves of intact plants and excised panicle stems subjected to a ± stem-girdling treatment during grain fill. Total Se concentrations in the flag leaves and grain were quantified by inductively coupled plasma mass spectrometry. Spatial accumulation was investigated using synchrotron X-ray fluorescence microtomography. Selenomethionine (SeMet) and selenomethylcysteine (SeMeSeCys) were transported to the grain more efficiently than selenite and selenate. SeMet and SeMeSeCys were translocated exclusively via the phloem, while inorganic Se was transported via both the phloem and xylem. For SeMet- and SeMeSeCys-fed grain, Se dispersed throughout the external grain layers and into the endosperm and, for SeMeSeCys, into the embryo. Selenite was retained at the point of grain entry. These results demonstrate that the organic Se species SeMet and SeMeSeCys are rapidly loaded into the phloem and transported to the grain far more efficiently than inorganic species. Organic Se species are distributed more readily, and extensively, throughout the grain than selenite.


Evaluation of the single-injection plasma disappearance of technetium-99m mercaptoacetyltriglycine method for determination of effective renal plasma flow in dogs with normal or abnormal renal function.
Effective renal plasma flow (ERPF) was evaluated, using continuous-infusion p-aminohippurate clearance (CLPAH) and single-injection plasma clearance of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3; CLMAG3) methods. Simultaneous clearance determinations were made in 6 dogs: 2 determinations for each dog before, and 1 determination after renal failure was induced by administration of amphotericin B. Linear regression analysis was used to derive an equation to estimate ERPF from CLMAG3 after the single IV injection. A Student's t-test was used to compare pharmacokinetics between the dogs when they were healthy and when they were in renal failure. An F-test was used to determine the appropriate Student's t-test. Results indicated that CLMAG3 correlated reasonably well (r = 0.83, P < 0.0001) with ERPF obtained from the CLPAH value. The volume of distribution and elimination of 99mTc-MAG3 decreased during renal failure. Although there was minimal binding of 99mTc-MAG3 to erythrocytes, it was significantly (P = 0.0008) lower during renal failure. Protein binding was not significantly different during renal failure. All dogs had signs of nausea and emesis at variable times after injection of 99mTc-MAG3. Determination of CLMAG3 after a single injection provides an adequate means to rapidly assess ERPF in dogs. The technique could easily be performed in dogs with renal disease, thus providing valuable information regarding progression of naturally acquired renal failure.


Barriers to utilizing long-acting injectable antipsychotic medications.
Long-acting injectable (LAI) antipsychotic medications are superior to their oral equivalents in reducing relapse, yet schizophrenia treatment guidelines favor oral formulations. A minority of eligible patients receive LAI preparations in the United States. The purpose of the present study is to examine barriers faced by psychiatrists in implementing the use of LAI antipsychotics. An internet survey sent to Michigan State University-affiliated psychiatrists examined psychiatrists' practice locations and characteristics, access, opinions, and barriers to utilizing LAI antipsychotic medications in patients with schizophrenia. Thirty-six psychiatrists completed the survey. Thirty-three psychiatrists (83%) acknowledged having patients in their practices who would benefit from LAI antipsychotics; however, only 22 (61%) had the capacity to utilize these formulations. Barriers to utilizing LAI antipsychotic medications included: 1) lack of ancillary support at the practice location; 2) personal preference for oral compounds; and 3) limited insurance coverage. Psychiatrists who had the capability of administering LAI antipsychotic compounds were 10 times more likely to utilize them when compared with others who lacked the capacity to do so (9.67% [SD=10] vs 1.43% [SD=3]; df=1; F=8.59; P<.005). Psychiatrists practicing in Michigan face formidable barriers to utilizing LAI agents. Strategies to mitigate these barriers are reviewed.


Raft association and lipid droplet targeting of flotillins are independent of caveolin.
Lipid rafts are liquid ordered platforms that dynamically compartmentalize membranes. Caveolins and flotillins constitute a group of proteins that are enriched in these domains. Caveolin-1 has been shown to be an essential component of caveolae. Flotillins were also discovered as an integral component of caveolae and have since been suggested to interact with caveolins. However, flotillins are also expressed in non-caveolae-containing cells such as lymphocytes and neuronal cells. Hence, a discrepancy exists in the literature regarding the caveolin dependence of flotillin expression and their subcellular localization. To address this controversy, we used mouse embryonic fibroblasts (MEFs) from caveolin-1 knockout (Cav-1(-/-)) and wild-type mice to study flotillin expression and localization. Here we show that both membrane association and lipid raft partitioning of flotillins are not perturbed in Cav-1(-/-) MEFs, whereas membrane targeting and raft partitioning of caveolin-2, another caveolin family protein, is severely impaired. Moreover, we demonstrate that flotillin-1, but not flotillin-2, associates with lipid droplets upon oleic acid treatment and that this association is completely independent of caveolin. Taken together, our results show that flotillins are localized in lipid rafts independent of caveolin-1 and that translocation of flotillin-1 to lipid droplets is a caveolin-independent process.


International evidence-based guideline on assessment and management of PCOS-A Nordic perspective.
Polycystic ovary syndrome (PCOS) affects about 12% of women of reproductive age. In 2018, the first evidence-based guideline on assessment and management of PCOS was published, and an updated extended guideline was released in August 2023. These guidelines followed best practice and are endorsed by 39 organizations worldwide, making them the most robust source of evidence to guide clinical practice. In the 2023 guideline, diagnostic criteria have been further refined as polycystic ovary morphology can now be assessed with gynecological ultrasound or elevated anti-Müllerian hormone levels. A healthy lifestyle should be at the focus of care for all women with PCOS; however, with no specific diet or physical exercise recommended. The latest evidence on medical treatments and fertility management are reviewed, including special considerations regarding long-term follow-up of metabolic and psychiatric comorbidities and pregnancy in women with PCOS. Here we summarize the recommendations from a Nordic perspective.


The use of radioactive marker as a tool to evaluate the drug release in plasma and particle biodistribution of block copolymer nanoparticles.
Diblock copolymer nanoparticles encapsulating a paclitaxel prodrug, Propac 7, have been used to demonstrate the usefulness of a nonmetabolizable radioactive marker, cholesteryl hexadecyl ether (CHE), to evaluate nanoparticle formulation variables. Since CHE did not exchange out of the nanoparticles, the rate of clearance of the CHE could be used as an indicator of nanoparticle stability in vivo. We simultaneously monitored prodrug circulation and carrier circulation in the plasma and the retention of CHE relative to the retention of prodrug in the plasma was used to distinguish prodrug release from nanoparticle plasma clearance. Nanoparticles labelled with CHE were also used to evaluate accumulation of nanoparticles in the tumour. This marker has provided relevant data which we have applied to optimise our nanoparticle formulations.


Probiotics for preventing ventilator-associated pneumonia.
Ventilator-associated pneumonia (VAP) is common in intensive care units (ICUs). Some evidence indicates that probiotics may reduce the incidence of VAP. Several additional published studies have demonstrated that probiotics are safe and efficacious in preventing VAP in ICUs. We aimed to systematically summarise the results of all available data to generate the best evidence for the prevention of VAP. To evaluate the effectiveness and safety of probiotics for preventing VAP. We searched CENTRAL (2014, Issue 8), MEDLINE (1948 to September week 1, 2014) and EMBASE (2010 to September 2014). Randomised controlled trials (RCTs) comparing probiotics with placebo or another control (excluding RCTs that use probiotics in both study groups) to prevent VAP. Two review authors independently assessed eligibility and the quality of trials, and extracted data. We included eight RCTs, with 1083 participants. All studies compared a form of probiotic (Lactobacillus casei rhamnosus; Lactobacillus plantarum; Synbiotic 2000FORTE; Ergyphilus; combination Bifidobacterium longum + Lactobacillus bulgaricus + Streptococcus thermophilus) versus a control group (placebo; glutamine; fermentable fibre; peptide; chlorhexidine). The analysis of all RCTs showed that the use of probiotics decreased the incidence of VAP (odds ratio (OR) 0.70, 95% confidence interval (CI) 0.52 to 0.95, low quality evidence). However, the aggregated results were uncertain for ICU mortality (OR 0.84, 95% CI 0.58 to 1.22 very low quality evidence), in-hospital mortality (OR 0.78, 95% CI 0.54 to 1.14, very low quality evidence), incidence of diarrhoea (OR 0.72, 95% CI 0.47 to 1.09, very low quality evidence), length of ICU stay (mean difference (MD) -1.60, 95% CI -6.53 to 3.33, very low quality evidence), duration of mechanical ventilation (MD -6.15, 95% CI -18.77 to 6.47, very low quality evidence) and antibiotic use (OR 1.23, 95% CI 0.51 to 2.96, low quality evidence). Antibiotics for VAP were used for a shorter duration (in days) when participants received probiotics in one small study (MD -3.00, 95% CI -6.04 to 0.04). However, the CI of the estimated effect was too wide to exclude no difference with probiotics. There were no reported events of nosocomial probiotic infections in any included study.The overall methodological quality of the included studies, based on our 'Risk of bias' assessments, was moderate with half of the included studies rated as a 'low' risk of bias; however, we rated four included studies as a 'high' risk of bias across one or more of the domains. The study limitations, differences in probiotics administered and participants, and small sample sizes across the included studies mean that the power to detect a trend of overall effect may be limited and chance findings cannot be excluded.To explore the influence of some potential confounding factors in the studies, we conducted an intention-to-treat (ITT) analysis, which did not change the inference of per-protocol analysis. However, our sensitivity analysis did not indicate a significant difference between groups for instances of VAP. Evidence suggests that use of probiotics is associated with a reduction in the incidence of VAP. However, the quality of the evidence is low and the exclusion of the one study that did not provide a robust definition of VAP increased the uncertainty in this finding. The available evidence is not clear regarding a decrease in ICU or hospital mortality with probiotic use. Three trials reported on the incidence of diarrhoea and the pooled results indicate no clear evidence of a difference. The results of this meta-analysis do not provide sufficient evidence to draw conclusions on the efficacy and safety of probiotics for the prevention of VAP in ICU patients.


Phase II study of irinotecan and amrubicin in patients with relapsed non-small cell lung cancer: Okayama Lung Cancer Study Group Trial 0402.
The survival advantage achieved by existing anti-cancer agents as second-line therapy for relapsed non-small cell lung cancer (NSCLC) is modest and further improvement of treatment outcome is desired. Combination chemotherapy with irinotecan and amrubicin for advanced NSCLC has not been fully evaluated. The primary endpoint of this phase II clinical trial was objective response. Patients with NSCLC who had been treated previously with one or two chemotherapy agents were enrolled. Irinotecan and amrubicin were both administered on Days 1 and 8 of a 21-day cycle, at doses of 100 mg/m(2) and 40 mg/m(2), respectively. Between 2004 and 2006, 31 patients received a total of 101 courses; the median number of courses administered was three (range, one to six). Objective response was obtained in nine of the 31 patients (29.0% response rate; 95% confidence interval (CI), 12.1-46.0%). With a median follow-up time of 43.9 months, median survival time and the median progression-free survival time were 14.2 and 4.0 months, respectively. Myelosuppression was the most frequently observed adverse event, with grade 3/4 neutropenia in 51% of patients. Febrile neutropenia developed after nine courses (9%) and resulted in one treatment-related death. Cardiac toxicity and diarrhea, possibly specific for both agents, were infrequent and manageable. Combination chemotherapy with irinotecan and amrubicin is effective in patients with NSCLC but showed moderate toxicities in second- or third-line settings.


Self-organization of spindle-like microtubule structures.
Microtubule self-organization is an essential physical process underlying several essential cellular functions, including cell division. In cell division, the dominant arrangement is the mitotic spindle, a football-shaped microtubule-based machine responsible for separating the chromosomes. We are interested in the underlying fundamental principles behind the self-organization of the spindle shape. Prior biological works have hypothesized that motor proteins control the proper formation of the spindle. Many of these motor proteins are also microtubule-crosslinkers, so it is unclear if the critical aspect is the motor activity or the crosslinking. In this study, we seek to address this question by examining the self-organization of microtubules using crosslinkers alone. We use a minimal system composed of tubulin, an antiparallel microtubule-crosslinking protein, and a crowding agent to explore the phase space of organizations as a function of tubulin and crosslinker concentration. We find that the concentration of the antiparallel crosslinker, MAP65, has a significant effect on the organization and resulted in spindle-like arrangements at relatively low concentration without the need for motor activity. Surprisingly, the length of the microtubules only moderately affects the equilibrium phase. We characterize both the shape and dynamics of these spindle-like organizations. We find that they are birefringent homogeneous tactoids. The microtubules have slow mobility, but the crosslinkers have fast mobility within the tactoids. These structures represent a first step in the recapitulation of self-organized spindles of microtubules that can be used as initial structures for further biophysical and active matter studies relevant to the biological process of cell division.


Egg oral immunotherapy in nonanaphylactic children with egg allergy.
There is no current active treatment for food allergy. Traditional injection immunotherapy has been proved unsafe, and thus there is a need for other forms of immunotherapy. The purpose was to study the safety and immunologic effects of egg oral immunotherapy (OIT). The short-term goal was to desensitize subjects to protect against accidental ingestion reactions. The eventual goal was to induce lasting clinical and immunologic tolerance. Subjects with a history of egg allergy but without a history of anaphylaxis to egg underwent a 24-month egg OIT protocol involving modified rush, build-up, and maintenance phases. Double-blind, placebo-controlled food challenges were performed at study conclusion. Egg-specific IgE and IgG concentrations were followed. Seven subjects completed the protocol. Egg-specific IgG concentrations increased significantly, whereas egg-specific IgE concentrations did not significantly change. Three subjects tolerated known or possible accidental egg ingestions while receiving OIT. During double-blind, placebo-controlled food challenges at study conclusion, all tolerated significantly more egg protein than at study onset and than that found in the typical accidental exposure. Two subjects demonstrated oral tolerance. This study provides proof of concept that OIT can be safely used for patients with egg allergy without a history of anaphylaxis to egg. Egg OIT does not heighten sensitivity to egg and might protect against reaction on accidental ingestion. Whether OIT will induce clinical oral tolerance cannot be concluded from this initial cohort. Use of allergen-specific OIT to protect subjects with food allergy from reaction on accidental ingestion would represent a significant paradigm change in the treatment of food allergy.


Association of dairy intake with cardiovascular disease and mortality in 21 countries from five continents (PURE): a prospective cohort study.
Dietary guidelines recommend minimising consumption of whole-fat dairy products, as they are a source of saturated fats and presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Evidence for this contention is sparse and few data for the effects of dairy consumption on health are available from low-income and middle-income countries. Therefore, we aimed to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease. The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35-70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre. Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9·1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0·84, 95% CI 0·75-0·94; ptrend=0·0004), total mortality (0·83, 0·72-0·96; ptrend=0·0052), non-cardiovascular mortality (0·86, 0·72-1·02; ptrend=0·046), cardiovascular mortality (0·77, 0·58-1·01; ptrend=0·029), major cardiovascular disease (0·78, 0·67-0·90; ptrend=0·0001), and stroke (0·66, 0·53-0·82; ptrend=0·0003). No significant association with myocardial infarction was observed (HR 0·89, 95% CI 0·71-1·11; ptrend=0·163). Higher intake (>1 serving vs no intake) of milk (HR 0·90, 95% CI 0·82-0·99; ptrend=0·0529) and yogurt (0·86, 0·75-0·99; ptrend=0·0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0·88, 0·76-1·02; ptrend=0·1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1·09, 95% CI 0·90-1·33; ptrend=0·4113). Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort. Full funding sources are listed at the end of the paper (see Acknowledgments).


Hepatic effects of phenobarbitone in female mice fed sublethal levels of dietary cyanide.
Female albino mice were fed sublethal doses of KCN (approx. 10 micrograms/mouse/day) for 7 days, injected intraperitoneally with phenobarbitone (50 mg/kg body wt/day) in the subsequent 3 days, and sacrificed 24 hr after the last injection. Phenobarbitone sleeping time was increasingly shortened (16-27%) daily in cyanide-fed mice in comparison with cyanide-free controls. Both compounds administered singly or simultaneously increased the liver weight/body weight ratios by not more than 10%. Aniline hydroxylase, glucose-6-phosphatase, NADPH- and NADH-cytochrome c reductase activities were similarly increased. Aniline hydroxylase activity was most markedly increased (by a factor of 4). The toxicological implications of these results are discussed.


Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs.
We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci.


Acute experimental infection of bats and ferrets with Hendra virus: Insights into the early host response of the reservoir host and susceptible model species.
Bats are the natural reservoir host for a number of zoonotic viruses, including Hendra virus (HeV) which causes severe clinical disease in humans and other susceptible hosts. Our understanding of the ability of bats to avoid clinical disease following infection with viruses such as HeV has come predominantly from in vitro studies focusing on innate immunity. Information on the early host response to infection in vivo is lacking and there is no comparative data on responses in bats compared with animals that succumb to disease. In this study, we examined the sites of HeV replication and the immune response of infected Australian black flying foxes and ferrets at 12, 36 and 60 hours post exposure (hpe). Viral antigen was detected at 60 hpe in bats and was confined to the lungs whereas in ferrets there was evidence of widespread viral RNA and antigen by 60 hpe. The mRNA expression of IFNs revealed antagonism of type I and III IFNs and a significant increase in the chemokine, CXCL10, in bat lung and spleen following infection. In ferrets, there was an increase in the transcription of IFN in the spleen following infection. Liquid chromatography tandem mass spectrometry (LC-MS/MS) on lung tissue from bats and ferrets was performed at 0 and 60 hpe to obtain a global overview of viral and host protein expression. Gene Ontology (GO) enrichment analysis of immune pathways revealed that six pathways, including a number involved in cell mediated immunity were more likely to be upregulated in bat lung compared to ferrets. GO analysis also revealed enrichment of the type I IFN signaling pathway in bats and ferrets. This study contributes important comparative data on differences in the dissemination of HeV and the first to provide comparative data on the activation of immune pathways in bats and ferrets in vivo following infection.


The duration of Plasmodium falciparum infections.
Plasmodium vivax and Plasmodium ovale are often considered the malaria parasites best adapted to long-term survival in the human host because of their latent exo-erythrocytic forms. The prevailing opinion until the middle of the last century was that the maximum duration of Plasmodium falciparum infections was less than two years. Case reports and series investigating blood donors following accidental malaria infection of blood transfusion recipients and other sporadic malaria cases in non-endemic countries have shown clearly that asymptomatic P. falciparum infections may persist for up to a decade or longer (maximum confirmed 13 years). Current policies in malaria-free countries of excluding blood donors who have lived in malarious areas are justified. Vigilance for longer than three years after declaring elimination in an area may be needed.


The Association of Obstructive Sleep Apnea and Pain Outcomes in Adults: A Systematic Review.
The specific link between obstructive sleep apnea (OSA) and pain is unknown, but it has been hypothesized that OSA patients are hyperalgesic because of fragmented sleep and hypoxemia that enhance sensitivity to pain, promote inflammation, and increase spontaneous pain. We conducted a systematic review of the literature assessing whether OSA is a risk factor for subjective pain intensity and experimental pain tolerance and threshold. A search of published studies in English in MEDLINE, PubMed, Embase, and the Cochrane Database of Systematic Reviews from database inception through May 2017 was performed. Search terms included "sleep apnea," "continuous positive airway pressure," "CPAP," "pain," and "chronic pain." We included any study that reported an association between OSA or polysomnogram assessments with pain outcomes or reported the effect of CPAP on pain outcomes. Controlled studies, cohort studies, and case-control studies were included. We identified 448 studies from PubMed and 959 studies from Embase, giving a combined 1,333 studies after removing duplicates. After detailed selection, 28 articles were reviewed in full and 12 met study inclusion criteria. Whereas several studies found an association between OSA and pain intensity or experimental pain, there was considerable variability among study outcomes. Delivery of CPAP may improve pain and decrease opioid use, although the exact nature of the relationship between pain and the various pathophysiologic components of OSA is unclear. This systematic review summarizes the current evidence for the association of OSA and pain outcomes. Further research is needed to identify the differential effects of nocturnal hypoxemia and fragmented sleep on pain intensity. Clinicians might consider screening patients with chronic pain for OSA.


Aerobic exercise interventions for adults living with HIV/AIDS.
Access to combination antiretroviral therapy has turned HIV into a chronic and manageable disease for many. This increased chronicity has been mirrored by increased prevalence of health-related challenges experienced by people living with HIV (Rusch 2004). Exercise is a key strategy for people living with HIV and by rehabilitation professionals to address these disablements; however, knowledge about the effects of exercise among adults living with HIV still is emerging. To examine the safety and effectiveness of aerobic exercise interventions on immunologic and virologic, cardiopulmonary, psychologic outcomes and strength, weight, and body composition in adults living with HIV. Searches of MEDLINE, EMBASE, SCIENCE CITATION INDEX, CINAHL, HEALTHSTAR, PsycINFO, SPORTDISCUS and Cochrane Review Group Databases were conducted between 1980 and June 2009. Searches of published and unpublished abstracts and proceedings from major international and national HIV/AIDS conferences were conducted, as well as a handsearch of reference lists and tables of contents of relevant journals and books. We included studies of randomised controlled trials (RCTs) comparing aerobic exercise interventions with no aerobic exercise interventions or another exercise or treatment modality, performed at least three times per week for at least four weeks among adults (18 years of age or older) living with HIV. Data on study design, participants, interventions, outcomes, and methodological quality were abstracted from included studies by two reviewers. Meta-analyses, using RevMan 5 computer software, were performed on outcomes when possible. A total of 14 studies met inclusion criteria for this review and 30 meta-analyses over several updates were performed. Main results indicated that performing constant or interval aerobic exercise, or a combination of constant aerobic exercise and progressive resistive exercise for at least 20 minutes at least three times per week for at least five weeks appears to be safe and may lead to significant improvements in selected outcomes of cardiopulmonary fitness (maximum oxygen consumption), body composition (leg muscle area, percent body fat), and psychological status (depression-dejection symptoms). These findings are limited to participants who continued to exercise and for whom there were adequate follow-up data. Aerobic exercise appears to be safe and may be beneficial for adults living with HIV. These findings are limited by the small sample sizes and large withdrawal rates described in the studies. Future research would benefit from participant follow-up and intention-to-treat analysis. Further research is required to determine the optimal parameters in which aerobic exercise may be most beneficial for adults living with HIV.


Adolescent vegetarians. A behavioral profile of a school-based population in Minnesota.
To compare a population-based sample of vegetarian and nonvegetarian adolescents regarding food intake patterns, disordered eating, and a range of other non-food-related health-compromising and health-promoting behaviors. A cross-sectional school-based survey. Public schools within nonurban areas of Minnesota. Adolescents (n = 107) aged 12 to 20 years who reported on the Minnesota Adolescent Health Survey that they follow a vegetarian diet and a comparison group of nonvegetarian youth (n = 214) matched for sex, age, and ethnicity. The percentage of self-identified vegetarians in the study population was relatively low (0.6%); most of the vegetarians were female (81%). Food intake patterns, disordered eating (frequent dieting, binge eating, self-induced vomiting, and laxative use), health-compromising behaviors (tobacco, alcohol, and marijuana use and suicide attempts), and health-promoting behaviors (seat belt use, physical activity, and brushing teeth regularly). Vegetarian adolescents were twice as likely to consume fruits and vegetables (P < .001), one third as likely to consume sweets (P < .001), and one fourth as likely to eat salty snack foods (P < .001) more than once a day compared with nonvegetarians. Vegetarians were almost twice as likely to report frequent dieting (P < .001), 4 times as likely to report intentional vomiting (P < .001), and 8 times as likely to report laxative use (P < .001) than nonvegetarians. Overall, associations with other health-compromising and health-promoting behaviors were not apparent. A vegetarian diet may be beneficial because of increased fruit and vegetable consumption and decreased consumption of foods high in fat, salt, and sugar. However, adolescents following a vegetarian diet need to be screened for adequate food intake and potential disordered eating behaviors.


GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles-continuous outcomes.
Presenting continuous outcomes in Summary of Findings tables presents particular challenges to interpretation. When each study uses the same outcome measure, and the units of that measure are intuitively interpretable (e.g., duration of hospitalization, duration of symptoms), presenting differences in means is usually desirable. When the natural units of the outcome measure are not easily interpretable, choosing a threshold to create a binary outcome and presenting relative and absolute effects become a more attractive alternative. When studies use different measures of the same construct, calculating summary measures requires converting to the same units of measurement for each study. The longest standing and most widely used approach is to divide the difference in means in each study by its standard deviation and present pooled results in standard deviation units (standardized mean difference). Disadvantages of this approach include vulnerability to varying degrees of heterogeneity in the underlying populations and difficulties in interpretation. Alternatives include presenting results in the units of the most popular or interpretable measure, converting to dichotomous measures and presenting relative and absolute effects, presenting the ratio of the means of intervention and control groups, and presenting the results in minimally important difference units. We outline the merits and limitations of each alternative and provide guidance for meta-analysts and guideline developers.


Survivin gene promoter polymorphism -31G/C as a risk factor for keratocystic odontogenic tumor development.
Several single nucleotide polymorphisms in survivin gene promoters, notably -31G/C, have been shown to modulate the expression and activity of the survivin protein. Consequently, the -31G/C polymorphism has been identified as a risk factor for the development of several types of tumors. The aim of this study was to investigate a possible association between the -31G/C polymorphism and the risk for keratocystic odontogenic tumor (KCOT) development. DNA from 52 biopsy specimens of KCOTs and from 82 buccal swabs of healthy individuals was subjected to PCR restriction fragment length polymorphism analysis to identify individual genotypes. The distribution of genotypes in KCOT and control groups, respectively, was: GG: 30 (57.7%) vs. 26 (31.7%); CG: 17 (32.7%) vs. 45 (54.9%); and CC: 5 (9.6%) vs. 11 (13.4%), respectively. These differences were statistically significant. The G allele was more common in the KCOT group than in the control group: 76 (74%) vs. 96 (59%), respectively. Logistic regression analysis showed that GC heterozygotes had a considerably decreased susceptibility for KCOTs compared with GG homozygotes. The same was true for GC+CC vs. GG. The GG genotype of the -31G/C polymorphism might be a risk factor for KCOT development.


Variation of two forms of DNA polymerase-alpha during a HeLa cell cycle.
HeLa cells contain two forms of DNA polymerase-alpha (P-I and P-II) with varied affinity to DNA, separable on a DNA-cellulose column. The activity of each form was followed during a cell cycle of synchronized culture of the HeLa cells. P-I was recovered from the nuclear extract and P-II from the cytoplasmic fraction. The P-I activity remained at a low level during M to G1 phase until a marked increase between late G1 and S phases, while P-II activity increased gradually throughout the period. Both activities attained their highest level at mid-S phase and then the P-I activity declined more rapidly than the P-II. Addition of hydroxyurea at mid-S phase inhibited the decrease of both enzyme activities. The enzyme activity of nuclear extract from S phase cells was not inhibited by mixing with extract from M phase cells. When the cytoplasmic fraction from M phase cells was chromatographed on a DNA-cellulose column, single activity peak was observed at the position of P-II. These results suggest that the decrease in P-I activity is neither due to the presence of an inhibitor nor to mere release of the enzyme from chromosomes.


The exploitation argument against commercial surrogacy.
This paper discusses the exploitation argument against commercial surrogacy: the claim that commercial surrogacy is morally objectionable because it is exploitative. The following questions are addressed. First, what exactly does the exploitation argument amount to? Second, is commercial surrogacy in fact exploitative? Third, if it were exploitative, would this provide a sufficient reason to prohibit (or otherwise legislatively discourage) it? The focus throughout is on the exploitation of paid surrogates, although it is noted that other parties (e.g. 'commissioning parents') may also be the victims of exploitation. It is argued that there are good reasons for believing that commercial surrogacy is often exploitative. However, even if we accept this, the exploitation argument for prohibiting (or otherwise legislatively discouraging) commercial surrogacy remains quite weak. One reason for this is that prohibition may well 'backfire' and lead to potential surrogates having to do other things that are more exploitative and/or more harmful than paid surrogacy. It is concluded therefore that those who oppose exploitation should (rather than attempting to stop particular practices like commercial surrogacy) concentrate on: (a) improving the conditions under which paid surrogates 'work'; and (b) changing the background conditions (in particular, the unequal distribution of power and wealth) which generate exploitative relationships.


Plasma catecholamine responses to change of posture in alcoholics during withdrawal and after continued abstinence from alcohol.
Plasma catecholamine, blood pressure and heart rate responses to standing were measured in ten alcoholics during withdrawal, ten alcoholics after 2-7 weeks of abstinence from alcohol, six abstinent alcoholics with orthostatic hypotension and ten normal control subjects. Withdrawing alcoholics had supine and standing heart rates and plasma noradrenaline and adrenaline concentrations that were higher than in abstinent alcoholics or control subjects. Supine blood pressures were also higher in withdrawing alcoholics than in abstinent alcoholics or control subjects, but on standing blood pressures in withdrawing alcoholics fell, four patients having a fall of more than 30/5 mmHg. Abstinent alcoholics without orthostatic hypotension had higher basal and standing concentrations of noradrenaline than control subjects but normal heart rates and adrenaline concentrations. Abstinent alcoholics with orthostatic hypotension showed a wide range of basal plasma noradrenaline concentrations and were found to have variable plasma noradrenaline responses to standing, three subjects having normal responses and three subjects having no or little increase in plasma noradrenaline on standing. It is concluded that alcohol withdrawal is associated with increased sympathetic nervous activity, as reflected by raised supine and standing plasma concentrations of catecholamines, and that even after 2-7 weeks of abstinence from alcohol plasma noradrenaline concentrations may be higher than in control subjects. Despite increased sympathetic nervous responses to standing, alcoholics during withdrawal have impaired blood pressure control and some may exhibit orthostatic hypotension. Orthostatic hypotension may also be observed in alcoholics during continuing abstinence from alcohol; in some of these patients failure of reflex noradrenaline release in response to standing may contribute to orthostatic hypotension.


Aspergillus baeticus sp. nov. and Aspergillus thesauricus sp. nov., two species in section Usti from Spanish caves.
Two novel species of Aspergillus that are clearly distinct from all known species in section Usti were revealed during a study of microfungal communities in Spanish caves. The novel species identified in this study and additional species of Aspergillus section Usti are associated with places and substrates related to human activities in caves. Novel species are described using data from four loci (ITS, benA, caM and rpb2), morphology and basic chemical and physiological analyses. Members of the species Aspergillus thesauricus sp. nov. were isolated from various substrates, including decaying organic matter, cave air and cave sediment of the Cueva del Tesoro Cave (the Treasure cave); the species is represented by twelve isolates and is most closely related to the recently described Aspergillus germanicus. Members of the species Aspergillus baeticus sp. nov. were isolated from cave sediment in the Gruta de las Maravillas Cave (the Grotto of the Marvels); the species is represented by two isolates. An additional isolate was found in the Cueva del Tesoro Cave and in the Demänovská Peace Cave (Slovakia), suggesting a potentially wide distribution of this micro-organism. The species is related to Aspergillus ustus and Aspergillus pseudoustus. Both species were unable to grow at 37 °C, and a weakly positive, light greenish yellow Ehrlich reaction was observed in A. thesauricus. Unique morphological features alone are sufficient to distinguish both species from related taxa.