Hypertension after liver transplantation: a predictive role for pretreatment hemodynamics and effects of isradipine on the systemic and renal circulations.
Hypertension developing after liver transplantation during immunosuppression with cyclosporine A reflects an unusual hemodynamic transition from peripheral vasodilation to systemic and renal vasoconstriction. Although dihydropyridine calcium channel blockers are often administered for their efficacy in promoting vasodilation, some liver transplant recipients report marked symptomatic intolerance to these agents. In the present study we examined systemic and renal responses to isradipine using systemic (thoracic bioimpedance) and renal hemodynamic measurements in 15 liver transplant recipients studied at the time of initial diagnosis of posttransplant hypertension and after 3 months of treatment. Circadian blood pressure patterns were examined by overnight ambulatory blood pressure monitoring before and during antihypertensive therapy. During isradipine administration, blood pressure decreased from 151 +/- 3/91 +/- 2 to 130 +/-3/81 +/- 2 mm Hg (P < .01) without change in renal blood flow (406 +/- 43 to 425 +/- 52 mL/min/1.73m2, P = NS) or renal vascular resistance index (25,674 +/-3312 to 20,520 +/- 2311 dynes x sec x cm(-5)/m2, P = NS). Pre-treatment differences in systemic vascular tone persisted during treatment and predicted the tendency for symptomatic tachycardia and flushing, predominantly in those with hyperdynamic circulations. Twice daily dosing of isradipine was associated with partial and significant restoration of the nocturnal decrease in blood pressure (systolic blood pressure decreased 5.5%, normal 13%), usually absent early after transplantation. Our results demonstrate the ability of hemodynamic measurements to predict the symptomatic response to antihypertensive therapy in the posttransplant setting.


Glabridin improves autoimmune disease in Trex1-deficient mice by reducing type I interferon production.
The cGAS-STING signaling pathway is an essential section of the natural immune system. In recent years, an increasing number of studies have shown a strong link between abnormal activation of the cGAS-STING signaling pathway, a natural immune pathway mediated by the nucleic acid receptor cGAS, and the development and progression of autoimmune diseases. Therefore, it is important to identify an effective compound to specifically downregulate this pathway for disease. The effect of Glabridin (Glab) was investigated in BMDMs and Peripheral blood mononuclear cell (PBMC) by establishing an in vitro model of cGAS-STING signaling pathway activation. An activation model stimulated by DMXAA was also established in mice to study the effect of Glab. On the other hand, we investigated the possible mechanism of action of Glab and the effect of Glab on Trex1-deficient mice. In this research, we report that Glab, a major component of licorice, specifically inhibits the cGAS-STING signaling pathway by inhibiting the level of type I interferon and inflammatory cytokines (IL-6 and TNF-α). In addition, Glab has a therapeutic effect on innate immune diseases caused by abnormal cytoplasmic DNA in Trex1-deficient mice. Mechanistically, Glab can specifically inhibit the interaction of STING with IRF3. Glab is a specific inhibitor of the cGAS-STING signaling pathway and may be used in the clinical therapy of cGAS-STING pathway-mediated autoimmune diseases.


Cancer surgery on the global stage: Updates and progress.
Over 5 billion people lack access to basic surgical procedures, and it is estimated, the number of surgical procedures needed for cancer care will increase by 5 million from 2018 to 2040. The greatest increase in demand will occur in low- and middle-income countries. In this article, we highlight progress made in surgical cancer care globally and gaps that still needs to be addressed. We highlight political support, workforce progress and shortages, impact of the COVID-19 pandemic, and the importance of high value cancer care.


[Surgical correction of multivalvular defects in patients who had earlier undergone heart surgery].
The article analyses the results of surgical treatment of 45 patients with multivalvular acquired heart diseases which had been previously treated by operation. Stage III (terminal) circulatory disorders were diagnosed in 11 (24.1%) patients. A pathological condition of the tricuspid valve was found in almost all patients with the terminal stage of circulatory disorders. Eleven (24.4%) patients died after the operation. The most frequent causes of the fatal outcomes were: cardiac failure (in 6 patients) and hemorrhage (in 2 patients during the operation and in 1 patients on the 6th post-operative day; the bleeding occurred from varicose veins of the stomach and esophagus). Severe initial circulatory insufficiency was the main factor of operative risk. The criteria of operability must be elaborated for this contingent of patients suffering from severe cardiac insufficiency on the eve of the operation.


Structural transitions in nanoparticle assemblies governed by competing nanoscale forces.
Assembly of nanoscale materials from nanoparticle (NP) building blocks relies on our understanding of multiple nanoscale forces acting between NPs. These forces may compete with each other and yield distinct stimuli-responsive self-assembled nanostructures. Here, we report structural transitions between linear chains and globular assemblies of charged, polymer-stabilized gold NPs, which are governed by the competition of repulsive electrostatic forces and attractive poor solvency/hydrophobic forces. We propose a simple quantitative model and show that these transitions can be controlled by the quality of solvent, addition of a salt, and variation of the molecular weight of the polymer ligands.


Giving the tap the elbow? An observational study.
Handwashing is viewed as the most important barrier to cross-infection. Incorrect use of clinical handwash basins may lead to cross-infection either from contaminated water or due to failure to decontaminate hands. Elbow-operated taps used correctly prevent recontamination of hands during operation. Many elbow-operated taps are installed incorrectly, with the handle flush with the back panel, making it difficult to open using the elbow. To determine the effect of altering the angle of the handle of elbow-operated taps on handwashing technique. An observational study was conducted using two rooms; in one the handles of the elbow-operated taps were flush with the inspection panel behind, and in the other they were set at 35°. Thirty-five staff members washed their hands in both rooms. Hands were used to turn on the taps in 97% of instances. In 57% of washes hands were recontaminated when used to turn the tap off. Only six individuals consistently used their elbows to turn outlets off. Surprisingly, more individuals used their elbows to operate taps whose handles were flush with the inspection panel behind. Greater emphasis needs to be placed on correct use of elbow-operated outlets. The decision to use elbow- or sensor-operated outlets is not clear-cut, as each has pros and cons. There is much room for improvement in design and standardization of handwash basins. Given the importance of handwashing it is surprising that these gaps exist.


Corneal thinning syndromes.
We performed central pachymetry on two patients with pellucid and Terrien's corneal marginal degeneration with mean central corneal thicknesses of .487 mm and .466 mm, respectively. We believe that differential corneal thickness measurements may assist in the differential diagnosis of the corneal thinning syndromes.


Evidence for cross-linking of cyclic AMP to constituents of brain tissue by aldehyde fixatives: potential utility in histochemical procedures.
The amount of cyclic AMP recovered from unfixed tissue sections of brain carried through immunohistochemical procedures was found to be small (less than 2 pmoles/mg protein) and constant despite wide variations in the amount accumulated prior to freezing and sectioning. However, treatment of brain slices with glutaraldehyde or formaldehyde in buffered sucrose solutions for one to two hours at 0 degrees rendered insoluble as much as 60% of the total accumulated cyclic AMP as judged by filtration of homogenates of treated tissue. Immunoreactive cyclic AMP was recovered from filters by extraction with warm, dilute acid. The fraction of filter-bound cyclic AMP was relatively constant over a wide range of initial tissue levels. The persistence of insoluble cyclic AMP was greatest in homogenates of slices treated with formaldehyde when maintained above pH 8.5; about 40% of this fraction was lost after two hours at 0 degrees. Incubation of tissue homogenates with formaldehyde and radioactive nucleoside or nucleotide derivatives of adenine, guanine, and cytosine resulted in a time-dependent appearance of insoluble radioactivity; compounds lacking an amino function were inactive. Pure proteins, including polylysine, also reacted with formaldehyde and 3H-cyclic AMP to produce radioactivity resistant to adsorption by charcoal. The reaction between cyclic AMP or adenosine, formaldehyde, and alkyl amines was examined using UV spectrometry. It is tentatively concluded that at 0 degrees formaldehyde is capable of rapidly producing a methylene-bridged adduct between primary alkylamines and the N6-amino function of purine nucleosides or nucleotides. Application of these results to the development of immunohistochemical procedures for the cellular localization of cyclic AMP will require the generation of antibody preparations with high reactivity for cyclic AMP derivatized at the N6-position.


User assisted separation of reflections from a single image using a sparsity prior.
When we take a picture through transparent glass the image we obtain is often a linear superposition of two images: the image of the scene beyond the glass plus the image of the scene reflected by the glass. Decomposing the single input image into two images is a massively ill-posed problem: in the absence of additional knowledge about the scene being viewed there are an infinite number of valid decompositions. In this paper we focus on an easier problem: user assisted separation in which the user interactively labels a small number of gradients as belonging to one of the layers. Even given labels on part of the gradients, the problem is still ill-posed and additional prior knowledge is needed. Following recent results on the statistics of natural images we use a sparsity prior over derivative filters. This sparsity prior is optimized using the terative reweighted least squares (IRLS) approach. Our results show that using a prior derived from the statistics of natural images gives a far superior performance compared to a Gaussian prior and it enables good separations from a modest number of labeled gradients.


Morbidity in family medicine: the potential for individual nutritional counseling, an analysis from the Nijmegen Continuous Morbidity Registration.
Nutritional counseling is a common primary care intervention but few empirical data are available. This study analyzed morbidity in family medicine practices and the relevance of nutritional counseling. Morbidity data from the Nijmegen University family medicine Continuous Morbidity Registration were studied. Since 1967 four practices (seven family physicians) have recorded all new episodes of illness. Physicians were trained and supervised monthly in their coding and classification of morbidity with diagnostic criteria. Two experienced family physicians assessed the nutrition sensitivity of all 400 diagnostic rubrics of the classification list. Incidence and prevalence of all morbidity and of nutrition-sensitive morbidity were calculated. The most common (chronic) diseases in family practice were a mixture of diseases of organ and body systems: hypertension, obesity, cardiovascular disease, chronic arthritis, asthma, chronic obstructive pulmonary disease, eczema, and diabetes mellitus. The prevalence of these diseases gradually increased in the past decade. Forty-eight diagnostic rubrics were considered to be nutrition sensitive, accounting for 16.5% of diagnoses recorded. Their prevalence also increased in the past decade. The survey supports the importance of nutrition-related interventions in family medicine but underlines that these interventions are directed at a variety of illnesses and patient groups. Common nutritional intervention techniques that can be applied in the personal care of patients in the context of their family life should be developed.


Multifocality and opportunity structure: towards a mixed embeddedness model for transnational migrant entrepreneurship.
This article addresses transnational migrant entrepreneurship, which refers to migrants involved in cross-border entrepreneurial activities. Previous models and concepts in migrant entrepreneurship studies have not fully succeeded in recognising the role played by differential groups and places in the pursuit of opportunities by transnational migrant entrepreneurs. This is due to a tendency to focus on the country of residence as well as on the inclination to view migrant entrepreneurs as members of a coherent ethnic or national group. To help fill this gap, we propose a new model combining the concept of multifocality, covering the simultaneous involvement of migrant entrepreneurs in both multiple places and multiple groups, with group modes of behaviour as an additional dimension influencing the opportunity structure. The case of Moroccan transnational entrepreneurs in Amsterdam shows that the role of multifocality in place, in combination with group modes of behaviour, is critical when it comes to pursuing entrepreneurial opportunities.


Different sized wheat bran fibers as fat mimetic in biscuits: its effects on dough rheology and biscuit quality.
The aim of this study is to investigate the effects of various particle sized and different amount of plant fibers as fat mimetic for biscuit formulations instead of biscuit fat. The fibers with different particle sizes were obtained from wheat bran and used instead of fat in biscuit formulations. The texture, rheology and quality analyses of low-fat biscuit (30, 20 and 10% fat) were performed and compared with those of the full-fat control sample (40% fat). Results showed that wheat bran fiber with bigger particle size (Long Fiber, LF) were more favorable in terms of textural properties of the dough and the quality parameters of biscuits while the fibers with smaller particle size (Medium Fiber, MF and Small Fiber, SF) improved viscoelastic properties of dough similar to the control. Although the use of these fibers in the production of low-fat biscuits were suitable in terms of workability of dough increasing fiber content and/or reducing fiber size resulted in harder biscuits with lower spread ratio. This study showed that the texture of biscuits was greatly dependent on the texture of the dough.


Action of the pyrethroid insecticide cypermethrin on rat brain IIa sodium channels expressed in xenopus oocytes.
Pyrethroid insecticides bind to a unique site on voltage-dependent sodium channels and prolong sodium currents, leading to repetitive bursts of action potentials or use-dependent nerve block. To further characterize the site and mode of action of pyrethroids on sodium channels, we injected synthetic mRNA encoding the rat brain IIa sodium channel alpha subunit, either alone or in combination with synthetic mRNA encoding the rat sodium channel beta1 subunit, into oocytes of the frog Xenopus laevis and assessed the actions of the pyrethroid insecticide [1R,cis,alphaS]-cypermethrin on expressed sodium currents by two-electrode voltage clamp. In oocytes expressing only the rat brain IIa alpha subunit, cypermethrin produced a slowly-decaying sodium tail current following a depolarizing pulse. In parallel experiments using oocytes expressing the rat brain IIa alpha subunit in combination with the rat beta1 subunit, cypermethrin produced qualitatively similar tail currents following a depolarizing pulse and also induced a sustained component of the sodium current measured during a step depolarization of the oocyte membrane. The voltage dependence of activation and steady-state inactivation of the cypermethrin-dependent sustained current were identical to those of the peak transient sodium current measured in the absence of cypermethrin. Concentration-response curves obtained using normalized tail current amplitude as an index of the extent of sodium channel modification by cypermethrin revealed that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit increased the apparent affinity of the sodium channel binding site for cypermethrin by more than 20-fold. These results confirm that the pyrethroid binding site is intrinsic to the sodium channel alpha subunit and demonstrate that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit alters the apparent affinity of this site for pyrethroids.


[Prognostic factors in acute digitalis poisoning (author's transl)].
The prognostic significance of various clinical and biochemical factors was investigated in 179 patients who had absorbed more than 2 mg of digitoxin. The mortality rate in this series was 17%. Supraventricular arrythmias had no influence on prognosis, but the death risk was higher in males and in patients with A-V block. It increased with age, with digitoxin and potassium serum levels and even more with persistent hyperkalemia. Two other factors, previous heart disease and vomiting, were also significant in patients without heart block. Calculated on the basis of 4 clinical factors, the mortality rate varied from 2 to 74%. The death risk in acute digitalis poisoning can therefore be easily assessed from simple clinical criteria.


Latex agglutination test for rapid on-site serodiagnosis of Japanese encephalitis in pigs using recombinant NS1 antigen.
Japanese encephalitis (JE) is a mosquitoe-borne viral zoonotic disease and globally around three billion people are at the risk of disease. The occurrence of JE cases has shown a rising trend during last decade in India. Pig is the amplifying host for JE virus and serves as a suitable sentinel model for the prediction of disease outbreak in humans. The development of a diagnostic test that is suitable for surveillance of JE in pigs is the need of the hour. The existing tests require elaborate laboratory facilities which make their application in rural settings difficult. Therefore, realizing the need for a rapid test, efforts were made to standardize a latex agglutination test (LAT) for serodiagnosis of JE in pigs. Standardization of LAT by physical adsorption of recombinant NS1 (non-structural) protein of JE virus onto latex beads was done by altering six different variables, namely the antigen concentration, sensitization condition, surface blocking agent, blocking condition, particle concentration and reaction time. The standardized latex-protein complex was used for screening 246 pig serum samples under optimal conditions. The test was standardized with a diagnostic sensitivity and specificity of 82.24 and 87.83%, respectively. Screening of 246 field pig serum samples using standardized LAT showed a seropositivity of 50.4%. The results were available within 5 min after addition of test serum sample to the sensitized beads. The findings of the study highlight the potential of LAT as a rapid on-site assay for JE diagnosis in pigs which would aid in predicting JE outbreaks in humans.


How did Ebola information spread on twitter: broadcasting or viral spreading?
Information and emotions towards public health issues could spread widely through online social networks. Although aggregate metrics on the volume of information diffusion are available, we know little about how information spreads on online social networks. Health information could be transmitted from one to many (i.e. broadcasting) or from a chain of individual to individual (i.e. viral spreading). The aim of this study is to examine the spreading pattern of Ebola information on Twitter and identify influential users regarding Ebola messages. Our data was purchased from GNIP. We obtained all Ebola-related tweets posted globally from March 23, 2014 to May 31, 2015. We reconstructed Ebola-related retweeting paths based on Twitter content and the follower-followee relationships. Social network analysis was performed to investigate retweeting patterns. In addition to describing the diffusion structures, we classify users in the network into four categories (i.e., influential user, hidden influential user, disseminator, common user) based on following and retweeting patterns. On average, 91% of the retweets were directly retweeted from the initial message. Moreover, 47.5% of the retweeting paths of the original tweets had a depth of 1 (i.e., from the seed user to its immediate followers). These observations suggested that the broadcasting was more pervasive than viral spreading. We found that influential users and hidden influential users triggered more retweets than disseminators and common users. Disseminators and common users relied more on the viral model for spreading information beyond their immediate followers via influential and hidden influential users. Broadcasting was the dominant mechanism of information diffusion of a major health event on Twitter. It suggests that public health communicators can work beneficially with influential and hidden influential users to get the message across, because influential and hidden influential users can reach more people that are not following the public health Twitter accounts. Although both influential users and hidden influential users can trigger many retweets, recognizing and using the hidden influential users as the source of information could potentially be a cost-effective communication strategy for public health promotion. However, challenges remain due to uncertain credibility of these hidden influential users.


Characterization of OT4-1 Alloy by Multi-Dome Forming Test.
In this study, the rheological characteristics of a titanium alloy have been obtained by multi-dome bulging test. Free bulging process is an experimental technique that can be used to characterize material in conditions of biaxial tension during superplastic, as well as conventional, hot forming. The constitutive constants are calculated on a base of the information about the bulge geometry, applied pressure, and forming time. A multi-dome forming test allows one to reduce the number of the experiments required for the characterization, since every multi-dome test produces several domes of different size. In this study, a specific die for multi-dome test was used. The die has six holes with different radiuses of 20, 25, 30, 35, 40, and 45 mm. During a test, the specimen is clamped between blank holder and die holder, heated to a specific temperature, and formed by applying constant gas pressure. The experiments were conducted at different temperatures for OT4-1 titanium alloy. The constitutive constants were obtained by processing the experimental data using two different techniques and compared with tensile test results. In order to estimate the influence of friction on the experimental results and to verify obtained material characteristics, finite element (FE) simulation was performed. Finally, the results of FE simulation were compared with the experimental data. The results of the simulation show the advantage of material characterization based on multi dome tests and its interpretation by inverse analysis. The deviations produced by the effect of friction are more significant when the direct approach is applied instead of inverse analysis with a semi analytical model of the bulging process.


Degree of Response to Homeopathic Potencies Correlates with Dipole Moment Size in Molecular Detectors: Implications for Understanding the Fundamental Nature of Serially Diluted and Succussed Solutions.
The use of solvatochromic dyes to investigate homeopathic potencies holds out the promise of understanding the nature of serially succussed and diluted solutions at a fundamental physicochemical level. Recent studies have shown that a range of different dyes interact with potencies and, moreover, the nature of the interaction is beginning to allow certain specific characteristics of potencies to be delineated. The study reported in this article takes previous investigations further and aims to understand more about the nature of the interaction between potencies and solvatochromic dyes. To this end, the UV-visible spectra of a wide range of potential detectors of potencies have been examined using methodologies previously described. Results presented demonstrate that solvatochromic dyes are a sub-group of a larger class of compounds capable of demonstrating interactions with potencies. In particular, amino acids containing an aromatic bridge also show marked optical changes in the presence of potencies. Several specific features of molecular detectors can now be shown to be necessary for significant interactions with homeopathic potencies. These include systems with a large dipole moment, electron delocalisation, polarizability and molecular rigidity. Analysis of the optical changes occurring on interaction with potencies suggests that in all cases potencies increase the polarity of molecular detectors to a degree that correlates with the size of the compound's permanent or ground dipole moment. These results can be explained by inferring that potencies themselves have polarity. Possible candidates for the identity of potencies, based on these and previously reported results, are discussed.


Salicylates used in inflammatory bowel disease and colchicine impair interferon-gamma induced HLA-DR expression.
Colonic epithelial cells express HLA-DR in inflammatory bowel disease. The effect of drugs used in the treatment of inflammatory bowel disease and colchicine on interferon-gamma (IFN-gamma) induced DR expression has been investigated. HT-29 cells were cultured in 25 cm2 flasks. At 48 hours interferon-gamma (0, 50, or 100 U/ml) +/- drug were added. At 120 hours the cells were stained for HLA-DR and analysed by flow cytometry. 10(-2) M 5ASA reduced DR expression induced by 50 U/ml interferon-gamma from 62 (12)% of cells (mean SD) to 29 (20)% (p less than 0.005). Corresponding figures for 10(-2) M N-acetyl 5ASA were 68 (16)% to 39 (17)% (p less than 0.05); for 10(-2) M 4ASA, 61 (4)% to 57 (4)% (p = 0.6); for 10(-2) M N-acetyl 4ASA, 60 (12)% to 35 (13)% (p less than 0.05); for 10(-2) M olsalazine, 72 (9)% to 3 (1)% (p less than 0.001); for 10(-3) M olsalazine, 72 (9)% to 16 (10)% (p less than 0.001); for 10(-6) M colchicine, 62 (13)% to 5 (3)% (p less than 0.001); and for 10(-7) M colchicine, 62 (13)% to 10 (3)%. Similar results were obtained when DR was induced by 100 U/ml of interferon-gamma except with 10(-2) M 4ASA which reduced expression from 77 (4)% to 68 (3)% (p less than 0.05). Sulphapyridine, prednisolone, indomethacin and cyclosporin A had no effect. Concurrent staining with propidium iodide showed that these results were unchanged when viable cells alone were analysed. Prior incubation of cells with drug, followed by washing, had no effect on interferon-gamma induced DR expression. 5ASA, N-acetyl 5ASA, 4ASA, N-acetyl 4ASA, olsalazine and colchicine reduce interferon-gamma induced HLA-DR expression. In inflammatory bowel disease these compounds may impair antigen presentation by the colonic epithelium.


A Qualitative Study on the Motivators, Barriers and Supports to Participation in a Pediatric Produce Prescription Program in Hawai'i.
Produce prescriptions that provide vouchers to individuals to purchase fresh FVs at a specified retail outlet have the potential to positively impact food security status, diet, and chronic disease risk. However, maximizing program participation is vital to ensuring program success. This research describes motivators, barriers, and support for participation in a child produce prescription program among a population of Native Hawaiian and Other Pacific Islanders, who are underrepresented in this field of research. This qualitative grounded theory study was nestled within a quasi-experimental pilot intervention trial and included semi-structured interviews with pediatric program participants. Twenty-five interviews were conducted, which represented one-third of program participants. The top support factors for program participation included: ease of voucher use, program convenience, health center/pediatrician endorsement and positive communications with farmers' market vendors. Key motivators for program participation were produce enjoyment, child support, financial support, and positive impacts on family. Three themes emerged consistently as barriers to participation amongst participants, (1) difficult use of vouchers, (2) conflicting schedules, and (3) online market concerns. (4) Conclusions: This research offers insight into policy implications as the number of produce prescription programs has grown. These findings suggest that key program design characteristics can enhance and support program participation.


Potential determinants of obesity among children and adolescents in Germany: results from the cross-sectional KiGGS Study.
Obesity among children and adolescents is a growing public health problem. The aim of the present paper is to identify potential determinants of obesity and risk groups among 3- to 17-year old children and adolescents to provide a basis for effective prevention strategies. Data were collected in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), a nationally representative and comprehensive data set on health behaviour and health status of German children and adolescents. Body height and weight were measured and body mass index (BMI) was classified according to IOTF cut-off points. Statistical analyses were conducted on 13,450 non-underweight children and adolescents aged 3 to 17 years. The association between overweight, obesity and several potential determinants was analysed for this group as well as for three socio-economic status (SES) groups. A multiple logistic regression model with obesity as the dependent variable was also calculated. The strongest association with obesity was observed for parental overweight and for low SES. Furthermore, a positive association with both overweight (including obesity) and obesity was seen for maternal smoking during pregnancy, high weight gain during pregnancy (only for mothers of normal weight), high birth weight, and high media consumption. In addition, high intakes of meat and sausages, total beverages, water and tea, total food and beverages, as well as energy-providing food and beverages were significantly associated with overweight as well as with obesity. Long sleep time was negatively associated with obesity among 3- to 10-year olds. Determinants of obesity occurred more often among children and adolescents with low SES. Parental overweight and a low SES are major potential determinants of obesity. Families with these characteristics should be focused on in obesity prevention.


Rhesus monkey TRIM5α SPRY domain recognizes multiple epitopes that span several capsid monomers on the surface of the HIV-1 mature viral core.
The restriction factor TRIM5α binds to the capsid protein of the retroviral core and blocks retroviral replication. The affinity of TRIM5α for the capsid is a major host tropism determinant of HIV and other primate immunodeficiency viruses, but the molecular interface involved in this host-pathogen interaction remains poorly characterized. Here we use NMR spectroscopy to investigate binding of the rhesus TRIM5α SPRY domain to a selection of HIV capsid constructs. The data are consistent with a model in which one SPRY domain interacts with more than one capsid monomer within the assembled retroviral core. The highly mobile SPRY v1 loop appears to span the gap between neighboring capsid hexamers making interhexamer contacts critical for restriction. The interaction interface is extensive, involves mobile loops and multiple epitopes, and lacks interaction hot spots. These properties, which may enhance resistance of TRIM5α to capsid mutations, result in relatively low affinity of the individual SPRY domains for the capsid, and the TRIM5α-mediated restriction depends on the avidity effect arising from the oligomerization of TRIM5α.


Evaluation of factors affecting the healing process of venous ulcers: a 12-week longitudinal study.
The process of healing venous ulcers is complex and influenced by many factors. By identifying the risk factors that influence a slower healing process, it is possible to predict impending delays and plan an individualized care plan. We analyzed our database of patients with venous ulcers and identified clinical and demographic factors that delay the healing process. The research analyzed the medical records of 754 patients with VLUs at Chronic Wound Treatment Unit of the University Hospital treated between 2001 and 2019. RESULTS: In study, the majority (64.3%) were women, the mean age was 65.7 years. The median duration of Chronic Venous Insufficiency was 24 years, 52% patients had had the disease >20 years, and 296 (39.3%) had experienced ulceration >12 months. Most of the patients (85.8%) had comorbidities, 84% were obese. At 12-week follow-up, 432 of the 754 ulcers had healed. Identified independent predictors of slower ulcer healing rates: wound area greater than 8.25 cm2 , location of the ulceration other than the medial ankle area, underlying disease >20 years, the presence of multiple comorbidities, depth of the ulcer, the presence of an unpleasant smell and alert pathogens. The presence of redness resulted in faster healing of VLUc. Many factors influence the healing process of venous ulceration. The results of the study can help in planning patient care and implementing appropriate early strategies to promote healing.


Matrix Metallopeptidase 14: A Candidate Prognostic Biomarker for Diffuse Large B-Cell Lymphoma.
Matrix metallopeptidase 14 (MMP14) is an important gene in the regulation of T-cell function. However, the correlation between MMP14 expression, prognosis, and immune cell infiltration in diffuse large B-cell lymphoma (DLBCL) remains unclear. We investigated the influence of MMP14 on clinical prognosis using data obtained from three Gene Expression Omnibus (GEO) database sets (GSE98588, GSE10846, and GSE4475). The expression of MMP14 was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA). The correlation between MMP14 and immune cell infiltration was investigated using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Tumor Immune Estimation Resource (TIMER) tools. In addition, the correlation between MMP14 expression and immune gene markers was analyzed by TIMER and GEPIA. MMP14 expression positively correlated with favorable progression-free survival (PFS; GSE98588, P = 0.02) and overall survival (OS; GSE98588, P = 0.003; GSE10846, P = 5.517e-05; and GSE4475, P = 9.85e-04). Moreover, MMP14 expression was higher in DLBCL tumors than in normal tissues. Regarding clinical characteristics, high MMP14 expression was found to be correlated with race. MMP14 expression was also correlated with immune cell infiltration and had a remarkable correlation with various immune marker sets. It was found that M0 macrophages were the immune cells most related to survival, decreasing with the increase in Ann Arbor clinical stage. The results especially showed that MMP14 was a prognostic biomarker and related to the macrophages M0. The results suggest that MMP14 is a novel prognostic molecular marker for DLBCL and is related to the immune cell infiltration, especially related to the macrophages M0. Our study provides insights for understanding the potential roles of MMP14 in tumor immunology and its suitability as a prognosis biomarker in DLBCL.


Humoral immunity in the pig.
The newborn pig relies on colostrum as its sole source for serum antibody and milk for its intestinal antibody during most of the post natal period. Colostrum and milk are well adapted to perform their very different immune functions--immunoglobulin in colostrum being derived from serum, whereas milk antibodies are locally produced in the mammary gland and mirror the immunoglobulin profile of adult intestinal juice. Intramammary vaccination is far superior to intramuscular vaccination because it produces not only a local but a systemic response. Oral vaccination is similarly effective. Vaccination of one mammary gland results in antibody activity in the secretion of all glands. Irrespective of the route of vaccination, antibody activity is found in all immunoglobulin classes. The main site of immunoglobulin-containing cells is the lamina propria of the intestinal tract, suggesting that the gut is a major site of immunoglobulin formation. In the piglet, immunoglobulin producing cells first appear in the gut at the end of the first week of life and reach a mature profile after a month. During this period the piglet is likely to be capable of responding to orally presented antigens.


NMR analysis of the monomeric form of a mutant unliganded bovine neurophysin: comparison with the crystal structure of a neurophysin dimer.
Determination of the structure of the unliganded monomeric state of neurophysin is central to an understanding of the allosteric relationship between neurophysin peptide-binding and dimerization. We examined this state by NMR, using the weakly dimerizing H80E mutant of bovine neurophysin-I. The derived structure, to which more than one conformer appeared to contribute, was compared with the crystal structure of the unliganded des 1-6 bovine neurophysin-II dimer. Significant conformational differences between the two proteins were evident in the orientation of the 3,10 helix, in the 50-58 loop, in beta-turns, and in specific intrachain contacts between amino- and carboxyl domains. However, both had similar secondary structures, in independent confirmation of earlier circular dichroism studies. Previously suggested interactions between the amino terminus and the 50-58 loop in the monomer were also confirmed. Comparison of the observed differences between the two proteins with demonstrated effects of dimerization on the NMR spectrum of bovine neurophysin-I, and preliminary investigation of the effects of dimerization on H80E spectra, allowed tentative distinction between the contributions of sequence and self-association differences to the difference in conformation. Regions altered by dimerization encompass most binding site residues, providing a potential explanation of differences in binding affinity between the unliganded monomeric and dimeric states. Differences between monomer and dimer states in turns, interdomain contacts, and within the interdomain segment of the 50-58 loop suggest that the effects of dimerization on intrasubunit conformation reflect the need to adjust the relative positions of the interface segments of the two domains for optimal interaction with the adjacent subunit and/or reflect the dual role of some residues as participants both at the interface and in interdomain contacts.


Guidelines for the treatment of childhood-onset Graves' disease in Japan, 2016.
Purpose behind developing these guidelines: Over one decade ago, the "Guidelines for the Treatment of Graves' Disease with Antithyroid Drug, 2006" (Japan Thyroid Association (JTA)) were published as the standard drug therapy protocol for Graves' disease. The "Guidelines for the Treatment of Childhood-Onset Graves' Disease with Antithyroid Drug in Japan, 2008" were published to provide guidance on the treatment of pediatric patients. Based on new evidence, a revised version of the "Guidelines for the Treatment of Graves' Disease with Antithyroid Drug, 2006" (JTA) was published in 2011, combined with the "Handbook of Radioiodine Therapy for Graves' Disease 2007" (JTA). Subsequently, newer findings on pediatric Graves' disease have been reported. Propylthiouracil (PTU)-induced serious hepatopathy is an important problem in pediatric patients. The American Thyroid Association's guidelines suggest that, in principle, physicians must not administer PTU to children. On the other hand, the "Guidelines for the Treatment of Graves' Disease with Antithyroid Drug, 2011" (JTA) state that radioiodine therapy is no longer considered a "fundamental contraindication" in children. Therefore, the "Guidelines for the Treatment of Childhood-Onset Graves' Disease with Antithyroid Drug in Japan, 2008" required revision.


Tunnel osteolysis post-ACL reconstruction: a systematic review examining select diagnostic modalities, treatment options and rehabilitation protocols.
The purpose of this systematic review was to (1) identify the optimal diagnostic modality for tunnel widening in skeletally mature patients; (2) identify potentially modifiable risk factors for tunnel widening, such as graft type, and (3) determine what elements of a post-operative rehabilitation program exert the most influence on TW. The electronic databases MEDLINE, EMBASE, PubMed, and Cochrane Library were searched from database inception to January 2018. Studies that discussed tunnel widening following anterior cruciate ligament reconstruction (ACLR) of skeletally mature patients and written in English were included. Descriptive statistics, such as means, ranges, and measures of variance (e.g. standard deviations, 95% confidence intervals (CI)) are presented where applicable. 103 studies (6,383 patients) were included. Plain radiographs were the most commonly used diagnostic modality, but radiographs on average required 10 months longer than CT and 2 months longer on average than MRI to diagnose tunnel widening after ACLR. Although CT was the least commonly used modality, it was the shortest time to diagnose tunnel widening at 9.5 months after ACLR. Bone-patellar tendon-bone (BPTB) allograft had the largest average tunnel widening overall. BPTB autograft had the lowest average tunnel widening overall. Double-bundle hamstring graft configuration had a lower average tunnel widening than single-bundle configuration. Rehabilitation protocols after ACLR that used a full weight-bearing prescription in rehabilitation showed a greater average femoral tunnel widening than partial weight-bearing, and partial weight-bearing showed a greater average tibial tunnel widening than full weight-bearing. Based on this systematic review and the descriptive data evaluated, CT demonstrated a time of 9.5 months on average from ACLR to diagnosing tunnel osteolysis post-ACLR. With respect to graft types, double-bundle hamstring autografts reported lower average femoral and tibial TW than single-bundle hamstring autografts. BPTB autografts reported the lowest average TW and BPTB allograft the largest average TW of all the grafts. Furthermore, extension-locked bracing had the lowest TW of all the brace protocols. Lastly, several other surgical technical parameters influencing tunnel osteolysis remain to be determined. No definitive recommendations can be made at this time due to the high heterogeneity of data and the lack of comparative studies analysed in this systematic review. IV.


Comparative analysis of liver transcriptome reveals adaptive responses to hypoxia environmental condition in Tibetan Chicken.
Tibetan chickens, which have unique adaptations to extreme high-altitude environments, exhibit phenotypic and physiological characteristics that are distinct from those of lowland chickens. However, the mechanisms underlying hypoxic adaptation in the liver of chickens remain unknown. RNA-sequencing (RNA-Seq) technology was used to assess the differentially expressed genes (DEGs) involved in hypoxia adaptation in highland chickens (native Tibetan chicken [HT]) and lowland chickens (Langshan chicken [LS], Beijing You chicken [BJ], Qingyuan Partridge chicken [QY], and Chahua chicken [CH]). A total of 352 co-DEGs were specifically screened between HT and four native lowland chicken breeds. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these co-DEGs were widely involved in lipid metabolism processes, such as the peroxisome proliferator-activated receptors (PPAR) signaling pathway, fatty acid degradation, fatty acid metabolism and fatty acid biosynthesis. To further determine the relationship from the 352 co-DEGs, protein-protein interaction (PPI) network was carried out that eight genes (ACSL1, CPT1A, ACOX1, PPARC1A, SCD, ACSBG2, ACACA and FASN) were identified as the potential regulating genes that are responsible for the altitude difference between the HT and other four lowland chicken breeds. This study provides novel insights into the molecular mechanisms regulating hypoxia adaptation via lipid metabolism in Tibetan chickens and other highland animals.


RFC1 expansions are a common cause of idiopathic sensory neuropathy.
After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sjögren's syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies.


Involvement of adenosine in cerebral hypoxic hyperemia in the dog.
Theophylline, a competitive adenosine antagonist, was used to evaluate the role of adenosine in cerebral hypoxic hyperemia. Cerebral venous outflow was measured by the Rapela-Green technique in mongrel dogs anesthetized with pentobarbital sodium and ventilated artificially. Theophylline was infused locally into the cerebral arterial system during moderate [cerebral venous O2 tension (PO2) 27-29 mmHg] or severe (cerebral venous PO2 = 10-15 mmHg) hypoxia; theophylline had no direct vascular effects at the concentration used. Cerebral hyperemia was completely reversed during moderate hypoxia, but only partially reversed during severe hypoxia when theophylline was infused during maintained hypoxia. Theophylline had no effect on cerebral; perfusion pressure, blood flow, or vascular resistance during normoxia. In another group, theophylline had no effect on the cerebral hyperemia induced by hypercapnia. In separate experiments, local cerebral arterial infusion of adenosine or AMP during normoxia had no effect on cerebral hemodynamics at any infusion rate tested (up to 100 micrograms/min). This study supports the hypothesis that adenosine is involved in the hyperemia associated with cerebral hypoxia. However, the degree of involvement may be dependent on the degree of hypoxia.


Detection of the Ah receptor in rainbow trout: use of 2-azido-3-[125I]iodo-7,8-dibromodibenzo-p-dioxin in cell culture.
The Ah receptor was detected in RTG-2 cells (rainbow trout embryonic gonad cells) following the addition of the photoaffinity ligand, [125I]2-azido-3-iodo-7,8-dibromodibenzo-p-dioxin, to cells in culture. Cytosolic and nuclear extracts were prepared and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and revealed one radiolabeled band. Very little non-specific binding was observed under the conditions employed when compared to photoaffinity labeling RTG-2 cytosolic extracts in vitro. The photoaffinity-labeled Ah receptor in RTG-2 cytosol was analyzed by sucrose density centrifugation. The cytosolic form was observed to sediment at approximately 9.8S and the high salt nuclear extract form at approximately 7.5S. The relative molecular weight of the Ah receptor was determined to be 145 kDa under denaturing conditions and is considerably larger than the Ah receptor from mammalian sources. Inhibition of photoaffinity ligand binding to the RTG-2 cytosolic Ah receptor by competing ligands revealed the same rank order of ligand affinity as that previously demonstrated for the mouse Ah receptor.


[Current status of vaginal ultrasound--a worldwide survey].
In the last five years, vaginosonography has become a routine procedure in Obstetrics and Gynaecology. Many obstetricians, gynaecologists, radiologists and ultrasonographers have recognized the advantages of this method. A number of manufacturers of ultrasound equipment offer several types of vaginal probes. Nevertheless, the rapid development of vaginosonography has led to some disadvantages concerning a standardised terminology and image display. In this study we collected data on the current standards of vaginosonography. To gain data on the current use of vaginosonography, we sent out questionnaires to the 1107 departments of Obstetrics/Gynaecology in the FIGO Registry of 1985. In an accompanying letter we asked the chairmen to pass on the questionnaire to the appropriate specialist. The questionnaire was designed to gather information about the personnel performing vaginosonography and such as technique, transducer frequency, position of the patient and image display used. We received 366 responses. Vaginosonographic investigations are performed in 84% of the Obstetrics/Gynaecological University Departments, of which 90% of vaginosonography was performed by an obstetrician or gynaecologist, 5% by a radiologist and 5% by a technician. Predominantly end firing scanners were preferred. The number of electronic and mechanical scanners were nearly identical (55% vs 45%). The preference for a scanner with a narrow (less than 120 degrees) or wide angle (greater than 120 degrees) was very similar (53% vs 47%). More than half of the replies indicated (54%) used a transducer frequency of 5 MHz, 46% preferred scanners with a frequency between 5.5 and 7.5 MHz. In 55%, the gynaecological examination table was considered superior to a flat table.(ABSTRACT TRUNCATED AT 250 WORDS)


A-form conformational motifs in ligand-bound DNA structures.
Recognition and biochemical processing of DNA requires that proteins and other ligands are able to distinguish their DNA binding sites from other parts of the molecule. In addition to the direct recognition elements embedded in the linear sequence of bases (i.e. hydrogen bonding sites), these molecular agents seemingly sense and/or induce an "indirect" conformational response in the DNA base-pairs that facilitates close intermolecular fitting. As part of an effort to decipher this sequence-dependent structural code, we have analyzed the extent of B-->A conformational conversion at individual base-pair steps in protein and drug-bound DNA crystal complexes. We take advantage of a novel structural parameter, the position of the phosphorus atom in the dimer reference frame, as well as other documented measures of local helical structure, e.g. torsion angles, base-pair step parameters. Our analysis pinpoints ligand-induced conformational changes that are difficult to detect from the global perspective used in other studies of DNA structure. The collective data provide new structural details on the conformational pathway connecting A and B-form DNA and illustrate how both proteins and drugs take advantage of the intrinsic conformational mechanics of the double helix. Significantly, the base-pair steps which exhibit pure A-DNA conformations in the crystal complexes follow the scale of A-forming tendencies exhibited by synthetic oligonucleotides in solution and the known polymorphism of synthetic DNA fibers. Moreover, most crystallographic examples of complete B-to-A deformations occur in complexes of DNA with enzymes that perform cutting or sealing operations at the (O3'-P) phosphodiester linkage. The B-->A transformation selectively exposes sugar-phosphate atoms, such as the 3'-oxygen atom, ordinarily buried within the chain backbone for enzymatic attack. The forced remodeling of DNA to the A-form also provides a mechanism for smoothly bending the double helix, for controlling the widths of the major and minor grooves, and for accessing the minor groove edges of individual base-pairs.


Evaluating respondent-driven sampling in a major metropolitan area: Comparing injection drug users in the 2005 Seattle area national HIV behavioral surveillance system survey with participants in the RAVEN and Kiwi studies.
To empirically evaluate respondent-driven sampling (RDS) recruitment methods, which have been proposed as an advantageous means of surveying hidden populations. The National HIV Behavioral Surveillance system used RDS to recruit 370 injection drug users (IDU) in the Seattle area in 2005 (NHBS-IDU1). We compared the NHBS-IDU1 estimates of participants' area of residence, age, race, sex, and drug most frequently injected to corresponding data from two previous surveys, the RAVEN and Kiwi Studies, and to persons newly diagnosed with HIV/AIDS and reported from 2001 through 2005. The NHBS-IDU1 population was estimated to be more likely to reside in downtown Seattle (52%) than participants in the other data sources (22%-25%), be older than 50 years of age (29% vs. 5%-10%), and report multiple races (12% vs. 3%-5%). The NHBS-IDU1 population resembled persons using the downtown needle exchange in age and race distribution. An examination of cross-group recruitment frequencies in NHBS-IDU1 suggested barriers to recruitment across different areas of residence, races, and drugs most frequently injected. The substantial differences in age and area of residence between NHBS-IDU1 and the other data sources suggest that RDS may not have accessed the full universe of Seattle area injection networks. Further empirical data are needed to guide the evaluation of RDS-generated samples.


A Novel Robot-Aided Upper Limb Rehabilitation Training System Based on Multimodal Feedback.
During robot-aided rehabilitation exercises, monotonous, and repetitive actions can, to the subject, feel tedious and tiring, so improving the subject's motivation and active participation in the training is very important. A novel robot-aided upper limb rehabilitation training system, based on multimodal feedback, is proposed in this investigation. To increase the subject's interest and participation, a friendly graphical user interface and diversiform game-based rehabilitation training tasks incorporating multimodal feedback are designed, to provide the subject with colorful and engaging motor training. During this training, appropriate visual, auditory, and tactile feedback is employed to improve the subject's motivation via multi-sensory incentives relevant to the training performance. This approach is similar to methods applied by physiotherapists to keep the subject focused on motor training tasks. The experimental results verify the effectiveness of the designed multimodal feedback strategy in promoting the subject's participation and motivation.


Dietary DHA prevents cognitive impairment and inflammatory gene expression in aged male rats fed a diet enriched with refined carbohydrates.
The consumption of a processed foods diet (PD) enriched with refined carbohydrates, saturated fats, and lack of fiber has increased in recent decades and likely contributed to increased incidence of chronic disease and weight gain in humans. These diets have also been shown to negatively impact brain health and cognitive function in rodents, non-human primates, and humans, potentially through neuroimmune-related mechanisms. However, mechanisms by which PD impacts the aged brain are unknown. This gap in knowledge is critical, considering the aged brain has a heightened state of baseline inflammation, making it more susceptible to secondary challenges. Here, we showed that consumption of a PD, enriched with refined carbohydrate sources, for 28 days impaired hippocampal- and amygdalar-dependent memory function in aged (24 months), but not young (3 months) F344 × BN rats. These memory deficits were accompanied by increased expression of inflammatory genes, such as IL-1β, CD11b, MHC class II, CD86, NLRP3, and complement component 3, in the hippocampus and amygdala of aged rats. Importantly, we also showed that when the same PD is supplemented with the omega-3 polyunsaturated fatty acid DHA, these memory deficits and inflammatory gene expression changes were ameliorated in aged rats, thus providing the first evidence that DHA supplementation can protect against memory deficits and inflammatory gene expression in aged rats fed a processed foods diet. Lastly, we showed that while PD consumption increased weight gain in both young and aged rats, this effect was exaggerated in aged rats. Aging was also associated with significant alterations in hypothalamic gene expression, with no impact by DHA on weight gain or hypothalamic gene expression. Together, our data provide novel insights regarding diet-brain interactions by showing that PD consumption impairs cognitive function likely through a neuroimmune mechanism and that dietary DHA can ameliorate this phenomenon.


Parathyroid imaging with pertechnetate plus perchlorate/MIBI subtraction scintigraphy: a fast and effective technique.
We set up a modified technetium-99m (Tc-99m) pertechnetate/Tc-99m MIBI (Tc-MIBI) subtraction scintigraphy for parathyroid imaging by introducing the use of potassium perchlorate (KCLO4). Initially, the effect of KCLO4 on technetium thyroid wash-out was evaluated in five healthy volunteers: 40-minute dynamic studies of the thyroid were obtained 20 minutes after the injection of technetium 150 MBq (4 mCi), both in baseline conditions and after the oral administration of 400 mg KCLO4. After an average latency time of 10.5 minutes, KCLO4 administration resulted in fast and relevant technetium thyroid wash-out with a mean half-time of 16.2 minutes (the half-time was 142.8 minutes in baseline conditions), and a 40-minute reduction of thyroid activity of 78% (it was 14% in baseline conditions). Based on these findings, a new Tc-MIBI subtraction procedure was established as follows: 1) 150 MBq technetium (4 mCi) injection; 2) 400 mg KCLO4 administered orally; 3) patient neck immobilization; 4) acquisition of a 5-minute technetium thyroid scan; 5) 500 MBq MIBI (13.5 mCi) injection; 6) acquisition of a sequence of seven MIBI images, each lasting 5 minutes; and 7) processing (image realignment when necessary, background subtraction, normalization of MIBI images to the maximum pixel count of the technetium image, and subtraction of the technetium image from the MIBI images). In addition, high-resolution neck ultrasound (US) was performed in all cases on the same day as the scintigraphic evaluation. Eighteen consecutive patients with primary hyperparathyroidism were enrolled in the study. Tc-MIBI scintigraphy revealed a single adenoma in all cases and US showed this finding in 15 of 18 cases (83.3%). Furthermore, in three patients, a thyroid nodule associated with hyperparathyroidism was detected by technetium thyroid scans and neck US. In all patients, the parathyroid adenoma was easily identified on both the 20- to 40-minute MIBI and subtracted (MIBI-Tc) images. Regarding the scintigraphic parameters, no difference was found between parathyroid adenomas located in the region of the thyroid bed or in ectopic sites and in parathyroid adenomas with a retrothyroid location. Surgical findings confirmed the presence of a single parathyroid adenoma in all cases. In the three patients with a concomitant thyroid nodule, thyroid lobectomy was performed. These preliminary data suggest that 1) double-tracer subtraction scintigraphy, combined with neck US, appears to be the preferable preoperative imaging procedure in hyperparathyroidism patients with concomitant thyroid nodular disease, 2) in the Tc-MIBI parathyroid scan, the use of KCLO4 results in a rapid and relevant technetium thyroid clearance, improving the quality of MIBI images and making the visualization of parathyroid adenomas, particularly those located behind the thyroid gland, easier.


Innate immunity correlates with host fitness in wild boar (Sus scrofa) exposed to classical swine fever.
Constitutive humoral immunity (CHI) is thought to be a first-line of protection against pathogens invading vertebrate hosts. However, clear evidence that CHI correlates with host fitness in natural conditions is still lacking. This study explores the relationship between CHI, measured using a haemagglutination-haemolysis assay (HAHL), and resistance to classical swine fever virus (CSFV) among wild boar piglets. The individual dynamics of HAHL during piglet growth was analysed, using 423 serum samples from 92 piglets repeatedly captured in the absence of CSFV (in 2006) within two areas showing contrasting food availability. Natural antibody levels increased with age, but, in the youngest piglets antibody levels were higher in individuals from areas with the highest food availability. Complement activity depended on natural antibody levels and piglets' body condition. In the presence of CSFV (i.e., in 2005 within one area), serum samples from piglets that were repeatedly captured were used to assess whether piglet HAHL levels affected CSFV status at a later capture. The correlation between CHI and resistance to CSFV was tested using 79 HAHL measures from 23 piglets captured during a CSFV outbreak. Both natural antibodies and complement activity levels measured at a given time correlated negatively to the subsequent probability of becoming viremic. Finally, capture-mark-recapture models showed that piglets with medium/high average complement activity, independently of their age, were significantly less at risk of becoming viremic and more likely to develop a specific immune response than piglets with low complement activity. Additionally, piglets with high average complement activity showed the highest survival prospects. This study provides evidence linking CHI to individual fitness within a natural mammal population. The results also highlight the potential of HAHL assays to explore the dynamics and co-evolution between wildlife mammal hosts and blood-borne parasites interacting with the CHI.


Convergence of Groundwater Discharge through the Hyporheic Zone of Streams.
Significant attention has been given to hyporheic water fluxes induced by hydromorphologic processes in streambeds and the effects they have on stream ecology. However, the impact of hyporheic fluxes on regional groundwater flow discharge zones as well as the interaction of these flows are much less investigated. The groundwater-hyporheic interactive flow not only governs solute mass and heat transport in streams but also controls the retention of solute and contamination following the discharge of deep groundwater, such as naturally occurring solutes and leakage from geological waste disposal facilities. Here, we applied a physically based modeling approach combined with extensive hydrologic, geologic and geographical data to investigate the effect of hyporheic flow on groundwater discharge in the Krycklan catchment, located in a boreal landscape in Sweden. Regional groundwater modeling was conducted using COMSOL Multiphysics by considering geologic heterogeneity and infiltration constraint of the groundwater circulation intensity. Moreover, the hyporheic flow was analyzed using an exact spectral solution accounting for the fluctuating streambed topography and superimposed with the regional groundwater flow. By comparing the discharge flow fields with and without consideration of hyporheic flows, we found that the divergence of the discharge was substantially enhanced and the distribution of the travel times of groundwater was significantly shifted toward shorter times due to the presence of hyporheic flow. Particularly important is that the groundwater flow paths contract near the streambed interface due to the hyporheic flow, which leads to a phenomenon that we name "fragmentation" of coherent areas of groundwater upwelling in pinhole-shaped stream tubes.


Impaired lung homeostasis in neonatal mice exposed to cigarette smoke.
In infants, smoke exposure is associated with more respiratory illnesses and decreased lung function. We hypothesized that perinatal lung is particularly susceptible to the damaging effects of cigarette smoke (CS) and that exposure to CS during this period may alter expression of immune response genes and adversely affect lung growth. To test this, we exposed neonatal mice to 14 days of CS. Immediately after exposure to CS, pulmonary gene expression profiling was performed on 2-week-old CS-exposed lung and age-matched control lung. Nitrotyrosine, TUNEL, MAC3, and phospho-SMAD-2 (p-SMAD2) staining was also performed. At 8 weeks of age, lung volume measurements were determined and mean linear intercept measurements were calculated. Pulmonary gene expression profiling revealed that CS exposure significantly inhibited type 1 and type 2 interferon pathway genes in neonatal lung, compared with age-matched control lung. Neonatal CS-exposed lung also had a significant increase in n-tyrosine, TUNEL, and p-SMAD2 staining when compared with adult CS-exposed lung and age-matched control lung. Lung volumes at 8 weeks of age were modestly but significantly decreased in mice exposed to CS in the neonatal period compared with age-matched controls, consistent with impaired lung growth. The results of this study indicate that exposure to CS during the neonatal period inhibits expression of genes involved in innate immunity and mildly impairs postnatal lung growth. These findings may in part explain the increased incidence of respiratory symptoms in infants and children exposed to CS.


Morphology Development in Solution-Processed Functional Organic Blend Films: An In Situ Viewpoint.
Solution-processed organic films are a facile route to high-speed, low cost, large-area deposition of electrically functional components (transistors, solar cells, emitters, etc.) that can enable a diversity of emerging technologies, from Industry 4.0, to the Internet of things, to point-of-use heath care and elder care. The extreme sensitivity of the functional performance of organic films to structure and the general nonequilibrium nature of solution drying result in extreme processing-performance correlations. In this Review, we highlight insights into the fundamentals of solution-based film deposition afforded by recent state-of-the-art in situ measurements of functional film drying. Emphasis is placed on multimodal studies that combine surface-sensitive X-ray scattering (GIWAXS or GISAXS) with optical characterization to clearly define the evolution of solute structure (aggregation, crystallinity, and morphology) with film thickness.


Dynamic and static light scattering studies on self-aggregation behavior of biodegradable amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) triblock copolymers in aqueous solution.
The self-aggregation behavior of two amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) triblock copolymer samples with nearly identical PHB block lengths but different PEO block lengths, PEO-PHB-PEO(2000-810-2000) and PEO-PHB-PEO(5000-780-5000), was studied with dynamic and static light scattering (DLS and SLS), in combination with fluorescence spectroscopy and transmission electron microscopy (TEM). The formation of polymeric micelles by the two PEO-PHB-PEO triblock copolymers was confirmed with fluorescence technique and TEM. DLS analysis showed that the hydrodynamic radius (R(h)) of the monodistributed polymeric micelles increased with an increase in PEO block length. The relative thermostability of the triblock copolymer micelles was studied by SLS and DLS at different temperatures. The aggregation number and the ratio of the radius of gyration over hydrodynamic radius were found to be independent of temperature, probably due to the strong hydrophobicity of the PHB block. The combination of DLS and SLS studies indicated that the polymeric micelles were composed of a densely packed core of hydrophobic PHB blocks and a corona shell formed by hydrophilic PEO blocks. The aggregation numbers were found to be approximately 53 for PEO-PHB-PEO(2000-810-2000) micelles and approximately 37 for PEO-PHB-PEO(5000-780-5000) micelles. The morphology of PEO-PHB-PEO spherical micelles determined by DLS and SLS measurements was further confirmed by TEM.


Effect of 2-acetylaminofluorene on the binding of epidermal growth factor to microsomal and Golgi fractions of rat liver cells.
The livers of rats fed the hepatocarcinogen 2-acetylaminofluorene (0.02%) with chow showed a sharp decrease in the binding of epidermal growth factor to microsomes and Golgi fractions. The binding to the latter decreased from 15.3% specific binding per 0.1 mg protein in controls to 9.4% after 2 days and reached a nadir of 0.8% after 21 days. The binding to microsomes decreased from 26.3% specific binding per 0.5 mg protein in the controls to 17.4% after 4 days and reached a nadir of 7.5% after 46 days. The low binding which persisted until the end of the experiment (85 days) was due to the apparent decrease in the number of receptors without significant changes in their affinity. Also, there was only partial recovery in rats fed 2-acetylaminofluorene for 90 to 107 days and taken off the carcinogen for 30 to 75 days. In vitro, neither 2-acetylaminofluorene nor its metabolites hydroxy- and acetocy -2-acetylaminofluorene significantly decreased epidermal growth factor binding to the isolated microsomal fraction.


A novel locus for restless legs syndrome on chromosome 13q.
Restless legs syndrome (RLS) is a sensorimotor disorder in which affected individuals suffer from uncomfortable sensations and an urge to move their lower limbs; it occurs mainly in resting situations during the evening or at night. Multiple chromosomal loci have been mapped for RLS through family-based linkage analysis, and genome-wide association studies but causative mutations have not been identified yet. We identified an RLS family from the eastern part of central Turkey which has 10 patients suffering from this syndrome. Whole genome linkage analysis was performed in family members who consented for study (9 affected and 2 unaffected). A theoretical maximum logarithm of the odds score of 3.29 was identified at chromosome 13q32.3-33.2. This result shows strong genetic linkage to this locus. We demonstrated a genetic linkage at chromosome 13 in a RLS family. Further investigation in this linkage area may reveal a causative gene leading to RLS phenotype and may illuminate the pathogenesis of this disease. This study supports the genetic heterogeneity in the pathogenesis of this syndrome.


Comparison of Sonography versus Digital Breast Tomosynthesis to Locate Intramammary Marker Clips.
Introduction: This study aimed to compare the accuracy of sonography versus digital breast tomosynthesis to locate intramammary marker clips placed under ultrasound guidance. Patients and Methods: Fifty patients with suspicion of breast cancer (lesion diameter less than 2 cm [cT1]) had ultrasound-guided core needle biopsy with placement of a marker clip in the center of the tumor. Intramammary marker clips were subsequently located with both sonography and digital breast tomosynthesis. Results: Sonography detected no dislocation of intrammammary marker clips in 42 of 50 patients (84 %); dislocation was reported in 8 patients (16 %) with a maximum dislocation of 7 mm along the x-, y- or z-axis. Digital breast tomosynthesis showed accurate placement without dislocation of the intramammary marker clip in 48 patients (96 %); 2 patients (4 %) had a maximum clip dislocation of 3 mm along the x-, y- or z-axis (p < 0.05). Conclusion: The use of digital breast tomosynthesis could improve the accuracy when locating intramammary marker clips compared to sonography and could, in future, be used to complement or even completely replace sonography.


Investigation of Realizing Both Antibacterial Property and Osteogenic Cell Compatibility on Titanium Surface by Simple Electrochemical Treatment.
Recently, the problem of infection on implanted devices caused by the formation of biofilms has been recognized. Surface treatment to prevent the initial stages of bacterial adhesion and subsequent bacterial growth is the only possible solution against such infection. In this study, simple electrochemical treatment was used for introducing silver, an antibiotic agent, on the titanium surface. A porous oxide layer containing small amounts of silver was formed on the metal of the substrate. This was done by microarc oxidation using the electrolyte with silver nitrate. The porous oxide layer was almost amorphous with a small fraction of anatase phase. The samples prepared using the electrolyte containing 0.04 mM or a higher concentration of silver nitrate showed an excellent antibacterial effect against both E. coli and S. aureus. However, the proliferation of osteoblast-like cells in the samples was not affected when a concentration of 0.5 mM or lower was used. Moreover, samples containing silver showed no harmful effects on the process of bone differentiation. Furthermore, the calcification process of the cells on the samples treated with and without silver were more promoted than that on untreated Ti. Thus, we found that it is possible to use this optimum concentration of silver to realize the conflicting biofunctions: its antibacterial property and osteogenic cell compatibility.


New Insights into the Physiology of Iron Transport: An Interdisciplinary Approach.
The TransCure project entitled 'Iron Transporters DMT1 and FPN1' took an interdisciplinary approach combining structural biology, chemistry and physiology to gain new insights into iron transport. Proteins studied included Divalent Metal Transporter 1 (DMT1, SLC11A2), enabling the import of Fe2+ into the cytoplasm, and the iron efflux transporter Ferroportin (FPN1, SLC40A1). The physiology and pathophysiology, and the mechanisms underlying iron transport in the gut, across the placenta and in bone were investigated. Small molecule high-throughput screening was used to identify improved modulators of DMT1. The characterization of DMT1 inhibitors have provided first detailed insights into the pharmacology of a human iron transport protein. In placental physiology, the identification of the expressional and functional alterations and underlying mechanisms in trophoblast cells clarified the association between placental iron transport by DMT1/FPN1 and gestational diabetes mellitus. In bone, iron metabolism was found to differ between cells of the monocyte/ macrophage lineages, including osteoclasts. Osteoclast development and activity depended on exogenous iron, the expression of high levels of the transferrin receptor (TFR) and low levels of FPN1 suggesting the expression of an "iron storage" phenotype by these cells. The principles and main findings of the TransCure studies on transmembrane iron transport physiology are summarized in this review.


Forest transitions in Eastern Europe and their effects on carbon budgets.
Forests often rebound from deforestation following industrialization and urbanization, but for many regions our understanding of where and when forest transitions happened, and how they affected carbon budgets remains poor. One such region is Eastern Europe, where political and socio-economic conditions changed drastically over the last three centuries, but forest trends have not yet been analyzed in detail. We present a new assessment of historical forest change in the European part of the former Soviet Union and the legacies of these changes on contemporary carbon stocks. To reconstruct forest area, we homogenized statistics at the provincial level for ad 1700-2010 to identify forest transition years and forest trends. We contrast our reconstruction with the KK11 and HYDE 3.1 land change scenarios, and use all three datasets to drive the LPJ dynamic global vegetation model to calculate carbon stock dynamics. Our results revealed that forest transitions in Eastern Europe occurred predominantly in the early 20th century, substantially later than in Western Europe. We also found marked geographic variation in forest transitions, with some areas characterized by relatively stable or continuously declining forest area. Our data suggest extensive deforestation in European Russia already prior to ad 1700, and even greater deforestation in the 18th and 19th centuries than in the KK11 and HYDE scenarios. Based on our reconstruction, cumulative carbon emissions from deforestation were greater before 1700 (60 Pg C) than thereafter (29 Pg C). Summed over our entire study area, forest transitions led to a modest uptake in carbon over recent decades, with our dataset showing the smallest effect (<5.5 Pg C) and a more heterogeneous pattern of source and sink regions. This suggests substantial sequestration potential in regrowing forests of the region, a trend that may be amplified through ongoing land abandonment, climate change, and CO2 fertilization.


Role of cholecystokinin in pancreatic adaptation to massive enterectomy.
Since pancreatic adaptation to massive proximal small bowel resection (PSBR) may be modulated through cholecystokinin (CCK) secretion, we tested the effect of the CCK antagonist CR-1409 on this response. Male Wistar rats (n = 72) weighing 220-225 g were randomised to receive either PSBR or transection/resuture followed by saline or CR-1409 (12 mg/kg daily subcutaneously). Rats were killed one, two, and three weeks post-operatively, at which time blood was obtained for CCK assay and the pancreas was assessed for proliferative activity by three parameters: nucleic acid and protein content, bromode-oxyuridine (BrdUrd) labelling index, and proliferating cell nuclear antigen (PCNA) expression. PSBR increased plasma CCK concentration by 83-102% at 1-3 weeks, irrespective of CR-1409 administration. Total pancreatic DNA content per 100 g body weight increased by 34% at two weeks (p less than 0.05) and by 82% at three weeks (p less than 0.05), while RNA content increased by 60% and 178% (p less than 0.001) and protein content by 20% and 57% (p less than 0.05). PSBR increased the BrdUrd labelling index and the percentage of PCNA immunoreactive cells. CR-1409 completely abolished this proliferative response and also prevented the rise in nucleic acid and protein contents. Apart from growth stimulation, PSBR also enhanced pancreatic exocrine function, as shown by ultrastructural evidence of an appreciable decrease in zymogen granules; CR-1409 also inhibited this functional effect of hypercholecystokininaemia. The results confirm the tropic role of CCK after PSBR, and CR-1409 prevents this pancreatic adaptation.


Onychomycosis in systemic lupus erythematosus: a case control study.
Immunosuppressed patients are prone to develop onychomycosis. In systemic lupus erythematosus (SLE) there are no previous studies. We aimed to establish the prevalence, clinical characteristics, and organisms causing onychomycosis in SLE patients compared with controls. Fifty consecutive patients with SLE seen on an outpatient basis and 50 sex and age matched controls. Samples were obtained when abnormal nails were found: distal and lateral subungual onychomycosis (DLSO), white superficial, proximal subungual (PSO), endonyx, and total dystrophic (TDO). The nail specimens were evaluated in a blinded fashion, by mycologic examination and culture. Of the SLE patients, there were 12 (24%) with onychomycosis confirmed. The distribution of the clinical forms were TDO 6/12 (50%), DLSO 4/12 (33%), and PSO 2/12 (17%). The causative organisms were isolated in 6 cases: Trichophyton rubrum 3/6 (50%), Trichophyton mentagrophytes 2/6 (33%), Microsporum canis 1/6 (17%). Direct microscopy examination revealed fungal elements in the other 6 cases. Of the 50 controls, 4 (8%) presented onychomycosis [p = 0.029; OR 3.63 (95% CI 1.04-14.68)]: DLSO 2/4 (50%), and TDO 2/4 (50%). Trichophyton rubrum was isolated in 1 and Trichophyton mentagrophytes in 1 (50%). These data suggest a higher prevalence of onychomycosis in SLE versus controls, the predominant organism was Trichophyton rubrum, an anthropophilic dermatophyte. Toenails were more frequently affected and the most common clinical presentation was TDO. PSO, a rare pattern in immunocompetent subjects, was exclusively found in the lupus group.


Matching, behavioral economics, and teleological behaviorism: Final cause analysis of substance use and health behavior.
Howard Rachlin and his contemporaries pioneered basic behavioral science innovations that have been usefully applied to advance understanding of human substance use disorder and related health behaviors. We briefly summarize the innovations of molar behaviorism (the matching law), behavioral economics, and teleological behaviorism. Behavioral economics and teleological behaviorism's focus on final causes are especially illuminating for these applied fields. Translational and applied research are summarized for laboratory studies of temporal discounting and economic demand, cohort studies of alcohol and other drug use in the natural environment, and experimental behavioral economic modeling of health behavior-related public health policies. We argue that the teleological behavioral perspective on health behavior is conducive to and merges seamlessly with the contemporary socioecological model of health behavior, which broadens the contextual influences (e.g., community, economic, infrastructure, health care access and policy) of individuals' substance use and other health risk behaviors. Basic-to-applied translations to date have been successful and bode well for continued applications of basic science areas pioneered by Howard Rachlin and his contemporaries.


Spectroelectrochemical flow cell with temperature control for investigation of electrocatalytic systems with surface-enhanced Raman spectroscopy.
We describe a method for investigating the reaction mechanism of fuel cell systems by designing a spectroelectrochemical cell with functions of temperature and flow control to mimic the reaction condition of fuel cell systems and utilizing Au core Pt shell (Au@Pt) nanoparticles to enhance the Raman signal of the surface species on the surface of electrocatalysts. The cell consists of three parts: a thin-layer spectroelectrochemical reaction chamber with an optical window for Raman measurement, the heating chamber right beneath the reaction chamber, and a long spiral flow channel to preheat the solution to the desired temperature and effectively exchange the solution. The temperature of the solution can be easily controlled from room temperature to 80 degrees C, and the flow rate can be as high as 945 microl s(-1). The temperature and flow control is demonstrated by monitoring the changes in the cyclic voltammograms and the Raman signals. By synthesizing Au@Pt nanoparticles and assembling them on a Pt substrate, we can significantly enhance the Raman signal of surface species on the Pt shell surface, which allows us to detect strong signal of CO as the dissociative product of formic acid as well as the intermediate species of the oxidation process. The further development and perspectives of using SERS to study the electrocatalytic systems are discussed.


Pleiotropy of systemic lupus erythematosus risk alleles and cardiometabolic disorders: A phenome-wide association study and inverse-variance weighted meta-analysis.
To test the hypothesis that genetic predisposition to systemic lupus erythematosus (SLE) increases the risk of cardiometabolic disorders. Using 41 single nucleotide polymorphisms (SNPs) associated with SLE, we calculated a weighted genetic risk score (wGRS) for SLE. In a large biobank we tested the association between this wGRS and 9 cardiometabolic phenotypes previously associated with SLE: atrial fibrillation, ischemic stroke, coronary artery disease, type 1 and type 2 diabetes, obesity, chronic kidney disease, hypertension, and hypercholesterolemia. Additionally, we performed a phenome-wide association analysis (pheWAS) to discover novel clinical associations with a genetic predisposition to SLE. Findings were replicated in the Electronic Medical Records and Genomics (eMERGE) Network. To further define the association between SLE-related risk alleles and the selected cardiometabolic phenotypes, we performed an inverse variance weighted regression (IVWR) meta-analysis. The wGRS for SLE was calculated in 74,759 individuals of European ancestry. Among the pre-selected phenotypes, the wGRS was significantly associated with type 1 diabetes (OR [95%CI] =1.11 [1.06, 1.17], P-value = 1.05x10-5). In the PheWAS, the wGRS was associated with several autoimmune phenotypes, kidney disorders, and skin neoplasm; but only the associations with autoimmune phenotypes were replicated. In the IVWR meta-analysis, SLE-related risk alleles were nominally associated with type 1 diabetes (P = 0.048) but the associations were heterogeneous and did not meet the adjusted significance threshold. A weighted GRS for SLE was associated with an increased risk of several autoimmune-related phenotypes including type I diabetes but not with cardiometabolic disorders.


A Novel Recessive RPGRIP1 Mutation Causing Leber Congenital Amaurosis.
Leber congenital amaurosis is an early-onset childhood severe retinal dystrophy, of significant genetic heterogeneity. RPGRIP1 is ubiquitously expressed, but mutations in RPGRIP1 lead to a retina-restricted phenotype, such as Leber congenital amaurosis and cone-rod dystrophy. We analysed a consanguineous family from Egypt in which one individual, a four-year-old girl, was affected with Leber congenital amaurosis. IROme, a proprietary enrichment system for retinal dystrophy genes, was applied and high throughput sequencing was performed. Severe visual impairment was reported during infancy. The fundus of the affected patient exhibited disc pallor and attenuated vessels. Neurodevelopmental delay and brain atrophy in the CT scan were reported. Genomic sequencing identified a novel homozygous deletion, c.[420delG], in RPGRIP1. This mutation was not detected in 80 ethnically matched controls and has not been reported elsewhere. Identifying new mutations in Leber congenital amaurosis-related genes and their clinical manifestations can improve our understanding of the disease and could help to stratify the population for potential therapies.


A Systematic Review and Network Meta-analyses to Assess the Effectiveness of Human Immunodeficiency Virus (HIV) Self-testing Distribution Strategies.
We conducted a systematic review and network meta-analysis to identify which human immunodeficiency virus (HIV) self-testing (HIVST) distribution strategies are most effective. We abstracted data from randomized controlled trials and observational studies published between 4 June 2006 and 4 June 2019. We included 33 studies, yielding 6 HIVST distribution strategies. All distribution strategies increased testing uptake compared to standard testing: in sub-Saharan Africa, partner HIVST distribution ranked highest (78% probability); in North America, Asia, and the Pacific regions, web-based distribution ranked highest (93% probability), and facility based distribution ranked second in all settings. Across HIVST distribution strategies HIV positivity and linkage was similar to standard testing. A range of HIVST distribution strategies are effective in increasing HIV testing. HIVST distribution by sexual partners, web-based distribution, as well as health facility distribution strategies should be considered for implementation to expand the reach of HIV testing services.


Too late to vaccinate? The incremental benefits and cost-effectiveness of a delayed catch-up program using the 4-valent human papillomavirus vaccine in Norway.
Human papillomavirus (HPV) vaccines are ideally administered before HPV exposure; therefore, catch-up programs for girls past adolescence have not been readily funded. We evaluated the benefits and cost-effectiveness of a delayed, 1-year female catch-up vaccination program in Norway. We calibrated a dynamic HPV transmission model to Norwegian data and projected the costs and benefits associated with 8 HPV-related conditions while varying the upper vaccination age limit to 20, 22, 24, or 26 years. We explored the impact of vaccine protection in women with prior vaccine-targeted HPV infections, vaccine cost, coverage, and natural- and vaccine-induced immunity. The incremental benefits and cost-effectiveness decreased as the upper age limit for catch-up increased. Assuming a vaccine cost of $150/dose, vaccination up to age 20 years remained below Norway's willingness-to-pay threshold (approximately $83 000/quality-adjusted life year gained); extension to age 22 years was cost-effective at a lower cost per dose ($50-$75). At high levels of vaccine protection in women with prior HPV exposure, vaccinating up to age 26 years was cost-effective. Results were stable with lower coverage. HPV vaccination catch-up programs, 5 years after routine implementation, may be warranted; however, even at low vaccine cost per dose, the cost-effectiveness of vaccinating beyond age 22 years remains uncertain.


[Dynamics of granulocyte proteins after lymphocytapheresis in patients with rheumatoid arthritis].
The authors studied concentrations of granulocytic proteins, lactoferrin, leukocytic thermostable alpha-glycoprotein in the blood plasma of patients with rheumatoid arthritis. High concentrations of the above proteins were observed in RA patients.


Risk factors for post-traumatic stress disorder symptoms following critical illness requiring mechanical ventilation: a prospective cohort study.
Post-traumatic stress disorder (PTSD) has been identified in a significant portion of intensive care unit (ICU) survivors. We sought to identify factors associated with PTSD symptoms in patients following critical illness requiring mechanical ventilation. Forty-three patients who were mechanically ventilated in the medical and coronary ICUs of a university-based medical center were prospectively followed during their ICU admission for delirium with the Confusion Assessment Method for the ICU. Additionally, demographic data were obtained and severity of illness was measured with the APACHE II (Acute Physiology and Chronic Health Evaluation II) score. Six months after discharge, patients were screened for PTSD symptoms by means of the Post-Traumatic Stress Syndrome 10-Questions Inventory (PTSS-10). Multiple linear regression was used to assess the association of potential risk factors with PTSS-10 scores. At follow-up, six (14%) patients had high levels of PTSD symptoms. On multivariable analysis, women had higher PTSS-10 scores than men by a margin of 7.36 points (95% confidence interval [CI] 1.62 to 13.11; p = 0.02). Also, high levels of PTSD symptoms were less likely to occur in older patients, with symptoms declining after age 50 (p = 0.04). Finally, although causation cannot be assumed, the total dose of lorazepam received during the ICU stay was associated with PTSD symptoms; for every 10-mg increase in cumulative lorazepam dose, PTSS-10 score increased by 0.39 (95% CI 0.17 to 0.61; p = 0.04). No significant relationship was noted between severity of illness and PTSD symptoms or duration of delirium and PTSD symptoms. High levels of PTSD symptoms occurred in 14% of patients six months following critical illness necessitating mechanical ventilation, and these symptoms were most likely to occur in female patients and those receiving high doses of lorazepam. High levels of PTSD symptoms were less likely to occur in older patients.


An active-learning course model to teach pharmacotherapy in geriatrics.
To describe the development, implementation, and assessment of a geriatric pharmacotherapy elective course emphasizing a patient-centered approach and active, self-directed learning strategies. The course content included fundamental concepts in aging, geriatric syndromes, activities involving assessment of medically complex older adults, presentation of controversies in clinical geriatrics, book and film clubs, an Adopt-a-Patient project, and scientific and reflective writing. Students participated in site visits to interview and interact with older adults. Student evaluation of the course was assessed with the teaching evaluation tool, an end-of-semester survey, a follow-up P4 survey, and reflective writings. Students strongly agreed that course goals were achieved. Learning how to communicate with older adults and assess complex medication regimens were the areas of highest importance to students. P4 students strongly agreed that skills learned in the course were important to their success in advanced pharmacy practice experiences (APPEs). A pharmacotherapy course emphasizing active and self-directed learning in geriatrics through innovative teaching was adaptable to doctor of pharmacy (PharmD) students at various stages of their training and improved students' perceptions of aging.


Extraction, preparation, and presentation of patient classification-data for the benefit of management overviews.
In the Free University Hospital, the nursing staff enters data daily into the computerized patient classification system. The computer calculates and gives a retrospective overview of the patient workload per day and per nursing unit. The present system does not comply with the information needs of the middle and higher management. This is due to differences in the manner of working on the various nursing units. For these reasons, the patient classification data was extracted from the central HIS database and copied to a PC environment. Here, the data was further ordered and processed to produce overviews for the nursing management. This was done by developing a user friendly interface with the spreadsheet program QuattroPro.


[Should one operate on bifocal tubal lesions in 1984? Apropos of 54 cases].
We have analysed 54 cases where the patients had two lesions in the tubes and were treated with microsurgery. The results of histological examinations show that chronic salpingitis in the major lesion. Infection was the aetiological cause in 76% of the cases. The results of microsurgical treatment are poor with a low rate of intra-uterine pregnancy: [19.4% (0.08-0.42) at 24-30 months for pregnancies that were continuing and for abortions, 11.7% (0.04-0.33) at 24-30 months using actuarial techniques for estimating pregnancies that were continuing]. There was a high risk of extra-uterine pregnancy [35% (0.18-0.58) at 24-30 months]. These results make us wonder whether microsurgery or in vitro fertilisation should be the treatment of preference in these cases where the tubes are affected in two areas.


iDASH: integrating data for analysis, anonymization, and sharing.
iDASH (integrating data for analysis, anonymization, and sharing) is the newest National Center for Biomedical Computing funded by the NIH. It focuses on algorithms and tools for sharing data in a privacy-preserving manner. Foundational privacy technology research performed within iDASH is coupled with innovative engineering for collaborative tool development and data-sharing capabilities in a private Health Insurance Portability and Accountability Act (HIPAA)-certified cloud. Driving Biological Projects, which span different biological levels (from molecules to individuals to populations) and focus on various health conditions, help guide research and development within this Center. Furthermore, training and dissemination efforts connect the Center with its stakeholders and educate data owners and data consumers on how to share and use clinical and biological data. Through these various mechanisms, iDASH implements its goal of providing biomedical and behavioral researchers with access to data, software, and a high-performance computing environment, thus enabling them to generate and test new hypotheses.