Chimeric inheritance and crown-group acquisitions of carbon fixation genes within Chlorobiales: Origins of autotrophy in Chlorobiales and implication for geological biomarkers.
The geological record of microbial metabolisms and ecologies primarily consists of stable isotope fractionations and the diagenetic products of biogenic lipids. Carotenoid lipid biomarkers are particularly useful proxies for reconstructing this record, providing information on microbial phototroph primary productivity, redox couples, and oxygenation. The biomarkers okenane, chlorobactane, and isorenieratene are generally considered to be evidence of anoxygenic phototrophs, and provide a record that extends to 1.64 Ga. The utility of the carotenoid biomarker record may be enhanced by examining the carbon isotopic ratios in these products, which are diagnostic for specific pathways of biological carbon fixation found today within different microbial groups. However, this joint inference assumes that microbes have conserved these pathways across the duration of the preserved biomarker record. Testing this hypothesis, we performed phylogenetic analyses of the enzymes constituting the reductive tricarboxylic acid (rTCA) cycle in Chlorobiales, the group of anoxygenic phototrophic bacteria usually implicated in the deposition of chlorobactane and isorenieretane. We find phylogenetically incongruent patterns of inheritance across all enzymes, indicative of horizontal gene transfers to both stem and crown Chlorobiales from multiple potential donor lineages. This indicates that a complete rTCA cycle was independently acquired at least twice within Chlorobiales and was not present in the last common ancestor. When combined with recent molecular clock analyses, these results predict that the Mesoproterzoic lipid biomarker record diagnostic for Chlorobiales should not preserve isotopic fractionations indicative of a full rTCA cycle. Furthermore, we conclude that coupling isotopic and biomarker records is insufficient for reliably reconstructing microbial paleoecologies in the absence of a complementary and consistent phylogenomic narrative.


Use of progressive glaucomatous optic disk change as the reference standard for evaluation of diagnostic tests in glaucoma.
Progressive change in optic disk appearance has been suggested as the best available reference standard for glaucoma diagnosis. We evaluated the accuracy of scanning laser polarimetry (SLP) with variable corneal compensation to discriminate patients with documented progressive optic disk change from healthy subjects. Observational case-control study. Glaucoma patients with documented evidence of progressive optic disk change as assessed by stereoscopic photographs were selected. Healthy control subjects had normal visual fields and normal clinical examination. All subjects underwent imaging with the GDx VCC scanning laser polarimeter. Receiver-operating characteristic (ROC) curves, sensitivities at fixed specificities, and likelihood ratios were calculated. Sixty-five eyes were healthy control patients. Seventy-one eyes had progressive optic disk change, of which 41 (58%) had abnormal visual field tests closest to the imaging date (perimetric glaucomatous optic neuropathy [GON]), and 30 (42%) eyes had normal visual fields (preperimetric GON). The GDx VCC parameter nerve fiber indicator performed best for discrimination between perimetric GON and normal eyes (AUC = 0.94; sensitivity = 93% for specificity > or =80%) as well as for the discrimination between preperimetric GON and normal eyes (AUC = 0.89; sensitivity = 83% for specificity > or =80%). SLP differentiated patients with documented progressive optic disk change from normal subjects and detected abnormalities in patients with confirmed diagnosis of preperimetric GON, suggesting that it may be useful for early glaucoma diagnosis. We suggest that progressive optic disk change should be used in the evaluation of diagnostic accuracy of imaging instruments for glaucoma.


Susceptibility to TNF in the presence of inhibitors of transcription or translation is dependent on the activity of cytosolic phospholipase A2 in human melanoma tumor cells.
In this study, we have examined the relationship between the expression of the high molecular weight, cytosolic form of PLA2 (cPLA2) and ability of inhibitors of transcription or translation (ITT) to induce susceptibility to TNF. S Susceptibility to lysis was assayed by 51CR release, and the expression of cPLA2 was assayed by activity assay and by Western blot. The panel of cells that we examined included two murine cell lines, six human melanoma-derived cell lines, two samples of freshly explanted melanoma tumor tissue, and a culture of normal epidermal melanocytes. Our experiments revealed a near perfect correlation between the activity of cPLA2 per cell and susceptibility to TNF in the presence of either cycloheximide (CHI) or actinomycin D (r = 0.97). These results suggest that the activity of cPLA2 is both necessary and rate-limiting in this form of programmed cell death, conclusions that were confirmed in transfection experiments and in experiments with antisense oligonucleotides. Over-expression of cPLA2 in two melanoma-derived cell lines, WM793 and SK-MEL-131, led to enhanced susceptibility to TNF and CHI. Conversely, suppression of cPLA2 with antisense oligonucleotides dramatically decreased susceptibility to TNF and CHI in C3HA fibroblasts. These experiments also revealed a coupled, transformation-released change in the expression of cPLA2 and susceptibility to lysis. Normal melanocytes contained the lowest levels of cPLA2 and were completely resistant to sensitization with ITT. In contrast, all of the melanoma-derived cell lines and samples of melanoma tumor tissue we examined has higher levels of cPLA2 and could be killed, to some extent, by treatment with TNF and ITT.


Investigating the Antioxidant Capacity of Coffee!
In the 1990s we began to understand that free radical damage is involved in artery-clogging atherosclerosis and health problems like vision loss, cancer or chronic diseases. Studies have shown that the damage especially affects people with a low consumption of antioxidant-rich fruits, vegetables...and coffee. Is this just a fairy tale promoted by the coffee industry? Scientists at the Zurich University of Applied Sciences (ZHAW) in Wädenswil wanted to get to the bottom of the question.


Chronologic improvement in hair yield with follicular unit excision with changes in punch devices: A 10-year experience of a single center.
Follicular unit excision (FUE), which is a newer hair transplant procedure was thought to be only usable in limited areas at the beginning. However, it is the most preferred technique these days. It is known transection rates have decreased with punch technology (and experience) over the years. We analyzed the data from so-so many male patients who underwent hair transplantation by FUE method at our clinic retrospectively to elucidate how the development of punch technology affected the number of total grafts and FU containing multiple hairs. Between the years 2011 and 2020, male hair transplant patients operated with the FUE method at the author's dermatology clinic, was investigated retrospectively. Overall 1415 cases were included in the study. Total graft numbers and 1-4 hair FUs were calculated. There was a statistically significant difference in terms of number of total grafts, one hair follicular unit (I FU) three hair follicular unit (III FU) distributions according to operation year and punch type (p < 0.05). The serrated punch resulted in a significant increase in the numbers of total grafts and the trumpet punch resulted in a significant increase in the number of 3FU grafts. Our study has shown that hair yield has been increased with new punch technologies. With an increasing hair yield by the aid of evolving punch technology, hair transplantation with the FUE method has become the first choice for hair transplantation preferred by both doctors and patients.


An update on surgery for vesicovaginal and urethrovaginal fistulae.
This review offers a comprehensive summary of the recent publications on the treatment of vesicovaginal fistula. Most reports are related to obstetric fistula in the developing world but in the developed world fistula treatment remains a challenge. The quality of the research in this field is improving. Efforts are being made to improve the classification of fistula as a prognostic tool. Surgical innovations are few in this field. Laparoscopic approaches are reported but only on a very limited amount of patients. The surgical management of fistula remains a two-track item: the gigantic experience on obstetric fistula of fistula surgeons in Africa and Asia and the limited experience of some Western centres with mostly a small series of iatrogenic fistula. Advances are made in both worlds. The previously isolated fistula surgeons are now better organized and they stimulate scientific research in countries with very limited resources. The centres in the developed world explore new surgical approaches such as laparoscopy and minimally invasive treatments.


Systemic and cavernous plasma levels of endothelin (1-21) during different penile conditions in healthy males and patients with erectile dysfunction.
The role of the sympathetic adrenergic nerves in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic transmitters are involved in this process. The peptide endothelin-1 (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated by various authors that ET-1 might be involved in the pathophysiology of erectile dysfunction. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels registered in systemic and cavernous blood cavities taken from healthy males and patients with ED during different penile conditions (flaccidity, tumescence/rigidity, detumescence). Thirty-two healthy adult males and 25 patients were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET-1/-2 was determined in plasma aliquots by means of an enzyme-linked immunoassay (ELISA).Mean systemic and cavernous plasma level of ET-1/-2 in blood samples obtained from the volunteers was 0.2-0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernous blood during penile tumescence, rigidity and detumescence. In the group of patients, mean plasma ET-1/-2 levels in the phase of penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernous blood (flaccidity: 0.52 ± 0.38 fmol/ml vs. 0.48 ± 0.46 fmol/ml, respectively; detumescence: 0.53 ± 0.33 fmol/ml vs. 0.27 ± 0.11 fmol/ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and psychogenic etiology of ED. In the phase of detumescence, the mean ET-1/-2 level was lower in the cavernous blood cavities taken from the patients than in the samples obtained from the healthy males.Our study revealed a difference in the profiles of ET-1/-2 registered in the cavernous blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seems to be of no physiological significance, our data counteract the hypothesis of an ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding an involvement of ET-1 in the pathophysiology of erectile dysfunction.


Persistent accommodative spasm nine years after head trauma.
Spasm of the near reflex is most often seen on a functional basis in young adults with underlying emotional problems. In particular, when convergence spasm is associated with miosis on attempted lateral gaze, a functional basis for the disorder should be suspected. Patients who experience spasm of the near reflex following trauma commonly follow a benign course with spontaneous resolution of their ocular complaints within 1-2 years. Accommodative spasm, manifested by pseudomyopia, or spasm of convergence, alone, or in combination with miosis, may be found as isolated signs of spasm of the near reflex. We report a patient who continues to demonstrate accommodative spasm 9 years after a motor vehicle accident.


[Changes in systemic and regional hemodynamics in experimental renal hypertension].
The changes in the cardiac output were studied by the dye-dilution method in rat experiments in different periods of experimentally induced renal hypertension, as well as the distribution of the cardiac output among the tissues and organs. Four days after the procedure a distinct increase of the cardiac output is noted, by the 14th day it returned to the initial level, by the 135th day it clearly tended to decrease. The total peripheral resistance, on the contrary, was steadily growing beginning with the 14th day, thus bringing about an elevation of the arterial pressure. The distribution of the cardiac output among the organs and tissues did not change significantly under hypertensive conditions. The only exception is the cardiac output fraction that is supplied to the spleen.


A long-term follow-up of cognitive, emotional, and behavioural sequelae to Reye syndrome.
Eighteen adolescents who had survived Reye syndrome (RS) in early childhood were assessed on cognitive, emotional, and behavioural variables in a second follow-up study tracking this group. Siblings were used as controls. The entire group with RS had survived with no obvious neurological damage at the first follow-up study. Indeed, current findings suggested that long-term cognitive, emotional, and behavioural functioning was comparable to siblings in approximately half of the group with RS. However, two factors were associated with a less favourable outcome. Cognitive, emotional, and behavioural functioning were significantly poorer in the subgroup of survivors whose illness had occurred in the first year of life. In addition, loss of consciousness, although the association with poor outcome was not as noticeable, was also associated with relative deficits on some scales of cognitive ability. Many of these deficits had not been obvious at the first follow-up and the importance of neurodevelopmental factors are considered. Finally, the implications of these findings for research and interventions in RS and other such encephalopathies are discussed.


SNP discovery using Paired-End RAD-tag sequencing on pooled genomic DNA of Sisymbrium austriacum (Brassicaceae).
Single nucleotide polymorphisms SNPs are rapidly replacing anonymous markers in population genomic studies, but their use in non model organisms is hampered by the scarcity of cost-effective approaches to uncover genome-wide variation in a comprehensive subset of individuals. The screening of one or only a few individuals induces ascertainment bias. To discover SNPs for a population genomic study of the Pyrenean rocket (Sisymbrium austriacum subsp. chrysanthum), we undertook a pooled RAD-PE (Restriction site Associated DNA Paired-End sequencing) approach. RAD tags were generated from the PstI-digested pooled genomic DNA of 12 individuals sampled across the species distribution range and paired-end sequenced using Illumina technology to produce ~24.5 Mb of sequences, covering ~7% of the specie's genome. Sequences were assembled into ~76 000 contigs with a mean length of 323 bp (N(50) = 357 bp, sequencing depth = 24x). In all, >15 000 SNPs were called, of which 47% were annotated in putative genic regions based on homology with the Arabidopsis thaliana genome. Gene ontology (GO) slim categorization demonstrated that the identified SNPs covered extant genic variation well. The validation of 300 SNPs on a larger set of individuals using a KASPar assay underpinned the utility of pooled RAD-PE as an inexpensive genome-wide SNP discovery technique (success rate: 87%). In addition to SNPs, we discovered >600 putative SSR markers.


Allergic rhinoconjunctivitis doubles the risk for incident asthma--results from a population study in Helsinki, Finland.
To examine the incidence of allergic rhinoconjunctivitis and asthma, and to assess allergic rhinoconjunctivitis as a risk factor for incident asthma, we performed a 11-year follow-up postal survey. The original study population was a random population sample of 8000 inhabitants of Helsinki aged 20-69 years in 1996. Participants in the first postal questionnaire survey, 6062 subjects, were invited to this follow-up study, and provided 4302 (78%) answers out of 5484 traced subjects in 2007. Cumulative incidence of asthma from 1996 to 2007 was 4.0% corresponding to an annual incidence rate of 3.7/1000/year. After exclusion of those with asthma medication or physician-diagnosed chronic bronchitis or COPD at baseline in 1996, the cumulative incidence decreased to 3.5% (incidence rate 3.2/1000/year), and further to 2.7% (2.5/1000/year) when also those reporting recurrent wheeze or shortness of breath during the last year in 1996 were omitted from the population at risk. Remission of asthma occurred in 43 subjects and was 16.9% over 11 years. Cumulative 11-year incidence of allergic rhinoconjunctivitis was 16.9% corresponding to 16.8/1000/year, and cumulative remission was 18.1%. Incidence of allergic rhinoconjunctivitis was significantly lower among those who had lived in the countryside or on a farm during the first 5 years of life, but this was not true for asthma. In multivariate analysis, farm living during the first 5 years of life was protective for the development of allergic rhinoconjunctivitis, OR 0.75 (95%CI 0.57-0.99). Allergic rhinoconjunctivitis was a significant independent risk factor for incident asthma, OR 2.15 (95%CI 1.54-3.02). In the cohort, the prevalence of rhinoconjunctivitis increased from 38.0% in 1996 to 40.9% in 2007, physician-diagnosed asthma from 6.8% to 9.4%, while current smoking decreased from 31.3% to 23.3%. Incidence of allergic rhinoconjunctivitis was higher than in earlier studies, while asthma incidence remained on similar level, both being significantly higher in women. Allergic rhinoconjunctivitis doubled the risk for incident asthma.


Geometric calibration for a dual tube/detector micro-CT system.
The authors describe a dual tube/detector micro-computed tomography (micro-CT) system that has the potential to improve temporal resolution and material contrast in small animal imaging studies. To realize this potential, it is necessary to precisely calibrate the geometry of a dual micro-CT system to allow the combination of projection data acquired with each individual tube/detector in a single reconstructed image. The authors present a geometric calibration technique that uses multiple projection images acquired with the two imaging chains while rotating a phantom containing a vertical array of regularly spaced metallic beads. The individual geometries of the imaging chains are estimated from the phantom projection images using analytical methods followed by a refinement procedure based on nonlinear optimization. The geometric parameters are used to create the cone beam projection matrices required by the reconstruction process for each imaging chain. Next, a transformation between the two projection matrices is found that allows the combination of projection data in a single reconstructed image. The authors describe this technique, test it with a series of computer simulations, and then apply it to data collected from their dual tube/detector micro-CT system. The results demonstrate that the proposed technique is accurate, robust, and produces images free of misalignment artifacts.


Abdominal tuberculosis: CT evaluation.
The computed tomography (CT) scans of 27 patients with abdominal tuberculosis were reviewed retrospectively to determine the range of abdominal involvement. Most patients had been at increased risk because of intravenous drug abuse, alcoholism, acquired immunodeficiency syndrome (AIDS), cirrhosis, or steroid therapy. The etiologic agent was Mycobacterium tuberculosis in 23 patients and M. avium-intracellulare in four patients with AIDS. In five patients, tuberculosis was limited to the abdomen. CT findings included adenopathy, splenomegaly, hepatomegaly, ascites, bowel involvement, pleural effusion, intrasplenic masses, and intrahepatic masses. Characteristic features were a tendency for adenopathy to prominently involve peripancreatic and mesenteric compartments, low-density centers within enlarged nodes, complex nature of the ascites, and adenopathy adjacent to sites of gastrointestinal tract involvement. Recognition of these manifestations and maintenance of an index of suspicion, especially in patients at risk, should help optimize the correct diagnosis and management of intraabdominal tuberculosis.


[Morbidity and treatment of penile cancer (based on data from the Moscow Municipal Oncology Dispensary)].
Penis carcinoma morbidity in the city of Moscow in 1973-1979 was 0.5 per 100,000 of male population, most of the patients being older than 60 years. On primary application, stage I of the disease was identified in 17.5%; stage II -- 42.9%; stage III -- 34.9% and stage IV in 4.7% of patients. Therefore, advanced tumors were found in 39.6% of patients. Combined treatment was given to 31.6%, radiation alone -- 37.5%, surgery -- 21.3% and symptomatic therapy -- 7.4% of cases. Three patients refused to take therapy.


The Bacillus subtilis cysP gene encodes a novel sulphate permease related to the inorganic phosphate transporter (Pit) family.
Sulphate permeases in the plasma membrane are responsible for uptake of environmental sulphate used in the sulphate assimilation pathway in bacteria and plants. Here it is reported that the ORF designated cysP, located on the Bacillus subtilis chromosome between cysH and five putative genes involved in sulphate assimilation, encodes a sulphate permease. cysP is able to complement Escherichia coli cysteine auxotrophs with mutations affecting either the membrane or periplasmic components of the sulphate-thiosulphate permease. Transport studies with cell suspensions of a cysA97 E. coli strain transformed with a plasmid expressing the B. subtilis cysP gene indicated that CysP catalyses sulphate uptake. Analysis of the primary sequence showed that CysP (354 amino acids, estimated molecular mass 24 kDa) is a highly hydrophobic protein which has 11 putative transmembrane helices. Sequence comparisons revealed that CysP, together with the phosphate permease of Neurospora crassa, Pho-4, and E. coli PitA, belongs to the family of related transporters, the inorganic phosphate transporter (Pit) family. Among the putative phosphate permeases, CysP shows a similar size and the same domain organization as the archaeal transporters. This is the first report of a sulphate permease in a Gram-positive organism.


An integrative framework for sensor-based measurement of teamwork in healthcare.
There is a strong link between teamwork and patient safety. Emerging evidence supports the efficacy of teamwork improvement interventions. However, the availability of reliable, valid, and practical measurement tools and strategies is commonly cited as a barrier to long-term sustainment and spread of these teamwork interventions. This article describes the potential value of sensor-based technology as a methodology to measure and evaluate teamwork in healthcare. The article summarizes the teamwork literature within healthcare, including team improvement interventions and measurement. Current applications of sensor-based measurement of teamwork are reviewed to assess the feasibility of employing this approach in healthcare. The article concludes with a discussion highlighting current application needs and gaps and relevant analytical techniques to overcome the challenges to implementation. Compelling studies exist documenting the feasibility of capturing a broad array of team input, process, and output variables with sensor-based methods. Implications of this research are summarized in a framework for development of multi-method team performance measurement systems. Sensor-based measurement within healthcare can unobtrusively capture information related to social networks, conversational patterns, physical activity, and an array of other meaningful information without having to directly observe or periodically survey clinicians. However, trust and privacy concerns present challenges that need to be overcome through engagement of end users in healthcare. Initial evidence exists to support the feasibility of sensor-based measurement to drive feedback and learning across individual, team, unit, and organizational levels. Future research is needed to refine methods, technologies, theory, and analytical strategies.


Disseminated Trichosporon infection. Occurrence in an immunosuppressed patient with chronic active hepatitis.
A 62-year-old woman with chronic active hepatitis receiving immunosuppressive drugs was initially admitted with sepsis secondary to an intra-abdominal abscess caused by Klebsiella pneumoniae. She had a stormy course despite adequate antimicrobial therapy. Her postoperative course was further complicated by a fungal infection. Blood, urine, and sputum cultures were positive for Trichosporon. Antifungal therapy was given but her condition deteriorated and she died. At autopsy, a disseminated fungal infection was found. Diagnosis and management of such infections in the immunosuppressed host are difficult.


Adrenal synthesis of corticosterone in response to ACTH in rats is influenced by leukotriene A4 and by lipoxygenase intermediates.
The possible involvement of the lipoxygenase pathway of arachidonic acid metabolism in the events which take place during ACTH-induced stimulation of corticosterone secretion has been studied using an isolated rat adrenal cell system. Incubation with arachidonic acid resulted in an inhibition of ACTH-stimulated corticosterone production. The lipoxygenase pathway inhibitors nordihydroguaretic acid (NDGA), eicosatetraynoic acid (ETYA) and compound BW755C also produced inhibition of ACTH-stimulated corticosterone synthesis. The concentrations of the inhibitors at which 50% inhibition occurred were 15, 34 and 37 mumol/l respectively. The inhibitions produced by NDGA and ETYA were independent of cyclic AMP output. NDGA also inhibited corticosterone production induced by dibutyryl cyclic AMP but had no effect on corticosterone synthesis induced by pregnenolone. Preincubation of adrenal cells with the lipoxygenase products 5, 12 and 15 hydroxyeicosatetraenoic acid (HETE) and with leukotrienes A4, B4, C4, D4 and E4 resulted in significant inhibitions of corticosterone production in response to ACTH with leukotriene A4 (LTA4) and with 15HETE and 5HETE. Conversely, incubation with glutathione (GSH), which is known to reduce intracellular LTA4 levels, produced stimulation (at 5 mmol GSH/l) and inhibition (at 50 mmol GSH/l) of corticosterone output. These studies suggest that the lipoxygenase pathway may be involved in ACTH-stimulated corticosterone synthesis.


Mild stimulation for in vitro fertilization.
It has been proven that the use of high gonadotropin dose does not necessarily improve the final outcome of IVF. Mild ovarian stimulation is based on the principle of optimal utilization of competent oocytes/embryos and endometrial receptivity. There is growing evidence that the pregnancy or live birth rates with mild-stimulation protocols are comparable to those with conventional IVF; the cumulative pregnancy outcome has been shown to be no different, despite having fewer numbers of oocytes or embryos available with milder ovarian stimulation. Although equally effective, mild-stimulation IVF is associated with a greater safety profile, in terms of the incidence of ovarian hyperstimulation syndrome and venous thromboembolism. It is also found to be better tolerated by patients and less expensive. Emerging research evidence may lead to widespread acceptance of mild IVF, by both patients and IVF providers, and make IVF more accessible to women and couples worldwide.


Live cell imaging reveals plant aurora kinase has dual roles during mitosis.
The proper segregation of chromosomes during mitosis is required for accurate distribution of genetic information by two daughter cells. Here, we used live cell imaging of microtubules and kinetochores after treatment with an Aurora kinase inhibitor, hesperadin, in tobacco BY-2 cells to analyze the function of plant Aurora kinase during mitosis. Hesperadin treatment induced the delay of CenH3 alignment on the spindle equator. Furthermore, two types of dynamics of lagging CenH3s were observed during chromosome segregation. The findings indicate that the plant Aurora kinase has dual roles; correction of aberrant kinetochore-microtubule attachment and dissociation of cohesin during chromosome alignment and segregation.


Subcellular localization and role of lipin-1 in human macrophages.
The lipins have been described as metabolic enzymes that regulate lipid biosynthesis and also signaling processes by controlling the cellular concentration of bioactive lipids, phosphatidic acid, and diacylgycerol. In the present work we have studied the subcellular localization and role of lipin-1 in human monocyte-derived macrophages. Human macrophages express lipin-1 isoforms α and β. A transfected lipin-1α-enhanced GFP construct associates with membranes of cellular organelles that can be stained with Nile Red. Colocalization experiments with lipid droplet (LD)-specific proteins such as adipophilin/adipose differentiation-related protein/perilipin 2 or TIP47/perilipin 3 show that both proteins colocalize with lipin-1α in the same cellular structures. Reduction of the expression levels of lipin-1 by small interfering RNA technology does not impair triacylglycerol biosynthesis but reduces the size of LDs formed in response to oleic acid. In agreement with these data, peritoneal macrophages from animals that carry a mutation in the Lpin-1 gene (fld animals) also produce less and smaller LDs in response to oleic acid. Mass spectrometry determinations demonstrate that the fatty acid composition of triacylglycerol in isolated LDs from lipin-1-deficient cells differs from that of control cells. Moreover, activation of cytosolic group IVA phospholipase A(2)α, a proinflammatory enzyme that is also involved in LD biogenesis, is also compromised in lipin-1-deficient cells. Collectively, these data suggest that lipin-1 associates with LDs and regulates the activation of cytosolic group IVA phospholipase A(2)α in human monocyte-derived macrophages.


Transfer center can control, manage admissions.
Despite Federal laws restricting inter-hospital transfers, some hospitals continue to transfer patients for purely financial reasons. To combat the financial strain of receiving inappropriate transfers, some large hospitals have established a centralized office to coordinate transfers. A well-run transfer center can aid in the overall treatment of appropriately transferred patients as well as reduce hospital costs.


Identification and analysis of mtDNA genomes attributed to Finns reveal long-stagnant demographic trends obscured in the total diversity.
In Europe, modern mitochondrial diversity is relatively homogeneous and suggests an ubiquitous rapid population growth since the Neolithic revolution. Similar patterns also have been observed in mitochondrial control region data in Finland, which contrasts with the distinctive autosomal and Y-chromosomal diversity among Finns. A different picture emerges from the 843 whole mitochondrial genomes from modern Finns analyzed here. Up to one third of the subhaplogroups can be considered as Finn-characteristic, i.e. rather common in Finland but virtually absent or rare elsewhere in Europe. Bayesian phylogenetic analyses suggest that most of these attributed Finnish lineages date back to around 3,000-5,000 years, coinciding with the arrival of Corded Ware culture and agriculture into Finland. Bayesian estimation of past effective population sizes reveals two differing demographic histories: 1) the 'local' Finnish mtDNA haplotypes yielding small and dwindling size estimates for most of the past; and 2) the 'immigrant' haplotypes showing growth typical of most European populations. The results based on the local diversity are more in line with that known about Finns from other studies, e.g., Y-chromosome analyses and archaeology findings. The mitochondrial gene pool thus may contain signals of local population history that cannot be readily deduced from the total diversity.


[Our experience of biomaterial use for lamellar keratoplasty].
The results of use of biomaterial Alloplant (BMA) for lamellar keratoplasty (LKP) were analyzed. The most part of patients had ocular burns (40.2%), i.e. the most severe damage. Combined variants of BMA for LKP with other alloplants were studied. The most often used combination was alloplant for LKP with alloplant for conjunctiva reconstruction and allotendinous threads (24.5%), this combination let to cover extensive corneal and conjunctival defects. Significant improvement of visual acuity in 241 patients after long-term follow-up was achieved. The complications of LKP with BMA transplantation are discussed.


Science Signaling Podcast for 24 January 2017: Tissue-specific regulation of L-type calcium channels.
This Podcast features an interview with Johannes Hell and Manuel Navedo, senior authors of two Research Articles that appear in the 24 January 2017 issue of Science Signaling, about tissue-specific regulation of the L-type calcium channel CaV1.2. This channel is present in many tissues, including the heart, vasculature, and brain, and allows calcium to flow into cells when it is activated. Signaling through the β-adrenergic receptor (βAR) stimulates CaV1.2 activity in heart cells and neurons to accelerate heart rate and increase neuronal excitability, respectively. Using mouse models, Qian et al found that βAR-mediated enhancement of CaV1.2 activity in the brain required phosphorylation of Ser1928, whereas βAR-mediated enhancement of CaV1.2 activity in the heart did not require phosphorylation of this residue. In a related study, Nystoriak et al demonstrated that phosphorylation of Ser1928 in arterial myocytes was required for vasoconstriction during acute hyperglycemia and in diabetic mice. These findings demonstrate tissue-specific differences in CaV1.2 regulation and suggest that it may be possible to design therapies to target this channel in specific tissues.Listen to Podcast.


Tsetse and trypanosomiasis control problems in south-east Uganda: past, present and alternative strategies.
Tsetse and trypanosomiasis in South-East Uganda are reviewed. This paper examines why in nearly 100 years no appreciable progress has been made in tsetse and trypanosomiasis control. It points out that tsetse control strategies in the past have relied on sophisticated technologies such as aerial spraying, which are inappropriate to Uganda's economic and environmental situation. With the vector, G. f. fuscipes, being peridomestic and the transmission cycle undoubtedly domestic animal-fly-man, community participation using appropriate technologies such as low-cost traps/targets and integrating farming activity with tsetse control seem to be the most appropriate approach in South-East Uganda. Savings in expenditure on vector control are discussed in light of diminishing resources.


[The difference of conformation of apoB-100 in lipoproteins of low and very low density. The modified lipoproteins and destructive inflammation in intima of arteries: a lecture].
The formation of ligand occurs in phylogenetically earlier lipoproteins of very low density and later lipoproteins of very low density when apoB- 100 takes active conformation in association with essential polyenoic fatty acids, in form of ethers with alcohol cholesterol, palmitic and oleic triglycerides. In lipoproteins of low density apoB-100-domain-ligand is formed, in lipoproteins of very low density apoE/B-100-ligand is formed. The ligand lipoproteins absorb cells using apoE/B-100 and apoB-100 receptor endocytosis. In cases of excess of palmitic triglycerides. and lipoproteins of very low density of the same name in blood, damage of primary structure of post-heparin, hepatic lipoprotein lipase and co-enzymes apoC-II and apoC-II, phenotype E2/E2 blood accumulates pre-ligand lipoproteins rich in triglycerides. In case of pathology of apoB-100-receptor post-ligand lipoproteins of low density with low content of triglycerides are cumulated. All non-ligand lipoproteins in a physiological way denature neutrophils. The presence of pathology induces modification in case of action of other agents (glyco-toxins). The pre-lipoproteins form in the intima of arteries soft voluminous plaques and such destructive inflammatory process as athero-thrombosis. The post-lipoproteins form flat plaques and destructive inflammatory atheromatosis. The atherosclerosis can be labeled as disease ofconformation. The surplus of palmitic saturated fatty acids in food, phenotype E2/E2 and deletion of gene apoB-100-receptor are causes of intima lesion. The non-ligand lipoproteins form destructive process, dying foam cells and macrophages--inflammatory component. The atheromatosis is a result of realization of biological function of endoecology, support of "purity" of intercellular medium.


Technical and safety performance of CT-guided percutaneous microwave ablation for lung tumors: an ablate and resect study.
Percutaneous image-guided thermal ablation has an increasing role in the treatment of primary and metastatic lung tumors. Achieving acceptable clinical outcomes requires better tools for pre-procedure prediction of ablation zone size and shape. This was a prospective, non-randomized, single-arm, multicenter study conducted by Medtronic (ClinicalTrials.gov ID: NCT02323854). Subjects scheduled for resection of metastatic or primary lung nodules underwent preoperative percutaneous microwave ablation. Ablation zones as measured via CT imaging following ablation immediately and before resection surgically versus predicted ablation zones as prescribed by the investigational system software were compared. This CT scan occurred after the ablation was finished but the antenna still in position. Time (minutes) from antenna placement to removal was 23.7±13.1 (n=14); median: 21.0 (range, 6.0 to 48.0). The definition of the secondary endpoint of complete ablation was 100% non-viable tumor cells based on nicotinamide adenine dinucleotide hydrogen (NADH) staining. Safety endpoints were type, incidence, and severity of adverse events. Fifteen patients (mean age 58.9 years; 67% male; 33% female) were enrolled in the study, 33.3% (5/15) with previous thoracic surgery, 73% (11/15) with metastasis, and 27% (4/15) with primary lung tumors. All underwent percutaneous microwave ablation followed by surgical resection the same day. Complete ablation was detected in 54.4% (6/11), incomplete ablation in 36.4% (4/11), and delayed necrosis in 9.1% (1/11). There were no device-related adverse events. Ablation zone volume was overestimated in all patients. Histological complete ablation was observed in 55% of subjects. CT scanning less than an hour after ablation and tissue shrinkage may account for the smaller zone of ablation observed compared to predicted by the investigational system software.


Evaluation by electron beam computed tomography of intracardiac masses suspected by transoesophageal echocardiography.
To assess the suitability of electron beam computed tomography (EBT) in evaluating and subsequently managing cardiac masses suspected as a result of examination by transthoracic and transoesophageal cross sectional echocardiography. In 76 consecutive patients with suspected cardiac masses, the impact of the EBT examination was analysed by reviewing whether EBT examination altered management by confirming or excluding a mass, whether EBT imaging substantially contributed to decision-making, and lastly whether EBT influenced the decision to operate on the patient. EBT modified the diagnosis or confirmed results which had been questionable with cross sectional echocardiography in 53 cases (70%): these cases included those with anatomical features such as dense calcifications or fatty structures (n = 20), lipomatous lesions (n = 5), equivocal thrombi (n = 5), pericardial masses (n = 5), or hydatid cysts (n = 2). EBT gave information over and above cross sectional echocardiography in all patients with malignant tumours (n = 16) by providing a better delineation of the relation between intracavity masses and normal structures, including the mural site of tumour attachment and tumour extension to the great vessels and the adjacent extracardiac mediastinal structures. EBT provided no additional information over cross sectional echocardiography in the remaining patients (n = 23), particularly in those with myxomas (n = 11) or small valvar lesions (n = 6). EBT only confirmed that the lesion was well demarcated, limited in extent, or not associated with a mass. EBT has considerable potential for clinical management and surgical planning and may help clinicians to decide against surgery, particularly in patients with unresectable tumours.


Highly efficient targeted mutagenesis in axolotl using Cas9 RNA-guided nuclease.
Among tetrapods, only urodele salamanders, such as the axolotl Ambystoma mexicanum, can completely regenerate limbs as adults. The mystery of why salamanders, but not other animals, possess this ability has for generations captivated scientists seeking to induce this phenomenon in other vertebrates. Although many recent advances in molecular biology have allowed limb regeneration and tissue repair in the axolotl to be investigated in increasing detail, the molecular toolkit for the study of this process has been limited. Here, we report that the CRISPR-Cas9 RNA-guided nuclease system can efficiently create mutations at targeted sites within the axolotl genome. We identify individual animals treated with RNA-guided nucleases that have mutation frequencies close to 100% at targeted sites. We employ this technique to completely functionally ablate EGFP expression in transgenic animals and recapitulate developmental phenotypes produced by loss of the conserved gene brachyury. Thus, this advance allows a reverse genetic approach in the axolotl and will undoubtedly provide invaluable insight into the mechanisms of salamanders' unique regenerative ability.


Analgesic and anti-inflammatory activities of a fraction rich in gaultherin isolated from Gaultheria yunnanensis (FRANCH.) REHDER.
The analgesic and anti-inflammatory activities of a salicylate derivatives fraction (SDF) isolated from Gaultheria yunnanensis (FRANCH.) REHDER and the mechanisms of actions were investigated in the present study. The major constituent of SDF, which represented around 50% of this fraction, was a methyl salicylate diglycoside named gaultherin. SDF showed a significant inhibition on the hind paw edema in rats (200, 400 mg/kg body wt., p.o.) and ear swelling in mice (200, 400, 800 mg/kg body wt., p.o.) caused by carrageenin and croton oil, respectively. In addition, SDF (400, 800 mg/kg body wt., p.o.) inhibited only the second phase (inflammatory) in the formalin test, and showed no effect in the hot-plate test in mice. The antinociceptive activity of SDF was predominantly peripheral and independent of the opioid system. These findings demonstrate that SDF from Gaultheria yunnanensis (FRANCH.) REHDER possesses analgesic and anti-inflammatory activities, which may be mediated, at least partly, through the suppression of inflammatory mediators or their release suggested by the animal experiment. The observed effects of SDF are probably due to the presence of high content of salicylate derivatives (80%), including gaultherin, MSTG-A and MSTG-B.


Management options for the drooling patient.
Drooling is a considerable disability in the neurologically disabled, but it will respond to treatment. For more than 10 years, a team approach has been successfully used in more than 400 such patients to assess and recommend appropriate therapy and its outcome. Bilateral submandibular duct relocation with simultaneous removal of the sublingual glands has evolved as the surgical procedure of choice and is associated with a satisfactory outcome in the majority of these cases.


CD19/CD22 targeting with co-transduced CAR T-cells to prevent antigen negative relapse after CAR T-cell therapy of B-ALL.
CD19-negative relapse is a leading cause of treatment failure after Chimeric antigen receptor (CAR) T-cell therapy for ALL. We investigated a CAR T-cell product targeting CD19 and CD22 generated by lentiviral co-transduction with vectors encoding our previously-described fast-off rate CD19CAR (AUTO1) combined with a novel CD22CAR capable of effective signalling at low antigen density. Twelve patients with advanced B-ALL were treated (CARPALL study, NCT02443831), a third of whom had failed prior licensed CAR therapy. Toxicity was similar to that of AUTO1 alone, with no cases of severe cytokine release syndrome. Ten of 12 patients (83%) achieved a Measurable Residual Disease (MRD) negative complete remission at 2 months post infusion. Of 10 responding patients, 5 had emergence of MRD (2) or relapse (3) with CD19 and CD22 expressing disease associated with loss of CAR T-cell persistence. With a median follow-up of 8.7 months there were no cases of relapse due to antigen-negative escape. Overall survival was 75% (95%CI: 41-91%) at 6 and 12 months. Six and 12-month event free survival (EFS) were 75% (95%CI: 41-91%) and 60% (95%CI: 23-84%). These data suggest dual targeting with co-transduction may prevent antigen negative relapse after CAR T-cell therapy.


Preventing blindness and visual impairment in Europe: What do we have to do?
Severe visual impairment and blindness are significant public health problems worldwide. Four-fifths of cases of blindness can be prevented or cured. The World Health organisation's 'Universal Eye Health: A Global Action Plan 2014-2019' and the European Society of Ophthalmology's Pilot Committee on Public Eye Health are aiming to decrease the prevalence of blindness in Europe and around the world. Starting discussions addressing possible actions and advocacies to improve current circumstances in public eye health is a common task of ophthalmologists and public health specialists in Europe.


[A method of determining the permeability of erythrocyte membranes for monovalent ions].
A modified method for the determination of red cell membrane permeability for sodium and potassium monovalent ions is described. The described modification essentially cuts down the time of investigation and accelerates potassium ion transport. Instead of ouabain, an imported reagent, strophanthin K glycoside manufactured in the USSR is used in the test.


A review on grain and nut deterioration and design of the dryers for safe storage with special reference to Turkish hazelnuts.
Turkey produces about 80% of the total hazelnut crop of the world. About 75% of the production are exported. In Turkey hazelnuts are traditionally sun dried, and may be subject to mold growth and subsequent mycotoxin formation due to prolonged drying time under humid and rainy weather conditions. Drying hazelnuts in a reasonable time after harvest is necessary for mycotoxin-free, high-quality products. In general, nuts and cereals contaminated by the toxins pose a potential hazard not only to the people of the producer countries, but also to people of the importing countries, if they should be regarded as safe by inefficient sampling plans, therefore preventing toxin formation actually benefits very large populations. Deterioration and health hazards associated with toxin contaminated hazelnuts and other nuts and cereals have similar causes and consequences; therefore, deterioration of the nuts and cereals in storage has been reviewed by considering as many grains and nuts as possible, then special reference was made to hazelnuts. Proper preharvest practices followed by proper drying and safe storage reduces the hazards associated with contamination by the toxins. This article reviews the pre- and post-harvest practices, and the grain- and nut-drying systems required for toxin-free products. Because drying is the major unit operation involving this process, the drying systems and the mathematical models required for their design is also discussed.


The influence of changes in clinical factors on high-security forensic custody dispositions.
The demand for forensic psychiatric beds is increasing, while many individuals are "stuck" in the system. Index offense severity and other legal considerations are associated with longer forensic stays but factors amenable to change such as symptoms of mental illness and aggression may also influence forensic decisions. We examined forensic review board decisions over time among 89 men admitted to a high-security forensic hospital. Almost half received a disposition to remain at their first hearing. Overall, dispositions were not associated with violence risk. The odds of a disposition to remain were higher for men with more in-hospital assaults and higher scores on a measure of clinical factors. Dispositions changed over time and this change was sensitive to clinical factors. We conclude that decisions were consistent with a cascading system of loosening security over time. Further longitudinal research following large samples through the forensic system is recommended.


An assessment of immediate newborn care readiness and availability in Nepal.
Global neonatal mortality necessitates access to immediate newborn care interventions. In Nepal, disparities persist in the readiness and availability of newborn care services within health facilities. This study aimed to assess this status and compare facilities that had implemented an intensive newborn resuscitation capacity building and retention programme in the past five years with those that had not. Our observational cross-sectional study involved 154 health facilities across Nepal. Through on-site inspections and maternal log reviews, we evaluated the immediate newborn care readiness and availability. The mean immediate newborn care intervention availability score of 52.8% (SE = 21.5) and the readiness score averaged 79.6% (SE = 12.3). Encouragingly, 96% of facilities ensured newborns were dried and wrapped for warmth, and 69.9% provided newborn resuscitation. Practices such as delayed cord clamping (42.0%), skin-to-skin contact (28.6%), and early breastfeeding (63.5%) showed room for improvement. Only 16.1% of health facilities administered Vitamin K1 prophylaxis.Domain-specific scores demonstrated a high level of facility readiness in infrastructure (97.5%), medicine, equipment, and supplies (90.6%), and staff training (90.9%), but a lower score for neonatal resuscitation aids (28.8%). Disparities in readiness and availability were evident, with rural areas and the Madhesh province reporting lower scores. Variations among health facility types revealed provincial and private hospitals outperforming local-level facilities. A positive association was observed between the LDSC/SSN mentoring programme and both the readiness and availability of immediate newborn care services. This study highlights the gap between healthcare facility readiness and the actual availability of immediate newborn care interventions in Nepal. Addressing disparities and barriers, particularly in rural areas and local-level facilities, is crucial for improving neonatal survival. The positive link between the LDSC/SSN programme and service availability and facility readiness emphasises the significance of targeted training and mentorship programmes in enhancing newborn care across Nepal.


Eugenics for the doctors: medicine and social control in 1930s Turkey.
This article aims to add a new dimension to the analysis of the relationship between medicine and eugenics via a discussion of the community of Turkish physicians in the period between the two World Wars. It argues that even though the relationship between the two fields has been discussed before in terms of the professional ideology of doctors, the medical community itself has not come under scrutiny by scholars. It is the purpose of this article to show eugenics as the main unifying edifice of that community and argue that eugenics is to be found in the patterns of social reproduction of the doctors as part of the professional middle class in addition to being those who transfer knowledge of medicine. As can be seen in Turkey in the 1930s, the doctors, in their efforts to construct themselves as the pioneers of modern scientific medicine, as well as the new ruling class of the country, used eugenics extensively both as a means of self-identification, and as a way to build a professional class "fit" to rule the country.


Primary biliary cholangitis presenting as acute ischemic stroke: A rare association.
Primary biliary cholangitis is associated with hyperlipidemia, but studies show that the condition does not increase cardiovascular risks. The case presents acute ischemic stroke with no underlying risk factors and subsequent new diagnosis of primary biliary cholangitis, which can suggest possible association between primary biliary cholangitis and acute stroke.


N-Methylnornicotinium ion, a new in vivo metabolite of R-(+)-nicotine.
N-Methylnornicotinium ion has been identified as a metabolite in the urine of male Hartley guinea pigs that had been chronically dosed ip with R-(+)-nicotine. Under similar conditions, S-(-)-nicotine is not biotransformed into this metabolite. The metabolite was isolated and purified by preparative high performance cation-exchange liquid chromatography. The structural identity of the metabolite was determined by UV spectrophotometric analysis and sodium borohydride reduction followed by GLC-mass spectrometric analysis, and Fourier transform 1H NMR spectrometric analysis. The formation of this metabolic product from nicotine represents a unique example of N-demethylation and N-methylation reactions both occurring within the same molecule.


X-linked myotubular myopathy in Rottweiler dogs is caused by a missense mutation in Exon 11 of the MTM1 gene.
Congenital and inherited myopathies in dogs are faithful models of human muscle diseases and are being recognized with increasing frequency. In fact, canine models of dystrophin deficient muscular dystrophy and X-linked myotubular myopathy are of tremendous value in the translation of new and promising therapies for the treatment of these diseases. We have recently identified a family of Australian Rottweilers in which male puppies were clinically affected with severe muscle weakness and atrophy that resulted in early euthanasia or death. X-linked myotubular myopathy was suspected based on the early and severe clinical presentation and histopathological changes within muscle biopsies. The aim of this study was to determine the genetic basis for myopathy in these dogs and compare and contrast the clinical presentation, histopathology, ultrastructure, and mutation in this family of Rottweiler dogs with the previously described myotubular myopathy in Labrador retrievers. Histopathology, histochemistry, and ultrastructural examination of muscle biopsies from affected Rottweiler puppies were consistent with an X-linked myotubular myopathy. An unusual finding that differed from the previously reported Labradors and similar human cases was the presence of excessive autophagy and prominent autophagic vacuoles. Molecular investigations confirmed a missense mutation in exon 11 of MTM1 that was predicted to result in a non-functional phosphatase activity. Although the clinical presentations and histopathology were similar, the MTM1 p.(Q384P) mutation is different from the p.(N155K) mutation in exon 7 affecting Labrador retrievers with X-linked myotubular myopathy. Here we describe a second pathogenic mutation in MTM1 causing X-linked myotubular myopathy in dogs. Our findings suggest a variety of MTM1 mutations in dogs as seen in human patients. The number of MTM1 mutations resulting in similar severe and progressive clinical myopathy and histopathological changes are likely to increase as canine myopathies are further characterized.


The msp1 beta multigene family of Anaplasma marginale: nucleotide sequence analysis of an expressed copy.
A gene for the beta subunit of the immunoprotective surface antigen MSP-1 of Anaplasma marginale was previously cloned and expressed in Escherichia coli. A nucleic acid probe based on this gene detects A. marginale infection in carrier cattle and in the tick vector. We report here the sequence and structural features of the cloned msp1 beta gene and expressed polypeptide. The gene codes for a polypeptide of 756 amino acids that contains domains of tandemly repeated sequence and glutamine-rich regions at the N and C termini. The cloned copy is a member of a multigene family with multiple restriction fragment length polymorphisms in isolates of this rickettsia from different geographical regions. The availability of the sequence will allow use of the polymerase chain reaction in diagnostic assays and the preparation and testing of different vaccine constructs in cattle.


Greener Strategy for Lupanine Purification from Lupin Bean Wastewaters Using a Molecularly Imprinted Polymer.
Lupanine is an alkaloid used in the pharma industry as a building block or precursor in the synthesis of sparteine and also explored for drug synthesis in the pharma industry as a chiral selector. This alkaloid is found in lupin bean processing wastewaters originated from the debittering process to make these beans edible. In this work, a computational chemistry approach was taken to design molecularly imprinted polymers (MIPs) selecting itaconic acid, a biobased building block, as a functional monomer that can provide higher affinities for lupanine. MIP-1 was prepared using lupanine as the template, itaconic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linker by bulk polymerization. Lupanine was concentrated from lupin bean wastewater by nanofiltration, extracted with ethyl acetate, and purified using the synthesized MIP. MIP-1 was able to selectively recognize lupanine and improve the purity of lupanine from 78 to 88%, with 82% recovery of the alkaloid. These results show the potential application of this strategy to render the industrial process more sustainable.


Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 6: magnetic resonance imaging and discography for patient selection for lumbar fusion.
Discography is an exquisitely sensitive but not specific diagnostic test for the diagnosis of discogenic low-back pain. The restriction of the definition of a positive discographic study to one that elicits concordant pain from a morphologically abnormal disc improves the definition's accuracy. Fusion surgery based on discography alone, however, is not reliably associated with clinical success. Therefore, discography is not recommended as a standalone test for treatment decisions in patients with low-back pain. Magnetic resonance imaging is a sensitive and noninvasive test for the presence of degenerative disc disease. Discography should not be attempted in patients with normal lumbar MR images. Discography appears to have a role in the evaluation of patients with low-back pain, but it is best limited to the evaluation of abnormal interspaces identified on MR imaging, the investigation of adjacent-level disc disease, and as a means to rule out cases of nonorganic pain from surgical consideration.


[Indications and contraindications for epididymo-deferens vesiculography from a current viewpoint].
69 years after the introduction of x-ray examination of the seminal duct, the indication and contraindication are reviewed according to current interdisciplinary aspects, basing on 31 cases studied over a period of two years. The procedure followed in the roentgenological visualization of carcinoma of the prostate is generally recognized, whereas controversial opinions are held with regard to patients with occlusive azoospermia. The possibility of lesions and damage caused by some contrast media is an established fact. Differences in the lumen of the ductus epididymidis prevented complete visualization of the epididymis when using the previous, highly concentrated, sticky contrast media which were insoluble in water. These drawbacks have been eliminated by Amipaque. Today epididymograms are no longer considered necessary, although there are exceptions. Experience and a sophisticated technique are mandatory. If refertilization is envisaged, it is permissible during operation only to effect a descending x-ray for the purpose of clarifying the outflow conditions.


Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation.
The biosynthetic rates for both the transferrin receptor (TfR) and ferritin are regulated by iron. An iron-responsive element (IRE) in the 5' untranslated portion of the ferritin messenger RNA (mRNA) mediates iron-dependent control of its translation. In this report the 3' untranslated region of the mRNA for the human TfR was shown to be necessary and sufficient for iron-dependent control of mRNA levels. Deletion studies identified a 678-nucleotide fragment of the TfR complementary DNA that is critical for this iron regulation. Five potential stem-loops that resemble the ferritin IRE are contained within the region critical for TfR regulation. Each of two of the five TfR elements was independently inserted into the 5' untranslated region of an indicator gene transcript. In this location they conferred iron regulation of translation. Thus, an mRNA element has been implicated in the mediation of distinct regulatory phenomena dependent on the context of the element within the transcript.


β-PIX is critical for transplanted mesenchymal stromal cell migration.
Bone marrow-derived mesenchymal stromal cells (MSCs) have been used successfully as a source of stem cells for treating neurodegenerative diseases. However, for reasons that are not clear, autologous MSC transplants have not yielded successful results in human trials. To test one possible reason, we compared the migratory ability of MSCs from amyotrophic lateral sclerosis (ALS) patients with those of healthy controls. We found that MSCs derived from ALS patients (ALS-MSCs) had a reduced ability to migrate, which may explain why autologous transplantation is not successful. We also found that expression of one of the intracellular factors implicated in migration, β-PIX, was significantly reduced in ALS-MSCs compared with healthy stem cells. Restoration of β-PIX expression by genetic manipulation restored the migratory ability of ALS-MSCs, and inhibition of β-PIX expression with shRNA reduced the migration of healthy MSCs. We suggest that transplantation of allogeneic or genetically modified autologous stem cells might be a more promising strategy for ALS patients than transplantation of autologous stem cells.


Agreement in patient-therapist alliance ratings and its relation to dropout and outcome in a large sample of cognitive behavioral therapy for panic disorder.
Objective The therapeutic alliance is related to treatment outcome but less is known about the agreement on alliance between patients and therapists and its relationship to outcomes. We examined the association of patient-therapist congruence of alliance perceptions, early and late in cognitive behavioral therapy for panic disorder in relation to symptom reduction and dropout. Method: Patients (n = 181) and their therapists provided alliance ratings early and late during 11-session treatment. Independent evaluators rated patients' symptomatic levels post-treatment. Polynomial regression and response surface analysis were used to examine congruence as a predictor of outcome. Results: Early in therapy, stronger combined patient-therapist alliances, regardless of agreement, predicted lower symptom severity at the end of therapy and a lower likelihood of dropout. Late in treatment, the outcome was worse when therapist ratings of the alliance were higher than those of the patient. Conclusions: Therapist-patient agreement on the strength of the alliance is important for symptom improvement and dropout. The study highlights the importance of understanding the dyadic nature of the alliance and its impact on therapeutic change.


Biological characterization of SN32976, a selective inhibitor of PI3K and mTOR with preferential activity to PI3Kα, in comparison to established pan PI3K inhibitors.
Multiple therapeutic agents have been developed to target the phosphatidylinositol 3-kinase (PI3K) signaling pathway, which is frequently dysregulated in cancer promoting tumor growth and survival. These include pan PI3K inhibitors, which target class Ia PI3K isoforms and have largely shown limited single agent activity with narrow therapeutic windows in clinical trials. Here, we characterize SN32976, a novel pan PI3K inhibitor, for its biochemical potency against PI3K isoforms and mTOR, kinase selectivity, cellular activity, pharmacokinetics, pharmacodynamics and antitumor efficacy relative to five clinically-evaluated pan PI3K inhibitors: buparlisib, dactolisib, pictilisib, omipalisib and ZSTK474. SN32976 potently inhibited PI3K isoforms and mTOR, displaying preferential activity for PI3Kα and sparing of PI3Kδ relative to the other inhibitors, while showing less off-target activity than the clinical inhibitors in a panel of 442 kinases. The major metabolites of SN32976 were also potent PI3K inhibitors with similar selectivity for PI3Kα as the parent compound. SN32976 compared favorably with the clinically-evaluated PI3K inhibitors in cellular assays, inhibiting pAKT expression and cell proliferation at nM concentrations, and in animal models, inducing a greater extent and duration of pAKT inhibition in tumors than pictilisib, dactolisib and omipalisib at similarly tolerated dose levels and inhibiting tumor growth to a greater extent than dactolisib and ZSTK474 and with similar efficacy to pictilisib and omipalisib. These results suggest that SN32976 is a promising clinical candidate for cancer therapy with enhanced kinase selectivity and preferential inhibition of PI3Kα compared to first generation pan PI3K inhibitors, while retaining comparable anticancer activity.


Dose-response and comparative efficacy and tolerability of quetiapine across psychiatric disorders: a systematic review of the placebo-controlled monotherapy and add-on trials.
The atypical antipsychotic, quetiapine, is frequently prescribed on-label and off-label for the treatment of a variety of psychiatric disorders. As quetiapine has variable affinity for dozens of receptors, its clinical effects should also show a large variation as a function of dose and diagnostic category. This study attempts to elucidate the dose-response and comparative efficacy and tolerability (metabolic data) of quetiapine across psychiatric disorders. A systematic search was carried out in the electronic databases, PubMed and EMBASE, using the keywords 'quetiapine' and 'placebo'. Both monotherapy and add-on studies were included. A total of 41 studies were identified. In unipolar and bipolar depression, studies consistently found quetiapine to be effective versus placebo, at doses of approximately 150-300 and 300-600 mg per day, respectively. In bipolar mania, they consistently found quetiapine to be effective at doses of approximately 600 mg per day. In acute exacerbation of schizophrenia, the majority of studies found quetiapine to be effective at doses of approximately 600 mg per day; however, a few large studies found no difference versus placebo. In contrast, studies consistently found quetiapine to be more effective than placebo for stable schizophrenia. In obsessive-compulsive disorder, studies did not consistently find quetiapine to be effective at doses of approximately 300 mg per day. However, studies may have underestimated the efficacy of quetiapine for obsessive-compulsive disorder due to concomitant administration of antidepressants and the utilization of treatment-refractory patients. In generalized anxiety disorder, studies consistently found quetiapine to be effective at doses of approximately 150 mg per day. Finally, analysis of metabolic tolerability data suggests that even low doses of quetiapine may lead to increase in weight and triglycerides across psychiatric disorders. Interestingly, however, quetiapine-induced elevations in low-density lipoprotein and total cholesterol seem to be restricted to schizophrenia patients.


Ultrasound Appearances of the Acrania-Anencephaly Sequence at 10 to 14 Weeks' Gestation.
The acrania-anencephaly sequence is a lethal condition with a high detection rate in experienced hands after 10 weeks' gestation. However, earlier in gestation, many cases remain undetected. Different phenotypic appearances have been described and might help increase the detection rate in less experienced hands and also earlier in gestation. The purpose of this study was to assess interobserver reliability in classifying cases of the acrania-anencephaly sequence during first trimester in 6 different subtypes according to their ultrasound appearances. This was a retrospective descriptive cohort study at 3 centers for fetal imaging. Each case was classified according to its phenotypic appearance by 2 independent operators as "bilobular," "cystic," "elongated," "irregular," "foreshortened," or "overhanging." Frequencies of each type are described, and interoperator agreement was assessed with the intraclass correlation coefficient. From the 88 included cases, the frequencies of the different subtypes classified as overhanging, elongated, bilobular, cystic, foreshortened, and irregular were 31%, 25%, 19%, 11%, 8%, and 6%, respectively. The interoperator reliability was good, with an intraclass correlation coefficient of 0.903 (95% confidence interval, 0.853-0.937; P < .001). Using different subtypes may improve the detection of the acrania-anencephaly sequence. An accurate early diagnosis could lead to timely, less traumatic, and safer management of affected pregnancies.


Role of insects in the transmission of bovine leukosis virus: potential for transmission by mosquitoes.
Bovine leukosis virus (BLV) was transmitted to sheep in a simulated mechanical transmission experiment, using the following species of mosquitoes; Anopheles freeborni, A stephensi, A quadrimaculatus, and A albimanus. Mosquitoes were fed on blood taken from a BLV-infected cow with persistent lymphocytosis. Mouthparts and heads of mosquitoes were removed immediately after feeding, placed in RPMI 1640 medium, and inoculated subcutaneously into sheep. Nine sheep were inoculated with mouthparts and heads from 37 to 122 mosquitoes. Infection was determined serologically. Three monthly serum samples were collected from the sheep and were tested for the presence of antibodies to BLV, using the agar-gel immunodiffusion (AGID) test. Sera that were negative by AGID at 3 months were tested by radioimmunoassay. Results from radioimmunoassay agreed with those obtained by AGID. Four of the 9 sheep developed antibody to BLV. Sheep that seroconverted were inoculated with mouthparts and heads from as few as 54 mosquitoes.


Persistent hypocalcaemia in a Chinese girl due to a novel de-novo activating mutation of the calcium-sensing receptor gene.
A significant proportion of patients formerly diagnosed with idiopathic hypoparathyroidism actually have activating mutation of the calcium-sensing receptor (CaSR) gene. Awareness of the possibility of activating mutation of CaSR gene in patients with sporadic idiopathic hypoparathyroidism is important because of its relevance to clinical management. This report is of a novel activating mutation of the CaSR gene identified in a 10-year-old Chinese girl who was initially diagnosed as having idiopathic hypoparathyroidism at 6 years of age after presenting with seizures. Her serum calcium level was difficult to maintain near the lower limit of normal despite treatment with high-dose calcitriol. Treatment with calcitriol produced significantly elevated urinary calcium-to-creatinine ratio. Direct sequencing of the CaSR gene showed a novel heterozygous mutation (p.Q735P (c.2204A>C)). Molecular genetic analysis of her parents demonstrated that both parents did not harbour the child's mutation, indicating that her mutation had arisen de novo.


Lactofermented Annurca Apple Puree as a Functional Food Indicated for the Control of Plasma Lipid and Oxidative Amine Levels: Results from a Randomised Clinical Trial.
Atherosclerotic cardiovascular diseases are preferential targets of healthy diet and preventive medicine partially through strategies to improve lipid profile and counteract oxidative metabolites. Ninety individuals with cardiovascular disease (CVD) risk factors were randomized (1:1:1 ratio) to three arms, according to a four-week run-in, eight-week intervention, and four-week follow up study, testing the effects of a lactofermented Annurca apple puree (lfAAP), compared to unfermented apple puree (AAP) or probiotic alone (LAB) on plasma lipid profile and trimethylamine-N-oxide (TMAO) levels. By comparing the treatments, data indicated for the subjects tested with lfAAP a higher variation of the following serum parameters, in respect to the other treatment groups: high density lipoprotein cholesterol (HDL-C), +61.8% (p = 0.0095); and TMAO levels, -63.1% (p = 0.0042). The present study would suggest lfAAP as an effective functional food for beneficial control of plasma HDL-C and TMAO levels.


Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility.
Right ventricular dysfunction (RVD) is the leading cause of death in pulmonary arterial hypertension (PAH), but no RV-specific therapy exists. We showed microtubule-mediated junctophilin-2 dysregulation (MT-JPH2 pathway) causes t-tubule disruption and RVD in rodent PAH, but the druggable regulators of this critical pathway are unknown. GP130 (glycoprotein 130) activation induces cardiomyocyte microtubule remodeling in vitro; however, the effects of GP130 signaling on the MT-JPH2 pathway and RVD resulting from PAH are undefined. Immunoblots quantified protein abundance, quantitative proteomics defined RV microtubule-interacting proteins (MT-interactome), metabolomics evaluated the RV metabolic signature, and transmission electron microscopy assessed RV cardiomyocyte mitochondrial morphology in control, monocrotaline, and monocrotaline-SC-144 (GP130 antagonist) rats. Echocardiography and pressure-volume loops defined the effects of SC-144 on RV-pulmonary artery coupling in monocrotaline rats (8-16 rats per group). In 73 patients with PAH, the relationship between interleukin-6, a GP130 ligand, and RVD was evaluated. SC-144 decreased GP130 activation, which normalized MT-JPH2 protein expression and t-tubule structure in the monocrotaline RV. Proteomics analysis revealed SC-144 restored RV MT-interactome regulation. Ingenuity pathway analysis of dysregulated MT-interacting proteins identified a link between microtubules and mitochondrial function. Specifically, SC-144 prevented dysregulation of electron transport chain, Krebs cycle, and the fatty acid oxidation pathway proteins. Metabolomics profiling suggested SC-144 reduced glycolytic dependence, glutaminolysis induction, and enhanced fatty acid metabolism. Transmission electron microscopy and immunoblots indicated increased mitochondrial fission in the monocrotaline RV, which SC-144 mitigated. GP130 antagonism reduced RV hypertrophy and fibrosis and augmented RV-pulmonary artery coupling without altering PAH severity. In patients with PAH, higher interleukin-6 levels were associated with more severe RVD (RV fractional area change 23±12% versus 30±10%, P=0.002). GP130 antagonism reduces MT-JPH2 dysregulation, corrects metabolic derangements in the RV, and improves RVD in monocrotaline rats.


A coordinate-based ALE functional MRI meta-analysis of brain activation during verbal fluency tasks in healthy control subjects.
The processing of verbal fluency tasks relies on the coordinated activity of a number of brain areas, particularly in the frontal and temporal lobes of the left hemisphere. Recent studies using functional magnetic resonance imaging (fMRI) to study the neural networks subserving verbal fluency functions have yielded divergent results especially with respect to a parcellation of the inferior frontal gyrus for phonemic and semantic verbal fluency. We conducted a coordinate-based activation likelihood estimation (ALE) meta-analysis on brain activation during the processing of phonemic and semantic verbal fluency tasks involving 28 individual studies with 490 healthy volunteers. For phonemic as well as for semantic verbal fluency, the most prominent clusters of brain activation were found in the left inferior/middle frontal gyrus (LIFG/MIFG) and the anterior cingulate gyrus. BA 44 was only involved in the processing of phonemic verbal fluency tasks, BA 45 and 47 in the processing of phonemic and semantic fluency tasks. Our comparison of brain activation during the execution of either phonemic or semantic verbal fluency tasks revealed evidence for spatially different activation in BA 44, but not other regions of the LIFG/LMFG (BA 9, 45, 47) during phonemic and semantic verbal fluency processing.


Coral reefs promote the evolution of morphological diversity and ecological novelty in labrid fishes.
Although coral reefs are renowned biodiversity hotspots it is not known whether they also promote the evolution of exceptional ecomorphological diversity. We investigated this question by analysing a large functional morphological dataset of trophic characters within Labridae, a highly diverse group of fishes. Using an analysis that accounts for species relationships, the time available for diversification and model uncertainty we show that coral reef species have evolved functional morphological diversity twice as fast as non-reef species. In addition, coral reef species occupy 68.6% more trophic morphospace than non-reef species. Our results suggest that coral reef habitats promote the evolution of both trophic novelty and morphological diversity within fishes. Thus, the preservation of coral reefs is necessary, not only to safeguard current biological diversity but also to conserve the underlying mechanisms that can produce functional diversity in future.


UV-irradiation depletes antioxidants and causes oxidative damage in a model of human skin.
The degree to which antioxidant loss occurs in human skin after UV irradiation is unknown, as is the cascade of events that might occur. We have, therefore, evaluated a tissue culture model of human skin for its usefulness for studying oxidative injury by UV-irradiation. Human skin equivalents, a tissue culture model, were irradiated using a full solar UV spectrum (UVA and UVB, 280-400 nm) (0 to 16.8 J/cm2, 0-12 minimal erythemal dose, MED), then incubated from 1 to 24 h. Ubiquinol was the most UV-light sensitive antioxidant and was depleted by 2.1 J/cm2 (1.5 MED, p < .004); ubiquinone decreased with 4.2 J/cm2 (3 MED, p < .0007). A linear decrease in alpha-tocopherol occurred--approximately 1.7 pmol tocopherol/cm2 surface were destroyed per J/cm2 UV-light. Urate was depleted by irradiation with 8.4 J/cm2 (6 MED), while ascorbate was depleted by 16.8 J/cm2 (12 MED). Cellular protein carbonyls and lactic dehydrogenase (LDH) leakage into the medium were only increased at 1 h incubation following exposure to 16.8 J/cm2 (12 MED). At 24 h incubation, PGE2 was increased in the medium of cells exposed to UV-irradiation at 0.35 J/cm2 (0.25 MED) compared with sham-exposed cells (p < .04); higher UV exposures lead to significant increases in both PGE2 (p < .001) and LDH (p < .001) in the medium. In conclusion, human skin equivalents respond to suberythemal levels of UV-irradiation by increasing production of PGE2; higher levels of UV-irradiation (at least 1 MED) were needed to deplete cellular antioxidants and induce immediately detectable oxidative damage.


Antifungal combination therapy: clinical potential.
Combination antifungal therapy has been an area of research and clinical interest since systemic antifungals became available decades ago. In vitro and clinical data were generated for some of the more common invasive fungal infections, especially candidiasis, but until very recently few clinical studies were performed. The first invasive fungal infection to be examined in clinical trials with adequate statistical power was cryptococcal meningitis and several of these trials stand out as classical studies in the clinical evaluation of combination antifungal therapy. More recently, since the availability of the newer antifungal agents, including the echinocandins and extended-spectrum triazoles, there has been a growing interest in examining combination antifungal therapy for invasive fungal disease, especially invasive aspergillosis. This is by no means a comprehensive review of all existing experimental data. Instead, the focus is on the clinical data that have been generated to date and on providing insights into potential future clinical directions. For instance, recent clinical data for cryptococcosis confirm that amphotericin B plus flucytosine is the most active combination for patients with cryptococcal meningitis. A recently completed clinical trial in candidaemia suggests a trend towards improved outcomes among patients receiving amphotericin B plus fluconazole versus fluconazole alone. In aspergillosis, several experimental models suggest benefit of a variety of antifungal combinations, but have not been confirmed in prospective clinical trials. Ultimately, the goal is to provide the reader with a comprehensive but useful review to this complicated and often confusing therapeutic dilemma.


Meso-Scale Particle Image Velocimetry Studies of Neurovascular Flows In Vitro.
Particle image velocimetry (PIV) is used in a wide variety of fields, due to the opportunity it provides for precisely visualizing and quantifying flows across a large spatiotemporal range. However, its implementation typically requires the use of expensive and specialized instrumentation, which limits its broader utility. Moreover, within the field of bioengineering, in vitro flow visualization studies are also often further limited by the high cost of commercially sourced tissue phantoms that recapitulate desired anatomical structures, particularly for those that span the mesoscale regime (i.e., submillimeter to millimeter length scales). Herein, we present a simplified experimental protocol developed to address these limitations, the key elements of which include 1) a relatively low-cost method for fabricating mesoscale tissue phantoms using 3-D printing and silicone casting, and 2) an open-source image analysis and processing framework that reduces the demand upon the instrumentation for measuring mesoscale flows (i.e., velocities up to tens of millimeters/second). Collectively, this lowers the barrier to entry for nonexperts, by leveraging resources already at the disposal of many bioengineering researchers. We demonstratethe applicability of this protocol within the context of neurovascular flow characterization; however, it is expected to be relevant to a broader range of mesoscale applications in bioengineering and beyond.


Impact of boost technique on outcome in early-stage breast cancer patients treated with breast-conserving therapy.
We reviewed our institution's experience treating early-stage breast cancer patients with breast-conserving therapy (BCT) to determine the impact of boost technique on outcome. A total of 552 patients with stage I and II breast cancer were managed with BCT. All patients were treated with a partial mastectomy and radiation therapy (RT). RT consisted of 45 Gy to 50 Gy external beam irradiation to the whole breast followed by a boost to the tumor bed using either electrons (232 patients), photons (15 patients), or an interstitial implant (316 patients). Local control and cosmetic outcome was compared among three patient groups based on the type of boost used. Forty-one patients had a recurrence of cancer in the treated breast for 5-, 10-, and 13-year actuarial local recurrence rates of 2.8%, 7.5%, and 11.2%, respectively. There were no significant differences in the local recurrence rates or cosmetic outcome using electrons, photons, or an interstitial implant. On multivariate analysis, only young age and margin status were associated with local recurrence. Stage I and II breast cancer patients undergoing BCT can be effectively managed with electron, photon, or interstitial implant boost techniques. Long-term local control and cosmetic outcome are excellent regardless of which boost technique is used.


Evidence of active transport involvement in morphine transport via MDCKII and MDCK-PGP cell lines.
Several transporters appear to be important in transporting various drugs. Many patients, who receive morphine as analgesic medication, also receive other medications with potency of changing morphine transport by affecting P-glycoprotein (P-GP) and oatp2 transport system. This could influence morphine pharmacokinetics and pharmacodynamics. The aim of present study was to elucidate the transport mechanisms involved in transporting morphine via MDCKII and MDCK-PGP cells. Morphine permeability was examined in the presence of various compounds with ability in inhibiting different transport systems including: digoxin, probenecid and d- glucose. The effect of morphine concentration changes on its transport was also examined. Morphine concentration was measured using HPLC with electrochemical detector. Morphine permeability via a MDCK II cells was greater than sucrose permeability, and reduced when a P-GP expressed cell line was used. Its permeability was increased significantly in the presence of a strong P-GP inhibitor. Morphine permeability decreased significantly in the presence of digoxin but not in the presence of d-glucose or probenecid. These results showed that morphine was a P-GP substrate, and digoxin related transporters such as oatp2 were involved in its transport. Morphine was not substrate for glucose or probenecid-sensitive transporters.


The luteinizing hormone-releasing hormone receptor in human prostate cancer cells: messenger ribonucleic acid expression, molecular size, and signal transduction pathway.
Evidence has accumulated indicating that LHRH might behave as an autocrine/paracrine growth inhibitory factor in some peripheral tumors. However, LHRH receptors in tumor cells have not been fully characterized, so far. The present experiments were performed to analyze: 1) the messenger RNA expression; 2) the molecular size; and 3) the signal transduction pathway of LHRH receptors in prostate cancer. For these studies, the human androgen-dependent LNCaP and androgen-independent DU 145 prostate cancer cell lines were used. 1) By RT-PCR, a complementary DNA product, which hybridized with a 32P-labeled oligonucleotide probe specific for the pituitary LHRH receptor complementary DNA, was found both in LNCaP and in DU 145 cells. 2) Western blot analysis, using a monoclonal antibody raised against the human pituitary LHRH receptor, revealed the presence of a protein band of approximately 64 kDa (corresponding to the molecular mass of the pituitary receptor) in both cell lines. 3) In LNCaP and DU 145 cells, pertussis toxin completely abrogated the antiproliferative action of a LHRH agonist (LHRH-A). Moreover, LHRH-A substantially antagonized the pertussis toxin-catalyzed ADP-ribosylation of a Galpha(i) protein. Finally, LHRH-A significantly counteracted the forskolin-induced increase of intracellular cAMP levels in both cell lines. These data demonstrate that the LHRH receptor, which is present in prostate cancer cells, independently of whether they are androgen-dependent or not, corresponds to the pituitary receptor, in terms of messenger RNA expression and protein molecular size. However, at variance with the receptor of the gonadotrophs, prostate cancer LHRH receptor seems to be coupled to the Galpha(i) protein-cAMP signal transduction pathway, rather than to the Galpha(q/11)-phospholipase C signaling system. This might be responsible for the different actions of LHRH in anterior pituitary and in prostate cancer.


Prevalence of sunburn and sun-related behaviour in the Danish population: a cross-sectional study.
In Denmark, the incidence of melanoma has been increasing since the 1960s. Intermittent exposure to ultraviolet radiation and a history of sunburn and sunbed use are known risk factors. We describe the association between use of protective measures, sun-related behaviour and experience of sunburn in the Danish population three months after the start of the campaign. A population-based sample of 3,499 persons aged 15-59 years completed a questionnaire that included items on exposure to ultraviolet radiation. We examined the relations between sunburn and sun-related behaviour by logistic regression analysis. Within the previous 12 months, 35% of the study population had experienced sunburn. Sunburn became less frequent with age (odds ratio (OR) 4.44; 15-19 vs. 50-59) and skin type (OR 2.57; I vs. III). Sunburn was negatively associated with shade and clothing and positively with use of sunscreens. We found no significant difference in sunscreen use between intentional tanners who experienced sunburn and those who did not. A larger fraction of unintentional tanners with sunburn than those who were not sunburnt had used sunscreen. Sunscreen was used to prolong the time spent in the sun by 66% of sunburnt people; however, we found no association between duration of sun exposure and sunscreen use. Future campaigns to reduce the prevalence of sunburn in the Danish population must especially target young persons and intentional tanning, and they should emphasize that sunscreen cannot be used to extend the time spent in the sun and that shade and clothing provide the best protection against sunburn.


Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wistar rats.
Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction. We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one; 3-30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats. Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected. Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.


Electromyographic signals analysis to assess the response of a proprioceptive neuromuscular facilitation pattern execution.
Proprioceptive Neuromuscular Facilitation is a rehabilitation technique that consists of the stimulation of a healthy muscle in one extremity of the body to produce an activation effect of a damaged muscle in another extremity, laterally or contralaterally. The use of the analysis of the electromyographic response during the process allows us to describe and evaluate if the damaged muscle produces an activation. This paper presents the progress of the results of a clinical protocol where PNF is explored in healthy subjects, manipulating the upper limb, and recording the electromyographic response of the lower limbs in three different muscles in both inferior limbs. Four activation patterns (movement sequence) with three different stages with different intensities of resistance are considered. Lateral plane video recording analysis is performed to extract the trajectory of the manipulated limb and correlate this information with electromyography signals. The electromyography signals are analyzed in their temporal response by integrating the rectified and smoothed signal according to the beginning and end of the trajectory of the manipulated superior limb. Additionally, the spectrogram analysis of the signals is performed. The partial results of the protocol allow us to establish that the response in the most distal muscles to the manipulated upper limb has been non-significant for the subjects, compared to the response of the proximal muscles, where a relationship with activation and trajectory of the arm is observed. particularly in the process with greater resistance. The observed changes in signal frequency across the spectrogram correspond to low-frequency changes in the 15 to 20Hz band.Clinical Relevance- This work presents a strategy to assess the rehabilitation process based on proprioceptive neuromuscular facilitation by analyzing the time and time-frequency response of the electromyographic signal.


Do you want /ʃoloka/ on a /bistɔk/? On the scope of transposed-phoneme effects with non-adjacent phonemes.
We conducted two lexical decision experiments and one replication study to examine the scope of transposed-phoneme effects when the transposition involves non-adjacent phonemes. The critical stimuli were non-words derived from a real word (the base-word) either by transposing two phonemes or by substituting the same phonemes with different phonemes. In Experiment 1, the transposed phonemes belonged either to the same syllable (e.g. /bis.tɔk/ for the French base-word /bis.kɔt/) or to a different syllable (e.g. /ʃo.lo.ka/ for the French base-word /ʃo.ko.la/) and were located either at the beginning of the speech signal (e.g. /sib.kɔt/ for /bis.kɔt/; /ko.ʃo.la/ for /ʃo.ko.la/) or at the end (e.g. /bis.tɔk/ for /bis.kɔt/; /ʃo.lo.ka/ for /ʃo.ko.la/). Experiment 2 compared within-syllable and between-syllable transpositions derived from the same set of bi-syllabic base-words (e.g., /sib.kɔt/, /bik.sɔt/, /bis.tɔk/ for the base-word /biskɔt/). In both experiments, we found clear transposed-phoneme effects with longer "no" decisions for transposed-phoneme non-words compared with the matched substituted-phoneme non-words. The effect was of similar magnitude when the transposed phonemes occurred in the same syllable and across different syllables. Also, for both the within- and between-syllable transpositions, the size of the transposed-phoneme effect did not vary as a function of the position of the transposition. Overall, our results suggest that phonemes can migrate across their respective positions not only within a syllable, but also across syllables. More importantly, they also suggest that position-independent phonemes exert a continuous influence during the entire processing of the auditory stimulus to the extent that there is sufficient time for this influence to manifest itself.


Solubility of Carbon Dioxide, Hydrogen Sulfide, Methane, and Nitrogen in Monoethylene Glycol; Experiments and Molecular Simulation.
Knowledge on the solubility of gases, especially carbon dioxide (CO2), in monoethylene glycol (MEG) is relevant for a number of industrial applications such as separation processes and gas hydrate prevention. In this study, the solubility of CO2 in MEG was measured experimentally at temperatures of 333.15, 353.15, and 373.15 K. Experimental data were used to validate Monte Carlo (MC) simulations. Continuous fractional component MC simulations in the osmotic ensemble were performed to compute the solubility of CO2 in MEG at the same temperatures and at pressures up to 10 bar. MC simulations were also used to study the solubility of methane (CH4), hydrogen sulfide (H2S), and nitrogen (N2) in MEG at 373.15 K. Solubilities from experiments and simulations are in good agreement at low pressures, but deviations were observed at high pressures. Henry coefficients were also computed using MC simulations and compared to experimental values. The order of solubilities of the gases in MEG at 373.15 K was computed as H2S > CO2 > CH4 > N2. Force field modifications may be required to improve the prediction of solubilities of gases in MEG at high pressures and low temperatures.


TARGET OF RAPAMYCIN is essential for asexual vegetative reproduction in Kalanchoë.
The unique mechanism by which leaf margin cells regain potency and then form a plantlet in Kalanchoë spp. remains elusive but involves organogenesis and embryogenesis in response to age, day length, nutrient availability, and drought stress. In light of this, we investigated whether TARGET OF RAPAMYCIN (TOR), a conserved protein kinase in eukaryotes that controls cell growth and metabolism in response to nutrient and energy availability, may regulate plantlet formation. Kalanchoë daigremontiana TOR (KdTOR) was expressed in the leaf margin at the site of plantlet initiation, in the early plantlet cotyledons, and in the root tip of the developed plantlet. Both chemical and genetic inhibition of TOR Kinase activity in Kalanchoë daigremontiana leaves disrupted plantlet formation. Furthermore, downregulation of KdTOR in transgenic plants led to wide-ranging transcriptional changes, including decreased K. daigremontiana SHOOTMERISTEMLESS and K. daigremontiana LEAFYCOTYLEDON1 expression, whereas auxin treatments induced KdTOR expression in the plantlet roots. These results suggest that the KdTOR pathway controls plantlet development in cooperation with auxin, organogenesis, and embryogenesis pathways. The ancient and highly conserved TOR Kinase therefore controls diverse and unique developmental pathways, such as asexual reproduction within the land plant lineage.