An electrophysiological characterisation of long-term potentiation in cultured dissociated hippocampal neurones.
Long-term potentiation (LTP) of synaptic transmission is under intense investigation. It is believed that the mechanisms involved in its induction and expression are critically involved in synaptic processes that are important for learning and memory and other physiological functions. A reliable means of inducing LTP in dissociated cultured neurones would facilitate investigations into the molecular basis of LTP but has been hard to achieve. Here we report a mechanism for inducing LTP in postnatal dissociated hippocampal neurones using transient depolarisation. This form of LTP is prevented by NMDA receptor antagonists and by chelating Ca2+ in the postsynaptic neurone. It is manifest primarily as an increase in the frequency of mEPSCs.


Fetal responses to maternal exercise: effect on fetal breathing and body movement.
This study was conducted to determine the impact of maternal exercise on fetal breathing and fetal body movement, which are commonly used for assessing fetal well-being. Twelve healthy patients with a range of gestational ages of 26 to 36 weeks, who actively exercised throughout pregnancy, participated in the study. The patients walked on a motorized treadmill using a modified Bruce protocol until the maternal heart rate reached 75% of the age-predicted maximal heart rate. Fetal activities (fetal breathing and fetal body movement) were continuously monitored with real-time ultrasonography for 20 minutes before and after the standardized exercise test. Our results demonstrate that there is a significant increase in maternal heart rate and blood pressure associated with exercise. In addition, there is a significant decrease in the total duration and frequency of fetal breathing and fetal body movements following acute maternal exercise.


Genetic modifiers in mice: the example of the fragile X mouse model.
Modifiers play an important role in most, if not all human diseases, and mouse models. For some disease models, such as the cystic fibrosis knockout mouse model, the effect of genetic factors other than the causative mutation has been well established and a modifier gene has been mapped. For other mouse models, including those of the fragile X syndrome, a common form of inherited mental retardation, controversies between test results obtained in different laboratories have been well recognized. Yet, the possibility that modifiers could at least explain part of the discrepancies is only scarcely mentioned. In this review we compare the test results obtained in different laboratories and provide evidence that modifiers may affect disease severity in the fragile X knockout mouse.


Plasma concentrations and comparisons of brain and atrial natriuretic peptide in normal subjects and in patients with essential hypertension.
We have developed a radioimmunoassay for the measurement of immunoreactive BNP (1-32) in human plasma. Simultaneous measurement of ANP have also been carried out to allow for direct comparison between circulating BNP and ANP. Plasma levels of immunoreactive BNP (means +/- SEM) were 1.1 +/- 0.1 pmol/l in 36 normal healthy subjects and were significantly elevated in 50 patients with essential hypertension (1.6 +/- 0.2 pmol/l, P < 0.02). Similarly, in patients with essential hypertension plasma levels of ANP were also significantly raised (5.5 +/- 0.6 pmol/l, P < 0.001) when compared with the group of normal healthy subjects (2.8 +/- 0.2 pmol/l). ANP was significantly higher than BNP in normal subjects and in patients with essential hypertension, with ANP/BNP ratios of 2.8 +/- 0.2 and 3.8 +/- 0.3, respectively, in these two groups. A major finding was a significant and positive association between plasma levels of both BNP and ANP within the healthy subjects (r = 0.49, P < 0.05, n = 36) and within the hypertensive subjects (r = 0.76, P < 0.001, n = 50). When all plasma values for BNP and ANP were taken together for both groups, there was an overall correlation coefficient of 0.65 (P < 0.001, n = 86). Both BNP and ANP had significant positive associations with age in hypertensive patients, with correlation coefficients of 0.53 (P < 0.001, n = 50) and of 0.53 (P < 0.001, n = 50) for BNP and ANP, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Real-world experience with CLAIRYG® 50 mg/mL (intravenous immunoglobulin) in children under 12 years with primary immunodeficiency or immmune thrombocytopenia: a post-approval safety study.
This study presents the results of a real-life, multicenter, prospective, post-approval safety evaluation of Clairyg® 50 mg/mL, a 5% intravenous immunoglobulin (IVIg) liquid, in 59 children (aged < 12 years) with primary immunodeficiency diseases (PID) (n = 32) or immune thrombocytopenia (ITP) (n = 27) in France. The primary objective of the study was to assess the safety and tolerability of Clairyg®, recording all serious and non-serious adverse events (AEs), whether related (rAEs) or not related to the product. Secondary objectives aimed at evaluating the administration of Clairyg® under routine conditions and the available efficacy data to better document the benefit/risk ratio in this pediatric population. An exploratory objective was added to evaluate the potential factors associated with the occurrence of rAEs. Patients received Clairyg® according to the approved dosage under normal conditions of prescriptions over a median follow-up period of 11.8 months. A total of 549 infusions (PID: n = 464 and ITP: n = 85), were administered, of which 58.8% were preceded by premedication. The most frequent rAEs were headache, vomiting, and pyrexia in both indications. Most of them were considered non-serious and mild or moderate in intensity. A severe single rAE was observed (aseptic meningitis) in a 4-year-old girl presenting with chronic ITP. The exploratory multivariate analysis of potential co-factors showed that the occurrence of rAEs is significantly linked to high IVIg doses and possibly to female gender. The annualized rate of serious bacterial infections was 0.11 for patients with PID. For patients with ITP, 74.1% experienced at least one bleeding episode during the follow-up, mostly a cutaneous one, and none had gastrointestinal, genitourinary, or central nervous system bleeding. Clairyg® was well tolerated and allowed for control of serious bacterial infection in PID and serious bleeding in ITP, which are the main complications in these respective pediatric disorders. No new safety signal was detected in children less than 12 years-old in real-life conditions of use.


Deletion of the gene rpoZ, encoding the omega subunit of RNA polymerase, in Mycobacterium smegmatis results in fragmentation of the beta' subunit in the enzyme assembly.
A deletion mutation in the gene rpoZ of Mycobacterium smegmatis causes reduced growth rate and a change in colony morphology. During purification of RNA polymerase from the mutant strain, the beta' subunit undergoes fragmentation but the fragments remain associated with the enzyme and maintain it in an active state until the whole destabilized assembly breaks down in the final step of purification. Complementation of the mutant strain with an integrated copy of the wild-type rpoZ brings back the wild-type colony morphology and improves the growth rate and activity of the enzyme, and the integrity of the beta' subunit remains unaffected.


Ectopic POU5F1 in the male germ lineage disrupts differentiation and spermatogenesis in mice.
Expression levels of the pluripotency determinant, POU5F1, are tightly regulated to ensure appropriate differentiation during early embryogenesis. POU5F1 is also present in the spermatogonial stem cell/progenitor cell population in mice and it is downregulated as spermatogenesis progresses. To test if POU5F1 downregulation is required for SSCs to differentiate, we produced transgenic mice that ubiquitously express POU5F1 in Cre-expressing lineages. Using a Vasa-Cre driver to produce ectopic POU5F1 in all postnatal germ cells, we found that POU5F1 downregulation was necessary for spermatogonial expansion during the first wave of spermatogenesis and for the production of differentiated spermatogonia capable of undergoing meiosis. In contrast, undifferentiated spermatogonia were maintained throughout adulthood, consistent with a normal presence of POU5F1 in these cells. The results suggest that POU5F1 downregulation in differentiating spermatogonia is a necessary step for the progression of spermatogenesis. Further, the creation of a transgenic mouse model for conditional ectopic expression of POU5F1 may be a useful resource for studies of POU5F1 in other cell lineages, during tumorogenesis and cell fate reprogramming.


GOE-GUE-Poisson transitions in the nearest-neighbor spacing distribution of magnetoexcitons.
Recent investigations on the Hamiltonian of excitons by Schweiner et al.. [Phys. Rev. Lett. 118, 046401 (2017)]PRLTAO0031-900710.1103/PhysRevLett.118.046401 revealed that the combined presence of a cubic band structure and external fields breaks all antiunitary symmetries. The nearest-neighbor spacing distribution of magnetoexcitons can exhibit Poissonian statistics, the statistics of a Gaussian orthogonal ensemble (GOE), or a Gaussian unitary ensemble (GUE) depending on the system parameters. Hence, magnetoexcitons are an ideal system to investigate the transitions between these statistics. Here we investigate the transitions between GOE and GUE statistics and between Poissonian and GUE statistics by changing the angle of the magnetic field with respect to the crystal lattice and by changing the scaled energy known from the hydrogen atom in external fields. Comparing our results with analytical formulas for these transitions derived with random matrix theory, we obtain a very good agreement and thus confirm the Wigner surmise for the exciton system.


Characterization of Entamoeba histolytica alpha-actinin.
We have cloned, expressed and characterized a alpha-actinin-like protein of Entamoeba histolytica. Analysis of the primary structure reveals that the essential domains of the alpha-actinin protein family are conserved: an N-terminus actin-binding domain, a C-terminus calcium-binding domain and a central helical rod domain. However, the rod domain of this Entamoeba protein is considerably shorter than the rod domain in alpha-actinins of higher organisms. The cloned Entamoeba 63 kDa protein is recognized by conventional alpha-actinin antibodies as well as binds and cross-links filamentous actin and calcium ions in the same manner as alpha-actinins. Despite the shorter rod domain this protein has conserved the most important functions of alpha-actinins. Therefore, it is suggested that this 63 kDa protein is an atypical and ancestral alpha-actinin.


Transcription factor networks in aged naïve CD4 T cells bias lineage differentiation.
With reduced thymic activity, the population of naïve T cells in humans is maintained by homeostatic proliferation throughout adult life. In young adults, naïve CD4 T cells have enormous proliferative potential and plasticity to differentiate into different lineages. Here, we explored whether naïve CD4 T-cell aging is associated with a partial loss of this unbiased multipotency. We find that naïve CD4 T cells from older individuals have developed a propensity to develop into TH9 cells. Two major mechanisms contribute to this predisposition. First, responsiveness to transforming growth factor β (TGFβ) stimulation is enhanced with age due to an upregulation of the TGFβR3 receptor that results in increased expression of the transcription factor PU.1. Secondly, aged naïve CD4 T cells display altered transcription factor profiles in response to T-cell receptor stimulation, including enhanced expression of BATF and IRF4 and reduced expression of ID3 and BCL6. These transcription factors are involved in TH9 differentiation as well as IL9 transcription suggesting that the aging-associated changes in the transcription factor profile favor TH9 commitment.


[Results 13 years after ACL plasty using a carbon prosthesis].
The retrospective results of carbon prostheses for ACL plasty from 1985 to 1989 are reported. The aim of this study was to determine the number and kind of necessary revisions and the rate of arthrosis and instability of the operated joints. 101 patients out of 136 patients with ACL plasty using a carbon prosthesis could be reviewed clinically in this retrospective study. All patients answered a questionnaire. Additionally, the tibial translation was examined with the KT1000 at maximum power. Conventional X-rays were taken of the knee joints. The results were evaluated using different scores. 70 % of the patients had pathological findings in the clinically tested tibial translation and had a positive Lachmann sign. 66 patients had a tibial translation of 2 mm or above when tested with the KT1000 at maximum power. Radiological studies had shown a gonarthrosis of grades III and IV in 93 patients. An average of 77 points was found using the Lysholm score. The results 13.5 years after ACL plasty using a carbon prosthesis are unsatisfactory concerning joint stability and development of secondary arthrosis. There is a discrepancy between the results of the clinical tests and the subjective complaints of the patients.


Cooperative Sorption on Porous Materials.
The functional shape of a sorption isotherm is determined by underlying molecular interactions. However, doubts have been raised on whether the sorption mechanism can be understood in principle from analyzing sorption curves via a range of competing models. We have shown recently that it is possible to translate a sorption isotherm to the underlying molecular interactions via rigorous statistical thermodynamics. The aim of this paper is to fill the gap between the statistical thermodynamic theory and analyzing experimental sorption isotherms, especially of microporous and mesoporous materials. Based on a statistical thermodynamic approach to interfaces, we have derived a cooperative isotherm, as a generalization of the Hill isotherm and our cooperative solubilization model, without the need for assumptions on adsorption sites, layers, and pore geometry. Instead, the statistical characterization of sorbates, such as the sorbate-interface distribution function and the sorbate number distribution, as well as the existence of statistically independent units of the interface, underlies the cooperative sorption isotherm. Our isotherm can be applied directly to literature data to reveal a few key system attributes that control the isotherm: the cooperative number of sorbates and the free energy of transferring sorbates from the saturated vapor to the interface. The sorbate-sorbate interaction is quantified also via the Kirkwood-Buff integral and the excess numbers.


MR imaging and clinical characteristics of Lermoyez syndrome.
Background: Lermoyez syndrome (LS) is a rare auditory disorder, the details of LS remain unclear.Objectives: To investigate the grades of endolymphatic hydrops (ELH) and clinical characteristics of clinically diagnosed LS.Material and methods: Nine patients with clinically diagnosed LS were included. three-dimensional-real-infra red imaging characteristics were analyzed. ELH grades and detailed clinical characteristics were evaluated.Results: The group consisted of two women and seven men with an age at presentation of 48.4 ± 10.9 (28-61) years, an onset age of 40.9 ± 12.0 (23-58) years, and a disease duration of 7.6 ± 7.5 years. Of the nine patients, ELH was observed in 100% of the patients on the clinically affected side. In addition, 22.2% of vestibular ELH and 77.8% of cochlear ELH were classified as mild or moderate in grade.Conclusions and significance: The patients with LS had Meniere's triad, fluctuation of hearing that occurred in a reverse relationship to that of the vertiginous attack, and vestibular and cochlear ELH, which may suggest that LS is a variant of MD. However, the sex difference and milder cochlear ELH in LS compared with those in typical MD may indicate an underlying intrinsic difference in the mechanism of LS.


Tyrosine and tyrosinate fluorescence of bovine testes calmodulin: calcium and pH dependence.
At physiological pH, bovine testes calmodulin (t-CaM) upon excitation at 278 nm shows typical tyrosine fluorescence at 305 nm and a spectral band characteristic of emission from tyrosinate , at 330-350 nm. In addition, a new band at 312-320 nm appears upon excitation at 288 nm. The pH dependence of the excitation spectra demonstrates that the intense tyrosinate emission at 330-355 nm originates from direct excitation of ground-state tyrosinate . The tyrosinate emission shows complex pH dependence and reaches its highest intensities at pH 7.0 and 8.5, in both apo (Ca free) and holo (Ca saturated) t-CaM. The evidence suggests that the major contribution to the tyrosinate emission at 330-350 nm originates from Tyr-99. In holo t-CaM, the tyrosine emission at 305 nm is quenched at basic pH values and exhibits a sigmoidal pH titration curve with pK(app) 7.0. The tyrosine emission in apo t-CaM is weaker and is almost insensitive to changes in pH. The pH dependence of the emission at 316 nm is the same as the pH dependence of the tyrosine emission in both apo and holo t-CaM. The differences between the fluorescence of apo and holo t-CaM are attributed to a Ca2+-induced shift in the pKa of carboxylic side chains located in the immediate vicinity of the tyrosine residues. The enhancement of the fluorescence by Ca2+ is pH dependent and is maximal at pH 6.5. Above pH 8.0, there is almost no Ca2+ effect on the fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)


Estrogen receptor α promotes lung cancer cell invasion via increase of and cross-talk with infiltrated macrophages through the CCL2/CCR2/MMP9 and CXCL12/CXCR4 signaling pathways.
Data analysis of clinical samples suggests that higher estrogen receptor α (ERα) expression could be associated with worse overall survival in some patients with non-small-cell lung cancer (NSCLC). Immunofluorescence results further showed that higher ERα expression was linked to larger numbers of infiltrated macrophages in NSCLC tissues. However, the detailed mechanisms underlying this phenomenon remain unclear. Results from in vitro studies with multiple cell lines revealed that, in NSCLC cells, ERα can activate the CCL2/CCR2 axis to promote macrophage infiltration, M2 polarization, and MMP9 production, which can then increase NSCLC cell invasion. Mechanistic studies using chromatin immunoprecipitation and promoter luciferase assays demonstrated that ERα could bind to estrogen response elements (EREs) on the CCL2 promoter to increase CCL2 expression. Furthermore, ERα-increased macrophage infiltration can induce a positive feedback mechanism to increase lung cancer cell ERα expression via the up-regulation of the CXCL12/CXCR4 pathway. Targeting these newly identified pathways, NSCLC ERα-increased macrophage infiltration or the macrophage-to-NSCLC CXCL12/CXCR4/ERα signal, with anti-estrogens or CCR2/CXCR4 antagonists, may help in the development of new alternative therapies to better treat NSCLC.


PKC-α Triggers EGFR Ubiquitination, Endocytosis and ERK Activation in Podocytes Stimulated with High Glucose.
Protein Kinase C-α (PKC-α) and epidermal growth factor receptor (EGFR) are both involved in diabetic kidney disease; however, the connection between these two proteins during high glucose-induced podocyte injury remains uncertain. Diabetes was induced in SD rats by streptozotocin (STZ). Fourteen days later, the kidney cortex was removed and subjected to plasma membrane isolation and lipid raft fractionation. In vitro study human podocyte cell line was differentiated and subjected to various treatments. The levels of membranous protein and endocytosis were assessed by biotinylation and sodium 2-mercaptoethane sulfonate (MesNa) treatment. Gö6976 and PYR-41 were used as inhibitors of PKC-α and ubiquitin activating E1 enzyme, respectively. In diabetic rats, the abundance of PKC-α in the membranous fraction and the lipid raft domain is elevated, whereas the EGFR level is reduced. Consistently, in vitro high glucose treated podocytes, membranous EGFR is downregulated with increased PKC-α. Furthermore, the ubiquitination and endocytosis of EGFR are enhanced accompanied by extracellular signal-regulated kinase (ERK) signaling activation and podocyte damage during hyperglycemia. However, these processes can be ameliorated by inhibition of either PKC-α or ubiquitin activating E1 enzyme. During hyperglycemia, PKC-α mediates podocytic EGFR ubiquitination, endocytosis from cell surface and the subsequent ERK activation, which contributes to podocyte injury.


A simulation study of the strength of evidence in the recommendation of medications based on two trials with statistically significant results.
A typical rule that has been used for the endorsement of new medications by the Food and Drug Administration is to have two trials, each convincing on its own, demonstrating effectiveness. "Convincing" may be subjectively interpreted, but the use of p-values and the focus on statistical significance (in particular with p < .05 being coined significant) is pervasive in clinical research. Therefore, in this paper, we calculate with simulations what it means to have exactly two trials, each with p < .05, in terms of the actual strength of evidence quantified by Bayes factors. Our results show that different cases where two trials have a p-value below .05 have wildly differing Bayes factors. Bayes factors of at least 20 in favor of the alternative hypothesis are not necessarily achieved and they fail to be reached in a large proportion of cases, in particular when the true effect size is small (0.2 standard deviations) or zero. In a non-trivial number of cases, evidence actually points to the null hypothesis, in particular when the true effect size is zero, when the number of trials is large, and when the number of participants in both groups is low. We recommend use of Bayes factors as a routine tool to assess endorsement of new medications, because Bayes factors consistently quantify strength of evidence. Use of p-values may lead to paradoxical and spurious decision-making regarding the use of new medications.


Rate of blood flow and growth of the corpora lutea of pregnancy and of previous cycles throughout pregnancy in the rat.
The rate and distribution of ovarian blood flow was measured with radioactive microspheres in nulliparous rats at Days 4, 7, 10, 13, 16 and 22 of gestation; term is Day 23. Ovaries were dissected into large corpora lutea (or CL of pregnancy), small CL, assumed to be those of previous cycles, and the ovarian stroma which included follicles and additional small CL. Total ovarian blood flow was similar over Days 4-10, but then increased progressively to reach 916 +/- 69 microliter/min at Day 22. The main cause of this increase was a 786% rise in blood flow to the large CL over Days 10-22. Weight of the CL of previous cycles increased by 289% over Days 10-16 and their rate of blood flow and histological appearance were similar to those of the large CL. These results indicate that neither reduced blood flow nor vascular degeneration, as determined by light microscopic examination, initiates the reported fall in progesterone secretion near term. At least some of the CL of previous cycles are maintained and indeed grow during gestation and have a blood circulation and histological appearance characteristic of steroidogenic tissue.


The impact of spectral modulations on the contrast of pulses of nonlinear chirped-pulse amplification systems.
A detrimental pulse distortion mechanism inherent to nonlinear chirped-pulse amplification systems is revealed and analyzed. When seeding the nonlinear amplification stage with pulses possessing weak side-pulses, the Kerr-nonlinearity causes a transfer of energy from the main pulse to side pulses. The resulting decrease in pulse contrast is determined by the accumulated nonlinear phase-shift (i.e., the B-integral) and the initial pulse-contrast. The energy transfer can be described by Bessel-functions. Thus, applications relying on a high pulse-contrast demand a low B-integral of the amplification system and a master-oscillator that exhibits an excellent pulse-contrast. In particular, nonlinear fiber CPA-systems operated at B-integrals far beyond pi have to be revised in this context.


Desensitization for Allergic Reactions to Chemotherapy.
Drug desensitization is procedure by which patients can be tolerized to medications that have previously induced hypersensitivity reactions. Initially used in treating hypersensitivity reactions to antibiotics, desensitization is now frequently used in the setting of allergy to chemotherapy drugs and biologics, thus widening the clinical applicability of this procedure which has been proven to be quite safe and effective in improving clinical outcomes, mainly by allowing patients to remain on preferred first-line therapy. This paper reviews the history, application, and safety studies of drug desensitization for chemotherapy and biologics.


Inflammation of rat dorsal root ganglia below a mid-thoracic spinal transection.
Macrophages and T-lymphocytes invade the spinal cord in and around a lesion and spinal microglia are converted into macrophages. After spinal transection at T8 in rats, T-lymphocyte and major histocompatibility complex II+ (MHC II+) macrophage numbers were increased within dorsal root ganglia (DRGs) below the lesion. Inflammation was greater in DRGs closer to the site of transection. After 8 weeks, MHC II+cell density had fallen by 30% but T-lymphocyte numbers were undiminished. In lumbosacral DRGs, inflammation preceded inflammation within the spinal cord. The responses in distant DRGs are hard to reconcile with the limited damage to sensory neurons produced by the lesion. Inflammation of DRGs after spinal injury may contribute to hyper-reflexia and pain.


[Which vaccinations for which travel-destination?].
Several vaccinations are recommended to protect international travellers, especially to tropical countries, from diseases in other parts of the world. Firstly, the routine schedule of childhood vaccinations and booster shots according to the Swiss immunisation programme should be checked, updated or even completed. Additional vaccinations against hepatitis A and B, typhoid fever, poliomyelitis, rabies or Japanese encephalitis may be recommended. This will depend on a number of factors including the exact destination and route (developing countries, rural areas), planned activities (backpacker, family visit, business trip), duration of travel, season, age of the traveller and current health status including the current medication and previous vaccinations. Some vaccinations, such as yellow fever, may be required for travellers to certain countries and the international certificate of vaccination may even be required when entering a country from another country where yellow fever is endemic. The international certificate of vaccination (or a letter of exemption when appropriate) is considered valid only if it is administered by an approved vaccination centre. Furthermore, the meningococcal vaccination (A, C, W, Y) is required for pilgrims to Saudi Arabia. It is recommended to start the vaccinations four to six weeks before departure to ensure enough time to administer all the necessary doses for an adequate immune response. All commonly used vaccines can be administered on the same day. The basic health insurance does not usually cover travel vaccines.


Increasing testicular self-examination in active duty soldiers: an intervention study.
In this intervention study, the researchers assessed the knowledge of and health beliefs regarding testicular cancer and testicular self-examination (TSE) in active duty Army Soldiers.


Magnetic resonance imaging in the diagnosis of subglottic cysts of infancy: case report and review.
Subglottic cysts can cause stridor and respiratory distress in the infant. The diagnosis of subglottic cysts is often confirmed during direct laryngoscopy and bronchoscopy. We describe the case of a 6-month-old boy with bilateral subglottic cysts that were preoperatively diagnosed by magnetic resonance imaging (MRI). We also review the current literature on the diagnosis and treatment of subglottic cysts. Up until now, 63 cases of subglottic cysts were reported in the literature since 1966, and most were diagnosed by direct endoscopy. In this article, we describe a new case and we provide the first published report of the novel use of MRI in diagnosing this lesion.


Dimensions, domains and principles of the new nutrition science.
Following the agreed principles, definition and dimensions of the new nutrition science, to elaborate its overall guiding principles, to propose some domains of its biological, social and environmental dimensions, and to propose a series of principles to govern and guide these dimensions and domains. This paper, part of The New Nutrition Science project, is initial work in progress towards a comprehensive typology of the science, and is designed to stimulate further work. A review that takes into account the discussions of the Giessen workshop on the new nutrition science, and in particular the workshop agreement as expressed in The Giessen Declaration. Three outlines of the evolutionary, historical and ecological general principles to guide the new nutrition science are given in boxed texts. The suggested specific principles, taken mostly from 14 associated papers and workshop discussion, are an informal supplement to the Declaration. They are presented as further work in progress, to be developed, revised and agreed at future meetings designed to develop the new nutrition science. An essential aspect of the theory and the practice of the new nutrition science--in common with any scientific discipline and indeed any ordered human activity--is a specification of its dimensions and their domains, with definitions; and also considered and agreed principles to govern and guide its work.


Nuclear fusions contribute to polyploidization of the gigantic nuclei in the chalazal endosperm of Arabidopsis.
Somatic polyploidization is recognized as a means to increase gene expression levels in highly active metabolic cells. The most common mechanisms are endoreplication, endomitosis and cell fusion. In animals and plants the nuclei of multinucleate cells are usually prevented from fusing. Here, we report that the nuclei from the syncytial cyst of the chalazal endosperm of Arabidopsis thaliana (L.) Heynh. are polyploid with some intermediate ploidy levels that cannot be attributed to endoreplication, suggesting nuclear fusion. Analysis of isolated nuclei, together with fluorescent in situ hybridization (FISH), revealed that nuclei from the chalazal endosperm are two or three times bigger than the nuclei from the peripheral endosperm and have a corresponding increase in ploidy. Together with the consistent observation of adjoined nuclei, we propose that nuclear fusion contributes, at least in part, to the process of polyploidization in the chalazal endosperm. Confocal analysis of intact seeds further suggested that free nuclei from the peripheral endosperm get incorporated into the chalazal cyst and likely participate in nuclear fusions.


Cyst Nematode Parasitism Induces Dynamic Changes in the Root Epigenome.
A growing body of evidence indicates that epigenetic modifications can provide efficient, dynamic, and reversible cellular responses to a wide range of environmental stimuli. However, the significance of epigenetic modifications in plant-pathogen interactions remains largely unexplored. In this study, we provide a comprehensive analysis of epigenome changes during the compatible interaction between the beet cyst nematode Heterodera schachtii and Arabidopsis (Arabidopsis thaliana). Whole-genome bisulfite sequencing was conducted to assess the dynamic changes in the methylome of Arabidopsis roots in response to H. schachtii infection. H. schachtii induced widespread hypomethylation of protein-coding genes and transposable elements (TEs), preferentially those adjacent to protein-coding genes. The abundance of 24-nt siRNAs was associated with hypermethylation of TEs and gene promoters, with influence observed for methylation context and infection time points. mRNA sequencing revealed a significant enrichment for the differentially methylated genes among the differentially expressed genes, specifically those with functions corresponding to primary metabolic processes and responses to stimuli. The differentially methylated genes overlapped with more than one-fourth of the syncytium differentially expressed genes and are of functional significance. Together, our results provide intriguing insights into the potential regulatory role of differential DNA methylation in shaping the biological interplay between cyst nematodes and host plants.


Is there a gender difference in a factorial structure of the positive and negative syndrome scale? A test by structural equation modeling.
By means of the multisample structured means strategy, we examined gender differences in a five-factorial structure model of Positive and Negative Syndrome Scale (PANSS) ratings of 308 patients of both sexes with DSM-IV schizophrenia with comparable age at investigation and overall symptomatic severity across sex. The test indicated that the factors and component symptoms were common across sex, whereas the factor loadings might be different. However, the model that incorporated the difference in the factor loadings did not improve model fit indices. Therefore, it is concluded that this investigation elicited only minimal gender differences, and on the whole confirmed the PANSS five-factor structure for both sexes.


Direct-Coupling Analysis of nucleotide coevolution facilitates RNA secondary and tertiary structure prediction.
Despite the biological importance of non-coding RNA, their structural characterization remains challenging. Making use of the rapidly growing sequence databases, we analyze nucleotide coevolution across homologous sequences via Direct-Coupling Analysis to detect nucleotide-nucleotide contacts. For a representative set of riboswitches, we show that the results of Direct-Coupling Analysis in combination with a generalized Nussinov algorithm systematically improve the results of RNA secondary structure prediction beyond traditional covariance approaches based on mutual information. Even more importantly, we show that the results of Direct-Coupling Analysis are enriched in tertiary structure contacts. By integrating these predictions into molecular modeling tools, systematically improved tertiary structure predictions can be obtained, as compared to using secondary structure information alone.


[Measurement of normal eyeball position and its application for evaluation of exophthalmos in craniofacial synostosis].
The chronologic changes in eyeball position in relation to bony landmarks were studied by CT scans. The results were applied to the preoperative evaluation in 16 craniofacial synostosis patients. Ten subjects from each age group were selected from more than 2000 subjects who underwent CT scanning of the skull without any brain and skull diseases. These age groups ranged from birth to 20 years of age. The following four distances were measured on the CT section incorporating lenses: (1) the distance from the dorsum sellae to the lenses, (2) the distance between the lateral orbital rim and the lenses, (3) the distance from the nasal root to the lenses, and (4) the width between the lenses. These distances also were measured in 16 craniofacial synostosis patients preoperatively, and the results were compared with those of the healthy individuals in the same age group. The distances of the lenses from the nasal root and from the lateral orbital rim were larger than in the healthy individuals in almost all craniofacial synostosis patients. However, the distance from the dorsum sellae to lenses was the same as that in healthy individuals on the whole.


Outcome of Expedited Rotator Cuff Surgery in Injured Workers: Determinants of Successful Recovery.
Work-related rotator cuff injuries are a common cause of disability and employee time loss. To examine the effectiveness of expedited rotator cuff surgery in injured workers who underwent rotator cuff decompression or repair and to explore the impact of demographic, clinical, and psychosocial factors in predicting the outcome of surgery. Case series; Level of evidence, 4. Injured workers who were seen at a shoulder specialty program and who underwent expedited arthroscopic rotator cuff decompression or repair were observed for a period of 6 to 12 months based on their type of surgery and recovery trajectory. The primary outcome measure was the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form. The impact of surgery was assessed by whether the change in the ASES score exceeded the minimal clinically important difference (MCID) of 17 points. Secondary outcomes were range of motion (ROM), medication consumption, and work status. One hundred forty-six patients (43 women [29%], 103 men [71%]; mean age, 52 years; SD, 8 years) completed the study. Sixty-seven (46%) patients underwent rotator cuff repair. The mean time between the date the patient consented to have surgery and the date of surgery was 82 (SD, 44) days. There was a statistically significant improvement in ASES score and ROM and work status (52 returned to regular duties and 59 to modified duties) (P < .0001). Eighty-four percent (n = 122) of patients exceeded the MCID of 17 points. Individual factors that affected patient overall disability were preoperative ASES, work status prior to surgery, access to care, and autonomy at work. Achieving a minimal clinically meaningful change was influenced by perceived access to care, autonomy and stress at work, and overall satisfaction with the job. Expedited rotator cuff surgery improved disability, ROM, and work status in injured workers. Successful recovery after work-related shoulder injuries may further be facilitated by improving the psychosocial work environment and increasing access to care.


Comprehensive analysis of the association of seasonal variability with maternal and neonatal nutrition in lowland Nepal.
To provide a comprehensive seasonal analysis of pregnant mothers' eating behaviour and maternal/newborn nutritional status in an undernourished population from lowland rural Nepal, where weather patterns, agricultural labour, food availability and disease prevalence vary seasonally. Secondary analysis of cluster-randomised Low Birth Weight South Asia Trial data, applying cosinor analysis to predict seasonal patterns. Maternal mid-upper arm circumference (MUAC), BMI, dietary diversity, meals per day, eating down and food aversion in pregnancy (≥31 weeks' gestation) and neonatal z-scores of length-for-age (LAZ), weight-for-age (WAZ) and head circumference-for-age (HCAZ) and weight-for-length (WLZ). Rural areas of Dhanusha and Mahottari districts in plains of Nepal. 2831 mothers aged 13-50 and 3330 neonates. We found seasonal patterns in newborn anthropometry and pregnant mothers' anthropometry, meal frequency, dietary diversity, food aversion and eating down. Seasonality in intake varied by food group. Offspring anthropometry broadly tracked mothers'. Annual amplitudes in mothers' MUAC and BMI were 0·27 kg/m2 and 0·22 cm, with peaks post-harvest and nadirs in October when food insecurity peaked. Annual LAZ, WAZ and WLZ amplitudes were 0·125, 0·159 and 0·411 z-scores, respectively. Neonates were the shortest but least thin (higher WLZ) in winter (December/January). In the hot season, WLZ was the lowest (May/June) while LAZ was the highest (March and August). HCAZ did not vary significantly. Food aversion and eating down peaked pre-monsoon (April/May). Our analyses revealed complex seasonal patterns in maternal nutrition and neonatal size. Seasonality should be accounted for when designing and evaluating public heath nutrition interventions.


Changes in hemodynamics after rescue surfactant administration.
To evaluate the hemodynamic changes occurring after rescue surfactant dosing in relation to the clinical respiratory response in preterm infants with respiratory distress syndrome. We studied 20 infants who received surfactant (poractant alfa) after failing continuous positive airway pressure (CPAP) beyond 2 h of life. Consecutive echocardiograms were performed before the surfactant dose, 10 min after and 1 h after the surfactant dose. Superior vena cava flow, right ventricular output, atrial and patent ductus arteriosus diameter and direction of shunting were measured. A surfactant responder (SR) was defined as an infant whose inspired fraction of oxygen was reduced to air (0.21) by 3 h after surfactant administration. A surfactant non-responder (SNR) was defined as an infant who remained on more than 0.21 at 3 h postsurfactant administration. Concurrent physiological parameters (heart rate, transcutaneous CO2, mean arterial blood pressure, mean airway pressure) were also recorded. Subject characteristics were compared relative to noted hemodynamic effects. Of the 20 infants enrolled in the study, 12 were SR. These infants received surfactant earlier and had increased measures of systemic blood flow after receipt of surfactant compared with baseline. SNR did not have changes in systemic blood flow from baseline after surfactant dosing. There was no change in ductal shunting or atrial shunting between the two groups. A good clinical response to rescue surfactant is seen in infants who received surfactant earlier and is associated with increase in systemic blood flow. Timing of rescue surfactant administration needs to be further evaluated in larger prospective studies.


Heterotrimeric G Protein-Mediated Signaling Is Involved in Stress-Mediated Growth Inhibition in Arabidopsis thaliana.
Heterotrimeric G protein-mediated signaling plays a vital role in physiological and developmental processes in eukaryotes. On the other hand, because of the absence of a G protein-coupled receptor and self-activating mechanism of the Gα subunit, plants appear to have different regulatory mechanisms, which remain to be elucidated, compared to canonical G protein signaling established in animals. Here we report that Arabidopsis heterotrimeric G protein subunits, such as Gα (GPA1) and Gβ (AGB1), regulate plant growth under stress conditions through the analysis of heterotrimeric G protein mutants. Flg22-mediated growth inhibition in wild-type roots was found to be caused by a defect in the elongation zone, which was partially blocked in agb1-2 but not gpa1-4. These results suggest that AGB1 may negatively regulate plant growth under biotic stress conditions. In addition, GPA1 and AGB1 exhibited genetically opposite effects on FCA-mediated growth inhibition under heat stress conditions. Therefore, these results suggest that plant G protein signaling is probably related to stress-mediated growth regulation for developmental plasticity in response to biotic and abiotic stress conditions.


Children and war: the work of the Children and War Foundation.
The Children and War Foundation was established after the authors' experiences following the civil war in former Yugoslavia in the mid-1990s. Many organizations tried to mitigate the effects of the war on children but few interventions were based on evidence and fewer were properly evaluated. The Foundation was established in Norway with the aim of promoting better evidence-based interventions to help children after wars and natural disasters.The Foundation has developed a number of empirically grounded manuals that aim to help children learn strategies that will lessen the stress reactions that they have developed. The manuals are designed to be delivered by personnel who are not necessarily very experienced in child mental health. They are aimed at groups of children using a public health approach to reach large numbers in a short space of time. The strategies are not intended as individual therapy.The Teaching Recovery Techniques manual has been used following a number of earthquakes and other natural disasters and data from a number of these will be discussed. A Writing for Recovery manual is aimed at helping adolescents and is based on the seminal work of James Pennebaker. It is currently being evaluated in three separate studies. A group-based manual to help children bereaved by war or disaster has recently been developed.


Assessment of basal insulin requirement using fasting tests in insulin-treated patients with type 2 diabetes mellitus.
Characterizing the time course of the rise of blood glucose concentrations in the fasting state during the day and night in patients with type 2 diabetes. 40 consecutive insulin-treated patients with type 2 diabetes underwent fasting tests on two different days with either no breakfast and lunch (fasting time of 20 hours) or no dinner (fasting time of 21 hours). Glucose-lowering medication was stopped prior to the test according to the half-life of the medication prescribed. At the start of the fasting tests, blood glucose concentrations were lowered to below 7 mmol/L using an insulin infusion. 26 men and 14 women were included in the study. Mean (+/-SD) age was 61+/-10 years, BMI 31+/-7 kg/m (2), and HbA1c 7.5+/-1%. Diabetes duration was 14+/-8 years and duration of insulin therapy had been prescribed for a mean of 6+/-6 years. During the daytime fast, plasma glucose concentrations rose by a mean of 0.8+/-1.6 mmol/L. During the nighttime fast, plasma glucose concentrations increased particularly after midnight, by 4.3+/-2.1 mmol/L, i.e. significantly more than during the daytime fast. Fasting blood glucose concentrations in the majority of insulin-treated patients with type 2 diabetes increase markedly after midnight. No similar increase is observed during the day. Thus, for most patients with type 2 diabetes, an intermediate- or long-acting insulin injected at bedtime with a peak action six to eight hours after injection should be appropriate.


Isolation and characterization of a hemocyte aggregation inhibitor from hemolymph of Manduca sexta larvae.
A protein that inhibits hemocyte aggregation has been isolated from hemolymph of Manduca sexta larvae and named hemocyte aggregation inhibitor protein (HAIP). HAIP has a M(r) = 50,000, pI = 8.5, and contains 7% carbohydrate. It is present at 230 +/- 20 micrograms/ml in hemolymph of day 3 fifth instar larvae. Antibodies to HAIP do not cross-react with M. sexta hemolin, which is similar in size and charge and also inhibits hemocyte aggregation. HAIP and hemolin have some similarity in amino acid composition and NH2-terminal sequence, but are different in overall secondary structure, as determined by CD spectroscopy. The concentration of HAIP in hemolymph is not affected by injection of larvae with bacteria. A protein of approximately 50,000 daltons that reacts with antibody to M. sexta HAIP is present in hemolymph of Bombyx mori, Heliothis zea, and Galleria mellonella. Although the function of HAIP in vivo is not yet clear, it may have a role in modulating adhesion of hemocytes during defensive responses.


The effect of cannabinoid receptor 1 blockade on adipokine and proinflammatory cytokine concentration in adipose and hepatic tissue in mice with nonalcoholic fatty liver disease.
In high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD), there is an increase in the endocannabinoid system activity, which significantly contributes to steatosis development. The aim of our study was to investigate the effects of cannabinoid receptor type 1 blockade on adipokine and proinflammatory cytokine content in adipose and hepatic tissue in mice with NAFLD. Male mice C57BL/6 were divided into a control group fed with a control diet for 20 weeks (C, n = 6) a group fed with a HFD for 20 weeks (HF, n = 6), a group fed with a control diet and treated with rimonabant after 18 weeks (R, n = 9), and a group fed with HFD and treated with rimonabant after 18 weeks (HFR, n = 10). Rimonabant significantly decreased leptin, resistin, apelin, visfatin, interleukin 6 (IL-6), and interferon-γ (IFN-γ) concentration in subcutaneous and visceral adipose tissue in the HFR group compared to the HF group (p < 0.01). Rimonabant reduced hepatic IL-6 and IFN-γ concentration as well as plasma glucose and insulin concentration and the homeostatic model assessment index in the HFR group compared to the HF group (p < 0.01). It can be concluded that the potential usefulness of CB1 blockade in the treatment of HFD-induced NAFLD is due to modulation of the adipokine profile and proinflammatory cytokines in both adipose tissues and liver as well as glucose metabolism.


Privacy, Employees and Human Resources: A Case Report.
Health practitioners are well versed in the need to maintain privacy and confidentiality of patients/clients in healthcare relationships. This need for confidentiality is likewise required when an employee of a healthcare institution becomes a patient of that institution. The question which arises is whether any information which emerges as a result of the employee also being a patient can or should be disclosed to the administration of the employing institution where such information may affect the employee or others in the workplace.


Theory of mind and Verstehen (understanding) methodology.
Theory of mind is a prominent, but highly controversial, field in psychology, psychiatry, and philosophy of mind. Simulation theory, theory-theory and other views have been presented in recent decades, none of which are monolithic. In this article, various views on theory of mind are reviewed, and methodological problems within each view are investigated. The relationship between simulation theory and Verstehen (understanding) methodology in traditional human sciences is an intriguing issue, although the latter is not a direct ancestor of the former. From that perspective, lessons for current clinical psychiatry are drawn.


Three-dimensional evaluation of social smile asymmetry in patients with unilateral impacted maxillary canine: a 3D stereophotogrammetry study.
This study aimed to evaluate social smile asymmetry in patients with unilateral impacted maxillary canine on 3D stereophotogrammetric images. The 3D social smile images of participants with unilateral impacted maxillary canine (n:20) and without impaction as a control group (n:20) were included. The images were recorded with a hand-held 3D stereophotogrammetry device (Fuel3D® Scanify®) and Geomagic Essentials 2 reverse engineering software were used for analyses. After the orientation process of the 3D records, the tissues around the smile area were divided into five morphological regions: cheek, upper lip lateral and medial, and lower lip lateral and medial. The deviation margins in the negative and positive directions for the 95% mesh rate and the total percentages of meshes between - 0.5- and + 0.5-mm deviations were calculated. ICC, paired samples t test, independent samples t test, and the Mann-Whitney U test were used for statistical analyses. In individuals with impacted canine, the amount of maximum positive deviation in the upper lip medial was 5.64 mm ± 1.46 and maximum negative deviation was - 4.6 mm ± 1.17. In the control group, mean of deviation limits for all parameters was less than 1.19 mm ± 2.62, while in individuals with unilateral impacted maxillary canine, the maximum value was 8.34 mm ± 2.23. The mesh percentage between - 0.5 and 0.5-mm deviations was over 95% in all morphological areas in the control group, while in the impacted canine group, the number of meshes within the specified deviation limits was less than 95%. Individuals with unilateral impacted maxillary canine exhibit greater asymmetry in social smile compared to the control group, with the asymmetry being most prominent near the corners of the mouth and cheeks. Amount of asymmetry was higher in impaction group compared to the control group in social smile. The quantification of a possible smile asymmetry due to the impacted canine is crucial for the diagnosis and treatment planning of orthodontic and/or orthognathic cases for ideal aesthetic results. Hence, smile asymmetry should not be overlooked and should be considered in diagnosis and treatment planning.


[Iron and age-related macular degeneration: a new track].
Iron has a fundamental role for cell physiology and especially in retina as a cofactor of many pathways of the visual transduction. A tightly regulated homeostasis avoids the accumulation of prooxidant and proinflammatory free iron. A dysfunction of iron retinal homeostasis is associated with many genetic or age-related degenerative diseases such as age-related macular degeneration (AMD). Here, we describe various mechanisms reported during AMD, enhanced by iron accumulation and its homeostasis dysregulation. We have investigated a local treatment with transferrin, the natural iron carrier, to control these pathological pathways and iron dysfunction, without side effects. Iron has a central role in pathogenesis of AMD and is a target for futures therapies.


A novel function of interferon regulatory factor-1: inhibition of Th2 cells by down-regulating the Il4 gene during Listeria infection.
Infection with certain pathogens induces a shift of the Th subset balance to a Th1 dominant state. This, in turn, results in the suppression of Th2 responses. We focused on the involvement of interferon regulatory factor-1 (IRF-1) in the suppression of Th2 cells during Listeria infection. We found that the inhibition of IL-4 production by Th2 cells is mediated by a soluble factor (LmSN) produced by Listeria-infected antigen-presenting cells. The inhibition is not observed with T cells from Irf1 gene-targeted mice. IRF-1 suppresses transcription of the Il4 gene in Th2 cells. Under the influence of the LmSN, IRF-1 binds to the 3' untranslated region (UTR) region of the Il4 gene and down-regulates Il4 gene transcription. Finally, we identified IL-1α and IL-1β as the mediator of the LmSN activity. Signaling through IL-1R induces the stabilization and/or nuclear translocation of IRF-1. We propose that IRF-1 functions to induce the T-cell subset shift via a novel mechanism. Under the influence of IL-1, IRF-1 translocates into the nucleus and acts on the 3'UTR region of the Il4 gene, thus inhibiting its transcription in Th2 cells. As a result, the immune system shifts predominantly to a Th1 response during Listeria infection, resulting in effective protection of the host.


Issues and implications of establishing guidelines for the use of behavioral techniques.
Several guidelines surrounding the use of behavioral procedures have recently appeared, the best of which is that of the National Association of Retarded Citizens (NARC). Some issues and implications of the establishment of guidelines are briefly reviewed in the context of the NARC guidelines. Issues include the factual versus opinion bases for guidelines and the need to continue the development of explicit behavioral criteria for assessing staff competence. Implications for programs include the impact of guidelines on the professional boundaries, administrative decision-making, and budgeting, together with the dangers of expanding the regulatory bureaucracy. Several miscellaneous impacts are noted, including a potential for curbing innovative behavioral technology.


Epidemiology of Helicobacter pylori infection in Barbados.
The epidemiology of Helicobacter pylori infection in Barbadian patients and controls was studied. H. pylori was isolated from biopsies from 50/100 (50%) adult patients undergoing endoscopy for investigation of upper gastrointestinal tract symptoms. Urease was detected in biopsies from 54 patients and gastritis was detected by histology in 71 patients. Serology was performed using a commercial ELISA method. Using an IgG concentration of 10 U/ml as a threshold, antibodies were detected in 78% of 100 patients undergoing endoscopy, 72% of 230 blood donors and 22% of 50 children. The mean antibody concentration was significantly higher in patients (92 U/ml) than in blood donors (49 U/ml) or in children (9.5 U/ml). Culture-positive patients (120 U/ml) had higher IgG concentrations than culture-negative patients (64 U/ml). Using isolation of H. pylori or a positive biopsy urease test as a measure of true prevalence of infection, the sensitivity of serology was 96%, the specificity 42%, positive predictive value 67% and negative predictive value 90%. Seroprevalence increased with age, to a peak of more than 90% in blood donors aged 50-59 years and in patients aged over 60 years. The epidemiology of H. pylori in Barbados is similar to that in developed countries, where few children are infected, but resembles other developing countries in the high seroprevalence observed in middle-aged adults. Our results confirm the utility of serology for detecting H. pylori by a non-invasive technique.


[The regulation of mast cell migration. Part 2: mast cell chemoattractants].
There are many humoral factors that regulate the migration of mast cell progenitors from the blood into tissues and the migration of mature mast cells within tissues, leading to the rapid accumulation that occurs in diverse pathological conditions. First of all, mast cell migration is stimulated by some chemokines, such as RANTES, eotaxin, and IL-8. Moreover, many cytokines induce the migration of mast cells (i.e. SCF, TNF, IL-15). Finally, the migration of mast cells is also stimulated by many other humoral factors, including those involved in inflammatory process, such as C3a, C5a, histamine, PAF, and CRP. Because mast cells play an essential role in diverse physiological and pathological processes, it seems to be of great importance to know the mechanisms underlying the migration of immature and mature mast cells. However, current knowledge about these processes is still insufficient.


Smoking habits and coenzyme Q10 status in healthy European adults.
Coenzyme Q10 (CoQ10) is a lipophilic endogenously synthesised antioxidant that is present in nearly all human tissues and plays an important role in mitochondrial energy production. It has been postulated that smoking has a consumptive effect on CoQ10. To further define the relation between smoking and the serum CoQ10 status, 276 healthy volunteers aged 19 to 62 years were grouped into non-smokers (n = 113; 77 male, 36 female) and smokers (n = 163; 102 male, 61 female). Serum lipid profile was analysed by standard clinical chemistry. Coenzyme Q10 concentration and redox status were analysed by high-pressure liquid chromatography with electrochemical detection. Male smokers showed higher serum CoQ10 levels than female smokers. This sex-related difference was accounted for when CoQ10 was related to low-density lipoprotein (LDL) cholesterol as the main carrier of CoQ10 in the circulation. Neither LDL-adjusted CoQ10 concentration nor redox status significantly differed when smokers and non-smokers were compared. Regarding the smoking history, the number of cigarettes consumed per day did not significantly affect the CoQ10 status. Interestingly, with increasing time of smoking habit we observed increasing levels of LDL-adjusted serum CoQ10 concentration (Spearman's p < 0.002) and of the reduced form of CoQ10 (Spearman's p < 0.0001). As an adaptive response to oxidative stress in long-term smokers an increased demand for antioxidant capacity may be covered by increasing levels of LDL-adjusted CoQ10 serum concentrations and by a concomitantly increased availability of the reduced, active form of CoQ10, possibly by induction of enzymes that are involved in converting CoQ10ox to CoQ10red.


Diagnosis and Resection Treatment of Triplet Hepatocellular Carcinomas with a non-B non-C Background in a Middle Aged Man over a Period of 6-years.
We report a 71-year-old man with non-B non-C chronic liver damage who had been regularly visiting our hospital since he was 38 years of age. He underwent three partial hepatectomies for hepatocellular carcinoma (HCC) diagnosed at 65, 67, and 71 years of age, respectively. A histopathological examination showed moderately-differentiated HCC, and chronic hepatitis with mild fibrosis stage in non-tumor areas. alpha-fetoprotein (AFP) and PIVKAII were not useful for the early prediction of HCC, but TERT promotor mutation (C228T) in serum cell-free DNA was useful. This is the first report on the importance of long-term follow-up in non-B non-C chronic liver damage, regardless of the fibrosis stage.


Glycans modulate immune responses in helminth infections and allergy.
Infections of humans and animals by parasitic helminths share key features with atopic diseases, such as allergic asthma. Both diseases lead to the induction of high levels of Th2- type cytokines associated with abundant IgE production and eosinophilia. This immunological association has raised strong interest in the nature of the molecules that promote Th2 and regulatory T cell responses, and the molecular mechanism. Complex carbohydrates are potent inducers of Th2 responses, and carbohydrate antigens (Ags) can stimulate the production of different classes of glycan-specific antibodies (Abs), including Th2 associated IgG but also non-specific IgE. In this review we focus on the immunological responses towards glycan Ags derived from allergens and parasitic helminths, especially schistosomes. Biological effects of carbohydrate Ags are dependent on recognition of these Ags by carbohydrate- binding proteins (lectins). Cell-surface C-type lectin receptors (CLRs), such as DCSIGN, L-SIGN, the mannose receptor, macrophage galactose binding lectin, and other lectins, such as the soluble collectins and galectin-3, recognize particular glycan Ags of schistosomes and allergens, which may contribute to orchestrate Th2 associated adaptive responses. Remarkably, schistosomes express 'self glycan' Ags that are recognized by CLRs on DCs, whose principal function is thought to capture self-glycan Ags and generate regulatory T-cells to induce tolerance to these Ags. By expressing such self-glycan Ags, schistosomes may deceive the host immune system to their own benefit. The host protects itself against too much damage by down-regulating helminth-induced Th2 immune responses, and may thus simultaneously be protected against excessive Th2 cell-mediated allergic responses.


Rapid detection of single cell bacteria as a novel approach in food microbiology.
Solid-phase cytometry (SPC) is a novel technique that allows rapid detection of bacteria at the single cell level, without the need for a growth phase. After filtration of the sample, the retained microorganisms are fluorescently labeled on the membrane filter and automatically counted by a laser scanning device. Each fluorescent spot can be visually inspected with an epifluorescence microscope connected to the ChemScan by a computer-driven moving stage. Depending on the fluorogenic labels used, information on the identity and the physiological status of the microorganisms can be obtained within a few hours. Although SPC was originally recommended for the determination of the total viable microbial count in water and other liquid samples, it may also be a promising technique for the detection and enumeration of bacteria in food samples, provided they can be isolated from the unfilterable matrix. The short detection time inherent in this approach is a considerable advantage over conventional plate counting, especially for slow-growing microorganisms. The basic principles of SPC are discussed as well as its potential for the detection of Mycobacterium paratuberculosis, a model example of a slow-growing bacterium in milk.


[Bf groups in ankylosing spondylitis].
The phenotypes Bf were studied in 50 patients (42 men and 8 women) with definite ankylosing spondylitis and in certain of their relatives. The alleles BfF and BfS were most frequently encountered and the rare allele BfF1 in one case only. There may exist a preferential transmission of the haplotype HLA B27- Bf S. In 11 patients without B27 antigen, the distribution of the phenotypes was similar to that in a control group. It is probable that the locus Bf cannot be used as a preferential marker for ankylosing spondylitis.


The Student-Teacher Relationship Quality of Abused Children.
Considering the association between children's quality of relationships with teachers and their academic adjustment, information pertaining to how abused children are functioning in their relationships with teachers could be useful in promoting their academic success- yet there has been limited research in this area. The purpose of this study was to use cluster analyses to explore within-group differences in relational schemas and quality of student-teacher relationships for 70 abused children. Two clusters of abused children emerged, and as hypothesized, there were significant differences in student-teacher relationships for the two clusters. The cluster with more positive relational schemas had less conflict and less dependency reported by their teachers compared to the cluster with negative relational schemas. However, there were no differences between the clusters in terms of closeness with teachers. Implications for practice in schools is discussed.


Immunological aspects of age-related diseases.
The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of naïve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by anti-inflammatory (M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to age-related diseases. Underlying biochemical and metabolic studies will open nutritional treatment.


Evaluation of a scheme for predicting the gram-staining reaction of organisms causing bovine mastitis.
The accuracy of a scheme for predicting the gram-staining reaction of organisms causing bovine mastitis in cows with systemic signs of disease (anorexia) was evaluated over 1 year. Criteria for making the predictions included: season of year, stage of lactation, appearance of milk, detection and duration of teat injuries, and milk odor. It was possible to determine the cause by microbiologic culture of specimens from 136 of the 147 cows of the study. Of 78 infections caused by gram-negative (mostly coliform) organisms, 62 (79%) were predicted accurately to be caused by gram-negative organisms. Of 57 infections caused by gram-positive organisms, 45 (79%) were predicted correctly to be caused by gram-positive organisms. Correctly predicted as gram-positive organisms causing infection were: Actinomyces pyogenes in 20 of 21 (95%) cows; Staphylococcus sp in 14 of 22 (64%) cows; Streptococcus sp in 10 of 13 (77%) cows and Bacillus sp in 1 cow. Overall accuracy, in those instances when bacteria were isolated (136 cows), was 78%.


Human subjects--are they protected?
From the time of Hippocrates, physicians have sworn to "abstain from all intentional wrongdoing and harm," (Lifton, 1986). They are guided by ethical principles and theories that are intended to help them in their practice of medicine and scientific research. The purpose of this paper was to define research and human subjects, to review cases of abuse, address benefits and risks of human experimentation, discuss regulations governing experiments on humans, and address ethical principles and theories regarding this type of research. Human experimentation is an important activity of great societal benefit that must be conducted in a manner consistent with basic societal beliefs and values about the rights and worth of an individual (Gray, 1975). Ethical issues in human experimentation defy definite solutions, and the problems involved in human experimentation will almost certainly continue to receive active attention in future years.


Urine screening for clients with learning disabilities.
This article describes a study carried out to explore how common urinary tract infections are among adults with learning disabilities who use continence products. The study also evaluated the use of a product to assist urine sample collection with this client group.


[Studies on the effects of chromium complexes].
The existence of chromium complexes in nature, their industrial uses, and their health impacts were reviewed in this paper. The toxic and the formation of Cr(V/IV) complexes and the mechanisms of DNA damage were discussed in particular. The major damaging species responsible for the genotoxicity were Cr(V) or Cr(IV) complexes. However, the function of reactive organic intermediates could not be excluded.


[Development of functional 1H MRI probes based on nanoparticle design].
Visualization of biomolecules in living bodies has attracted increasing attention in recent years. Magnetic resonance imaging (MRI) is a noninvasive technique that yields high-resolution structural information of deep anatomical regions; therefore, it has promising applications in the development of probes to visualize biological functions. By using stimuli-responsive polymers, we developed (1)H MRI probes to measure the pH of aqueous solutions. The longitudinal relaxivity of P-Gd, a conjugate of n-octylamine-modified poly(SM-EVE) with Gd(3+) complexes, increased as the pH of the solution decreased from neutral to acidic. Fluorometric investigation confirmed that the side chains of P-Gd were more rotationally restricted in acidic pH than in neutral pH conditions. In order to improve the magnitude of relaxivity, we developed novel probes C10-Gd and C30-Gd on the basis of cross-linked polymer nanoparticles. The relaxivities of these probes were measured, and the values showed that these nanoparticle-based probes also possessed pH-responsive molecular switches. In addition, their relaxivities were much larger than those of non-cross-linked probes. These nanoparticle-based MRI probes would be useful for the diagnosis of various diseases such as cancer and inflammatory diseases.


Determination of thyroxine in urine by cathodic stripping square-wave voltammetry.
A square-wave polarographic method for the determination of the amino acid thyroxine in urine, after isolation from the matrix on a C18 Sep-Pak cartridge and subsequent elution through a column packed with Amberlite IRA-400 anionic resin, was developed. The optimal working conditions for the application of the method were found to be pH 10, provided by a carbonate buffer, and a potential of -0.690 V during 10 min. The equilibration time was applied during 5 s, and potential scans were performed at a square-wave amplitude of 100 mV and a scan rate of 300 mV s-1, with a square-wave frequency of 100 Hz. The measuring-system response was linear over the thyroxine concentration range from 10 to 60 ng ml-1 and the detection limit achieved was 2.71 ng ml-1. The relative error and relative standard deviation obtained were 1.18 and 4.67%, respectively.


A Year of Advances in Precision Therapy for Blood Cancers.
Recent advances in precision therapies of blood cancers are highlighted here, adapted from the 13th edition of the annual AACR Cancer Progress Report (https://cancerprogressreport.aacr.org/progress/) to U.S. Congress and the public.


Effect of the angiotensin II receptor antagonist telmisartan on lipoprotein lipase mass in preheparin serum.
Lipoprotein lipase protein exists in preheparin serum (preheparin LpL mass), even though lipoprotein lipase activity is rarely detected. Recent clinical studies have clarified that low preheparin LpL mass concentration is an important coronary risk factor. The aim of this study was to clarify the effect of telmisartan, which is an angiotensin II receptor antagonist with partial peroxisome proliferator-activated receptor-gamma agonist activity, on preheparin LpL mass concentration in the serum of patients with hypertension. Fifty untreated hypertensive patients were treated with telmisartan 40 mg/day for 12 weeks and the subjects were divided into two groups by their mean value of preheparin LpL mass concentration at baseline (cut-off level: Male 55 ng/mL, Female 65 ng/mL). Before telmisartan therapy, low preheparin LpL mass concentration was closely associated with the pathogenesis of insulin resistance and the presence of coronary atherosclerosis. Preheparin LpL mass concentration significantly increased after telmisartan therapy in subjects with a low preheparin LpL mass concentration (baseline/12 weeks after, 46 +/- 12 ng/mL/54 +/- 14 ng/mL, p=0.001). This finding indicated that telmisartan could prevent the occurrence of coronary events in subjects with hypertension by increasing the preheparin LpL mass concentration.


Function-based classification of hazardous biological sequences: Demonstration of a new paradigm for biohazard assessments.
Bioengineering applies analytical and engineering principles to identify functional biological building blocks for biotechnology applications. While these building blocks are leveraged to improve the human condition, the lack of simplistic, machine-readable definition of biohazards at the function level is creating a gap for biosafety practices. More specifically, traditional safety practices focus on the biohazards of known pathogens at the organism-level and may not accurately consider novel biodesigns with engineered functionalities at the genetic component-level. This gap is motivating the need for a paradigm shift from organism-centric procedures to function-centric biohazard identification and classification practices. To address this challenge, we present a novel methodology for classifying biohazards at the individual sequence level, which we then compiled to distinguish the biohazardous property of pathogenicity at the whole genome level. Our methodology is rooted in compilation of hazardous functions, defined as a set of sequences and associated metadata that describe coarse-level functions associated with pathogens (e.g., adherence, immune subversion). We demonstrate that the resulting database can be used to develop hazardous "fingerprints" based on the functional metadata categories. We verified that these hazardous functions are found at higher levels in pathogens compared to non-pathogens, and hierarchical clustering of the fingerprints can distinguish between these two groups. The methodology presented here defines the hazardous functions associated with bioengineering functional building blocks at the sequence level, which provide a foundational framework for classifying biological hazards at the organism level, thus leading to the improvement and standardization of current biosecurity and biosafety practices.


The effect of amniotic fluid on intraperitoneal adhesion formation--an experimental study.
In an attempt to investigate the relative paucity of intraperitoneal adhesions after cesarean sections, we tested the effect of amniotic fluid on adhesion formation in rat model. Trauma was induced to the uterine serosa in 40 rats. Amniotic fluid was intraperitoneally instilled in 20 rats and saline in another 20 rats acting as controls. No inhibitory effect of the amniotic fluid could be demonstrated. The effect of the amniotic fluid and the saline solutions on fibroblastic proliferation was examined in vitro using fibroblastic cell cultures. No direct effect on fibroblast proliferation was found. It is concluded that it is not the direct effect of the spilled amniotic fluid that inhibits adhesion formation after the performance of cesarean sections.


Papillary stenosis.
The present state of papillary stenosis is reviewed. ERCP manometry has become the most important means of evaluating sphincter of Oddi dynamics. Pressure measurements in the sphincter segment appear useful to differentiate patients with sphincter of Oddi dysfunction from patients with an organic stenosis. The author's experience with sphincter of Oddi manometry, with endoscopic sphincterotomy and hydrostatic balloon dilation of the sphincter of Oddi, and the results of an international inquiry, are presented.


The vertical dimension: the high-angle problem.
When the patient who has excessive anterior facial height desires treatment for the correction of a malocclusion, the dimension of the dentition should be respected. The clinician must adhere to the anterior, posterior, vertical, and lateral limits of each patient's dentition--providing the musculature is normal--when the treatment plan is formulated. The goals of esthetics, health and function, stability, and treatment in harmony with growth are as valid for the high-angle patient as they are for a patient with a more normal vertical dimension. The diagnostic decisions made for the high-angle patient should be predicated on nonexpansion of the mandibular arch. Mandibular incisors must be overly upright. In addition, a decision on the mandibular third molars must be made prior to anchorage preparation-because their relationship to the mandibular second molars is critical if anchorage is to be properly prepared. A discussion of these topics as well as an illustrative case report are presented in this article.


Aspergillosis in Chronic Granulomatous Disease.
Patients with chronic granulomatous disease (CGD) have the highest life-time incidence of invasive aspergillosis and despite the availability of antifungal prophylaxis, infections by Aspergillus species remain the single most common infectious cause of death in CGD. Recent developments in curative treatment options, such as haematopoietic stem cell transplantation, will change the prevalence of infectious complications including invasive aspergillosis in CGD patients. However, invasive aspergillosis in a previously healthy host is often the first presenting feature of this primary immunodeficiency. Recognizing the characteristic clinical presentation and understanding how to diagnose and treat invasive aspergillosis in CGD is of utmost relevance to improve clinical outcomes. Significant differences exist in fungal epidemiology, clinical signs and symptoms, and the usefulness of non-culture based diagnostic tools between the CGD host and neutropenic patients, reflecting underlying differences in the pathogenesis of invasive aspergillosis shaped by the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase deficiency.


A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol.
Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. NCT02720822; Pre-results.


Fully Automated Quantitative Estimation of Volumetric Breast Density from Digital Breast Tomosynthesis Images: Preliminary Results and Comparison with Digital Mammography and MR Imaging.
To assess a fully automated method for volumetric breast density (VBD) estimation in digital breast tomosynthesis (DBT) and to compare the findings with those of full-field digital mammography (FFDM) and magnetic resonance (MR) imaging. Bilateral DBT images, FFDM images, and sagittal breast MR images were retrospectively collected from 68 women who underwent breast cancer screening from October 2011 to September 2012 with institutional review board-approved, HIPAA-compliant protocols. A fully automated computer algorithm was developed for quantitative estimation of VBD from DBT images. FFDM images were processed with U.S. Food and Drug Administration-cleared software, and the MR images were processed with a previously validated automated algorithm to obtain corresponding VBD estimates. Pearson correlation and analysis of variance with Tukey-Kramer post hoc correction were used to compare the multimodality VBD estimates. Estimates of VBD from DBT were significantly correlated with FFDM-based and MR imaging-based estimates with r = 0.83 (95% confidence interval [CI]: 0.74, 0.90) and r = 0.88 (95% CI: 0.82, 0.93), respectively (P < .001). The corresponding correlation between FFDM and MR imaging was r = 0.84 (95% CI: 0.76, 0.90). However, statistically significant differences after post hoc correction (α = 0.05) were found among VBD estimates from FFDM (mean ± standard deviation, 11.1% ± 7.0) relative to MR imaging (16.6% ± 11.2) and DBT (19.8% ± 16.2). Differences between VDB estimates from DBT and MR imaging were not significant (P = .26). Fully automated VBD estimates from DBT, FFDM, and MR imaging are strongly correlated but show statistically significant differences. Therefore, absolute differences in VBD between FFDM, DBT, and MR imaging should be considered in breast cancer risk assessment.


Overexpression of OsMYB305 in Rice Enhances the Nitrogen Uptake Under Low-Nitrogen Condition.
Excessive nitrogen fertilizer application causes severe environmental degradation and drives up agricultural production costs. Thus, improving crop nitrogen use efficiency (NUE) is essential for the development of sustainable agriculture. Here, we characterized the roles of the MYB transcription factor OsMYB305 in nitrogen uptake and assimilation in rice. OsMYB305 encoded a transcriptional activator and its expression was induced by N deficiency in rice root. Under low-N condition, OsMYB305 overexpression significantly increased the tiller number, shoot dry weight and total N concentration. In the roots of OsMYB305-OE rice lines, the expression of OsNRT2.1, OsNRT2.2, OsNAR2.1, and OsNiR2 was up-regulated and 15NO3 - influx was significantly increased. In contrast, the expression of lignocellulose biosynthesis-related genes was repressed so that cellulose content decreased, and soluble sugar concentration increased. Certain intermediates in the glycolytic pathway and the tricarboxylic acid cycle were significantly altered and NADH-GOGAT, Pyr-K, and G6PDH were markedly elevated in the roots of OsMYB305-OE rice lines grown under low-N condition. Our results revealed that OsMYB305 overexpression suppressed cellulose biosynthesis under low-nitrogen condition, thereby freeing up carbohydrate for nitrate uptake and assimilation and enhancing rice growth. OsMYB305 is a potential molecular target for increasing NUE in rice.


Stepping into the shoes of the policy maker: Results of a Participatory Value Evaluation for the Dutch long term COVID-19 strategy.
The COVID-19 outbreak early 2020 was followed by an unprecedented package of measures. The relative calmness of the pandemic early 2022 provides a momentum to prepare for various scenarios. As acceptance of COVID-19 measures is key for public support we investigated citizens' preferences towards imposing measures in four scenarios: 1) spring/summer scenario with few hospitalizations; 2) autumn/winter scenario with many hospitalizations; 3) a new contagious variant, the impact on hospitalizations is unclear; 4) a new contagious variant, hospitalizations will substantially increase. Study 1 comprised a Participatory Value Evaluation (PVE) in which 2011 respondents advised their government on which measures to impose in the four scenarios. Respondents received information regarding the impact of each measure on the risk that the health system would be overloaded. To triangulate the results, 2958 respondents in Study 2 evaluated the acceptability of the measures in each scenario. Measures were ranked similarly by respondents in Study 1 and 2: 1) the majority of respondents thought that hygiene measures should be upheld, even in the spring/summer; 2) the majority supported booster vaccination, working from home, encouraging self-testing, and mandatory face masks from scenario 2 onwards; 3) even in scenario 4, lockdown measures were not supported by the majority. Young respondents were willing to accept more risks for the health system than older respondents. The results suggest that policies that focus on prevention (through advising low-impact hygiene measures) and early response to moderate threats (by scaling up to moderately restrictive measures and boostering) can count on substantial support. There is low support for lockdown measures even under high-risk conditions, which further emphasizes the importance of prevention and a timely response to new threats. Our results imply that young citizens' concerns, in particular, should be addressed when restrictive COVID-19 measures are to be implemented.


Investigation of upper gastrointestinal bleeding after implantation of drug-eluting stents; prospective cohort study.
After implantation of drug-eluting stents (DES), two or more anti-thrombotic agents are required. The risk of upper gastrointestinal bleeding (UGIB) in cases of DES implantation is thought to be significant. However, the incidence of UGIB has not yet been investigated in DES-implanted patients. This study aimed to investigate the incidence of UGIB after DES implantation and the awareness among cardiologists about this complication. Subjects were 397 consecutive patients implanted with DES from August 2004 to September 2007 at two institutions. Endoscopic examinations were performed on DES-implanted patients who presented with hematemesis and/or tarry stools. The concomitant use of acid-suppressing agents was left to the cardiologists. In addition, 37 cardiologists were administered a questionnaire regarding UGIB after DES implantation. Low-dose aspirin and ticlopidine were prescribed in all patients. Forty-six patients had a past history of peptic ulcer. Acid-suppressing agents were concomitantly prescribed to 224 patients (56%) including 32 patients (70%) with a past history of peptic ulcer. UGIB due to gastric ulcers developed in 5 cases (1.3%). One case had received a half dose of H2-RA. No bleeding occurred in patients who received proton pump inhibitors (PPI). The incidence of UGIB was 4.0 per 1000 patient-years. The cardiologists who were surveyed recognized the risk of UGIB after DES implantation and the necessity for its prevention. However, they indicated that adequate management for preventing this complication has not been established. This study reassuringly demonstrated a low incidence of UGIB after DES implantation. Further study regarding the prophylaxis for UGIB after DES implantation is necessary.


A retrospective study of emergency department potassium disturbances: severity, treatment, and outcomes.
Disturbances in potassium (K) levels are relatively common and may be associated with significant morbidity and mortality; however, treatments vary. Our purpose was to determine the incidence, treatments, and outcomes associated with hyperkalemia and hypokalemia in emergency department (ED) patients. We performed a structured, retrospective review of electronic medical records of consecutive adult ED patients with K measured while in the ED. Demographic, clinical, and laboratory data as well as treatments, disposition, and in-hospital complications were collected. Univariate and multivariate analyses, presented as adjusted odds ratios, were used to compare outcomes by K levels. Of 100,260 visits in 2014, an ED K level was ordered in 48,827 (49%). A total of 1,738 patients (3.6%) were excluded because of sample hemolysis. The K was low (<3.5 mEq/L) in 5.5%, normal (3.5 to 5.0 mEq/L) in 90.9%, and elevated (>5.0 mEq/L) in 3.6% of patients. Patients with hyperkalemia were older (64 vs. 49 years, P<0.001) and more likely male (58% vs. 40%, P<0.001). Treatment for hyperkalemia varied greatly. After adjusting for confounders, both hyperkalemia and hypokalemia were associated with inpatient hospitalization and death. At least one medication was used to manage hyperkalemia in 11.5% of patients with a K of 5.1 to 5.4 mEq/L, 36.4% of those with a K 5.5 to 6 mEq/L and 77.0% of the cohort with K >6 mEq/L. Hyperkalemia or hypokalemia occur in 1 of 11 ED patients and are associated with inpatient admission and mortality. Treatment of hyperkalemia varies greatly suggesting the need for evidence-based treatment guidelines.


Endothelin-1 and nitric oxide levels in patients with mitral annulus calcification.
Mitral annulus calcification (MAC) is a chronic degenerative noninflammatory process. The goal of this study was to determine endothelin-1 (ET-1) and nitric oxide (NOx) levels in patients with MAC and compare them with those in normal subjects. The study group included 39 patients [26 females (66%), age, 63 +/- 8 years] with MAC and 20 [11 females (55%), age, 61 +/- 7 years] healthy subjects. The patients were divided into two subgroups, group A with severe MAC and group B with mild MAC, according to the severity of the MAC. Plasma ET-1 levels were higher and NOx levels were lower in patients than controls [(6.5 +/- 5.6 pg/mL vs 3.7 +/- 2.9 pg/mL for ET-1 and 35.0 +/- 10.6 micromol/L vs 42.3 +/- 9.9 micromol/L for NOx; P < 0.05 for both)]. In the subgroups, ET-1 levels were higher in group A than group B (8.65 +/- 6.84 pg/mL vs 4.74 +/- 3.45 pg/mL, P < 0.05) and the control group (8.65 +/- 6.84 pg/mL vs 3.70 +/- 2.88 pg/mL, P < 0.05). There was no difference between group B and the control group. Plasma NOx levels were significantly decreased in group A compared to controls (32.22 +/- 11.88 micromol/L vs 42.25 +/- 9.99 micromol/L, P < 0.05). However, no significant difference was observed between group B (37.38 +/- 9.06 micromol/L) and the other groups. Diabetes mellitus, coronary artery disease, and dyslipidemia were significantly associated with ET-1 levels. However, this association was not observed for NOx. In conclusion, patients with MAC have increased ET-1 and decreased NOx levels. This seems to be more prominent in patients with severe MAC.


The estimated benefits of vitamin D for Germany.
This article gives an overview of the vitamin D status in Germany, provides evidence for an independent association of vitamin D deficiency with various chronic diseases, and discusses preventive measures for improving vitamin D status in Germany. The prevalence of vitamin D insufficiency is 40-45% in the general German population. An additional 15-30% are vitamin D deficient. Vitamin D can prevent falls and osteoporotic fractures in older people. There is also accumulating evidence that vitamin D may prevent excess mortality and may probably prevent some chronic diseases that occur in early life such as type 1 diabetes and multiple sclerosis. Adherence to present sun safety policy (avoidance of the sun between 11 am and 3 pm) and dietary recommendations (5-10 microg daily for adults) would, however, definitively lead to vitamin D deficiency. The estimated cost saving effect of improving vitamin D status in Germany might be up to 37.5 billion euro annually. It should be the goal of nutrition and medical societies to erase vitamin D deficiency in Germany within the next 5-10 years. To achieve this goal, the daily production of at least 25 microg of vitamin D in the skin or an equivalent oral intake should be guaranteed.


How many cores should be taken in a repeat biopsy on patients in whom atypical small acinar proliferation has been identified in an initial transrectal prostate biopsy?
To compare cancer detection rates according to the number of biopsy cores in patients on whom a repeat prostate biopsy was performed for atypical small acinar proliferation (ASAP). The data of 4950 consecutive patients on whom prostate biopsies were performed were assessed retrospectively. A total of 107 patients were identified as having ASAP following an initial prostate biopsy, and they were included in the study. A six-core prostate biopsy (PBx) was performed on 15 of the 107 patients, 12 PBx on 32 patients, and 20 PBx on 60 patients. Cancer detection rates were compared according to the number of biopsy cores. The localization of the cancer foci was also evaluated. The cancer detection rates in patients on whom 6 PBx, 12 PBx, and 20 PBx were performed were 20% (3/15), 31% (10/32), and 58% (35/60), respectively, and a statistically significant difference was found (p = 0.005). When cancer detection rates in patients with total prostate specific antigen (PSA) < 10ng/mL, PSA density ≥ 0.15, normal digital rectal examination, and prostate volume ≥ 55mL were compared according to the number of biopsy cores, a significant difference was identified (p = 0.02, 0.03, 0.006, and 0.04, respectively). Seventy-five percent of the foci where cancer was detected were at the same and/or adjacent sites as the ASAP foci in the initial biopsy, and 54% were identified in contralateral biopsies in which ASAP foci were present. As the biopsy core number increases, the cancer detection rate increases significantly in patients on whom a repeat biopsy is performed due to ASAP. The highest cancer rate is found in 20-core repeat biopsies performed equally from all foci.


Deep shaving and transanal disc excision in large endometriosis of mid and lower rectum: the Rouen technique.
Colorectal resection is performed in a majority of patients presenting with large endometriosis of mid and lower rectum; however, it may negatively and irreversibly impact postoperative rectal function. To avoid such unfavourable outcomes, we propose an original technique combining laparoscopic deep rectal shaving and transanal disc excision using a semi-circular stapler. The video presents the procedure performed in a 29-year-old nullipara referred with a large endometriotic nodule infiltrating the lower rectum on more than 30 mm length. The first step is laparoscopic and involves deep rectal shaving performed using exclusively the plasma energy. Then, transanal excision of shaved area is performed, by placing traction parachute sutures in the middle and outside the shaved area. Their traction induces the prolapse of shaved area that is resected using a semicircular stapler. Insufflating the rectum with air checks the integrity of the staple line. Operative time was 210 min. Immediate postoperative outcomes were uneventful, and bowel movements were normal beginning with day 6. Our technique is suitable in large rectal nodules located up to 10 cm above the anus, infiltrating the rectum on up to 6 cm length, and these parameters are preoperatively assessed using MRI and computed tomography. To date, it was successfully carried out in 29 women with large deep endometriosis of the mid and lower rectum. Rectovaginal fistula was recorded in one patient (3.6 %) and transitory bladder dysfunction in seven patients (25 %). Digestive function assessment using standardized questionnaires revealed an overall improvement, without de novo anal continence troubles. Postoperative pregnancy rate was 78 % with a majority of patients having conceived spontaneously. Based on our experience, we believe that our conservative technique is feasible and reproducible in large mid and lower rectal endometriosis and might avoid the risk of unfavourable outcomes related to low colorectal resection.


Invited Commentary: Population Health in Peril-Needed US Science and Public Policy Action.
With unprecedented increases, mortality trends in the United States have received significant attention in recent years. To date, research on this topic has emphasized specific causes of death and proximal behavioral or physiological determinants. In this commentary, I consider novel contributions of Zheng and Echave (Am J Epidemiol. 2021;190(11):2242-2255) in examining trends in mental health, health behaviors, and physiological dysregulation. I then discuss broader developments in related research and make a case for: 1) not allowing recent health trends among Whites to overshadow the urgent work that needs to be done to mitigate persistent racial inequities, 2) further investigation of what accounts for increases in income inequality and its life-span health consequences, and 3) broadening the scope of mechanisms considered to include underdiscussed topics such as the role of increases in social media use or environmental toxicant exposures. Underlying several potential explanations for observed trends in health and mortality is the fact that substantial change has occurred on multiple fronts in US society and that policy responses to these changes have been insufficient. An enhanced emphasis on innovative population health research will be essential to provide the evidence base needed for policy makers to rise to these urgent challenges.