Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.
Glucokinase is a key regulatory enzyme in the pancreatic beta-cell. It plays a crucial role in the regulation of insulin secretion and has been termed the glucose sensor in pancreatic beta-cells. Given its central role in the regulation of insulin release it is understandable that mutations in the gene encoding glucokinase (GCK) can cause both hyper- and hypoglycemia. Heterozygous inactivating mutations in GCK cause maturity-onset diabetes of the young (MODY) subtype glucokinase (GCK), characterized by mild fasting hyperglycemia, which is present at birth but often only detected later in life during screening for other purposes. Homozygous inactivating GCK mutations result in a more severe phenotype presenting at birth as permanent neonatal diabetes mellitus (PNDM). A growing number of heterozygous activating GCK mutations that cause hypoglycemia have also been reported. A total of 620 mutations in the GCK gene have been described in a total of 1,441 families. There are no common mutations, and the mutations are distributed throughout the gene. The majority of activating mutations cluster in a discrete region of the protein termed the allosteric activator site. The identification of a GCK mutation in patients with both hyper- and hypoglycemia has implications for the clinical course and clinical management of their disorder.


The value of measuring height and weight of schoolchildren.
The measurements of height and weight in the Stockholm school health service was appraised in relation to the screening value, the costs and benefits. The concept of a doubtful screening value of growth surveillances at school age was supported. Investment costs and running expenses were very low. The measurement procedure used only 2% of the total time spent by the nurses in the school health service. The growth data were an appropriate prerequisite for the reassurance of adolescents about their developing identity and body image. The growth data also constituted an appropriate indicator for public heath research. The benefits and low costs may justify maintenance of the measurements in the school health service despite a low screening value.


Comparison of antihypertensive effects of nicardipine with nitroglycerin for perioperative hypertension.
To compare the efficacy of intravenous (iv) nicardipine with nitroglycerin for the treatment for patients with perioperative hypertension. Forty patients with perioperative hypertension randomly divided into two groups were treated with intravenous calcium entry blocker, nicardipine, or vasodilator, nitroglycerin. Haemodynamic measurements including mean arterial and pulmonary arterial pressure, central venous and pulmonary capillary wedge pressure, and cardiac output were recorded; peripheral and pulmonary vascular resistance were calculated. Both medications were effective in reducing blood pressure and controlling haemodynamics. During the maintenance by continuous iv infusion, nicardipine controlled hypertension more rapidly than nitroglycerin (nicardipine 10.5 +/- 2.5 min and nitroglycerin 18.7 +/- 2.8 min, p < 0.05) without significant alteration in heart rate. The total frequency of dose adjustments required to achieve therapeutic response was significantly less in the nicardipine-treated group (2.5 +/- 0.3 for nicardipine and 6.2 +/- 1.4 for nitroglycerin, p < 0.05). Incidence of hypotensive episodes during the infusion were observed in both groups [nicardipine 5% (1/20) and nitroglycerin 30% (6/20), p < 0.05]. Intravenous nicardipine is as effective as nitroglycerin in the treatment of perioperative hypertension. Specific advantages have been identified such as stable dose-response effect, less hypotensive and tachycardial effects during the use of iv nicardipine in treatment of hypertensive patients.


Oblique color vision in an open-habitat bird: spectral sensitivity, photoreceptor distribution and behavioral implications.
Color vision is not uniform across the retina because of differences in photoreceptor density and distribution. Retinal areas with a high density of cone photoreceptors may overlap with those with a high density of ganglion cells, increasing hue discrimination. However, there are some exceptions to this cell distribution pattern, particularly in species with horizontal visual streaks (bands of high ganglion cell density across the retina) that live in open habitats. We studied the spectral sensitivity and distribution of cone photoreceptors involved in chromatic and achromatic vision in the Canada goose (Branta canadiensis), which possesses an oblique rather than horizontal visual streak at the ganglion cell layer. Using microspectrophotometry, we found that the Canada goose has a violet-sensitive visual system with four visual pigments with absorbance peaks at 409, 458, 509 and 580 nm. The density of most cones involved in chromatic and achromatic vision peaked along a band across the retina that matched the oblique orientation of the visual streak. With the information on visual sensitivity, we calculated chromatic and achromatic contrasts of different goose plumage regions. The regions with the highest visual saliency (cheek, crown, neck and upper tail coverts) were the ones involved in visual displays to maintain flock cohesion. The Canada goose oblique visual streak is the retinal center for chromatic and achromatic vision, allowing individuals to sample the sky and the ground simultaneously or the horizon depending on head position. Overall, our results show that the Canada goose visual system has features that make it rather different from that of other vertebrates living in open habitats.


Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia.
A compound identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) was found in higher concentrations in urine samples of children with autism compared to age and sex appropriate controls and in an adult with recurrent diarrhea due to Clostridium difficile infections. The highest value measured in urine samples was 7500 mmol/mol creatinine, a value 300 times the median normal adult value, in a patient with acute schizophrenia during an acute psychotic episode. The psychosis remitted after treatment with oral vancomycin with a concomitant marked decrease in HPHPA. The source of this compound appears to be multiple species of anaerobic bacteria of the Clostridium genus. The significance of this compound is that it is a probable metabolite of m-tyrosine (3-hydroxyphenylalanine), a tyrosine analog which depletes brain catecholamines and causes symptoms of autism (stereotypical behavior, hyperactivity, and hyper-reactivity) in experimental animals.


Dual effect of nerve growth factor on cell death of PC12 cells Induced by serum deprivation.
The effect of nerve growth factor (NGF) on the cell death of PC12 cells that is induced by serum deprivation was examined in the floating and attached cells to the extracellular matrix. NGF suppressed cell death occurred in the floating cells. The onset of cell death in the attached cells was much slower than in the floating cells. Moreover, the cell death in the attached cells was either accelerated in a high-density culture (over approximately 50% confluent), or inhibited in a low-density culture by NGF. While nucleosomal DNA fragmentation and poly (ADP-ribose) polymerase degradation was observed in both the floating and attached cells, the incidence of nuclear fragmentation and chromatin condensation was much lower in the attached cells than in the floating cells. The delayed onset of cell death in the attached cells was due to the signals that are generated from the extracellular matrix that is formed by PC12 cells, together with cell-to-cell interaction. The acceleration of cell death in the NGF-treated cells was anoikis, caused by the loss of the anchorage of the cell via the action of increased activities of matrix metalloproteinases (MMP2, MMP9). These results suggest that NGF has a different role in the cell death of PC12 cells that is induced by serum deprivation, depending on the cell-matrix, as well as the cell-cell interaction.


Self-suspended suspensions of covalently grafted hairy nanoparticles.
Dispersions of small particles in liquids have been studied continuously for almost two centuries for their ability to simultaneously advance understanding of physical properties of fluids and their widespread use in applications. In both settings, the suspending (liquid) and suspended (solid) phases are normally distinct and uncoupled on long length and time scales. In this study, we report on the synthesis and physical properties of a novel family of covalently grafted nanoparticles that exist as self-suspended suspensions with high particle loadings. In such suspensions, we find that the grafted polymer chains exhibit unusual multiscale structural transitions and enhanced conformational stability on subnanometer and nanometer length scales. On mesoscopic length scales, the suspensions display exceptional homogeneity and colloidal stability. We attribute this feature to steric repulsions between grafted chains and the space-filling constraint on the tethered chains in the single-component self-suspended materials, which inhibits phase segregation. On macroscopic length scales, the suspensions exist as neat fluids that exhibit soft glassy rheology and, counterintuitively, enhanced elasticity with increasing temperature. This feature is discussed in terms of increased interpenetration of the grafted chains and jamming of the nanoparticles.


Natural occurrence of the diamond hexagonal structure in silicon nanowires grown by a plasma-assisted vapour-liquid-solid method.
Silicon nanowires have been grown by a plasma-assisted vapour-liquid-solid method using tin as the catalyst. Transmission electron microscopy in the [12[combining macron]10] zone axis shows that the diamond hexagonal (P63/mmc) crystal structure is present in several nanowires. This is the first unambiguous proof of the natural occurrence of this metastable phase to our knowledge.


Altered expression of testis-specific genes, piRNAs, and transposons in the silkworm ovary masculinized by a W chromosome mutation.
In the silkworm, Bombyx mori, femaleness is strongly controlled by the female-specific W chromosome. Originally, it was presumed that the W chromosome encodes female-determining gene(s), accordingly called Fem. However, to date, neither Fem nor any protein-coding gene has been identified from the W chromosome. Instead, the W chromosome is occupied with numerous transposon-related sequences. Interestingly, the silkworm W chromosome is a source of female-enriched PIWI-interacting RNAs (piRNAs). piRNAs are small RNAs of 23-30 nucleotides in length, which are required for controlling transposon activity in animal gonads. A recent study has identified a novel mutant silkworm line called KG, whose mutation in the W chromosome causes severe female masculinization. However, the molecular nature of KG line has not been well characterized yet. Here we molecularly characterize the KG line. Genomic PCR analyses using currently available W chromosome-specific PCR markers indicated that no large deletion existed in the KG W chromosome. Genetic analyses demonstrated that sib-crosses within the KG line suppressed masculinization. Masculinization reactivated when crossing KG females with wild type males. Importantly, the KG ovaries exhibited a significantly abnormal transcriptome. First, the KG ovaries misexpressed testis-specific genes. Second, a set of female-enriched piRNAs was downregulated in the KG ovaries. Third, several transposons were overexpressed in the KG ovaries. Collectively, the mutation in the KG W chromosome causes broadly altered expression of testis-specific genes, piRNAs, and transposons. To our knowledge, this is the first study that describes a W chromosome mutant with such an intriguing phenotype.


NME1 Drives Expansion of Melanoma Cells with Enhanced Tumor Growth and Metastatic Properties.
Melanoma is a lethal skin cancer prone to progression and metastasis, and resistant to therapy. Metastasis and therapy resistance of melanoma and other cancers are driven by tumor cell plasticity, largely via acquisition/loss of stem-like characteristics and transitions between epithelial and mesenchymal phenotypes (EMT/MET). NME1 is a metastasis suppressor gene that inhibits metastatic potential when its expression is enforced in melanoma and other cancers. Herein, we have unmasked a novel role for NME1 as a driver of melanoma growth distinct from its canonical function as a metastasis suppressor. NME1 promotes expansion of stem-like melanoma cells that exhibit elevated expression of stem cell markers (e.g., Sox2, Sox10, Oct-4, KLF4, and Ccnb-1), enhanced growth as melanoma spheres in culture, and enhanced tumor growth and lung colonizing activities in vivo. In contrast, NME1 expression did not affect the proliferation of melanoma cell lines in monolayer culture conditions. Silencing of NME1 expression resulted in a dramatic reduction in melanoma sphere size, and impaired tumor growth and metastatic activities of melanoma sphere cells when xenografted in immunocompromised mice. Individual cells within melanoma sphere cultures displayed a wide range of NME1 expression across multiple melanoma cell lines. Cell subpopulations with elevated NME1 expression were fast cycling and displayed enhanced expression of stem cell markers. IMPLICATIONS: Our findings suggest the current model of NME1 as a metastasis-suppressing factor requires refinement, bringing into consideration its heterogeneous expression within melanoma sphere cultures and its novel role in promoting the expansion and tumorigenicity of stem-like cells.


Management of severe acute malnutrition in children under 5 years through the lens of health care workers in two rural South African hospitals.
Despite the widespread implementation of the World Health Organization (WHO) guidelines for the management of severe malnutrition in South Africa, poor treatment outcomes for children under 5 years are still observed in some hospitals, particularly in rural areas. To explore health care workers' perceptions about upstream and proximal factors contributing to poor treatment outcomes for severe acute malnutrition in two district hospitals in South Africa. An explorative descriptive qualitative study was conducted. Four focus group discussions were held with 33 hospital staff (senior clinical and management staff, and junior clinical staff) using interview guide questions developed based on the findings from an epidemiological study that was conducted in the same hospitals. Qualitative data were analysed using the framework analysis. Most respondents believed that critical illness, which was related to early and high case fatality rates on admission, was linked to a web of factors including preference for traditional medicine over conventional care, gross negligence of the child at household level, misdiagnosis of severe malnutrition at the first point of care, lack of specialised skills to deal with complex presentations, shortage of patient beds in the hospital and policies to discharge patients before optimal recovery. The majority believed that the WHO guidelines were effective and relatively simple to implement, but that they do not make much difference among severe acute malnutrition cases that are admitted in a critical condition. Poor management of cases was linked to the lack of continuity in training of rotating clinicians, sporadic shortages of therapeutic resources, inadequate staffing levels after normal working hours and some organisational and system-wide challenges beyond the immediate control of clinicians. Findings from this study suggest that effective management of paediatric severe acute malnutrition in the study setting is affected by a multiplicity of factors that manifest at different levels of the health system and the community. A verificatory study is encouraged to collaborate these findings.


IgG4-related sclerosing disease: a critical appraisal of an evolving clinicopathologic entity.
An elevated serum titer of immunoglobulin G4 (IgG4), the least common (3% to 6%) of the 4 subclasses of IgG, is a surrogate marker for the recently characterized IgG4-related sclerosing disease. The syndrome affects predominantly middle-aged and elderly patients, with male predominance. The patients present with symptoms referable to the involvement of 1 or more sites, usually in the form of mass lesions. The prototype is IgG4-related sclerosing pancreatitis (also known as autoimmune pancreatitis), most commonly presenting as painless obstructive jaundice with or without a pancreatic mass. Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, but practically any organ-site can be affected, such as retroperitoneum, aorta, mediastinum, soft tissue, skin, central nervous system, breast, kidney, prostate, upper aerodigestive tract, and lung. The patients usually have a good general condition, with no fever or constitutional symptoms. Common laboratory findings include raised serum globulin, IgG, IgG4, and IgE, whereas lactate dehydrogenase is usually not raised. Some patients have low titers of autoantibodies (such as antinuclear antibodies and rheumatoid factor). The disease often shows excellent response to steroid therapy. The natural history is characterized by the development of multiple sites of involvement with time, sometimes after many years. However, the disease can remain localized to 1 site in occasional patients. The main pathologic findings in various extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, accompanied by atrophy and loss of the specialized structures of the involved tissue (such as secretory acini in pancreas, salivary gland, or lacrimal gland). The relative predominance of the lymphoplasmacytic and sclerotic components results in 3 histologic patterns: pseudolymphomatous, mixed, and sclerosing. Immunostaining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). The lymph nodes show multicentric Castleman disease-like features, reactive follicular hyperplasia, interfollicular expansion, or progressive transformation of germinal centers, with the unifying feature being an increase in IgG4+ plasma cells on immunostaining. The nature and pathogenesis of IgG4-related sclerosing disease are still elusive. Occasionally, the disease can be complicated by the development of malignant lymphoma and possibly carcinoma.


Decreased insulin receptor tyrosine kinase activity and plasma cell membrane glycoprotein-1 overexpression in skeletal muscle from obese women with gestational diabetes mellitus (GDM): evidence for increased serine/threonine phosphorylation in pregnancy and GDM.
The cellular mechanisms for the insulin resistance of pregnancy and gestational diabetes mellitus (GDM) are unknown. The membrane protein plasma cell membrane glycoprotein-1 (PC-1) has been identified as an inhibitor of insulin receptor tyrosine kinase (IRTK) activity. We investigated insulin receptor function and PC-1 levels in muscle from three groups of obese subjects: women with GDM, pregnant women with normal glucose tolerance, and nonpregnant control subjects. Subjects (n = 6 for each group) were similar in age and degree of obesity (body fat >30%). IRTK activity, insulin receptor tyrosine phosphorylation, and protein levels of membrane glycoprotein PC-1 were determined in rectus abdominus muscle biopsies obtained at the time of either elective cesarean section or gynecological surgery. No significant differences were evident in basal insulin receptor tyrosine phosphorylation or IRTK activity in the three groups. After maximal insulin (10(-7) mol/l) stimulation, IRTK activity measured with the artificial substrate poly(Glu,Tyr) increased in all subjects but was lower in women with GDM by 25% (P < 0.05) and 39% (P < 0.001) compared with pregnant and nonpregnant control subjects, respectively. Similarly, insulin receptor tyrosine phosphorylation was significantly decreased in subjects with GDM (P < 0.05) compared with pregnant and nonpregnant control subjects. Treatment of the insulin receptors with alkaline phosphatase to dephosphorylate serine/threonine residues increased insulin-stimulated IRTK activity significantly in pregnant control and GDM subjects (P < 0.05), but these rates were still lower compared with nonpregnant control subjects (P < 0.05). PC-1 content in muscle from GDM subjects was increased by 63% compared with pregnant control subjects (P < 0.05) and by 206% compared with nonpregnant control subjects (P < 0.001). PC-1 content was negatively correlated with insulin receptor phosphorylation (r = -0.55, P < 0.05) and IRTK activity (r = -0.66, P < 0.05). These results indicate that pregnant control and GDM subjects had increased PC-1 content and suggest excessive phosphorylation of serine/threonine residues in muscle insulin receptors and that both may contribute to decreased IRTK activity. These changes worsen in women with GDM when controlling for obesity. These postreceptor defects in insulin signaling may contribute to the pathogenesis of GDM and the increased risk for type 2 diabetes later in life.


Infant feeding practices and determinants of poor breastfeeding behavior in Kinshasa, Democratic Republic of Congo: a descriptive study.
Although breastfeeding is almost universally accepted in the Democratic Republic (DR) of Congo, by the age of 2 to 3 months 65% of children are receiving something other than human milk. We sought to describe the infant feeding practices and determinants of suboptimal breastfeeding behaviors in DR Congo. Survey questionnaire administered to mothers of infants aged ≤ 6 months and healthcare providers who were recruited consecutively at six selected primary health care facilities in Kinshasa, the capital. All 66 mothers interviewed were breastfeeding. Before initiating breastfeeding, 23 gave their infants something other than their milk, including: sugar water (16) or water (2). During the twenty-four hours prior to interview, 26 (39%) infants were exclusively breastfed (EBF), whereas 18 (27%), 12 (18%), and 10 (15%) received water, tea, formula, or porridge, respectively, in addition to human milk. The main reasons for water supplementation included "heat" and cultural beliefs that water is needed for proper digestion of human milk. The main reason for formula supplementation was the impression that the baby was not getting enough milk; and for porridge supplementation, the belief that the child was old enough to start complementary food. Virtually all mothers reported that breastfeeding was discussed during antenatal clinic visit and half reported receiving help regarding breastfeeding from a health provider either after birth or during well-child clinic visit. Despite a median of at least 14 years of experience in these facilities, healthcare workers surveyed had little to no formal training on how to support breastfeeding and inadequate breastfeeding-related knowledge and skills. The facilities lacked any written policy about breastfeeding. Addressing cultural beliefs, training healthcare providers adequately on breastfeeding support skills, and providing structured breastfeeding support after maternity discharge is needed to promote EBF in the DR Congo.


Photomutagenicity of retinyl palmitate by ultraviolet a irradiation in mouse lymphoma cells.
Retinyl palmitate (RP), a storage form of vitamin A, is frequently used as a cosmetic ingredient, with more than 700 RP-containing cosmetic products on the U.S. market in 2004. There are concerns for the possible genotoxicity and carcinogenicity of RP when it is exposed to sunlight. To evaluate the photomutagenicity of RP in cells when exposed to ultraviolet A (UVA) light, L5178Y/Tk+/- mouse lymphoma cells were treated with different doses of RP alone/or in the presence of UVA light. Treatment of the cells with RP alone at the dose range of 25-100 microg/ml did not increase mutant frequencies (MFs) over the negative control, whereas treatment of cells with 1-25 microg/ml RP under UVA light (82.8 mJ/cm2/min for 30 min) produced a dose-dependent mutation induction. The mean induced MF (392 x 10(-6)) for treatment with 25 microg/ml RP under UVA exposure was about threefold higher than that for UVA alone (122 x 10(-6)), a synergistic effect. To elucidate the underlying mechanism of action, we examined the mutants for loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome 11, on which the Tk gene is located. The mutational spectrum for the RP + UVA treatment was significantly different from the negative control, but not significantly different from UVA exposure alone. Ninety four percent of the mutants from RP + UVA treatment lost the Tk+ allele, and 91% of the deleted sequences extended more than 6 cM in chromosome length, indicating clastogenic events affecting a large segment of the chromosome. These results suggest that RP is photomutagenic in combination with UVA exposure in mouse lymphoma cells, with a clastogenic mode-of-action.


Downregulation of Akt and FAK phosphorylation reduces invasion of glioblastoma cells by impairment of MT1-MMP shuttling to lamellipodia and downregulates MMPs expression.
Human malignant glioblastomas are highly invasive tumors. Increased cell motility and degradation of the surrounding extracellular matrix are essential for tumor invasion. PI3K/Akt signaling pathway emerges as a common pathway regulating cellular proliferation, migration and invasion; however, its contribution to particular process and downstream cascades remain poorly defined. We have previously demonstrated that Cyclosporin A (CsA) affects glioblastoma invasion in organotypic brain slices and tumorigenicity in mice. Here we show that CsA impairs migration and invasion of human glioblastoma cells by downregulation of Akt phosphorylation. Interference with PI-3K/Akt signaling was crucial for CsA effect on invasion, because overexpression of constitutively active myr-Akt antagonized drug action. Furthermore, the drug was not effective in T98G glioblastoma cells with constitutively high level of phosphorylated Akt. CsA, comparably to pharmacological inhibitors of PI3K/Akt signaling (LY294002, A443654), reduced motility of glioblastoma cells, diminished MMP-2 gelatinolytic activity and MMP-2 and MT1-MMP expression. The latter effect was mimicked by overexpression of dominant negative Akt mutants. We demonstrate that CsA and LY294002 reduced MMP transcription partly via modulation of IκB phosphorylation and NFκB transcriptional activity. Those effects were not mediated by inhibition of calcineurin, a classical CsA target. Additionally, CsA reduced phosphorylation and activity of focal adhesion kinase that was associated with rapid morphological alterations, rearrangement of lamellipodia and impairment of MT1-MMP translocation to membrane protrusions. Our results document novel, Akt-dependent mechanisms of interference with motility/invasion of human glioblastoma cells: through a rapid modulation of cell adhesion and MT1-MMP translocation to membrane protrusions and delayed, partly NFκB-dependent, downregulation of MMP-2 and MT1-MMP expression. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.


A novel murine cytomegalovirus vaccine vector protects against Mycobacterium tuberculosis.
Tuberculosis remains a global health problem so that a more effective vaccine than bacillus Calmette-Guérin is urgently needed. Cytomegaloviruses persist lifelong in vivo and induce powerful immune and increasing ("inflationary") responses, making them attractive vaccine vectors. We have used an m1-m16-deleted recombinant murine CMV (MCMV) expressing Mycobacterium tuberculosis Ag 85A to show that infection of mice with this recombinant significantly reduces the mycobacterial load after challenge with M. tuberculosis, whereas control empty virus has a lesser effect. Both viruses induce immune responses to H-2(d)-restricted epitopes of MCMV pp89 and M18 Ags characteristic of infection with other MCMVs. A low frequency of 85A-specific memory cells could be revealed by in vivo or in vitro boosting or after challenge with M. tuberculosis. Kinetic analysis of M. tuberculosis growth in the lungs of CMV-infected mice shows early inhibition of M. tuberculosis growth abolished by treatment with NK-depleting anti-asialo ganglio-N-tetraosylceramide Ab. Microarray analysis of the lungs of naive and CMV-infected mice shows increased IL-21 mRNA in infected mice, whereas in vitro NK assays indicate increased levels of NK activity. These data indicate that activation of NK cells by MCMV provides early nonspecific protection against M. tuberculosis, potentiated by a weak 85A-specific T cell response, and they reinforce the view that the innate immune system plays an important role in both natural and vaccine-induced protection against M. tuberculosis.


Association of central hemodynamics with estimated 24-h urinary sodium in patients with hypertension.
High salt intake is known to be the most pivotal environmental factor in the pathogenesis of hypertension. However, the association of high sodium intake with central hemodynamics in hypertensive individuals has not been well defined. Here, we determined the association of estimated 24-h urine sodium and potassium excretion estimated from a spot urine analysis with parameters of central pulse wave analysis in 515 hypertensive individuals. Fasting spot urine samples were obtained in the early morning after the first void, and estimated 24-h urine sodium and potassium excretion were estimated from measurement of urine sodium, potassium and creatinine. Central hemodynamics and arterial stiffness parameters were assessed via pulse wave analysis of the radial artery. The estimated 24-h sodium and potassium excretion values were 150 ± 40 and 49 ± 10 mEq, respectively. There was a step-wise decrease in pulse pressure amplification with increasing estimated 24-h urine sodium excretion. Multiple linear regression analyses revealed that both estimated 24-h urine sodium excretion and sodium/potassium ratio were independently associated with increases in central pulse pressure, augmented aortic pressure and augmentation index and were inversely associated with pulse pressure amplification. The estimated 24-h urinary sodium excretion is independently associated with central hemodynamics. This may provide the basis for prospective interventional studies of epidemiologic scale to determine the potential beneficial effects of reduced salt consumption on central hemodynamics.


The effects of left or right hemispheric epilepsy on language networks investigated with semantic decision fMRI task and independent component analysis.
Chronic and progressive brain injury, as seen in epilepsy, may alter brain networks that underlie cognitive functions. To evaluate the effect of epilepsy on language functions we investigated the neuroanatomical basis of semantic processing in patients with left (LHE) or right (RHE) hemispheric onset epilepsy using semantic decision fMRI paradigm and group independent component analysis (ICA); we then compared the results of our investigations with language networks in healthy subjects examined with the same language task (Kim K, Karunanayaka P, Privitera M, Holland S, Szaflarski J. Semantic association investigated with fMRI and independent component analysis. In press). Group ICA is a data-driven technique capable of revealing the functional organization of the human brain based on fMRI data. In addition to providing functional connectivity information, ICA can also provide information about the temporal dynamics of underlying networks subserving specific cognitive functions. In this study, we implemented two complementary analyses to investigate group differences in underlying network dynamics based on associated independent component (IC) time courses (a priori defined criterion or a posteriori identified maximum likelihood descriptor). We detected several differences between healthy controls and patients with epilepsy not previously observed with standard fMRI analysis methods. Our analyses confirmed the presence of different effects of LHE or RHE on the behavior of the language network. In particular, a major difference was noted in the nodes subserving verbal encoding and retrieval in the bilateral medial temporal regions. These effects were dependent on the side of the epilepsy onset; that is, effects were different with left or right hemispheric epilepsy. These findings may explain the differences in verbal and nonverbal memory abilities between patients with left and those with right hemispheric epilepsy. Further, although the effects on other nodes of the network were more subtle, several deviations from normal network function were observed in patients with LHE (e.g., alterations in the functions of the primarily left frontotemporal network module) or in patients with RHE (e.g., differences in the medial retrosplenial module responsible for mental imagery or in the anterior cingulate module subserving attention control). These findings not only highlight the negative effects of epilepsy on the main left hemispheric language network nodes in patients with LHE, but also document the effects of epilepsy on other language network nodes whether exerted by LHE or RHE. Further, these results document the advantages of using group ICA for investigating the effects of disease state (e.g., epilepsy) on the network subserving cognitive processing and provide an interesting avenue for further exploration.


Effects of sinus lifting on voice quality. A prospective study and risk assessment.
A variety of potential complications associated with sinus lift surgery have been reported in the literature. However, potential alterations of voice quality following sinus elevation have so far not been mentioned or evaluated scientifically. For the majority of patients, slight changes of the voice pattern are of no importance. However, for voice professionals, whose voices have become part of their distinctive profession or trademark, minimal changes may have dramatic consequences. This specific group of patients, such as speakers, actors and singers, depend on the particular quality and timbre of their voice for their livelihood. Consequently, the purpose of this study was to assess the effects of sinus lifting on voice quality in the above patient group. In a collaborative interdisciplinary effort, the Departments of Oral Surgery and Otorhinolaryngology, Section of Phoniatrics and Logopedics, thoroughly evaluated a series of voice parameters of four patients undergoing sinus lifting pre- and postoperatively. The parameters analyzed included pitch, dynamic range, sound pressure level, percent jitter, percent shimmer and noise-to-harmonics ratio with special emphasis on formant analysis. No changes were detected in any of the commonly evaluated parameters. These were rated subjectively by patients and their friends or relatives and objectively with instrumental tools under isolated phoniatric lab conditions. In conclusion, sinus lift surgery appears to be a safe, predictable evidence-based method for regenerating the highly atrophic posterior maxilla, which does not jeopardize the individual characteristic voice pattern of high-profile patients critically dependent on their voices for their livelihood.


Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: phase 1 trial outcomes.
The US Food and Drug Administration-approved trial, "A Phase 1, Open-Label, First-in-Human, Feasibility and Safety Study of Human Spinal Cord-Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis, Protocol Number: NS2008-1," is complete. Our overall objective was to assess the safety and feasibility of stem cell transplantation into lumbar and/or cervical spinal cord regions in amyotrophic lateral sclerosis (ALS) subjects. Preliminary results have been reported on the initial trial cohort of 12 ALS subjects. Here, we describe the safety and functional outcome monitoring results for the final trial cohort, consisting of 6 ALS subjects receiving 5 unilateral cervical intraspinal neural stem cell injections. Three of these subjects previously received 10 total bilateral lumbar injections as part of the earlier trial cohort. All injections utilized a novel spinal-mounted stabilization and injection device to deliver 100,000 neural stem cells per injection, for a dosing range up to 1.5 million cells. Subject assessments included detailed pre- and postsurgical neurological outcome measures. The cervical injection procedure was well tolerated and disease progression did not accelerate in any subject, verifying the safety and feasibility of cervical and dual-targeting approaches. Analyses on outcome data revealed preliminary insight into potential windows of stem cell biological activity and identified clinical assessment measures that closely correlate with ALS Functional Rating Scale-Revised scores, a standard assessment for ALS clinical trials. This is the first report of cervical and dual-targeted intraspinal transplantation of neural stem cells in ALS subjects. This approach is feasible and well-tolerated, supporting future trial phases examining therapeutic dosing and efficacy.


Association between heavy precipitation events and waterborne outbreaks in four Nordic countries, 1992-2012.
We conducted a matched case-control study to examine the association between heavy precipitation events and waterborne outbreaks (WBOs) by linking epidemiological registries and meteorological data between 1992 and 2012 in four Nordic countries. Heavy precipitation events were defined by above average (exceedance) daily rainfall during the preceding weeks using local references. We performed conditional logistic regression using the four previous years as the controls. Among WBOs with known onset date (n = 89), exceedance rainfall on two or more days was associated with occurrence of outbreak, OR = 3.06 (95% CI 1.38-6.78), compared to zero exceedance days. Stratified analyses revealed a significant association with single household water supplies, ground water as source and for outbreaks occurring during spring and summer. These findings were reproduced in analyses including all WBOs with known outbreak month (n = 186). The vulnerability of single households to WBOs associated with heavy precipitation events should be communicated to homeowners and implemented into future policy planning to reduce the risk of waterborne illness.


Effectiveness of internet-supported cognitive behavioral and chronobiological interventions and effect moderation by insomnia subtype: study protocol of a randomized controlled trial.
DSM-V criteria for insomnia disorder are met by 6 to 10% of the adult population. Insomnia has severe consequences for health and society. One of the most common treatments provided by primary caregivers is pharmacological treatment, which is far from optimal and has not been recommended since a 2005 consensus report of the National Institutes of Health. The recommended treatment is Cognitive Behavioral Therapy for Insomnia. Effectiveness, however, is still limited. Only a few studies have evaluated the effectiveness of chronobiological treatments, including the timed application of bright light, physical activity and body warming. Another opportunity for optimization of treatment is based on the idea that the people suffering from insomnia most likely represent a heterogeneous mix of subtypes, with different underlying causes and expected treatment responses. The present study aims to evaluate the possibility for optimizing insomnia treatment along the principles of personalized and stratified medicine. It evaluates the following: 1. The relative effectiveness of internet-supported cognitive behavioral therapy, bright light, physical activity and body warming; 2. Whether the effectiveness of internet-supported cognitive behavioral therapy for insomnia can be augmented by simultaneous or prior application of bright light, physical activity and body warming; and 3. Whether the effectiveness of the interventions and their combination are moderated by the insomnia subtype. In a repeated measures, placebo-controlled, randomized clinical trial that included 160 people diagnosed with insomnia disorder, we are evaluating the relative effectiveness of 4 intervention weeks. Primary outcome is subjective sleep efficiency, quantified using a sleep diary. Secondary outcomes include other complaints of sleep and daytime functioning, health-related cost estimates and actigraphic objective sleep estimates. Compliance will be monitored both subjectively and objectively using activity, light and temperature sensors. Insomnia subtypes will be assessed using questionnaires. Mixed effect models will be used to evaluate intervention effects and moderation by insomnia subtype ratings. The current study addresses multiple opportunities to optimize and personalize treatment of insomnia disorder. Netherlands National Trial Register NTR4010, 4 June 2013.


"It's More than Just Needing money": The Value of Supporting Networks of Care.
It is well established in research, practice, and policy that unpaid caregivers (family and friends of people with care needs) experience stress in their role. Supports that have been put in place by policy planners and program developers to support caregivers may not be accessed by caregivers at all or may do little to reduce their stress. Accessing personal resources (education, finances), in addition to social resources (individual connections) and societal resources (community supports) are critical in fostering resilience in caregivers (helping them adapt to stress and adversity). Social capital theorists argue that creating connections at various levels can improve access to resources. This research, through qualitative interviews (n = 21), identifies the different levels of resources required to address the needs of caregivers. Our findings indicate that interventions that focus on access to personal-level resources (education, funding) are important, but are on their own insufficient. Of more importance were interventions that work to improve relationships between formal providers and families; access to interdisciplinary teams; cross-sectoral collaborations; and inter-organization relationships, highlighting that a system that works together is likely to improve caregivers' access to resources.


Long-term outcomes in thoracoabdominal aortic aneurysm repair for chronic type B dissection.
Open repair for chronic aortic dissection remains a challenging surgical option. Different centers report diverse experiences and outcomes pertaining to thoracoabdominal aortic aneurysm repair (TAAAR) for chronic type B dissection. We highlight our center's experience and results on a background of published literature and current evidence. We reviewed 214 open TAAAR performed between October 1998 and February 2014. Of these, chronic type B dissection was present in 62 (29.0%) patients. We reviewed these patients in terms of demographics, operative characteristics and outcomes. Thirteen (21.0%) patients had surgery on the descending thoracic aorta [Category A =2 (3.2%), B =0 (0%), C =11 (17.7%)] and 49 (79.0%) in the thoracoabdominal thoracic aorta [Crawford extent I =5 (8.1%), extent II =39 (62.9%), extent III =4 (6.5%), extent IV =1 (1.6%)]. Left heart bypass was used in 12 (19.4%) patients. The composite in-hospital endpoint, adverse outcome-defined as operative death, renal failure necessitating dialysis at discharge, stroke, or permanent paraplegia or paraparesis-occurred after 28 (45.2%) procedures. There were 14 (22.6%) operative deaths. In-hospital mortality was seven (16.3%) out of 43 elective patients, and increased to seven (36.8%) of the 19 non-elective ones. Permanent paraplegia or paraparesis occurred after two (3.2%) cases, stroke occurred after seven (11.3%) and renal failure requiring dialysis occurred after 16 (25.8%). Mean follow-up time was 3.2 years and actuarial 5-year mortality was 27.4% [nine (14.5%) elective and eight (12.9%) non-elective patients]. TAAAR in chronic type B dissection carries a substantial risk of early adverse outcomes. The results could be well alleviated with cases directed towards specialized regional and supra-regional centers. Although the endovascular approaches offer relatively low mortality and morbidity, there is a lack of long-term data and guidelines on their use. There is a need for a multidisciplinary international registry on the management of thoracoabdominal aortic aneurysms and dissection. This would provide a degree of guidance on relevant clinical and surgical judgments and outcomes.


The multidimensionality of peer pressure in adolescence.
A sample of 689 adolescents (grades 7-12) from two Midwestern communities who had been identified by peers as members of one of three major peer groups responded to a self-report survey measuring perceptions of peer pressure in five areas of behavior: involvement with peers, school involvement, family involvement, conformity to peer norms, and misconduct. Perceived pressures toward peer involvement were particularly strong, whereas peer pressures concerning misconduct were relatively ambivalent. Perceived pressures toward misconduct increased across grade levels and pressures to conform to peer norms diminished; grade differences in perceived peer pressures concerning family involvement were community specific. Compared to druggie-toughs, jock-populars perceived stronger peer pressures toward school and family involvement, and less pressure toward (stronger pressure against) misconduct; patterns of perceived pressure among loners were more variable across communities. Results elaborated the process of peer influence in adolescent socialization and identity development.


Clinical inquiries. How long is expectant management safe in first-trimester miscarriage?
More than 80% of women with a first-trimester spontaneous abortion have complete natural passage of tissue within 2 to 6 weeks with no higher complication rate than that from surgical intervention (strength of recommendation [SOR]: A, based on multiple randomized controlled trials [RCTs] and cohort studies). Expectant management is successful within 2 to 6 weeks without increased complications in 80% to 90% of women with first-trimester incomplete spontaneous abortion and 65% to 75% of women with first-trimester missed abortion or anembryonic gestation (presenting with spotting or bleeding and ultrasound evidence of fetal demise) (SOR: B, based on multiple cohort studies). There is no difference in short-term psychological outcomes between expectant and surgical management (SOR: B, based on RCT). Women experiencing spontaneous abortion with unstable vital signs, uncontrolled bleeding, or evidence of infection should be considered for surgical evacuation (SOR: C, expert opinion).


Clinical simulation in maternity (CSiM): interprofessional learning through simulation team training.
Focusing on interprofessional relations in team performance to improve patient safety is an emerging priority in obstetrics. A review of the literature found little information on roles and teamwork in obstetric emergency training. Qualitative research was undertaken through a Clinical Simulation in Maternity programme which gives interprofessional rural clinicians the opportunity to learn collaboratively through simulated obstetric emergencies. This research aimed to determine how interprofessional simulation team training improved maternity emergency care and team performance. This research used thematic inductive analysis using data from in-depth interviews. In total 17 participants and four facilitators who took part in the Clinical Simulation in Maternity workshops were invited to participate in an interview 1-2 weeks postworkshop and then again 3-6 months later. Data were deidentified then coded manually and with the assistance of computer program NVivo 7 (QSR International). Of the major themes identified, Collaboration in Teambuilding was separated into four subthemes (Personal Role Awareness, Interpositional Knowledge, Mutuality and Leadership). This research highlights the significance of interprofessional training, particularly through simulation learning in a team where rural clinicians are able to learn more about each other and gain role clarity, leadership skills and mutuality in a safe environment.


When Science Replaces Religion: Science as a Secular Authority Bolsters Moral Sensitivity.
Scientific and religious thinking compete with each other on several levels. For example, activating one generally weakens the other. Since priming religion is known to increase moral behaviour and moral sensitivity, priming science might be expected to have the opposite effect. However, it was recently demonstrated that, on the contrary, science priming increases moral sensitivity as well. The present set of studies sought to replicate this effect and test two explanations for it. Study 1 used a sentence unscrambling task for implicitly priming the concept of science but failed to replicate its effect on moral sensitivity, presumably due to a ceiling effect. Study 2 replicated the effect with a new measure of moral sensitivity. Study 3 tested whether science-related words create this effect by activating the idea of secular authority or by activating analytic thinking. It was demonstrated that words related to secular authority, but not words related to analytic thinking, produced a similar increase in moral sensitivity. Religiosity level of the participants did not influence this basic finding. The results are consistent with the hypothesis that science as a secular institution has overtaken some of the functions of religion in modern societies.


Children's and teachers' perspectives on adjustments needed in school settings after acquired brain injury.
Children with acquired brain injury (ABI) often present with functional deficits that influence their societal participation and well-being. Successful reintegration into school calls for individual support to meet each child's adjustment needs. The adjustment needs of children with ABI in school settings have not previously been explored. The objectives of the present study were (a) to describe adjustment needs in school settings for children with ABI and (b) to explore differences and similarities between reports from the children and their teachers. In this cross-sectional study, 20 children with ABI (mean age 12.8 ± 3.4 years; class grade 1-10) and their teachers were interviewed individually, using the School Setting Interview (SSI). Data were analyzed with descriptive and with non-parametric statistics. (a) In the overall group, children rated that 55.6% of the 16 activities in the SSI needed no adjustment. The corresponding percentage for teachers was 48.4%. (b) In the child-teacher pairs, there was a positive relationship between teachers' and children's responses only in 3 out of 16 school activities and agreement varied strongly according to the activity in question. It is important for occupational therapists and other professionals to specifically consider adjustment needs relating to school activities from various perspectives when aiming to provide individualized interventions.


Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms.
Social play behavior is a characteristic form of social behavior displayed by juvenile and adolescent mammals. This social play behavior is highly rewarding and of major importance for social and cognitive development. Social play is known to be modulated by neurotransmitter systems involved in reward and motivation. Interestingly, psychostimulant drugs, such as amphetamine and cocaine, profoundly suppress social play, but the neural mechanisms underlying these effects remain to be elucidated. In this study, we investigated the pharmacological underpinnings of amphetamine- and cocaine-induced suppression of social play behavior in rats. The play-suppressant effects of amphetamine were antagonized by the alpha-2 adrenoreceptor antagonist RX821002 but not by the dopamine receptor antagonist alpha-flupenthixol. Remarkably, the effects of cocaine on social play were not antagonized by alpha-2 noradrenergic, dopaminergic, or serotonergic receptor antagonists, administered either alone or in combination. The effects of a subeffective dose of cocaine were enhanced by a combination of subeffective doses of the serotonin reuptake inhibitor fluoxetine, the dopamine reuptake inhibitor GBR12909, and the noradrenaline reuptake inhibitor atomoxetine. Amphetamine, like methylphenidate, exerts its play-suppressant effect through alpha-2 noradrenergic receptors. On the other hand, cocaine reduces social play by simultaneous increases in dopamine, noradrenaline, and serotonin neurotransmission. In conclusion, psychostimulant drugs with different pharmacological profiles suppress social play behavior through distinct mechanisms. These data contribute to our understanding of the neural mechanisms of social behavior during an important developmental period, and of the deleterious effects of psychostimulant exposure thereon.


Sequential assessment of prey through the use of multiple sensory cues by an eavesdropping bat.
Predators are often confronted with a broad diversity of potential prey. They rely on cues associated with prey quality and palatability to optimize their hunting success and to avoid consuming toxic prey. Here, we investigate a predator's ability to assess prey cues during capture, handling, and consumption when confronted with conflicting information about prey quality. We used advertisement calls of a preferred prey item (the túngara frog) to attract fringe-lipped bats, Trachops cirrhosus, then offered palatable, poisonous, and chemically manipulated anurans as prey. Advertisement calls elicited an attack response, but as bats approached, they used additional sensory cues in a sequential manner to update their information about prey size and palatability. While both palatable and poisonous small anurans were readily captured, large poisonous toads were approached but not contacted suggesting the use of echolocation for assessment of prey size at close range. Once prey was captured, bats used chemical cues to make final, post-capture decisions about whether to consume the prey. Bats dropped small, poisonous toads as well as palatable frogs coated in toad toxins either immediately or shortly after capture. Our study suggests that echolocation and chemical cues obtained at close range supplement information obtained from acoustic cues at long range. Updating information about prey quality minimizes the occurrence of costly errors and may be advantageous in tracking temporal and spatial fluctuations of prey and exploiting novel food sources. These findings emphasize the sequential, complex nature of prey assessment that may allow exploratory and flexible hunting behaviors.


Interaction between innate immune cells and a bacterial type III secretion system in mutualistic and pathogenic associations.
Animals house a community of bacterial symbionts in their digestive tracts that contribute to their well being. The medicinal leech, Hirudo verbana, has a remarkably simple gut population carrying two extracellular microbes in the crop where the ingested blood is stored. This simplicity renders it attractive for studying colonization factors. Aeromonas veronii, one of the leech symbionts, can be genetically manipulated and is a pathogen of mammals. Screening transposon mutants of A. veronii for colonization defects in the leech, we found one mutant, JG752, with a transposon insertion in an ascU homolog, encoding an essential component of type III secretion systems (T3SS). Competing JG752 against the wild type revealed that JG752 was increasingly attenuated over time (10-fold at 18 h and >10,000-fold at 96 h). This colonization defect was linked to ascU by complementing JG752 with the operon containing ascU. Fluorescence in situ hybridization analysis revealed that at 42 h 38% of JG752 cells were phagocytosed by leech macrophage-like cells compared with <0.1% of the parental strain. Using mammalian macrophages, a lactate dehydrogenase release assay revealed that cytotoxicity was significantly reduced in macrophages exposed to JG752. In a mouse septicemia model, JG752 killed only 30% of mice, whereas the parent strain killed 100%, showing the importance of T3SS for both pathogenesis and mutualism. Phagocytic immune cells are important not only in defending against pathogens but also in maintaining the mutualistic symbiont community inside the leech, demonstrating that animals use similar, conserved mechanisms to control bacterial populations, even when the outcomes differ dramatically.


Relationships between body reserve dynamics and rearing performances in meat ewes1.
The main objective of this work was to study the relationships between body reserve (BR) dynamics and rearing performance (PERF) traits in ewes from a Romane meat sheep flock managed extensively on "Causse" rangelands in the south of France. Flock records were used to generate data sets covering 14 lambing years (YR). The data set included 1,146 ewes with 2 ages of first lambing (AGE), 3 parities (PAR), and 4 litter sizes (LS). Repeated measurements of the BW and BCS were used as indicators of BR. The ewe PERF traits recorded were indirect measurements for maternal abilities and included prolificacy, litter weight and lamb BW at lambing and weaning, ADG at 1, 2, and 3 mo after lambing, and litter survival from lambing to weaning. The effects of different BW and BCS trajectories (e.g., changes in BW and BCS across the production cycle), previously been characterized in the same animals, on PERF traits were investigated. Such trajectories reflected different profiles at the intraflock level in the dynamics of BR mobilization-accretion cycles. Genetic relationships between BR and PERF traits were assessed. All the fixed variables considered (i.e., YR, AGE, PAR, LS, and SEX ratio of the litter) have significant effects on the PERF traits. Similarly, BW trajectories had an effect on the PERF traits across the 3 PARs studied, particularly during the first cycle (PAR 1). The BCS trajectories only affected prolificacy, lamb BW at birth, and litter survival. Most of the PERF traits considered here showed moderate heritabilities (0.17-0.23) except for prolificacy, the lamb growth rate during the third month and litter survival which showed very low heritabilities. With exception of litter survival and prolificacy, ewe PERF traits were genetically, strongly, and positively correlated with BW whatever the physiological stage. A few weak genetic correlations were found between BCS and PERF traits. As illustrated by BW and BCS changes over time, favorable genetic correlations were found, even if few and moderate, between BR accretion or mobilization and PERF traits, particularly for prolificacy and litter weight at birth. In conclusion, our results show significant relationships between BR dynamics and PERF traits in ewes, which could be considered in future sheep selection programs aiming to improve robustness.


Sleep and alertness in a 12-hour rotating shift work environment.
Industrial workers on rotating shifts were evaluated for the effects of rotating shift work. Twenty-five (86%) of 29 workers in the study area who work 12-hour shifts in a scheduled 16-day rotation participated. The mean number of hours of sleep at home after working day shifts (5.6 hours) was less than after the first three night shifts (6.0, 6.4, and 6.6 hours, respectively). At work, the mean number of hours at reported peak alertness was greater during the night shift (6.1 hours) than the day shift (4.9 hours), but the perceived alertness levels were relatively lower on the night shift. Increased perceived difficulty working and decreased perceived productivity and safety were reported on the first night of the night shift. We demonstrate that workers on rotating shift work exhibit low alertness-related outcomes on both shifts. These workers have early shift work starting times that appear to disrupt sleep patterns on both day and night shifts. At this work site, a number of interventions to lessen the effects of rotating shift work are being evaluated.


Ten species of Culicoides Latreille (Diptera: Ceratopogonidae) newly recorded from Thailand.
A survey of biting midges in animal sheds, mangroves and beaches along the Andaman coastal region in southern Thailand between April 2012 and May 2013 collected 10 species of Culicoides which were not previously known from Thailand. These new records are C. arenicola, C. flavipunctatus, C. hui, C. kinari, C. kusaiensis, C. parabubalus, C. quatei, C. spiculae, C. pseudocordiger and C. tamada. An updated checklist of species of Culicoides reported from Thailand is provided.


Tabula viva chirurgic: a living surgical document.
The purpose of this article is to present the results of a private cardiac surgical practice. This information could also serve as a hermeneutical text for new wisdom. A personal database of 1 750 consecutive patients who had had coronary artery bypass graft (CABG) surgery was statistically analysed. Mortality and major morbidity figures were compared with large registries. Risk factors for postoperative death were determined. Over a period of 12 years, 1 344 (76.8%) males and 406 (23.2%) females were operated on. The observed mortality rate was 3.03% and the expected mortality rate (EuroSCORE) was 3.87%. After stepwise logistic regression, independent risk factors for death were urgency (intra-aortic balloon pump), renal impairment (chronic kidney disease, stage III), re-operation and an additional procedure. Apart from the 53 deaths, another 91 patients had major complications. Mortality and morbidity rates compared favourably with other international registries. Mortality was related to co-morbidities. This outcome contributes to a hermeneutical understanding focusing on new spiritual wisdom and meaning for the surgeon.


Novel Insights into the Pathogenesis of Spinal Sarcopenia and Related Therapeutic Approaches: A Narrative Review.
Spinal sarcopenia is a complex and multifactorial disorder associated with a loss of strength, increased frailty, and increased risks of fractures and falls. In addition, spinal sarcopenia has been associated with lumbar spine disorders and osteoporosis, which renders making decisions on treatment modalities difficult. Patients with spinal sarcopenia typically exhibit lower cumulative survival, a higher risk of in-hospital complications, prolonged hospital stays, higher postoperative costs, and higher rates of blood transfusion after thoracolumbar spine surgery. Several studies have focused on the relationships between spinal sarcopenia, appendicular muscle mass, and bone-related problems-such as osteoporotic fractures and low bone mineral density-and malnutrition and vitamin D deficiency. Although several techniques are available for measuring sarcopenia, each of them has its advantages and shortcomings. For treating spinal sarcopenia, nutrition, physical therapy, and medication have been proven to be effective; regenerative therapeutic options seem to be promising owing to their repair and regeneration potential. Therefore, in this narrative review, we summarize the characteristics, detection methodologies, and treatment options for spinal sarcopenia, as well as its role in spinal disorders.


Brugada disease: chronology of discovery and paternity. Preliminary observations and historical aspects.
The Brugada disease, the last clinico-cardiologic entity described in the 20th century, initially called right bundle branch block syndrome with ST segment elevation from V1 to V2 or V3 and sudden cardiac death, is genetically determined in a dominant autosomal mode, and it affects the alpha subunit of the Na+ channel by alteration of chromosome 3 and mutation in the SCN5A gene. In clinical diagnosis the mentioned electrocardiographic pattern in a patient without structural heart disease and positivity in pharmacological tests are considered major criteria. As minor criteria, the following are considered: positive family history, presence of syncope with unknown origin, documented episode of VT/VF, inducibility in electrophysiologic study and positivity of genetic study. The long-standing technology of ECG, with more than a century of existence, remains as the supplementary method with highest value in diagnosis, and currently new electrocardiographic criteria are suggested, which indicate high risk of VF. Natural history indicates a somber diagnosis in symptomatic patients with a high index of arrhythmic SCD secondary to very fast polymorphic ventricular tachycardia bursts, which degenerate into VF. Asymptomatic individuals with only a Brugada-type electrocardiographic pattern have a low risk. The prognosis seems to depend more on clinical facts, since a positive electrophysiologic study has an accuracy of just around 50%. We propose that this entity should be promoted to the category of disease, since it has a characteristic set of signs and symptoms, and an identified genetic defect.


Cue relevance effects in conjunctive visual search: cueing for location, color, and orientation.
Performance in visual search tasks where the target differs from distractors by a conjunction of features can improve when a precue signals observers to limit their search by attending to a subset of elements. The current experiments were designed to study the temporal characteristics of precueing the location or feature (color or orientation) of targets in color-orientation conjunctive searches. Color (sensory or symbolic), location, or orientation precues preceded the search stimulus with cue-to-stimulus onset asynchrony (SOA) in the range of 50-750 ms. The stimuli consisted of elements formed by combining horizontal/vertical and red/green features. Observers responded to the presence/absence of an odd element in an "odd-man-out" paradigm. Reaction time and accuracy were used as measures of performance. Color and location precues improved search performance. The magnitude of improvement did not vary as the SOA changed. The color and location cues exhibited their effects in guiding visual search even at 50 ms after cue onset. However, orientation precue did not facilitate nor inhibit the search processing. These results indicate that in conjunctive search it takes at most 50 ms after cue onset for the visual system to exert the guidance effects using color and location precueing. We speculate that color may be a stronger feature than orientation for segmenting the search elements, thus facilitating visual search.


Comparative evaluation of the fracture resistances of endodontically treated teeth filled using five different root canal filling systems.
The aim of this study was to compare the fracture resistances of teeth filled using different root canal sealers and rials. One hundred and twenty single rooted mandibular human incisor teeth with single canals were divided into 5 experimental groups of 20 teeth with 2 control groups of 10 teeth each. After root canal shaping using K3 rotary instruments, root canals were filled as follows: Group 1: (-) control, Group 2: (+) control, Group 3: Gutta-percha/AH Plus, Group 4: Thermafil/AH Plus, Group 5: Resilon/Epiphany self-etch (Epiphany SE), Group 6: Gutta-percha/Epiphany SE ve Group 7: EndoREZ sealer/EndoREZ cone. After the root canal sealers set, the apical 4 mm. portions of the specimens were embedded in cold curing acrylic and a fracture resistance test was applied in a universal testing machine. The load at which fracture occurred was recorded for each group and statistically analyzed using one-way ANOVA and Tukey's honestly significant difference tests. Resilon/Epiphany SE ve EndoREZ sealer/EndoREZ cone groups had lower fracture resistances compared with the negative control group consisted of teeth without root canal shaping (P < 0.05). Gutta-percha/AH Plus, Thermafil/AH Plus and Gutta-percha/Epiphany SE groups showed similar fracture resistances (P > 0.05). The fracture resistance of the instrumented, but unfilled positive control group was significantly lower compared with (-) control, Gutta-percha/AH Plus, Thermafil/AH Plus (P < 0.01) and Gutta-percha/Epiphany SE (P < 0.05) groups. There were no significant differences between the fracture resistances of the Resilon/Epiphany SE and EndoREZ sealer/EndoREZ cone and positive control groups (P > 0.05). Root canal shaping procedures decrease the fracture resistance of teeth, and lateral condensation performed with AH Plus sealer and Gutta-percha and the Thermafil technique were found to be more successful.


Fumonisins in conventional and transgenic, insect-resistant maize intended for fuel ethanol production: implications for fermentation efficiency and DDGS co-product quality.
Mycotoxins in maize grain intended for ethanol production are enriched in co-product dried distiller's grains and solubles (DDGS) and may be detrimental to yeast in fermentation. This study was conducted to examine the magnitude of fumonisin enrichment in DDGS and to analyze the impacts of insect injury, Fusarium ear rot severity, and fumonisin contamination on final ethanol yield. Samples of naturally-contaminated grain (0 to 35 mg/kg fumonisins) from field trials conducted in 2008-2011 were fermented and DDGS collected and analyzed for fumonisin content. Ethanol yield (determined gravimetrically) was unaffected by fumonisins in the range occurring in this study, and was not correlated with insect injury or Fusarium ear rot severity. Ethanol production was unaffected in fumonisin B1-spiked grain with concentrations from 0 to 37 mg/kg. Bacillus thuringiensis (Bt) maize often has reduced fumonisins due to its protection from insect injury and subsequent fungal infection. DDGS derived from Bt and non-Bt maize averaged 2.04 mg/kg and 8.25 mg/kg fumonisins, respectively. Fumonisins were enriched by 3.0× for 50 out of 57 hybrid × insect infestation treatment combinations; those seven that differed were <3.0 (1.56 to 2.56×). This study supports the industry assumption of three-fold fumonisin enrichment in DDGS, with measurements traceable to individual samples. Under significant insect pest pressures, DDGS derived from Bt maize hybrids were consistently lower in fumonisins than DDGS derived from non-Bt hybrids.


Cost-effectiveness of 2009 pandemic influenza A(H1N1) vaccination in the United States.
Pandemic influenza A(H1N1) (pH1N1) was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination. A computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects) were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted. For vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000-$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery. Vaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial impact on the cost-effectiveness of vaccination.


Adverse reactions from community directed treatment with ivermectin (CDTI) for onchocerciasis and loiasis in Ondo State, Nigeria.
Onchocerciasis is an endemic disease in Ondo state, Nigeria. Community directed distribution of ivermectin is currently on-going in some local government areas of the state. Randomly selected persons (2331 males and 2469 females) were interviewed using a modified rapid assessment procedure for Loa loa (RAPLOA) to assess community directed treatment with ivermectin. The retrospective study evaluated the coverage, impacts and adverse reactions to the drug treatment. A questionnaire was administered by house-to-house visit in six local government areas, implementing community directed treatment with ivermectin (CDTI) in this bioclimatic zone. A total of 2,398 respondents were reported to have participated in the treatment. The overall ivermectin coverage of 49.96% was recorded (range 0-52% in different communities). Adverse reactions from ivermectin administration were experienced in 38% of individuals. Diverse adverse reactions experienced included predominantly itching (18.50%); oedema, especially of the face and the limbs (8.2%); rashes (3.4%) and body weakness (2.4%). Expulsion of intestinal worms occurred in 0.96% of the respondents. The occurrence of adverse reactions in relation to age categories was statistically significant. Neither fatal nor severe adverse reactions were reported by respondents. Significantly, despite experienced adverse reactions, continued participation, acceptability and compliance to ivermectin treatment was expressed by the various communities. This attitude is in consonance with the African Programme for Onchocerciasis Control (APOC) objectives. Rev. Biol.


Crystallization, molecular replacement solution, and refinement of tetrameric beta-amylase from sweet potato.
Sweet potato beta-amylase is a tetramer of identical subunits, which are arranged to exhibit 222 molecular symmetry. Its subunit consists of 498 amino acid residues (Mr 55,880). It has been crystallized at room temperature using polyethylene glycol 1500 as precipitant. The crystals, growing to dimensions of 0.4 mm x 0.4 mm x 1.0 mm within 2 weeks, belong to the tetragonal space group P4(2)2(1)2 with unit cell dimensions of a = b = 129.63 A and c = 68.42 A. The asymmetric unit contains 1 subunit of beta-amylase, with a crystal volume per protein mass (VM) of 2.57 A3/Da and a solvent content of 52% by volume. The three-dimensional structure of the tetrameric beta-amylase from sweet potato has been determined by molecular replacement methods using the monomeric structure of soybean enzyme as the starting model. The refined subunit model contains 3,863 nonhydrogen protein atoms (488 amino acid residues) and 319 water oxygen atoms. The current R-value is 20.3% for data in the resolution range of 8-2.3 A (with 2 sigma cut-off) with good stereochemistry. The subunit structure of sweet potato beta-amylase (crystallized in the absence of alpha-cyclodextrin) is very similar to that of soybean beta-amylase (complexed with alpha-cyclodextrin). The root-mean-square (RMS) difference for 487 equivalent C alpha atoms of the two beta-amylases is 0.96 A. Each subunit of sweet potato beta-amylase is composed of a large (alpha/beta)8 core domain, a small one made up of three long loops [L3 (residues 91-150), L4 (residues 183-258), and L5 (residues 300-327)], and a long C-terminal loop formed by residues 445-493. Conserved Glu 187, believed to play an important role in catalysis, is located at the cleft between the (alpha/beta)8 barrel core and a small domain made up of three long loops (L3, L4, and L5). Conserved Cys 96, important in the inactivation of enzyme activity by sulfhydryl reagents, is located at the entrance of the (alpha/beta)8 barrel.


The brain injury case management taxonomy (BICM-T); a classification of community-based case management interventions for a common language.
Case management is a complex intervention. Complexity arises from the interaction of different components: the model (theoretical basis), implementation context (service), population and health condition, focus for the intervention (client and/or their family), case manager's actions (interventions) and the target of case management (integrated care and support, client's community participation). There is a lack of understanding and a common language. To our knowledge there is no classification (taxonomy) for community-based case management. To develop a community-based case management in brain injury taxonomy (BICM-T), as a common language and understanding of case management for use in quality analysis, policy, planning and practice. The mixed qualitative methods used multiple sources of knowledge including scoping, framing and a nominal group technique to iteratively develop the Beta version (draft) of the taxonomy. A two part developmental evaluation involving case studies and mapping to international frameworks assessed the applicability and acceptability (feasibility) before finalization of the BICM-T. The BICM-T includes a definition of community-based case management, taxonomy trees, tables and a glossary. The interventions domain tree has 9 main actions (parent category): engagement, holistic assessment, planning, education, training and skills development, emotional and motivational support, advising, coordination, monitoring; 17 linked actions (children category); 8 related actions; 63 relevant terms defined in the glossary. The BICM-T provides a knowledge map with the definitions and relationships between the core actions (interventions domain). Use of the taxonomy as a common language will benefit practice, quality analysis, evaluation, policy, planning and resource allocation.


Development and test-retest reliability of a new, self-report questionnaire assessing healthcare use and personal costs in people with inflammatory bowel disease: the Inflammatory Bowel Disease Resource Use Questionnaire (IBD-RUQ).
The increasing prevalence of inflammatory bowel disease (IBD) poses a substantial economic burden globally on health systems and societies. Validated instruments to collect data on healthcare and other service utilisation by patients with IBD are lacking. We developed a self-report patient questionnaire to capture key resource utilisation from health services, patient and societal perspectives. The IBD Resource Use Questionnaire (IBD-RUQ), developed by a multidisciplinary team, including patients, comprises 102 items across the six categories of outpatient visits, diagnostics, medication, hospitalisations, employment and out-of-pocket expenses over the past three months. The test-retest reliability of the IBD-RUQ was studied by administering it twice among patients with IBD with a 2-week time gap. The intraclass correlation coefficients and the average cost from the healthcare, societal and patient perspectives, between test and retest assessments, overall and by service category, were summarised. The IBD-RUQ captures health service use, employment and out-of-pocket expenses. Of 55 patients who completed the first questionnaire, 48 completed the retest questionnaires and were included in the analyses. Test-retest reliability for categories of medications, diagnostics, specialist outpatient and inpatient services, and days off work due to IBD ranged from moderate to excellent; primary care visits showed more limited reliability. The annualised average self-reported health service, out-of-pocket and loss of productivity costs were £4844, £320 and £545 per patient, respectively. The IBD-RUQ is a reliable and valid self-report measure of resource utilisation in adults with IBD and can be used to measure costs associated with IBD.


The full-length and N-terminal deletion of ORF2 protein of hepatitis E virus can dimerize.
Hepatitis E virus is a human RNA virus containing three open reading frames. Of these ORF2 encodes, the major capsid protein (pORF2), may possess regulatory functions, in addition to a structural one. In this study, we have shown using the yeast two-hybrid system and in vitro immobilization experiments that full-length pORF2 is capable of self-association, thus forming a homodimer. Using mutational analysis we have studied dimerization of various truncated versions of the ORF2 capsid protein using the yeast two-hybrid system and supported our findings with in vitro immobilization experiments. Deletions of pORF2 reveal a loss of the dimerization potential for all deletions except an N-terminal 127-amino-acid deletion. Our studies suggest that the dimerization property of pORF2 may not be amino-acid sequence-dependent but instead a complex formation of a specific tertiary structure that imparts pORF2 its property to self-associate.


Quantitative real-time PCR for the measurement of 11beta-HSD1 and 11beta-HSD2 mRNA levels in tissues of healthy dogs.
The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) exists in two isoforms, 11beta-HSD1 and 11beta-HSD2. 11beta-HSD1 generates active cortisol from cortisone and appears to be involved in insulin resistant states. 11beta-HSD2 protects the mineralocorticoid receptor from inappropriate activation by glucocorticoids and is important to prevent sodium retention and hypertension. The purposes of the present study were to develop two real-time PCR assays to assess 11beta-HSD1 and 11beta-HSD2 mRNA expression and to evaluate the tissue distribution of the two isoforms in dogs. Thirteen different tissues of 10 healthy dogs were evaluated. Both real-time PCR assays were highly specific, sensitive and reproducible. Highest 11beta-HSD1 mRNA expression was seen in liver, lung, and renal medulla; highest 11beta-HSD2 mRNA expression in renal cortex, adrenal gland, and renal medulla. Higher 11beta-HSD1 than 11beta-HSD2 mRNA levels were found in all tissues except adrenal gland, colon, and rectum. Our results demonstrate that the basic tissue distribution of 11beta-HSD1 and 11beta-HSD2 in dogs corresponds to that in humans and rodents. In a next step 11beta-HSD1 and 11beta-HSD2 expression should be assessed in diseases like obesity, hypercortisolism, and hypertension to improve our knowledge about 11beta-HSD activity, to evaluate the dog as a model for humans and to potentially find new therapeutic options.


Force spectroscopy of barnase-barstar single molecule interaction.
Results of the single molecule force spectroscopy study of specific interactions between ribonuclease barnase and its inhibitor barstar are presented. Experimental data obtained for the force loading rate ranging 2-70 nN/s are well approximated by a single straight line, from which the dissociation barrier of the width of 0.12 nm and height of 0.75-0.85 × 10(-19)J can be inferred. The measured value of specific interaction does not depend on the NaCl concentration. This apparently contradicts the well-known dependence of the binding energy of this pair on the salt concentration, but such a "contradiction" is explained by the insensitivity of the force spectroscopy data to the relatively long-range electrostatic interaction. The latter essentially contributes to the value of barnase-barstar binding energy revealed by biochemical measurements, and it is exactly this electrostatic interaction which is influenced by the salt concentration.


Identification of a Western blot pattern for the specific diagnosis of Trypanosoma cruzi infection in human sera.
A Western blot (WB) method using a lysate from Trypanosoma cruzi (Maracay strain) epimastigotes was evaluated. Serum samples from 37 patients with confirmed Chagas disease (cohort I), 27 Spanish patients with visceral leishmaniasis caused by Leishmania infantum (cohort II), and 28 Colombian patients with cutaneous leishmaniasis caused by L. panamensis and negative serology for Chagas disease (cohort III) were tested. The negative controls were 55 healthy seronegative subjects for T. cruzi and Leishmania; 28 of the negative controls were from a region endemic for Chagas disease and Leishmania (cohort IV), and 27 of the negative controls were from a non-endemic area for Leishmania and T. cruzi (cohort V). A homogeneous standard band pattern consisting of six antigenic bands corresponding to 28, 32, 38, 39, 40, and 48 kDa was recognized simultaneously for all Chagasic patients' sera. Sera from Leishmania-infected patients showed a heterogeneous band pattern that was easily differentiated from the pattern of patients with Chagas disease. WB with T. cruzi epimastigote antigen is an efficient method for diagnosis and may be used as an alternative to confirm T. cruzi and detect cross-reactivity with Leishmania.


Thermal Conversion Characteristics of Molasses.
Agroindustrial biomass residues are considered potential feedstocks for renewable fuels and chemical production through processes such as thermal conversion. In this regard, thermal conversion characteristics of molasses, a byproduct from sugar production, have not been investigated. In this study, thermal conversion properties of molasses at temperatures of 700-900 °C have been studied using a single-particle reactor. Fuel swelling, combustion times, CO gas yields and gasification reactivities, and NO emissions and release of K and Cl during combustion and gasification were the thermal conversion characteristics of the molasses studied. In addition, the melting behavior of molasses ash produced at 500 °C was assessed using FactSage thermodynamic modeling and differential scanning calorimetry-thermogravimetric analysis measurements. Results of the molasses thermal conversion properties were compared with those of vinasse and black liquor samples from the integrated sugar-ethanol mill and soda pulping of hardwood, respectively. The results show that the molasses droplets had the least swelling tendency and the longest combustion time in the temperature range used, suggesting a lower conversion rate of molasses in an industrial boiler than the vinasse and black liquor. Moreover, at temperatures relevant for industrial gasification processes, that is, ≥800 °C, the gasification rates of molasses were lower than those of the vinasse and black liquor, probably owing to the lower total concentration of catalytic alkali and alkaline earth metals in the molasses. The release of K and Cl to a high degree from molasses during combustion and gasification and the low melting temperature of molasses ash make it a challenging fuel to utilize using the current thermal conversion technologies. Nevertheless, a black liquor recovery boiler type with a simpler (or an oxidizing) lower furnace than that of a black liquor recovery boiler and an entrained flow gasifier of the type demonstrated for black liquor may be potential options for the production of energy and recovery of inorganic chemicals from molasses.


Annual precipitation regulates spatial and temporal drivers of lake water clarity.
Understanding how and why lakes vary and respond to different drivers through time and space is needed to understand, predict, and manage freshwater quality in an era of rapidly changing land use and climate. Water clarity regulates many characteristics of aquatic ecosystems and is responsive to watershed features, making it a sentinel of environmental change. However, whether precipitation alters the relative importance of features that influence lake water clarity or the spatial scales at which they operate is unknown. We used a data set of thousands of northern temperate lakes and asked (1) How does water clarity differ between a very wet vs. dry year? (2) Does the relative importance of different watershed features, or the spatial extent at which they are measured, vary between wet and dry years? (3) What lake and watershed characteristics regulate long-term water clarity trends? Among lakes, water clarity was reduced and less variable in the wet year than in the dry year; furthermore, water clarity was reduced much more in high-clarity lakes during the wet year than in low-clarity lakes. Climate, land use/land cover, and lake morphometry explained most variance in clarity among lakes in both years, but the spatial scales at which some features were important differed between the dry and wet years. Watershed percent agriculture was most important in the dry year, whereas riparian zone percent agriculture (around each lake and upstream features) was most important in the wet year. Between 1991 and 2012, water clarity declined in 23% of lakes and increased in only 6% of lakes. Conductance influenced the direction of temporal trend (clarity declined in lakes with low conductance), whereas the proportion of watershed wetlands, catchment-to-lake-area ratio, and lake maximum depth interacted with antecedent precipitation. Many predictors of water clarity, such as lake depth and landscape position, are features that cannot be readily managed. Given trends of increasing precipitation, eliminating riparian zone agriculture or keeping it <10% of area may be an effective option to maintain or improve water clarity.


Identification and characterization of a Drosophila ortholog of WRN exonuclease that is required to maintain genome integrity.
The premature human aging Werner syndrome (WS) is caused by mutation of the RecQ-family WRN helicase, which is unique in possessing also 3'-5' exonuclease activity. WS patients show significant genomic instability with elevated cancer incidence. WRN is implicated in restraining illegitimate recombination, especially during DNA replication. Here we identify a Drosophila ortholog of the WRN exonuclease encoded by the CG7670 locus. The predicted DmWRNexo protein shows conservation of structural motifs and key catalytic residues with human WRN exonuclease, but entirely lacks a helicase domain. Insertion of a piggyBac element into the 5' UTR of CG7670 severely reduces gene expression. DmWRNexo mutant flies homozygous for this insertional allele of CG7670 are thus severely hypomorphic; although adults show no gross morphological abnormalities, females are sterile. Like human WS cells, we show that the DmWRNexo mutant flies are hypersensitive to the topoisomerase I inhibitor camptothecin. Furthermore, these mutant flies show highly elevated rates of mitotic DNA recombination resulting from excessive reciprocal exchange. This study identifies a novel WRN ortholog in flies and demonstrates an important role for WRN exonuclease in maintaining genome stability.


Trends in snakebite deaths in India from 2000 to 2019 in a nationally representative mortality study.
The World Health Organization call to halve global snakebite deaths by 2030 will require substantial progress in India. We analyzed 2833 snakebite deaths from 611,483 verbal autopsies in the nationally representative Indian Million Death Study from 2001 to 2014, and conducted a systematic literature review from 2000 to 2019 covering 87,590 snakebites. We estimate that India had 1.2 million snakebite deaths (average 58,000/year) from 2000 to 2019. Nearly half occurred at ages 30-69 years and over a quarter in children < 15 years. Most occurred at home in the rural areas. About 70% occurred in eight higher burden states and half during the rainy season and at low altitude. The risk of an Indian dying from snakebite before age 70 is about 1 in 250, but notably higher in some areas. More crudely, we estimate 1.11-1.77 million bites in 2015, of which 70% showed symptoms of envenomation. Prevention and treatment strategies might substantially reduce snakebite mortality in India.


The Microbiological Landscape of Anaerobic Infections in Hidradenitis Suppurativa: A Prospective Metagenomic Study.
Hidradenitis suppurativa (HS) is a frequent and severe disease of the skin, characterized by recurrent or chronic skinfold suppurative lesions with a high impact on quality of life. Although considered inflammatory, antimicrobial treatments can improve or lead to clinical remission of HS, suggesting triggering microbial factors. Indeed, mixed anaerobic microbiota are associated with a majority of HS lesions. Our aim in this study was to characterize the landscape of anaerobic infections in HS using high-throughput sequencing. We sampled and cultured 149 lesions and 175 unaffected control skinfold areas from 65 adult HS patients. The microbiome of 80 anaerobic lesions was compared to that of 88 control samples by 454 high-throughput sequencing after construction of 16S ribosomal RNA gene libraries. Bacterial cultures detected anaerobes in 83% of lesions vs 53% of control samples, combined with milleri group streptococci and actinomycetes in 33% and 26% of cases, respectively. High-throughput sequencing identified 43 taxa associated with HS lesions. Two gram-negative anaerobic rod taxa, Prevotella and Porphyromonas, predominated, contrasting with a reduced abundance of aerobic commensals. These rare taxa of normal skinfold microbiota were associated with lesions independently of gender, duration and familial history of HS, body mass index, and location. Two main additional taxa, Fusobacterium and Parvimonas, correlated with the clinical severity of HS. In this study we reveal the high prevalence and particular landscape of mixed anaerobic infection in HS, paving the way for rationale targeted antimicrobial treatments.


Magneto-optical plasmonic heterostructure with ultranarrow resonance for sensing applications.
Currently, sensors invade into our everyday life to bring higher life standards, excellent medical diagnostic and efficient security. Plasmonic biosensors demonstrate an outstanding performance ranking themselves among best candidates for different applications. However, their sensitivity is still limited that prevents further expansion. Here we present a novel concept of magnetoplasmonic sensor with ultranarrow resonances and high sensitivity. Our approach is based on the combination of a specially designed one-dimensional photonic crystal and a ferromagnetic layer to realize ultralong-range propagating magnetoplasmons and to detect alteration of the environment refractive index via observation of the modifications in the Transversal Magnetooptical Kerr Effect spectrum. The fabrication of such a structure is relatively easy in comparison with e.g. nanopatterned samples. The fabricated heterostructure shows extremely sharp (angular width of 0.06°) surface plasmon resonance and even sharper magnetoplasmonic resonance (angular width is 0.02°). It corresponds to the propagation length as large as 106 μm which is record for magnetoplasmons and promising for magneto-optical interferometry and plasmonic circuitry as well as magnetic field sensing. The magnitude of the Kerr effect of 11% is achieved which allows for detection limit of 1∙10(-6). The prospects of further increase of the sensitivity of this approach are discussed.


Decreased severity of ovarian cancer and increased survival in hens fed a flaxseed-enriched diet for 1 year.
With the exception of the laying hen, no other animal model of spontaneous ovarian surface epithelial cancer replicates the human disease. Flaxseed is the richest vegetable source of omega-3 fatty acids, which are chemopreventive in breast cancer and may be important in other cancers. The objective of this study was to determine if a flaxseed-enriched diet had a chemopreventive effect on ovarian cancer in the laying hen. White Leghorn hens were fed with 10% flaxseed-enriched or standard diet for 1 year. The incidence and severity of ovarian cancer were determined by gross pathology and histology in the two groups. General health markers were also measured. Eggs were collected and analyzed by gas chromatography to determine omega-3 fatty acid levels. A significant reduction in late stage ovarian tumors was detected in the flaxseed-fed hens. Incidence rates of ovarian cancer were not significantly different between the two groups. The results indicate that a flaxseed diet increases overall survival in the laying hen. Flaxseed-fed hens' eggs incorporated significantly more omega-3 fatty acids compared to control hens. These findings show that 10% flaxseed supplementation for 1 year in the laying hen results in a significant reduction in the severity of ovarian cancer, but no change in the incidence of the disease. Hens fed flaxseed had overall better health and reduced mortality. These findings may provide the basis for a clinical trial that evaluates the efficacy of flaxseed as a chemosuppressant of ovarian cancer in women.