Phosphoproteomics and bioinformatics analyses of spinal cord proteins in rats with morphine tolerance.
Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance. To better understand the mechanism that causes morphine tolerance, we induced tolerance in rats at the spinal cord level by giving them twice-daily injections of morphine (20 µg/10 µL) for 4 days. We confirmed tolerance by measuring paw withdrawal latencies and maximal possible analgesic effect of morphine on day 5. We then carried out phosphoproteomic analysis to investigate the global phosphorylation of spinal proteins associated with morphine tolerance. Finally, pull-down assays were used to identify phosphorylated types and sites of 14-3-3 proteins, and bioinformatics was applied to predict biological networks impacted by the morphine-regulated proteins. Our proteomics data showed that repeated morphine treatment altered phosphorylation of 10 proteins in the spinal cord. Pull-down assays identified 2 serine/threonine phosphorylated sites in 14-3-3 proteins. Bioinformatics further revealed that morphine impacted on cytoskeletal reorganization, neuroplasticity, protein folding and modulation, signal transduction and biomolecular metabolism. Repeated morphine administration may affect multiple biological networks by altering protein phosphorylation. These data may provide insight into the mechanism that underlies the development of morphine tolerance.


Steroid-induced glaucoma: an avoidable cause of irreversible blindness.
A man in his 70s on regular follow-up with an ophthalmologist for 10 years presented with blurry vision in his right eye for 4 days. He was diagnosed with elevated intraocular pressure (IOP) bilaterally 18 months earlier and treated with antiglaucoma eye-drops. On direct questioning, he admitted to using fixed combination tobramycin 0.3%/dexamethasone 0.1% eye-drops frequently to relieve ocular redness and discomfort in both eyes for 3.5 years without his ophthalmologist's knowledge. Examination disclosed markedly elevated IOP, advanced optic disc cupping and tunnel vision due to steroid-induced glaucoma bilaterally. After cessation of the eye-drops and 2 weeks of antiglaucoma therapy, his IOP returned to normal and his visual field remained stable for 4 years.Our case highlights the danger of habitual self-treatment of prescription medications containing corticosteroids and the importance of taking a detailed medication history in the diagnosis and management of steroid-induced glaucoma.


Clinical manifestations of a unique X-linked retinal disorder in a large New Zealand family with a novel mutation in CACNA1F, the gene responsible for CSNB2.
To describe the phenotype in a New Zealand family with an unusual severe X-linked retinal disorder with a novel I745T mutation in CACNA1F, the gene responsible for incomplete congenital stationary night blindness (CSNB2). Members of the family tree were invited for clinical, psychophysical and electrodiagnostic evaluation. Male family members had severe non-progressive visual impairment, abnormal colour vision, congenital nystagmus, hyperopia and normal fundi. Some were intellectually disabled. Female family members had congenital nystagmus and decreased visual acuity frequently associated with high myopia. Electroretinograms (ERG) identified reduced rod and cone responses with negative waveform in male and female family members, with atypical features for CSNB2. Although there were similarities to CSNB2, distinctive features in male family members included severity of phenotype, and association of intellectual disability. Moreover, all female heterozygotes had clinical and ERG abnormalities. CACNA1F encodes the Ca(v)1.4 alpha1 subunit of a voltage-gated calcium channel, which may mediate neurotransmitter release from photoreceptors. Molecular analyses, reported separately, identified a novel I745T CACNA1F mutation that was associated in vitro with major alterations in gating and kinetics of the Ca(v)1.4 channel. It is speculated that the unique phenotype described in this family may reflect similarly altered function of Ca(v)1.4 channel activity in vivo.


Relationship between vitamin A and iron in the liver.
Anemia associated with vitamin A deficiency and increased liver iron has implicated vitamin A in the regulation of iron release from the liver. To study this relationship further, groups of weanling rats were fed diets as follows: low iron/low vitamin A, low iron/high vitamin A, normal iron/normal vitamin A, high iron/low vitamin A and high iron/high vitamin A. After 6 weeks the animals were killed, and blood and liver samples were taken for analyses of hemoglobin, hematocrit, red blood cell count, serum and liver vitamin A, serum and liver iron and total iron-binding capacity. Low dietary iron, but not low vitamin A intake, affected hemoglobin, hematocrit and red blood cell counts but not serum vitamin A levels. Mean serum vitamin A levels were not significantly lower in groups fed high dietary iron. High dietary iron was also associated with lower mean liver vitamin A levels; these differences were statistically significant only for the low vitamin A diet group. A high vitamin A intake was associated with a significantly lower mean hepatic iron level for the high dietary iron intake group. These data support the hypothesis that vitamin A is involved in the regulation of iron release from the liver.


Homozygous nonsense mutation in helix 2 of K14 causes severe recessive epidermolysis bullosa simplex.
We have studied a consanguineous family containing two children with severe, generalized epidermolysis bullosa simplex (EBS). Electron microscopy of skin biopsies from the affected individuals showed that basal keratinocytes were devoid of tonofilament bundles, although some single intermediate filament were visible. Genetic linkage analysis with the microsatellite probe D12S96 excluded the type II keratin gene cluster in this family. However, homozygosity by descent was observed with the polymorphic probes KRT9, KRT10 Ava II, and D17S1787 in both affected children, consistent with a recessive defect in a type I keratin. Immunoreactivity to keratin K5 and K15 was normal, but monoclonal antibodies LL001 and RCK107 against K14 showed no staining, suggesting a deficiency of K14 in these individuals. mRNA extracted from biopsy material was amplified by RT-PCR to obtain full-length K14 cDNA. Direct automated sequencing identified a homozygous nonsense mutation, W305X. A Hinf I restriction enzyme site is created by this nucleotide transition, which was used to confirm the presence of the mutation in this kindred and exclude it from 100 normal chromosomes. This is the fourth kindred with severe recessive EBS for whom a mutation has been found in the K14 gene. In this instance, the premature termination codon is the farthest downstream of the reported cases, occurring in the helix 2 domain and so giving a much longer translation product. Nevertheless, the heterozygous carriers are unaffected by the disease and display no epidermal fragility. We postulate that translation of the potentially dominant-negative truncated K14 might be down-regulated due to instability of the mutant mRNA, as observed in previous cases with similar mutations.


Differential expression and functional roles of chemokine (C-C motif) ligand 23 and its receptor chemokine (C-C motif) receptor type 1 in the uterine endometrium during early pregnancy in pigs.
Many chemokines expressed by cells of the uterine endometrium of mammals are involved in cell-cell interactions. However, little is known about expression and functional roles of chemokine (C-C motif) ligand 23 (CCL23) in the uterine endometrium. Results of this study demonstrated that CCL23 and its receptor, chemokine (C-C motif) receptor type 1 (CCR1), are up-regulated in porcine endometria during pregnancy. CCL23 and CCR1 mRNAs were strongly expressed in endometrial glandular (GE) and luminal (LE) epithelial cells. Treatment of porcine uterine luminal epithelial (pLE) cells with recombinant CCL23 increased the abundances of PCNA and cyclin D1, and enhanced proliferation and cell cycle progression in pLE cells. CCL23 also stimulated phosphorylation of cell signaling molecules including AKT and MAPKs in pLE cells. Furthermore, ER stress-related molecules were reduced by CCL23. These results suggest that CCL23-CCR1 signaling is important for endometrial development and establishment of pregnancy in pigs.


[Cognitive reserve and linguistic skills in healthy elderly persons].
One research strategy that can be used with the cognitive reserve is to establish groups of elderly persons who differ in key variables that affect the cognitive reserve and then compare their performance in cognitive tests. To determine which of the variables that have an influence on the cognitive reserve (measured by means of the cognitive reserve questionnaire) are related with performance in the Boston Naming Test, and in the vocabulary and grammar comprehension tests from the ECCO_Senior battery. The sample consisted of 83 elderly persons aged between 60 and 75 years. Schooling, parents' schooling, job and reading habits are closely related to the performance of the elderly in naming, grammar comprehension and vocabulary. Schooling affects the comprehension of sentences with a higher propositional density, and reading habits seem to be closely related with the comprehension of sentences that are more complex in terms of their syntax. Schooling and job affect the performance obtained when dealing with verbs in the vocabulary test.


Temporal matching of sensory-motor behavior and limbic theta rhythm deteriorates in aging rats.
The correlations between investigatory sniffing and rhythmic slow-wave activity (RSA) in the dorsal hippocampal formation were studied during free behavior in Fischer 344 rats aged 3, 18, 30, and 36 months. The amount and vigor of spontaneous exploratory behavior was reduced in older animals, and the frequency distributions of investigatory sniffing and hippocampal RSA both shifted with age toward the lower end of their normal ranges. In the youngest animals, the dominant frequency of sniffing matched that of hippocampal RSA (frequency entrainment) more often than would be predicted by chance; preferred phase differences between sniffing and hippocampal RSA were reliably observed in the 5-9 Hz range; and these preferred phase differences varied linearly as a function of frequency, implying an underlying latency relationship. These correlations changed progressively with age as follows: the incidence of frequency entrainments decreased; the frequency range within which preferred phase differences were observed became lower and narrower; and the incidence of preferred phase differences decreased. However, animals of all ages exhibited similar preferred phase differences for those frequencies at which significant preferences were expressed. These findings are discussed in relation to the hypothesis that alterations of forebrain theta rhythms may accompany aberrations of the medial septum-diagonal band-nucleus basalis complex and may be importantly involved in aging-related impairments of cognitive and learning abilities.


The troublesome semantics of conflict of interest.
The sensible response to conflicts of interest is impaired by misconceptions and sloppy usage of terminology. Apparent and potential are widely misused modifiers for conflicts. Excessive legislative focus on financial interests limits understanding of the scope and significance of researchers' conflicts of interest. There is no moral or ethical failing in having a conflict of interest; the problem occurs when conflicts are not disclosed appropriately and when conflicts are allowed to bias research, teaching, or practice. Avoidance and prevention should be applied to bias, not conflicts.


Changes in the LH response to GnRH in the ovine fetus and neonate.
The in vivo responsiveness of the ovine fetal and neonatal pituitary was investigated using acute and chronic preparations. Several studies were performed on six fetuses and six lambs from 112 days' gestation through 5 weeks after birth. Ten micrograms of gonadotropin-releasing hormone (GnRH) was injected intravenously into each fetus and lamb, and serial blood samples were collected from the fetus, ewe and lamb. The luteinizing hormone (LH) content of each sample was determined by species-specific radioimmunoassay. Both the fetus and the neonate showed a response to GnRH. A significant elevation of LH was found in all animals by 15 minutes. There was no response in the ewe when GnRH was injected into its fetus. Great variability in response was noted among various age groups and between animals, with the maximum individual LH response reaching 33.7 ng/ml. The maximum LH response of the neonate during the first week of life was significantly depressed (p < 0.05) as compared to that of the fetus and the older neonate.


A study of human-type ABH antigens on erythrocytes and in saliva of sheep.
The results of serological investigations of human type ABH antigens and antibodies of 116 sheep are presented. Traces of ABH antigens on sheep erythrocytes are recognized by elution. Agglutinins with anti-AA1, anti-B and sometimes anti-H specificity besides of heteroagglutinins were differentiated by cross-absorption experiments. It was established that the sheep saliva also contains H antigens and sometimes A and/or A1 antigens. On the basis of their serological characteristics the sheep divided into 11 serological groups. In order to explain some serological peculiarities in sheep the existence of genes for regulation, the production of ABH antigens in glucolipid form and genes for regulation of the same antigens in glucoprotein form were postulated.


[Employment of older people in the modern labor market.]
The article examines the employment of older people in the context of disrupted technological, medical and demographic changes. The relevance of the research topic is due to the demographic aging of the population, modern medical advances and changes in the nature of labor operations as a result of scientific and technological progress. In this article, the following competing hypotheses are tested: the productivity of older workers is below the level of profitability due to a steady decline in health, or vice versa, the value of older workers in the modern labor market is increasing due to the increasing role of experience, skills and qualifications. Additionally, the question of the impact of pension systems on the motivation of older people to continue working is analyzed. To test these hypotheses, based on OECD statistics, we analyzed the overall level of employment, labor force participation and unemployment, as well as temporary and underemployment for several age groups in the range of 15-65+ years. To assess the dynamics, the situation for 2000 and 2019 was analyzed. In general, the author concludes that the quantitative and qualitative parameters of employment of older people are inferior to the average working age, but over time, the use of the human capital of older people is growing. In the field of gerontology, it is recommended to pay increased attention to improving the health of the 65+ age cohort and changing labor legislation in order to stimulate the continuation of work.


Pollution caused by mining reshaped the structure and function of bacterial communities in China's largest ion-adsorption rare earth mine watershed.
Ion-adsorption rare earth mining results in the production of high levels of nitrogen, multiple metals, and strong acidic mine drainage (AMD), the impacts of which on microbial assembly and ecological functions remain unclear. To address this knowledge gap, we collected river sediments from the watershed of China's largest ion-adsorption rare earth mine and analyzed the bacterial community's structure, function, and assembly mechanisms. Results showed that bacterial community assembly was weakly affected by spatial dispersion, and dispersal limitation and homogeneous selection were the dominant ecological processes, with the latter increasing with pollution gradients. Bacterial alpha diversity decreased with pollution, which was mainly influenced by lead (Pb), pH, rare earth elements (REEs), and electrical conductivity (EC). However, bacteria developed survival strategies (i.e., enhanced acid tolerance and interspecific competition) to adapt to extreme environments, sustaining species diversity and community stability. Community structure and function showed a consistent response to the polluted environment (r = 0.662, P = 0.001). Enhanced environmental selection reshaped key microbial-mediated biogeochemical processes in the mining area, in particular weakening the potential for microbial denitrification. These findings provide new insights into the ecological response of microbes to compound pollution and offer theoretical support for proposing effective remediation and management strategies for polluted areas.


The influence of prazosin and propranolol on serum lipids and atherosclerosis in standard fed pigs.
The influence of prazosin and propranolol on serum lipids and atherosclerosis was evaluated in standard fed pigs during a nine months experimental period. The incidence and severity of atherosclerotic lesions was very low, and no difference could be observed neither between the two drugs nor between the drug groups and the placebo group. Prazosin and propranolol induced no marked change in the serum lipid profile. The results could be explained by the very low fat content, 3.6 per cent, in the present standard diet.


Long-term evaluation of the remineralization of interproximal caries-like lesions adjacent to glass-ionomer restorations: a micro-CT study.
To compare the remineralization of incipient artificial interproximal caries in the presence of three glass-ionomer cements (highly-filled glass-ionomer cement, compomer, resin-modified glass-ionomer cement) and a resin composite (control). Proximal restorations were simulated by placing tooth specimens and the various glass-ionomer cements in closed containers with artificial saliva at 37 degrees C and pH 7.0 for 30 days with constant circulation. Tomographic images were obtained with a micro CT scanner at 90, 180, and 270 days, and density-measuring software was used to calculate the micro-density of artificial caries lesions in the specimens. The mean density changes were compared between groups in order to evaluate the effects of remineralization. All data were analyzed using one-way ANOVA and the post-hoc Tukey multiple comparison test at P < 0.05. While the density of artificial caries lesions increased for all treatments, the increases for the three glass-ionomer groups were significantly higher than that for the resin group in each 3-month period. As time increased, the amount of density also increased for the glass-ionomer groups, and significant differences were found between the remineralization effects of the glass-ionomer groups. The micro CT proved to be an effective evaluation method.


Two-dimensional time resolved measurements of toroidal velocity correlated with density blobs in magnetized plasmas.
A new method for toroidal velocity measurements with Mach probes is presented. This technique is based on the conditional sampling technique, the triggering events being density blobs. A reconstruction of the time resolved two-dimensional profile of electron density, electron temperature, plasma potential, and toroidal velocity is possible with a single point measurement on a shot-to-shot basis.


Delayed consecutive exotropia following 7-millimeter bilateral medial rectus recession for congenital esotropia.
The rate of delayed consecutive exotropia after bilateral 7-millimeter medial rectus recession for large angle congenital esotropia in 88 patients was 27% (24/88), larger than previously reported. The rate was 38% (8/21) in infants having surgery prior to 7 months of age, 20% (10/49) in infants undergoing surgery at 7 to 12 months of age, and 33% (6/18) in patients undergoing surgery at 13 months of age or later. The onset of consecutive exotropia averaged 26.8 months postoperatively, allowing a long period of good alignment for binocular vision to develop before exotropia surgery was required. Physicians and parents should be aware that delayed consecutive exotropia may develop several years postoperatively. Since delayed consecutive exotropia may be characteristic of the 7-millimeter recession procedure or characteristic of all patients who have had surgery for congenital esotropia, a prospective long-term study to compare the 7-millimeter procedure with the three- and four-muscle procedure would be helpful.


Elevational gradient in species richness pattern of epigaeic beetles and underlying mechanisms at east slope of Balang Mountain in southwestern China.
We report on the species richness patterns of epigaeic beetles (Coleoptera: Carabidae and Staphylinidae) along a subtropical elevational gradient of Balang Mountain, southwestern China. We tested the roles of environmental factors (e.g. temperature, area and litter cover) and direct biotic interactions (e.g. foods and antagonists) that shape elevational diversity gradients. Beetles were sampled at 19 sites using pitfall traps along the studied elevational gradient ranging from 1500 m-4000 m during the 2004 growing season. A total of 74416 specimens representing 260 species were recorded. Species richness of epigaeic beetles and two families showed unimodal patterns along the elevational gradient, peaking at mid-elevations (c. 2535 m), and the ranges of most beetle species were narrow along the gradient. The potential correlates of both species richness and environmental variables were examined using linear and second order polynomial regressions. The results showed that temperature, area and litter cover had strong explanatory power of beetle species richness for nearly all richness patterns, of beetles as a whole and of Carabidae and Staphylinidae, but the density of antagonists was associated with species richness of Carabidae only. Multiple regression analyses suggested that the three environmental factors combined contributed most to richness patterns for most taxa. The results suggest that environmental factors associated with temperature, area and habitat heterogeneity could account for most variation in richness pattern of epigaeic beetles. Additionally, the mid-elevation peaks and the small range size of most species indicate that conservation efforts should give attention to the entire gradient rather than just mid-elevations.


A new screening method for antimitotic substances and isolation of glycolipids as stimulators of tubulin polymerization from Okinawan sponge Pseudoceratina sp.
A new screening method to detect antimitotic substances utilizing purified porcine brain microtubule proteins was developed. This method observes the inhibitory and stimulatory activities on microtubule polymerization and inhibitory activity on depolymerization in sequence. Two glycolipids, 1-O-beta-D-galactopyranosyl-2,3-di-O-acylglycerol and 1-O-tetrahydroxycyclopentyl-2-O-acyl-3-O-alkylglycerol were isolated from Okinawan marine sponge Pseudoceratina sp. by this screening method. These compounds stimulated the microtubule polymerization at 10 degrees C.


Spectral dependence of principal axes in anti-resonant hollow-core fibers with different numbers of capillaries.
We report on measurements highlighting the spectral dependence of the principal axes' angular orientation that is present within three hollow-core fibers samples of various geometries. Hollow-core anti-resonant fibers (ARFs) with six, five, and four capillaries are investigated in several transmission windows. It is shown that the six-capillary fiber structure demonstrates a much smaller shift in the principal axes' orientation, in comparison with five- and four-capillary structures. The four-capillary structure has a 90° shift of its principal axes' orientation inside even- and odd-numbered transmission windows. These results corroborate the suggestion that the six-capillary ARF structure is a great candidate for polarization-maintaining operation over a wide spectral bandwidth.


Transference and new records in Neoibidionini (Coleoptera, Cerambycidae).
Compsibidion trinidadense (Gilmour, 1963) is transferred to Glomibidion Napp Martins, 1985. Thirteen new records for species of Compsibidion Thomson, 1864, and Heterachthes Newman, 1840 are provided. Heterachthes delicatus Martins, 2009, formerly known only from Brazil (Caatinga Biome) is recorded for the first time for French Guiana (tropical moist forests). Additionally, three forgotten records are noted.


Community perceptions, attitude, practices and treatment seeking behaviour for schistosomiasis in L. Victoria islands in Uganda.
Over 200,000 people, most of them infected with Schistosoma mansoni inhabit 150 islands in Lake Victoria in Uganda. Although a programme to control the disease has been ongoing since 2003, its implementation in islands is inadequate due to high transport costs on water. In 2011 and 2012, the Global Network for Neglected Tropical Diseases (GNNTD) through Schistosomiasis Control Initiative (SCI) provided financial support to ease treatment delivery on the islands and over the period, therapeutic coverage has been increasing. We conducted a study with an objective to assess community awareness of existence of the disease, its signs, symptoms, causes and transmission as well as attitude, practice and health seeking behavior. This was a cross sectional descriptive study which used pre-tested interviewer administered questionnaire among purposively selected individuals in schools, health facilities and communities. Frequency distribution tables, graphs and cross tabulations were the main forms of data presentation. Our results showed that there are numerous challenges that must be overcome to achieve effective control of schistosomiasis in the islands. Many people especially young men are constantly on the move from island to island in search for richer fishing grounds and such groups are commonly known to miss treatment by mass chemotherapy. Unfortunately case management in health facilities is very poor; health facilities are few and understaffed mainly with unskilled personnel who are overburdened by other illnesses such as malaria and HIV and the supply of praziquantel in health facilities is inadequate. Furthermore, sanitation is appalling, no clean water and community knowledge about schistosomiasis is low even among biomedical staff. Rather than elimination, our results indicate that the programme should continue to target morbidity control beyond the 2020s until preventive measures have been instituted. The government should provide adequate trained health workers and stock praziquantel in all island health facilities.


Genetic screening of SCNN1B and SCNN1G genes in early-onset hypertensive patients helps to identify Liddle syndrome.
Liddle syndrome is an autosomal dominant form of monogenic hypertension. Phenotypic variability makes it difficult to identify patients with Liddle syndrome, resulting in misdiagnosis and severe complications at early age. To identify mutation in SCNN1B and SCNN1G genes in an adolescent with suspicious Liddle syndrome and his family members and to explore the screening target subjects of Liddle syndrome. Genetic analysis of the C-terminus of SCNN1B and SCNN1G genes was conducted in an adolescent, with treatment-resistant hypertension and hypokalemia, who was suspected of having Liddle syndrome, and his family members. A Medline research of the reported cases with Liddle syndrome was also performed. A recurrent SCNN1B mutation, c.1853C>A (p.P618H), was detected in the 19-year-old male patient, and family screening identified five additional members who were heterozygous for the mutation. The diagnosis of Liddle syndrome was made in all affected individuals. Despite the phenotypic variability, a systematic review of 54 reported index cases revealed the early-onset hypertension, aged no more than 30 years, as a common feature. Genetic screening for Liddle syndrome should be considered in hypertensive subjects with early penetrance, maybe no more than 30 years, after exclusion of common secondary causes of hypertension.


Immunological characterization of a mammary tumour virus from Swiss mice: multiple epitopes associated with the viral gene products.
The major antigens of a mouse mammary tumour virus (MMTV) isolated from the milk of exogenously infected MB+ Swiss mice were compared with the viral components of other MMTV strains by using the methodology developed by Teramoto et al. (1977 a). The anti-gp47 (Swiss) serum differentiated between type- and group-specific antigenic determinants on the major glycoprotein; two distinct type-reactivities were demonstrated, one of them being shared by the MMTVs (Swiss) and (RIII), and the other by the MMTVs (C3H) and (GR). The MMTVs (Swiss) and (RIII) also reacted identically in a 'type-specific' assay using an anti-p28 (Swiss) serum, but a distinct reactivity was observed with the MMTV (C3H). In the isologous test where an anti-(total RIII) serum was used to bind intact, externally labelled RIII virions, the Swiss virus was seen to possess a type-specific determinant on its surface which distinguished itself from both MMTVs (RIII) and (C3H). The Swiss/fC57BL mice (which are devoid of the milk virus and for this reason are referred to as MB-), expressed only the internal virus antigens in their mammary glands. Under the 'type-specific' assay conditions, the p28 antigen present in the mammary gland extracts of the MB+ mice was indistinguishable from the p28 antigen purified from the Swiss virion, but was clearly distinct from the p28 reactivity present in the mammary gland extracts of the MB- mice. The p28 (MB-) antigen may thus represent the expression of an endogenous virus sequence different from the milk virus genome.


Usefulness of non-invasive spectrophotometric haemoglobin estimation for detecting low haemoglobin levels when compared with a standard laboratory assay for preoperative assessment.
Delay in diagnosis of anaemia during preoperative assessment poses logistic problems, leading to multiple clinic visits, inadequate preoperative management, and unnecessary delay of surgery. Therefore, we tested an instant spectrophotometric haemoglobin (SpHb) measurement technique to facilitate this assessment. We evaluated portable instant SpHb vs standard laboratory screening of anaemia between March 2012 and December 2013. Paired Hb measurements were performed on 726 patients using SpHb (Pronto-7, Masimo Corporation, Irvine, CA, USA) and Hb measured on the same day using an automated analyser. The results were obtained from a group of 638 patients from the pre-anaesthetic clinic with expected normal Hb values, and 88 patients from the oncology clinic with known low Hb. Median (range) SpHb was 129.5 (67-171) compared with 136 g litre(-1) (63-178) Hb measured using the automated system. Identifying Hb below a threshold of 130 g litre(-1) for males had a high sensitivity (93%), while identifying a threshold of 120 g litre(-1) for females had lower sensitivity (75%). The specificity for males (77%) and females (81%) was similar. Mean measurement bias and agreement: tolerability interval ratio was -8.1 g litre(-1) and 2.78 for men and -3.1 g litre(-1) and 2.44 for women. SpHb was sensitive as a preliminary screening tool for detecting true low Hb values in males, but less sensitive in females. Instant SpHb measurement may enable prompt routine preoperative anaemia management, but its precision was lower than expected. This study is approved by the Tasmanian Human Ethics Committee, Australia and was registered prospectively in the Australian and New Zealand Clinical Trials Registry (http://www.ANZCTR.org.au/ ACTRN12611001256965) and the World Health Organization Clinical Trials Registry (http://apps.who.int/trialsearch/trial.aspx?trialid=ACTRN12611001256965).


[Recovery of oral function following surgical treatment for an oral cavity cancer].
Ablative surgery for oral cancer results in loss or alterations of anatomical structures, which may impair oral functions, such as speech, mastication, and swallowing. Oral functions are impaired further by significant side-effects of additional postoperative radiation therapy. Improvement of oral functions may be achieved by implant-supported prosthetic rehabilitation. The recommended treatment is a 4-implants retained overdenture. A fixed 2 unit implant-supported partial denture seems a feasible alternative treatment.


Genetically engineered islets and alternative sources of insulin-producing cells for treating autoimmune diabetes: quo vadis?
Islet transplantation is a promising therapy for patients with type 1 diabetes that can provide moment-to-moment metabolic control of glucose and allow them to achieve insulin independence. However, two major problems need to be overcome: (1) detrimental immune responses, including inflammation induced by the islet isolation/transplantation procedure, recurrence autoimmunity, and allorejection, can cause graft loss and (2) inadequate numbers of organ donors. Several gene therapy approaches and pharmaceutical treatments have been demonstrated to prolong the survival of pancreatic islet grafts in animal models; however, the clinical applications need to be investigated further. In addition, for an alternative source of pancreatic β-cell replacement therapy, the ex vivo generation of insulin-secreting cells from diverse origins of stem/progenitor cells has become an attractive option in regenerative medicine. This paper focuses on the genetic manipulation of islets during transplantation therapy and summarizes current strategies to obtain functional insulin-secreting cells from stem/progenitor cells.


Primary structure and mapping of the hupA gene of Salmonella typhimurium.
In bacteria, the complex nucleoid structure is folded and maintained by negative superhelical tension and a set of type II DNA-binding proteins, also called histonelike proteins. The most abundant type II DNA-binding protein is HU. Southern blot analysis showed that Salmonella typhimurium contained two HU genes that corresponded to Escherichia coli genes hupA (encoding HU-2 protein) and hupB (encoding HU-1). Salmonella hupA was cloned, and the nucleotide sequence of the gene was determined. Comparison of hupA of E. coli and S. typhimurium revealed that the HU-2 proteins were identical and that there was high conservation of nucleotide sequences outside the coding frames of the genes. A 300-member genomic library of S. typhimurium was constructed by using random transposition of MudP, a specialized chimeric P22-Mu phage that packages chromosomal DNA unidirectionally from its insertion point. Oligonucleotide hybridization against the library identified one MudP insertion that lies within 28 kilobases of hupA; the MudP was 12% linked to purH at 90.5 min on the standard map. Plasmids expressing HU-2 had a surprising phenotype; they caused growth arrest when they were introduced into E. coli strains bearing a himA or hip mutation. These results suggest that IHF and HU have interactive roles in bacteria.


A comparative study of smoking, drinking and dietary habits in population samples in France, Italy, Spain and Switzerland. II. Tobacco smoking.
This paper describes the smoking habits of six populations in France, Switzerland, Italy and Spain. A total of 2,965 men and 2,369 women have been interviewed. The proportion of ever smoking men is almost the same (75 to 80%) everywhere but in Geneva and Calvados a higher proportion of smokers quitted the habit (over 30%). In females, on the contrary, the prevalences of ever smokers is higher in Torino (42%) and Geneva (36%) than in Spain (25%) and Calvados (19%). Young females, however, tend to smoke more and intercountry differences tend to disappear. In both sexes successive generations begin to smoke earlier. Exclusive use of black tobacco is still very high in Calvados (90%) and Navarra (80%) whilst it tends to disappear in Italy (30%). Plain cigarettes decrease everywhere, especially in Spain and Varese, but they are still smoked by the majority of men in Calvados. The results suggest that the tobacco epidemic is still increasing in those areas where it began more recently.


HilE Regulates HilD by Blocking DNA Binding in Salmonella enterica Serovar Typhimurium.
The Salmonella type three secretion system (T3SS), encoded in the Salmonella pathogenicity island 1 (SPI1) locus, mediates the invasion of the host intestinal epithelium. SPI1 expression is dependent upon three AraC-like regulators: HilD, HilC, and RtsA. These regulators act in a complex feed-forward loop to activate each other and hilA, which encodes the activator of the T3SS structural genes. HilD has been shown to be the major integration point of most signals known to activate the expression of the SPI1 T3SS, acting as a switch to control induction of the system. HilE is a negative regulator that acts upon HilD. Here we provide genetic and biochemical data showing that HilE specifically binds to HilD but not to HilC or RtsA. This protein-protein interaction blocks the ability of HilD to bind DNA as shown by both an in vivo reporter system and an in vitro gel shift assay. HilE does not affect HilD dimerization, nor does it control the stability of the HilD protein. We also investigated the role of HilE during the infection of mice using competition assays. Although deletion of hilE does not confer a phenotype, the hilE mutation does suppress the invasion defect conferred by loss of FliZ, which acts as a positive signal controlling HilD protein activity. Together, these data suggest that HilE functions to restrict low-level HilD activity, preventing premature activation of SPI1 until positive inputs reach a threshold required to fully induce the system.IMPORTANCESalmonella is a leading cause of gastrointestinal and systemic disease throughout the world. The SPI1 T3SS is required for Salmonella to induce inflammatory diarrhea and to gain access to underlying tissue. A complex regulatory network controls expression of SPI1 in response to numerous physiological inputs. Most of these signals impinge primarily on HilD translation or activity. The system is triggered when HilD activity crosses a threshold that allows efficient activation of its own promoter. This threshold is set by HilE, which binds to HilD to prevent the inevitable minor fluctuations in HilD activity from inappropriately activating the system. The circuit also serves as a paradigm for systems that must integrate numerous environmental parameters to control regulatory output.


miR-566 expression and immune changes in patients with intracranial aneurysm.
Our study aims to investigate the correlations of micro ribonucleic acid (miR)-566 expression with the changes in immune-related indexes and differential genes in patients with intracranial aneurysm (IA). Aneurysm wall tissues from a total of 50 IA cases and the corresponding normal arterial wall tissues from 50 individuals were selected. The miR-566 expression, differential gene expression profile, and expression level of differential gene proteins were detected and analyzed by fluorescence quantitative polymerase chain reaction (qPCR), RNAseq technique and western blotting, respectively. The miR-566 level was significantly higher in intracranial aneurysm tissues than that in normal arterial wall tissues (P<0.05). The levels of cluster of differentiation (CD)3+, CD4+, CD8+, CD4+/CD8+ and CD23+ T lymphocytes in the peripheral blood of IA patients significantly declined compared with those in the control group (P<0.05). RNAseq detection showed that there were 16 immune-inflammation-related genes significantly differentially expressed in aneurysm wall tissues compared with normal arterial wall tissues in the control group. The levels of VHL and NIK in aneurysm wall tissues were significantly decreased, while those of VEGF and ALOX5 were obviously increased. Both mRNA and protein levels of these four genes also had significant changes, which had linear relations to the expression of miR-566. The abnormal expression of miR-566 affects the immune function, thus promoting the occurrence and deterioration of intracranial aneurysm.


The Relation of Light-to-Moderate Alcohol Consumption to Glucose Metabolism and Insulin Resistance in Nondiabetic Adults: the Moderating Effects of Depressive Symptom Severity, Adiposity, and Sex.
We examined the relation of alcohol consumption to glucose metabolism and insulin resistance (IR) as a function of depressive symptoms, adiposity, and sex. Healthy adults (aged 18-65 years) provided fasting blood samples and information on lifestyle factors. Alcohol intake was categorized as never, infrequent (1-3 drinks/month), occasional (1-7 drinks/week), and regular (≥2 drinks/day) drinkers. The Beck Depression Inventory (BDI) was used to assess symptom severity. Primary outcomes were fasting insulin, glucose, and IR assessed by the homeostasis model assessment (HOMA). In univariate analysis, alcohol consumption was negatively associated with HOMA-IR (p = 0.03), insulin (p = 0.007), and body mass index (BMI) (p = 0.04), but not with glucose or BDI. Adjusting for potential confounders including BMI, alcohol consumption was associated with HOMA-IR (p = 0.01) and insulin (p = 0.009) as a function of BDI and sex. For women with minimal depressive symptoms, light-to-moderate alcohol consumption was associated with lower HOMA-IR and insulin. Alcohol consumption was not associated with metabolic markers in women with higher depressive symptoms and in men. In analysis using BMI as a continuous moderator, alcohol consumption was only associated with insulin (p = 0.004). Post-hoc comparisons between BMI groups (<25 vs ≥25 kg/m2) revealed that light-to-moderate alcohol consumption was associated with lower insulin but only in subjects with BMI ≥ 25 kg/m2. The benefits of light-to-moderate alcohol consumption on fasting insulin and IR are sex dimorphic and appear to be independently moderated by adiposity and depressive symptom severity.


Genome-wide DNA methylation profiling integrated with gene expression profiling identifies PAX9 as a novel prognostic marker in chronic lymphocytic leukemia.
In chronic lymphocytic leukemia (CLL), epigenomic and genomic studies have expanded the existing knowledge about the disease biology and led to the identification of potential biomarkers relevant for implementation of personalized medicine. In this study, an attempt has been made to examine and integrate the global DNA methylation changes with gene expression profile and their impact on clinical outcome in early stage CLL patients. The integration of DNA methylation profile (n = 14) with the gene expression profile (n = 21) revealed 142 genes as hypermethylated-downregulated and; 62 genes as hypomethylated-upregulated in early stage CLL patients compared to CD19+ B-cells from healthy individuals. The mRNA expression levels of 17 genes identified to be differentially methylated and/or differentially expressed was further examined in early stage CLL patients (n = 93) by quantitative real time PCR (RQ-PCR). Significant differences were observed in the mRNA expression of MEIS1, PMEPA1, SOX7, SPRY1, CDK6, TBX2, and SPRY2 genes in CLL cells as compared to B-cells from healthy individuals. The analysis in the IGHV mutation based categories (Unmutated = 39, Mutated = 54) revealed significantly higher mRNA expression of CRY1 and PAX9 genes in the IGHV unmutated subgroup (p < 0.001). The relative risk of treatment initiation was significantly higher among patients with high expression of CRY1 (RR = 1.91, p = 0.005) or PAX9 (RR = 1.87, p = 0.001). High expression of CRY1 (HR: 3.53, p < 0.001) or PAX9 (HR: 3.14, p < 0.001) gene was significantly associated with shorter time to first treatment. The high expression of PAX9 gene (HR: 3.29, 95% CI 1.172-9.272, p = 0.016) was also predictive of shorter overall survival in CLL. The DNA methylation changes associated with mRNA expression of CRY1 and PAX9 genes allow risk stratification of early stage CLL patients. This comprehensive analysis supports the concept that the epigenetic changes along with the altered expression of genes have the potential to predict clinical outcome in early stage CLL patients.


Pathogenicity of newly isolated coxsackievirus B4 for mouse pancreas.
Coxsackievirus B4 fresh isolates from patients with upper respiratory illness and aseptic meningitis were studied for their pathogenicity in the pancreas of SJL/J mice. Out of 12 virus isolates, 7 induced hypoglycaemia in mice 2 to 4 days after virus inoculation. All 3 isolates from faeces of patients induced hypoglycaemia in contrast to 3 viruses isolated from the cerebrospinal fluid which did not. Six isolates from throat swabs were either pathogenic (4 isolates) or non-pathogenic (2 isolates). It is concluded that at least two biologically distinct coxsackieviruses B4 prevail among humans.


High-order harmonic generation from Rydberg atoms in inhomogeneous fields.
We theoretically investigate the high-order harmonic generation (HHG) from Rydberg atoms considering the spatial inhomogeneity of the driving field. It is found that in the inhomogeneous field, the effect of the cutoff extension in the harmonic spectrum from Rydberg atoms can be extended to multi-cycle regime, while in the homogeneous field case, the extension of the harmonic cutoff is limited to the few-cycle regime (less than two optical cycles). The underlying physics of the cutoff extension from Rydberg atoms in the inhomogeneous field is analyzed based on the classical and quantum-mechanical models. Furthermore, by optimizing the field inhomogeneity, the electron dynamics can be well controlled to generate a smooth supercontinuum in the extended spectral region. This can support the efficient generation of isolated attosecond pulses in Rydberg atoms from multi-cycle laser fields.


Contemporary Modalities to Image the Fetal Brain.
Fetal brain ultrasound remains as the mainstay for screening fetal intracranial anatomy. One of its main advantages is the availability of 3 dimensional and other ultrasound modalities for a better understanding of fetal neurodevelopment. Neurosonography is performed when findings, suggestive of an abnormality, are present on a screening ultrasound or if a high-risk situation of brain injury is present. This technique offers the use of complementary imaging planes, axial, coronal and sagittal, and the ability to image intracranial anatomy from the transabdominal and transvaginal approaches. Fetal brain magnetic resonance imaging is more sensitive than ultrasound. As an adjunctive imaging modality, magnetic resonance imaging offers additional sequences to complete the information on neurodevelopment from different perspectives, such as brain metabolism, microstructure, and connectivity.


Systematic review of the prevalence of gastric intestinal metaplasia and its area-level association with smoking.
We aimed to show an area-level association between the frequency of intestinal metaplasia (IM) in Helicobacter pylori-infected patients and tobacco consumption. We systematically reviewed the literature to retrieve data on the prevalence of IM in different countries and performed an ecological analysis to quantify the association between the prevalence of IM among infected subjects and smoking, using data on national tobacco availability. Articles evaluating IM in the general population or in dyspeptic patients were identified by a MEDLINE search. We selected one study per country, giving preference to those for which the study design/populations evaluated provided the highest external validity and inter-study comparability of methodology. This systematic review of published data retrieved information for 29 countries from 5 continents depicting a wide variation in the prevalence of IM among H. pylori-infected subjects in different regions, ranging from 3% in Argentina to 55% in New Zealand. In countries exhibiting a simultaneously high prevalence of infection and low incidence of gastric cancer, IM was also relatively infrequent (Thailand, 6%; India, 8.2%; Nigeria, 11.1%; Gambia, 11.8%; Saudi Arabia, 15.5%; Iran, 15.6%; Egypt, 24.4%). A significant correlation was observed between IM prevalence in infected subjects and tobacco availability (r = 0.45; p = 0.02). Our results show that the concept of the African and Asian "enigmas" may be extended to precancerous lesions. Tobacco availability was positively associated with the prevalence of IM among H. pylori-infected subjects at an area level.


A differential scanning calorimetric study of the thermal unfolding of apo- and holo-cytochrome b562.
Cytochrome b562 is a four-helix-bundle protein containing a non-covalently bound b-type heme prosthetic group. In the absence of heme, cytochrome b562 remains highly structured under native conditions. Here we report thermodynamic data for the thermal denaturation of the holo- and apoproteins as determined by differential scanning calorimetry. Thermal denaturation of holocytochrome b562 is a highly reversible process, and unexpectedly does not involve dissociation of the heme prosthetic group. Thermal denaturation of the corresponding apoprotein, with the heme group chemically removed, remains a cooperative, reversible process. Apocytochrome b562 is substantially destabilized relative to the holoprotein: the t1/2 is more than ten degrees lower, and enthalpy and heat capacity changes are about one-half of the holoprotein values. However, the energetic parameters of apocytochrome b562 denaturation are within the range of observed values for small proteins.


Suicides in San Mateo County.
The usual surveys of completed suicides, encompassing, as they do, large geographical areas, are of limited value to physicians of a particular community. The unique and differentiating characteristics of the suicides in his locale may be "washed out" in these large surveys.San Mateo County has an annual suicide rate of 17 per 100,000 and a disproportionately high incidence in persons over 65 years old. In this particular county females, widows and Orientals are more prone to suicide than has usually been reported elsewhere. Alcohol was directly or indirectly involved in a significant number of instances. Many of the persons who killed themselves were under a physician's care at the time of self-destruction. There are probably important ecological and sociological variables as well as personal factors involved in the suicidal process that are of significance to any suicide prevention program. It is urged that there be more extensive and comparative research in this important public health problem.


Nurse's use of power to standardise nursing terminology in electronic health records.
To describe nurses' use of power to influence the incorporation of standardised nursing terminology within electronic health records. Little is known about nurses' potential use of power to influence the incorporation of standardised nursing terminology within electronic health records. The theory of group power within organisations informed the design of the descriptive, cross-sectional study used a survey method to assess nurses' use of power to influence the incorporation of standardised nursing terminology within electronic health records. The Sieloff-King Assessment of Group Power within Organizations© and Nursing Power Scale was used. A total of 232 nurses responded to the survey. The mean power capability score was moderately high at 134.22 (SD 18.49), suggesting that nurses could use power to achieve the incorporation of standardised nursing terminology within electronic health records. The nurses' power capacity was significantly correlated with their power capability (r = 0.96, P < 0.001). Nurses may use power to achieve their goals, such as the incorporation of standardised nursing terminology within electronic health records. Nurse administrators may use their power to influence the incorporation of standardised nursing terminology within electronic health records. If nurses lack power, this could decrease nurses' ability to achieve their goals and contribute to the achievement of effective patient outcomes.


Influence of melatonin associated with the Bio-Gide® membrane on osteoblast activity: an in vitro Study.
Melatonin (MLT) is a hormone responsible for regulating several physiological processes. It has been shown that MLT can be an important mediator in bone formation and stimulation, promoting osteoblast differentiation. In clinical practice, in tissue regeneration procedures, it is necessary to use membranes or barriers, associated with biomaterials, or not. The aim of this in vitro study was to assess the effect of melatonin on the activity of osteoblastic cells, associated, or not, with a resorbable collagen membrane (Bio-Gideä). For this, mice-derived pre-osteoblastic cells MC3T3 obtained from the ATCC (American Type Culture Collection) were used. Cultured cells were subject to the following treatments: MLT with a concentration of 1mM, a Bio-Gideä membrane and a membrane associated with MLT (Bio-Gideä + MLT). Proliferation and cell viability assays and protein lysate (ELISA test) quantification for the BMP-2 protein were carried out, in periods of 72 hours, 7 days and 10 days. After analyzing the data (one-way ANOVA, alpha=5%) it was observed that when MLT was used in isolation, there was an increase in cell proliferation and viability in osteoblastic cells (p<0.05). But, when MLT was associated with resorbable membranes, there was an inverse behavior, both in terms of proliferation and viability (p<0.05). In the case of the ELISA test, no secretion of BMP-2 was detected in any of the analyzed groups. It is concluded that MLT has a stimulatory effect on osteoblasts, but, when associated with Bio-Gideä resorbable membranes, it does not show any viable action in osteoblastic cell stimulation.


Osteomyelitis due to Mycobacterium haemophilum in a cardiac transplant patient: case report and analysis of interactions among clarithromycin, rifampin, and cyclosporine.
We describe a case of osteomyelitis due to Mycobacterium haemophilum in a cardiac transplant recipient and review the two other reported cases of M. haemophilum infection in cardiac transplant patients. Our patient had an excellent response to a prolonged course of therapy with clarithromycin and rifampin. We examine in detail the interactions between these two antibiotics and cyclosporine, including the apparently offsetting effects of clarithromycin/rifampin combination therapy on blood levels of cyclosporine.


Ectopic expression of Nav1.7 in spinal dorsal horn neurons induced by NGF contributes to neuropathic pain in a mouse spinal cord injury model.
Neuropathic pain (NP) induced by spinal cord injury (SCI) often causes long-term disturbance for patients, but the mechanisms behind remains unclear. Here, our study showed SCI-induced ectopic expression of Nav1.7 in abundant neurons located in deep and superficial laminae layers of the spinal dorsal horn (SDH) and upregulation of Nav1.7 expression in dorsal root ganglion (DRG) neurons in mice. Pharmacologic studies demonstrated that the efficacy of the blood-brain-barrier (BBB) permeable Nav1.7 inhibitor GNE-0439 for attenuation of NP in SCI mice was significantly better than that of the BBB non-permeable Nav1.7 inhibitor PF-05089771. Moreover, more than 20% of Nav1.7-expressing SDH neurons in SCI mice were activated to express FOS when there were no external stimuli, suggesting that the ectopic expression of Nav1.7 made SDH neurons hypersensitive and Nav1.7-expressing SDH neurons participated in central sensitization and in spontaneous pain and/or walking-evoked mechanical pain. Further investigation showed that NGF, a strong activator of Nav1.7 expression, and its downstream JUN were upregulated after SCI in SDH neurons with similar distribution patterns and in DRG neurons too. In conclusion, our findings showed that the upregulation of Nav1.7 was induced by SCI in both SDH and DRG neurons through increased expression of NGF/JUN, and the inhibition of Nav1.7 in both peripheral and spinal neurons alleviated mechanical pain in SCI mice. These data suggest that BBB permeable Nav1.7 blockers might relieve NP in patients with SCI and that blocking the upregulation of Nav1.7 in the early stage of SCI via selective inhibition of the downstream signaling pathways of NGF or Nav1.7-targeted RNA drugs could be a strategy for therapy of SCI-induced NP.


Soluble material secreted from Penicillium chrysogenum isolate exhibits antifungal activity against Cryphonectria parasitica- the causative agent of the American Chestnut Blight.
The American chestnut (Castanea dentata) was once the dominant canopy tree along the eastern region of the United States. Cryphonectria parasitica, the causative agent of chestnut blight, was introduced from Asia in the early 1900's, and obliterated the chestnut population within 50 years. We sought to identify environmental microbes capable of producing factors that were fungicidal or inhibited growth of C. parasitica in the hopes developing a biological control of chestnut blight. We isolated a filamentous fungus that significantly inhibited the growth of C. parasitica upon co-cultivation. Extracellular fractions of this fungal isolate prevented C. parasitica growth, indicating that a potential fungicide was produced by the novel isolate. Sequence analysis of 18S rRNA identified this inhibitory fungus as Penicillium chrysogenum. Furthermore, these extracellular fractions were tested as treatments for blight in vivo using chestnut saplings. Scarred saplings that were treated with the P. chrysogenum extracellular fractions healed subjectively better than those without treatment when inoculated with C. parasitica. These data suggest that material secreted by P. chrysogenum could be used as a treatment for the American chestnut blight. This work may assist the reclamation of the American chestnut in association with breeding programs and blight attenuation. Specifically, treatment of small groves under the right conditions may allow them to remain blight free. Future work will explore the mechanism of action and specific target of the extracellular fraction.


Lipid management in 13,000 high risk cardiovascular patients treated under daily practice conditions: LIMA Registry.
We aimed to document the drug management of patients at high cardiovascular risk in daily practice, with the special focus on lipid-lowering treatment. In this prospective noninterventional study in 2387 outpatient centers throughout Germany, a total of 13,942 high-risk patients (mean age 65.7 years, 61.6% males) were treated with simvastatin 40 mg/day at entry as monotherapy. All patients were followed up for 12 months in terms of drug utilization, laboratory values, target attainment, and clinical events (including death, hospitalization, vascular events, and dialysis). Patients had coronary heart disease in 35.0%, diabetes mellitus in 24.4%, and the combination of coronary heart disease plus diabetes mellitus in 25.7%. In 21% of patients, a cholesterol absorption inhibitor was added to statin therapy at the entry visit, and in 23%, this was added at the follow up visit 6 months later. The target values for low-density lipoprotein-cholesterol (<2.6 mmol/L) were reached by 31.8% of patients at entry and by 50.0% at the end of this registry after 12 months. Mean blood pressure decreased (from 135.9/80.5 mmHg at baseline) by 3.1/1.9 mmHg after 12 months. In patients with documented diabetes, the targeted glycated hemoglobin (HbA1c <6.5%) was reached by 33.5% at baseline and by 40.0% after 12 months. Clinical events occurred in 11.7% of patients between baseline and month 6, and in 12.0% between months 6 and 12. In patients at high risk for cardiovascular events, comprehensive management under daily practice conditions leads to improvement of lipid, glucose, and blood pressure parameters. There is a need to improve secondary prevention among high-risk patients.


Chromosome mapping in Staphylococcus aureus.
The genome of Staphylococcus aureus was mapped by enumerating mutants induced by nitrosoguanidine during synchronous chromosomal replication following release from phenethanol inhibition. Both chromosomal replication time and cell division time were 120 min for this strain of S. aureus. Duplication of genes occurred within a 10-min period of the 120 min required for chromosomal replication. A high-resolution method was devised to determine the gene order of four genes that duplicated in the same 10-min interval of replication of the chromosome. A genomic map locating the positions of 10 genes was derived.


Secretion of different types of gelatinases from cultured human keratinocytes.
We investigated gelatinolytic enzymes derived from cultured human keratinocytes. Using a zymograph, we detected 92 kDa and 72 kDa gelatinases as major components and 83 kDa as a minor component from a conditioned cultured medium (BSL-K110, Kyokutoseiyaku Co.) of keratinocytes. After several passages, the 72 kDa band disappeared, and the 83 kDa band became dominant in another conditioned culture medium (K-GM, Kurashikibouseki Co.); these keratinocytes had a relatively differentiated appearance. These results suggest that some mechanism may regulate the secretion of selected types of gelatinase from keratinocytes under different conditions.


Synaptotagmins 1 and 7 Play Complementary Roles in Somatodendritic Dopamine Release.
The molecular mechanisms underlying somatodendritic dopamine (DA) release remain unresolved, despite the passing of decades since its discovery. Our previous work showed robust release of somatodendritic DA in submillimolar extracellular Ca2+ concentration ([Ca2+]o). Here we tested the hypothesis that the high-affinity Ca2+ sensor synaptotagmin 7 (Syt7), is a key determinant of somatodendritic DA release and its Ca2+ dependence. Somatodendritic DA release from SNc DA neurons was assessed using whole-cell recording in midbrain slices from male and female mice to monitor evoked DA-dependent D2 receptor-mediated inhibitory currents (D2ICs). Single-cell application of an antibody to Syt7 (Syt7 Ab) decreased pulse train-evoked D2ICs, revealing a functional role for Syt7. The assessment of the Ca2+ dependence of pulse train-evoked D2ICs confirmed robust DA release in submillimolar [Ca2+]o in wild-type (WT) neurons, but loss of this sensitivity with intracellular Syt7 Ab or in Syt7 knock-out (KO) mice. In millimolar [Ca2+]o, pulse train-evoked D2ICs in Syt7 KOs showed a greater reduction in decreased [Ca2+]o than seen in WT mice; the effect on single pulse-evoked DA release, however, did not differ between genotypes. Single-cell application of a Syt1 Ab had no effect on train-evoked D2ICs in WT SNc DA neurons, but did cause a decrease in D2IC amplitude in Syt7 KOs, indicating a functional substitution of Syt1 for Syt7. In addition, Syt1 Ab decreased single pulse-evoked D2ICs in WT cells, indicating the involvement of Syt1 in tonic DA release. Thus, Syt7 and Syt1 play complementary roles in somatodendritic DA release from SNc DA neurons.SIGNIFICANCE STATEMENT The respective Ca2+ dependence of somatodendritic and axonal dopamine (DA) release differs, resulting in the persistence of somatodendritic DA release in submillimolar Ca2+ concentrations too low to support axonal release. We demonstrate that synaptotagmin7 (Syt7), a high-affinity Ca2+ sensor, underlies phasic somatodendritic DA release and its Ca2+ sensitivity in the substantia nigra pars compacta. In contrast, we found that synaptotagmin 1 (Syt1), the Ca2+ sensor underlying axonal DA release, plays a role in tonic, but not phasic, somatodendritic DA release in wild-type mice. However, Syt1 can facilitate phasic DA release after Syt7 deletion. Thus, we show that both Syt1 and Syt7 act as Ca2+ sensors subserving different aspects of somatodendritic DA release processes.


Adding remifentanil to propofol and etomidate in cardioversion anesthesia.
To compare their effects on cardiorespiratoy and recovery parameters and side effects. This study was performed in The Ministry of Health Ankara Numune Research and Training Hospital, Ankara, Turkey, from January to May 2005. The 40 American Society of Anesthesiology II/III patients were randomized into 2 groups. All patients received remifentanil 0.75 microgram.kg(-1); and then received either etomidate 0.1 mg.kg(-1) (group E, n=20) or propofol 0.5 mg.kg(-1) (group P, n=20). Cardiorespiratory data, induction time, recovery parameters, pain scores, number of shocks (NS), total amount of energy used (TE), side effects, and patient/cardiologist satisfaction were recorded. Induction time and recovery parameters were shorter in group P. No differences were seen between the groups in NS and mean TE required. In group P, a statistically significant decrease in mean blood pressure occurred after induction and returned to its baseline levels in 6 minutes. After cardioversion over 2 minutes, the respiratory rates were decreased significantly more in group P when compared with group E. Two patients in group P became apneic and needed assisted ventilation. Pain scores, side effects and patient/cardiologist satisfaction were similar in both groups. No patients in either group had myoclonus. We can induce hypnosis with propofol 0.5 mg.kg(-1) or etomidate 0.1 mg.kg(-1) by adding remifentanil 0.75 microgram.kg-1 in cardioversion anesthesia. Although recovery parameters were longer in group E, and cardiorespiratory parameters were less stable in group P, their usage with remifentanil was both acceptable for cardioversion anesthesia.


INDIRECT SELECTION OF STIGMA POSITION IN IPOMOPSIS AGGREGATA VIA A GENETICALLY CORRELATED TRAIT.
Experimental manipulation of a trait can be used to distinguish direct selection from selection of correlated traits and to identify mechanisms of selection. Here we use experiments to investigate phenotypic selection of stigma position in angiosperm flowers. In natural populations of the subalpine herb Ipomopsis aggregata, plants with more strongly exserted stigmas receive more pollen per flower, indicating selection favoring stigma exsertion during the pollination stage of the life cycle. We pose four hypotheses for this association, two involving direct selection on stigma position and two involving indirect selection of a correlated floral trait. The first three hypotheses were tested using hand pollinations that mimicked natural hummingbird visitation, and by presenting captive hummingbirds with a series of flowers that differed in stigma and anther positions, sex ratio, and presence of anthers. In these experiments, pollen deposition either was independent of stigma exsertion or was highest on inserted stigmas, suggesting direct selection against exserted stigmas. In natural populations, however, stigma exsertion is highly correlated with time spent by the protandrous flowers in the pistillate phase. When we manipulated the latter trait in the field, pollen deposition increased with duration of exposure to hummingbirds, indicating indirect selection for stigma exsertion. Stigma exsertion and time spent in the pistillate phase are genetically and phenotypically correlated, as shown by a quantitative genetic experiment conducted in the field with paternal half sibships. Our results suggest that the evolution of stigma position can be driven by selection of a genetically correlated trait.


Potential plasma biomarkers at low altitude for prediction of acute mountain sickness.
Ascending to high altitude can induce a range of physiological and molecular alterations, rendering a proportion of lowlanders unacclimatized. The prediction of acute mountain sickness (AMS) prior to ascent to high altitude remains elusive. A total of 40 participants were enrolled for our study in the discovery cohort, and plasma samples were collected from all individuals. The subjects were divided into severe AMS-susceptible (sAMS) group, moderate AMS-susceptible (mAMS) group and non-AMS group based on the Lake Louise Score (LLS) at both 5000m and 3700m. Proteomic analysis was conducted on a cohort of 40 individuals to elucidate differentially expressed proteins (DEPs) and associated pathways between AMS-susceptible group and AMS-resistant group at low altitude (1400m) and middle high-altitude (3700m). Subsequently, a validation cohort consisting of 118 individuals was enrolled. The plasma concentration of selected DEPs were quantified using ELISA. Comparative analyses of DEPs among different groups in validation cohort were performed, followed by Receiver Operating Characteristic (ROC) analysis to evaluate the predictive efficiency of DEPs for the occurrence of AMS. The occurrence of the AMS symptoms and LLS differed significantly among the three groups in the discovery cohort (p<0.05), as well as in the validation cohort. Comparison of plasma protein profiles using GO analysis revealed that DEPs were primarily enriched in granulocyte activation, neutrophil mediated immunity, and humoral immune response. The comparison of potential biomarkers between the sAMS group and non-AMS group at low altitude revealed statistically higher levels of AAT, SAP and LTF in sAMS group (p=0.01), with a combined area under the curve(AUC) of 0.965. Compared to the mAMS group at low altitude, both SAP and LTF were found to be significantly elevated in the sAMS group, with a combined AUC of 0.887. HSP90-α and SAP exhibited statistically higher levels in the mAMS group compared to the non-AMS group at low altitude, with a combined AUC of 0.874. Inflammatory and immune related biological processes were significantly different between AMS-susceptible and AMS-resistant groups at low altitude and middle high-altitude. SAP, AAT, LTF and HSP90-α were considered as potential biomarkers at low altitude for the prediction of AMS.


B cells contribute to MS pathogenesis through antibody-dependent and antibody-independent mechanisms.
For many years, central dogma defined multiple sclerosis (MS) as a T cell-driven autoimmune disorder; however, over the past decade there has been a burgeoning recognition that B cells contribute to the pathogenesis of certain MS disease subtypes. B cells may contribute to MS pathogenesis through production of autoantibodies (or antibodies directed at foreign bodies, which unfortunately cross-react with self-antigens), through promotion of T cell activation via antigen presentation, or through production of cytokines. This review highlights evidence for antibody-dependent and antibody-independent B cell involvement in MS pathogenesis.


Cryoablation and immunity in non-small cell lung cancer: a new era of cryo-immunotherapy.
Despite remarkable advances in tumor response and patient survival in the past decade, systemic immunotherapies for lung cancer result in an objective response in only around half of patients treated. On the basis of this limitation, combination strategies are being investigated to improve response rates. Cryoablation has been proposed as one such technique to induce immunogenic cell death and synergize with systemic immunotherapies, including immune checkpoint inhibitors. Cryoablation has been traditionally delivered percutaneously with imaging guidance although recent technological advances allow for bronchoscopic delivery. Herein, we review the pre-clinical and clinical evidence for the use of cryoablation in non-small cell lung cancer and potential induction of anti-tumor immunity. We highlight ongoing studies involving this approach and propose areas of future investigation.


Polysaccharide Regulation of Intestinal Flora: A Viable Approach to Maintaining Normal Cognitive Performance and Treating Depression.
The intestinal tract of a healthy body is home to a large variety and number of microorganisms that will affect every aspect of the host's life. In recent years, polysaccharides have been found to be an important factor affecting intestinal flora. Polysaccharides are widely found in nature and play a key role in the life activities of living organisms. In the intestinal tract of living organisms, polysaccharides have many important functions, such as preventing the imbalance of intestinal flora and maintaining the integrity of the intestinal barrier. Moreover, recent studies suggest that gut microbes can influence brain health through the brain-gut axis. Therefore, maintaining brain health through polysaccharide modulation of gut flora deserves further study. In this review, we outline the mechanisms by which polysaccharides maintain normal intestinal flora structure, as well as improving cognitive function in the brain via the brain-gut axis by virtue of the intestinal flora. We also highlight the important role that gut microbes play in the pathogenesis of depression and the potential for treating depression through the use of polysaccharides to modulate the intestinal flora.


Specific causes of morbidity among Swedish horses insured for veterinary care between 1997 and 2000.
The principal aim of this study was to analyse the incidence of disease due to general and more specific causes among over 100,000 horses covered by complete insurance for veterinary care by a Swedish insurance company during 1997 to 2000. The database was used to calculate the rate of cause-specific morbidity in horses of different ages, sexes and breed groups kept in different regions with different human population densities. The joints were the most commonly affected part of the body, followed by unspecified/whole body, the skin and the digestive system. The most common specific diagnosis was fetlock arthritis, followed by lameness of undefined origin, other locomotor problems, traumatic injuries to the skin, arthritis in several joints, and colic. Geldings had the highest rate of at least one disease event in the joints, unspecified/whole body, skeletal or respiratory system, whereas in the other four major systems the difference between the sexes was marginal.


[Dermatological and rheumatic symptoms in neoplasmas].
Some of the symptoms that occur in neoplasmas are not directly related to tumor mass or metastasis. These may be an expression of paraneopastic syndromes and occur simultaneously or during neoplastic disease, but it is extremely important that they can precede the first symptoms of malignancy by several months or years. The clinical picture of paraneopastic syndromes often includes symptoms of defined disease or symptoms which resemble them. The association of neoplasmas and certain dermatological or rheumatic diseases is complex. Most of them are more likely to occur as primary diseases, therefore it is important for dermatologist and rheumatologist have an oncological awareness, especially in cases which are not routinely treated.


Significant reduction of fluoroscopy repetition with lumbar localization system in minimally invasive spine surgery: A prospective study.
The conventional location methods for minimally invasive spinal surgery (MISS) were mainly based on repeated fluoroscopy in a trial-and-error manner preoperatively and intraoperatively. Localization system mainly consisted of preoperative applied radiopaque frame and intraoperative guiding device, which has the potential to minimize fluoroscopy repetition in MISS. The study aimed to evaluate the efficacy of a novel lumbar localization system in reducing radiation exposure to patients.Included patients underwent minimally invasive transforaminal lumbar interbody fusion (MISTLIF) or percutaneous transforaminal endoscopic discectomy (PTED). Patients treated with novel localization system were regarded as Group A, and patients treated without novel localization system were regarded as Group B.For PTED, The estimated effective dose was 0.41 ± 0.13 mSv in Group A and 0.57 ± 0.14 mSv in Group B (P < .001); the fluoroscopy exposure time of PTED was 22.18 ± 7.30 seconds in Group A and 30.53 ± 7.56 seconds in Group B (P < .001); The estimated cancer risk of radiation exposure was 22.68 ± 7.38 (10) in Group A and 31.20 ± 7.96 (10) in Group B (P < .001). For MISTLIF, the estimated effective dose was 0.45 ± 0.09 mSv in Group A and 0.58 ± 0.09 mSv in Group B (P < .001); The fluoroscopy exposure time was 25.41 ± 5.52 seconds in Group A and 32.82 ± 5.03 seconds in Group B (P < .001); The estimated cancer risk was 24.90 ± 5.15 (10) in Group A and 31.96 ± 5.04 (10) in Group B (P < .001). There were also significant differences in localization time and operation time between the 2 groups either for MISTLIF or PTED.The lumbar localization system could be a potential protection strategy for minimizing radiation hazards.


NT-proBNP: is it a more significant risk factor for mortality than troponin T in incident hemodialysis patients?
Numerous studies have demonstrated that cardiac biomarkers are significant predictors of cardiovascular (CV) and all-cause mortality in ESRD patients, but most of the studies were retrospective or included small numbers of patients, only prevalent dialysis patients, or measured 1 or 2 biomarkers. This study was to analyze the association between 3 cardiac biomarkers and mortality in incident HD patients. A prospective cohort of 864 incident HD patients was followed for 30 months. Based on the median values of baseline NT-proBNP, cTnT, and hsCRP, the patients were divided into "high" and "low" groups, and CV and all-cause mortality were compared between each group. Additionally, time-dependent ROC curves were constructed, and the NRI and IDI of the models with various biomarkers were calculated. The CV survival rates were significantly lower in the "high" NT-proBNP and cTnT groups compared to the corresponding "low" groups, while there was no significant difference in CV survival rate between the 2 hsCRP groups. However, all-cause mortality rates were significantly higher in all 3 "high" groups compared to each lower group. In multivariate analyses, only Ln NT-proBNP was found to be an independent predictor of mortality. Moreover, NT-proBNP was a more prognostic marker for mortality compared to cTnT. In conclusion, NT-proBNP is the biomarker that results in the most added prognostic value on top of traditional risk factors for CV and all-cause mortality in incident HD patients.


Protective Effect of Calcium Fructoborate Against Carbon Tetrachloride-Induced Toxicity in Rats.
Carbon tetrachloride (CCl4) is a xenbiotic that can cause cellular damage with free radical production. Calcium fructoborate (CFB) is a boron-based nutritional supplement with antioxidant properties. Calcium fructoborate used in our study is marketed by Future Ceutical Corporation as FruiteX-B, which has a chemical structure similar to the natural form of boron found in edible plants. In this study, it was aimed to determine the antioxidant activity, DNA damage, and histopathological effects of CFB on the liver and kidney tissues of rats in the toxicity induced by CCl4. During 14 days of treatment, 42 wistar albino rats were divided into 7 in each group, control group, olive oil (0.25 ml twice a week), CFB (1 mg/day), CFB-CCl4 (1 mg/day, twice a week 0.5 ml), ZY-CFB (0.25 ml/twice a week, 1 mg/2 times day twice), and CCl4 (0.5 ml twice a week). AST, ALT, HDL, LDH, urea, creatinine, triglyceride, total protein and albumin levels were analyzed in the blood serum of rats. The antioxidant defense system enzymes CAT, GR, GPx, SOD activities and GSH, MDA and 8-OHdG levels in liver and kidney tissues were determined and evaluated. In addition, liver and kidney tissues were examined with only hispatological tests. As a result of the findings, it shows that CCl4 disrupts antioxidant defense mechanisms by disrupting some enzyme systems in the kidney and liver. CFB (Fruit-XB), a boronbased dietary supplement, regulates antioxidant metabolism by strengthening biochemical metabolic profiles against oxidation, and also has a protective effect against DNA damage caused by oxidation. Thus, it was concluded that CFB has antioxidant property against CCl4-induced liver and kidney toxicity.


IOTA: integration optimization, triage and analysis tool for the processing of XFEL diffraction images.
Serial femtosecond crystallography (SFX) uses an X-ray free-electron laser to extract diffraction data from crystals not amenable to conventional X-ray light sources owing to their small size or radiation sensitivity. However, a limitation of SFX is the high variability of the diffraction images that are obtained. As a result, it is often difficult to determine optimal indexing and integration parameters for the individual diffraction images. Presented here is a software package, called IOTA, which uses a grid-search technique to determine optimal spot-finding parameters that can in turn affect the success of indexing and the quality of integration on an image-by-image basis. Integration results can be filtered using a priori information about the Bravais lattice and unit-cell dimensions and analyzed for unit-cell isomorphism, facilitating an improvement in subsequent data-processing steps.


Purification of the tetrodotoxin-binding component associated with the voltage-sensitive sodium channel from Electrophorus electricus electroplax membranes.
The tetrodotoxin-binding component associated with the voltage-sensitive sodium channel from electroplax membranes of Electrophorus electricus has been purified. The toxin-binding site could be efficiently solubilized with Lubrol-PX, resulting in an extract of high initial specific activity. Purification was facilitated by the development of a rapid, quantitative binding assay. The binding component was stabilized during purification by the use of mixed lipid/detergent micelles of defined composition, and by the saturation of the site with tetrodotoxin. The purification was achieved by means of a highly selective adsorption of the toxin-binding component to DEASE-Sephadex A-25, followed by desorption at high ionic strength and chromatography over Sepharose 6B. Final peak specific activities were at least 50% of the specific activity expected for a pure, undenatured toxin-binding componenet of 230,000 molecular weight. The purified material exhibited a sedimentation coefficient of approximately 8 S and an unusual Stokes radius of 95 A. Purified material showed a relatively simple pattern on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, being comprised of only three polypeptides.


Prenatal bisphenol A exposure alters sex-specific estrogen receptor expression in the neonatal rat hypothalamus and amygdala.
Bisphenol A (BPA) exposure is ubiquitous, and in laboratory animals, early-life BPA exposure has been shown to alter sex-specific neural organization, neuroendocrine physiology, and behavior. The specific mechanisms underlying these brain-related outcomes, however, remain largely unknown, constraining the capacity to ascertain the potential human relevance of neural effects observed in animal models. In the perinatal rat brain, estrogen is masculinizing, suggesting that BPA-induced perturbation of estrogen receptor (ESR) expression may underpin later in-life neuroendocrine effects. We hypothesized that prenatal BPA exposure alters sex-specific ESR1 (ERα) and ESR2 (ERβ) expression in postnatal limbic nuclei. Sprague Dawley rats were mated and gavaged on gestational days (GDs) 6-21 with vehicle, 2.5 or 25 μg/kg bw/day BPA, or 5 or 10 μg/kg bw/day ethinyl estradiol. An additional group was restrained but not gavaged (naïve control). Offspring were sacrificed the day after birth to quantify ESR gene expression throughout the hypothalamus and amygdala by in situ hybridization. Relative to the vehicle group, significant effects of BPA were observed on ESR1 and ESR2 expression throughout the mediobasal hypothalamus and amygdala in both sexes. Significant differences in ESR expression were also observed in the mediobasal hypothalamus and amygdala of the naïve control group compared with the vehicle group, highlighting the potential for gavage to influence gene expression in the developing brain. These results indicate that ESR expression in the neonatal brain of both sexes can be altered by low-dose prenatal BPA exposure.


Inhibition of human spermatozoon-oocyte interaction in vitro by monoclonal antibodies to CD46 (membrane cofactor protein).
CD46 (membrane cofactor protein) is a cell surface complement regulatory glycoprotein that facilitates enzymatic cleavage of complement component C3b; it is expressed by both human oocytes and acrosome-reacted spermatozoa. Murine anti-CD46 monoclonal antibody (mAb) has been reported to decrease significantly the ability of human spermatozoa to penetrate hamster oocytes. We have investigated the effect of purified anti-CD46 mAbs on spermatozoon-oocyte interaction in an autologous zona-free oocyte penetration test. Oocytes and/or spermatozoa were preincubated with either of two anti-CD46 murine mAbs, TRA.2.10 (a non-blocking mAb) and MH61 (a mAb that functionally blocks C3b-ligand binding activity), or a control isotype-matched mAb, in medium supplemented with human serum albumin. Preincubation of both spermatozoa and zona-free oocytes with TRA.2.10, but not MH61, caused a significant decrease in the number of oocytes showing sperm binding and pronuclear formation (9/23) compared with controls (21/26) in this complement component-depleted medium. This effect was not observed if oocytes or spermatozoa alone were preincubated. These data suggest that CD46 has a role in human spermatozoon-oocyte interaction at the level of the oocyte plasma membrane, and indicate that a novel function other than direct C3b binding could be involved.


Omicron new variant BA.2.86 (Pirola): Epidemiological, biological, and clinical characteristics - a global data-based analysis.
Since December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a threatening situation worldwide. The new variant of SARS-CoV-2, BA.2.86, also known as Pirola, is an Omicron subvariant that causes great concern because it has been found to contain a large number of mutations. This study aims to investigate and identify the biological and clinical characteristics of this threatening new variant of SARS-CoV-2, which is BA.2.86. This observational study was performed in the Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. The literature was searched using the key terms including "SARS-CoV-2, Omicron, BA.2.86, Pirola, epidemiology, clinical characteristics". The data on Omicron BA.2.86 were obtained from the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), the Global Initiative on Sharing All Influenza Data (GSIAD), PubMed, Web of Science, regional ministries, research institutes, and international print media. Initially, 26 documents were identified and 10 documents were included for the data analysis. The information on the prevalence and the biological characteristics of the new variant of SARS-CoV-2, Omicron BA.2.86, was recorded and synthesized for analysis. The Omicron BA.2.86 has been identified in 23 countries with 264 confirmed cases as of September 28, 2023. The number and distribution of these cases encompass the United Kingdom 66 (25.0%), USA 34 (12.87%), Denmark 31 (11.74%), Sweden 25 (9.46%), South Africa 20 (7.57%), Spain 20 (7.57%), France 15 (5.68%), Portugal 7 (2.65%), Japan 6 (2.27%), Canada 5 (1.89%), Thailand 5 (1.89%), Israel 5 (1.89%), Greece 5 (1.89%), Germany 3 (1.13%), Belgium 3 (1.13%), Luxembourg 3 (1.13%), Netherlands 3 (1.13%), South Korea 3 (1.13%). However, one case in each country has been reported in Australia, Italy, Iceland, Switzerland, and China. The disease has been reported more frequently in females (71.0%) than males (29.0%). To date, no deaths have been reported. The novel variant has spread more swiftly than other variants of SARS-CoV-2 and has crossed many international borders. The new Omicron variant BA.2.86 has affected 264 people in 23 countries. The disease is more common in females than males and mainly affects old age people (over 60 years of age). However, no deaths have been reported. The variant is spreading swiftly and transmitted more rapidly. The clinical manifestations in patients with Omicron BA.2.86 variant are not well documented and may be similar to earlier strains of COVID-19 by presenting with mild infectious symptoms, including headache, body ache, cough, fever, generalized myalgia, and severe fatigue. The global health authorities must take preventive measures to stop the outbreak of this emerging variant across the globe to minimize the disease burden.


Renal transplantation update.
Various factors affect the outcome of renal transplants in humans. Matching for HLA-A, -B, and -DR histocompatibility antigens improves survival rates for renal allografts from first cadaver donors. Zero-HLA-A- and -B-antigen-mismatched grafts and two-HLA-DR-antigen-matched grafts do better, although results differ depending on the recipient's primary renal disease. Pretransplant third-party blood transfusions significantly improve survival rates of cadaver donor allografts. The mechanism of this beneficial effect has not been identified; however, blood transfusions probably do not "select out" high responders among potential recipients by stimulating the production of lymphocytotoxic antibodies. Cyclosporine has been heralded as a potent, nonspecific immunosuppressive agent that will significantly improve renal allograft survival rates. The selectivity of cyclosporine's effect on T lymphocytes is advantageous; however, its side effects, especially nephrotoxicity, may limit its usefulness. Attention to the potential surgical complications of renal transplantation can significantly reduce morbidity and mortality.


The Dockstore: enabling modular, community-focused sharing of Docker-based genomics tools and workflows.
As genomic datasets continue to grow, the feasibility of downloading data to a local organization and running analysis on a traditional compute environment is becoming increasingly problematic. Current large-scale projects, such as the ICGC PanCancer Analysis of Whole Genomes (PCAWG), the Data Platform for the U.S. Precision Medicine Initiative, and the NIH Big Data to Knowledge Center for Translational Genomics, are using cloud-based infrastructure to both host and perform analysis across large data sets. In PCAWG, over 5,800 whole human genomes were aligned and variant called across 14 cloud and HPC environments; the processed data was then made available on the cloud for further analysis and sharing. If run locally, an operation at this scale would have monopolized a typical academic data centre for many months, and would have presented major challenges for data storage and distribution. However, this scale is increasingly typical for genomics projects and necessitates a rethink of how analytical tools are packaged and moved to the data. For PCAWG, we embraced the use of highly portable Docker images for encapsulating and sharing complex alignment and variant calling workflows across highly variable environments. While successful, this endeavor revealed a limitation in Docker containers, namely the lack of a standardized way to describe and execute the tools encapsulated inside the container. As a result, we created the Dockstore ( https://dockstore.org), a project that brings together Docker images with standardized, machine-readable ways of describing and running the tools contained within. This service greatly improves the sharing and reuse of genomics tools and promotes interoperability with similar projects through emerging web service standards developed by the Global Alliance for Genomics and Health (GA4GH).


Cost of nursing most frequent procedures performed on severely burned patients.
to identify the mean direct cost (MDC) of the most frequent procedures performed by nursing professionals on severely burned patients in an Intensive Care Unit. exploratory-descriptive quantitative single-case study. The MDC was calculated by multiplying time (timed) spent by nursing professionals in the performance of the procedures by the unit cost of direct labor, and adding the costs of material and medicine/solutions. a MDC of US$ 0.65 (SD=0.36) was obtained for "vital signs monitoring"; US$ 10.00 (SD=24.23) for "intravenous drug administration"; US$ 5.90 (SD=2.75) for "measurement of diuresis"; US$ 0.93 (SD=0.42) for "capillary blood glucose monitoring"; and US$ 99.75 (SD=129.55) for "bandaging". the knowledge developed can support managerial decision-making, contribute to the efficiency distribution of the resources involved and, when possible, provide cost-containment or cost-minimization strategies without impairing the quality of nursing care.


Genomic alterations in advanced gastric cancer endoscopic biopsy samples using targeted next-generation sequencing.
Gastric cancer (GC) remains the second tumor caused death threat worldwide, and personalized medicine for GC is far from expectation. Finding novel, recurrently mutated genes through next-generation sequencing (NGS) is a powerful and productive approach. However, previous genomic data for GC are based on surgical resected samples while a large proportion of advanced gastric cancer (AGC) patients have already missed the chance for operation. The aim of this study is to assess frequent genomic alteration in AGC via biopsy samples. Here we performed targeted genomic sequencing of 78 AGC patients' tumor biopsies along with matched lymphocyte samples based on a 118 cancer related gene panel. In total, we observed 301 somatic nonsynonymous genomic alterations in 92 different genes, as well as 37 copy number gain events among 15 different genes (fold change 2-12), and validated the fold changes of ERBB2 copy number gains with IHC and FISH test showed an accuracy of 81.8%. Previously reported driver genes for gastric cancer (TP53, KMT2D, KMT2B, EGFR, PIK3CA, GNAQ, and ARID1A), and several unreported mutations (TGFBR2, RNF213, NF1, NSD1, and LRP2) showed high non-silent mutation prevalence (7.7%-34.6%). When comparing intestinal-type gastric cancer (IGC) with diffuse-type gastric cancer (DGC), TP53 and GNAQ appear to be more frequently mutated in IGC (P=0.028 and P=0.023, respectively), whereas LRP2, BRCA2 and FGFR3 mutations are not observed in IGC, but have 12.8%, 7.7% and 7.7% mutation rates, respectively, in DGC patients. Patients with one or more mutations in adherens junction pathway (CREBBP, EP300, CDH1, CTNNB1, EGFR, MET, TGFBR2 and ERBB2) or TGF-β signaling pathway (CREBBP, EP300, MYST4, KRAS and TGFBR2) showed significantly better overall survival (P=0.007 and P=0.014, respectively), consistent with The Cancer Genome Atlas (TCGA) cohort data. Importantly, 57 (73.1%) patients harbored at least one genomic alteration with potential treatments, making NGS-based drug target screening a viable option for AGC patients. Our study established a comprehensive genomic portrait of AGC, and identified several mutation signatures highly associated with clinical features, survival outcomes, which may be used to design future personalized treatments.


[Diagnosis and staging of Hodgkin lymphoma].
DIAGNOSIS AND STAGING OF HODGKIN LYMPHOMA. Hodgkin lymphoma (HL) is composed of two distinct disease entities: classical HL (cHL) and nodular lymphocyte predominant HL (NLPHL). NLPHL is a rare entity with a specific therapeutic management. The subgroups of cHL are nodular sclerosis, mixed cellularity, lymphocyte depletion and lymphocyte-rich HL. The initial diagnosis of HL is made by a biopsy to analyze with accuracy the architecture of the lymph node. Most HL patients present with supradiaphragmatic lymphadenopathy. Initial staging is determined by positron emission tomography (PET) scan and bone marrow biopsy is now avoided of initial staging. This staging allows the definition of prognostic groups to determine a risk-adapted initial therapy to maintain a high level of curability and reduce long-term therapeutic side effects. Before initial treatment, cardiac ultrasound and pulmonary function tests are needed. The question of fertility preservation is important to address before treatment and for older patients the requirement of geriatric assessment.


Consumption of Bt Maize Pollen Containing Cry1Ie Does Not Negatively Affect Propylea japonica (Thunberg) (Coleoptera: Coccinellidae).
Propylea japonica (Thunberg) (Coleoptera: Coccinellidae) are prevalent predators and pollen feeders in East Asian maize fields. They are therefore indirectly (via prey) and directly (via pollen) exposed to Cry proteins within Bt-transgenic maize fields. The effects of Cry1Ie-producing transgenic maize pollen on the fitness of P. japonica was assessed using two dietary-exposure experiments in the laboratory. In the first experiment, survival, larval developmental time, adult fresh weight, and fecundity did not differ between ladybirds consuming Bt or non-Bt maize pollen. In the second experiment, none of the tested lethal and sublethal parameters of P. japonica were negatively affected when fed a rapeseed pollen-based diet containing Cry1Ie protein at 200 μg/g dry weight of diet. In contrast, the larval developmental time, adult fresh weight, and fecundity of P. japonica were significantly adversely affected when fed diet containing the positive control compound E-64. In both experiments, the bioactivity of the Cry1Ie protein in the food sources was confirmed by bioassays with a Cry1Ie-sensitive lepidopteran species. These results indicated that P. japonica are not affected by the consumption of Cry1Ie-expressing maize pollen and are not sensitive to the Cry1Ie protein, suggesting that the growing of Bt maize expressing Cry1Ie protein will pose a negligible risk to P. japonica.


[Coxitis fugax. The sonographic and radiologic picture in 65 cases].
Sonography is a valuable technique for the detection of hip joint effusion in children with transient synovitis. In a retrospective study of 65 patients distension of the anterior recess was found to be increased by 2 mm or more in all patients investigated. A sonographic follow-up examination was carried out in 30 patients. These patients showed complete regression of hip effusion after 4 weeks. The importance of attention to sonographic changes of the adjacent bony outline and femoral head deformity in connection with other hip diseases is emphasized. In 45 patients in this study (62% of the cases) conventional radiography showed one or more indirect signs such as displacement, blurring or even obliteration of the fatty intermuscular planes or an increased joint space. In uncomplicated cases with clear sonographic and clinical findings a pelvic radiogram is unnecessary.