The Wolbachia strain wAu provides highly efficient virus transmission blocking in Aedes aegypti.
Introduced transinfections of the inherited bacteria Wolbachia can inhibit transmission of viruses by Aedes mosquitoes, and in Ae. aegypti are now being deployed for dengue control in a number of countries. Only three Wolbachia strains from the large number that exist in nature have to date been introduced and characterized in this species. Here novel Ae. aegypti transinfections were generated using the wAlbA and wAu strains. In its native Ae. albopictus, wAlbA is maintained at lower density than the co-infecting wAlbB, but following transfer to Ae. aegypti the relative strain density was reversed, illustrating the strain-specific nature of Wolbachia-host co-adaptation in determining density. The wAu strain also reached high densities in Ae. aegypti, and provided highly efficient transmission blocking of dengue and Zika viruses. Both wAu and wAlbA were less susceptible than wMel to density reduction/incomplete maternal transmission resulting from elevated larval rearing temperatures. Although wAu does not induce cytoplasmic incompatibility (CI), it was stably combined with a CI-inducing strain as a superinfection, and this would facilitate its spread into wild populations. Wolbachia wAu provides a very promising new option for arbovirus control, particularly for deployment in hot tropical climates.


pH-dependent solution structure and activity of a reduced form of the host-defense peptide myticin C (Myt C) from the mussel Mytilus galloprovincialis.
Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found in fish cells overexpressing this HDP. However, the potential antimicrobial properties of any synthetic analogue of Myt C has not yet been analysed. Thus, in this work we have synthesised the sequence of the mature peptide of Myt C variant c and analysed the structure activity relationships of its reduced (non-oxidized) form (red-MytCc). In contrast to results previously reported for oxidized isoforms of mussel myticins, red-MytCc was not active against bacteria at physiological pH and showed a moderate antiviral activity against the viral haemorrhagic septicaemia (VHS) rhabdovirus. However, its chemotactic properties remained active. Structure/function studies in neutral and acid environments by means of infrared spectroscopy indicated that the structure of red-MytCc is pH dependent, with acid media increasing its alpha-helical content. Furthermore, red-MytCc was able to efficiently aggregate artificial phospholipid membranes at low pH, as well as to inhibit the Escherichia coli growth, suggesting that this activity is attributable to its more structured form in an acidic environment. All together, these results highlight the dynamic and environmentally sensitive behavior of red-Myt C in solution, and provide important insights into Myt C structure/activity relationships and the requirements to exert its antimicrobial/immunomodulatory activities. On the other hand, the pH-dependent direct antimicrobial activity of Myt C suggests that this HDP may be a suitable template for the development of antimicrobial agents that would function selectively in specific pH environments, which are sorely needed in this "antibiotic-resistance era".


A pyridine-containing Cu²⁺-selective probe based on naphthalimide derivative.
A new fluorescent probe P derived from naphthalimide bearing a pyridine group has been synthesized and characterized. The proposed probe P shows high selectivity and sensitivity to Cu2+ in aqueous media. Under optimized conditions, the linear response of P (2 μM) toward Cu2+ was 0.05-0.9 μM in ethanol-water solution (3:2, v:v, 50 mM HEPES, pH 7.4), and the detection limit was 0.03 μM.


Palladium-catalyzed decarboxylative α-allylation of thiazolidinones and azlactones with sulfonamido-substituted acyclic allylic carbonates.
A palladium-catalyzed decarboxylative α-allylation of thiazolidinones and azlactones with aza-π-allylpalladium zwitterionic intermediates, in situ generated from sulfonamido-substituted allylic carbonates, is successfully developed. This method allows the formation of a series of structurally diverse 5-alkylated thiazolidinones and 2-piperidones under mild conditions in moderate to high yields (up to 99% yield).


Comparison of abnormal isoform of prion protein in prion-infected cell lines and primary-cultured neurons by PrPSc-specific immunostaining.
We established abnormal isoform of prion protein (PrPSc)-specific double immunostaining using mAb 132, which recognizes aa 119-127 of the PrP molecule, and novel PrPSc-specific mAb 8D5, which recognizes the N-terminal region of the PrP molecule. Using the PrPSc-specific double immunostaining, we analysed PrPSc in immortalized neuronal cell lines and primary cerebral-neuronal cultures infected with prions. The PrPSc-specific double immunostaining showed the existence of PrPSc positive for both mAbs 132 and 8D5, as well as those positive only for either mAb 132 or mAb 8D5. This indicated that double immunostaining detects a greater number of PrPSc species than single immunostaining. Double immunostaining revealed cell-type-dependent differences in PrPSc staining patterns. In the 22 L prion strain-infected Neuro2a (N2a)-3 cells, a subclone of N2a neuroblastoma cell line, or GT1-7, a subclone of the GT1 hypothalamic neuronal cell line, granular PrPSc stains were observed at the perinuclear regions and cytoplasm, whereas unique string-like PrPSc stains were predominantly observed on the surface of the 22 L strain-infected primary cerebral neurons. Only 14 % of PrPSc in the 22 L strain-infected N2a-3 cells were positive for mAb 8D5, indicating that most of the PrPSc in N2a-3 lack the N-terminal portion. In contrast, nearly half PrPSc detected in the 22 L strain-infected primary cerebral neurons were positive for mAb 8D5, suggesting the abundance of full-length PrPSc that possesses the N-terminal portion of PrP. Further analysis of prion-infected primary neurons using PrPSc-specific immunostaining will reveal the neuron-specific mechanism for prion propagation.


Ought we to require emotional capacity as part of decisional competence?
The preceding commentary by Louis Charland suggests that traditional cognitive views of decision-making competence err in not taking into account patients' emotional capacities. Examined closely, however, Charland's argument fails to escape the cognitive bias that he condemns. However, there may be stronger arguments for broadening the focus of competence assessment to include emotional capacities, centering on the ways in which emotions aid humans in processing information. Before emotional capacities are added to the list of functions essential for decisional competence, though, the feasibility and utility of such a reorientation must be demonstrated.


The epidemiology of blast lung injury during recent military conflicts: a retrospective database review of cases presenting to deployed military hospitals, 2003-2009.
Blast injuries are becoming increasingly common in military conflicts as the nature of combat changes from conventional to asymmetrical warfare and counter-insurgency. This article describes a retrospective database review of cases from the UK joint theatre trauma registry from 2003 to 2009, containing details of over 3000 patients, mainly injured in Iraq and Afghanistan. During this period, 1678 patients were injured by explosion of whom 113 had evidence of blast lung injury. Of the 50 patients who survived to reach a medical facility, 80 per cent required ventilatory support. Injuries caused by explosion are increasing when compared with those caused by other mechanisms, and blast lung represents a significant clinical problem in a deployed military setting. Management of these patients should be optimized from point of wounding to definitive care.


Midazolam for urethral catheterisation in female infants with suspected urinary tract infection: a case-control study.
Based on the 2010 Israeli Medical Association recommendations, young children with suspected urinary tract infection (UTI) are mildly sedated with oral or intranasal midazolam to reduce the distress associated with urethral catheterisation (UC). The primary objective of this study was to examine the rate of urine culture contamination (UCC) in infants who underwent UC with and without sedation. Other objectives were to evaluate serious adverse events and emergency department (ED) length of stay. A retrospective case-control study was conducted in a paediatric ED. Two cohorts of patients who underwent UC were compared, 164 female infants who were sedated with midazolam (case subjects) and 173 who were not (controls). Cases and controls had a mean temperature of 38.3°C and 38.2°C, respectively. One hundred and forty-one patients were treated with oral midazolam and 23 received the drug intranasally. Cases and controls had a UCC rate of 20/164 (12%) and 45/173 (26%), respectively. Compared with controls, cases had lower odds of UCC (OR=0.39, 95% CI 0.21 to 0.73).Serious adverse events related to midazolam were not recorded. Case subjects and controls had a mean ED length of stay of 2.96 h and 2.50 h, respectively. The difference between the groups was statistically significant (p<0.014, 95% CI 0.10 to 0.90 for difference between means). In this cohort of febrile infants, sedation with oral or intranasal midazolam reduced the risk of culture contamination during UC without causing serious adverse events. However, patients who were treated with sedation had longer length of stay in the ED.


Effect of quality of care on preventable perinatal mortality.
This study assessed and quantified the effect of quality of care on death preventability, independent of social and biological variables. One hundred and eighty-one avoidable perinatal deaths (cases) were compared to 341 non-avoidable ones (controls). Judgement criteria on death preventability were based predominantly on compliance with explicit hospital medical care standards, determined by peer review. The overall perinatal mortality rate was 24.8 per 1000 births and could be reduced by 35% if all avoidable perinatal deaths were prevented. Sixteen per cent of the deaths presented structural and 31.2% process deficiencies; both predominated among avoidable perinatal deaths (35.4% vs 5.3%, p < 0.000; and 79.3% vs 5.9%, p < 0.000, respectively). Structural deficiencies increased the risk of an avoidable perinatal death eleven-fold (95% confidence interval (CI) 4.1, 26.9; p < 0.001) and process deficiencies eighty-eightfold (95% CI 37.2, 204.5, p < 0.001), after controlling for confounders. The strength of the association between quality of care and preventable perinatal mortality was estimated.


Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease.
The inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis, are chronic inflammatory disorders of the digestive tract. The pathogenesis of IBD is complicated, and it is widely accepted that immunologic, environmental and genetic components contribute to its etiology. To identify genetic susceptibility factors in CD, we performed a genome-wide association study in Japanese patients and controls using nearly 80,000 gene-based single nucleotide polymorphism (SNP) markers and investigated the haplotype structure of the candidate locus in Japanese and European patients. We identified highly significant associations (P = 1.71 x 10(-14) with odds ratio of 2.17) of SNPs and haplotypes within the TNFSF15 (the gene encoding tumor necrosis factor superfamily, member 15) genes in Japanese CD patients. The association was confirmed in the study of two European IBD cohorts. Interestingly, a core TNFSF15 haplotype showing association with increased risk to the disease was common in the two ethnic groups. Our results suggest that the genetic variations in the TNFSF15 gene contribute to the susceptibility to IBD in the Japanese and European populations.


Local responses to French medical imperialism in late nineteenth-century Algeria.
This article offers the first account of the lives of Algerian-born doctors working in the French colonial medical service between 1870 and 1900. Their stories reveal the manner in which the idea of medical imperialism had collapsed in Algeria, as a result of maladministration, racial policies, competition between civil and military authorities, budgetary constraints and the rise of the colons. The article also indicates the way in which medicine became a locus of opposition to French rule. It shows how the first decades of the Third Republic were critical in terms of a shift from the earlier idea of medicine serving as an emblem of the mission civilisatrice to the ideological potential of medicine being seen in much more nuanced terms by both French settlers and Algerian locals. It is argued that the notion of cultural resistance to imperialism through medicine emerges in the 1870s and 1880s, thereby prefiguring the work of Fanon and the Front de Liberation Nationale's later analysis of the 'sickness' of colonial Algerian society.


Use of Massive Allografts to Manage Hydatid Bone Disease of the Femur.
Hydatid disease is caused by the parasitic tapeworm Echinococcus granulosus. Osseous involvement accounts for 0.5% to 4% of cases in humans. Patients usually are from endemic zones and are initially asymptomatic, presenting with pain and edema at a later stage of disease. However, large lesions may present initially as pathologic fractures. Standard radiographs usually show expansive osteolytic lesions associated with initial cortical thinning, with compromise of the metaphysis or epiphysis, and may involve the diaphysis. The finding of periosteal reaction, osteocondensation, calcification, and clear delimitation of the lesions excludes the diagnosis of osseous hydatidosis. However, there are no specific radiographic signs in the affected bone. There is no generally accepted treatment algorithm for osseous hydatid disease. The usual treatment is surgical resection of the affected bone, followed by antihelmintic therapy. Some patients can be treated with intralesional procedures, such as curettage and allograft or polymethyl methacrylate cement. However, in some advanced cases, such as those with pathologic fractures or recurrences, wide resection may be needed. Several reconstructive alternatives have been reported, such as megaprosthesis, massive allograft, or alloprosthesis composite. The authors retrospectively reviewed 2 cases of femoral hydatidosis treated with wide resection and reconstruction with massive bone allograft. One patient had 5 years of follow-up, and the other had 9 years. No signs of relapse or complications were recorded, and functional outcomes evaluated with the Musculoskeletal Tumor Society scale showed excellent results. These 2 cases support the use of a massive bone allograft as a valid alternative to reconstruction after extensive bone resection for hydatidic disease.


Soil matrix tracer contamination and canopy recycling did not impair ¹³CO₂ plant-soil pulse labelling experiments.
When conducting (13)CO(2) plant-soil pulse labelling experiments, tracer material might cause unwanted side effects which potentially affect δ(13)C measurements of soil respiration (δ(13)C(SR)) and the subsequent data interpretation. First, when the soil matrix is not isolated from the atmosphere, contamination of the soil matrix with tracer material occurs leading to a physical back-diffusion from soil pores. Second, when using canopy chambers continuously, (13)CO(2) is permanently re-introduced into the atmosphere due to leaf respiration which then aids re-assimilation of tracer material by the canopy. Accordingly, two climate chamber experiments on European beech saplings (Fagus sylvatica L.) were conducted to evaluate the influence of soil matrix (13)CO(2) contamination and canopy recycling on soil (13)CO(2) efflux during (13)CO(2) plant-soil pulse labelling experiments. For this purpose, a combined soil/canopy chamber system was developed which separates soil and canopy compartments in order to (a) prevent diffusion of (13)C tracer into the soil chamber during a (13)CO(2) canopy pulse labelling and (b) study stable isotope processes in soil and canopy individually and independently. In combination with laser spectrometry measuring CO(2) isotopologue mixing ratios at a rate of 1 Hz, we were able to measure δ(13)C in canopy and soil at very high temporal resolution. For the soil matrix contamination experiment, (13)CO(2) was applied to bare soil, canopy only or, simultaneously, to soil and canopy of the beech trees. The obtained δ(13)C(SR) fluxes from the different treatments were then compared with respect to label re-appearance, first peak time and magnitude. By determining the δ(13)C(SR) decay of physical (13)CO(2) back-diffusion from bare soils (contamination), it was possible to separate biological and physical components in δ(13)C(SR) of a combined flux of both. A second pulse labelling experiment, with chambers permanently enclosing the canopy, revealed that (13)CO(2) recycling at canopy level had no effect on δ(13)C(SR) dynamics.


Whiteboards and discharge traffic lights: visual management in acute care.
Flinders Medical Centre was experiencing issues with timely discharge and knowing the potential discharges and in-patient bed capacity for the next day. This case study describes the application of 'visual management' theory to discharge processes. The solutions developed were 'patient journey boards' and 'discharge traffic lights'. The implementation of these visual management systems has enabled the hospital to improve its discharge processes.


Purification of haemagglutinin and neuraminidase from influenza virus strain 3QB and isolation of a peptide from an antigenic region of haemagglutinin.
Methods were developed for the purification of the surface, membrane-bound glycoproteins haemagglutinin and neuraminidase of influenza virus strain 3QB, in antigenically active forms. The methods employed in the purification included selective removal of the neuraminidase with the proteinase, bromelain, and subsequent disruption of the residual virus particle with the detergent Sarkosyl to release the haemagglutinin. Using techniques for proteolytic digestion of intact, native proteins an antigenically active peptide was isolated from the purified haemagglutinin, the surface glycoprotein against which the major antigenic response is directed. The amino acid composition of this peptide was determined. This was a 16-residue peptide with amino-terminal isoleucine and composition Ile1 Val1 Asx2 Thr1 Ser2 Glx2 Pro1 Gly3 Ala1 Leu1 Lys1.


[Research projects in mental health care speciality: mentoring and lived experiences].
The goal of the present study is to describe the methodology followed in the implementation of the mentoring research projects developed by the three residents of mental health during the 2009-10 academic years and present the results obtained and recognition. We designed eight targeted monthly tutorials and educational material complementing the methodological support. The development of the project followed an established pattern that allowed progressively advancing in the various phases. When completed the projects, the most relevant were selected for presentation at the XI National Meeting of Residents of Mental Health Nursing, and planned a public presentation of all projects. The main findings from the evaluation work were made for every resident of the experience and the quality of the tutorials. In his narrative are the positive enrichment achieved during the year of residency from the perspective of learning as well as relationship with mentors. In the individual assessment reflect relevant aspects of the authorization process as closeness, trust, resolving doubts, guidelines for intervention. The project presented at the national meeting took second award.


Lymph node metastases in hamster tongue cancer induced with 9,10-dimethyl-1,2-benzanthracene: association between histological findings and the incidence of neck metastases, and the clinical implications for patients with tongue cancer.
An experimental study was carried out in hamster tongue cancer induced with 9,10-dimethyl-1,2-benzanthracene (DMBA) to examine the association between the histological features and the incidence of lymph node metastases. Squamous cell carcinoma was induced in 64 of 71 hamsters exposed to DMBA 3 times weekly for a period of 10-24 weeks, and lymph node metastases were found in 8 necks. Various histological variables in the primary lesion were examined, and the mode of invasion, degree of keratinization, and stage of invasion were found to be closely related to the development of neck metastases. We then did a prospective study in 37 human patients with T1-2 tongue cancer, which also showed a close association between the incidence of neck metastases and the histological variables of mode of invasion and degree of keratinization. These experimental and clinical studies suggest that the mode of invasion and degree of keratinization may be risk factors for neck metastases that are independent of T stage, and that the indications for elective neck dissection should be re-evaluated in that light.


Tri-Substituted Triazole-Enabled C-H Activation of Benzyl and Aryl Amines by Iron Catalysis.
The design of trisubstituted triazoles set the stage for proximity-induced iron-catalyzed C-H activation of benzyl and aryl amines with ample scope. Thereby, C-H alkylations and C-H arylations proved viable with high levels of chemo and positional selectivities by means of racemization-free iron catalysis with the reusable triazole being removed in a traceless fashion.


Death From Butane Inhalation Abuse in Teenagers: Two New Case Studies and Review of the Literature.
The ready availability of butane makes butane abuse frequent. Fatalities are rare. This study presents two cases of death by butane overdose. The postmortem analyses were carried out using headspace gas chromatography-mass spectrometry. It revealed femoral blood butane concentrations of 18 and 22 mg/L, respectively, as well as specific combinations of adjuvants in each victim. In one of the victims, brain and fatty tissue also contained butane, pointing to chronic consumption. The originality of this study is to show that the identification of specific combinations of adjuvants can be helpful for identifying the brand of deodorant used. Also, sampling the skin and mucosa can help identify the method of drug delivery. The histological examination documented both the direct toxic effect of the gas on the respiratory mucosa and signs of chronic abuse. Volatile substance intoxications should be systematically considered in case of sudden death in a teenager.


Inhibition of hepatic stellate cell collagen synthesis by N-(methylamino)isobutyric acid.
The increased deposition of extracellular matrix by hepatic stellate cells following liver injury, in a process known as activation, is considered a key mechanism for increased collagen content of liver during the development of liver fibrosis. We report that N-(methylamino)isobutyric acid (MeAIB), a specific inhibitor of System A-mediated amino acid uptake, reduces the accumulation of collagen in CFSC-2G hepatic stellate cell cultures and in a rat model of liver injury and fibrosis. Rat CFSC-2G cells were cultured in 0-5mM MeAIB, and the accumulation and synthesis of collagen were measured by binding to Sirius red F3B and pulse-labeling with [3H]-proline, respectively. The effect of MeAIB on collagen accumulation in vivo was evaluated utilizing a rat model of hepatic fibrosis. MeAIB inhibited collagen accumulation in CFSC-2G cultures in a concentration-dependent manner with 5mM MeAIB reducing collagen 44.6+/-1.2% compared with the control. In CFSC-2G cultures, MeAIB selectively inhibited the incorporation of proline into cellular macromolecules by 43+/-4%, while the synthesis of proteins containing leucine was not affected. In vivo, oral administration of 160mg MeAIB/kg body weight per day to rats significantly reduced the hepatic collagen accumulation in response to 1 week of CCl(4)-induced liver injury. MeAIB reduces the accumulation of collagen in CFSC-2G hepatic stellate cell cultures and in a CCl(4)-induced rat model of liver injury and fibrosis.


Established and novel NF-κB inhibitors lead to downregulation of TLR3 and the proliferation and cytokine secretion in HNSCC.
The transcriptional activation of NF-κB signalling has been identified as a major pathway involved in inflammation and tumor aggressiveness in a number of human cancers. Here we identify the impact of miscellaneous known and so far unknown NF-κB inhibitors originating from different drug classes on the function and proliferation of HNSCC. In detail: HNSCC cell lines were exposed to Acetylsalicylic Acid (ASA), Celecoxib, Dexamethasone, Curcumin and EPs 7630. Our major interest was to detect upstream alterations in cell signalling after applying NF-κB inhibiting substances. The inhibition of NF-κB signalling leads to an upstream regulation of Toll-like-receptor 3 (TLR3), a predominant receptor driving cell expansion. We find a marked downregulation of TLR3 and IKK complex, documenting upstream responses to NF-κB inhibition by every agent tested. In a second step we further analyse proliferation, cytokine production and alterations in the expression of downstream proteins such as cyclin D1 and c-Myc. Our data demonstrate decreased proliferation in response to incubation with aforementioned agents. Modulation of TLR3 and NF-κB expression is accompanied by altered profiles of IL-6 and IL-8 which are relevant cytokines in HNSCC progression. Proto-oncogenes cyclin D1 and c-myc are downregulated by all substances. Apart from the interplay of cytokines and TLR3, we substantiated EPs 7630 as a new and natural NF-κB inhibitor.


Interobserver variation in assessment of gastric premalignant lesions: higher agreement for intestinal metaplasia than for atrophy.
Either atrophy or intestinal metaplasia of the gastric mucosa are considered premalignant lesions. The new operative link for gastritis assessment staging system is based on the detection of atrophy, and the operative link for assessment of intestinal metaplasia staging system is based on the detection of intestinal metaplasia. Good interobserver agreement is necessary for identification of any premalignant condition. The aim of this study was to compare the agreement between findings of gastric atrophy and intestinal metaplasia by expert and general pathologists and to analyze the possible reasons behind any possible disagreement. Patients with dyspeptic symptoms, aged 55 years and above, without previous Helicobacter pylori eradication were enrolled and analyzed according to the updated Sydney Classification by two expert pathologists and an experienced general pathologist; the results were compared with the consensus driven by the two experts. Gastric biopsy specimens from 121 patients (91 women) were included in the analysis; the mean age of the patients was 67.4 years. H. pylori infection was present in 61.2% of patients. The level of agreement between the general pathologist and the two experts (κ-value) was 0.12, 0.46, and 0.87, respectively, for detecting atrophy in the corpus; 0.77, 0.77, and 0.65, respectively, for detecting intestinal metaplasia in the corpus; 0.06, 0.51, and 0.54, respectively, for detecting atrophy in the antrum; and 0.69, 0.85, and 0.79, respectively, for detecting metaplasia in the antrum. The agreement was substantially higher for intestinal metaplasia than for atrophy. This could result in discrepancies when the operative link for gastritis assessment and operative link for assessment of intestinal metaplasia staging systems are applied and can be caused by differences in the criteria used to define atrophy.


Generation of Naïve Blastoderm Explants from Zebrafish Embryos.
Due to their optical clarity and rapid development, zebrafish embryos are an excellent system for examining cell behaviors and developmental processes. However, because of the complexity and redundancy of embryonic signals, it can be challenging to discern the complete role of any single signal during early embryogenesis. By explanting the animal region of the zebrafish blastoderm, relatively naïve clusters of embryonic cells are generated that can be easily cultured and manipulated ex vivo. By introducing a gene of interest by RNA injection before explantation, one can assess the effect of this molecule on gene expression, cell behaviors, and other developmental processes in relative isolation. Furthermore, cells from embryos of different genotypes or conditions can be combined in a single chimeric explant to examine cell/tissue interactions and tissue-specific gene functions. This article provides instructions for generating zebrafish blastoderm explants and demonstrates that a single signaling molecule - a Nodal ligand - is sufficient to induce germ layer formation and extension morphogenesis in otherwise naïve embryonic tissues. Due to their ability to recapitulate embryonic cell behaviors, morphogen gradients, and gene expression patterns in a simplified ex vivo system, these explants are anticipated to be of great utility to many zebrafish researchers.


Cobalt(II) and cadmium(II) square grids supported with 4,4'-bipyrazole and accommodating 3-carboxyadamantane-1-carboxylate.
In poly[[bis(μ-4,4'-bi-1H-pyrazole-κ(2)N(2):N(2'))bis(3-carboxyadamantane-1-carboxylato-κO(1))cobalt(II)] dihydrate], {[Co(C12H15O4)2(C6H6N4)2]·2H2O}n, (I), the Co(2+) cation lies on an inversion centre and the 4,4'-bipyrazole (4,4'-bpz) ligands are also situated across centres of inversion. In its non-isomorphous cadmium analogue, {[Cd(C12H15O4)2(C6H6N4)2]·2H2O}n, (II), the Cd(2+) cation lies on a twofold axis. In both compounds, the metal cations adopt an octahedral coordination, with four pyrazole N atoms in the equatorial plane [Co-N = 2.156 (2) and 2.162 (2) Å; Cd-N = 2.298 (2) and 2.321 (2) Å] and two axial carboxylate O atoms [Co-O = 2.1547 (18) Å and Cd-O = 2.347 (2) Å]. In both structures, interligand hydrogen bonding [N...O = 2.682 (3)-2.819 (3) Å] is essential for stabilization of the MN4O2 environment with its unusually high (for bulky adamantanecarboxylates) number of coordinated N-donor co-ligands. The compounds adopt two-dimensional coordination connectivities and exist as square-grid [M(4,4'-bpz)2]n networks accommodating monodentate carboxylate ligands. The interlayer linkage is provided by hydrogen bonds from the carboxylic acid groups via the solvent water molecules [O...O = 2.565 (3) and 2.616 (3) Å] to the carboxylate groups in the next layer [O...O = 2.717 (3)-2.841 (3) Å], thereby extending the structures in the third dimension.


An unusual case of posterior reversible encephalopathy syndrome in a patient being weaned from intrathecal morphine.
Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity based on clinical signs, including headache, visual abnormalities, and seizures, and radiological abnormalities mostly consisting of vasogenic brain edema predominantly in the posterior parietal-temporal-occipital regions. PRES typically develops in the setting of a significant " systemic process", including preeclampsia, transplantation, infection/sepsis/shock, autoimmune disease, and cancer chemotherapy, in which hypertension often plays an important role. We present a case of PRES in a 63-year-old female patient with an infected intrathecal morphine pump on a cocktail of antibiotics, morphine, clonidine, diazepam, and amitriptyline. It is the first PRES case in a chronic pain patient, which illustrates that PRES can occur in the absence of any of the established risk factors. We hypothesize it may have been caused by antibiotic treatment in our patient.


SilkPathDB: a comprehensive resource for the study of silkworm pathogens.
Silkworm pathogens have been heavily impeding the development of sericultural industry and play important roles in lepidopteran ecology, and some of which are used as biological insecticides. Rapid advances in studies on the omics of silkworm pathogens have produced a large amount of data, which need to be brought together centrally in a coherent and systematic manner. This will facilitate the reuse of these data for further analysis. We have collected genomic data for 86 silkworm pathogens from 4 taxa (fungi, microsporidia, bacteria and viruses) and from 4 lepidopteran hosts, and developed the open-access Silkworm Pathogen Database (SilkPathDB) to make this information readily available. The implementation of SilkPathDB involves integrating Drupal and GBrowse as a graphic interface for a Chado relational database which houses all of the datasets involved. The genomes have been assembled and annotated for comparative purposes and allow the search and analysis of homologous sequences, transposable elements, protein subcellular locations, including secreted proteins, and gene ontology. We believe that the SilkPathDB will aid researchers in the identification of silkworm parasites, understanding the mechanisms of silkworm infections, and the developmental ecology of silkworm parasites (gene expression) and their hosts. http://silkpathdb.swu.edu.cn.


Thoracic radiculopathy related to collapsed thoracic vertebral bodies.
Three cases are presented of thoracic radiculopathy related to collapsed thoracic vertebral bodies. In all cases proximal weakness of the legs was present, leading to the diagnosis of myopathy in two cases. Sensory symptoms were present in two cases. In one, anterior thigh paresthesias lead to a diagnosis of meralgia paresthetica. This diagnostic entity must be remembered if appropriate corroborative tests are to be performed. In cases of trauma this diagnosis should be considered if thoracic vertebral collapse is present. Conversely, an evaluation of proximal weakness should include a review of thoracic radiographs for vertebral collapse, especially in the presence of sensory findings in the lower abdominal or proximal thigh region.


Editorial Perspective: Mental health needs of children and young people of Black ethnicity.1 Is it time to reconceptualise racism as a traumatic experience?
We explore racial inequality in relation to Black children and young people (CYP) and Child and Adolescent Mental Health Services (CAMHS). We argue that the experience of racism should be universally considered an Adverse Childhood Experience (ACE). We argue that racism and the vicarious trauma arising from exposure to frequent media reports of racially motivated violence against persons of Black ethnicity can all predispose Black CYP to increased risk of mental health problems. We make recommendations to improve Black CYP's early access to CAMHS, and to reduce their overrepresentation in psychiatric in-patient settings in the UK. This would require making CAMHS more welcoming to Black CYP and consideration of the impact of racism and trauma in the diagnostic and treatment formulation for Black CYP. This should include: the impact of racism in staff training, improving the cultural competence of CAMHS staff, and supporting Black CYP to articulate their experiences of racism and related traumas whilst facilitating their development of coping strategies to manage these experiences.


Partial purification and characterization of exudate gelatinase in the acute phase of carrageenin-induced inflammation in rats.
Gelatinase has been partially purified from exudate in the acute phase of carrageenin-induced inflammation in rats. The enzyme occurs in a latent form that can be activated with 4-aminophenylmercuric acetate (APMA). The latent gelatinase was separated into an active gelatinase and a protein fraction by zinc-chelating Sepharose 6B column chromatography in the final step of purification, suggesting that the latent gelatinase is an enzyme-inhibitor complex. The pH optimum of the active gelatinase is about 7.5 and no reactivity toward native type I collagen or alpha-casein was detected. The molecular weights of the latent and active gelatinases were about 245,000 and about 185,000, respectively, as determined by gel filtration on Sephadex G-200. On the other hand, both latent and active gelatinases occurred in multiple forms in SDS-substrate polyacrylamide gel electrophoresis; the latent gelatinase showed two bands with molecular weights of 105,000 and 69,000, and two additional bands of 88,000 and 83,000 appeared when the latent gelatinase was activated with APMA, while the active gelatinase showed all four species. The active gelatinase was inhibited by metallo-proteinase inhibitors, but not by serine- or cysteine-proteinase inhibitors, suggesting that the exudate gelatinase is a metallo-proteinase. The active gelatinase was also inhibited by serum proteins such as albumin and gamma-globulin, suggesting that gelatinase does not remain in an active form in the inflammatory lesion, where the vascular permeability is increased.


Distributed Poloidal Magnetic Field Measurement in Tokamaks Using Polarization-Sensitive Reflectometric Fiber Optic Sensor.
Determination of the poloidal magnetic field distribution in tokamaks is of prime importance for the successful operation of tokamaks. In this paper, we propose a polarization-sensitive reflectometry-based optical fiber sensor for measuring the spatial distribution of the poloidal magnetic field in tokamaks. The measurement method exploits the Rayleigh backscattering and Faraday magneto-optic effect in optical fibers. The former is an intrinsic property of optical fibers and enables distributed polarization measurements, while the latter arises in the presence of a magnetic field parallel to the optical fiber axis and rotates the polarization state of the light. When an optical fiber is looped around a toroidal section of the vacuum vessel, the local polarization rotation of the light is proportional to the local poloidal magnetic field in the tokamak. The proposed method is discussed theoretically and experimentally using the results from JET. The obtained magnetic field measurement shows a good agreement with that of the internal discrete coils. A potential solution to recover the magnetic field data from the noise-affected region of the optical measurement is proposed and is demonstrated through simulations using the JET magnetic field configuration.


DNA barcoding and morphological taxonomy: identification of lanternfish (Myctophidae) larvae in the Gulf of Mexico.
Accurate identification of fish larval stages is complicated and time-consuming due to the lack of diagnostic morphological characters, especially during early developmental stages. The distribution of lanternfish (Myctophidae) has been described based on the morphological identification of adult stages. Larvae of only a few species of Myctophidae have been described, and the description is not always precise. In this study, larvae were collected and morphologically identified as Diaphus mollis, Hygophum hygomii, H. reinhardtii, H. taaningi, Myctophum obtusirostre and M. selenops. The DNA barcode region of the mitochondrial cytochrome oxidase I gene (COI) was determined for all larvae. The COI sequences matched reference barcodes available in GenBank for 14 of the identified larvae. The remaining COI sequences matched reference barcodes for different species of Myctophidae including Centrobranchus nigroocellatus, Diogenichthys atlanticus and Lepidophanes guentheri. This effort demonstrated the importance of integrated morphological and molecular analysis of species diversity and distribution of the Myctophidae in the Gulf of México.


Robustness analysis of the detailed kinetic model of an ErbB signaling network by using dynamic sensitivity.
The ErbB receptor signaling pathway plays an important role in the regulation of cellular proliferation, survival and differentiation, and dysregulation of the pathway is linked to various types of human cancer. Mathematical models have been developed as a practical complementary approach to deciphering the complexity of ErbB receptor signaling and elucidating how the pathways discriminate between ligands to induce different cell fates. In this study, we developed a simulator to accurately calculate the dynamic sensitivity of extracellular-signal-regulated kinase (ERK) activity (ERK*) and Akt activity (Akt*), downstream of the ErbB receptors stimulated with epidermal growth factor (EGF) and heregulin (HRG). To demonstrate the feasibility of this simulator, we estimated how the reactions critically responsible for ERK* and Akt* change with time and in response to different doses of EGF and HRG, and predicted that only a small number of reactions determine ERK* and Akt*. ERK* increased steeply with increasing HRG dose until saturation, while showing a gently rising response to EGF. Akt* had a gradual wide-range response to HRG and a blunt response to EGF. Akt* was sensitive to perturbations of intracellular kinetics, while ERK* was more robust due to multiple, negative feedback loops. Overall, the simulator predicted reactions that were critically responsible for ERK* and Akt* in response to the dose of EGF and HRG, illustrated the response characteristics of ERK* and Akt*, and estimated mechanisms for generating robustness in the ErbB signaling network.


Burst stimulation for refractory angina pectoris - A case report.
Refractory angina pectoris (RAP) is a chronic, severe chest pain associated with coronary artery disease that cannot be resolved using optimal medical or surgical approaches. Spinal cord stimulation (SCS) is a suitable treatment option. Conventional waveforms of SCS have shown a potent effect on the tempering of RAP. However, SCS is associated with undesired paresthesia. The new burst SCS waveforms have been reported to have fewer adverse effects. We reviewed a case in which RAP was successfully treated with burst SCS in a middle-aged male, with a tonic waveform employed for breakthrough pain as needed. Appropriate use of tonic and burst stimulations according to the symptoms is expected to maximize the effect of relieving chest pain induced by RAP.


Radiographic characteristics of canine subungual keratoacanthoma.
Subungual keratoacanthoma (SKA) is a rare benign nail bed tumor in dogs, and its radiographic characteristics have not been reported based on the authors' review of the literature. The purpose of this multicenter, retrospective, observational, descriptive study was to describe the radiographic features of SKA in dogs. Twelve dogs for a total of 12 digits with histologically confirmed SKA met the inclusion criteria. The radiographs of the manus or pes were reviewed by two veterinary radiologists and one veterinarian. The radiology reports were interpreted based on a consensus. In six dogs, there was lysis of both the middle phalanx (P2) and the distal phalanx (P3), whereas in the other six dogs, there was only lysis of P3. In all dogs with osteolysis of P2, the lysis involved the distal articular surface. Osteolysis of P3 was more severe in the ungual process than in the ungual crest in all dogs. The margins of the lytic regions of P2 and P3 were well defined and smoothly marginated in most dogs. Expansile changes in the P3 crest were observed in 83.3% (10/12 dogs), and the nail of the affected digit was enlarged and deformed in 91.6% (11/12 dogs). In summary, the radiographic features of canine SKA include severe pressure resorption of the P3 ungual process, expansile change of the P3 ungual crest, and nail enlargement and deformation. With these radiographic features, SKA should be considered as a differential diagnosis.


Image-enhanced endoscopy is specific for the diagnosis of non-erosive gastroesophageal reflux disease.
We assessed the performance characteristics of image-enhanced endoscopy with i-Scan or narrow band imaging (NBI) in patients with non-erosive gastroesophageal reflux disease (GERD) compared to controls without heartburn. Image-enhanced endoscopic findings of vascularity at the squamocolumnar junction, distal esophageal micro-erosions, and non-round pit pattern at the squamocolumnar junction were assessed in cases (heartburn not responsive to PPIs, positive results on validated GERD questionnaire, no esophageal erosions, esophageal biopsies with histologic evidence of GERD (basal cell hyperplasia, elongation of papillae and dilation of intercellular spaces all required)) and in controls (no GERD symptoms or esophageal erosions). Twenty cases and 60 controls were compared. The pre-defined features were more common in cases vs. vascularity RR = 4.9 (95% CI: 2.4-10.0), specificity = 86.7%; micro-erosions RR = 9.7 (3.6-26.5), specificity = 93.3%; non-round pit pattern RR = 2.4 (1.7-3.3), specificity = 60.0%; combination of vascularity and micro-erosions RR = 30.0 (4.1-220), specificity = 98.3%. These differences were consistent with both i-Scan and NBI. Image-enhanced endoscopic findings of vascularity and micro-erosions were very specific for non-erosive GERD. Image-enhanced endoscopy may be useful in real-time diagnosis of non-erosive GERD when patients undergo upper endoscopy for heartburn. The relative utility of image-enhanced endoscopy vs. pH-impedance monitoring, based on efficacy, cost and patient acceptance, requires additional study.


Occipital cortex dysgenesis with white matter changes due to mutations in Laminin a2.
Yiş U, Dixit V, Işıkay S, Karakaya M, Baydan F, Diniz G, Polat İ, Hız-Kurul S, Çırak S. Occipital cortex dysgenesis with white matter changes due to mutations in Laminin a2. Turk J Pediatr 2017; 59: 338-341. Laminin α2 related congenital muscular dystrophy is one of the most common congenital muscular dystrophies of childhood with or without clinical evidence of central nervous system involvement. It may be associated with significant white matter abnormalities resembling leukodystrophies. In this study, we elaborated on two cases with laminin α2 related congenital muscular dystrophy who had occipital cortex dysgenesis in addition to characteristic white matter abnormalities. Although laminin α2 related congenital muscular dystrophy with white matter abnormalities is known, the association with occipital cortex dysplasia has been not well recognized by clinical colleagues.


Profile of Ets gene expression in human breast carcinoma.
Ets genes encode a family of transcription factors that play key roles in cell proliferation, differentiation and apoptosis. Fusions of Ets genes with other targets have been described in Ewing's sarcoma, chronic myelomonocytic leukemia and more recently prostate carcinoma. Ets expression in breast carcinoma has not been comprehensively studied, and is the focus of this study. RT-Q-PCR was used to determine the expression of Ets genes in a panel of ten common breast cancer cell lines, two immortalized normal breast epithelial cell lines, and one primary culture of human mammary epithelial cells. Ets with altered expression in cancer cell lines were verified in primary breast tumors. Transcripts of 21 of the 27 Ets genes were detected in either normal or cancer cells. Of the 21 detectable genes, 14 were expressed at a similar level in both normal and breast cancer cell lines. Four genes, Ehf, Elf3, Elf5 and Pdef, were expressed at higher levels in breast cancer cells than normal epithelials. Surprisingly, the expression of Elk3, Etsl and Flil was repressed in breast cancer cells. The protein status of Ehf, Elf3, Pdef, Elk3, Etsl and Flil, strongly correlated with the transcript data, suggesting that Ets expression is regulated primarily at the transcriptional level. Similarly, Elf3, Pdef and Tel2 were overexpressed, while Elk3, Etsl and Flil were under-expressed in primary breast tumor specimens in comparison with normal mammary tissues. Our study identified a subset of Ets genes with altered expression in breast carcinoma, implicating their roles in mammary tumorigenesis. While the Ets over-expression pattern is useful to uncover recurrent genetic alterations involving Ets genes, the repressed expression of several Ets genes suggests that some Ets proteins may play suppressor roles during breast cancer progression. Our results warrant detailed studies of individual Ets activity during mammary gland neoplasia.


First transcriptome analysis of bryozoan Fredericella sultana, the primary host of myxozoan parasite Tetracapsuloides bryosalmonae.
Bryozoans are aquatic invertebrate moss animals that are found worldwide. Fredericella sultana is a freshwater bryozoan and is the most common primary host of myxozoan parasite, Tetracapsuloides bryosalmonae. However, limited genomic resources are available for this bryozoan, which hampers investigations into the molecular mechanisms of host-parasite interactions. To better understand these interactions, there is a need to build a transcriptome dataset of F. sultana, for functional genomics analysis by large-scale RNA sequencing. Total RNA was extracted from zooids of F. sultana cultivated under controlled laboratory conditions. cDNA libraries were prepared and were analyzed by the Illumina paired-ends sequencing. The sequencing data were used for de novo transcriptome assembly and functional annotation. Approximately 118 million clean reads were obtained, and assembled into 85,544 contigs with an average length of 852 bp, an N50 of 1,085 bp, and an average GC content 51.4%. A total of 23,978 (28%) contigs were annotated using BLASTX analysis. Of these transcripts, 4,400 contigs had highest similarity to brachiopod species Lingula anatina. Based on Gene ontology (GO) annotation, the most highly scored categories of biological process were categorized into cellular process (27%), metabolic process (24%), and biological regulation (8%) in the transcriptome of F. sultana. This study gives first insights into the transcriptome of F. sultana and provides comprehensive genetic resources for the species. We believe that the transcriptome of F. sultana will serve as a useful genomic dataset to accelerate research of functional genomics and will help facilitate whole genome sequencing and annotation. Candidate genes potentially involved in growth, proteolysis, and stress/immunity-response were identified, and are worthy of further investigation.


Treatment of acute hepatic failure by hemoperfusion over baboon and human livers: alphafetoprotein levels in serum.
Twelve patients with acute liver failure, two patients with cirrhotic failure of the liver, and one patient in the terminal stage of cirrhotic liver were treated. The patients had grade IV or V hepatic coma. Twenty-seven perfusions were carried out, each lasting 8 to 27 hours, with one to four perfusions per patient. Eight patients with acute liver failure were brought out of the coma. Six of them showed sufficient clinical symptoms of hepatic regeneration; five of these could be discharged. These results suggest that 50% of complete clinical recovery of consciousness from grade IV or V coma in acute hepatic failure is possible with this therapy. The three patients with liver cirrhosis treated with a total of five hemoperfusions did awaken, but died because of insufficient hepatic regeneration. The serum alphafetoprotein (AFP) levels were examined. In those patients brought out of the coma, a rapid increase of AFP up to 260--500 ng/ml was observed. These levels remained high for several weeks in the patients who survived. In the patients who died of liver insufficiency, AFP levels increased only slightly or briefly, so AFP could be a good criterion for determining the prognosis for coma patients with this treatment.


Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rd1 mouse retina.
Kinetic studies of photoreceptor cell death in the retinal degeneration (rd1) mouse model suggest that photoreceptor degeneration could result from cumulative damage. Since alterations in glutamate metabolism have been described in different models of retinitis pigmentosa, we investigated in the present work whether changes in glutamate turnover occur in the degenerating rd1 retina and whether glutamate-mediated excitotoxic mechanisms may contribute to rod photoreceptor death in this model. Free amino acid levels were quantified in rd1 and wild-type retinas using an amino acid analyzer selecting times corresponding to early, intermediate, and terminal phases of rod photoreceptor degeneration. Reverse transcription-polymerase chain reaction (RT-PCR) was used to compare the mRNA expression levels of the glial L-glutamate/L-aspartate transporter GLAST, glutamine synthetase (GS), and vimentin, a marker for retinal glia, between rd1 and wild-type mouse retinas. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of both AMPA and kainate subtypes of ionotropic glutamate receptors, was then daily administered from postnatal day 3 (PN3) to PN21 to rd1 mice while control rd1 mice received only physiological saline solution (7 per treatment). At PN22, the respective numbers of surviving rods in CNQX- and saline-treated mice were estimated using an unbiased stereological approach. Gradual increases in free glutamate and glutamine levels were observed during photoreceptor degeneration in rd1 retinas and were associated with increases in GLAST and GS expression levels. Administration of CNQX induced a statistically significant morphological rescue of rods (>25%, p<0.05). Our data demonstrated that, in the rd1 mouse retina, photoreceptor degeneration was associated with excessive free glutamate levels and with an upregulation of glutamate turnover (i.e., increases in GLAST, GS, and free glutamine levels). This may indicate that excessive glutamate levels further contribute to rod cell degeneration, thus implying the occurrence of non-cell autonomous mechanisms in the degenerative process in the rd1 retina.


Techniques for the diagnosis of malaria.
Malaria is endemic in large parts of the world and is subject to control by health authorities. The microscopic examination of many thousands of blood films for parasites, an essential component of surveillance and control schemes, is a tedious and time-consuming task. In recent years research has been directed at alternative methods to improve the mass diagnosis of malaria. These include immunoassays for the detection of antigen and the use of genetic probes. The techniques at present available are reviewed and some of the merits and disadvantages of the various tests discussed.


Linking autism measures with the ICF-CY: functionality beyond the borders of diagnosis and interrater agreement issues.
This study aims to: (1) link measurements used in the diagnosis of children with autism spectrum disorders (ASDs) with the International Classification of Functioning, Disability and Health - Children and Youth Version (ICF-CY) and (2) analyse issues relating with interrater agreement within this process. Three instruments for ASD diagnosis were linked with the ICF-CY using deductive content analysis. Correspondences between items' content and ICF-CY dimensions were identified for all ICF-CY components, except for environmental factors. Interrater agreement varied with the content of the units analyzed. The linkage between the ICF-CY and the analyzed measures provides a way to document assessment-intervention outcomes using a common language, as well as to integrate diagnostic and functional data. Diagnostic measurements provide functional information beyond the diagnostic criteria defined for autism. A functional perspective is added to diagnostic outcomes, thus better informing educational and rehabilitation practices for children with ASD.


Emerging ethical issues in instructions to authors of high-impact biomedical journals.
Public interest in issues concerning the maintenance of high ethical standards in the conduct of scientific research and its publication has been increasing. Some of the developments in these issues as reflected in the publication of the medical literature are traced here. This paper attempts to determine whether public interest is reflected in the specific requirements for authors for manuscript preparation as stated in the "Instructions to Authors" for articles being prepared for submission to 124 "high-impact" journals. The instructions to authors of these journals were read on the Web for references to ethical standards or requirements. The ethical issues that the instructions most often covered were specifically related to the individual journal's publication requirements. The results suggest that while the editors and publishers of the biomedical literature are concerned with promoting and protecting the rights of the subjects of the experiments in the articles they publish, and while these concerns are not yet paramount, they are evolving and growing.


Perceived Risk of HIV Infection Among Drug-Using African American Male Prisoners: One Year After Community Re-entry.
African Americans represent 13% of the U.S. population but 46% of people living with HIV and nearly 40% of state and federal prisoners. Disproportionate rates of HIV among African American males involved in the criminal justice system have been associated with risk factors, including: contracting sexually transmitted infections (STIs), substance misuse, and inconsistent condom use. However, many African American males may not perceive an elevated risk of HIV upon re-entering the community. The current study examines correlates of perceived HIV risk among incarcerated African American drug-using males about one year after release from prison. Derived from a larger Health Services Utilization study, interviewing (N = 661) incarcerated men at baseline with a 92% follow-up rate approximately one year after community re-entry, the current study is a secondary data analyses from self-identified African American men (N = 250). After list-wise deletion, the total N = 221 for the final study results. An ordered logistic regression model examining perceived risk of HIV as the dependent variable found age, cocaine use before sex, and condom use were significant correlates in the model. Alcohol use before sex mediated the relationship between cocaine use before sex and perceived HIV risk. Results suggest men in this study are engaged in HIV risk behaviors and risk perception varies. Implications for individual-level, community-level and policy interventions are discussed.


Outcomes of patients with hepatocellular carcinoma presenting with variceal bleeding.
Variceal bleeding is an important manifestation of hepatocellular carcinoma (HCC). However, little has been documented in the literature regarding the outcomes of HCC patients presenting with variceal bleeding. This study evaluated the clinical characteristics, management, and outcomes of this specific group of patients. A retrospective analysis of a prospectively collected database comprising 2,928 HCC patients managed from January 1989 to December 2002 identified 78 patients who had presented with variceal bleeding. Their clinical outcomes were compared to those patients who did not present with variceal bleeding, and a multivariate analysis was performed to identify prognostic factors for their survival. HCC patients who presented with variceal bleeding had more severe cirrhosis than those who did not, with a significantly higher serum bilirubin level, lower albumin level, lower platelet count, and longer prothrombin time. They had significantly smaller HCCs but more frequent portal vein thrombosis. There was a significant difference in the overall survival between HCC patients who presented with variceal bleeding and those who did not (median 3.5 months vs 7.5 months, p < 0.001). In the variceal bleeding group, by multivariate analysis, treatment with transarterial chemoembolization was the only significant independent prognostic factor for survival (odds ratio 17.16, 95% CI: 2.81-104.91, p= 0.002). HCC patients who presented with variceal bleeding can be expected to have a significantly worse survival outcome than the general HCC patients. However, transarterial chemoembolization may offer some survival benefit to a selected group of HCC patients presenting with variceal bleeding.


Biochemistry in Endeavor Adventure Racers Study (BEARS).
Adventure sports events consist of a combination of two or more endurance disciplines, such as orienteering, running, and rock climbing, that range from a day's to a week's duration. No studies have examined acute kidney injury (AKI) in adventure sports athletes. To describe the prevalence of AKI in participants in the Endeavor Team Challenge, a 30-hour, 40-mile adventure race. In this prospective observational study, body weights were recorded at race registration. At the finish line, blood sample results by point-of-care testing and weights were recorded. Changes in serum creatinine (Cr) from an estimated baseline value and severity of AKI were calculated, with "risk of injury" defined as 1.5 x baseline Cr, and "injury" defined as 2 x baseline Cr. These two categories of AKI were combined to calculate the total prevalence. Results: There were 88 enrolled study participants with complete data available on 46 (52%). The mean age of those enrolled in the study was 36.8 years (+/- 7.7), 90% were males, and body mass index (BMI) was 25.7 kg/m2 (+/- 2.4). Of the competitors who completed the study, 34 (73%) had some degree of AKI, with 27 (58%) found to be at "risk" and seven (15%) with "injury". There was a significant correlation between weight loss and elevated Cr (r = -0.29, p = 0.047), with a trend towards nonsteroidal anti-inflammatory drug (NSAID) use being correlated with AKI (p = 0.058). Acute kidney injury was observed in the majority of the Endeavor Team Challenge adventure racers, similar to what has been observed in multistage ultramarathons, and greater than after standard marathons and single-stage ultramarathons.


Ophthalmic nurses' knowledge, attitude, and practice toward venous thromboembolic prevention: a dual-center cross-sectional survey.
Venous thromboembolism (VTE) is a severe preventable complication among ophthalmic surgical patients. The knowledge, attitude, and practice (KAP) of nurses play a key role in effective VTE prevention. However, little is known about the KAP of ophthalmic nurses' VTE prevention. This study aimed to examine the level of KAP toward VTE prevention among Chinese ophthalmic nurses and to investigate the influencing factors of their VTE practice. A total of 610 ophthalmic nurses from 17 cities in Hunan and Zhejiang Provinces, China, participated in this study. Data was collected via the Sojump online platform from March to April 2021. A self-administered VTE questionnaire was developed to assess nurses' KAP toward VTE prevention. Multiple linear regression analysis was used to analyze the influencing factors of ophthalmic nurses' VTE prevention practice. The scores (correct rates) of ophthalmic nurses' knowledge, attitude, and practice were 103.87 ± 20.50 (76.4%), 21.96 ± 2.72, and 48.96 ± 11.23 (81.6%), respectively. The three lowest-scored knowledge items were related to VTE complications, physical prevention, and risk assessment. The three lowest-scored attitude items were related to nurses' training, VTE risk, and patient education. The three lowest-scored practice items were related to the assessment scale, VTE assessment, and patient education. Nurses' knowledge, attitude, and practice were significantly correlated with each other. Multiple linear regression analysis showed that Hunan Province (B = 2.77, p = 0.006), general hospital (B = 2.97, p = 0.009), outpatient department (B = 3.93, p = 0.021), inpatient department (B = 2.50, p = 0.001), previous VTE prevention training (B = 3.46, p < 0.001), VTE prevention management in hospital (B = 4.93, p < 0.001), better knowledge (B = 0.04, p = 0.038), and positive attitude towards VTE prevention (B = 1.35, p < 0.001) were all significantly and positively associated with higher practice scores in VTE prevention. Our study provided a comprehensive understanding of the ophthalmic nurses' knowledge, attitude, and practice in VTE prevention, as well as identified specific items in each dimension for improvement. In addition, our study showed multiple factors were associated with ophthalmic nurses' practice in VTE prevention, including environmental factors, training and management, knowledge and attitudes toward VTE prevention. Our findings provide important implications and guidance for future intervention programs to improve the ophthalmic nurses' knowledge, attitude, and practice in VTE prevention.


Malignant transformation of liver adenoma: an analysis of the literature.
As adenoma in other locations, hepatic adenoma (HA) may transform into hepatocellular carcinoma (HCC) and hepatocyte dysplasia is most probably the intermediate step between both conditions. Malignant HA may appear as microscopic or macroscopic areas of HCC within the HA. These areas are typically well differentiated and without vascular extension or satellite nodules. AFP measurements are not reliable as they are usually normal. The risk of malignant transformation of HA cannot be reliably quantified yet. Several series are concordant to show that approximately 5% of patients whose HA have been resected had pathological evidence of HCC within their HA. This figure however does not take into account fully transformed HA where evidence of the preexisting benign lesion might have disappeared. The risk of malignant transformation is correlated with the diameter of the HA and it is very unusual when it is <5 cm and the same holds true for patients with multiple HA. These results suggest that small HA could be safely observed as they are also at low risk of bleeding. These conclusions might not apply to male patients who are at lower risk of HA, except in specific conditions, but appear to be at a much higher risk of malignant changes.


Clinical outcome of oocyte cryopreservation after slow cooling with a protocol utilizing a high sucrose concentration.
Recently, interest in oocyte cryopreservation has steadily increased. Newly developed protocols have dramatically improved survival rates, removing perhaps the major hurdle that has prevented this approach from becoming a fully established form of treatment. However, the clinical efficiency of these protocols has not been exhaustively explored and therefore remains controversial. Morphologically normal oocytes displaying the first polar body were frozen-thawed with a slow cooling protocol that utilized 1.5 mol/l propane-1,2-diol (PrOH) and 0.3 mol/l sucrose. A total of 927 oocytes from 146 patients were frozen-thawed, achieving a 74.1% survival rate. Over 76% of microinjected oocytes displayed two pronuclei 16 h post-insemination, while the proportion of embryos at 44-46 h post-insemination was 90.2%. At this time point, the majority (68.3%) of embryos were at the two-cell stage, showing in most cases (78.7%) minimal or moderate fragmentation. Eighteen clinical pregnancies, three of which were twin, were observed, giving rise to rates of 12.3 and 9.7%, calculated per patient and per embryo transfer, respectively. The implantation rate was 5.2%. To date, four children have been born and three pregnancies resulted in spontaneous abortions, while the remaining pregnancies are ongoing. Our data indicate that although the combination of slow cooling and high sucrose concentration ensures high rates of oocyte survival, it is not sufficient to guarantee a high standard of clinical efficiency.


Cadmium-Tolerant Rhizospheric Bacteria of the C3/CAM Intermediate Semi-Halophytic Common Ice Plant (Mesembryanthemum crystallinum L.) Grown in Contaminated Soils.
The common ice plant, Mesembryanthemum crystallinum L., has recently been found as a good candidate for phytoremediation of heavy-metal polluted soils. This semi-halophyte is a C3/CAM (Crassulacean acid metabolism) intermediate plant capable of tolerating extreme levels of cadmium in the soil. The aim of the work was to obtain and characterize novel, Cd-tolerant microbial strains that populate the root zone of M. crystallinum performing different types of photosynthetic metabolism and growing in Cd-contaminated substrates. The plants exhibiting either C3 or CAM photosynthesis were treated for 8 days with different CdCl2 doses to obtain final Cd concentrations ranging from 0.82 to 818 mg⋅kg-1 of soil d.w. The CAM phase was induced by highly saline conditions. After treatment, eighteen bacterial and three yeast strains were isolated from the rhizosphere and, after preliminary Cd-resistance in vitro test, five bacterial strains were selected and identified with a molecular proteomics technique. Two strains of the species Providencia rettgeri (W6 and W7) were obtained from the C3 phase and three (one Paenibacillus glucanolyticus S7 and two Rhodococcus erythropolis strains: S4 and S10) from the CAM performing plants. The isolates were further tested for Cd-resistance (treatment with either 1 mM or 10 mM CdCl2) and salinity tolerance (0.5 M NaCl) in model liquid cultures (incubation for 14 days). Providencia rettgeri W7 culture remained fully viable at 1 mM Cd, whereas Rh. erythropolis S4 and S10 together with P. glucanolyticus S7 were found to be resistant to 10 mM Cd in the presence of 0.5 M NaCl. It is suggested that the high tolerance of the common ice plant toward cadmium may result from the synergic action of the plant together with the Cd/salt-resistant strains occurring within rhizospheral microbiota. Moreover, the isolated bacteria appear as promising robust microorganisms for biotechnological applications in bio- and phytoremediation projects.


[Consultation of congenital heart diseases in pediatric cardiology in Mauritania].
The aim of this study is to describe the epidemiological profile of congenital heart diseases in Mauritanian children. Our population was composed of children referred by the different cardiologists of the country on the occasion of two missions of pediatric cardiologists in December 2001 and November 2002. All patients had physical examination, chest radiogram, electrocardiogram, and echocardiogram. There were 84 patients aged between 2 months and 16 years. Mean age was 6.1 +/- 5.0 years. Forty eight children (57.1%) were males and 36 (43.9%) females (sex ratio was 1.3). Ventricular septal defect (17%), tetralogy of Fallot (13%) and pulmonary stenosis (12%) were the predominant pathologiese. Surgery was initially indicated for in 61 infants (73%), realized in 22 of them (26%) and considered out of date in 10 patients (12%). Congenital heart diseases pose a major problem of treatment in Mauritania. They are dominated by the left to right shunts. The age of diagnosis is relatively late (6 years) exposing to the risk of complications. Therefore, a team of paediatric cardiologists on the spot and the setting up of cardiovascular surgery facilities are necessary.


An overview of the aging population in Korea.
The author examines demographic aging in South Korea in light of the country's near-completion of the demographic transition. "An attempt is made to describe the general features of the present situation of the Korean elderly by reviewing several aspects of the aging phenomenon in Korea, namely, the demographic, family, psychological, and social welfare aspects." (SUMMARY IN KOR)


An unusual cause of acute carpal tunnel syndrome.
Acute carpal tunnel syndrome following anticoagulation is uncommon. We describe a case in which the diagnosis was missed on three previous presentations by several clinicians. Although the presentation is typical, lack of awareness of this complication, inability to notice subtle signs and failure to do INR may lead to missing the diagnosis.


Hierarchically structured nanoporous carbon tubes for high pressure carbon dioxide adsorption.
Mesoscopic, nanoporous carbon tubes were synthesized by a combination of the Stoeber process and the use of electrospun macrosized polystyrene fibres as structure directing templates. The obtained carbon tubes have a macroporous nature characterized by a thick wall structure and a high specific surface area of approximately 500 m²/g resulting from their micro- and mesopores. The micropore regime of the carbon tubes is composed of turbostratic graphitic areas observed in the microstructure. The employed templating process was also used for the synthesis of silicon carbide tubes. The characterization of all porous materials was performed by nitrogen adsorption at 77 K, Raman spectroscopy, infrared spectroscopy, thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) as well as transmission electron microscopy (TEM). The adsorption of carbon dioxide on the carbon tubes at 25 °C at pressures of up to 30 bar was studied using a volumetric method. At 26 bar, an adsorption capacity of 4.9 mmol/g was observed. This is comparable to the adsorption capacity of molecular sieves and vertically aligned carbon nanotubes. The high pressure adsorption process of CO2 was found to irreversibly change the microporous structure of the carbon tubes.


Wettability of pear leaves from three regions characterized at different stages after flowering using the OWRK method.
A better understanding of leaf surface wettability is critical to improve the adhesion of liquid pesticides. Leaf surface wettability is dependent on the property of the liquid as well as the physical and chemical properties of the leaf, which vary with climate and growth stage. The aim of this study was to characterize the wettability of pear leaves from three different climatic regions at different stages after flowering. The contact angles of different test liquids were measured on both adaxial and abaxial pear leaf surfaces and the Owens-Wendt-Rabel-Kaelble (OWRK) method was used to calculate surface free energy (SFE) and its polar and non-polar components. The results demonstrated that the SFE of both the adaxial and abaxial surface of the pear leaf, and the proportion of polar component, increased with increasing time after flowering. At early growth stages, pear leaves were highly hydrophobic, similar to a polytetrafluoroethylene surface, whereas at later growth stages, pear leaves were hydrophobic, more similar to a polymethylmethacrylate surface. Also, the SFE differed with climatic region. Factors influencing these changes are discussed. Changes in contact angles and SFE correlated with the change of the leaf surface wettability. Leaves became easier to wet (higher SFE), with an overall increasing polar component to the surface, with increasing age after flowering. As expected, changes in wettability were found in pear leaves at different stages after flowering and in different regions (P < 0.05). Pear leaves from Yuanping were easier to wet than leaves from Yuci and Linyi, and adaxial surfaces were easier to wet than abaxial surfaces. These results provide beneficial information for the application of agrochemicals for improved wetting and spreading behavior. © 2018 Society of Chemical Industry.


Identification of State Markers in Anorexia Nervosa: Replication and Extension of Inflammation Associated Biomarkers Using Multiplex Profiling in Anorexia Nervosa and Atypical Anorexia Nervosa.
Proteomics provides an opportunity for detection and monitoring of anorexia nervosa (AN) and its related variant, atypical-AN (atyp-AN). However, research to date has been limited by the small number of proteins explored, exclusive focus on adults with AN, and lack of replication across studies. This study performed Olink Proseek Multiplex profiling of 92 proteins involved in inflammation among females with AN and atyp-AN (N = 64), all < 90% of expected body weight, and age-matched healthy controls (HC; N=44). After correction for multiple testing, nine proteins differed significantly in the AN/atyp-AN group relative to HC group ( lower levels: CXCL1, HGF, IL-18R1, TNFSF14, TRANCE; higher levels: CCL23, Flt3L, LIF-R, MMP-1). The expression levels of three proteins ( lower IL-18R1, TRANCE; higher LIF-R) were uniquely disrupted in females with AN. No unique expression levels emerged for atyp-AN. Across the whole sample, twenty-one proteins correlated positively with BMI (ADA, AXIN1, CD5, CD244, CD40, CD6, CXCL1, FGF-21, HGF, IL-10RB, IL-12B, IL18, IL-18R1, IL6, LAP TGF-beta-1, SIRT2, STAMBP, TNFRSF9, TNFSF14, TRAIL, TRANCE) and six (CCL11, CCL23, FGF-19, IL8, LIF-R, OPG) were negatively correlated with BMI. Overall, our results replicate the prior study demonstrating a dysregulated inflammatory status in AN, and extend these results to atyp-AN (AN/atyp-AN all < 90% of expected body weight). Of the 27 proteins correlated with BMI, 18 were replicated from a prior study using similar methods, highlighting the promise of inflammatory protein expression levels as biomarkers of disease monitoring. Additional studies of individuals across the entire weight spectrum are needed to understand the role of inflammation in atyp-AN.


Emergence of a latent TSHoma pituitary macroadenoma on a background of primary autoimmune hypothyroidism
The coexistence of primary hypothyroidism and thyroid-stimulating hormone (TSH)-stimulating pituitary macroadenoma can be a rare occurrence and can make diagnosis very challenging. We describe a case of a 44-year-old female with a history of fatigue, poor concentration, weight gain and amenorrhoea together with biochemical evidence of primary autoimmune hypothyroidism. Her initial TSH levels were elevated with low normal free thyroxine (T4) levels. Levothyroxine treatment was initiated and the dose was gradually titrated to supraphysiologic doses. This led to the normalisation of her TSH levels but her free T4 and triiodothyronine (T3) levels remained persistently elevated. This prompted a serum prolactin check which returned elevated at 2495 μ/L, leading onto pituitary imaging. A MRI of the pituitary gland revealed a pituitary macroadenoma measuring 2.4 × 2 × 1.6 cm. Despite starting her on cabergoline therapy with a reduction in her prolactin levels, her TSH levels began to rise even further. Additional thyroid assays revealed that she had an abnormally elevated alpha subunit at 3.95 (age-related reference range <3.00). This corresponded to a thyroid-secreting hormone pituitary macroadenoma. She went on to have a transphenoidal hypophysectomy. Histology revealed tissues staining for TSH, confirming this to be a TSH-secreting pituitary macroadenoma. This case highlighted the importance of further investigations with thyroid assay interferences, heterophile antibodies, alpha subunit testing and anterior pituitary profile in cases of resistant and non-resolving primary hypothyroidism. Learning points: •• Levothyroxine treatment in primary hypothyroidism can potentially unmask the presence of a latent TSH-secreting pituitary macroadenoma, which can make diagnosis very challenging. •• A high index of suspicion should prompt clinicians to further investigate cases of primary hypothyroidism which despite increasing doses of levothyroxine treatment with normalisation of TSH, the free T4 and T3 levels remain persistently elevated. •• Clinicians should consider investigating for adherence to levothyroxine, thyroid assay interference, heterophile antibodies, TSH dilution studies, alpha subunit and anterior pituitary profile testing to further clarity the diagnosis in these patients. •• Although coexistent cases of TSHoma with primary hypothyroidism are rare, it should always be in the list of differential diagnoses in cases of unresolving primary hypothyroidism.


A randomized controlled trial to evaluate and assess the effect of comprehensive pre-end stage kidney disease education on home dialysis use in veterans, rationale and design.
Informed dialysis selection and greater home dialysis use are the two long-desired, underachieved targets of advanced chronic kidney disease (CKD) care in the US healthcare system. Observational institutional studies have shown that comprehensive pre-kidney failure, conventionally referred to as end stage kidney disease education (CPE) can improve both these outcomes. However, lack of validated protocols, well-controlled studies, and systemic models have limited wide-spread adoption of CPE in the US. We hypothesized that a universal CPE and patient-centered initiation of kidney replacement therapy can improve multiple clinical, patient-centered and health service outcomes in advanced CKD and kidney failure requiring dialysis therapy. Trial to Evaluate and Assess the effects of CPE on Home dialysis in Veterans (TEACH-VET) is a multi-method randomized controlled trial aimed to evaluate the effects of a system-based approach for providing CPE to all Veterans with advanced CKD across a regional healthcare System. The study will randomize 544 Veterans with non-dialysis stage 4 and 5 CKD in a 1:1 allocation stratified by their annual family income and the stage of CKD to an intervention (CPE) arm or control arm. Intervention arm will receive a two-phase CPE in an intent-to-teach manner. Control arm will receive usual clinical care supplemented by resources for the freely-available kidney disease information. Participants will be followed after intervention/control for the duration of the study or until 90-days post-kidney failure, whichever occurs earlier. The primary outcome will assess the proportion of Veterans using home dialysis at 90-days post-kidney failure, and secondary outcomes will include post-intervention/control CKD knowledge, confidence in dialysis decision and home dialysis selection. Qualitative arm of the study will use semi-structured interviews to in-depth assess Veterans' satisfaction with the intervention, preference for delivery, and barriers and facilitators to home dialysis selection and use. Several post-kidney failure clinical, patient-centered and health services outcomes will be assessed 90-days post-kidney failure as additional secondary outcomes. The results will provide evidence regarding the need and efficacy of a system-based, patient-centered approach towards universal CPE for all patients with advanced CKD. If successful, this may provide a blueprint for developing such programs across the similar healthcare infrastructures throughout the country. NCT04064086 .


Characteristics of convergence insufficiency.
Convergence insufficiency (CI) is a well-known syndrome of binocular visual dysfunction. In a review of 58 papers, considerable variation was noted in the criteria used to define the condition. Symptoms and decreased positive fusional vergences (both at the nearpoint) were the only criteria named in more than one-half of the studies. An extended nearpoint of convergence (NPC) and increased exophoria at near were criteria in about one-third of the papers. Examination of data in the reviewed papers shows that although considerable variability was noted, the distance exodeviation, distance negative vergences, visual acuity, refraction, and stereopsis were about the same as population norms. Positive vergences, negative vergence at near, and NPC were somewhat less than population norms. Vergences relative to Sheard's criterion, the near exophoria, accommodative amplitude, and the AC/A ratio were consistently below those derived from population norms. This considerable variation may largely be a result of different criteria used for diagnosis, subpopulations within the data, and other confounding factors.


Clinical relevance of a CD4+ T cell immune function assay in the diagnosis of infection in pediatric living-donor liver transplantation.
The aim of the present study was to investigate the potential of the Immuknow immune cell function assay for the diagnosis of infection after pediatric living-donor liver transplantation (LDLT). Based on clinical data obtained following liver transplantation, 66 patients were divided into infection (n=28) and non-infection (n=38) groups. The following factors were considered in the present analysis: Primary disease, lymphocyte count, tacrolimus plasma concentration/dose (C0/D) ratio, CD4+ T lymphocyte ATP levels, at pre-transplant stage and at weeks 1-4, and 2 and 3 months post-transplant. The CD4+ T lymphocyte ATP values were plotted in a receiver operating characteristic (ROC) curve. The CD4+ T lymphocyte ATP value of the infection group was significantly lower compared with that of the non-infection group (188.6±93.5 vs. 424.4±198.1 ng/ml, respectively; P<0.05). No correlation was observed between the ATP value and tacrolimus plasma C0/D ratio (R2=0.0001484); however, a correlation was reported between the ATP value and lymphocyte count (R2=0.2149). Analysis of the ROC curve indicated that the ATP levels of CD4+ T cells were significantly associated with the diagnostic value of infection (area under the curve=0.866). These findings suggest that low CD4+ T lymphocyte ATP levels may be an independent risk factor for infection following pediatric LDLT, and that the Immuknow assay may be used as a tool to evaluate T lymphocyte function in such patients to predict the risk of infection.


Glucocorticoid receptor gene polymorphisms and childhood adversity are associated with depression: New evidence for a gene-environment interaction.
The hypothalamic-pituitary-adrenal (HPA)-axis regulates the response to stressful events and is expected to be involved in the pathogenesis of depression. The glucocorticoid receptor (GR) regulates the activity of the HPA-axis. Both GR gene polymorphisms and childhood adversity are known to be associated with increased risk for depression. In the Longitudinal Aging Study Amsterdam, a large population based sample of older men and women, 906 subjects were genotyped. An association study was performed to determine the relationship between GR gene polymorphisms, childhood adversity, HPA-axis markers and depressive symptoms. A gene-environment interaction between the GR polymorphisms 22/23EK and 9beta and childhood adversity resulted in an increased risk of clinically relevant depressive symptoms. Without childhood adversity no increased risk was present. The 22/23EK variant was also associated with a lower Free Cortisol Index in the presence of childhood adversity. Persons that are heterozygous for the BclI variant, in contrast with wild-type and BclI-homozygotes, had lower serum levels of cortisol binding globulin and had no increased risk of recurrent depressive symptoms in the presence of childhood adversity. We found a gene-environment (G x E) interaction between common variants of the GR gene and childhood adversity, demonstrating a vulnerable phenotype for developing clinically relevant depressive symptoms at old age. This G x E interaction also influenced HPA-axis markers providing support for the involvement of the HPA-axis in both stress regulation and the pathogenesis of depression.


A Rapid qPCR for the Detection of Verticillium nonalfalfae MLST2 - A Highly Pathogenic Fungus on Kiwifruit.
A highly pathogenic fungus characterized as Verticillium nonalfalfae multilocus sequence type 2 (MLST2) is an emerging fungal pathogen causing Verticillium wilt on kiwifruit. Although V. nonalfalfae MLST2 has not been reported outside Chile, there is a risk that this pathogen could spread through the global movement of germplasms to other countries. Current diagnostic methods for this fungus rely on a laborious and time-consuming plating assay for morphological identification and DNA sequence analysis. In this study, we describe the development and validation of a novel quantitative polymerase chain reaction (qPCR) assay for rapid and specific detection of V. nonalfalfae MLST2 in plant tissues. The assay targets the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene and was shown to detect all tested isolates of V. nonalfalfae MLST2 with a detection limit of approximately 2 pg of pathogen genomic DNA. There was no cross-reaction with V. nonalfalfae MLST1, other Verticillium species, or non-target fungal species found on kiwifruit. This assay was duplexed with a plant internal control for simultaneous detection of the pathogen and cytochrome oxidase gene from the host plant. This new specific and sensitive qPCR assay is a valuable molecular diagnostic tool for rapid screening of imported plant material and would also be useful for testing samples collected from field surveillance activities to monitor the presence of V. nonalfalfae MLST2.


Role of surgery in cerebral venous sinus thrombosis.
Cerebral venous sinus thrombosis (CVST) usually is taken care of by medical management or neuro-interventional vascular techniques. Some cases of CVST may take a malignant course if the intracranial pressure increases excessively. This increase in pressure is because of oedema in brain tissue due to impediment in venous return and/or intracerebral haemorrhage. Neurosurgical experience has shown remarkable recovery in these moribund patients if appropriate surgical intervention is done within reasonable time. Emergent decompressive craniotomy or other neurosurgical interventions are the only appropriate treatment in these malignant forms of CVST to prevent mortality and severe morbidity.


Growing up in a world with AIDS: social advantages of having AIDS in Brazil.
Could HIV/AIDS become a positive factor for a child's life? This contradiction is explored in this paper based on anthropological fieldwork and research in Brazil. I used participant observation and informal interviewing both with children living with HIV/AIDS and uninfected street children to obtain qualitative data. Brazil is known as a country leader in social responses towards the AIDS epidemic. Not only has access to antiretroviral medications been assured, but also a series of help networks guarantee that the human rights of HIV-infected people be respected. Children and adolescents benefit equally from these social gains. As such, many children born to HIV-positive women have reached adolescence and have 'normal' lives. This article explores the life experiences of children and adolescents infected by HIV and compares them to the life experiences of street children. Even though the AIDS epidemic is linked to death, infected children and adolescents dream about their lives and futures. Contradictorily, street children, who have not acquired the virus and are considered healthy from a biological stand point, have no prospective plans and answer without hope to questions about the future.


Effect of salt intake on bioavailability of mizoribine in healthy Japanese males.
Bioavailability of mizoribine in subjects with the concentrative nucleoside transporter 1 (CNT1, SLC28A1) 565-A/A allele is significantly lower than that in subjects with the SLC28A1 565-G/G allele. The aims of the present study were to investigate the cellular uptake of mizoribine in CNT1- and CNT2-expressing Madin-Darby canine kidney type II (MDCKII) cells, and to evaluate the effect of salt intake on bioavailability of mizoribine in healthy Japanese volunteers with SLC28A1 565-A/A and -G/A alleles. Eight healthy males participated in the present study, and took 150 mg mizoribine concomitantly with/without 300 mg salt. Bioavailability of mizoribine was estimated by total cumulative urinary excretion of the drug. Mizoribine was taken up Na(+)-dependently into not only CNT1-expressing but also CNT2-expressing MDCKII cells, indicating that mizoribine is a substrate for both CNT1 and CNT2. Mean bioavailability of mizoribine taken with salt (83.8%) was significantly higher than that taken without salt (73.0%). These findings suggest that the salt intake is expected to improve the bioavailability of mizoribine in patients with insufficient intestinal absorption.


GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro.
Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human? The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro. Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary. This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015. Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups. The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples. GnRHa co-administered with chemotherapy agents stimulated its receptors and raised intracellular cAMP levels. But it neither activated anti-apoptotic pathways nor prevented follicle loss, DNA damage and apoptosis induced by these drugs. Our findings do not conclusively rule out the possibility that GnRHa may offer protection, if any, through some other mechanisms in vivo. GnRH agonist treatment with chemotherapy does not prevent or ameliorate ovarian damage and follicle loss in vitro. These data can be useful when consulting a young patient who may wish to receive GnRH treatment with chemotherapy to protect her ovaries from chemotherapy-induced damage.


Age-related differences in skeletal muscle insulin signaling: the role of stress kinases and heat shock proteins.
Aging is associated with an increase in insulin resistance in skeletal muscle, yet the underlying mechanism is not well established. We hypothesize that with aging, a chronic increase in stress kinase activation, coupled with a decrease in oxidative capacity, leads to insulin resistance in skeletal muscle. In aged (24 mo old) and young (3 mo old) Fischer 344 rats, 2-deoxyglucose uptake and insulin signaling [as measured by phosphorylation of insulin receptor substrate-1 (IRS-1), Akt (protein kinase B), and Akt substrate of 160 kDa (AS160)] decreased significantly with age. Activation of, c-Jun NH(2)-terminal kinase (JNK), glycogen serine kinase-3beta (GSK-3beta), and degradation of IkappaBalpha by the upstream inhibitor of kappa B kinase (IKKbeta), as measured by Western blot analysis, were increased with age in both soleus and epitrochlearis (Epi) muscles. However, much higher activation of these kinases in Epi muscles from young rats compared with soleus results in a greater effect of these kinases on insulin signaling in fast-twitch muscle with age. Heat shock protein (HSP) 72 expression and phosphorylation of HSP25 were higher in soleus compared with Epi muscles, and both parameters decreased with age. Age and fiber type differences in cytochrome oxidase activity are consistent with observed changes in HSP expression and activation. Our results demonstrate a significant difference in the ability of slow-twitch and fast-twitch muscles to respond to insulin and regulate glucose with age. A greater constitutive HSP expression and lower stress kinase activation may account for the ability of slow-twitch muscles to preserve the capacity to respond to insulin and maintain glucose homeostasis with age.


TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial.
The purpose of this analysis was to provide 6-year follow-up of the CLL3X trial, which studied reduced-intensity allogeneic hematopoietic stem cell transplantation (HSCT) in patients with poor-risk chronic lymphocytic leukemia (CLL), and to investigate the effect of TP53, SF3B1, and NOTCH1 mutations on HSCT outcome. For 90 allografted patients, 6-year overall survival (OS) was 58% and 6-year event-free survival (EFS) was 38%. TP53, SF3B1, and NOTCH1 mutations were found in 30%, 26%, and 14% of the trial population, respectively. By univariate and multivariate analyses, the mutational status of the TP53, SF3B1, and NOTCH1 genes had no significant effect on OS and EFS. Studies of minimal residual disease confirmed durability of CLL eradication in mutated patients. We conclude that HSCT can provide long-term disease control in patients with poor-risk CLL independent of the presence of TP53, SF3B1, and NOTCH1 mutations. The trial has been registered at the US National Cancer Institute as #EU-20554, NCT00281983.


[Experimental study of a new technic of sutureless tubal anastomosis in the rabbit].
The authors have tested an original method of tubal anastomosis in the rabbit, which does not require suture material. The principle of the operation is the intubation of the ovarian tube by a silicone elastomere tube which acts as a guide for healing. From the 11 rabbits operated, the authors obtained 7 pregnancies, i.e. 63,6%. The results of this series do not appear to be any different from the pregnancy rates obtained by other teams with microsurgical techniques in the rabbit. The authors conclude that their method is as reliable, but more simple.