Extracting relations from texts using vector language models and a neural network classifier.
The article investigates the possibility of identifying the presence of SKOS (Simple Knowledge Organization System) relations between concepts represented by terms on the base of their vector representation in general natural language models. Several language models of the Word2Vec and GloVe families are considered, on the basis of which an artificial neural network (ANN) classifier of SKOS relations is formed. To train and test the efficiency of the classifier, datasets formed on the basis of the DBPedia and EuroVoc thesauri are used. The experiments performed have shown the high efficiency of the classifier trained using GloVe family models, while training it with use of Word2Vec models looks impossible in the bounds of considered ANN-based classifier architecture. Based on the results, a conclusion is made about the key role of taking into account the global context of the use of terms in the text for the possibility of identifying SKOS relations.


Botrytis cinerea B05.10 promotes disease development in Arabidopsis by suppressing WRKY33-mediated host immunity.
The large WRKY transcription factor family is mainly involved in regulating plant immune responses. Arabidopsis WRKY33 is a key transcriptional regulator of hormonal and metabolic processes towards Botrytis cinerea strain 2100 infection and is essential for resistance. In contrast to B. cinerea strain 2100, the strain B05.10 is virulent on wild-type (WT) Col-0 Arabidopsis plants highlighting the genetic diversity within this pathogen species. We analysed how early WRKY33-dependent responses are affected upon infection with strain B05.10 and found that most of these responses were strongly dampened during this interaction. Ectopic expression of WRKY33 resulted in complete resistance towards this strain indicating that virulence of B05.10, at least partly, depends on suppressing WRKY33 expression/protein accumulation. As a consequence, the expression levels of direct WRKY33 target genes, including those involved in the biosynthesis of camalexin, were also reduced upon infection. Concomitantly, elevated levels of the phytohormone abscisic acid (ABA) were observed. Molecular and genetic studies revealed that ABA negatively influences defence to B05.10 and effects jasmonic acid/ethylene (JA/ET) and salicylic acid (SA) levels. Susceptibility/resistance was determined by the antagonistic effect of ABA on JA, and this crosstalk required suppressing WRKY33 functions at early infection stages. This indicates that B. cinerea B05.10 promotes disease by suppressing WRKY33-mediated host defences.


Microarray Analysis of Differential Gene Expression Between Traumatic Temporomandibular Joint Fibrous and Bony Ankylosis in a Sheep Model.
BACKGROUND The type of traumatic temporomandibular joint (TMJ) ankylosis depends on the degree of severity of TMJ trauma. Here, we performed comprehensive differential molecular profiling between TMJ fibrous and bony ankylosis. MATERIAL AND METHODS Six sheep were used and a bilateral different degree of TMJ trauma was performed to induce fibrous ankylosis in one side and bony ankylosis in the other side. The ankylosed calluses were harvested at days 14 and 28 postoperatively and analyzed by Affymetrix OviGene-1_0-ST microarrays. DAVID was used to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Ten DEGs, including 7 hub genes from PPI analysis, were confirmed by real-time PCR. RESULTS We found 90 and 323 DEGs at least 2-fold at days 14 and 28, respectively. At day 14, bony ankylosis showed upregulated DEGs, such as TLR8, SYK, NFKBIA, PTPRC, CD86, ITGAM, and ITGAL, indicating a stronger immune and inflammatory response and cell adhesion, while genes associated with anti-adhesion (PRG4) and inhibition of osteoblast differentiation (SFRP1) had higher expression in fibrous ankylosis. At day 28, bony ankylosis showed increased biological process related to new bone formation, while fibrous ankylosis was characterized by a prolonged immune and inflammatory reaction. CONCLUSIONS This study provides a differential gene expression profile between TMJ fibrous and bony ankylosis. Further study of these key genes may provide new ideas for future treatment of TMJ bony ankylosis.


IFN-alpha promotes the rapid differentiation of monocytes from patients with chronic myeloid leukemia into activated dendritic cells tuned to undergo full maturation after LPS treatment.
Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease arising from the clonal expansion of a stem cell expressing the bcr/abl oncogene. CML patients frequently respond to treatment with interferon-alpha (IFN-alpha), even though the mechanisms of the response remain unclear. In the present study, we evaluated the role of IFN-alpha in differentiation and activity of monocyte-derived dendritic cells (DCs) from CML patients as well as in modulation of the cell response to lipopolysaccharide (LPS). Treatment of CML monocytes with IFN-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in the rapid generation of activated DCs (CML-IFN-DCs) expressing interleukin-15 (IL-15) and the antiapoptotic bcl-2 gene. These cells were fully competent to induce IFN-gamma production by cocultured autologous T lymphocytes and expansion of CD8(+) T cells. LPS treatment of CML-IFN-DCs, but not of immature DCs generated in the presence of IL-4/GM-CSF, induced the generation of CD8(+) T cells reactive against autologous leukemic CD34(+) cells. Altogether, these results suggest that (1) the generation of highly active monocyte-derived DCs could be important for the induction of an antitumor response in IFN-treated CML patients and (2) IFN-alpha can represent a valuable cytokine for the rapid generation of active monocyte-derived DCs to be utilized for vaccination strategies of CML patients.


Development and validation of the dizziness fear-avoidance behaviours and beliefs inventory for patients with vestibular disorders.
The purpose of this study is to present the development and analysis of the factorial structure and psychometric properties of a new self-administered questionnaire (Dizziness Fear-Avoidance Behaviours and Beliefs Inventory (D-FABBI)) designed to measure fear-avoidance behaviors and cognitions related to dizziness disability. A mixed-method design combining a qualitative study with an observational and cross-sectional study was employed to develop (content validity) and psychometrically validate (construct validity, reliability, and convergent/discriminant validity) a new instrument. A total of 198 patients with vestibular disorders (acute vestibular syndrome (AVS), 23.2%; chronic vestibular syndrome (CVS), 35.4%; and episodic vestibular syndrome (EVS) 41.4%) were recruited. Sociodemographic characteristics, the Dizziness Handicap Inventory (DHI) and the Hospital Anxiety and Depression Scale (HADS) and D-FABBI were evaluated. The final version of the D-FABBI consists of 17 items distributed across two subscales: activities of daily living fear-avoidance and movement fear-avoidance. The D-FABBI showed high internal consistency (Cronbach α = 0.932; 95% CI [0.91-0.94]) and so did the subscales (Cronbach α > 0.8). The exploratory structural equation model and confirmatory factor analysis provided better fit results, with a comparative fit index and root mean square error of approximation values of 0.907 to 0.081. No floor or ceiling effects were identified. There was a positive, significant, and moderate-strong magnitude correlation with the total DHI (r = 0.62) and low-moderate with respect to the HADS depression (r = 0.35) and HADS anxiety subscales (r = 0.26). The patients with CVS had a higher D-FABBI score than those with AVS or EVS. The D-FABBI appears to be a valid and reliable instrument for measuring the fear-avoidance behaviors and cognition related to dizziness disability of patients with vestibular disorders.


A prospective clinical trial comparing preformed metal crowns and cast restorations for defective first permanent molars.
This study investigated two methods for the restoration of permanent molars affected by amelogenesis imperfecta (AI) or severe enamel defects. A prospective clinical trial was carried out on 17 subjects affected by AI or severe enamel defects of first permanent molars. A split mouth design was used so that each right or left permanent molar in both jaws was restored using either a preformed metal crown (SSC) or a cast adhesive coping (CAC). Subjects were followed for up to 24 months and assessed for longevity and quality of the restorations. Sequential analysis was used to compare longevity. Records for 42 restorations (19 SSC; 23 CAC) were kept. The split mouth design was possible on 24 occasions (right versus left=14; maxilla versus mandible=10). Three restorations, one SSC (at 6 months) and two CAC (at 2 and 19 months) failed and required replacement. There was no significant statistical difference between the two types of restorations. While there was no difference between the two restorations for quality and longevity, the SSC was considerably cheaper to use and needed only one visit, but more tooth tissue was lost in preparation and fitting. The CAC was significantly more expensive but left nearly all of the tooth crown intact. The choice of which restoration to use is indicated by the immediate and long-term needs of each individual patient.


Predicting ESI/MS Signal Change for Anions in Different Solvents.
LC/ESI/MS is a technique widely used for qualitative and quantitative analysis in various fields. However, quantification is currently possible only for compounds for which the standard substances are available, as the ionization efficiency of different compounds in ESI source differs by orders of magnitude. In this paper we present an approach for quantitative LC/ESI/MS analysis without standard substances. This approach relies on accurately predicting the ionization efficiencies in ESI source based on a model, which uses physicochemical parameters of analytes. Furthermore, the model has been made transferable between different mobile phases and instrument setups by using a suitable set of calibration compounds. This approach has been validated both in flow injection and chromatographic mode with gradient elution.


Lipid abnormalities in patients with Rheumatoid Arthritis.
To determine the frequency of dyslipidemia in patients with Rheumatoid Arthritis. This is a prospective, cross-sectional, observational study, conducted at the 'Rheumatology Clinic' of Jinnah Postgraduate Medical Center (JPMC), Karachi, from November 2013 to May 2014. A total of 200 patients of Rheumatoid Arthritis (RA), diagnosed according to the ACR/EULAR criteria 2010, were included in the study. Laboratory investigations including creatinine, ALT, CBC, TSH and fasting lipid profile (LDL, HDL, and Total cholesterol) were done for all patients. Out of 200 patients, 23 (11.5%) were male and 177 (88.5%) were female. The mean age was 36.31±10.46 years and the mean duration of disease was 3.82±3.03 years. A total of 107 (53.5%) patients had dyslipidemia, and the commonest abnormality was a low HDL, seen in 83 (41.5 %) patients. Dyslipidemia was frequently observed in Rheumatoid Arthritis. This may be considered as a secondary impact of chronic inflammatory state, seen in RA. Lipid abnormalities should be sought at regular intervals, and corrective actions taken to mitigate increased cardiovascular disease risk.


Cell volume regulation during hyperosmotic shrinkage is mediated by Na+/K+-ATPase and Na+-K+-2Cl- cotransporter in Necturus gastrics surface epithelial cells.
Cell volume regulation was investigated in gastric surface epithelial cells during hypertonic conditions. Isolated Necturus antral mucosa was perfused on the serosal side with Ringer's solution (pH 7.25, 95%O2/5%CO2) and on the mucosal side successively with 150-500 mM NaCl. Amiloride, ouabain, and bumetanide were used to experimentally inhibit Na+/H+, Na+/K+ ATPase or Na+-K+-2Cl- ion transporters. Intracellular sodium activity and cell volume changes were measured with liquid sensor microelectrodes. The increase in intracellular sodium activity caused by luminal hyperosmolar exposure was mainly due to cell shrinkage. Inhibition of Na+/K+ ATPase or Na+-K+-2Cl- cotransporter increased hyperosmotic cell shrinkage (-52 +/- 5%, -85 +/- 19%, and -77 +/- 9% for control, ouabain, and bumetanide, respectively). Inhibition of Na+/K+ ATPase increased intracellular sodium activity (from 18 +/- 4 to 52 +/- 12 mM). Cell volume regulation in gastric epithelial surface cells during mucosal hyperosmolar exposure is maintained by the basolateral Na+-K+-2Cl- cotransporter, while Na+/K+ ATPase maintains sodium balance, but Na+/H+ antiport seems to have a less important role.


Long-term consumption of fermented soybean-derived Chungkookjang enhances insulinotropic action unlike soybeans in 90% pancreatectomized diabetic rats.
We previously reported that Chungkookjang (CKJ), fermented unsalted soybeans, exhibited better anti-diabetic action than cooked soybeans (CSB) in vitro, but its effectiveness and mechanism have not been studied in vivo. We investigated whether CKJ modulated insulin resistance, insulin secretion, and pancreatic beta-cell growth and survival in 90% pancreatectomized (Px) diabetic rats. The Px rats weighing 201 +/- 12 g were divided into four groups and fed for 8 weeks with a CSB diet, a CKJ diet, a casein diet, or a casein diet plus rosiglitazone (20 mg/kg body weight/day). With the exception of protein sources and contents of isoflavonoid aglycones and glycosides, the composition of the diets was made identical by adding soybean oil and cellulose to a casein diet. At the end of the experimental periods, hyperglycemic clamp was performed in conscious, unstressed and overnight fasted Px rats to measure insulin secretion capacity. Insulin/IGF-1 signaling was measured by immunoblotting in isolated islets from the treated rats, and beta-cell mass, proliferation and apoptosis were also determined by immunohistochemistry. After 8-week administration, CSB did not modulate glucose-stimulated insulin secretion, but surprisingly, CKJ enhanced insulin secretion. In addition, CKJ potentiated insulin/IGF-1 signaling in islets via the induction of insulin receptor substrate-2 expression, leading to increasing pancreatic duodenal homeobox-1, insulin promoter transcription factor. In parallel with the enhancement of the signaling, CKJ elevated pancreatic beta-cell hyperplasia by increasing its proliferation and decreasing apoptosis, whereas CSB did not. Based on these results, the fermentation of soybeans predominantly with Bacillus subtilis generated isoflavonoid aglycones and small peptides, which improved insulinotropic action in islets of type 2 diabetic rats. Overall, the anti-diabetic action of CKJ was superior to CSB in type 2 diabetic rats.


Genetic Polymorphisms in DEFB1 and miRNA202 Are Involved in Salivary Human β-Defensin 1 Levels and Caries Experience in Children.
The antimicrobial peptides human β-defensins (hBDs) are encoded by β-defensin genes (DEFBs) and are possibly involved in caries susceptibility. In this study we aimed (1) to investigate the relationship between salivary hBDs and caries and (2) to evaluate the association of genetic polymorphisms in DEFB1 and microRNA202 (miRNA202) with salivary levels of hBDs and caries experience. Two data sets were available for this study, totalizing 678 Brazilian children. Dental examination and saliva collection were performed in all included children. The salivary level for hDB1, hBD2, and hBD4 was assessed by ELISA sandwich technique in 168 children. The DNA was extracted from saliva, and polymorphisms in DEFB1 and miRNA202 were analyzed by real-time PCR. Statistical analysis was performed to investigate the associations between caries experience, hBD salivary level, genotype, and allele distribution, with an alpha of 0.05. The hBD1 level was significantly higher in caries-free children (p < 0.0001). The miRNA202 was associated with a lower level of salivary hBD1 (p < 0.05). Also, the polymorphic distribution of miRNA202 was associated with caries (p = 0.006). The polymorphisms in DEFB1 were not associated with hBD salivary level and caries experience (p > 0.05). In conclusion, our results indicate that genetic polymorphism in miRNA202 is involved in hBD1 salivary level as well as caries experience in children.


Physiological regulation of Paracoccus denitrificans methanol dehydrogenase synthesis and activity.
An enzyme-linked immunosorbent assay and a whole-cell activity assay were developed which allowed detection of methanol dehydrogenase (MDH) of Paracoccus denitrificans with increased sensitivity. By these methods, it was shown that MDH was not induced by its natural substrate, methanol. Relief from a catabolite repression-like mechanism seemed responsible for low-level MDH synthesis, while product induction was the hypothesized mechanism for synthesis of high amounts of MDH. In the latter process, formaldehyde may play an important role as effector. For a variety of culture conditions, inconsistencies were observed in the relation between amounts of MDH protein synthesized and enzyme activities measured in vitro. Regulation of pyrrolo-quinoline-quinone biosynthesis or a modulation of its incorporation and stability in MDH may constitute an overriding mechanism to ensure a correct tuning between metabolic rates of methanol consumption and the required methanol oxidation rates.


Could host cell receptor alteration prevent SARS-CoV-2 viral entry? - Hype or hope.
Cell-surface receptors are the inviters of many potent pathogens that can adjust to any kind of circumstance for their existence. Many of these organisms are highly resistant to the currently existing drugs and mutate to new strains with high levels of pathogenesis, posing life-threatening consequences. Owing to such concerns, antiviral strategies are being assessed based on host cell receptor targeting. Many natural compounds with a tendency to strip off the cell surface receptors are under evaluation. Compounds that are non-toxic, patient friendly, and yield a quick output are essential for the current scenario. Drugs targeting the cell surface receptors should, therefore, be developed and standardized for the effective management of SARS-CoV-2 viral infection.


Diabetic foot infection - diagnosis and treatment.
Diabetic foot (DF) is one of the most serious complications of diabetes, leading to high morbidity and mortality in patients with diabetes, significantly affecting their quality of life and placing a huge burden on the healthcare system. Diabetic foot infection (DFI) is a major factor in the non-healing of diabetic ulcerations of the lower limbs, increases the number of hospital admissions, prolongs their duration and is a frequent cause of increased number of amputations. The most serious form of foot infection is osteomyelitis. Management of infection in SDN includes proper diagnosis, including obtaining appropriate specimens for culture, indication of rational antimicrobial therapy or early surgical intervention, and provision of all other necessary wound care and overall patient care to prevent recurrence of DFI.


Immunochemical detection and identification of protein adducts of diclofenac in the small intestine of rats: possible role in allergic reactions.
Idiosyncratic adverse drug reactions are unpredictable, target multiple organ systems, and often become life-threatening events. Although the causes of idiosyncratic adverse drug reactions are not known in most cases, evidence suggests that they may be mediated through immunological mechanisms. It is generally thought that for a drug to lead to an immune response, it must first become covalently bound to a carrier protein. Since most drugs are unreactive, it is usually a reactive metabolite that is expected to form covalent adducts. However, it is not clear why more people do not develop immune reactions against drug-protein adducts. One possible explanation is that orally administered drugs may lead to oral tolerance in most individuals through mechanisms similar to that found with orally administered antigens. However, very little is known regarding the interaction of drugs with gut-associated lymphoid tissue of the small intestine, where oral tolerance can develop. As an initial step to test this hypothesis, we have investigated whether diclofenac, a commonly used nonsteroidal antiinflammatory drug, can lead to protein adducts in rat small intestine. Diclofenac was administered to rats by gastric gavage. Immunoblot analysis of small intestine homogenates and isolated enterocyte subcellular fractions with drug-specific antiserum revealed 142-, 130-, 110-, and 55-kDa protein adducts of diclofenac. The 142- and 130-kDa adducts of diclofenac were identified as aminopeptidase N (CD13) and sucrase-isomaltase, respectively, by amino acid sequence analyses and by their reactions with protein-specific antibodies. The adducts were localized by immunohistochemistry and found primarily in the mid-villus and villus-tip enterocytes and also in the dome overlying Peyer's patches. Similar adducts were detected immunochemically in villus-tip enterocytes of animals treated with halothane or acetaminophen. These results show that intestinal protein adducts of drugs can be formed in gut-associated lymphoid tissue where they may lead to the down-regulation of drug-induced allergic reactions in many individuals.


[Surrogate markers--substitute measurements. Easy to measure but irrelevant?].
Many treatments aim at making a patient feel better due to symptom relief or improved quality of life. Other treatments are given in order to prevent future complications, non-fatal or fatal. There are methodological difficulties in assessing subjective symptoms and quality of life. To document reduced risk of complications takes large, long-term, costly clinical trials. Thus, the use of a surrogate marker to document benefit may seem appealing. A well-validated surrogate marker can demonstrate benefit of a given treatment with fewer patients in a shorter time and at considerably lower cost. It is much easier to show in a 12-week study that a new compound lowers blood pressure than to show that it lowers the risk of stroke, myocardial infarction or renal impairment. One problem with surrogate markers is that very few are well-validated, another is that even those which are cannot be expected to reflect adverse effects, expected or unexpected, and are thus of limited value in the global assessment of benefit vs. risk. It is recommended that results obtained with surrogate markers be regarded as preliminary until results of large trials with clinically relevant outcomes are available.


Results of a prospective trial to compare normal urine supersaturation in children and adults.
Urinary stone disease is relatively rare in children but is often due to metabolic abnormalities. Urinary supersaturation (SS) indices have been suggested as more precise predictors of stone recurrence. We previously reported urinary metabolic evaluations in stone-forming children using adult references. We now assess normal SS values in children. A prospective trial was performed to assess urinary metabolic profiles in children with no personal or family history of urinary calculi. The 24-hour urine collections were performed and evaluated at an outside central laboratory. Urine chemistries were adjusted for urine creatinine. Urine pH and SS for calcium oxalate, calcium phosphate and uric acid were also assessed. The data were compared to a cohort of normal adults. A total of 168 samples from 168 adults (58% males) and 51 samples from 30 children (59% males) were evaluated. The mean age of the children was 8.8 years (range 5 to 18). Calcium oxalate SS was similar between children and adults, and urine pH was the major cause of differences seen in the calcium phosphate and uric acid SS indices. Children had a much higher excretion of calcium, oxalate and citrate when adjusted for creatinine. There are significant differences in the normal ranges of urine chemistries in children and adults. An understanding of normal supersaturation values may allow metabolic abnormalities in stone-forming children to be more precisely diagnosed and treated.


Computer-based auditory training (CBAT): benefits for children with language- and reading-related learning difficulties.
This article reviews the evidence for computer-based auditory training (CBAT) in children with language, reading, and related learning difficulties, and evaluates the extent it can benefit children with auditory processing disorder (APD). Searches were confined to studies published between 2000 and 2008, and they are rated according to the level of evidence hierarchy proposed by the American Speech-Language Hearing Association (ASHA) in 2004. We identified 16 studies of two commercially available CBAT programs (13 studies of Fast ForWord (FFW) and three studies of Earobics) and five further outcome studies of other non-speech and simple speech sounds training, available for children with language, learning, and reading difficulties. The results suggest that, apart from the phonological awareness skills, the FFW and Earobics programs seem to have little effect on the language, spelling, and reading skills of children. Non-speech and simple speech sounds training may be effective in improving children's reading skills, but only if it is delivered by an audio-visual method. There is some initial evidence to suggest that CBAT may be of benefit for children with APD. Further research is necessary, however, to substantiate these preliminary findings.


Different expression of cell surface fibronectin in spontaneously and X-ray transformed cells.
The presence of cell surface fibronectin was examined by indirect immunofluorescence in 8 groups of related rat fibroblast lines expressing an in vitro transformed phenotype. The transformed cells were selected for anchorage independent growth either after X-ray treatment (X-ray transformed cells) or from control cultures (spontaneously transformed cells). All transformed fibroblasts of the latter class showed reduced expression of fibronectin at the cell surface, whereas most of the X-ray transformed derivatives exhibited a fibronectin-positive phenotype, like the untransformed parents. Moreover, from the fibronectin-negative spontaneously transformed cells, ouabain-resistant variants were isolated, the majority of which had regained the capacity to form an extracellular matrix of fibronectin. These results emphasize the variability in the properties of transformed cells and suggest that the properties of in vitro transformed cells may depend on the cause of transformation.


Acute myeloid leukemia (AML-M2) with mast cell hyperplasia of bone marrow: a report of three cases.
Bone marrow mastocytosis, though infrequently documented in Indian patients, may be observed in association with many non mast cell hematological neoplasms, including acute myeloblastic leukemia (AML) and myelodysplastic syndromes (MDS). We report three cases of acute myeloid leukemia with excess of mast cells in the bone marrow (BM) samples. Mast cell hyperplasia may remain under diagnosed due to shortcoming of morphological identification and diagnostic workup.


Population-Based Surveillance of Birth Defects Potentially Related to Zika Virus Infection - 15 States and U.S. Territories, 2016.
Zika virus infection during pregnancy can cause serious birth defects, including microcephaly and brain abnormalities (1). Population-based birth defects surveillance systems are critical to monitor all infants and fetuses with birth defects potentially related to Zika virus infection, regardless of known exposure or laboratory evidence of Zika virus infection during pregnancy. CDC analyzed data from 15 U.S. jurisdictions conducting population-based surveillance for birth defects potentially related to Zika virus infection.* Jurisdictions were stratified into the following three groups: those with 1) documented local transmission of Zika virus during 2016; 2) one or more cases of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents; and 3) less than one case of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents. A total of 2,962 infants and fetuses (3.0 per 1,000 live births; 95% confidence interval [CI] = 2.9-3.2) (2) met the case definition.† In areas with local transmission there was a non-statistically significant increase in total birth defects potentially related to Zika virus infection from 2.8 cases per 1,000 live births in the first half of 2016 to 3.0 cases in the second half (p = 0.10). However, when neural tube defects and other early brain malformations (NTDs)§ were excluded, the prevalence of birth defects strongly linked to congenital Zika virus infection increased significantly, from 2.0 cases per 1,000 live births in the first half of 2016 to 2.4 cases in the second half, an increase of 29 more cases than expected (p = 0.009). These findings underscore the importance of surveillance for birth defects potentially related to Zika virus infection and the need for continued monitoring in areas at risk for Zika.


Catalytic Intermediate Crystal Structures of Cysteine Desulfurase from the Archaeon Thermococcus onnurineus NA1.
Thermococcus onnurineus NA1 is an anaerobic archaeon usually found in a deep-sea hydrothermal vent area, which can use elemental sulfur (S0) as a terminal electron acceptor for energy. Sulfur, essential to many biomolecules such as sulfur-containing amino acids and cofactors including iron-sulfur cluster, is usually mobilized from cysteine by the pyridoxal 5'-phosphate- (PLP-) dependent enzyme of cysteine desulfurase (CDS). We determined the crystal structures of CDS from Thermococcus onnurineus NA1 (ToCDS), which include native internal aldimine (NAT), gem-diamine (GD) with alanine, internal aldimine structure with existing alanine (IAA), and internal aldimine with persulfide-bound Cys356 (PSF) structures. The catalytic intermediate structures showed the dihedral angle rotation of Schiff-base linkage relative to the PLP pyridine ring. The ToCDS structures were compared with bacterial CDS structures, which will help us to understand the role and catalytic mechanism of ToCDS in the archaeon Thermococcus onnurineus NA1.


Non-conducting functions of voltage-gated ion channels.
Various studies, mostly in the past 5 years, have demonstrated that, in addition to their well-described function in regulating electrical excitability, voltage-dependent ion channels participate in intracellular signalling pathways. Channels can directly activate enzymes linked to cellular signalling pathways, serve as cell adhesion molecules or components of the cytoskeleton, and their activity can alter the expression of specific genes. Here, I review these findings and discuss the extent to which the molecular mechanisms of such signalling are understood.


Behavior life style analysis for mobile sensory data in cloud computing through MapReduce.
Cloud computing has revolutionized healthcare in today's world as it can be seamlessly integrated into a mobile application and sensor devices. The sensory data is then transferred from these devices to the public and private clouds. In this paper, a hybrid and distributed environment is built which is capable of collecting data from the mobile phone application and store it in the cloud. We developed an activity recognition application and transfer the data to the cloud for further processing. Big data technology Hadoop MapReduce is employed to analyze the data and create user timeline of user's activities. These activities are visualized to find useful health analytics and trends. In this paper a big data solution is proposed to analyze the sensory data and give insights into user behavior and lifestyle trends.


rpoE, the gene encoding the second heat-shock sigma factor, sigma E, in Escherichia coli.
In Escherichia coli, the heat shock response is under the control of two alternative sigma factors: sigma 32 and sigma E. The sigma 32-regulated response is well understood, whereas little is known about that of sigma E, except that it responds to extracytoplasmic immature outer membrane proteins. To further understand this response, we located the rpoE gene at 55.5' and analyzed the role of sigma E. sigma E is required at high temperature, and controls the transcription of at least 10 genes. Some of these might contribute to the integrity of the cell since delta rpoE cells are more sensitive to SDS plus EDTA and crystal violet. sigma E controls its own transcription from a sigma E-dependent promoter, indicating that rpoE transcription plays a role in the regulation of E sigma E activity. Indeed, under steady-state conditions, the transcription from this promoter mirrors the levels of E sigma E activity in the cell. However, it is unlikely that the rapid increase in E sigma E activity following induction can be accounted for solely by increased transcription of rpoE. Based upon homology arguments, we suggest that a gene encoding a negative regulator of sigma E activity is located immediately downstream of rpoE and may function as the target of the E sigma E inducing signal.


Advanced-Stage Nasopharyngeal Carcinoma: Restaging System after Neoadjuvant Chemotherapy on the Basis of MR Imaging Determines Survival.
Purpose To evaluate the prognostic value of the restaging system after neoadjuvant chemotherapy (NACT) in patients with advanced-stage nasopharyngeal carcinoma (NPC). Materials and Methods This study was approved by the clinical research committee and a written informed consent was required before enrolling in the study. Prospectively enrolled were 412 consecutive patients with stage III-IVb NPC treated with NACT followed by concurrent chemotherapy and radiation therapy. Patients were staged before NACT and restaged after NACT. The progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared by using the log-rank test. Results Post-NACT T classification (PFS, P = .001) and N classification (PFS, P < .001; DMFS, P = .001) resulted in better survival curve separations than pre-NACT T classification and N classification. Patients downstaged from N2-N3 to N0-N1 disease had a better prognosis than did patients who continued to have N2-N3 diseases (3-year PFS, 83.8% vs 66.6%, P = .001; 3-year DMFS, 88.0% vs 78.4%, P = .026). Multivariate analysis revealed that post-NACT T classification (hazard ratio [HR] = 1.67; 95% confidence interval [CI]: 1.18, 2.36; P = .003) and post-NACT N classification (HR = 1.54; 95% CI: 1.17, 2.03; P = .002) were independent prognostic factors for PFS; also, post-NACT N classification (HR = 1.48; 95% CI: 1.05, 2.07; P = .025) was an independent prognostic factor for DMFS. Multivariate analysis in patients with N2-N3 disease demonstrated that the N downstaging effects of NACT was the only independent prognostic factor for PFS (HR = 0.48; 95% CI: 0.29, 0.81; P = .006) and DMFS (HR = 0.52; 95% CI: 0.28, 0.97; P = .039). Conclusion The post-NACT stage is more representative of prognosis than the pre-NACT stage in advanced-stage NPC patients, which suggests that major clinical decisions should be based on the post-NACT stage. © RSNA, 2016 Online supplemental material is available for this article.


In Vitro and In Vivo Metabolic Activation of Obacunone, A Bioactive and Potentially Hepatotoxic Constituent of Dictamni Cortex.
Obacunone is one of the major bioactive constituents from Dictamni cortex, a traditional Chinese medicine widely used in China. Oral administration of obacunone or Dictamni cortex extract has been shown to cause liver injury in rats. Given that obacunone contains a furan ring, which is a structural alert, metabolic activation might be responsible for obacunone-induced liver injury. In this study, bioactivation pathways of obacunone in rat and human liver microsomes were investigated. Obacunone was first metabolized into cis-butene-1,4-dial, and then cis-butene-1,4-dial was captured by glutathione, N-acetyl-cysteine, and N-acetyl-lysine in the microsomal incubation system. A total of 13 adducts derived from the reaction of cis-butene-1,4-dial with glutathione and/or N-acetyl-lysine were detected and structurally identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. The major metabolite (M7) was identified to be the cyclic mono-glutathione conjugate of cis-butene-1,4-dial, which was detected in bile and urine of obacunone-treated rats. M9 and M10, obacunone-derived glutathione-cis-butene-1,4-dial-NAL conjugates, were detected in the microsomal incubations of obacunone fortified with glutathione and N-acetyl-lysine as trapping agents. M3 and M4, pyrroline-2-one derivatives, were also detected in microsomal incubations. Further phenotyping studies indicated that ketoconazole showed a strong inhibitory effect on the production of cis-butene-1,4-dial in a concentration-dependent manner. CYP3A4 was demonstrated to be the primary enzyme responsible for the bioactivation of obacunone by using individual recombinant human CYP450 enzymes. The current study provides an overview of CYP450-dominated bioactivation of obacunone and contributes to the understanding of the role of bioactivation in obacunone-induced liver injury.


Short total synthesis of 8,10-di-O-methylbergenin.
[reaction: see text] A short, high-yielding synthesis of the C-glucoside 8,10-di-O-methylbergenin is reported. Key elements of the synthesis are a stereoselective installation of a beta-C-aryl linkage, a palladium(0)-catalyzed aryl carbonylation, and a regioselective lactonization reaction. This pathway should allow access to a host of bergenin analogues.


Wettability and spontaneous penetration of a water drop into hydrophobic pores.
The penetration of a water drop into hydrophobic pores reflects its instability on a porous surface. To understand the mechanism of penetration and to predict the behavior of such a drop, an investigation was conducted through experimental study combined theoretical analysis. Water drops with volumes from 0.5 to 15μL were examined on Polydimethylsiloxane (PDMS) substrates containing pores of 800μm and less in diameter. Results showed a critical condition at which a drop starts to penetrate into a certain sized pore. The critical condition presents a parabolic relationship between the volume of a water drop and the size of a hydrophobic pore. This behavior was due to a net force resulting from Laplace pressure, and capillary pressure. This force was found to be affected by the porosity, wetting angle, and there after the critical condition. The finding of this research will be beneficial for future design of structured surfaces.


Evolution over time of mackinawite generated on carbon steel by the SRB metabolic activity: an in-operando Raman study.
Mackinawite was biologically synthetized by immersing carbon steel coupons in artificial seawater containing Sulphate-Reducing Bacteria (SRB) for 6 months. These coupons were removed from the culture medium solution and some were stored in air while others were placed in SRB-free culture medium solution. In operando Raman spectroscopy was used to analyse all these coupons immediately after extraction from the incubation medium and nanocrystalline, well-crystallized and partially oxidized mackinawite was detected. The evolution of these corrosion products was also monitored as a function of ageing time with this technique. Nanocrystalline and well-crystallised mackinawite transformed into partially oxidised mackinawite, greigite and sulphate green rust for an ageing time between 4 and 72 h. After 120 h, maghemite, magnetite, lepidocrocite, goethite appeared on the coupons placed in SRB-free culture medium solution as opposed to those stored in air atmosphere. Greigite and sulphate green rust were not observed for Raman measurements performed in air.


Acute central haemodynamic effects induced by intraperitoneal glucose instillation.
The supposed lack of a haemodynamic impact of peritoneal dialysis (PD) has been challenged recently by the finding of a mild increase of peripheral blood pressure (BP) during an acute dwell. It is not clear whether, besides the effect of changes in intraperitoneal (IP) volume and/or pressure, IP glucose instillation and absorption plays a role in this. Therefore, we tested the impact of IP instillation of glucose on the evolution of central haemodynamic parameters, using SphygmoCor, during an acute dwell with two different glucose concentrations. Stable, non-diabetic PD patients (N = 22) were treated consecutively in a randomized, cross-over design (A then B or B then A) with one 1.36% (A) and one 3.86% (B) physioneal dwell of 100 min. Central BP was measured with SphygmoCor and blood was sampled for serum glucose and insulin levels every 20 min. Insulin resistance was defined as a Homeostatic Model Assessment Index (HOMA-index) >1.4. Serum glucose levels rose during both the 1.36% and the 3.86% dwell, whereas insulin levels rose only during the 3.86% dwell. The increase of both glucose and insulin levels was more pronounced in patients with insulin resistance (11/22 patients). There was, however, no accompanying change versus baseline in haemodynamic parameters (carotid systolic blood pressure, diastolic BP, heart rate or augmentation index). Despite substantial increases in blood glucose and insulin levels, there was no accompanying change in central haemodynamic parameters during an acute PD dwell with low or high glucose concentrations.


[Clinical study on blocking mother-to-child transmission of hepatitis B virus with high viral load and HBeAg positivity during pregnancy in Guizhou province].
Objective: To observe the efficacy and safety related measures by blocking mother-to-child transmission of hepatitis B virus with high viral load and HBeAg positivity during pregnancy in Guizhou province. Methods: Outpatient and inpatient cases of the Department of Infectious Diseases and Obstetrics of Guizhou Medical University Affiliated Hospitals from May 2016 to July 2017 were retrospectively divided into intervention group, non-intervention group and non- hepatitis B pregnant women group; with 75 cases in each group. HBsAg and HBeAg were positive in the intervention group. Pregnant women with HBV DNA ≥10(6) IU/ml were treated with anti-HBV therapy for 24 to 28 weeks of gestation until delivery. According to oral drugs, they were divided into tenofovir (TDF) group or telbivudine (LDT) group, non-intervention group (HBsAg and HBeAg positive), HBV DNA positive pregnant women, pregnant women with no anti-HBV drugs, non-hepatitis B pregnant women (normal pregnant women without HBV infection). Infants and young children born to the three groups of women were immunized with the national viral hepatitis B action plan. The gestational weeks and Apgar scores at birth, delivery mode, feeding mode, sex and 7-months-old age were observed and counted. Serum hepatitis B markers (HBVM) and HBV DNA were quantitatively detected. HBVM was detected by time-resolved fluorescence immunoassay (TRFIA), and HBV DNA was detected by real-time PCR (FQ-PCR). The changes of liver parameters, HBsAg, HBeAg, HBV DNA, adverse drug reactions and treatment response of pregnant intervention group before medication (12-24 weeks of gestation), 4 weeks of medication (28-32 weeks of gestation), 36-40 weeks of gestation (36-40 weeks of gestation) were statistically calculated. A t-test was used to compare the data between the measurements. Data measurements within the groups were analyzed using rank -sum test. Results: In the intervention group, therapeutic medications showed no differences in demographic and clinical characteristics between TDF group and LDT group, including liver parameters, HBsAg, HBeAg and log10HBV DNA level. Compared with pre-treatment (TDF group: 4.84 ± 2.01; LDT group: 5.08 ± 1.99), TDF and LDT were significantly lower at the end of pregnancy (TDF group: 3.06 ± 0.66; LDT group: 3.51 ± 1.20). P < 0.05); and the treatment response rate was 100%. There were no serious adverse events in the intervention group. Infants and young children (7-months-old) in the intervention group had negative HBsAg, HBeAg and HBV DNA. The mother-to-child transmission rate of HBV was zero, with blocking rate of 100%. In addition, both infants and young children had different degrees of hepatitis B protective antibodies (anti-HBs, M: 144.33), and their antibody titers were higher than that of non-intervention group (anti-HBs, M: 65.91) and non-hepatitis B pregnant women (anti-HBs, M: 58.43). The difference was statistically significant (P < 0.05), and there was no significant correlation between the use of antiviral and the way of delivery and feeding. Outcomes of mother-to-child transmission of HBV infection in infants and young children (7-months-old) delivered by three groups of pregnant women in the non-intervention groups had 20.0% (15/75)/ 17.3% (13/75) HBsAg/HBeAg positivity rate, and 17.3% (13/75) HBV DNA positivity rate. Overall, mother-to-child transmission rate of HBV infection was 20% (15/75). Furthermore, the relationship between mother's HBV DNA load and infant HBV infection in the non-intervention group showed mother's HBV DNA ≥10(6) IU/ml. Conclusion: In the non-intervention group, mother-to-child transmission of HBV occurred, and infected mothers HBV DNA was ≥106 IU/ml before delivery. This suggests that HBeAg positive and high load HBV DNA replication were independent risk factors for mother-to-child transmission of hepatitis B. Therefore, prenatal drug intervention and postpartum standard immune blockade are necessary for high-risk pregnant women with hepatitis B to achieve zero mother-to-child transmission of hepatitis B in real- clinical practice.


Factor-analytic support for DSM-III's post-traumatic stress disorder for Vietnam veterans.
Found substantial support for DSM-III's criteria for Post-Traumatic Stress using 405 Vietnam combat veterans. The results also suggested that some additional symptoms such as depression and anger be included as major signs, especially when one is dealing with Vietnam veterans. A comparison of symptom intensity was made between Vietnam veterans and non-Vietnam veterans. The results of the second study showed that Vietnam veterans attested to experiencing significantly greater intensities of DSM-III criteria behaviors than did non-Vietnam veterans. However, no significant differences were found for symptoms related to depression.


Integrating Microbiome Analysis, Metabolomics, Bioinformatics, and Histopathology to Elucidate the Protective Effects of Pomegranate Juice against Benzo-alpha-pyrene-Induced Colon Pathologies.
Polycyclic aromatic hydrocarbons, e.g., benzo[a]pyrene (BaP), are common dietary pollutants with potential carcinogenic activity, while polyphenols are potential chemopreventive antioxidants. Although several health benefits are attributed to polyphenol-rich pomegranate, little is known about its interaction with BaP. This study integrates histochemical, microbiomic, and metabolomic approaches to investigate the protective effects of pomegranate juice from BaP-induced pathologies. To this end, 48 Sprague-Dawley rats received, for four weeks, either pomegranate, BaP, both, or neither (n = 12 rats per group). Whereas histochemical examination of the colon indicated tissue damage marked by mucin depletion in BaP-fed animals, which was partially restored by administration of pomegranate juice, the fecal microbiome and metabolome retained their resilience, except for key changes related to pomegranate and BaP biotransformation. Meanwhile, dramatic microbiome restructuring and metabolome shift were observed as a consequence of the elapsed time (age factor). Additionally, the analysis allowed a thorough examination of fecal microbiome-metabolome associations, which delineated six microbiome clusters (marked by a differential abundance of Lactobacillaceae and Prevotellaceae, Rumincococcaceae, and Erysipelotrichaceae) and two major metabolome clusters (a sugar- and amino-acids-dominated metabotype vs. a cluster of fatty acids and hydrocarbons), with sugar alcohols maintaining a unique signature. In conclusion, using paired comparisons to minimize inter-individual animal variations allowed the dissection of temporal vs. treatment-derived variations. Microbiome-metabolome association clusters may be further exploited for metabotype prediction and gut-health biomarker discovery.


Increased pyrethroid resistance in malaria vectors and decreased bed net effectiveness, Burkina Faso.
Malaria control is dependent on insecticides. Increases in prevalence of insecticide resistance in malaria vectors across Africa are well-documented. However, few attempts have been made to quantify the strength of this resistance and link it to the effectiveness of control tools. Using quantitative bioassays, we show that in Burkina Faso pyrethroid resistance in Anopheles gambiae mosquitoes has increased in intensity in recent years and now exceeds 1,000-fold. In laboratory assays, this level of resistance renders insecticides used to impregnate bed nets ineffective. Thus, the level of personal and community protection afforded by long-lasting insecticide-treated net campaigns will probably be reduced. Standardized methods are needed to quantify resistance levels in malaria vectors and link these levels to failure of vector control methods.


No association between attention-deficit hyperactivity disorder and catechol-O-methyltransferase gene in Chinese.
Previous studies suggested that the catecholaminergic systems may be involved in the pathogenesis of attention-deficit hyperactivity disorder(ADHD). Since catechel-O-methyltransferase (COMT) is an enzyme involved in the degradation of catecholaminergic neurotransmitters of the dopaminergic and noradrenergic systems,it is possible that COMT may play a role in ADHD. To test this hypothesis, we used two family-based analyses,the transmission disequilibrium test (TDT) and the haplotype-based haplotype relative risk (HHRR), to examine the possible association between COMT gene and DSM-IV-diagnosed ADHD in a Chinese sample consisting of 79 ADHD probands and their parents. Both TDT (chi2 = 1.03, df=1, P > 0.05) and HHRR (chi2 = 1.08, df = 1, P > 0.05) analyses failed to detect preferential transmission of a COMT allele to the ADHD children. Our data suggested that there was no association between ADHD and the COMT gene in the Chinese population.


Management of community-acquired pediatric pneumonia in an era of increasing antibiotic resistance and conjugate vaccines.
The antibiotic management of infants and children with pneumonia is based on the clinician's assessment of the most likely infecting pathogens, the susceptibilities of the infecting pathogens and the seriousness of the illness. The bacterial etiology of pneumonia changed significantly following the universal use of protein-conjugated vaccines for Haemophilus influenzae type b. Similar significant changes are likely to occur with universal use of protein-conjugated vaccines for Streptococcus pneumoniae, requiring the clinician to alter assumptions of the risk of invasive bacterial infection in the child who presents with pneumonia. New strategies are likely to require fewer ancillary tests (e.g. white blood cell count, C-reactive protein and blood culture) and suggest a decreased need for empiric antibiotic therapy. Although the majority of lower respiratory tract infections in children have a viral etiology and are not amenable to antibiotic therapy, for the seriously ill child who is thought to be likely to have pneumonia caused by a bacterial pathogen, recent changes in the susceptibility patterns of both common organisms such as S. pneumoniae and more unusual pulmonary pathogens such as Staphylococcus aureus have forced changes in the selection of both empiric and definitive antibiotic therapy. Third generation cephalosporins ceftriaxone and cefotaxime appear to be effective therapy for pneumonia caused by virtually all current isolates of S. pneumoniae. In contrast antibiotic regimens for life-threatening pulmonary infections in which Staphylococcus aureus is a suspected pathogen should include vancomycin.


Nanoscale bubble ultrasound contrast agents-mediated suicide gene therapy system, Nanoscale bubble-LV5-YCD-TK/GCV/5-FC, effectively inhibits bladder cancer cell growth.
Bladder cancer is the 2nd most common reason for human genitourinary cancer-associated mortality. This study aimed to investigate the effects of Nanoscale bubble ultrasound contrast agents-mediated yeast-cytosine-deaminase-thymidine kinase/ganciclovir (YCD-TK/GCV) or YCD-TK/5-fluorocytosine (5-FC) suicide gene therapy system on BIU-87 cell growth. Targeted nanoscale bubble ultrasound contrast agents were prepared by utilizing thin-film hydration-sonication approach. Nanoscale bubble-LV5-YCD-TK/GCV(5-FC) was constructed and transfected to BIU-87 cells. Hematoxylin and eosin (HE) staining was used to evaluate inflammation. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to examine cell viability. Cell-cycle distribution was analyzed with cell cycle assay. Flow cytometry assay was utilized to test apoptosis of BIU-87 cells. YCD-TK expression was examined using Western blot and quantitative Real Time-PCR (qRT-PCR), respectively. YCD-TK highly expressed in Nanoscale bubble mediated suicide gene therapy system. Nanoscale bubble-mediated suicide gene therapy system significantly induced inflammatory response and apoptosis compared to that of Nanoscale bubble group (p<0.05). Nanoscale bubble mediated suicide gene therapy system significantly reduced cell viability compared to that of the Nanoscale bubble group (p<0.05). Nanoscale bubble mediated suicide gene therapy system significantly inhibited cell cycle arrest compared to that of the Nanoscale bubble group (p<0.05). Nanoscale bubble-LV5-YCD-TK/GCV/5-FC therapy system significantly reduced BIU-87 cell viability compared to that of the Nanoscale bubble-associated groups (p<0.05). Nanoscale bubble-mediated suicide gene therapy system, bubble-LV5-YCD-TK/GCV/5-FC, acts as a novel therapeutic strategy for bladder cancer treatment.


Combining advanced networked technology and pedagogical methods to improve collaborative distance learning.
Making educational material be available on a network cannot be reduced to merely implementing hypermedia and interactive resources on a server. A pedagogical schema has to be defined to guide students for learning and to provide teachers with guidelines to prepare valuable and upgradeable resources. Components of a learning environment, as well as interactions between students and other roles such as author, tutor and manager, can be deduced from cognitive foundations of learning, such as the constructivist approach. Scripting the way a student will to navigate among information nodes and interact with tools to build his/her own knowledge can be a good way of deducing the features of the graphic interface related to the management of the objects. We defined a typology of pedagogical resources, their data model and their logic of use. We implemented a generic and web-based authoring and publishing platform (called J@LON for Join And Learn On the Net) within an object-oriented and open-source programming environment (called Zope) embedding a content management system (called Plone). Workflow features have been used to mark the progress of students and to trace the life cycle of resources shared by the teaching staff. The platform integrated advanced on line authoring features to create interactive exercises and support live courses diffusion. The platform engine has been generalized to the whole curriculum of medical studies in our faculty; it also supports an international master of risk management in health care and will be extent to all other continuous training diploma.


Cognitive complaints in women with fibromyalgia: Are they due to depression or to objective cognitive dysfunction?
Cognitive complaints are common in fibromyalgia, but it is unclear whether they represent an objective cognitive dysfunction or whether they could be explained by depressive symptoms. Here, we aim to elucidate the frequency of subjective cognitive complaints in a sample of women with fibromyalgia, in addition to analyzing associations between these subjective complaints and objective measures linked to the attention and executive cognitive domains. Finally, we aim to investigate the ability of demographic, clinical, and psychological variables to explain the subjective complaints observed. One hundred and five women aged 30-55 years diagnosed with fibromyalgia completed a neuropsychological assessment, which included measures of attention and executive functions. They also completed self-report inventories of subjective cognitive complaints, depression, anxiety, intensity of pain, sleep quality, everyday physical functioning, and quality of life. Eighty-four percent of the patients reported subjective cognitive complaints. Depression scores, everyday physical functioning, and working memory performance were most strongly associated with subjective cognitive complaints. These three variables were significant predictors for subjective cognitive complaints with a final model explaining 32% of the variance. Cognitive complaints are very frequent in patients with fibromyalgia, and these are related to functional and cognitive impairment as well as to depressive symptoms.


Management of congenital adrenal hyperplasia during pregnancy.
To provide an overview of the congenital adrenal hyperplasias (CAHs) and their management during pregnancy. Pathways of steroid biosynthesis and inherited deficiencies of required enzymes are reviewed, and applications to prenatal diagnosis and treatment of affected fetuses are discussed. The CAHs are a group of inherited enzymatic defects of adrenal steroid biosynthesis. During pregnancy, maternal problems are confined to women with 21-hydroxylase deficiency, 11b-hydroxylase deficiency, and 3b-hydroxysteroid dehydrogenase deficiency because other adrenal enzyme deficiencies are incompatible with fertility. The interposition of the placenta on the hypothalamic-pituitary-adrenal axis has a major effect on clinical evaluation of CAH during pregnancy. Women with severe forms of CAH have decreased fertility rates because of oligo-ovulation, and successful conception requires a combination of good therapeutic compliance, careful endocrine monitoring, and often induction of ovulation. 21-Hydroxylase deficiency in the fetus can now be diagnosed accurately prenatally by endocrine testing and molecular genetic techniques. Prenatal diagnosis of 11b-hydroxylase deficiency in the fetus by endocrine testing is not as sensitive. Prevention of masculinization of affected female fetuses by corticosteroid suppression has been attempted in both 21-hydroxylase deficiency and 11b-hydroxylase deficiency CAH, with variable degrees of success. To date, no reports have been published of prenatal diagnosis or treatment of affected female fetuses with 3b-hydroxysteroid dehydrogenase deficiency CAH. Endocrine and genetic studies of CAH during pregnancy have improved the diagnosis and management.


Determination of the radial coordinate of Cys-374 in F-actin using fluorescence resonance energy transfer spectroscopy: effect of phalloidin on polymer assembly.
In helically symmetric protein assemblies, fluorescence resonance energy transfer (FRET) spectroscopy can be used to determine the radial coordinates of fluorescent probes attached to specific amino acid side chains. This is done by separately labeling monomers with donor and acceptor probes, mixing them in different proportions, allowing the mixtures to self-assemble, and then measuring the fluorescence intensity. Provided the helical symmetry is known, and provided the donor- and acceptor-labeled monomers associate randomly, the radial coordinate of the probes can be calculated. Using different probe pairs, two different research groups have employed this method to show that the Cys-374 site of the actin filament (F-actin) is located at a radius of either 35-40 A [Taylor, D.L., Reidler, J., Spudich, J.A., & Stryer, L. (1981) J. Cell Biol. 89, 362-367] or 20-25 A [Kasprzak, A.A., Takashi, R., & Morales, M.F. (1988) Biochemistry 27, 4512-4522]. We have reinvestigated these disparate radius determinations using the same probe pairs employed by these authors with a wide range of acceptor molar fractions. Our results suggest that labeling actin with probes makes the association of monomers significantly nonrandom. This may be avoided by polymerizing actin in the presence of phalloidin. The nonrandomness also can be modeled using stochastic simulation. Taking the average diameters of the probes into account, we conclude that in phalloidin-stabilized F-actin, Cys-374 lies at a radius of (17-18) +/- 5 A. This value is consistent with radial coordinates determined by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)


Improved sample preparation for direct quantitative detection of Escherichia coli O157 in soil using qPCR without pre-enrichment.
The prominence of fresh produce as a vehicle for foodborne pathogens such as enterohaemorrhagic Escherichia coli (EHEC) O157 is rising, where disease cases can cause hospitalization and in some cases death. This rise emphasises the necessity for accurate and sensitive methods for detection of pathogens in soil, potential sources of contamination of fresh produce. The complexity of the soil matrix has previously proven prohibitive to pathogen detection via molecular methods without the use of a culture enrichment step, thereby excluding the detection of viable but non-culturable cells. Here, a sample preparation procedure to facilitate a direct qPCR assay is developed for the detection of E. coli O157 in soil, bypassing culture steps in favour of sample separation through pulsification release and filtration. In sand and peat-based compost, the method is sensitive to 10 CFU g-1 soil. When testing soils from agricultural sites, it was found that several were qPCR positive for E. coli O157 while being culture-negative, with peat-based compost possessing a concentration of 200 tir gene copies per gram. This procedure offers a rapid, quantitative assessment of the potential presence of E. coli O157 in soils which can act as a prescreen of their suitability to grow fresh produce safely.


Herd Behavior in Medicine: Examples From COVID-19.
Herd behavior is a commonly used term to describe the conduct of different individuals in a group acting without using an individual thought process. The term was first coined by British surgeon Wilfred Trotter in 1914. This editorial will elaborate on how herd behavior has affected the healthcare industry and will include examples from the coronavirus disease 2019 (COVID-19) pandemic. Many interventions were introduced during the initial period of the pandemic, some of them later proved to be either incorrect or only beneficial to a selected group of patients. The nonmedical intervention included personal protective equipment (PPE), the establishment of fever clinics, and telemedicine. Some of these interventions were beneficial and will likely continue after the pandemic. The aim of this editorial is to highlight observed herd behavior in medical practice during pandemics and endorses the need for evaluation of evidence rigorously.


Temperature-driven reversible rippling and bonding of a graphene superlattice.
In order to unravel the complex interplay between substrate interactions and film configuration, we investigate and characterize graphene on a support with non-three-fold symmetry, the square Ir(100). Below 500 °C, distinct physisorbed and chemisorbed graphene phases coexist on the surface, respectively characterized by flat and buckled morphology. They organize into alternating domains that extend on mesoscopic lengths, relieving the strain due to the different thermal expansion of film and substrate. The chemisorbed phase exhibits exceptionally large one-dimensional ripples with regular nanometer periodicity and can be reversibly transformed into physisorbed graphene in a temperature-controlled process that involves surprisingly few C-Ir bonds. The formation and rupture of these bonds, rather than ripples or strain, are found to profoundly alter the local electronic structure, changing graphene behavior from semimetal to metallic type. The exploitation of such subtle interfacial changes opens new possibilities for tuning the properties of this unique material.


Synthesis of bamboo-like 3C-SiC nanowires by microwave assisted carbothermal reduction.
In this paper, bamboo-like 3C-SiC nanowires were synthesized in minutes without a metal catalyst by a simple, fast, and low-cost microwave method. The as-synthesized nanowires were studied by X-ray diffraction, scanning electron microscopy, Raman spectra, and transmission electron microscopy. The results showed that the bamboo-like nanowires have a stem of cubic 3C-SiC and nodes consisting of a high number of stacking faults, which are crystalline 3C-SiC with a diameter of 20-100 nm and a length around several microns. A possible mechanism for growing bamboo-like SiC nanowires in a microwave is also proposed.


Noninvasive methods in the diagnosis of extracranial carotid artery disease: a correlation with carotid arteriography in eighty patients.
Five hundred fifty-nine patients were evaluated for carotid artery disease in the Blood Flow Laboratory by the following direct and indirect noninvasive methods: 1. Periorbital doppler examination; 2. Ocular pneumoplethysmography (Gee); 3. Pulsed doppler ultrasonic arteriography; and 4. Sound spectral analysis with a pulsed doppler. Carotid arteriograms were available for comparison with one hundred fifty-seven vessels (80 patients). Sensitivity, specificity and overall accuracy was established for each noninvasive modality by correlation with the angiographic findings. For detection of stenoses greater than 50% by diameter reduction, sensitivity was 98%. Sound spectral analysis and ultrasonic arteriography were found to yield a higher sensitivity when compared to the other noninvasive methods in detecting stenoses of less than 50%. In our hands, disturbed spectral flow patterns do not always correlate with the degree of stenosis in non-hemodynamic lesions. Our results indicate that proper patient selection for angiographic examination can be made through noninvasive screening.


Acridine Orange/exosomes increase the delivery and the effectiveness of Acridine Orange in human melanoma cells: A new prototype for theranostics of tumors.
Specifically targeted drug delivery systems with low immunogenicity and toxicity are deemed to increase efficacy of cancer chemotherapy. Acridine Orange (AO) is an acidophilic dye with a strong tumoricidal action following excitation with a light source at 466 nm. However, to date the clinical use of AO is limited by the potential side effects elicited by systemic administration. The endogenous nanocarrier exosomes have been recently introduced as a natural delivery system for therapeutic molecules. In this article, we show the outcome of the administration to human melanoma cells of AO charged Exosomes (Exo-AO), in both monolayer and spheroid models. The results showed an extended drug delivery time of Exo-AO to melanoma cells as compared to the free AO, improving the cytotoxicity of AO. This study shows that Exo-AO have a great potential for a real exploitation as a new theranostic approach against tumors based on AO delivered through the exosomes.


[The association cleido-cranial dysplasia and a Capdepont dysplasia (author's transl)].
The authors report a rare association: that of two hereditary dysplasias transmitted in a dominant manner. Cleido-cranial dysplasia or Pierre Marie and Saniton syndrome, a congenital polymorphous disease, affecting the bones during their growth with a Capadepont dysplasia or hereditary opalescent dentine, a condition affecting both dentitons.


Structural Insights into Azole-based Inhibitors of Heme Oxygenase-1: Development of Selective Compounds for Therapeutic Applications.
The development of isozyme-selective heme oxygenase (HO) inhibitors promises powerful pharmacological tools to elucidate the regulatory characteristics of the HO system. It is already known that HO has cytoprotective properties with a role in several disease states; thus, it is an enticing therapeutic target. Historically, the metalloporphyrins have been used as competitive HO inhibitors based on their structural similarity to the substrate, heme. However, heme's important role in several other proteins (e.g. cytochromes P450, nitric oxide synthase), results in non-selectivity being an unfortunate side effect. Reports that azalanstat and other non-porphyrin molecules inhibited HO led to a multi-faceted effort over a decade ago to develop novel compounds as potent, selective inhibitors of HO. The result was the creation of the first generation of non-porphyrin based, non-competitive inhibitors with selectivity for HO, including a subset with isozyme selectivity for HO-1. Using X-ray crystallography, the structures of several complexes of HO-1 with novel inhibitors have been elucidated and provided insightful information regarding the salient features required for inhibitor binding. This included the structural basis for non-competitive inhibition, flexibility and adaptability of the inhibitor binding pocket, and multiple, potential interaction subsites, all of which can be exploited in future drug-design strategies. Notably, HO-1 inhibitors are of particular interest for the treatment of hyperbilirubinemia and certain types of cancer. Key features based on this initial study have already been used by others to discover additional potential HO-1 inhibitors. Moreover, studies have begun to use selected compounds and determine their effects in some disease models.


Risks and benefits of therapy with menopausal hormones versus selective estrogen-receptor modulators in peri- and postmenopausal women at increased breast cancer risk.
Decision making about menopausal therapies is complex because of the number of clinical factors that must be considered. Menopausal hormone therapy can relieve the vasomotor symptoms of menopause, but the most common preparation, combination estrogen and progesterone, increases the risk of breast cancer. Both tamoxifen and raloxifene can reduce the risk of developing invasive breast cancer, but the adverse effects of these drugs differ substantially. Risk models have been built to identify women at high risk for developing breast cancer, but their application in clinical practice has been develop disappointingly low. We propose an approach for identifying and managing menopausal women at high risk for breast cancer that can be readily implemented in clinical practice. The first step is to identify women at sufficiently high risk for breast cancer to merit treatment. For women aged 45 or older, the presence of one or more first-degree relatives with breast cancer and one or more previous breast biopsies will identify those whose 5-year risk is 2% or higher. For women 55 years or older, the presence of either one of these risk factors is sufficient. Any woman with a family history of breast cancer should be assessed as to whether she is likely to carry a BRCA mutation and referred for genetic counseling and possible genetic testing. Decisions about treatment options should be based on the presence or absence of bothersome vasomotor symptoms, an intact uterus, and risk factors for cardiovascular disease. A simple algorithm is presented to streamline identification and management of menopausal women at high risk for breast cancer.


Gitelman Syndrome.
Gitelman syndrome (GS) is the most frequently inherited renal salt-wasting tubulointerstitial disease. It follows variable but usually asymptomatic benign course. We present a rare case of GS that remained clinical enigma. A 22-year male presented with severe episodic fatigue involving all limbs associated with episodes of sinking, palpitations, salt craving, increased thirst and frequent micturition hampering his routine daily activities. Laboratory workup revealed serum potassium, 2.7 mmol/L, serum magnesium, 0.69 mmol/L and metabolic alkalosis. Urine analysis showed surprising results, i.e. urine potassium 49.5 mmol/L, urine spot potassium creatinine ratio 5.1, chloride 93 mmol/L and low 24 hours urinary calcium excretion (1.19 mmol/day). Plasma active renin concentration was 135 mlU/L while plasma aldosterone was 1090 pmol/L, depicting secondary hyperreninemic hyperaldosteronism. Based on typical findings, a diagnosis of GS was made. Patient responded well to potassium and magnesium supplementation, 100 mg daily tablet aldactone® and liberal salt intake. The aim of this report is to revisit clinical approach to persistent hypokalemia with special emphasis to remember rare entities like GS in the differential diagnosis.


Externalizing behavior and the higher order factors of the Big Five.
The comorbidity of various externalizing behaviors stems from a broad predisposition that is strongly genetically determined (R. F. Krueger, B. M. Hicks, C. J. Patrick, S. R. Carlson, W. G. Iacono, & M. McGue, 2002). This finding raises the question of how externalizing behavior is related to broad personality traits that have been identified in normal populations and that also have a genetic component. Using structural equation modeling, the authors applied a hierarchical personality model based on the Big Five and their two higher order factors, Stability (Neuroticism reversed, Agreeableness, and Conscientiousness) and Plasticity (Extraversion and Openness). Cognitive ability was included to separate variance in Openness associated with Extraversion (hypothesized to be positively related to externalizing behavior) from variance in Openness associated with cognitive ability (negatively related to externalizing behavior). This model was used to predict a latent externalizing behavior variable in an adolescent male sample (N = 140) assessed through self- and teacher reports. As hypothesized, externalizing behavior was characterized by low Stability, high Plasticity, and low cognitive ability.


Anion encapsulation and dynamics in self-assembled coordination cages.
The ability of cationic coordination cages to act as anion receptors is reviewed, with an emphasis on the anion encapsulation chemistry and the dynamics of cage assembly, anion exchange, and other anion-induced structural transformations. The first part of the review describes various examples of anion-encapsulating coordination cages, categorized on the basis of their M(x)L(y) stoichiometry (M = metal cation; L = organic ligand). The second part deals with the dynamic aspects of anion encapsulation, including the kinetics and mechanism of anion binding, release, and exchange, as well as the structural evolution of the coordination complexes involved.


Suffering, meaning, and bioethics.
Suffering evokes moral and metaphysical reflection, the bioethics of suffering concerns the proper ethos of living with suffering. Because empirical and philosophical explorations of suffering are imprisoned in the world of immanent experience, they cannot reach to a transcendent meaning. Even if religious and other narratives concerning the meaning of suffering have no transcendent import, they can have aesthetic and moral significance. This understanding of narratives of suffering and of their custodians has substantial ecumenical implications: chaplains can function as general custodians of narratives and sustainers of a generic religious meaning. This understanding is contrary to traditional Christianity, which discloses a transcendent significance of human suffering found in a very particular history involving particular persons: Christ as the second Adam through the submission of the second Eve has taken on our nature so that we can be united with God. Human suffering is tied to human sin, not simply as a punishment for sin, much less as an opportunity to discharge a supposed temporal punishment due to sin. Human suffering is the result of our rebellious free choices. It provides an opportunity for humility and submission, so that, united to the cross of Christ, sin can be forgiven and suffering set aside in the Resurrection. Knowledge of this framing context for all human suffering is accessible not through rational argument. It is a knowledge garnered through repentance, purification of the heart, illumination by God's grace, and unification with God. Christian bioethics is embedded in the narrative of suffering, which is part of the history of salvation and which encompasses and places all of medicine in its terms.


Derivation and characterization of a cytocompatible scaffold from human testis.
Is it possible to derive a scaffold from human testis for the purpose of tissue engineering and regenerative medicine? We developed a method to produce a cytocompatible decellularized testicular matrix (DTM) while maintaining the native tissue-specific characteristics and components. The potential benefits of tissue-specific scaffolds consisting of naturally-derived extracellular matrix (ECM) have been demonstrated using a wide variety of animal and human tissue sources. However, so far, testis scaffolds have never been considered for constructive remodelling purposes. Human cadaveric testicular tissue was exposed for 24 or 48 h to 1% Triton X-100 and/or 1% sodium dodecyl sulphate (SDS). Acellular samples were used for further scaffold characterization purposes. The extent of decellularization was evaluated by histology. Confirmation of cell removal in DTM was done by a DNA quantification technique. Retention of testicular tissue-specific characteristics was evaluated by mass spectrometry, immunohistochemistry, Alcian blue staining and scanning electron microscopy. Soluble toxicity and testicular cell attachment was assessed to check the cytocompatibility of DTM scaffolds. Histological analysis showed that DTM could be obtained by mechanical agitation in 1% SDS for 24 h. The resulting DTM was found to be clear of cells while retaining the typical three-dimensional structure and the major components of the native tissue scaffold, including collagen type I and IV, fibronectin, laminin and glycosaminoglycans. In addition, using proteomic analysis, we revealed numerous additional ECM proteins in DTM, indicating its complex nature. The mass spectrometry data were deposited to the ProteomeXchange with identifier PXD001524. Importantly, we demonstrated that DTM scaffolds are not cytotoxic, as evidenced by MTT assay not showing an aberrant fibroblast proliferation activity after indirect exposure, and support testicular cell attachment and infiltration. The functionality of human testicular cells in DTM needs to be investigated. Our results suggest that the insights into the molecular composition of the testicular ECM provide new clues for the unravelling of its important yet poorly understood role in regulating testicular function, and DTM-based bioscaffolds are promising components for the development of human in vitro spermatogenesis as a treatment for various types of male fertility disorders.


Cryosurgery in the excision of a giant local recurrent sacral chordoma: a case report and literature review.
Chordoma is a low-grade malignant tumor with recurrence and metastasis tendency that originates from embryonic notochordal remnants. The sacrococcygeal region is the most commonly involved site. The aim of this paper is to report the results of the use of cryosurgery in the excision of a giant recurrent sacral chordoma and review of pertinent literature. A 64 years old female patient with a locally recurrent sacral chordoma came to our attention after ten interventions performed at another institute. A surgical treatment was performed using argon cryosurgery. In this case, it was not possible to perform a marginal or wide excision, but it was intralesional with the removal of three major blocks. The fragments sent for the histological analysis measured total 35 × 30 × 8 cm with a weight of 4.260 g. Given the gelatinous structure of the tumor and the possibility of contamination of operatory field, cryosurgery may be indicated when previous surgeries and the dimensions of tumor mass do not allow a resection with negative margins improving radiotherapy efficacy in the local control of tumor.


Use of the B-IIb tetanus toxin derived fragment as a specific neuropharmacological transport agent.
It has been previously demonstrated that the non-toxic B-IIb tetanus toxin-derived fragment is transported retrogradely within neurons of the rat peripheral nervous system. In the present work we have shown that when a foreign polypeptide, in this case the Ibc tetanus toxin fragment, is coupled to B-IIb by a disulfide bond, it is transported retrogradely from the axonal endings within muscle to the motoneuronal perikarya. In contrast, Ibc fragment alone was found not to be transported. From these results we draw the conclusion that fragments like B-IIb may serve as specific carriers for chemical and chemotherapeutic agents into the central nervous system.


Novel opportunities for computational biology and sociology in drug discovery.
Current drug discovery is impossible without sophisticated modeling and computation. In this review we outline previous advances in computational biology and, by tracing the steps involved in pharmaceutical development,explore a range of novel, high-value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery.These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use.Computation can also be used to model research teams and innovative regions and to estimate the value of academy-industry links for scientific and human benefit. Attention to these opportunities could promise punctuated advance and will complement the well-established computational work on which drug discovery currently relies.


Reduced virulence of rifampicin-resistant mutants of Francisella tularensis.
Rifampicin-resistant mutants of a live vaccine strain (LVS) of Francisella tularensis were produced and screened for virulence in mice; 4 avirulent clones with intraperitoneal (ip) LD50s > 10(6) cfu, compared with 10(2) cfu for LVS, were characterized. Growth characteristics at 37 degrees C, surface envelope proteins, and lipopolysaccharide profiles of resistant mutants were identical to those of LVS. Polymerase activity of the mutants was more resistant than the enzyme from LVS to the inhibitory action of rifampicin. Growth rates for mutants and LVS were similar during the first 5 h at 42 degrees C, but viability of the mutants decreased to < 0.01% at 24 h. LVS and mutants differed in their ability to grow in vitro in host macrophages: LVS increased 580-fold over 72 h; mutants increased 33-fold. After ip inoculation of the organisms into mice, increasing numbers of LVS from peritoneal cells were isolated; mutants decreased over 4 days.


[Regional inequalities of health status of pregnant women in Hungary - Long-term series analysis].
Monitoring the health status of populations is essential for good health policy decisions. This is particularly true in maternal and child health where targeted and timely interventions may have long-term consequences. Our objective was to describe changes in the health status of pregnant women at the national and county level during the period of 1997-2012. Data were extracted from the mandatory annual reports of district nurses responsible for primary maternal care. Information on the smoking status of expecting mothers, special care during pregnancy, pregnant women entering into maternity care after 28 weeks of pregnancy, borne woman without district nurse care were analysed using Microsoft Excel and STATA 13.0. The mean prevalence of smoking was 13.8% among pregnant women during the investigation period. The ratio of smoking pregnant women was higher (p<0.01) in Borsod-Abaúj-Zemplén, Nógrád, Heves, Szabolcs-Szatmár-Bereg, and Somogy counties. The ratio of pregnants requiring special care was higher (p<0.01) than the national average in Somogy, Szabolcs-Szatmár-Bereg, Borsod-Abaúj-Zemplén and Nógrád counties. More, than 1% of the pregnant women entered into care only after the 28th week of the pregnancy. Women who were registered by district nurses and gave birth less than 1% did not participate in pregnant nursing. National data hide significant regional disparities within the country which should be amended by targeted interventions, taking into account the large regional inequalities in the country. Orv Hetil. 2017; 158(29): 1131-1142.


Influence of foetal position on the degree of isolated antenatal hydronephrosis.
The effect of foetal position on the degree of antenatal hydronephrosis (ANH) is unknown. We hypothesized that foetal position is an important contextual factor in ANH, with consequences on prenatal counselling and postnatal management. The current study aimed to investigate the effect of foetal position on the degree of ANH. A retrospective study was carried out on consecutive pregnancies with isolated ANH over a 10-year period. Gestational age, foetal presentation (cephalic vs. breech), and degree of ANH (as measured by the AP diameter) were retrieved. Foetuses with other ultrasound findings of the renal tract (renal parenchymal abnormality, ureteric dilatation, or bladder abnormalities) were excluded. Logistic regression analysis was conducted to examine the relationship between the anterior-posterior diameter (APD) and the mode of presentation (cephalic or breech). A P-value of <0.05 was considered significant. Initially 745 scans were identified, with 436 included in the final analysis. Overall, there was an association between foetal presentation and APD regardless of trimester, with cephalic presentations having a greater APD (OR 1.07, 95% CI 1.02-1.11, P = 0.04). Cephalic presentations are associated with a significantly greater APD indicating that foetal position should be considered when stratifying ANH. Furthermore, foetal position may be a contributing factor in the mechanism of 'physiological' hydronephrosis.


Minimalist style boot improves running but not walking economy in trained men.
This study examined movement economy under load with 1000 g minimalist (MIN) vs. 1600 g traditional (TRD) style boots. Fourteen trained, male participants completed a VO2peak test (46.6 ± 7.3 ml/kg/min) while wearing a 16 kg external load. Treadmill speeds for the running economy (RE) trials were determined by the slowest pace in which participants completed a full stage with a running gait pattern during the VO2peak test. Walking economy (WE) pace was 1.6 km/h slower than RE pace. During the second session, participants completed 5-min exercise bouts at WE and RE pace under load wearing MIN and TRD. There were no differences for any measured variables during WE trials. In contrast, RE (MIN = 2.95 ± 0.28 vs. TRD = 3.04 ± 0.30 L/min; p = .003: Cohen's d = 0.32), respiratory exchange ratio (p < .001), and perceptual measures (p < .05) were all improved while wearing MIN. Practitioner summary: In trained men, 1000 g/pair minimalist style boots (MIN) resulted in improvements of approximately 3% and 5% for running economy and respiratory exchange ratio versus 1600 g/pair traditional boots while wearing a 16 kg kit. Perceptual responses, including comfort, also favoured MIN. These effects were not found at walking pace. Abbreviations: MIN: minimalist style boots; TRD: traditional style boots; RE: running economy; WE: walking economy; ES: effect size; RER: respiratory exchange ratio; HR: heart rate.


Syndecan-1 is a novel molecular marker for triple negative inflammatory breast cancer and modulates the cancer stem cell phenotype via the IL-6/STAT3, Notch and EGFR signaling pathways.
Inflammatory breast cancer (IBC), a particularly aggressive form of breast cancer, is characterized by cancer stem cell (CSC) phenotype. Due to a lack of targeted therapies, the identification of molecular markers of IBC is of major importance. The heparan sulfate proteoglycan Syndecan-1 acts as a coreceptor for growth factors and chemokines, modulating inflammation, tumor progression, and cancer stemness, thus it may emerge as a molecular marker for IBC. We characterized expression of Syndecan-1 and the CSC marker CD44, Notch-1 & -3 and EGFR in carcinoma tissues of triple negative IBC (n = 13) and non-IBC (n = 17) patients using qPCR and immunohistochemistry. Impact of siRNA-mediated Syndecan-1 knockdown on the CSC phenotype of the human triple negative IBC cell line SUM-149 and HER-2-overexpressing non-IBC SKBR3 cells employing qPCR, flow cytometry, Western blotting, secretome profiling and Notch pharmacological inhibition experiments. Data were statistically analyzed using Student's t-test/Mann-Whitney U-test or one-way ANOVA followed by Tukey's multiple comparison tests. Our data indicate upregulation and a significant positive correlation of Syndecan-1 with CD44 protein, and Notch-1 & -3 and EGFR mRNA in IBC vs non-IBC. ALDH1 activity and the CD44(+)CD24(-/low) subset as readout of a CSC phenotype were reduced upon Syndecan-1 knockdown. Functionally, Syndecan-1 silencing significantly reduced 3D spheroid and colony formation. Intriguingly, qPCR results indicate downregulation of the IL-6, IL-8, CCL20, gp130 and EGFR mRNA upon Syndecan-1 suppression in both cell lines. Moreover, Syndecan-1 silencing significantly downregulated Notch-1, -3, -4 and Hey-1 in SUM-149 cells, and downregulated only Notch-3 and Gli-1 mRNA in SKBR3 cells. Secretome profiling unveiled reduced IL-6, IL-8, GRO-alpha and GRO a/b/g cytokines in conditioned media of Syndecan-1 knockdown SUM-149 cells compared to controls. The constitutively activated STAT3 and NFκB, and expression of gp130, Notch-1 & -2, and EGFR proteins were suppressed upon Syndecan-1 ablation. Mechanistically, gamma-secretase inhibition experiments suggested that Syndecan-1 may regulate the expression of IL-6, IL-8, gp130, Hey-1, EGFR and p-Akt via Notch signaling. Syndecan-1 acts as a novel tissue biomarker and a modulator of CSC phenotype of triple negative IBC via the IL-6/STAT3, Notch and EGFR signaling pathways, thus emerging as a promising therapeutic target for IBC.


Towards the complete small RNome of Acinetobacter baumannii.
In recent years, the Gram-negative bacterium Acinetobacter baumannii has garnered considerable attention for its unprecedented capacity to rapidly develop resistance to antibacterial therapeutics. This is coupled with the seemingly epidemic emergence of new hyper-virulent strains. Although strain-specific differences for A. baumannii isolates have been well described, these studies have primarily focused on proteinaceous factors. At present, only limited publications have investigated the presence and role of small regulatory RNA (sRNA) transcripts. Herein, we perform such an analysis, describing the RNA-seq-based identification of 78 A. baumannii sRNAs in the AB5075 background. Together with six previously identified elements, we include each of these in a new genome annotation file, which will serve as a tool to investigate regulatory events in this organism. Our work reveals that the sRNAs display high expression, accounting for >50 % of the 20 most strongly expressed genes. Through conservation analysis we identified six classes of similar sRNAs, with one found to be particularly abundant and homologous to regulatory, C4 antisense RNAs found in bacteriophages. These elements appear to be processed from larger transcripts in an analogous manner to the phage C4 molecule and are putatively controlled by two further sRNAs that are strongly antisense to them. Collectively, this study offers a detailed view of the sRNA content of A. baumannii, exposing sequence and structural conservation amongst these elements, and provides novel insight into the potential evolution, and role, of these understudied regulatory molecules.


[Recombinant RNA-dependent DNA-polymerase from Rous sarcoma virus. Isolation and properties].
Preparations of recombinant reverse transcriptase RSV were isolated from E. coli HB101/pMF14 cell cultures. The enzyme purified to homogeneity was shown to be made up of two subunits with molecular masses of 97 +/- 4 and 61 +/- 3 kDa. A comparison of enzymatic properties of recombinant transcriptase to those of the enzyme isolated from the RSV (Rauss sarcoma) virus demonstrated that in the preparations under study the recombinant reverse transcriptase exists in a subunit form, alpha beta, and may acquire a relatively stable configuration, alpha 2.


Significance of imaging findings in the diagnosis of heterotopic spleen-an intrapancreatic accessory spleen (IPAS): Case report.
Accessory spleen (Heterotopic/Ectopic) or splenunculus has been attributed to the failure of the fusion of splenic primordial buds-derived from dorsal mesentery (mesodermal mesenchymal in origin) during the 5th week of embryonic organogenesis or to an extreme degree of splenic lobulation with pinching off of the spleen tissue. The most common locations for accessory spleens are the hilum of the spleen followed by adjacent to the tail of the pancreas. The patients usually present with no clinical symptoms. A 49-year-old female undergoing a routine medical examination- Abdominal Ultrasound revealed a pancreatic mass. She was admitted into the hospital for 3 days and was put under observation. There are no specific findings during the physical examination or any related abnormalities in the laboratory investigations. Heterotopic spleen-an intrapancreatic accessory spleen (IPAS). Noncontrast CT of the abdomen demonstrated a soft tissue mass with a clear boundary in the tail of the pancreas. On contrast examination-the arterial phase, it was markedly enhanced, homogenous congruity similar to that of spleen; on magnetic resonance imaging (MRI)-T2WI with fat suppressed sequence, it demonstrated a regular round clear edged mass in the pancreatic tail. On Diffusion Weighted Imaging (DWI), a mass with a clear boundary was observed within the parenchyma of the pancreatic tail. The mass showed a high signal on noncontrast MRI, while on contrast examination, the mass showed a strengthening signal with homogenous enhancement as that of spleen. Heterotopic spleen presentation is a very rare asymptomatic clinical condition. During the routine medical examination - it presents mostly as a solitary benign round or oval mass with a clear boundary or as an ectopic focus, either in the pancreatic tail or adjacent to the pancreatic appendage, as an incidental finding. On Contrast CT, it shows as a homogeneously enhanced density- a strengthening mass lesion, in the pancreatic tail, similar to that of spleen. Our case emphasizes the importance of recognizing IPAS radiological characteristics and typical variations in its presentation in an asymptomatic patient that could help the personnel to differentiate it from other mass lesions. Thus, recognizing imaging findings on Plain CT, Contrast CT and MRI plays a key role to form a conclusive diagnosis of an accessory spleen, which has to be clinically associated. So, surgeons should consider IPAS as a differential for which unnecessary resection and an unintended surgical procedure can be avoided.


Postictal mixed transcortical aphasia.
Postictal aphasia has been described in left temporal lobe seizures. It may be of fluent, non-fluent or global type. We present here a patient who displayed signs of mixed transcortical aphasia (MTCA). The patient was a 67 year old man who underwent excision of a left frontal parasagittal meningioma in 1987. Since then he has been treated with phenytoin for generalized tonic-clonic seizures (GTCS). He was admitted in status epilepticus. On awakening, the patient was non-fluent with palilalia and echolalia. His repetition was relatively preserved but all the other language functions were impaired. This picture faded away within a few hours. Brain CT, performed during this postictal state, was normal except for signs related to frontal craniotomy. SPECT, which was performed after language functions returned to normal, displayed left frontal, cingular and insular hypoperfusion. The postictal language dysfunction of the patient corresponded to MTCA. Although our case has frontal, he had no other structural lesion that could explain either diffuse ischemia of the left hemisphere or watershed areas secondary to the generalized seizures. The uniqueness of this case is the combination of postictal MTCA with good prognosis.


Driving transcriptional regulators in melanoma metastasis.
The progression of melanoma toward the metastatic phenotype occurs in a defined stepwise manner. While many molecular changes take place early in melanoma development, progression toward the malignant phenotype, most notably during the transition from the radial growth phase (RGP) to the vertical growth phase (VGP) involves deregulated expression of several transcription factors. For example, the switch from RGP to VGP is associated with the loss of the transcription factor AP2α and gain of transcriptional activity of cAMP-responsive element binding protein. Together with the upregulation of microphthalmia-associated transcription factor, activating transcription factor 2, nuclear factor kappa B, and other transcription factors, these changes lead to dysregulated expression or function of important cellular adhesion molecules, matrix degrading enzymes, survival factors, as well as other factors leading to metastatic melanoma. Additionally, recent evidence suggests that microRNAs and RNA editing machinery influence the expression of transcription factors or are regulated themselves by transcription factors. Many of the downstream signaling molecules regulated by transcription factors, such as protease activated receptor-1, interleukin-8, and MCAM/MUC18 represent new treatment prospects.