Effect of live yeast culture supplementation on apparent digestibility and rate of passage in horses fed a high-fiber or high-starch diet.
Eight crossbred male horses aged 12 +/- 5 yr and with BW of 305 +/- 18 kg were used in pairs in a 4 x 4 Latin square design with 4 ground and pelleted diets. Each pair included a cecum and right ventral colon-fistulated animal and a cecal-fistulated animal. The 4 horse diets were a high-fiber diet (HF+0) based on dehydrated alfalfa, a high-starch diet based on barley and wheat bran (HS+0), and the HF or HS diets supplemented with Saccharomyces cerevisiae (SC) CBS 493.94 (HF+SC and HS+SC). The probiotic preparation contained 4.5 x 10(9) cfu/g of live yeast mixed with the culture medium, and was top-dressed onto the feed pellets at a rate of 10 g/d, equally distributed between the 2 daily meals. All 4 diets were offered in the same quantities (18.0 g of pelleted feed DM + 3.5 g of long wheat straw/kg of BW per d). Each of the 4 experimental treatments was divided into a 21-d period of diet adaptation followed by a 10-d period of total fecal collection for digesta flow rate and apparent digestibility measurements. Three markers were used to measure mean retention time (MRT) of the feed particles: Yb bound to the pelleted feeds for MRT in the whole digestive tract (MRT(Yb)), Eu bound to the pelleted feeds, and Dy bound to the fecal particles for MRT in the hindgut (MRT(Eu) and MRT(Dy)). Apparent digestibilities of DM, OM, and CP were greater (P < 0.001) in the HS than HF diet, independently of SC supplementation, whereas ADF digestibility was greatest in the HF diet (P = 0.035). Cellulolytic activity estimated through the in vitro disappearance rate of the dietary ADF fraction (IVAD(ADF)) was less (P < 0.001) in the HS than the HF diet. There was no dietary effect on NDF digestibility due to the longer MRT(Eu) of small particles in the hindgut (P = 0.036), which compensated for the lower fibrolytic activity expressed per unit of time in the HS compared with the HF diet. Supplementation with SC improved ADF digestibility (P = 0.038) and stimulated DM (P = 0.030) and NDF (P = 0.038) intakes, but had no effect on the MRT of solid digesta. The absence of any significant diet x SC interaction supports the strategy of using SC to stimulate cellulose digestion and improve the nutritional status of horses under both HF and HS diets.


Improvement in Tongue Pressure Precedes Improvement in Dysphagia in Dermatomyositis.
Dysphagia is known to occur in patients with dermatomyositis. However, the sudden-onset dysphagia without other symptoms can make diagnosis and treatment challenging. Two patients who did not have a severe muscle weakness complained of the sudden inability to swallow solids and liquids. The muscle biopsy results showed the perifascicular atrophy, and the patients were diagnosed with dermatomyositis. Videofluoroscopy revealed an inadequate pharyngeal contraction and a decreased upper esophageal sphincter opening with silent aspiration. Both patients showed low tongue pressures. Patient 1 received intravenous and oral methylprednisolone, and patient 2 received intravenous immunoglobulin in addition to intravenous and oral methylprednisolone. Several months after the onset of the dysphagia, the swallowing function of both patients improved. The improvement in tongue pressure preceded an improvement in the subjective and objective measurements of dysphagia. In conclusion, tongue pressure may be useful for predicting early improvement in swallowing function.


Microwave sterilization of femoral head allograft.
The potential shortage of allograft bone has led to the need to investigate other sources of bone for allografts. Some allograft bone donated from primary total hip arthroplasty recipients must be discarded or treated to become usable as a result of bacterial contamination. Femoral head allografts were contaminated with Staphylococcus aureus and Bacillus subtilis. A domestic microwave oven was used. The contaminated bone was exposed to microwave irradiation for different time periods. The samples were then cultured to attempt to grow the two bacterial species. The contaminated bone samples failed to grow any organisms after 2 min of exposure to microwave irradiation. This study shows that sterilization of femoral head allografts contaminated with S. aureus and B. subtilis can be achieved with microwave irradiation in a domestic microwave oven. This method of sterilization of bone allografts is cheap, easily used, and an effective way to process contaminated bone.


TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy.
Persistent HPV infection is recognized as the main etiologic factor for cervical cancer. HPV expresses the oncoproteins E6 and E7, both of which play key roles in maintaining viral infection and promoting carcinogenesis. While siRNA-mediated targeting of E6 and E7 transcripts temporarily induces apoptosis in HPV-positive cells, it does not eliminate viral DNA within the host genome, which can harbor escape mutants. Here, we demonstrated that specifically targeting E6 and E7 within host DNA with transcription activator-like effector nucleases (TALENs) induces apoptosis, inhibits growth, and reduces tumorigenicity in HPV-positive cell lines. TALEN treatment efficiently disrupted E6 and E7 oncogenes, leading to the restoration of host tumor suppressors p53 and retinoblastoma 1 (RB1), which are targeted by E6 and E7, respectively. In the K14-HPV16 transgenic mouse model of HPV-driven neoplasms, direct cervical application of HPV16-E7-targeted TALENs effectively mutated the E7 oncogene, reduced viral DNA load, and restored RB1 function and downstream targets transcription factor E2F1 and cycling-dependent kinase 2 (CDK2), thereby reversing the malignant phenotype. Together, the results from our study suggest that TALENs have potential as a therapeutic strategy for HPV infection and related cervical malignancy.


A rapid and high-throughput multiplex genetic detection assay for detection, semi-quantification and virulence genotyping of Helicobacter pylori in non-invasive oral samples.
This study established a high-throughput multiplex genetic detection assay (HMGA) for rapid identification, semi-quantification and virulence analysis of Helicobacter pylori directly from the clinical non-invasive oral samples. The gastric mucosa and oral samples were collected from 242 patients in Shanghai from 2021 to 2022. All the samples were detected by routine clinical tests for H. pylori and Sanger sequenced for inconsistent results. A new multiplex PCR assay providing results within 4 hours was designed and optimized involving fluorescent dye-labeled specific primers targeted 16S rRNA gene, semi-quantitative gene ureC and 10 virulence genes of H. pylori. Semi-quantification was carried out by simulating the serial 10-fold dilutions of positive oral samples, and the H. pylori loads in different clinical samples were further compared. The mixed plasmids of virulence genes vacA s1, vacA m1 and vacA m2 were used to evaluate the performance on different genotypes. The consistency of 10 virulence genes in gastric mucosa, saliva, mouthwash and dental plaque of H. pylori-positive patients was compared. The non-invasive HMGA was highly specific for detection of all 12 targets of H. pylori and human internal reference gene β-globin, and the sensitivity to all target genes could reach 10 copies/μL. Compared with routine clinical tests and sequencing, non-invasive HMGA has a high level (>0.98) of sensitivity, specificity, accuracy, PPV, NPV and kappa coefficient for direct detection of H. pylori in oral samples. Moreover, by detecting peak area levels of ureC, it was confirmed that the H. pylori loads in gastric mucosa were significantly higher than those of the three kinds of oral samples (p<0.05). We also found that 45.0% (91/202) of patients had different H. pylori virulence genes in different oral samples. The concordance of positive detection rates of each virulence gene between saliva and gastric mucosa was more than 78% (p<0.05). The non-invasive HMGA proved to be a reliable method for the rapid H. pylori identification, semi-quantification and detection of 10 virulence genes directly in oral samples, providing a new idea for non-invasive detection of H. pylori.


Alteration in brain-derived neurotrophic factor (BDNF) after treatment of mice with herbal mixture containing Euphoria longana, Houttuynia cordata and Dioscorea japonica.
Literature data indicate that brain-derived neurotrophic factor (BDNF), cyclic-AMP response element-binding protein (CREB) and phospho-CREB (pCREB) may have a place in depression. BDNF belongs to the neurotrophin family that plays an important role in proliferation, survival and differentiation of different cell populations in the mammalian nervous system. The herbal mixture used in the present study consists of Euphoria longana, Houttuynia cordata and Dioscorea japonica. The purpose of the present study was to determine the neuroprotective effect of herbal mixture. We also tested the hypothesis that administration of herbs reverses memory deficits and promotes the protein expression of BDNF in the mouse brain. Mice were randomized into four different treatment groups (n = 10/group). Normal and stress groups received regular lab chow without stress and under stress conditions, respectively, for 3 weeks. The animals in the stress group were immobilized for 4 hours a day for 2 weeks. Different doses of herbal mixture (206 and 618 mg/kg) were administered for 3 weeks to those mice under stress conditions. Mice were analyzed by behavioral tests and immunoblotting examination in the hippocampus and cortex. An additional in vitro investigation was performed to examine whether herbs induce neurotoxicity in a human neuroblastoma cell line, SH-SY5Y cells. No significant toxicity of herbs on human neuroblastoma cells was observed. These herbs demonstrated an inductive effect on the expression of BDNF, pCREB and pAkt. For spatial working memory test, herbal mixture fed mice exhibited an increased level of spontaneous alternation (p < 0.01) compared to those in stress conditions. Moreover, herbal mixture produced highly significant (p < 0.01) reduction in the immobility time in the tail suspension test. Mice in the herbal mixture groups demonstrated lower serum corticosterone concentration than mice in the stress group (p < 0.05). Effects of the oral administration of herbal mixture on protein levels of BDNF in the hippocampi and cortices were significant. Our study showed that herbal mixture administration has antidepressant effects in mice. It is proposed that adverse events such as stress and depression can modulate the expression of molecular players of cellular plasticity in the brain.


Endometrial cancer cells can express fibrinogen: Immunohistochemistry and RT-PCR analysis.
We investigated whether endometrial cancer (EC) cells can express fibrinogen. Consecutive patients treated for EC were enrolled (cases). A control group of women who had hysterectomy for benign conditions was identified in a case:control ratio of 4:1. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were performed to identify the presence of fibrinogen and the mRNA of its three chains (α, β, γ) in the tissue specimens from both cases and controls. Sixteen EC cases and 4 benign controls were included. Immunohistochemistry failed in one case of EC. In 12/15 (80%) cases versus 0 controls, a moderate-to-intense positivity for fibrinogen was observed (p = 0.09; OR: 32.1; 95%CI: 1.4-752.9). Six (37.5%) women among the cases versus 0 controls expressed RNA for at least one chain of fibrinogen (p = 0.25). All the cases (6/6, 100%) with positive RT-PCR had moderate-to-intense positive immunohistochemistry. Molecular and immunohistochemistry show that some cases of EC have the capability to express fibrinogen and the mRNA of at least one of its chains.


Particle generation, functionalization and sortase A-mediated modification with targeting of single-chain antibodies for diagnostic and therapeutic use.
Antibody fusion to nonprotein materials such as contrast agents or radio-tracers, nano- or microparticles or small-molecule drugs is attracting major interest for molecular imaging and drug delivery. Nondirected bioconjugation techniques may impair antibody affinity, result in lower amounts of functional antibodies and generate multicomponent mixtures. We present a detailed protocol for the enzymatic bioconjugation of small recombinant antibodies to imaging particles, and we also describe the generation of and conjugation to a low-fouling capsule assembled for drug delivery from PEG and PVPON (poly(N-vinylpyrrolidone) by a layer-by-layer (LbL) technique. The single-chain variable fragment (scFv) is equipped with a short C-terminal LPETG tag and the fusion partners are functionalized with an N-terminal GGG nucleophilic group for sortase A conjugation. The LbL capsules are assembled through hydrogen bonding by depositing alkyne-modified poly(vinylpyrrolidone) and poly(methacrylic acid) layers on silica particles, followed by depositing alkyne-modified PEG. The generation of the antibodies and LbL capsules takes ∼1-2 weeks each. The conjugation and functional testing takes another 3-4 d.


Effect of calcium supplementation on urinary hydroxyproline in osteoporotic postmenopausal women.
Although calcium supplements are widely used to reduce bone resorption in osteoporosis, their beneficial effect is not conclusively established. We studied the effect of a calcium supplement (1 g/day for 8 days) in 14 postmenopausal osteoporotic women. The fasting urinary hydroxyproline/creatinine ratio decreased from 0.022 +/- 0.001 to 0.017 +/- 0.001 (p less than 0.005) indicating a significant reduction in bone resorption. Both the tubular maximum for phosphate reabsorption (1.12 +/- 0.06 to 1.34 +/- 0.07, p less than 0.005) and plasma phosphate concentration (1.04 +/- 0.04 to 1.14 +/- 0.04, p less than 0.01) increased, consistent with suppression of parathyroid hormone activity. These results support the concept that calcium supplementation is useful in the treatment of postmenopausal osteoporosis.


Tumor collagenase stimulatory factor (TCSF) expression and localization in human lung and breast cancers.
Tumor cell-derived collagenase stimulatory factor (TCSF) stimulates in vitro the biosynthesis of various matrix metalloproteinases involved in tumor invasion, such as interstitial collagenase, gelatinase A, and stromelysin 1. The expression of TCSF mRNAs was studied in vivo, using in situ hybridization and Northern blotting analysis, in seven normal tissues and in 22 squamous cell carcinomas of the lung, and in seven benign proliferations and in 22 ductal carcinomas of the mammary gland. By in situ hybridization, TCSF mRNAs were detected in 40 of 44 carcinomas, in pre-invasive and invasive cancer cells of both lung and breast cancers. TCSF mRNAs and gelatinase A mRNAs were both visualized in the same areas in serial sections in breast cancers, and were expressed by different cells, tumor cells, and fibroblasts. The histological results were confirmed by Northern blot analysis, which showed a higher expression of TCSF mRNAs in cancers than in benign and normal tissues. These observations support the hypothesis that TCSF is an important factor in lung and breast tumor progression.


Synthetic Landau levels for photons.
Synthetic photonic materials are an emerging platform for exploring the interface between microscopic quantum dynamics and macroscopic material properties. Photons experiencing a Lorentz force develop handedness, providing opportunities to study quantum Hall physics and topological quantum science. Here we present an experimental realization of a magnetic field for continuum photons. We trap optical photons in a multimode ring resonator to make a two-dimensional gas of massive bosons, and then employ a non-planar geometry to induce an image rotation on each round-trip. This results in photonic Coriolis/Lorentz and centrifugal forces and so realizes the Fock–Darwin Hamiltonian for photons in a magnetic field and harmonic trap. Using spatial- and energy-resolved spectroscopy, we track the resulting photonic eigenstates as radial trapping is reduced, finally observing a photonic Landau level at degeneracy. To circumvent the challenge of trap instability at the centrifugal limit, we constrain the photons to move on a cone. Spectroscopic probes demonstrate flat space (zero curvature) away from the cone tip. At the cone tip, we observe that spatial curvature increases the local density of states, and we measure fractional state number excess consistent with the Wen–Zee theory, providing an experimental test of this theory of electrons in both a magnetic field and curved space. This work opens the door to exploration of the interplay of geometry and topology, and in conjunction with Rydberg electromagnetically induced transparency, enables studies of photonic fractional quantum Hall fluids and direct detection of anyons.


Simulation of traveling-wave resonant tunneling diode oscillator waveguides.
In a traveling-wave resonant tunneling diode oscillator, the gain medium is encapsulated in a metallic waveguide. The geometrical parameters of the system and the skin penetration depth in the metal layers are of similar length scales. It confirms the need for a full-wave simulation, where the impedance boundary conditions can not be applied in a straightforward manner. In this work, a method of moments-based electromagnetic wave solver was developed and used to illustrate different traveling-wave RTD oscillator structures.


Transboundary flow modeling: the Zohor depression of Austria and the Slovak Republic.
Estimation of available ground water is a basic aspect of ground water management. Mathematical modeling is one of the methods that can be effectively used to obtain such estimates. A numerical model was used to calculate available ground water in the Zohor depression-an aquifer transcending national boundaries between the Slovak Republic and Austria. The aquifer, formed by Quaternary sediments overlying Neogene sequences, is composed of various clays interbedded with layers of sand, gravel, sandstones, and conglomerates. The AQUA computer model package was used to simulate flow in the aquifer. For model compilation, the following data were used: (1) effective precipitation; (2) surface water levels in surface water gauging profiles; and (3) withdrawal amounts. Hydraulic parameters of the aquifer were estimated based on information from 86 wells located in the area. The model was verified using data on ground water levels from a monitoring network. The simulation of the aquifer system permitted the estimation of the available ground water in the study area, showing that an additional 587 L/s can be abstracted. Ground water inflows to the Morava River, which flows through the region, range from 745 to 3100 L/s.


Lip prints (cheiloscopy).
External surface of the lip has many elevations and depressions forming a characteristic pattern called lip prints, examination of which is referred to as cheiloscopy. This is unique for individuals like the finger prints. The biological phenomenon of systems of furrows on the red part of the human lips was first noted and described by anthropologist R.S. Fischer, in 1902. However until 1930, anthropology merely mentioned the existence of furrows without suggesting a practical use for the phenomenon. Since 1950, the Japanese have carried out extensive research in this matter. In the period 1968 to 1971, Y.T Suchhihashi and T. Suzuki examined 1364 persons at the department of forensic odontology at Tokyo university and established that the arrangement of lines on the red part of the human lips is individual and unique for each human being. Lip print recording is helpful in forensic investigation that deals with identification of humans, based on lip traces. A lip print may be revealed as a surface with visible elements of lines representing the furrows. This characteristic pattern helps to identify the individuals since it is unique for individuals. When the lines are not clear (Only the shape of lines is printed), individual identification of human being based on this trace is extremely difficult, unless the trace contains more individual characteristics like scars, clefts etc, and often identification ends with group identification.


Psychotropic medications in lactation.
The use of psychotropic medications during lactation has not been investigated in a controlled and systematic fashion. The literature is laden with case reports and small case series containing numerous confounds that render the establishment of definitive treatment guidelines tenuous. The increasing number of women who plan to breast-feed and the high rate of psychiatric illness during the postpartum period underscore the need to develop such guidelines. A MEDLINE search was conducted for key words either in the titles or abstracts of publications citing the use of psychotropic medications in lactating women and describing the pharmacokinetics of medication excretion into breast milk. The publications identified span over three decades. The largest single study by one group of investigators examined 12 mother-infant pairs. The majority of studies report their results as a ratio of the breast milk concentration to the maternal serum concentration (milk/plasma [M/P]) ratio. Estimations that use the M/P ratio of the infant daily dose range from 0.1% to 6.2% of the maternal dose. Few studies attempt to account for the complex variations in the maternal, breast milk, and infant physiologic environments. The major confounds of the studies reviewed include (1) failure to document portion of breast milk assayed (foremilk versus hindmilk), (2) limited metabolite assay, (3) limited assay sensitivity (1-25 ng/mL), not of research quality, (4) concomitant maternal and/or infant medications, and (5) medication exposure during pregnancy. Despite these confounds, there are remarkably few reports of adverse effects on nursing infants exposed to psychotropic medications in breast milk. The limited data confirm that psychotropic medications are excreted into breast milk and that the infant is exposed to these medications. The ideal breast milk study that accounts for the confounds identified has not been completed. The complex matrix of breast milk and the changing infant metabolic capacity will require a more detailed analysis with assays of improved sensitivity. Despite the limited reports of adverse effects on nursing infants, the limitations of the available literature and minimal sample sizes make it premature to recommend specific medications from a given class. There is inadequate data on nursing infant exposure to multiple medications to support changing medication to a different agent in an otherwise stable patient. An individualized risk/benefit assessment with the empirical goal of minimizing infant exposure while maintaining maternal emotional health is the ideal approach.


Distinguishing Myasthenia Exacerbation from Severe Preeclampsia: A Diagnostic and Therapeutic Challenge.
Myasthenia gravis is an acquired, autoimmune neuromuscular disorder characterized by voluntary muscle weakness. Pregnant patients may have disease exacerbation, respiratory failure, crisis, adverse drug reaction, surprisingly enough remission at any trimester or postnatal period. Concurrence of myasthenia gravis with severe preeclampsia is a dreadful condition raising diagnostic and management issues. We hereby discuss a case of myasthenic woman who developed severe preeclampsia during pregnancy and presented in last trimester with clinical features mimicking signs of impending eclampsia. Keeping in mind the history of myasthenia gravis, urgent neurology review taken and diagnosis of myasthenic exacerbation was entertained. She responded well to injection neostigmine and in this way inadvertent use of magnesium sulphate was avoided.


She said, he said, judge said: analyzing judicial decision making in civil protection order hearings.
A modest body of research has examined judicial decision making in civil protection order (CPO) cases. A major finding of this prior research is that the factors expected to shape judicial responses to CPO requests are often found to be insignificant. Because such decisions are often rendered in an environment of vast judicial discretion and competing allegations, the question of "what matters?" assumes added importance. This study examines permanent/final restraining order (PRO) outcomes for intimate partner violence on a number of variables. Specifically, chi-square analyses were performed examining the associations between granting/denying a PRO and demographic, relationship, hearing, and allegation characteristics associated with the petitioner and respondent. These tests helped to reveal relationships at the bivariate level and aided in further model-building using logistic regression and decision-tree analysis. The findings show that the factors most associated with PRO outcomes, namely, the denial of a PRO, are those reflecting the licit rather than illicit behavior of the respondent.


[Does Barrett esophagus regress after total duodenal diversion?].
The outcome of Barrett's esophagus was evaluated in 21 patients who prospectively underwent total duodenal diversion and followed from 13 to 86 months. The total duodenal diversion procedure included troncular vagotomy, antrectomy and Roux-en-Y reconstruction incorporating a 70 cm loop. The diagnosis of Barrett's esophagus was made on endoscopy when a circular zone of columnar epithelium more than 3 cm long was found and was always corroborated by biopsies. All patients had esophagitis on endoscopy or acid reflux on pH-monitoring. During follow-up, for all cases, no esophagitis and no bile were detected in the stomach by successive endoscopies; none of the 16 pH-studies showed any aggressive reflux. The length of Barrett's esophagus was measured before and after Roux-en-Y duodenal diversion. In spite of the suppression of gastroesophageal reflux, regression of Barrett's esophagus was observed in one case only beginning 24 months after the diversion. No cases of adenocarcinoma or dysplasia were detected. In conclusion, regression of Barrett's esophagus is exceptional even after duodenal diversion.


Traditional home-brewed beer consumption and iron status in patients with esophageal cancer and healthy control subjects from Transkei, South Africa.
Consumption of home-brewed beer is associated with dietary iron excess and a high incidence of esophageal cancer in Transkei, South Africa. We examined the relationship between home-brewed beer consumption and body iron status in 234 patients with esophageal squamous cell carcinoma and 595 control subjects residing in Transkei. Subjects were screened for iron overload using transferrin saturation >45%, and/or serum ferritin >200 microg/l for women and >300 microg/l for men. A questionnaire was administered to all subjects, and iron content of randomly selected home-brewed beer samples was determined. The iron content of home-brewed beer was 258-fold higher than the commercial Castle Lager beer produced by South African Breweries. The prevalence of home-brewed beer consumption was 30.1% in esophageal cancer patients and 15.5% in control subjects and was found not to be a risk factor for esophageal cancer after adjustment for age, sex, and tobacco consumption (male subjects, odds ratio= 1.6 (95% confidence interval [CI]: 0.7-4.5); female subjects, odds ratio=1.7 (95% CI: 0.7-4.5). Iron overload as determined by transferrin saturation and elevated serum ferritin was observed in 4.3% of patients with esophageal cancer and 0.7% of control subjects and was not associated with the consumption of home-brewed beer. Consumption of home-brewed beer is not a risk factor for esophageal cancer and is not linked with iron overload in either cancer patients or control subjects; however, iron overload is likely to result from a combination of dietary intake and a genetic component.


The Tubulointerstitial Pathophysiology of Progressive Kidney Disease.
Accumulating evidence suggests that the central locus for the progression of CKD is the renal proximal tubule. As injured tubular epithelial cells dedifferentiate in attempted repair, they stimulate inflammation and recruit myofibroblasts. At the same time, tissue loss stimulates remnant nephron hypertrophy. Increased tubular transport workload eventually exceeds the energy-generating capacity of the hypertrophied nephrons, leading to anerobic metabolism, acidosis, hypoxia, endoplasmic reticulum stress, and the induction of additional inflammatory and fibrogenic responses. The result is a vicious cycle of injury, misdirected repair, maladaptive responses, and more nephron loss. Therapy that might be advantageous at one phase of this progression pathway could be deleterious during other phases. Thus, interrupting this downward spiral requires narrowly targeted approaches that promote healing and adequate function without generating further entry into the progression cycle.


[Progress in research of the pathogenesis of childhood MDS/MPN].
Recent research reveals novel insights into the pathogenesis of childhood myelodysplastic syndromes (MDS) in addition to that of juvenile myelomonocytic leukemia (JMML). In pediatric MDS, the genetic characteristics of which have been barely elucidated previously, germline mutations, particularly those in GATA2, SAMD9, and SAML9L, have been frequently identified, indicating the importance of germline predisposition in childhood MDS compared with adult MDS. In JMML, in addition to the known Ras-pathway mutations, novel secondary mutations and causative fusion genes have been reported. This review aims to summarize the recent progress in the research of the pathogenesis of childhood MDS and JMML.


Different effects of the DRD4 genotype on intrinsic brain network connectivity strength in drug-naïve children with ADHD and healthy controls.
The dopamine D4 receptor gene (DRD4) has been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). Recent studies have linked DRD4 to functional connectivity among specific brain regions. The current study aimed to compare the effects of the DRD4 genotype on functional integrity in drug-naïve ADHD children and healthy children. Resting-state functional MRI images were acquired from 49 children with ADHD and 37 healthy controls (HCs). We investigated the effects of the 2-repeat allele of DRD4 on brain network connectivity in both groups using a parameter called the degree of centrality (DC), which indexes local functional relationships across the entire brain connectome. A voxel-wise two-way ANCOVA was performed to examine the diagnosis-by-genotype interactions on DC maps. Significant diagnosis-by-genotype interactions with DC were found in the temporal lobe, including the left inferior temporal gyrus (ITG) and bilateral middle temporal gyrus (MTG) (GRF corrected at voxel level p < 0.001 and cluster level p < 0.05, two-tailed). With the further subdivision of the DC network according to anatomical distance, additional brain regions with significant interactions were found in the long-range DC network, including the left superior parietal gyrus (SPG) and right middle frontal gyrus (MFG). The post-hoc pairwise analysis found that altered network centrality related to DRD4 differed according to diagnostic status (p < 0.05). This genetic imaging study suggests that the DRD4 genotype regulates the functional integration of brain networks in children with ADHD and HCs differently. This may have important implications for our understanding of the role of DRD4 in altering functional connectivity in ADHD subjects.


Composite Resin Preheating Techniques for Cementation of Indirect Restorations.
Resin-based materials have been preheated by using different techniques and commercial devices. However, a consensus on the clinical protocol for cementing with preheated composite resins is lacking. The aim of this scoping review was to identify the different methods used for heating composite resins as used for cementing indirect adhesive restorations and to determine the benefits and limitations. Study Selection. A search was performed on PubMed/MEDLINE, Embase, Cochrane, Web of Science, Scopus, LIVIVO, and the nonpeer-reviewed literature database. Studies on preheating composite resins for cementing indirect restorations were included, with no restrictions on the type of study, year of publication, or language. The following data were extracted: preheating technique, the device used for preheating, preset temperature, and warming time. In total, 304 studies were identified. After removing duplicates, 270 articles were selected, and 14 articles were included in the final evaluation. Half of the included studies reported similar preheating techniques using the Calset device for composite resins. The temperatures of 54°C and 68°C were most frequently reported, with a mean warming time of 5 minutes. Preheating composite resins for the cementation of indirect restorations reduces viscosity, but the material must be used promptly after removal from the device. Practical Implications. Different methodologies for preheating composite resins have been reported and used in clinical dental practice. To achieve good results and guide the clinician on use, the techniques for heating composite resins for cementation need to be standardized. Keeping the material warm until the restorative procedure, the thickness of the indirect restoration, and the composition of the composite resins can directly affect the outcome of the procedure.


Atorvastatin Attenuates Metabolic Remodeling in Ischemic Myocardium through the Downregulation of UCP2 Expression.
Uncoupling protein 2 (UCP2) is primarily expressed in the myocardium and is closely related to myocardial ischemia/reperfusion injury and myocardial metabolism. To explore the effects and the mechanisms of UCP2 on atorvastatin-mediated myocardium protection, the rat model of myocardial ischemia was established by ligation of the left anterior descending coronary arteries (LADs). The rats were divided into the sham operation (SO) group, myocardial infarction (MI) group and MI-atorvastatin group. The study that atorvastatin reduced myocardial remodeling and improved the disturbed myocardial energy metabolism after MI. Furthermore, the mechanisms of myocardial metabolic remodeling affected by atorvastatin were explored. The atorvastatin group showed a significantly decreased expression of UCP2 mRNA and protein. Furthermore, the primary rat cardiomyocytes were cultured and treated with angiotensin II (Ang II) to induce cardiomyocyte hypertrophy. The results showed that in the atorvastatin group, the surface area of the cardiomyocytes, the total protein content per unit of cells, and the expression of the UCP2 protein were significantly decreased. These data suggested that atorvastatin significantly attenuated the myocardial remodeling by downregulating the expression of UCP2 that was found to improve the myocardial energy metabolism, inhibit myocardial hypertrophy, and eventually reduce myocardial remodeling.


Prevalence and Prognostic Significance of Functional Mitral and Tricuspid Regurgitation Despite Preserved Left Ventricular Ejection Fraction in Atrial Fibrillation Patients.
We investigated the prevalence and prognostic significance of functional mitral regurgitation (MR) and tricuspid regurgitation (TR) in patients with atrial fibrillation (AF) and preserved left ventricular ejection fraction (LVEF).Methods and Results:We retrospectively studied the cases of 11,021 consecutive patients who had undergone transthoracic echocardiography. AF appeared in 1,194 patients, and we selected 298 with AF and LVEF ≥50% but without other underlying heart diseases. Moderate or greater (significant) degree of functional MR and of TR was seen in 24 (8.1%) and in 44 (15%) patients, respectively (P=0.0045). In contrast, significant MR and TR were more frequently seen in patients with AF duration >10 years (28% vs. 25%, respectively). During the follow-up period of 24±17 months, 35 patients (12%) met the composite endpoint defined as cardiac death, admission due to heart failure, or mitral and/or tricuspid valve surgery. On Cox proportional hazard ratio analysis, both MR and TR grading predicted the endpoint, independently of other echocardiographic parameters. On Kaplan-Meyer analysis, presence of both significant functional MR and TR was associated with poor prognosis, with an event-free rate of only 21% at the mean follow-up period of 24 months. Significant functional MR and TR are seen in a substantial proportion of patients with longstanding AF, despite preserved LVEF. This MR/TR combination predicts poor outcome for AF patients, who may have to be treated more intensively.


[Small bowel obstruction caused by postoperative adhesions: personal experience and review of the literature].
Small bowel obstruction due to postoperative adhesions still remains an important matter in terms of frequency, diagnostic and therapeutic commitment and costs. The Authors report on a series observed over 14 years consisting of 63 patients (71 cumulative hospital admissions). Surgery was required in 42 cases (59.2%), 23 cases were treated in emergency and 19 cases after failure of conservative treatment. In 29 cases (69%) the surgical procedure was limited to adhesiolysis, whereas in 13 cases (31%) an intestinal resection was performed. During operation the mechanisms responsible for obstruction were: strangulation by an adhesive band (39.4%), angulation (34%), bowel loops and volvulus glued together (13.2% in each case). The operative mortality was 4.7% (2 cases). In 29 cases (40.8%), after medical treatment, the obstruction was completely resolved within a mean period of 4.15 days (range: 2-8). The results lead to the conclusion that diagnostic accuracy in cases of obstruction due to postoperative adhesions is still uncertain. The main aspects of treatment and surgical timing are left to the surgeon's personal experience. Medical treatment, however, should be the first therapeutic option and, in case of doubt, further diagnostic investigations are necessary (mainly CT) to identify those cases amenable to surgical treatment.


Single cell morphology distinguishes genotype and drug effect in Hereditary Spastic Paraplegia.
A central need for neurodegenerative diseases is to find curative drugs for the many clinical subtypes, the causative gene for most cases being unknown. This requires the classification of disease cases at the genetic and cellular level, an understanding of disease aetiology in the subtypes and the development of phenotypic assays for high throughput screening of large compound libraries. Herein we describe a method that facilitates these requirements based on cell morphology that is being increasingly used as a readout defining cell state. In patient-derived fibroblasts we quantified 124 morphological features in 100,000 cells from 15 people with two genotypes (SPAST and SPG7) of Hereditary Spastic Paraplegia (HSP) and matched controls. Using machine learning analysis, we distinguished between each genotype and separated them from controls. Cell morphologies changed with treatment with noscapine, a tubulin-binding drug, in a genotype-dependent manner, revealing a novel effect on one of the genotypes (SPG7). These findings demonstrate a method for morphological profiling in fibroblasts, an accessible non-neural cell, to classify and distinguish between clinical subtypes of neurodegenerative diseases, for drug discovery, and potentially for biomarkers of disease severity and progression.


Genetic and environmental correlation and path coefficient analysis of fruit yield per bush and other traits in black currants (Ribes nigrum L.).
Twenty-five F1 hybrid families of black currants (Ribes nigrum L.) originating from diallel crosses of five cultivars were assessed. Phenotypic correlation coefficient between full-sib family means (rFS), genetic correlation coefficient between full-sib family expected values (rG) and the environmental correlation were estimated on the basis of two years of observations for 12 quantitative characteristics studied. Evident repeatability of correlations in both years was proved. A considerable consistency between the values of genetic and phenotypic correlation coefficients was also observed. Coefficients of phenotypic and environmental correlation were significant for many pairs of traits. Most of the significant environmental correlation coefficients were found for the same pairs of characteristics for which phenotypic correlation coefficients were significant. This shows that genetic and environmental factors affected similar traits. Fruit yield expressed the largest number of significant correlations with other traits. Path coefficient analysis indicated that plant and berry size were the main factors influencing directly fruit yield in both years. It was proved that the number and length of one-year-old shoots via bush size had very large indirect effects on fruit yield per plant.


Attentive transformer deep learning algorithm for intrusion detection on IoT systems using automatic Xplainable feature selection.
Recent years have witnessed an in-depth proliferation of the Internet of Things (IoT) and Industrial Internet of Things (IIoT) systems linked to Industry 4.0 technology. The increasing rate of IoT device usage is associated with rising security risks resulting from malicious network flows during data exchange between the connected devices. Various security threats have shown high adverse effects on the availability, functionality, and usability of the devices among which denial of service (DoS) and distributed denial of service (DDoS), which attempt to exhaust the capacity of the IoT network (gateway), thereby causing failure in the functionality of the system have been more pronounced. Various machine learning and deep learning algorithms have been used to propose intelligent intrusion detection systems (IDS) to mitigate the challenging effects of these network threats. One concern is that although deep learning algorithms have shown good accuracy results on tabular data, not all deep learning algorithms can perform well on tabular datasets, which happen to be the most commonly available format of datasets for machine learning tasks. Again, there is also the challenge of model explainability and feature selection, which affect model performance. In this regard, we propose a model for IDS that uses attentive mechanisms to automatically select salient features from a dataset to train the IDS model and provide explainable results, the TabNet-IDS. We implement the proposed model using the TabNet algorithm based on PyTorch which is a deep-learning framework. The results obtained show that the TabNet architecture can be used on tabular datasets for IoT security to achieve good results comparable to those of neural networks, reaching an accuracy of 97% on CIC-IDS2017, 95% on CSE-CICIDS2018 and 98% on CIC-DDoS2019 datasets.


Successful use of blunt microdissection catheter in a chronic total occlusion of a celiomesenteric artery.
Chronic mesenteric ischemia is often a disabling condition associated with intestinal angina, weight loss, and sitophobia (a morbid aversion of food). Significant stenosis of two of the three main arteries of the gut is usually required to produce symptoms. Surgical therapy has included reimplantation and bypass grafting, usually with synthetic conduits and occasionally endarterectomy. Newer techniques have made endovascular treatment an emerging modality in managing some of the difficult lesions in the mesenteric circulation that cause chronic mesenteric ischemia. We describe the first reported case of blunt microdissection using a Frontrunner XP(R) CTO Catheter (Lumend, Redwood City, CA) to successfully cross, subsequently wire and stent a four-year-old chronic total occlusions in a celiac trunk, which also gave origin to the superior mesenteric artery.


[A case of non-specific interstitial pneumonia associated with psoriasis vulgaris and polymyalgia rheumatica].
We describe the first case, to the best of our knowledge, of non-specific interstitial pneumonia associated with psoriasis vulgaris and polymyalgia rheumatica (PMR). A 50-year-old woman was admitted with a dry cough and a bilateral basilar reticulonodular shadows on chest X-ray. Bronchoalveolar lavage fluid analysis revealed lymphocytosis and a decreased CD4/CD8 ratio. A thoracoscopic lung biopsy specimen showed evidence of non-specific interstitial pneumonia. During her clinical course, she began suffering from psoriasis vulgaris and polymyalgia rheumatica. Corticosteroid therapy had no effect, but maintained a stable condition during a follow-up period of 4 years.


Safety evaluation of water-soluble palm fruit bioactives.
Water-soluble palm fruit bioactives, derived from the aqueous stream of palm oil processing, have shown anti-diabetogenic effects in rodent models. To assess the safety of potential incorporation of this polyphenol-containing material in food, in vitro bacterial reverse mutation and in vitro chromosome aberration assays were conducted along with a 90-day subchronic toxicity study in Sprague-Dawley rats. Water-soluble palm fruit bioactives were inactive in the Ames and in vitro chromosome aberration assays up to the limit doses of 5000 μg/plate and 5000 μg/mL, respectively. In the 90-day feeding study, water-soluble palm fruit bioactives were administered via gavage at doses 0, 500, 1000 or 2000 mg/kg body weight/day. No significant effects were noted on body weight, food consumption, hematology, clinical chemistry, organ weights, and histopathological examination. The No Observable Adverse Effect Level was considered to be 2000 mg/kg body weight/day, the highest dose tested. These data provide evidence to support the safe use of water-soluble palm fruit bioactives in food or food ingredients.


Differential STAT5 activation and phenotypic marker expression by immune cells following low levels of ethanol consumption in mice.
Ethanol has been recognized as an immunosuppressive agent for many years. Effects of high levels of ethanol consumption on immune functions have been extensively studied, but little is known about the effects of low levels (scuh as 5% ethanol) of ethanol consumption. Herein we report that exposure of mice to 5% ethanol for 4-8 weeks decreases IL-2-augmented splenic NK cell activity, decreases the numbers of NK cells in spleen and liver, decreases the number of granulocytes (Gr-l+) in bone marrow and spleen, and decreases the percentages of B cells in liver. In contrast, the percentages of CD4+CD8+ thymocytes, CD4+CD8- splenocytes, CD4+CD8- liver nonparenchymal cells, CD3+ splenocytes, and CD3+ bone marrow cells were increased. Furthermore, exposure to 5% ethanol increases STAT5 activation in T cells and liver cells while decreases STAT5 activation in NK cells. Taken together, these findings suggest that low levels of ethanol consumption can differentially modulate immune cells in thymus, spleen, bone marrow and liver, which may be due to differential regulation of STAT5 activation by ethanol.


Acquired resistance to the 16-membered macrolides tylosin and tilmicosin by Mycoplasma bovis.
The molecular mechanism of acquired resistance to the 16-membered macrolides tylosin (Ty) and tilmicosin (Tm) was investigated in Mycoplasma bovis field isolates. Sequence analysis of domains II and V of the two 23S rRNA alleles and ribosomal proteins L4 and L22 was performed on 54 M. bovis isolates showing different minimal inhibitory concentrations (MIC). The presence of any one of the point mutations G748A, C752T, A2058G, A2059G or A2059C (Escherichia coli numbering) in one or both alleles of the 23S rRNAs was correlated with decreased susceptibility to Ty (8-1024 μg/ml) and to Tm (32 to >256 μg/ml) in 27/27 and 27/31 M. bovis isolates, respectively. Although a single mutation in domain II or V could be sufficient to cause decreased susceptibility to Ty, our data imply that a combination of mutations in two domains is necessary to achieve higher MICs (≥ 128 μg/ml). The influence of a combination of mutations in two domains II and V on enhancement of resistance to Tm was less clear. In addition, the amino acid (aa) substitution L22-Q90H was found in 24/32 representative M. bovis isolates with different MICs, but no correlation with decreased susceptibility to Ty or Tm was identified. Multiple aa substitutions were also identified in the L4 protein, including at positions 185-186 (positions 64 and 65 in E. coli) which are adjacent to the macrolide-binding site. This is the first description of the molecular mechanism of acquired resistance to the 16-membered macrolides in M. bovis.


[Current estimate of the number of patients for liver transplantation with Dutch mortality figures].
To estimate the number of liver transplantations needed in the Netherlands, using death rates of the two periods 1979-1981 and 1989-1991. Death rates of different liver diseases were divided into: generally accepted indications (transplantable liver diseases, TLD), alcoholic liver cirrhosis, ALC and primary liver cell carcinoma, PLC. The death rates in the two periods, 1979-1981 and 1989-1991, were compared, and the impact of liver transplantation was determined. Subsequently an estimate of the maximum number of patients for liver transplantation in the Netherlands was made, based on death rates. Mortality of TLD and PLC rose 14% and 7% respectively, while it dropped 13% for ALC. In the period 1989-1991 liver transplantation appeared to have had a quantitative effect on mortality, especially in the youngest age groups. In the age group 0-59 the maximum number of patients for liver transplantation per year was estimated to be 147, nearly 10 per million inhabitants, excluding ALC and PLC. In the period 1989-1991 21% of deceased TLD patients up to age 60 received liver transplantation in the Netherlands.


The properties of Co- and Fe-doped GDC for low-temperature processing of solid oxide fuel cell by electron-beam evaporation.
This study is transition metal oxides (FeO and CoO) were added to Gd-doped ceria (Gd0.1Ce0.9O1.95, GDC) powder for preparing the thin-film electrolyte used in the Ni-GDC anode-supported intermediate temperature solid oxide fuel cell (SOFC). Recently much attention was aimed at successful powder preparation with high sinter activity and conductivity. However, one of the challenges in preparing the GDC electrolytes is the densification issue. It is difficult to achieve the densification of GDC below 1600 degrees C. To overcome this drawback, attentions of the research on the densification of the GDC electrolyte is paid more on changing of the fabrication technology, the powder properties, and the sintering mechanism. Among them, Fe3+ and Co2+ showed the significant beneficial effect on the grain boundary conductivity. So, electrolyte powder made of Co- and Fe-doped GDC by solid-state reaction method. And thin-film electrolyte was fabricated on the presintered Ni-GDC cermet anode substrate by E-beam evaporating method and then co-sintered to form the electrolyte/anode bilayer. We realized crystal structure of Co and Fe doped Gd0.1Ce0.9O1.95 (GDC) electrolyte by X-ray diffraction (XRD). The morphology was measured by scanning electron microscopy (SEM) for the sintered samples were performed. The performance of the cells was evaluated over 500-800 degrees C using humidified hydrogen as fuel and air as oxidant.


[Off-pump coronary artery bypass grafting via a left thoracotomy in a patient with left main trunk disease].
We report a case of multiple coronary artery bypass grafting (CABG) via a left thoracotomy without cardiopulmonary bypass. A 54-year-old female with unstable angina pectoris associated with left main trunk disease underwent emergency CABG. Because the patient had a history of total arch and aortic root replacement due to type A aortic dissection, a left thoracotomy approach was selected. The proximal end of the Y-shaped saphenous vein graft was anastomosed to the left subclavian artery, rather than to the descending aorta, owing to the remaining aortic dissection. The distal end of the Y-shaped saphenous vein graft was anastomosed to the left anterior descending artery and the posterolateral branch without cardiopulmonary bypass. The postoperative course was uneventful. The results of this surgery seem to indicate that off-pump CABG via a left thoracotomy is a viable technique, especially for patients undergoing repeat CABG.


Measuring tobacco dependence in the general population: Evaluation of the Cigarette Dependence Scale (CDS-12) and its adaptation to smokeless tobacco use (STDS-12) in two Swedish surveys.
The 12-item Cigarette Dependence Scale (CDS-12) is an instrument suitable to assess tobacco dependence in non-clinical populations. The aim of this study was twofold: a) to evaluate the scale's performance in a smoking population including non-daily smokers; b) to explore the scale's adaptation to the assessment of dependence on smokeless tobacco. In a cross-sectional study we investigated performance and construct validity of the CDS-12 and of its adaptation to smokeless tobacco (STDS-12) in two Swedish population samples. The first sample consisted of young adults (1246 ever daily smokers and 1086 ever daily snus (the Swedish type of moist oral snuff) users between 19 and 28 years of age). The second sample included 1229 current smokers and 855 current users of snus between 16 and 84 years of age. Score distribution, internal consistency, factor structure, and associations with other indicators of tobacco dependence were analysed. Both scales had a small amount of missing answers (below 2% in most items) and had acceptable internal consistency. Factor analyses suggested a one-factor model. CDS-12 score and proportions classified as dependent were significantly higher among daily smokers compared to non-daily smokers, positively correlated with the number of cigarettes, and negatively with quit attempts as well as their duration. The same pattern was seen for STDS-12, apart from correlation with quit attempts. Both the CDS-12 and its adaptation to smokeless tobacco, tested for the first time in this study, appear to perform well in population-based samples including young and non-daily tobacco users.


The relationship between mercury and autism: A comprehensive review and discussion.
The brain pathology in autism spectrum disorders (ASD) indicates marked and ongoing inflammatory reactivity with concomitant neuronal damage. These findings are suggestive of neuronal insult as a result of external factors, rather than some type of developmental mishap. Various xenobiotics have been suggested as possible causes of this pathology. In a recent review, the top ten environmental compounds suspected of causing autism and learning disabilities were listed and they included: lead, methyl-mercury, polychorinated biphenyls, organophosphate pesticides, organochlorine pesticides, endocrine disruptors, automotive exhaust, polycyclic aromatic hydrocarbons, polybrominated diphenyl ethers, and perfluorinated compounds. This current review, however, will focus specifically on mercury exposure and ASD by conducting a comprehensive literature search of original studies in humans that examine the potential relationship between mercury and ASD, categorizing, summarizing, and discussing the published research that addresses this topic. This review found 91 studies that examine the potential relationship between mercury and ASD from 1999 to February 2016. Of these studies, the vast majority (74%) suggest that mercury is a risk factor for ASD, revealing both direct and indirect effects. The preponderance of the evidence indicates that mercury exposure is causal and/or contributory in ASD.


[Studies on chemical constituents of Tinospora hainanesis].
Tinospora hainanesis is a new species of Menispermaceae plant. It is used as folk remedy for joint pain and physical injury. Five compounds were isolated from the vine stalk of Tinospora hainanesis. By spectral analysis and chemical methods, the structures of the compounds were identified as makisterone A (I), 2,3-dimethoxy-9,10-dihydroxy-N-methyltetrahydroproto-berberine quaternary salt (II), palmatine (III), beta-amyrin (IV) and docosyl ferulate (V). II is a new quaternary alkaloid named as haitinosporine. I, IV and V were isolated for the first time from the plants of Tinospora genus.


Age-related mushroom body expansion in male sweat bees and bumble bees.
A well-documented phenomenon among social insects is that brain changes occur prior to or at the onset of certain experiences, potentially serving to prime the brain for specific tasks. This insight comes almost exclusively from studies considering developmental maturation in females. As a result, it is unclear whether age-related brain plasticity is consistent across sexes, and to what extent developmental patterns differ. Using confocal microscopy and volumetric analyses, we investigated age-related brain changes coinciding with sexual maturation in the males of the facultatively eusocial sweat bee, Megalopta genalis, and the obligately eusocial bumble bee, Bombus impatiens. We compared volumetric measurements between newly eclosed and reproductively mature males kept isolated in the lab. We found expansion of the mushroom bodies-brain regions associated with learning and memory-with maturation, which were consistent across both species. This age-related plasticity may, therefore, play a functionally-relevant role in preparing male bees for mating, and suggests that developmentally-driven neural restructuring can occur in males, even in species where it is absent in females.


Crypt cell thymidine incorporation in ileal urinary pouch. Preliminary report.
This is a brief communication about mucosal change in ileal urinary reservoirs, the earliest reported observations to date. Previous authors described early villous atrophy and crypt elongation, late panmucosal atrophy and metaplasia. Crypt cell proliferation should be a forerunner of these events and therefore warrants quantitative measurement. We studied continent pouches in dogs on postoperative days 42 and 43 using in vivo tritiated thymidine incorporation into crypt cell DNA, a novel application of autoradiography for urinary reservoirs. Adjacent normal ileum provided the internal control. Increased crypt cell thymidine incorporation was confirmed at this early time.


[Warning signs and symptoms on obstetric care. About their knowledge in women].
maternal mortality is caused by delays in recognizing complications at the medical facility. Maternal mortality increased during 2009 in Guanajuato, reflecting deficiencies in the care process. The objective was to determine the knowledge about signs and symptoms that pregnant and non-pregnant patients considered as obstetric emergency data during pregnancy, childbirth and postpartum. a descriptive and comparative study in 150 pregnant and 150 non pregnant women aged 18 to 40 years was performed. A structured questionnaire was applied. The statistical analysis was performed in NCSS 2007 program. alarm sign and symptoms during pregnancy were identified by 72.2 % of the non-pregnant; at birth 54.4 % and 46.2 % in puerperium. The 92.9 % of pregnant women identified alarm sign and symptoms during pregnancy, during childbirth only 62.7 % and in postpartum 25 %. There was an association between previous pregnancy and knowing alarm signs and symptoms and the number of inquiries received. knowing the warning signs is related to previous obstetrical deliveries and by the educational work of the family physician during prenatal care.


Association of OLE RNA with bacterial membranes via an RNA-protein interaction.
Ornate, large, extremophilic (OLE) RNAs are large, non-coding transcripts characterized by their ornate secondary structure and presence predominantly in Gram-positive, extremophilic bacteria. A gene for an OLE-associated protein (OAP) is almost always located immediately downstream of the OLE gene. OAP has no extensive homology to other proteins and is predicted to form multiple transmembrane domains. We show that this protein forms a ribonucleoprotein complex with OLE RNA using at least 2:1 protein : RNA stoichiometry. A series of truncated OLE RNA constructs was used to establish that most of the RNA can be deleted without eliminating protein binding. Two primary binding sites are present within the RNA, although additional binding determinants exist and extensive structural stabilization is induced by OAP. RNA fluorescence in situ hybridization (FISH) was used in Escherichia coli to demonstrate that ribonucleoprotein complex formation localizes the RNA near cell membranes of this heterologous system. Therefore, the majority of the complex structure formed by OLE RNA may perform a biochemical function that requires membrane localization.


Female repeat offenders negotiating identity.
This study examines the process of identity negotiation for Israeli female ex-convicts who were separated for extensive periods of time from their children and eventually lost custody over them. The content analysis of in-depth interviews reveals that these women were able to reconstruct their biographies and retrospectively account for their crimes and drug addiction in terms of the sexual, physical, and economic abuse they had endured and by appeal to higher loyalties, their children who they had to provide for. However, when having to account for their fallings as mothers, all biographical reconstruction, external blame, and accusation collapsed. Looking at themselves through their children's eyes, female offenders were simply unable to renegotiate the imputed identity of incompetent mother. They could neither confront their children's anger nor explain to them why they had abandoned them. Permanently alienated from the center of motherhood, these women were doomed to an existential chaos.


[SPRINT study: far lower systolic blood pressure].
There is still no consensus, which blood pressure value is the most profitable for the patients when treating the systolic hypertension in the context of reduction of cardiovascular events and cardiovascular and overall mortality.Researchers of the ACCORD study were comparing intensive treatment of systolic blood pressure bellow 120 mmHg and standard treatment reaching bellow 140 mmHg and showed no influence of intensive treatment on the primary goal in individuals with diabetes mellitus.Last autumn, SPRINT study was presented and published showing the favourable effect of intensive (i. e. bellow 120 mmHg) blood pressure lowering on combined primary goal which was myocardial infarction, other acute coronary syndromes, ischemic stroke, heart failure or death from cardiovascular reasons. On the other hand, intensive treatment also resulted in statistically significant occurrence of adverse events (hypotension, syncope, renal injury of failure).


The controversy over the age of blood: what do the clinical trials really teach us?
Red blood cell transfusions have been used in clinical practice for decades and represent the most common therapeutic procedure performed in hospitalised patients. Depending on the storage solution and national regulatory requirements, red blood cells can be stored in the refrigerator up to 42 days before transfusion. We reviewed five of the most recent randomised clinical trials that examined clinical outcomes in specific patient populations. Although these studies provide some comfort regarding our current standard of care, they do not address whether the oldest blood is associated with harm in certain patient populations.


GluN3A: an NMDA receptor subunit with exquisite properties and functions.
N-methyl-D-aspartate receptors (NMDAR) are pivotal for synaptic plasticity and memory formation. Conventional NMDAR consist of heterotetrameric structures composed of GluN1 and GluN2 subunits. A third subunit, GluN3, can also assemble with NMDAR subunits giving a remarkable modification of their heteromeric structure, forming a "nonconventional" NMDAR. As a consequence, the stoichiometry and kinetic properties of the receptors are dramatically changed. Among the GluN3 family, the GluN3A subunit has been the focus of a large amount of studies during recent years. These studies reveal that GluN3A is transiently expressed during development and could play a role in the fine tuning of neuronal networks as well as associated diseases. Moreover, GluN3A distribution outside the postsynaptic densities, including perisynaptic astrocytes, places it at a strategic position to play an important role in the interactions between neurons and glial cells. This review highlights GluN3A properties and addresses its role in neurophysiology and associated pathologies.


Salt intake and blood pressure in the general population: a controlled intervention trial in two towns.
A controlled trial was conducted in two Belgian towns to investigate the feasibility and effects of a reduction in salt consumption at the community level. The low-sodium intervention in one town was mainly directed at women and implemented through mass media techniques, while the control town was merely observed. Cross-sectional random sampling at baseline and 5 years later was employed, the participation rate being similar (67%) in the two towns. During the study a total of 2211 subjects were examined. In adult women (greater than or equal to 20 years) in the intervention town the 24-h urinary excretion of sodium (UVNa) decreased by 25 mmol/24 h (P less than 0.001) and this reduction differed (P = 0.01) from the concurrent trend in UVNa in the control town (+8 mmol/24 h). However, both systolic (SBP, -7.5 versus -7.9 mmHg) and diastolic (DBP, -2.3 versus -3.0 mmHg) pressures declined to a similar extent in the women from the two towns. In adult men in the intervention town, decreases were observed in UVNa (-12 mmol/24 h) and in SBP (-5.6 mmHg) and DBP (-2.4 mmHg), but these trends were not significantly different from the concurrent changes in the control town (-14 mmol/24 h, -4.9 and +0.2 mmHg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


The role of Na,K-ATPase in human sperm motility.
A fourth Na,K-ATPase alpha isoform, which was found to be abundant in testes, was proved to be a catalytical subunit of the enzyme. Recently, it has been shown that the alpha 4 isoform along with alpha 1 is expressed in the midpiece of the flagellum of mature rat sperm and the inhibition of alpha 4 with ouabain led to sperm immotility. In this study, sperm from 135 males with normal semen profile and 50 males with oligoasthenospermia were treated with 10-5 and 10-2 M ouabain solutions to inhibit alpha 4, and alpha 4 plus alpha 1 isoforms, respectively. In males with normal semen profile, sperm motility has been demonstrated to decrease with time to almost the same level with both ouabain solutions. In oligoasthenospermic males motility was also found almost completely lost. These observations showed us that the alpha 4 isoform may be held responsible for human sperm motility. When sperm plasma membrane Na,K-ATPase activity was assayed for both normal and oligoasthenospermic males, a significant decrease in enzyme activity of males with oligoasthenospermia was observed (p < 0.05). In our recent study, sperm motility was found decreased by treatment with peroxynitrite (ONOO-). To investigate the effect of ONOO- on sperm Na,K-ATPase activity, sperm plasma membranes were treated with 100 microM ONOO- and plasma membrane Na,K-ATPase activity was observed to be significantly decreased (p < 0.05). Although total sulfhydryl (SH) content of sperm plasma membrane was also found significantly lower, no correlation was found between Na,K-ATPase activity and SH content.


Open globe injuries in geriatric population in Iran: characteristics and outcomes.
To investigate the patterns and outcomes of open globe injuries in the elderly population in Iran. In this retrospective cross-sectional chart review, medical records of 248 patients (aged 60y and more) with the diagnosis of open globe injury from 2006 to 2016 were reviewed. Demographic features, type, and mechanism of open globe injury, ocular trauma score (OTS), visual acuity before and after treatment, the zone of injuries, and the associated injuries found at the presentation or thereafter were documented. A total of 248 eyes of 248 patients were included. The mean age was 69.2±5.8y (range: 60-90y). Male/ female ratio was about 3:1 (187 vs 61). The three most common causes of injury were falling (25.2%), sharp objects (18.9%), and tree branches (13.9%). Penetrating injury accounted for most of the geriatric ocular trauma (50.4%), followed by globe rupture (40.3%), intraocular foreign body (IOFB; 7.3%), and perforating injury (2.0%). The median raw OTS for the population was 60.5 and the most common OTS class was 3. The injuries tend to affect zone I more than zone II and zone III. The only predictor of final visual acuity was the class of OTS (P<0.001). Geriatric open globe injury should be valued specifically. The most common type of open globe injury in Iran is penetrating injuries but falling remain the main cause. The OTS class must be considered as an important predictor of final visual acuity.


Disordered eating behavior, health and motives to exercise in young men: cross-sectional population-based MOPO study.
Being overweight is an increasing problem among young people, among whom disordered eating behavior is linked with weight problems as well as unhealthy weight control. The aim of the present study was to investigate whether health factors and motives to exercise differ in young men by the type of disordered eating behavior. The population-based, cross-sectional MOPO study consisted of 2,096 young Finnish men (mean age 17.9, SD 0.7) attending compulsory call-ups for military service in the Oulu area in 2010, 2011, and 2013. They responded to a questionnaire that included two subscales of the Eating Disorder Inventory-3 indicating drive for thinness and bulimic behavior and questions on health, physical activity, and motives to exercise. The association between disordered eating behavior and related factors was analyzed by binary logistic regression. Altogether, 6.9 % (n = 145) of the men had symptoms of disordered eating, i.e., 5.4 % had a drive for thinness (n = 114) and 3.7 % had bulimic behavior (n = 77). Drive for thinness was associated with a perception of being overweight (OR 3.7; 95 % CI 2.2-6.1), poor self-rated health (2.3; 1.2-4.4), more leisure sitting time (1.1; 1.0-1.2), and body-related exercise motives (body acceptance: 3.0; 1.7-5.2; weight loss: 2.5; 1.4-4.4). Bulimic behavior was positively associated with poor self-rated health (2.6; 1.1-5.8) and several motives to exercise, i.e., due to another person's suggestion (2.8; 1.6-4.8), competitive sports (2.1; 1.2-3.7), body acceptance (2.1; 1.1-3.9), and weight loss (1.9; 1.1-3.3), but inversely associated with health/fitness-related exercise motives (health promotion: 0.3; 0.1-0.5; muscular strength or physical performance: 0.5; 0.2-0.9). In young men, disordered eating behavior was associated with being overweight, having poor self-rated health, and having a greater amount of leisure sitting time as well as non-health-related motives to exercise. In order to recognize those at risk for disordered eating behavior, evaluating these factors could be beneficial.


Mycobacterium tuberculosis metabolism.
Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances-in particular, the development of systems biology tools such as metabolomics-have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mechanisms of action of new and existing antituberculosis drugs is critical for the development of improved interventions to counter tuberculosis. This review provides a broad summary of mycobacterial metabolism, highlighting the adaptation of M. tuberculosis as specialist human pathogen, and discusses recent insights into the strategies used by the host and infecting bacillus to influence the outcomes of the host-pathogen interaction through modulation of metabolic functions.


The plight of parents/caregivers of children with heart disease in the rural areas of Namibia: a problem of coping.
Providing care for a child with heart disease is a daunting task for any parent/caregiver, particularly for those living in poor conditions in rural Namibia. A qualitative, exploratory, phenomenological and contextual study was conducted to describe such parents'/caregivers' experiences of providing care for a child with a heart disease. The study also examined the children's experiences of living with the burden of disease at home. The findings revealed experiences of emotional turmoil, disruptive social functioning and social relations, lack of support from the family, lack of organised forms of support from societal organisations, as well as experiences of low vitality among the children. These experiences together signify the overall poor coping by the parents/caregivers and the children. This paper presents the findings of a situational analysis of the experiences of caring for a child with heart disease and of living with heart disease.


Play therapy: a nursing intervention.
Play therapy is a viable nursing intervention used in a multitude of settings and in a multidisciplinary fashion. Therapeutic play interventions can be directed or non-directed, as well as used in recreational, therapeutic, or dramatic forms. Children need play opportunities.


Charge Oscillations in Bilayer Graphene Quantum Confinement Devices.
Quantum confinement structures are building blocks of quantum devices in fundamental physics exploration and technological applications. In this work, we fabricate dual-gated bilayer graphene Fabry-Pérot quantum Hall interferometers employing two different gating strategies and conduct finite element simulations to understand the electrostatics of the confinement structures and to guide device design and fabrication. We observe two types of resistance oscillations arising from the charging of quantum dots formed inside the interferometers. We obtain the size, location, and charging energy of the dots by measuring the dependence of the oscillations on the magnetic field, gate voltages, and dc bias. We analyze and discuss the origin of the quantum dots and their impact on quantum Hall edge state backscattering and interference. Insights gained in these studies shed light on the construction of van der Waals quantum confinement devices.


Experience with the recovery filter as a retrievable inferior vena cava filter.
This study evaluates clinical experience with the Recovery filter as a retrievable inferior vena cava (IVC) filter. One hundred seven Recovery filters were placed in 106 patients with an initial clinical indication for temporary caval filtration. Patients were followed up to assess filter efficacy, complications, eventual need for filter removal, time to retrieval, and ability to remove the filter. The patient cohort consisted of 62 men and 44 women with a mean age of 48 years (range, 18-90 y). Mean implantation time was 165 days. Indications for filter placement in patients with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) included contraindication to anticoagulation (n = 33), complications of anticoagulation (n = 8), poor cardiopulmonary reserve (n = 6), large clot burden (n = 3), and PE while receiving anticoagulation (n = 1). Indications for filter placement in patients without proven PE or DVT included immobility after trauma (n = 35); recent intracranial hemorrhage, neurosurgery, or brain tumor (n = 18); and other surgical or invasive procedure (n = 3). Three patients (2.8%) had symptomatic PE after placement of the Recovery filter. No caval thromboses were detected. No symptomatic filter migrations occurred. Recovery filter removal was attempted in 15 of 106 patients (14%) at a mean of 150 days after placement. The Recovery filter was successfully retrieved in 14 of 15 patients (93%); one removal was unsuccessful at 210 days after placement. Ninety-two filters (87%) currently remain in place. Although all the filters were placed with the intention of being removed, a large percentage of filters were not retrieved. The Recovery filter was safe and effective in preventing PE when used as a retrievable IVC filter.


Complex dark-field contrast and its retrieval in x-ray phase contrast imaging implemented with Talbot interferometry.
Under the existing theoretical framework of x-ray phase contrast imaging methods implemented with Talbot interferometry, the dark-field contrast refers to the reduction in interference fringe visibility due to small-angle x-ray scattering of the subpixel microstructures of an object to be imaged. This study investigates how an object's subpixel microstructures can also affect the phase of the intensity oscillations. Instead of assuming that the object's subpixel microstructures distribute in space randomly, the authors' theoretical derivation starts by assuming that an object's attenuation projection and phase shift vary at a characteristic size that is not smaller than the period of analyzer grating G₂ and a characteristic length dc. Based on the paraxial Fresnel-Kirchhoff theory, the analytic formulae to characterize the zeroth- and first-order Fourier coefficients of the x-ray irradiance recorded at each detector cell are derived. Then the concept of complex dark-field contrast is introduced to quantify the influence of the object's microstructures on both the interference fringe visibility and the phase of intensity oscillations. A method based on the phase-attenuation duality that holds for soft tissues and high x-ray energies is proposed to retrieve the imaginary part of the complex dark-field contrast for imaging. Through computer simulation study with a specially designed numerical phantom, they evaluate and validate the derived analytic formulae and the proposed retrieval method. Both theoretical analysis and computer simulation study show that the effect of an object's subpixel microstructures on x-ray phase contrast imaging method implemented with Talbot interferometry can be fully characterized by a complex dark-field contrast. The imaginary part of complex dark-field contrast quantifies the influence of the object's subpixel microstructures on the phase of intensity oscillations. Furthermore, at relatively high energies, for soft tissues it can be retrieved for imaging with a method based on the phase-attenuation duality. The analytic formulae derived in this work to characterize the complex dark-field contrast in x-ray phase contrast imaging method implemented with Talbot interferometry are of significance, which may initiate more activities in the research and development of x-ray differential phase contrast imaging for extensive biomedical applications.


Prediction of selective estrogen receptor beta agonist using open data and machine learning approach.
Estrogen receptors (ERs) are nuclear transcription factors that are involved in the regulation of many complex physiological processes in humans. ERs have been validated as important drug targets for the treatment of various diseases, including breast cancer, ovarian cancer, osteoporosis, and cardiovascular disease. ERs have two subtypes, ER-α and ER-β. Emerging data suggest that the development of subtype-selective ligands that specifically target ER-β could be a more optimal approach to elicit beneficial estrogen-like activities and reduce side effects. Herein, we focused on ER-β and developed its in silico quantitative structure-activity relationship models using machine learning (ML) methods. The chemical structures and ER-β bioactivity data were extracted from public chemogenomics databases. Four types of popular fingerprint generation methods including MACCS fingerprint, PubChem fingerprint, 2D atom pairs, and Chemistry Development Kit extended fingerprint were used as descriptors. Four ML methods including Naïve Bayesian classifier, k-nearest neighbor, random forest, and support vector machine were used to train the models. The range of classification accuracies was 77.10% to 88.34%, and the range of area under the ROC (receiver operating characteristic) curve values was 0.8151 to 0.9475, evaluated by the 5-fold cross-validation. Comparison analysis suggests that both the random forest and the support vector machine are superior for the classification of selective ER-β agonists. Chemistry Development Kit extended fingerprints and MACCS fingerprint performed better in structural representation between active and inactive agonists. These results demonstrate that combining the fingerprint and ML approaches leads to robust ER-β agonist prediction models, which are potentially applicable to the identification of selective ER-β agonists.


High dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma.
We report the results of peripheral blood stem cell (PBSC) collection performed after priming with a semi-intensive CHOP regimen in 70 patients with aggressive multiple myeloma (MM). Forty-one of the 44 previously untreated patients compared to 17 of the 26 patients with a refractory disease yielded stem cells enough for autotransplantation. Phenotypic and genotypic studies of collected mononuclear cells, even performed after depletion of monocytes and/or of T lymphocytes, did not reveal contamination by tumor plasma cells or clonal B cell precursors in any studied case. Forty-eight of the 58 patients with successful PBSC collection have been presently treated by high dose therapy followed by autologous blood stem cell transplantation (ABSCT). Among the 43 patients who received a regimen including total body irradiation, four died within six months after the autograft. All remainders responded and most often achieved an impressive tumor mass reduction. Ten relapsed and four died from disease progression. Nine to 70 months (median: 35 months) after blood stem cell collection, 29 patients are either in apparent complete remission or with a state of stable residual disease, most often minimal. Blood stem cell autograft was successful in all evaluable patients and the kinetic of hematologic recovery was roughly related to the amount of reinfused CFU-GM (2.1 to 50 x 10(4)/kg). Median delays for granulocytes greater than 500/mm3 and platelets greater than 25,000/mm3 were 15 days and 20 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Selective digestive decontamination in critically ill children: A survey of Canadian providers.
Selective digestive decontamination of the digestive tract involves the routine administration of oral, gastric, and intravenous antibiotics to mechanically ventilated children to prevent hospital-acquired infections. It has a strong evidence base in adults, with limited pediatric evidence. Current utilization of this intervention among pediatric physicians in North America is unknown. An electronic survey administered to pediatric critical care and pediatric infectious disease providers in Canada. Participants were surveyed on current institutional practices, their current knowledge of the evidence base, and perceptions of the risks and benefits of the intervention. Descriptive statistics were utilized. 50 out of 143 (35%) surveyed responded. No hospital in Canada routinely performs SDD and the majority of respondents (74%) have neutral opinions on the subject of SDD. There was concern for increasing antibiotic resistance (43%) and some disagreement with the intravenous component of SDD (46%). The majority of respondents stated a need for pediatric-specific evidence before integrating SDD into their practice, even if further, large adult RCTs were performed. Among surveyed providers, there is little knowledge and no use of selective digestive decontamination for the prevention of hospital-acquired infections. Before interventional studies are performed in pediatric practice, there is a need for study of facilitators, barriers and acceptability of SDD in practice.


A cell wall synthase accelerates plasma membrane partitioning in mycobacteria.
Lateral partitioning of proteins and lipids shapes membrane function. In model membranes, partitioning can be influenced both by bilayer-intrinsic factors like molecular composition and by bilayer-extrinsic factors such as interactions with other membranes and solid supports. While cellular membranes can departition in response to bilayer-intrinsic or -extrinsic disruptions, the mechanisms by which they partition de novo are largely unknown. The plasma membrane of Mycobacterium smegmatis spatially and biochemically departitions in response to the fluidizing agent benzyl alcohol, then repartitions upon fluidizer washout. By screening for mutants that are sensitive to benzyl alcohol, we show that the bifunctional cell wall synthase PonA2 promotes membrane partitioning and cell growth during recovery from benzyl alcohol exposure. PonA2's role in membrane repartitioning and regrowth depends solely on its conserved transglycosylase domain. Active cell wall polymerization promotes de novo membrane partitioning and the completed cell wall polymer helps to maintain membrane partitioning. Our work highlights the complexity of membrane-cell wall interactions and establishes a facile model system for departitioning and repartitioning cellular membranes.


Development of Low Molecular Weight Ligands for Integrin αvβ3.
We designed and synthesized non-peptide organic molecular ligands for integrin αvβ3. Candidate ligands featured amidino analog and carboxy groups as binding sites on either side of a spacer, which consisted of benzophenone or an analog, such as diphenyl sulfide, diphenyl sulfoxide, diphenyl sulfone, or diphenyl ether. Competitive binding assays to integrin αvβ3 with respect to [125I]echistatin were used to determine inhibitory activity of the synthetic ligands. Ligands bearing 2-aminobenzimidazoyl and glycyl groups separated by a benzophenone spacer demonstrated more potent binding than did a linear Arg-Gly-Asp (RGD) tripeptide that represents the native integrin αvβ3 binding motif. Ligands possessing 2-aminobenzimidazoyl and carboxy groups and diphenyl sulfoxide or diphenyl ether spacers inhibited binding of [125I]echistatin with IC50 values similar to that of the linear RGD tripeptide.


Nociceptin/orphanin FQ blocks the antinociception induced by mu, kappa and delta opioid agonists on the cold water tail-flick test.
Nociceptin/orphanin FQ (N/OFQ), a 17-amino-acid peptide, is an endogenous agonist whose receptor is similar in sequence to mu, delta and kappa opioid receptors. It has been reported that N/OFQ can block antinociceptive effects induced by opioid receptor agonists in the radiant heat tail-flick test and warm water tail-withdrawal test. The present study was designed to see the effect of N/OFQ on antinociception induced by opioid receptor agonists in the cold water tail-flick (CWT) test, which measures a different type of pain. In adult male Sprague-Dawley (S-D) rats given subcutaneous (s.c.) injections of saline or morphine (8 mg/kg), intracerebroventricular (i.c.v.) injection of N/OFQ (18 microg) 15 min later produced a significant reversal of morphine antinociception (P<0.01, ANOVA followed by Duncan's test), compared to the corresponding saline control group. Saline (t=+15 min, i.c.v.) had no effect on s.c. morphine antinociception (P>0.01), compared to the corresponding saline control group. When the kappa opioid receptor agonist spiradoline (80 mg/kg, s.c.) was used instead of morphine, similar results were observed. In another series of experiments, it was found that i.c.v. injection of N/OFQ (18 microg) reversed the antinociception induced by i.c.v. injection of the selective mu opioid agonist PL017 (2 microg), delta opioid agonist DPDPE (50 ng) and kappa opioid agonist dynorphin (21.5 microg), respectively. These results indicate that N/OFQ may be an endogenous anti-opioid peptide in the brain of rats in the CWT test.


Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway.
Oxidative stress has been identified as a major cause of cellular injury in a variety of neurodegenerative disorders. This study aimed to investigate the cytoprotective effects of piceatannol on hydrogen peroxide (H2O2)-induced pheochromocytoma-12 (PC-12) cell damage and explore the underlying mechanisms. Our findings indicated that piceatannol pre-treatment significantly attenuated H2O2-induced PC-12 cell death. Furthermore, piceatannol effectively improved mitochondrial content and mitochondrial function, including enhancing mitochondrial reactive oxygen species (ROS) elimination capacity and increasing mitochondrial transcription factor (TFAM), peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) and mitochondria Complex IV expression. Meanwhile, piceatannol treatment inhibited mitochondria-mediated autophagy as demonstrated by restoring mitochondrial membrane potential, reducing autophagosome formation and light chain 3B II/I (LC3B II/I) and autophagy-related protein 5 (ATG5) expression level. The protein expression level of SIRT3 was significantly increased by piceatannol in a concentration-dependent manner. However, the cytoprotective effect of piceatannol was dramatically abolished by sirtuin 3 (SIRT3) inhibitor, 3-(1H-1,2,3-Triazol-4-yl) pyridine (3-TYP), which led to an exacerbated mitochondrial dysfunction and autophagy in PC-12 cells under oxidative stress. In addition, the autophagy activator (rapamycin) abrogated the protective effects of piceatannol on PC-12 cell death. These findings demonstrated that piceatannol could alleviate PC-12 cell oxidative damage and mitochondrial dysfunction by inhibiting autophagy via the SIRT3 pathway.


Chryseobacterium chaponense sp. nov., isolated from farmed Atlantic salmon (Salmo salar).
Two bacterial strains, designated Sa 1147-06(T) and Sa 1143-06, were isolated from Atlantic salmon (Salmo salar) farmed in Lake Chapo, Chile, and were studied using a polyphasic approach. Both isolates were very similar; cells were rod-shaped, formed yellow-pigmented colonies and were Gram-reaction-negative. Based on 16S rRNA gene sequence analysis, strains Sa 1147-06(T) and Sa 1143-06 shared 100 % sequence similarity and showed 98.9 and 97.5 % sequence similarity to Chryseobacterium jeonii AT1047(T) and Chryseobacterium antarcticum AT1013(T), respectively. Sequence similarities to all other members of the genus Chryseobacterium were below 97.3 %. The major fatty acids of strain Sa 1147-06(T) were iso-C₁₃:₀, iso-C₁₅:₀, anteiso-C₁₅:₀ and iso-C₁₇:₁ω9c, with iso-C₁₅:₀ 3-OH, iso-C₁₆:₀ 3-OH and iso-C₁₇:₀ 3-OH constituting the major hydroxylated fatty acids. DNA-DNA hybridizations with C. jeonii JMSNU 14049(T) and C. antarcticum JMNSU 14040(T) gave relatedness values of 20.7 % (reciprocal 15.1 %) and 15.7 % (reciprocal 25.7 %), respectively. Together, the DNA-DNA hybridization results and differentiating biochemical properties showed that strains Sa 1147-06(T) and Sa 1143-06 represent a novel species, for which the name Chryseobacterium chaponense sp. nov. is proposed. The type strain is Sa 1147-06(T) (=DSM 23145(T) =CCM 7737(T)).


Breast cancer prognostication and prediction: are we making progress?
Currently, much effort is being invested in the identification of new, accurate prognostic and predictive factors in breast cancer. Prognostic factors assess the patient's risk of relapse based on indicators such as intrinsic tumor biology and disease stage at diagnosis, and are traditionally used to identify patients who can be spared unnecessary adjuvant therapy based only on the risk of relapse. Lymph node status and tumor size are accepted as well-defined prognostic factors in breast cancer. Predictive factors, in contrast, determine the responsiveness of a particular tumor to a specific treatment. Despite recent advances in the understanding of breast cancer biology and changing practices in disease management, with the exception of hormone receptor status, which predicts responsiveness to endocrine treatment, no predictive factor for response to systemic therapy in breast cancer is widely accepted. While gene expression studies have provided important new information with regard to tumor biology and prognostication, attempts to identify predictive factors have not been successful so far. This article will focus on recent advances in prognostication and prediction, with emphasis on findings from gene expression profiling studies.


Effect of NK cell immunotherapy on immune function in patients with hepatic carcinoma: A preliminary clinical study.
We investigated the effectiveness of adoptive transfer of KIR ligand-mismatched highly activated nature killer (HANK) cells in patients with hepatic carcinoma. Peripheral blood mononuclear cells were obtained and cultured in vitro to induce expansion and activation of HANK cells. After 12 d of culture, the cells were divided into 3 parts and infused intravenously on days 13 to 15. The patients (n = 16) were given one to 6 courses of immunotherapy. No side effects were observed. The lymphocyte subsets and cytokine, thymidine kinase 1 (TK1) and circulating tumor cell (CTC) levels were measured 1 day before treatment and 1 month after the final infusion: the absolute number of total T cells and NK cells and the IL-2 and TNF-β levels were significantly higher, and the TK1 and CTC levels were significantly lower at 1 month after treatment. The percentage of patients who experienced partial response, disease stabilization, and disease progression at 3 months after treatment was 18.8%, 50.0% and 31.2%, respectively. The total follow-up period was 2-12 months. The median progression-free survival from treatment was 7.5 months. This is the first study on the benefits of HANK cell immunotherapy for hepatic carcinoma These encouraging preliminary observations imply that HANK cell immunotherapy is safe, can improve the immune function of patients with liver cancer, and may even reduce the rate of tumor metastasis and recurrence. However, further studies on larger samples of patients with a longer follow-up period are required to confirm these findings.


2,5-Dicarboxyanilinium chloride monohydrate.
The title compound, C8H8NO4+.Cl-.H2O, is the chlorohydrated form of 2-aminobenzene-1,4-dicarboxylic acid, the basic crystal structure of which is still not known. Molecules are linked by classical N-H...O, O-H...O, N-H...Cl and O-H...Cl hydrogen bonds, mainly along the molecular plane, into sheets built by unusual R6(4)(26), R6(4)(22) and R4(3)(22) rings. The stacking between layers is stabilized by another N-H...Cl hydrogen bond and by pi-pi interactions between aromatic rings facing each other.


Experiences of distortions to the passage of time during the Argentinian Covid-19 pandemic.
The Coronavirus-19 global pandemic has forced many governments around the world to enforce "lockdowns" to curtail the spread of the virus. Studies conducted in the UK, France, Italy and Brazil have demonstrated that one consequence of these lockdowns is significant distortion to the speed of the passage of time. The current study sought to establish how the passage of time was experienced during the Argentinian lockdown. An online questionnaire was used to measure passage of time judgments for the day and the week, physical activity, satisfaction with social interaction, the extent to which daily routines had changed due to covid and demographic data. The results show that distortions to the passage of time were widely experienced during the lockdown in Argentina. There was a tendency for participants to report time passing more quickly than normal. A faster passage of time was associated with being a woman, of younger age and more physically active. A slower passage of time was therefore associated with being a man, of older age and less physically active. The results indicate that whilst distortions to the passage of time during the covid-19 crisis appear to be a global phenomenon, cross-cultural differences are apparent in the factors which influence temporal experience.


Effects of EphB4 receptor expression on colorectal cancer cells, tumor growth, vascularization and composition.
Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide. Increased expression of the molecular target, EphB4 receptor, has been observed in several cancer types. However, studies on the role of EphB4 receptor in CRC have yielded contradictory results. The aim of this study was to investigate the influence of EphB4 expression levels on CRC cell behavior and its contribution to tumor growth and vascularization. SW480, LIM2405 and CT26 CRC cell lines were transfected with EphB4 expression vector. High EphB4 expressing cells were compared to low EphB4 expressing empty vector controls. Proliferation and migration assays as well as EphrinB2-Fc cell stimulations were conducted in vitro and subcutaneous xenografts of CRC were analyzed in vivo. High EphB4 expression enhanced migratory ability of these CRC cell lines in vitro and contributed to a significant increase in tumor growth and vascularization in vivo. Tumours induced with high EphB4 expressing SW480 and LIM2405 cells yielded homogenous masses densely packed with cancer cells. EphrinB2-Fc cell stimulations induced cell clustering of high EphB4 expressing SW480 and LIM2405 in vitro. These results suggest that with enhanced vascularization and an increase in migratory abilities, the high EphB4 expressing cells may be able to metastasize more readily.