Effects of high-intensity strength training on quality-of-life parameters in cardiac rehabilitation patients.
Cardiac rehabilitation programs have not consistently been shown to improve the psychological well being of their patients. In our study of 38 cardiac patients (29 men and 9 women), a variety of quality-of-life parameters were assessed before and after they completed either 12 weeks of high-intensity strength training or flexibility training added to their outpatient cardiac rehabilitation aerobic exercise program. The strength-trained patients increased their self-efficacy scores for lifting (29% vs 4%, p <0.05), push-ups (65% vs. 17%, p <0.01), climbing (36% vs 0%, p <0.001), and jogging (100% vs -9%, p <0.001), when compared with the flexibility-trained patients. The strength group also had greater improvements in Profile of Mood States dimensions: total mood disturbance (123% vs 18%, p <0.05), depression/dejection (73% vs 15%, p <0.05), and fatigue/inertia (42% vs 3% p <0.05), than did the flexibility group. The Medical Outcome Survey Short Form 36 role emotional health domain scores were significantly improved in the strength group when compared with the flexibility group (64% vs 0%, p <0.05), and the role limitation scores improved in both groups. Increases in strength were associated with enhanced self efficacy and improved mood and well-being scores (n = 34, r = 0.30 to 0.53, p <0.05). High-intensity strength training added to a cardiac rehabilitation program of selected patients leads to improvements in quality-of-life parameters. These data, in conjunction with improvements in strength, strongly support the value of adding high-intensity strength training to cardiac rehabilitation programs.


Crystal structure and location of gp131 in the bacteriophage phiKZ virion.
Pseudomonas phage ϕKZ and its two close relatives ϕPA3 and 201ϕ2-1 are very large bacteriophages that form a separate branch in phage classification because their genomes are very different from the rest of GenBank sequence data. The contractile tail of ϕKZ is built from at least 32 different proteins, but a definitive structural function is assigned to only one of them-the tail sheath protein. Here, we report the crystal structure of the C-terminal domain of another phiKZ tail protein, gene product 131 (gp131C). We show that gp131 is located at the periphery of the baseplate and possibly associates with fibers that emanate from the baseplate. Gp131C is a seven-bladed β-propeller that has a shape of a skewed toroid. A small but highly conserved and negatively charged patch on the surface of gp131C might be important for substrate binding or for interaction with a different tail protein.


Antihypertensive therapy in elderly patients. Pilot trial of the European Working Party on High Blood Pressure in the Elderly.
A study protocol for a double-blind randomised control trial of hypotensive treatment in elderly hypertensive patients has been tested in a number of pilot centres throughout Europe. It was shown that this study is possible from the logistic point of view. In these elderly patients, hydrochlorothiazide + triamterene treatment with or without methyldopa, maintained a significant hypotensive effect in the absence of major electrolyte disturbances. The initiation of hypotensive therapy did not provoke an excess of cardiovascular complications. The influence of hypotensive therapy on the general well-being and on the morbidity and the mortality of elderly patients with high blood pressure, is thereby being assessed. The study will continue for 5 years and other centres are invited to join.


[Deconstructing schizophrenia. Dimensional models or division into subtypes?].
Against the background of the arrangements of ICD-11 and DSM-V, future approaches in order to diagnose schizophrenic psychoses are currently being discussed. In this context, the current concepts of schizophrenia are questioned because attempts at neurobiological validation and validation based on family and follow-up studies have not succeeded. Therefore, dimensional diagnostic models or a division into subtypes are suggested. Both of these proposals would imply a deconstruction of the current concept of schizophrenia. A historical review shows that the psychopathological roots of the current discussion can be traced back to Kurt Schneider's nominalistic concept of schizophrenia which is based upon the so-called first-rank symptoms. In contrast, the psychopathological foundation of dimensional concepts and a division into several subtypes date from contributions of Klaus Conrad and Karl Leonhard. A triaxial diagnostic system with the axes of syndromes, course types and aetiology could provide a bridge between the different approaches.


Nonsuicidal Self-injury and Barriers to Accessibility of Dialectical Behavior Therapy Among Black Youth.
Youth in communities of color are disproportionately affected by the current mental health crisis, as highlighted in the recent Declaration of National Emergency by the American Academy of Child and Adolescent Psychiatry (AACAP), the American Academy of Pediatrics (AAP), and the Children's Hospital Association (CHA).1 The structural racism that Black youth encounter is a social determinant of health that contributes to inequitable access to evidence-based mental health services. Black youth in the United States experience inequities in financial hardships, access to educational resources, and the undue burden of the coronavirus disease 2019 (COVID-19) pandemic, further exacerbating an already outsized mental health burden.2.


Corneal endothelial wound repair in normal and mitotically inhibited cultures.
The aim of the present study was to compare the morphology, proliferative activity and cytoskeletal organization of bovine corneal endothelial cells during wound healing under normal and mitotically inhibited conditions. Cell cultures were grown to confluency and incubated with the mitotic inhibitor 5-fluorouracil (5-FU; 2.5 micrograms/ml) followed by a touch wound. Control cultures were maintained without 5-FU. Mitotic activity, F-actin, vinculin, vimentin and connexin 43 localization were evaluated before, during and after wound closure. 5-FU inhibited irreversibly the mitotic activity of corneal endothelial cells during the whole wound healing process. In the presence of 5-FU, a high degree of polymegathism and delay in actin and vinculin redistribution to the cell borders after wound closure was observed. Vimentin and connexin 43 immunolabeling revealed only slight differences between 5-FU-treated and control cultures. Significant changes in cell geometry and cytoskeletal organization in the amitotic corneal endothelium became manifested only after wounding. These changes may influence cell-cell and cell-matrix interactions as well as functional restoration of the monolayer after wound closure.


Orientation of the agarose matrix by pulsed electric fields.
DNA molecules less than ~20 kilobase (kb) pairs in size are efficiently fractionated by unidirectional electrophoresis in agarose gels (1). The variation of DNA mobility with gel concentration can be described by the Ogston mechanism of pore size distribution, if the observed mobilities are first extrapolated to zero electric field strength (2). Therefore, sieving of the macromolecules by the matrix appears to be the dominant mechanism of mol wt separation in this size range.


Radiotherapy for pelvic nodal recurrences after radical prostatectomy: patient selection in clinical practice.
There is no general consensus on the optimal treatment for prostate cancer (PC) patients with intrapelvic nodal oligorecurrences after radical prostatectomy. Besides androgen deprivation therapy (ADT) as standard of care, both elective nodal radiotherapy (ENRT) and stereotactic body radiotherapy (SBRT) as well as salvage lymph node dissection (sLND) are common treatment options. The aim of our study was to assess decision making and practice patterns for salvage radiotherapy (RT) in this setting. Treatment recommendations from 14 Swiss radiation oncology centers were collected and converted into decision trees. An iterative process using the objective consensus methodology was applied to assess differences and consensus. PSMA PET/CT was recommended by 93% of the centers as restaging modality. For unfit patients defined by age, comorbidities or low performance status, androgen deprivation therapy (ADT) alone was recommended by more than 70%. For fit patients with unfavorable tumor characteristics such as short prostate-specific antigen (PSA) doubling time or initial high-risk disease, the majority of the centers (57-71%) recommended ENRT + ADT for 1-4 lesions. For fit patients with favorable tumor characteristics, there were low levels of consensus and a wide variety of recommendations. For 1-4 nodal lesions, focal SBRT was offered by 64% of the centers, most commonly as a 5-fraction course. As an alternative to ADT, ENRT or SBRT for pelvic nodal oligorecurrences of PC are commonly offered to selected patients, with large treatment variations between centers. The exact number of lymph nodes had a major impact on treatment selection.


Urinary Incontinence in People Referred for Pulmonary Rehabilitation: An Undisclosed Issue but a Real Problem.
Pulmonary rehabilitation (PR) is an evidence-based intervention to manage symptoms related to chronic obstructive respiratory diseases (CORD). Paradoxically, few people with CORD actually engage in PR, and of those, up to one-third do not complete the program. Additionally, some of those who complete the program do not achieve worthwhile benefits. Therefore, the main challenge for the next decades is to offer PR to as many people (that would potentially benefit from it) as possible. This raises questions about factors influencing participation, completion, and responsiveness to PR programs. Among these factors, urinary incontinence (UI) is highly prevalent among people with CORD (much more than in the general population) and may worsen during PR exercise sessions. Paradoxically, UI is poorly explored in routine and scarcely assessed in research, and none of the actual guidelines about PR mention it. However, its potential influence on engagement, completion, and response to PR is of real concern. Therefore, the aim of this perspective is to describe the mechanisms of UI, particularly in the context of CORD, as well as to highlight its prevalence among people with CORD, their burden, and how it could affect a PR approach based on sustained and regular physical activity.


Total and Differential Somatic Cell Count in Italian Local Cattle Breeds: Phenotypic Variability and Effect on Milk Yield and Composition.
Milk differential somatic cell count (DSCC) represents the percentage of polymorphonuclear neutrophils and lymphocytes out of the total somatic cell count (SCC) and has been proposed in recent years as a proxy for udder health in dairy cows. We investigated phenotypic factors affecting SCC and DSCC using 3978 records of 212 Alpine Grey and 426 Burlina cows farmed in Northern Italy. The linear mixed model accounted for the fixed effects of breed, parity, lactation stage, sampling season, and first-order interactions of breed with the other effects. Cow, herd-test-date nested within breed were random. Subsequently, four udder health status groups (UHS) were created by combining SCC and DSCC to assess the UHS impact on milk yield and quality. DSCC was greater in Alpine Grey (66.2 ± 0.8%) than Burlina cows (63.2 ± 0.6%) and, similarly to SCC, it increased with days in milk and parity regardless of breed. Milk yield and composition were affected by UHS in both breeds. These results suggest that also udder health of local breeds can be monitored on a large scale through SCC and DSCC for reduction in biodiversity loss and increased farm profitability. However, in addition to milk data, the introduction of mastitis recording and monitoring plans is advisable.


(2SR,3RS)-Methyl 2-(adamantan-1-yl)-3-phenyl-sulfonyl-3-(pyridin-2-ylsulfan-yl)propano-ate dichloro-methane hemisolvate.
The title compound, C(25)H(29)NO(4)S(2) 0.5CH(2)Cl(2), was obtained as a racemate. The pyridine and phenyl rings are arranged face-to-face, giving a weak intra-molecular π-π inter-action [centroid-centroid separation = 3.759 (3) Å]. These inter-actions are extended inter-molecularly, forming chains of stacked rings along [001] with separations of 3.859 (3) and 3.916 (3) Å. The solvent used for crystallization, CH(2)Cl(2), is located in voids between the chains of mol-ecules, with a site occupancy of 0.5.


Presence, behaviour and removal of selected organic micropollutants through drinking water treatment.
This paper investigates the occurrence and removal of 60 organic micropollutants (OMPs) including pharmaceuticals, personal care products, pesticides and per- and polyfluoroalkyl substances in a drinking water treatment plant (DWTP) treating raw water from the Ebro River (NE Spain). The behaviour of the OMPs was evaluated in each treatment: pre-ozonation, flocculation-coagulation-decantation-sand filtration, post-ozonation and granular activated carbon filtration. Thirty-one of the sixty OMPs studied were detected in source water with individual median concentrations below 10 ng L-1 for all the compounds except for caffeine (64.1 ng L-1). The highest concentration peaks in the source water were found for caffeine (124.5 ng L-1), terbuthylazine (52.0 ng L-1), imidacloprid (30.2 ng L-1) and paracetamol (25.6 ng L-1). Of the 31 compounds detected in the source water, 17 were also detected in the finished drinking water. Of these 17 compounds, 10 were PFASs, which indicated that this group of compounds had not been effectively removed throughout the drinking water treatments. The overall removal efficiencies of OMPs in the DWTP ranged from -50.9% to 100%. The most efficient removal technologies were ozonation and granular activated carbon.


Requirement of low oxidation-reduction potential for photosynthesis in a blue-green alga (Phormidium sp.).
Photosynthesis in a Phormidium species which forms dense conical-shaped structures in thermal springs is strongly inhibited by aeration but is stimulated by sulfide and other agents (cysteine, thioglycolate, sulfite) which lower the oxidation-reduction potential. The compact structures which this alga forms in nature may restrict oxygen penetration from the enviroment so that the anaerobic or microaerophilic conditions necessary ofr photosynthesis can develop. The alga may be defective in a regulatory mechanism that controls the reoxidation of reduced pyridine nucleotides formed during photosynthesis. It is suggested that other mat-forming and benthic blue-green algae may also prefer anaerobib conditions for growth and photosynthesis.


Intravenous glucose after out-of-hospital cardiopulmonary arrest: a community-based randomized trial.
Does the common practice of infusing small amounts of glucose after cardiopulmonary arrest worsen neurologic outcome? A community-based randomized trial in Seattle, WA. Paramedics treated all patients with out-of-hospital cardiac arrest in a standard fashion except that the intravenous infusion did or did not contain glucose; ie, patients received either usual treatment, with 5% dextrose in water (D5W), or alternative, with half normal saline (0.45S). The main outcome was awakening, defined as the patient having comprehensible speech or following commands as determined by chart review. Other outcomes were survival to hospital admission and to discharge. Over 2 years, paramedics randomized 748 patients. The type of fluid administered was not significantly related to awakening (16.7% for D5W versus 14.6% for 0.45S), admission (38.0% for D5W versus 39.8% for 0.45S), or discharge (15.1% for D5W versus 13.3% for 0.45S). As in previous studies, patients whose arrest had likely been on a cardiac basis with initial rhythms of ventricular fibrillation or asystole had admission blood glucose levels significantly related to awakening: mean = 309 mg/dl for never awakening and 251 mg/dl for awakening. Of note, the relation between glucose and awakening was reversed in the remaining patients, who had electromechanical dissociation or noncardiac mechanisms of arrest. Current practices of using limited amounts of glucose-containing solutions after cardiopulmonary arrest do not need to be changed. Blood glucose level on admission is a prognostic indicator but depends on the type of arrest.


Maximal precordial ST-segment depression in leads V4-V6 in patients with inferior wall acute myocardial infarction indicates coronary artery disease involving the left anterior descending coronary artery system.
In inferior wall acute myocardial infarction, maximal ST-segment depression in left precordial leads (V4-V6) has been shown to be associated with increased in-hospital mortality, presumably due to coronary artery disease involving the left anterior descending coronary artery system. We measured ST-segment deviation from baseline in the initial electrocardiogram of patients with inferior wall acute myocardial infarction, who subsequently underwent coronary angiography during their in-hospital stay. Patients were divided into three groups: (I) No precordial ST-segment depression (n = 34). (II) Maximal precordial ST-segment depression in leads V1-V3 (n = 44). (III) Maximal precordial ST-segment depression in leads V4-V6 (n = 14). The left anterior descending coronary artery or its diagonal branch were stenosed (> 50%) in 32%, 41%, and 71% of patients in groups I, II, and III, respectively (p = 0.04), and severely stenosed (> 70%) in 18%, 18% and 57% of patients in the respective groups (p = 0.007). In patients with inferior wall acute myocardial infarction, maximal precordial ST-segment depression in leads V4-V6 is suggestive of severe coronary artery disease involving the left anterior descending coronary artery or its diagonal branch.


Optimal treatment strategy for acute cholecystitis based on predictive factors: Japan-Taiwan multicenter cohort study.
Although early laparoscopic cholecystectomy is widely performed for acute cholecystitis, the optimal timing of a cholecystectomy in clinically ill patients remains controversial. This study aims to determine the best practice for the patients presenting with acute cholecystitis focused on disease severity and comorbidities. An international multicentric retrospective observational study was conducted over a 2-year period. Patients were divided into four groups: Group A: primary cholecystectomy; Group B: cholecystectomy after gallbladder drainage; Group C: gallbladder drainage alone; and Group D: medical treatment alone. The subjects of analyses were 5,329 patients. There were statistically significant differences in mortality rates between patients with Charlson comorbidity index (CCI) scores below and above 6 (P < 0.001). The shortest operative time was observed in Group A patients who underwent surgery 0-3 days after admission (P < 0.01). Multiple regression analysis revealed CCI and low body mass index <20 as predictive factors of 30-day mortality in Grade I+II patients. Also, jaundice, neurological dysfunction, and respiratory dysfunction were predictive factors of 30-day mortality in Grade III patients. In Grade III patients without predictive factors, there were no difference in mortality between Group A and Group B (0% vs. 0%), whereas Group A patients had higher mortality rates than that of Group B patients (9.3% vs. 0.0%) in cases with at least one predictive factor. Even patients with Grade III severity, primary cholecystectomy can be performed safely if they have no predictive factors of mortality. Gallbladder drainage may have a therapeutic role in subgroups with higher CCI or higher disease severity.


Impact of COVID-19 on pediatric emergencies and hospitalizations in Singapore.
Coronavirus disease 2019 (COVID-19) has impacted the provision of health services in all specialties. We aim to study the impact of COVID-19 on the utilization of pediatric hospital services including emergency department (ED) attendances, hospitalizations, diagnostic categories and resource utilization in Singapore. We performed a retrospective review of ED attendances and hospital admissions among children < 18 years old from January 1st to August 8th 2020 in a major pediatric hospital in Singapore. Data were analyzed in the following time periods: Pre-lockdown (divided by the change in Disease Outbreak Response System Condition (DORSCON) level), during-lockdown and post-lockdown. We presented the data using proportions and percentage change in mean counts per day with the corresponding 95% confidence intervals (CIs). We attended to 58,367 children with a mean age of 5.1 years (standard deviation, SD 4.6). The mean ED attendance decreased by 331 children/day during lockdown compared to baseline (p < 0.001), attributed largely to a drop in respiratory (% change - 87.9, 95% CI - 89.3 to - 86.3, p < 0.001) and gastrointestinal infections (% change - 72.4, 95%CI - 75.9 to - 68.4, p < 0.001). Trauma-related diagnoses decreased at a slower rate across the same periods (% change - 40.0, 95%CI - 44.3 to - 35.3, p < 0.001). We saw 226 children with child abuse, with a greater proportion of total attendance seen post-lockdown (79, 0.6%) compared to baseline (36, 0.2%) (p < 0.001). In terms of ED resource utilization, there was a decrease in the overall mean number of procedures performed per day during the lockdown compared to baseline, driven largely by a reduction in blood investigations (% change - 73.9, 95%CI - 75.9 to - 71.7, p < 0.001). We highlighted a significant decrease in infection-related presentations likely attributed to the lockdown and showed that the relative proportion of trauma-related attendances increased. By describing the impact of COVID-19 on health services, we report important trends that may provide guidance when planning resources for future pandemics.


Isolation, Identification, and Characterization of the Nematophagous Fungus Arthrobotrys oligospora from Kyrgyzstan.
Predatory fungi have been the subject of fundamental studies and their potential as biological control agents against parasitic plant nematodes has been assessed. The aim of the present study was to isolate and identify predatory fungi, performing in vitro and in vivo screening to select highly active strains to control parasitic nematodes. Different nutrient media were used to isolate predatory fungi and determine their morphological and cultural properties. Identification was performed by classical and molecular biology methods. In vitro and in vivo screening was conducted to select highly active strains. Twelve isolates of Arthrobotrys oligospora (Orbiliomycetes) found in nature were investigated for their predaceous efficacy against garlic stem nematodes (Ditylenchus dipsaci). The effect of temperature and pH on the growth rate and trap formation of representative isolates was determined and isolates were characterized by light microscopy and molecular markers. BLAST was used to sequence the rDNA internal transcribed spacer of A. oligospora isolate KTMU-7. The optimum growth of A. oligospora strains was achieved at 20-25 °C on 1-2% corn meal agar (CMA) within the pH range of 5.6-8.6. The factors responsible for the trap formation of these fungal strains were identified. In vitro and in vivo experiments were performed to evaluate the nematicidal activity of local predatory fungal isolates against soil nematodes. Preliminary studies proved A. oligospora to be a potentially effective biological control agent, immobilizing 85.7 ± 2.19% of garlic stem nematodes in soil from the rhizosphere of potato plants.


Immediate skeletal effects of rapid maxillary expansion at midpalatal suture opening with Differential, Hyrax and Haas expanders.
The aim of this study was to test the null hypothesis that there is no difference at the midpalatal suture opening after rapid maxillary expansion (RME) using Expander with Differential Opening (EDO), Hyrax-type and Haas-type expanders. Occlusal radiographs of 52 patients (19 males and 33 females; average age= 9.46?1.20 years) treated with RME were divided into three groups, according to the expander used: EDO (n=17), Hyrax-type (n=21) and Haas-type (n=14). The evaluated variables were: A) Distance between the maxillary central incisors at the incisal edge; B) Distance between the alveolar ridges at the midpalatal suture; C) Suture opening at 10-mm distance from the crest to posterior, at the midpalatal suture; D) Suture opening at 20-mm distance from the crest to posterior, at the midpalatal suture; and E) Suture opening at 30-mm distance from the crest to posterior, at the midpalatal suture. To assess the normality of variables, the Shapiro-Wilk test was performed. For intergroup comparison, ANOVA with a significance level of 5% was used. At the region A, Hyrax-type (4.66 mm) and EDO (4.87 mm) groups presented larger openings than the Haas-type group (3.43 mm). In regions B and C, EDO showed a statistically significant greater opening than the Haas-type group. In region D, a smaller opening of the midpalatal suture was observed in the Haas-type group, compared to the Hyrax-type and EDO groups. EDO and Hyrax-type produced greater immediate skeletal effects, compared with Haas-type, but these differences were about 1 mm and might not be clinically significant.


Interspecies pharmacokinetic scaling of BSH in mice, rats, rabbits, and humans.
Sodium mercaptoundecahydrododecaborate or BSH is an important compound for boron neutron capture therapy (BNCT). The total clearance and steady state volume of distribution of BSH in humans and in laboratory animals were analyzed as a function of species body weight using the allometric equation for interspecies scaling. Significant linear relationships were obtained between log CLt (Lh-1) and log W (kg) (r = 0.972; p = 0.028) as well as log VSS (L) and log W (kg) (r = 0.999; p = 0.0005). The corresponding allometric equations were CLt = 0.127 W0.68 and VSS = 1.557 W0.87, respectively. BSH clearance in various species was shown to be a constant fraction (0.26) of creatinine clearance, the relationship being independent of body weight. Thus BSH clearance in various species occurred at similar pace when measured by a physiological parameter (creatinine clearance) rather than chronological time. Interspecies scale-up of plasma concentration-time data for the four species using a complex Dedrick plot resulted in similar profiles. Our results indicate that the BSH data obtained in laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters in humans. These parameters can serve as guidelines for better planning of clinical studies.


Efficacy and tolerability of antidepressants in pediatric anxiety disorders: a systematic review and meta-analysis.
Randomized controlled trials have demonstrated that antidepressants are efficacious in the treatment of anxiety disorders in youth. However, there are no recent, systematic analyses of the efficacy, safety, or tolerability of these medications in pediatric anxiety disorders. A systematic review and meta-analysis of prospective, randomized, parallel-group, controlled trials of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) in pediatric patients with non-obsessive compulsive disorder (OCD) anxiety disorders was undertaken using a search of PubMed/Medline (1966-2014). The meta-analysis utilized random-effects models to evaluate change in the Pediatric Anxiety Rating Scale or similar anxiety scale, suicidality, and adverse events. Additionally, pharmacologic variables were explored with regard to effect size, although no correction for multiple comparisons was made with regard to these relationships. Nine trials involving 1,673 patients and six medications were included. All SSRI/SSNRIs evaluated demonstrated efficacy, and the meta-analytic estimate of effect was of moderate magnitude (Cohen's d = 0.62, confidence interval [CI]: 0.34-0.89, P = .009) and there was evidence of modest heterogeneity (I(2) = 0.29, P = .103). Activation trended toward being more likely with antidepressant treatment (OR: 1.86, CI: 0.98-3.53, P = .054), but no increased risk was observed for nausea/abdominal symptoms (P = .262), discontinuation as a result of an adverse event (P = .132), or suicidality (OR: 1.3, CI: 0.53-3.2, P = .514). Finally, the effect size correlated with the serotonergic specificity of the agent (R = .79, P = .021). Data for nine SSRI/SSNRIs suggest superiority of antidepressants relative to placebo for the treatment of pediatric anxiety disorders with a moderate effect size.


1-(2,5-Dimethyl-phen-yl)piperazine-1,4-diium tetra-chloridozincate monohydrate.
In the title compound, (C(12)H(20)N(2))[ZnCl(4)]·H(2)O, the two piperazine N atoms are protonated and the [ZnCl(4)](2-) anions adopt a slightly distorted tetra-hedral configuration. In the crystal, O-H⋯Cl hydrogen bonds link the tetra-chloridozincate anions and the water mol-ecules into corrugated inorganic chains parallel to [010]. The crystal structure is stabilized by N-H⋯Cl, N-H⋯O and O-H⋯Cl hydrogen bonds, with the N-H hydrogen bond originating from one of the two N atoms being trifurcated.


Successful computer guided planned synthesis of (4R)-thiazolidine carboxylic acid and its 2-substituted analogues as urease inhibitors.
By using internal combinatorial library we were able to identify (4R)-thiazolidines carboxylic acid and its 2-substituted analogs as active inhibitors of urease. Molecular modeling and virtual screening were utilized to find out potential compounds. Computational techniques were employed at database of 90,000 ligands and selected the structure representing the low energy conformations, Grid and FlexX docking algorithms were used and the top binding ligands were synthesized and screened in wet-lab.


Additivity of optical emissions applied to neodymium and praseodymium quantification in metallic didymium and (Nd,Pr)-Fe-B alloy samples by low-resolution atomic emission spectrometry: An evaluation of the mathematical approach used to solve spectral interferences.
In this work, the effectiveness of a mathematical approach to solve the spectral interferences involved in the optical emission of two chemical species (neodymium and praseodymium) when using monochromators with low-resolution in atomic spectrometry is evaluated. Although recent technological advances have promoted spectrometers equipped with high-resolution monochromators, which have a great instrumental capability in the separation of nearby lines and consequently avoid spectral interferences, many laboratories still have old spectrometers installed with insufficient resolution to overcome such interferences. In order to evaluate a mathematical approach based on Lambert-Beer's Law, the optical emissions of neodymium and praseodymium were monitored on a low-resolution (200 pm) flame atomic emission spectrometry (F-AES). These two elements were strategically chosen as an application model because they exhibit similar physicochemical properties, joint occurrence in nature and because they are increasingly used in the manufacture of super-magnets, a material increasingly required by the high technology industry. The effectiveness of the mathematical approach was evaluated in three different ways: (i) by recovery of the analytes in synthetic mixtures containing known quantities of the species; (ii) by spike and recovery trials on a representative blend of dissolved samples and (iii) by comparing the results obtained with another analytical method: Inductively coupled plasma optical emission spectrometry (ICP-OES) with a higher spectral resolution. The results indicate the effectiveness of this simple mathematical approach, allow the "survival" of instruments equipped with low-resolution monochromators and demonstrate the applicability of this approach to spectral correction. In addition, this work contributes an analytical method for the quantification of neodymium and praseodymium in metallic alloy samples involved in the production of super-magnets, aiding in the strict quality control of these materials.


Acridine orange fluorescence cytochemistry for detecting lymphocyte immunoreactivity.
Acridine orange staining reveals changes within 3 hours of in vitro stimulation of normal rat lymphocytes with mitogens, and of immune rat lymphocytes with the sensitizing antigen. An increased number of red fluorescent cytoplasmic organelles, presumably lysosomes are seen by fluorescence microscopy. Fluorimetry of the supernatants from stained cell suspensions suggests an overall decreased cell uptake of the dye. The microscopy and fluorimetry detected early events in the reaction of lymphocytes from tumour-bearing rats with the target tumour cells. It would appear that the changes in intracellular behaviour of the dye and in overall cell uptake after immune stimulation are a reflection of dissociated variations in internal and external cell membrane permeability, and may provide simple general means for recognizing cellular immune reactions.


Structural, rheological properties and antioxidant activities of polysaccharides from mulberry fruits (Murus alba L.) based on different extraction techniques with superfine grinding pretreatment.
The structural characteristics and biological activity of polysaccharides were influenced by different extraction methods. In this study, polysaccharides from mulberry fruits (Murus alba L., which were pre-treated with superfine grinding process) (MFP) were exacted using hot-water extraction (HWE), enzyme-assisted hot water extraction (EAHE), ultrasonic-assisted hot water extraction (UAHE), and high-speed shear homogenization-assisted hot water extraction (HSEHE). The extraction yield, structure, rheological properties and antioxidant activities of MFPs were investigated. MFP extracted using the HSEHE method have the highest extraction yields than other extraction methods. The smaller particle size of mulberry powder was found to improve the extraction yields. The MFPs were obtained by the combination between different extraction methods and superfine grinding pretreatment (through 100 mesh sieve) (MFP-HWE100, MFP-EAHE100, MFP-UAHE100, MFP-HSEHE100) showed the same levels of monosaccharide compositions and glycosyl linkages, However, these methods can produce MFP with different monosaccharide proportions, branching degree, different molecular weight, particle size and microstructure. MFP-HSEHE100 achieved the lowest molecular weight and particle size, which exhibited better thixotropy and antioxidant activities than other MFPs. This study identified that HSEHE was the most suitable extraction method for MFP.


One minute static stretch of plantar flexors transiently increases H reflex excitability and exerts no effect on corticospinal pathways.
What is the central question of this study? What mediates neural responses following static stretching, and how long do these influences last? What is the main finding and its importance? This study shows that 1 min of static stretching inhibits the tendon tap reflex and facilitates the H reflex without influencing motor-evoked potentials. The results indicate that at least two different mechanisms mediate neural responses after static stretching. The purpose of this study was to determine whether the neural responses observed after static stretching are mediated by sensitivity of muscle spindles, spinal excitability or cortical excitability and how long these influences last. Nineteen volunteers (25.7 ± 5.6 years old) were tested for the tendon tap reflex (T-reflex), H reflex and motor-evoked potentials on ankle flexors and extensors immediately, 5 and 10 min after 1 min static stretching applied at individual maximal ankle dorsiflexion, as well as immediately, 5 and 10 min after a control period of the same duration. Comparison of measurements collected immediately after stretching or control conditions revealed that the T-reflex was weaker after stretching than after control (-59.2% P = 0.000). The T-reflex showed a slow recovery rate within the first 150 s after stretching, but 5 min after the inhibition had disappeared. The H reflex increased immediately after stretching (+18.3%, P = 0.036), showed a quick tendency to recover and returned to control values within 5 min from stretching. Motor-evoked potentials were not affected by the procedure. These results suggest that 1 min of static stretching primarily decreases muscle spindle sensitivity and facilitates the H reflex, whereas effects on the motor cortex can be excluded.


Enantioselectivity of microsomal epoxide hydrolase toward arene oxide substrates.
The enantioselectivity of native and purified hepatic microsomal epoxide hydrolase toward one symmetrical arene oxide, phenanthrene 9,10-oxide, and the resolved enantiomers of the three chiral arene oxide substrates, benzo[a]pyrene 4,5- and 7,8-oxide and benzo[a]anthracene 5,6-oxide was examined. A model lipid system of nonionic detergent micelles was used to solubilize both substrates and products. The enantioselectivity of purified epoxide hydrolase in micellar solution was essentially the same as the microsomal enzyme in the absence of detergent. Regioselectivity of the enzyme was determined by a gas chromatographic-mass spectrometric procedure in which bis-trifluoroacetates of the dihydrodiols were pyrolyzed to trifluoroacetylphenols to locate the position of the enzyme-catalyzed incorporation of 18O from H218O into the dihydrodiol. Correlation of the enantio- and regioselectivity data with the known absolute configurations of the dihydrodiols permitted the assignment of the (4S,5R) and (5S,6R) absolute configurations to (+)-benzo[a]pyrene 4,5- and (+)-benzo[a]anthracene 5,6-oxide, respectively. A kinetic analysis of the hydration of arene oxide substrates in micellar solution is presented. The kinetic discrimination of the enzyme toward substrate enantiomers and the product enantioselectivity of the enzyme are discussed in terms of possible molecular deformations occurring in the transition state and the ability of the enzyme to bind and stabilize these transition states.


Newer antiepileptic drugs: evidence based use.
Several new antiepileptic drugs (AED's) have been approved by the FDA in the last 2 decades. The newer AED's score over the older ones, in terms of improved tolerability, safety, improved pharmacokinetics and lower drug-drug interactions. However, efficacy may not be significantly higher. This article reviews the newer antiepileptics approved in the pediatric age group and the evidence for or against their clinical use.


Photoelctrochemically Fabricated and Heated Cu2O/CuO Bilayers with Enhanced Photovoltaic Characteristics.
Cu2O/CuO bilayers were fabricated by electrodeposition of the CuO layer in a copper(II)-ammonia complex aqueous solution, followed by photoelectrochemical deposition of the Cu2O layer at potentials ranging from -0.3 to -1.0 V referenced to a Ag/AgCl electrode in a copper(II)-lactate complex aqueous solution under light irradiation, and the effects of varied potentials of the photoelectrochemical Cu2O depositions and post-heating conditions on their structural, optical, and photovoltaic characteristics were investigated with X-ray diffraction, field emission-scanning electron microscopy, optical absorption measurements, and external quantum efficiency (EQE) measurements with and without applied bias voltage. The Cu2O layers with a characteristic 2.1 eV band gap energy were adhesively stacked on the thorn-like grains of the CuO layers possessing a characteristic 1.5 eV band gap energy, and dense and defect-free Cu2O/CuO bilayers could be fabricated at the potentials of -0.4 and -0.5 V, but the grain size of Cu2O decreased at -0.5 V. In addition, the metallic Cu was deposited simultaneously at potentials less than -0.7 V. The Cu2O/CuO bilayer fabricated at -0.4 V revealed photovoltaic features at wavelengths ranging from 350 nm to approximately 900 nm, and a maximum EQE value of 56.8% was achieved at 510 nm in wavelength with a bias voltage of -0.1 V. The maximum EQE value, however, decreased to 1.2% accompanied with the peak wavelength shift to 580 nm, and no photovoltaic feature was observed at potentials of -0.3, -0.7, and -1.0 V. The photovoltaic performance for the Cu2O/CuO bilayer fabricated at -0.4 V was ameliorated by heating at 423 K, and the maximum EQE values were enhanced to 87.7% at 550 nm and 89.8% at 530 nm in an ambient atmosphere and vacuum. Both the Cu2O and CuO layers acted as photovoltaic layers in the Cu2O/CuO bilayer fabricated at -0.4 V and heated at 423 K, and the electrical characteristic including the carrier mobility affected the photovoltaic performance. The photovoltaic feature, however, disappeared by heating above 523 K due to the formation of nanopores inside the CuO layer and near the CuO heterointerface to the Cu2O and fluorine-doped tin oxide substrate.


Clinical value of the Eustachian Tube Function Scoring System T-ETDQ: a prospective diagnostic study.
Tubomanometry (TMM) and the seven-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) was integrated to establish the Tubomanometry Eustachian Tube Dysfunction Questionnaire (T-ETDQ), and its reliability, potential clinical application, and diagnostic value for Eustachian tube function were investigated. This prospective diagnostic study included patients visiting the ENT Department of our Hospital, between April and June 2021. Patients were grouped into Eustachian tube dysfunction (ETD) and control groups according to tympanometry diagnosis results. The diagnostic value of the T-ETDQ was evaluated using receiver-operating characteristic (ROC) curve analysis. There were 48 patients with Obstructive ETD and 24 patients without. The area under the ROC curve (AUC) of T-ETDQ was 0.898 (95% confidence interval [CI] 0.826-0.969), and the highest sensitivity and specificity were 76.7% and 86.7% respectively when the positive cutoff value was 4.72. The AUC of Eustachian tube score (ETS) was 0.731 (95% CI 0.625-0.837) and the highest sensitivity and specificity were 48.3% and 90.0% respectively when the positive cut-off value was 4.5. The ETS and T-ETDQ had kappa values of 0.311 and 0.585, respectively (P < 0.001 for both), showing both methods were comparable to tympanometry; however, T-ETDQ had more consistent results than ETS. T-ETDQ can effectively quantify and evaluate ETD severity in adults, has a higher diagnostic value than ETS, making it a suitable diagnostic tool.


Frog oocytes synthesize and completely process the precursor polypeptide to virion structural proteins after microinjection of avian myeloblastosis virus RNA.
After microinjection of Xenopus laevis oocytes with RNA from avian myeloblastosis virus, viral structural proteins p27, p19, p15, and p12 are formed by a sequence of posttranslational cleavages of a high-molecular-weight precursor polypeptide. The 60-70S RNA aggregate or its 30-40S RNA subunits obtained by heat or formamide treatment possess the same ability to serve as template in X. laevis oocytes. The processing pattern of virus-specific precursor polypeptides is the same in X. laevis oocytes as in chick embryo fibroblasts infected with avian myeloblastosis virus, but the processing takes place at a much slower rate.


FAM83A is amplified and promotes cancer stem cell-like traits and chemoresistance in pancreatic cancer.
Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), contribute to tumorigenesis, resistance to chemoradiotherapy and recurrence in human cancers, suggesting targeting CSCs may represent a potential therapeutic strategy. In the current study, we found family with sequence similarity 83, member A (FAM83A) is significantly overexpressed and associated with poorer overall survival and disease-free survival in pancreatic cancer. Overexpression of FAM83A markedly promoted, whereas inhibition of FAM83A decreased, CSC-like traits and chemoresistance both in vitro and in an in vivo mouse model of pancreatic cancer. Furthermore, overexpression of FAM83A activated the well-characterized CSC-associated pathways transforming growth factor-β (TGF-β) signaling and Wnt/β-catenin signaling. Importantly, the FAM83A locus was amplified in a number of human cancers and silencing FAM83A in associated cancer cell lines inhibited activation of the WNT/β-catenin and TGF-β signaling pathways and reduced tumorigenicity. Taken together, these results indicate that FAM83A has a vital oncogenic role to promote pancreatic cancer progression and may represent a potential clinical target.


Severe hepatotoxicity secondary to nintedanib.
Nintedanib is a multikinase inhibitor used for the treatment of pulmonary idiopathic fibrosis. We present the first report published to date of severe hepatotoxicity and jaundice secondary to nintedanib.


Efficacy of laser therapy for temporomandibular disorders: A systematic review and meta-analysis.
The aim of this systematic review was to evaluate the efficacy of laser therapy in temporomandibular disorders (TMD). Randomized controlled trials (RCTs) in regard to this issue were searched in electronic databases. Three investigators independently screened the eligible studies, and the quality of the included studies was assessed according to the risk of bias tool recommended by the Cochrane handbook. The primary outcome measure was the degree of pain, reported on a visual analog scale (VAS), and the secondary outcome measures were TMJ function, including maximum active vertical opening (MAVO), maximum passive vertical opening (MPVO), left and right lateral movement (LLE, RLE). Pooled effect sizes were calculated using random effects models and 95% confidence interval (95% CI). A total of 28 randomized controlled trials were included. Laser therapy had a more significant effect in terms of VAS (SMD=﹣1.88; 95% CI=﹣2.46 to﹣1.30; P < 0.00001; I2 =93%), MAVO (MD = 4.90; 95% CI= 3.29-6.50; P < 0.00001; I2 =72%), MPVO (MD=5.82; 95% CI= 4.62-7.01; P < 0.00001; I2 =40%) and RLE (MD = 0.73; 95% CI= 0.23-1.22; P = 0.004; I2 = 0%) as compared to placebo group. However, there was no significant difference in LLE between two groups (MD= 0.35; 95% CI=﹣0.31-1.01; P = 0.30; I2 =0%). Laser therapy can effectively reduce pain but have small effect on improving mandibular movement of TMD patients. More well-designed RCTs with large sample sizes are needed for further validation. And these studies should report detailed laser parameters and provide complete outcome measure data.


Fractal analysis improves tumour size measurement on computed tomography in pancreatic ductal adenocarcinoma: comparison with gross pathology and multi-parametric MRI.
Tumour size measurement is pivotal for staging and stratifying patients with pancreatic ductal adenocarcinoma (PDA). However, computed tomography (CT) frequently underestimates tumour size due to insufficient depiction of the tumour rim. CT-derived fractal dimension (FD) maps might help to visualise perfusion chaos, thus allowing more realistic size measurement. In 46 patients with histology-proven PDA, we compared tumour size measurements in routine multiphasic CT scans, CT-derived FD maps, multi-parametric magnetic resonance imaging (mpMRI), and, where available, gross pathology of resected specimens. Gross pathology was available as reference for diameter measurement in a discovery cohort of 10 patients. The remaining 36 patients constituted a separate validation cohort with mpMRI as reference for diameter and volume. Median RECIST diameter of all included tumours was 40 mm (range: 18-82 mm). In the discovery cohort, we found significant (p = 0.03) underestimation of tumour diameter on CT compared with gross pathology (Δdiameter3D = -5.7 mm), while realistic diameter measurements were obtained from FD maps (Δdiameter3D = 0.6 mm) and mpMRI (Δdiameter3D = -0.9 mm), with excellent correlation between the two (R2 = 0.88). In the validation cohort, CT also systematically underestimated tumour size in comparison to mpMRI (Δdiameter3D = -10.6 mm, Δvolume = -10.2 mL), especially in larger tumours. In contrast, FD map measurements agreed excellently with mpMRI (Δdiameter3D = +1.5 mm, Δvolume = -0.6 mL). Quantitative perfusion chaos was significantly (p = 0.001) higher in the tumour rim (FDrim = 4.43) compared to the core (FDcore = 4.37) and remote pancreas (FDpancreas = 4.28). In PDA, fractal analysis visualises perfusion chaos in the tumour rim and improves size measurement on CT in comparison to gross pathology and mpMRI, thus compensating for size underestimation from routine CT. • CT-based measurement of tumour size in pancreatic adenocarcinoma systematically underestimates both tumour diameter (Δdiameter = -10.6 mm) and volume (Δvolume = -10.2 mL), especially in larger tumours. • Fractal analysis provides maps of the fractal dimension (FD), which enable a more reliable and size-independent measurement using gross pathology or multi-parametric MRI as reference standards. • FD quantifies perfusion chaos-the underlying pathophysiological principle-and can separate the more chaotic tumour rim from the tumour core and adjacent non-tumourous pancreas tissue.


HLA-A*24:374-A novel allele encoding the HLA-A2403 specificity.
HLA-A*24:374 differs from A*24:03:01:01 by 2 exon 3 bases resulting in a substitution of T163E.


Cognitive Impairment in Heart Failure-A Review.
Cognitive impairment (CI) is common in heart failure (HF). Patients with HF demonstrate reduced global cognition as well as deficits in multiple cognitive domains compared to controls. Degree of CI may be related to HF severity. HF has also been associated with an increased risk of dementia. Anatomical brain changes have been observed in patients with HF, including grey matter atrophy and increased white matter lesions. Patients with HF and CI have poorer functional independence and self-care, more frequent rehospitalisations as well as increased mortality. Pathophysiological pathways linking HF and CI have been proposed, including cerebral hypoperfusion and impaired cerebrovascular autoregulation, systemic inflammation, proteotoxicity and thromboembolic disease. However, these mechanisms are poorly understood. We conducted a search on MEDLINE, Embase and Scopus for original research exploring the connection between HF and CI. We then reviewed the relevant literature and discuss the associations between HF and CI, the patterns of brain injury in HF and their potential mechanisms, as well as the recognition and management of CI in patients with HF.


Efficient removal of triclosan via peroxymonosulfate activated by a ppb level dosage of Co(II) in water: Reaction kinetics, mechanisms and detoxification.
Triclosan (TCS), an extensively used broad-spectrum antimicrobial agent, has raised significant environmental concerns regarding its widespread occurrence in waters. In this study, the removal of TCS in aqueous solution via peroxymonosulfate (PMS) activated by an extremely low-level Co2+ (0.02 μM) was systematically investigated. During preliminary test, TCS (10 μM) was totally degraded in 30 min by using 0.1 μM Co2+ and 40 μM PMS at pH 7.0 with a degradation rate constant of 0.1219 min-1. A first-order apparent degradation rate of TCS was found with respect to the PMS concentrations. At extremely low dosage of Co2+ (0.02 μM), the presence of NO3-, HCO3-, PLFA, and SRHA within test concentrations significantly inhibited TCS removal, while a dual effect of Cl- on the degradation rate of TCS was observed. The quenching experiments verified that SO4- was the dominant reactive oxygen species (ROS) rather than OH. Six major intermediates were identified using TOF-LC-MS, based on which we proposed three associated reaction pathways including hydroxylation, ether bond breakage, and dechlorination. Toxicity predictions by ECOSAR software exhibited aquatic toxicity reduction of TCS after Co2+/PMS treatment. We outlook these findings to advance the feasibility of organic contaminants removal via Co2+/PMS system with Co2+ at extremely low levels.


Conformational analysis, stereoelectronic interactions and NMR properties of 2-fluorobicyclo[2.2.1]heptan-7-ols.
Four diastereoisomers of 2-fluorobicyclo[2.2.1]heptan-7-ols were computationally investigated by using quantum-chemical calculations, and their relative energies were analyzed on the basis of stereoelectronic interactions, particularly the presence or otherwise of the F∙∙∙HO intramolecular hydrogen bond in the syn-exo isomer. It was found through NBO and AIM analyses that such an interaction contributes to structural stabilization and that the (1h)J(F,H(O)) coupling constant in the syn-exo isomer is modulated by the n(F)→σ*(OH) interaction, i.e., the quantum nature of the F∙∙∙HO hydrogen bond.


Maintenance of cancellous bone connectivity in primary hyperparathyroidism: trabecular strut analysis.
We previously demonstrated an increase in cancellous bone volume and trabecular number in patients with mild primary hyperparathyroidism (PHPT). To test the hypothesis that this increase is due to preservation of cancellous bone architecture, we conducted a trabecular strut analysis using a new method that measures trabecular connectivity. Iliac crest biopsies from 37 patients with PHPT, 14 men (28-68 years) and 23 women (26-68 years), were examined histomorphometrically and compared to cadaveric samples from 24 age-matched subjects, 17 men and 7 women. Two-dimensional indices of cancellous structure--node number (N.Nd), terminus number (N.Tm), node to node (Nd.Nd), node to terminus (Nd.Tm), and terminus to terminus (Tm.Tm) strut lengths, and total strut length (TSL)--were measured and the ratio of node number to terminus number (N.Nd/N.Tm) calculated. TSL, N.Nd, and Nd.Nd were significantly higher in patients than in controls. TSL and Nd.Nd, but not N.Nd or Nd/Tm, decreased significantly with age in PHPT, indicating that age-related bone loss in PHPT occurs without significant loss of trabecular connectivity. Two-dimensional indices reflecting connectivity or the amount of bone, that is, N.Nd, Nd.Nd, N.Nd/N.Tm, and TSL, correlated positively with cancellous bone volume (BV/TV) and trabecular number (Tb.N) and negatively with trabecular spacing (Tb.Sp) in both PHPT and controls. Trabecular thickness (Tb.Th) correlated positively with Nd.Nd and Tb.N and negatively with Tm.Tm in PHPT but not in controls. The present data show that in PHPT there is not only greater cancellous bone volume and trabecular number but preserved trabecular connectivity as well. The data further support the hypothesis that in PHPT cancellous bone architecture is maintained.


Using appropriate Kappa statistic in evaluating inter-rater reliability. Short communication on "Groundwater vulnerability and contamination risk mapping of semi-arid Totko river basin, India using GIS-based DRASTIC model and AHP techniques".
In this article, some misuses of Kappa statistic in the original paper [Chemosphere, 307, 135831] are discussed. By using DRASTIC and Analytic Hierarchy Process (AHP) models, the authors have assessed the groundwater vulnerability of Totko, India. High nitrate concentrations in groundwater have been found in highly vulnerable areas, and the accuracy of the models has been assessed through Pearson's correlation coefficient and Kappa coefficient. However, using Cohen's Kappa to estimate the intra-rater reliabilities (IRRs) of the two models is not appropriate on the condition of ordinal categorical variables in five categories in the original paper. We briefly introduce the Kappa statistic and propose to use weighted Kappa to compute IRRs under such conditions. To conclude, we recognize that this does not significantly alter the conclusions of the original paper, but it is necessary to ensure that the appropriate statistical tools are used.


Neurotrophins: Role in adverse pregnancy outcome.
Proper placental development is essential during pregnancy since it forms the interface between the maternal-foetal circulations and is critical for foetal nutrition and oxygenation. Neurotrophins such as nerve growth factor (NGF), brain derived neurotrophin (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) are naturally occurring molecules that regulate development of the placenta and brain. BDNF and NGF also involved in the regulation of angiogenesis. Recent studies suggest that the levels of BDNF and NGF are regulated by docosahexaenoic acid (DHA) which is an important omega-3 fatty acid and is a structural component of the plasma membrane. Oxidative stress during pregnancy may lower the levels of DHA and affecting the fluidity of the membranes leading to the changes in the levels and expression of BDNF and NGF. Therefore altered levels and expression of NGF and BDNF may lead to abnormal foetal growth and brain development that may increase the risk for cardiovascular disease, metabolic syndromes and neurodevelopmental disorders in children born preterm. This review discuss about the neurotrophins and their role in the feto-placental unit during critical period of pregnancy.


Immunotherapy in Thoracic Malignancies: New Treatment and New Hope.
Over these last two pandemic years, we have all experienced profound changes in how we practice, how we work, and how we live [...].


Evolutionary diversification of defensins and cathelicidins in birds and primates.
Divergent evolution for more than 310 million years has resulted in an avian immune system that is complex and more compact than that of primates, sharing much of its structure and functions. Not surprisingly, well conserved ancient host defense molecules, such as defensins and cathelicidins, have diversified over time. In this review, we describe how evolution influenced the host defense peptides repertoire, its distribution, and the relationship between structure and biological functions. Marked features of primate and avian HDPs are linked to species-specific characteristics, biological requirements, and environmental challenge.


Metastatic carcinoma of the gallbladder from renal cancer presenting as intraluminal polypoid mass.
We report a rare case of secondary involvement of the gallbladder by metastatic renal cell carcinoma. A 71-year-old man was diagnosed as having a polypoid mass within the gallbladder when he underwent right nephrectomy for a renal cell carcinoma. A preoperative diagnosis of simultaneous carcinoma of the gallbladder was made, and extended cholecystectomy with regional lymphadenectomy was performed five months after the initial operation. Postoperative histological examination of the polypoid mass within the gallbladder and a pancreatic mass excised during the second surgery revealed these resected tumors to be identical to the clear cell type of renal cell carcinoma. We feel that this case presents synchronous involvement of the gallbladder and pancreas by metastatic renal cell carcinoma of the right kidney.


Oncornavirus particles in lymphoid cultures from a howler monkey with Herpesvirus saimiri-induced disease.
Budding and extracellular oncornavirus particles were observed in cells of lymphoid cultures derived from the spleen, lymph node, and blood of a howler monkey (Alouatta caraya) that developed a malignant lymphoproliferative disease after infection with Herpesvirus saimiri. The various possible sources of origin of these particles are discussed.


Nuclear envelope-associated dynein drives prophase centrosome separation and enables Eg5-independent bipolar spindle formation.
The microtubule motor protein kinesin-5 (Eg5) provides an outward force on centrosomes, which drives bipolar spindle assembly. Acute inhibition of Eg5 blocks centrosome separation and causes mitotic arrest in human cells, making Eg5 an attractive target for anti-cancer therapy. Using in vitro directed evolution, we show that human cells treated with Eg5 inhibitors can rapidly acquire the ability to divide in the complete absence of Eg5 activity. We have used these Eg5-independent cells to study alternative mechanisms of centrosome separation. We uncovered a pathway involving nuclear envelope (NE)-associated dynein that drives centrosome separation in prophase. This NE-dynein pathway is essential for bipolar spindle assembly in the absence of Eg5, but also functions in the presence of full Eg5 activity, where it pulls individual centrosomes along the NE and acts in concert with Eg5-dependent outward pushing forces to coordinate prophase centrosome separation. Together, these results reveal how the forces are produced to drive prophase centrosome separation and identify a novel mechanism of resistance to kinesin-5 inhibitors.


Affective symptoms and AT(N) biomarkers in mild cognitive impairment and Alzheimer's disease: A systematic literature review.
Alzheimer's disease (AD) biomarkers such as amyloid, p-tau and neuronal injury markers have been associated with affective symptoms in cognitively impaired individuals, but results are conflicting. CINAHL, Embase, PsycINFO and PubMed were searched for studies evaluating AD biomarkers with affective symptoms in mild cognitive impairment and AD dementia. Studies were classified according to AT(N) research criteria. Forty-five abstracts fulfilled eligibility criteria, including in total 8,293 patients (41 cross-sectional studies and 7 longitudinal studies). Depression and night-time behaviour disturbances were not related to AT(N) markers. Apathy was associated with A markers (PET, not CSF). Mixed findings were reported for the association between apathy and T(N) markers; anxiety and AT(N) markers; and between agitation and irritability and A markers. Agitation and irritability were not associated with T(N) markers. Whereas some AD biomarkers showed to be associated with affective symptoms in AD, most evidence was inconsistent. This is likely due to differences in study design or heterogeneity in affective symptoms. Directions for future research are given.


Chronological changes of MRI findings on striatal damage after acute cyanide intoxication: pathogenesis of the damage and its selectivity, and prevention for neurological sequelae: a case report.
A 31-year-old male technician in an electroplating factory, who had been suffering from the temporal lobe epilepsy for 24 years and from hypertension for 2 years, took an unknown amount of potassium cyanide apparently over the lethal dose, in an attempt to commit suicide. He was treated successfully and survived without any neurological sequelae. The electroencephalograms and the nature of the seizures were not different before and after the poisoning. The T2-weighted magnetic resonance images at 9 and 51 days after the poisoning showed bilateral elevation of signals in the caudate nuclei and the putamina. At the 143th and 286th days. T2-weighted high-resonance areas were restricted to the lateral portion of the putamina. The T1-weighted images at the 51st day showed abnormal signal elevations in both putamina, while those of 9th, 143th and 286th days were mainly normal. Selective vulnerability of the putamen and the caudate nucleus may be due to their specific structural properties of high oxygen and glucose utilization, and enzyme distribution. Both chronological changes of striatal damage and the absence of neurological sequelae in this patient suggest the possibility that anti-epileptics and a calcium antagonist played a neuroprotective role in the acute cyanide intoxication.


FSH is superior to eCG for promoting ovarian response in Chinese Bamei gilts.
The Bamei gilt is a Chinese native breed located in northwest China, which adapts to the extremely dry and cold environment and is distinguished for its excellent reproductive and maternal characters. To ensure sufficient numbers of embryos for transgenic and nuclear transfer research, hormonal induction of gilt estrus and superovulation may be necessary. The objective of this study was to compare the superovulation effects of equine chorionic gonadotropin (eCG, Group A) and FSH (Groups B-D) in Chinese Bamei gilts. The results show that though eCG could produce more corpora lutea (CL, 14.3) than the control (CL, 9.2), and the FSH treatments had significantly increased the number of CL compared with the eCG treatment. Within the different FSH protocols, the numbers of CL were significantly greater in Groups B (CL, 77.8) and C (CL, 66.8) than in Group D (CL, 42.7), however, ovarian cysts were observed in Groups B and C, but not in Group D. These data suggest that Group D (280 IU FSH) is a suitable protocol to facilitate the development of ovarian follicles and increase the number of useful embryos per gilt for embryos recovery. The optimal FSH protocol of superovulation in Bamei gilts appears to be: D13/100 IU, D14/80 IU, D15/60 IU, D16/40 IU plus prostaglandin (PG) 0.2mg, D17/hCG 1000 IU.


Enrichment experiment of ventilation air methane (0.5%) by the mechanical tower.
Methane is one of the most important gases leading to the earth's air pollution. Ventilation air methane(VAM) is an important part of the gas discharged into the atmosphere. The volume concentration of methane is generally less than 0.5% in coal mines. Recycling low concentration is facing challenges. To explore the law of low concentration methane enrichment, the enrichment tower for methane was designed and manufactured. The experiment was divided into two types - free diffusion and weak eddy enrichment, and eight kinds of low concentration gas experimental program. Under free diffusion conditions, the maximum methane concentration of the top (middle) tower is 0.64% (0.53%). In the condition of weak eddy field, the maximum methane concentration is 0.67% (0.69%) in the top (middle) tower. The effect of methane enrichment in the weak eddy field is obvious. Methane enrichment method under the eddy current field can greatly increase methane enrichment efficiency and achieve the goal of CMM (coal mine methane) power generation.


Genomic alterations of human gliomas detected by restriction landmark genomic scanning.
Alterations of genomic DNA in eight primary astrocytic tumors and two glioma cell lines were examined using a recently developed two-dimensional gel electrophoresis method called restriction landmark genomic scanning (RLGS). RLGS allows us to detect amplifications, deletions, and methylation in genomic DNA in one procedure without requiring any polymorphic markers. Approximately 2000 spots (landmark sites) in tumor specimens were compared with those in normal brain tissue. The 10 spots with intensified signal were reproducibly detected in at least 50% of primary tumors, implying amplification of corresponding DNA sequences. Conversely, 12 spots with reduced signal were observed in more than 50% of all tumors, suggesting inactivation by allelic loss, homozygous deletion, or CpG island methylation. These results suggest that common genetic alterations are closely correlated with the genesis or progression of human gliomas.


Neuropeptide VF neurons promote sleep via the serotonergic raphe.
Although several sleep-regulating neuronal populations have been identified, little is known about how they interact with each other to control sleep/wake states. We previously identified neuropeptide VF (NPVF) and the hypothalamic neurons that produce it as a sleep-promoting system (Lee et al., 2017). Here we show using zebrafish that npvf-expressing neurons control sleep via the serotonergic raphe nuclei (RN), a hindbrain structure that is critical for sleep in both diurnal zebrafish and nocturnal mice. Using genetic labeling and calcium imaging, we show that npvf-expressing neurons innervate and can activate serotonergic RN neurons. We also demonstrate that chemogenetic or optogenetic stimulation of npvf-expressing neurons induces sleep in a manner that requires NPVF and serotonin in the RN. Finally, we provide genetic evidence that NPVF acts upstream of serotonin in the RN to maintain normal sleep levels. These findings reveal a novel hypothalamic-hindbrain neuronal circuit for sleep/wake control.


Repeatability of central aortic blood pressures measured non-invasively using radial artery applanation tonometry and peripheral pulse wave analysis.
To estimate the repeatability of radial pulse wave analysis (PWA) in measuring central systolic and diastolic blood pressures (cSBP/cDBP), pulse pressure (cPP), augmentation pressure (cAP) and pulse pressure amplification (PPA). After 15 min supine rest, 20 ambulant patients (aged 27-82 years; four female) underwent four SphygmoCor PWA measurements on a single occasion. Two nurses independently undertook two measurements in alternate order, blind to their colleague's measurements. Analysis was by Bland-Altman limits of agreement (LOA). Heart rate and brachial blood pressure (BP) were stable during assessment. Based on the average of two PWA measurements between-observer differences (LOA, mean difference +/- 2SD) were small (cSBP 1.5 +/- 10.9 mmHg; cDBP 0.4 +/- 5.2 mmHg; cAP 0.5 +/- 4.5 mmHg; cPP 1.1 +/- 10.5 mmHg; PPA -0.5% +/- 5.6%). Between-observer differences were much greater for single/initial PWA measurement (cSBP 3.6 +/- 15.9 mmHg; cDBP 2.8 +/- 8.8 mmHg; cAP 0.7 +/- 5.8 mmHg; cPP 0.8 +/- 13.6 mmHg; PPA -1.2 +/- 9.4%). Within-observer LOA were very similar for both nurse A (cSBP -4.2 +/- 14.1 mmHg; cDBP -4.6 +/- 13.1 mmHg; cAP -0.4 +/- 4.4 mmHg; cPP 0.5 +/- 11.0 mmHg; PPA 0.7% +/- 9.0%) and nurse B (cSBP 0.0 +/- 12.1 mmHg; cDBP 0.2 +/- 8.5 mmHg; cAP -0.1 +/- 4.4 mmHg; cPP -0.2 +/- 11.9 mmHg; PPA -0.7% +/- 10.6%). Non-invasive assessment of central aortic pressures using PWA on a single occasion is highly repeatable in ambulant patients even when used by relatively inexperienced staff.


Predicting postoperative gastric cancer prognosis based on inflammatory factors and machine learning technology.
There is a strong association between gastric cancer and inflammatory factors. Many studies have shown that machine learning can predict cancer patients' prognosis. However, there has been no study on predicting gastric cancer death based on machine learning using related inflammatory factor variables. Six machine learning algorithms are applied to predict total gastric cancer death after surgery. The Gradient Boosting Machine (GBM) algorithm factors accounting for the prognosis weight outcome show that the three most important factors are neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and age. The total postoperative death model showed that among patients with gastric cancer from the predictive test group: The highest accuracy was LR (0.759), followed by the GBM algorithm (0.733). For the six algorithms, the AUC values, from high to low, were LR, GBM, GBDT, forest, Tr and Xgbc. Among the six algorithms, Logistic had the highest precision (precision = 0.736), followed by the GBM algorithm (precision = 0.660). Among the six algorithms, GBM had the highest recall rate (recall = 0.667). Postoperative mortality from gastric cancer can be predicted based on machine learning.


Variation in burn wound management approaches for paediatric burn patients in Australia and New Zealand.
To date, no large-scale exploration of the profile of, and variance among paediatric patients who underwent a burn wound management procedure in theatre exists in an Australian and New Zealand context. This study aims to provide a profile of paediatric burn patients who underwent a burn wound management procedure in theatre during an acute admission and highlight specific areas of practice where there is variation between burn services that may affect treatment efficacy and efficiency. We performed a retrospective review of all paediatric patients (ages <16 years) who sustained a burn injury between July 2016 and June 2019 and underwent a burn wound management procedure in theatre, using data from the Burns Registry Australia New Zealand. The number of patients across burn services decreased as TBSA increased. Deep dermal burns represented the majority of cases across services. There was significant variation in time from injury to admission and the proportion of patients who received skin grafts across services. Significant differences in the patient profile and clinical practices were observed among burn services. A greater understanding of the factors underlying the variations at each particular service will also be helpful.


Genome structural evolution in Brassica crops.
The cultivated Brassica species include numerous vegetable and oil crops of global importance. Three genomes (designated A, B and C) share mesohexapolyploid ancestry and occur both singly and in each pairwise combination to define the Brassica species. With organizational errors (such as misplaced genome segments) corrected, we showed that the fundamental structure of each of the genomes is the same, irrespective of the species in which it occurs. This enabled us to clarify genome evolutionary pathways, including updating the Ancestral Crucifer Karyotype (ACK) block organization and providing support for the Brassica mesohexaploidy having occurred via a two-step process. We then constructed genus-wide pan-genomes, drawing from genes present in any species in which the respective genome occurs, which enabled us to provide a global gene nomenclature system for the cultivated Brassica species and develop a methodology to cost-effectively elucidate the genomic impacts of alien introgressions. Our advances not only underpin knowledge-based approaches to the more efficient breeding of Brassica crops but also provide an exemplar for the study of other polyploids.


Raman frequency shifts of an internal mode near the tricritical and second order phase transitions in NH4Cl.
This study gives our analysis for the frequency shifts of the v2 (1708 cm-1) Raman mode in NH4Cl close to its tricritical (P=1.6 kbar) and second order (P=2.8 kbar) phase transitions. From our analysis, we extract the values of the critical exponent which describes the critical behavior of the Raman frequency shifts for this internal mode for the pressure conditions studied in NH4Cl. Our exponent value of alpha approximately 0.2 for the tricritical phase transition is close to the values of 1/16 (T<Tc) and 1/8 (T>Tc) for the specific heat, predicted from a 3D Ising model. Our exponent values for the second order phase transition (P=2.8 kbar) for T<Tc and T>Tc are comparable with those reported in earlier studies.


LncRNA signature in colorectal cancer.
Colorectal cancer (CRC) is among the most frequent cancers and is associated with high mortality particularly when being diagnosed in advanced stages. Although several environmental and intrinsic risk factors have been identified, the underlying cause of CRC is not clear in the majority of cases. Several studies especially in the recent decade have pointed to the role of epigenetic factors in this kind of cancer. Long non-coding RNAs (lncRNAs) as important contributors in the epigenetic mechanisms are involved in the initiation, progression and metastasis of CRC. Tens of oncogenic lncRNAs and a lower number of tumor suppressor lncRNAs have been recently identified to be dysregulated in CRC cells and tissues. Notably, expressions of a number of these transcripts have been dysregulated in serum samples of CRC patients, providing a non-invasive route for detection of this kind of cancer. The involvement of lncRNAs in the regulation of autophagy has provided them the ability to modulate response of CRC cells to chemotherapeutic modalities. In the current manuscript, we review the studies which evaluated the role of lncRNAs in the pathogenesis and progression of CRC to appraise their application as diagnostic/ prognostic markers.


Effect of antioxidant treatment on the shear bond strength of composite resin to bleached enamel.
This study examined the antioxidant treatment on the shear bond strength of composite resin to enamel after bleaching with two different bleaching systems. Seventy flat enamel surfaces were prepared from freshly extracted human molars using a low speed diamond saw. Then the specimens were divided into seven random groups (n = 10) to apply different procedures; namely, bleaching with White Smile and bonding with composite resin (G1), bleaching with White Smile, treatment with ascorbic acid and bonding with composite resin (G2), bleaching with White Smile, immersing in artificial saliva for 2 weeks and bonding with composite resin (G3), bleaching with Opalesence and bonding with composite resin (G4), bleaching with Opalesence, treatment with ascorbic acid and bonding with composite resin (G5) and bleaching with Opalesence, immersing in artificial saliva for 2 weeks and bonding with composite resin (G6). Another group was used as a control group. Shear bond test was performed on all specimens and data were analyzed using one way ANOVA and Bonferroni's test (p < 0.05). Bond strengths of bleached specimens were significantly lower than those of non-bleached specimens. No statistical difference was found in bond strength between the bleached and non-bleached groups when the antioxidant treatment was carried out. Ten per cent ascorbic acid treatment was found to be an effective method to reverse the compromised bond strength.


A consideration of Euglena gracilis W3BUL as a cytoplasmic control for the wild-type phenylalanyl-tRNA synthetase system.
The studies described indicate that the UV bleached mutant, Euglena gracilis W3BUL does not serve as a suitable cytoplasmic control for the phenylalanyl-tRNA synthetase system. Chromatography of wild-type E. gracilis on Sephadex G100 revealed three peaks of activity identified as the chloroplastic, cytoplasmic and mitochondrial enzymes. The chloroplastic activity was greater in log than in stationary phase cells and was the only activity recovered from purified chloroplasts. Cell-free extracts of the achloroplstic mutant, E. gracilis W3BUL, contained wild-type levels of the cytoplasmic and mitochondrial phenylalanyl-tRNA synthetases. However, no chloroplastic synthetase was detected in the mutant extracts. Anomalies in the aminoacylation behavior of the W3BUL system were observed which suggest the possibility of a mutation affecting non-chloroplastic tRNAs in this UV-induced mutant. These anomalies significantly reduce the ability of the E. gracilis W3BUL mutant to serve as a cytoplasmic control in the phenylalanyl-tRNA synthetase system.


Exploring in vitro anti-proliferative and anti-inflammatory activities of Prasachandaeng remedy, and its bioactive compounds.
Prasachandaeng (PSD) remedy has been empirically used in Thai traditional medicine to treat fever in bile duct and liver and cancer patients through Thai folk doctors. However, there have been no scientific reports on the bioactive compounds and bioactivities related to inflammation-associated carcinogenesis or cytotoxicity against cancer cell lines. In this study, we investigated the chemical content of the remedy, and evaluated its cytotoxic activity against two cancer cell lines in comparison with a non-cancerous cell line and determined tumor necrosis factor-alpha (TNF-α) production in a murine macrophage cell line (RAW 264.7) to evaluate anti-inflammatory activity. A novel HPLC method was used for quality control of its chemical content. Pure compounds from the EtOH extract of D. cochinchinensis were isolated using bioassay-guided fractionation and chemical content of the PSD remedy was determined using HPLC. The cytotoxic activity against the hepatocarcinoma cell line (HepG2) and cholangiocarcinoma cell line (KKU-M156), in comparison with non-cancerous cell line (HaCaT), were investigated using antiproliferative assay (SRB). The anti-inflammatory activity measured by TNF-α production in RAW 264.7 was determined using ELISA. All crude extracts and isolated compounds exhibited significant differences from vincristine sulfate (****p < 0.0001) in their cytotoxic activity against HepG2, KKU-M156, and HaCaT. The PSD remedy exhibited cytotoxic activity against HepG2 and KKU-M156 with IC50 values of 10.45 ± 1.98 (SI = 5.3) and 4.53 ± 0.74 (SI = 12.2) µg/mL, respectively. Some constituents from C. sappan, D. cochinchinensis, M. siamensis, and M. fragrans also exhibited cytotoxic activity against HepG2 and KKU-M156, with IC50 values less than 10 µg/mL. The isolated compounds, i.e., Loureirin B (1), 4-Hydroxy-2,4'-dimethoxydihydrochalcone (2), and Eucomol (3) exhibited moderate cytotoxicity against two cancer cell lines. None of the crude extracts and isolated compounds showed cytotoxicity against HaCaT. D. cochinchinensis and PSD remedy exhibited higher anti-inflammatory activity measured as TNF-α production than acetaminophen. The findings provide evidence of bioactivity for EtOH extracts of PSD remedy and the isolated compounds of D. Cochinchinensis. The results consistent the use clinical activity and use of PSD remedy as a antipyretic treatment for liver and bile duct cancer patients by Thai traditional practitioners.


Interleukin-1, -6, and -8 levels in juvenile chronic arthritis.
The immunoinflammatory pathogenesis of juvenile chronic arthritis (JCA) involves the activation of many pathways including various cytokines. We have evaluated the levels of interleukin(IL)-1, IL-6 and IL-8 in 29 JCA patients. The age range was 1-16 with a mean of 10.1. A disease activity score was developed on the basis of: 1. constitutional symptoms and/or morning stiffness, 2. presence of joint swelling, 3.warmth, 4.limited range of motion, and 5.joint pain. This score correlated very significantly with laboratory disease activity markers such as erythrocyte sedimentation rate (ESR) and CRP (both p = 0.006) and also correlated with IL-1 and IL-6 levels. The levels of IL-1 decreased in four of the five patients with improved disease activity. IL-6 but not IL-1 correlated significantly with the number of inflamed joints (p = 0.013); IL-6 also strongly correlated with rheumatoid factor supporting this cytokine's role in B cell induction (p = 0). Haemoglobin values correlated negatively with the activity index, ESR, CRP, IL-1 and IL-6. IL-8 did not correlate with disease activity markers. In the systemic patients all cytokines tended to be higher. Our data suggest that interleukins 1 and 6 are effective in the pathogenesis of JCA. Whether cytokines may be used for monitoring therapy may be clarified with further studies.


Vasoactive intestinal polypeptide increases inositol phospholipid breakdown in the rat superior cervical ganglion.
The effects of VIP and of peptides of the VIP family: secretin, glucagon, the porcine histidine isoleucine containing peptide (PHI) and the rat hypothalamic growth hormone-releasing hormone (rhGRF) on the cyclic AMP and inositol phosphate contents of isolated rat superior cervical ganglia were investigated. We demonstrate that VIP is able to provoke a large inositol lipid breakdown by acting directly on ganglionic cells. This observation suggests the presence in rat superior cervical ganglia of a new type of receptors for VIP or for an unidentified peptide structurally related to VIP.


High level of B19 strain detection in Brazilian cattle semen.
Semen contaminated with microorganisms can disseminate serious diseases including brucellosis. The objectives of this study were to detect Brucella-specific antibodies and Brucella abortus DNA in samples of blood and fresh semen from 100 animals older than 20 months. The samples were collected on farms and in semen collection and processing centers (CCPS). The serum samples were evaluated by Rose Bengal test (RBT). B. abortus DNA was detected by a polymerase chain reaction (PCR) using BAB and IS771 primers. The difference between the vaccine field strain was identified using ery-1, ery-2, and ery-3 primers, using the hemi-nested PCR method. No anti-B. abortus antibodies were detected in the serum samples. Out of the total semen samples, 68% (68/100) presented amplifications of the B. abortus genes. All (68/68) were identified as B19 strain of Brucella abortus vaccine. It was concluded that even bulls that are seronegative for brucellosis can eliminate the bacteria in the semen. The presence in the DNA of the B19 vaccine strain should be investigated for a better understanding of the epidemiological importance of this strain in these animals.


[Polyendocrine syndromes in dogs].
The autoimmune polyendocrine syndrome (APS) refers to a combination of autoimmune endocrine disorders. It is rarely described in dogs. The most common combinations are hypoadrenocorticism and hypothyroidism, followed by diabetes mellitus, and less often hypoparathyroidism and orchitis. The diagnosis of the APS is based on the diagnosis of each endocrinopathy, as is the therapy, which involves the substitution of deficient hormones. If a patient was previously stable under treatment and is showing further signs (e.g. polyuria, polydipsia, or weight loss), the development of additional endocrinopathies like hypoadrenocorticism or diabetes mellitus should be considered. The diagnosis of the initially diagnosed endocrinopathy should also be critically questioned. This article summarizes some cases of our own animal hospital and selected cases published in the available literature.


Transition state analogs of 5'-methylthioadenosine nucleosidase disrupt quorum sensing.
5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) is a bacterial enzyme involved in S-adenosylmethionine-related quorum sensing pathways that induce bacterial pathogenesis factors. Transition state analogs MT-DADMe-Immucillin-A, EtT-DADMe-Immucillin-A and BuT-DADMe-Immucillin-A are slow-onset, tight-binding inhibitors of Vibrio cholerae MTAN (VcMTAN), with equilibrium dissociation constants of 73, 70 and 208 pM, respectively. Structural analysis of VcMTAN with BuT-DADMe-Immucillin-A revealed interactions contributing to the high affinity. We found that in V. cholerae cells, these compounds are potent MTAN inhibitors with IC(50) values of 27, 31 and 6 nM for MT-, EtT- and BuT-DADMe-Immucillin-A, respectively; the compounds disrupt autoinducer production in a dose-dependent manner without affecting growth. MT- and BuT-DADMe-Immucillin-A also inhibited autoinducer-2 production in enterohemorrhagic Escherichia coli O157:H7 with IC(50) values of 600 and 125 nM, respectively. BuT-DADMe-Immucillin-A inhibition of autoinducer-2 production in both strains persisted for several generations and caused reduction in biofilm formation. These results support MTAN's role in quorum sensing and its potential as a target for bacterial anti-infective drug design.


WITHDRAWN: Protein sumoylation and human diseases.
This review has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Delayed presentation of bone cement implantation syndrome requiring extracorporeal membrane oxygenation support.
Bone cement implantation syndrome is a rare and potentially fatal complication which may occur following cemented bone surgery. Herein, we present a case of delayed and fatal presentation of bone cement implantation syndrome following cemented spinal surgery, despite mechanical support with extracorporeal mechanical oxygenation.


Nutritional deficiencies after bariatric surgery.
Lifestyle intervention programmes often produce insufficient weight loss and poor weight loss maintenance. As a result, an increasing number of patients with obesity and related comorbidities undergo bariatric surgery, which includes approaches such as the adjustable gastric band or the 'divided' Roux-en-Y gastric bypass (RYGB). This Review summarizes the current knowledge on nutrient deficiencies that can develop after bariatric surgery and highlights follow-up and treatment options for bariatric surgery patients who develop a micronutrient deficiency. The major macronutrient deficiency after bariatric surgery is protein malnutrition. Deficiencies in micronutrients, which include trace elements, essential minerals, and water-soluble and fat-soluble vitamins, are common before bariatric surgery and often persist postoperatively, despite universal recommendations on multivitamin and mineral supplements. Other disorders, including small intestinal bacterial overgrowth, can promote micronutrient deficiencies, especially in patients with diabetes mellitus. Recognition of the clinical presentations of micronutrient deficiencies is important, both to enable early intervention and to minimize long-term adverse effects. A major clinical concern is the relationship between vitamin D deficiency and the development of metabolic bone diseases, such as osteoporosis or osteomalacia; metabolic bone diseases may explain the increased risk of hip fracture in patients after RYGB. Further studies are required to determine the optimal levels of nutrient supplementation and whether postoperative laboratory monitoring effectively detects nutrient deficiencies. In the absence of such data, clinicians should inquire about and treat symptoms that suggest nutrient deficiencies.


Biopsy techniques for the diagnosis of mesothelioma.
The incidence of mesothelioma continues to increase in the Western world and is likely to do so until 2011-2015. It commonly presents with breathlessness secondary to a pleural effusion, and whilst guidelines still advise thoracocentesis as the first line investigation, the sensitivity of this is low and a tissue diagnosis is usually required. Abrams needle biopsy also has a low diagnostic yield and high complication rate and is not recommended in guidelines on the investigation of mesothelioma. Computed tomography-guided biopsy or thoracoscopy both have a comparable sensitivity and low complication rates. Local anaesthetic thoracoscopy is increasingly used by respiratory physicians and has a comparable diagnostic sensitivity to Video-Assisted Thoracoscopic Surgery (VATS) without the need for a general anaesthetic. The requirement for prophylactic radiotherapy after pleural procedures in cases of mesothelioma is contentious, as the results from early trials suggesting it reduces tract seeding have been disputed by more recent trials.


White clot syndrome: a life-threatening complication of heparin therapy.
Nurses administering heparin should be aware that arterial or venous heparin-induced thrombosis may be a paradoxical effect of the heparin itself and can result in stroke, myocardial infarction, pulmonary embolism, loss of limb, and even death.


Predictors of functional shoulder recovery at 1 and 12 months after breast cancer surgery.
The objective of this study are (1) to determine if upper extremity function, as represented by shoulder ROM, self-reported symptoms and upper extremity functional limitations in activities of daily living could be predictively related to demographic and cancer characteristics post-surgery for breast cancer. And (2) to examine if variables related to early onset impairment contribute to late onset impairments in women after breast cancer surgery. Subjects were assessed preoperatively and 1, 3, 6, 9, and 12+ months post breast cancer surgery for impairments and symptoms and at 12+ months for shoulder functional limitations using a physical therapy surveillance model. Body weight, shoulder ROM, manual muscle testing, and upper limb volume were recorded. At 12+ months, the Harvard Alumni Health Study Physical Activity Questionnaire, and an Upper Limb Disability Questionnaire were administered. Symptoms and ROM impairments were compared by functional limitations. Characteristics significantly associated with early ROM impairment (but not later impairment) were axillary lymph node dissection, removal of ≥15 nodes, mastectomy surgery and stage II breast cancer. Positive nodes, older age, and BMI≥25 were significantly associated with reduced shoulder ROM at 12+ months. At 12+ months, only 10 % of the patients experienced ROM impairments while rates of self-reported symptoms in the affected upper extremity at 12+ months were as follows: pain-49%, weakness-47.1%, numbness-55.9%, feeling tired-42.5%. The majority of patients used the affected upper extremity for reaching without limitation, but ≥35% reported limitation with household chores, carrying and lifting. Difficulty carrying and lifting could be predicted by BMI≥25 and use of the dominant affected upper limb. Different factors are associated with early versus later ROM loss. Symptoms reported by breast cancer survivors are frequently associated with functional limitations in upper extremity tasks and warrant intervention. Physical therapy using a prospective surveillance model of care may reduce severity of ROM loss, symptoms and functional upper extremity limitations 1 year after breast cancer surgery.


Absence of uvomorulin in a slowly compacting variant of H6 embryonal carcinoma cells.
When allowed to aggregate in calcium-containing medium, the H6 embryonal carcinoma cell variant named 6B(NG)C25 compacted more slowly than wild-type cells, and aggregates of hybrids between it and wild-type cells also compacted slowly, as if the variation (mutation) acted in a dominant fashion. In agreement with this, we now have found that the cell adhesion molecule uvomorulin is markedly reduced or absent in 6B(NG)C25 cells, as well as in the hybrids. A small amount of a higher-molecular-weight protein reacting with the antibody is present, which might represent residual uvomorulin migrating at a slower rate, an altered uvomorulin, the known precursor to uvomorulin, or an unrelated cross-reacting protein.


Molecular dynamics simulations to study the role of biphenylalanine in promoting the antibacterial activity of ultrashort peptides.
The hydrophobic amino acid biphenylalanine (B) plays a key role in the antibacterial activity of ultrashort peptides. In this study, the interactions of tetrapeptide BRBR-NH2 (BRBR) and pentapeptide BRBRB-NH2 (BRBRB) with dioleoylphosphatidylcholine/dioleoylphosphatidylglycerol (DOPC/DOPG) mixed model membrane were studied by molecular dynamics simulation to assess the role of biphenylalanine in promoting the antibacterial activity of ultrashort peptides. At low peptide concentrations, both peptides presented amphiphilic conformations; residues B of the pentapeptide approached the membrane faster than those of the tetrapeptide and made more contacts with the membrane; BRBRB exhibited stronger membrane affinity than BRBR. However, due to the low peptide concentrations, the effects of these two peptides on the membrane were not significantly different. At high peptide concentrations, the strong affinity of BRBRB made it have more interaction with membrane than BRBR and most residues B of BRBRB inserted into the membrane; BRBRB was more prone to aggregation and caused the membrane more disordered and thinner than BRBR. Hydrophobic residues often act as anchors in the antibacterial activity of ultrashort antimicrobial peptides. Adding a hydrophobic residue B to the C-terminal of BRBR could improve the ability of the peptide to "grasp" the membrane. At high peptide concentrations, the addition of residue B might enhance the antibacterial activity of the peptide. Thus, our results will be helpful in designing efficient antibacterial drugs.


Schwannoma originating in the soft palate: A case report.
Schwannomas are relatively uncommon, benign, slow-growing neoplasms, which are derived from schwann cells that can arise from any cranial, peripheral, or autonomic nerves. The involvement of the palate is a rare presentation and hardly reported in the literature. Here, we report the case of a 39-year-old woman with a history of a foreign body sensation in the throat and difficult swallowing. Oral examination showed a smooth, non-tender, right-sided, soft palate mass. Computed tomography (CT) scan revealed a well-defined, non-enhancing, homogenous pedunculated soft tissue mass arising from the posterior edge of the right side of the soft palate. The mass was excised completely under local anesthesia in the clinical setting using a CO2 surgical laser. The mass was sent for histologic analysis, which confirmed the diagnosis of a benign schwannoma. Eventually, upon follow-up at six months post excision, no evidence of recurrence was detected.


Antidepressant-like effect of hydroalcoholic extract from barks of Rapanea ferruginea: Role of monoaminergic system and effect of its isolated compounds myrsinoic acid A and B.
Major Depressive Disorder (MDD) is a highly disabling condition and has been linked to increased inflammatory mediators. Hydroalcoholic extract from barks of Rapanea ferruginea (HEBRF) and the majoritary compounds-myrsinoic acid A (MAA) and B (MAB)-have been studied due to their anti-inflammatory potential, but there is no evidence about its antidepressant-like effects. This research investigated the HEBRF, MAA, and MAB antidepressant-like effect, besides the involvement of the monoaminergic system and MAO-A activity in the HEBRF antidepressant-like effect. HEBRF (50-300 mg/kg, p.o.), MAA (5-30 mg/kg, p.o.) or MAB (3-60 mg/kg, p.o.) were administrated to mice, and behavioral parameters were assessed using the tail suspension test (TST), splash test (ST) and open field test (OFT). The involvement of monoaminergic system in the HEBRF antidepressant-like effect was established through the pretreatment of mice with antagonists. The influence triggered by HEBRF in the monoamine oxidase A (MAO-A) activity was evaluated in the hippocampus (HIP) and prefrontal cortex (PFC) of mice. HEBRF (100-300 mg/kg) promoted antidepressant-like effect in the TST and augmented the total time of grooming in the ST, without compromising the locomotor activity. Pretreatment of mice with serotoninergic, dopaminergic, and noradrenergic antagonists, reversed the HEBRF antidepressant-like effect. Besides, HEBRF inhibited the MAO-A activity in the HIP and PFC. Moreover, MAA (5 mg/kg) and MAB (3 mg/kg) also promoted antidepressant-like and anti-anhedonic effects in mice. Data showed that monoaminergic system is involved in the HEBRF antidepressant-like effect, besides MAA and MAB possibly could be responsible for these pharmacological effects.