Safety of intravenous sedation administered by the operating oral surgeon: the first 7 years of office practice.
Outpatient intravenous sedation by properly trained personnel provides a safe, cost-effective means of anesthesia for numerous surgical procedures. The goal of this study was to provide a 7-year summary (December 1994 through November 2001) of anesthesia-related problems that occurred in the practice of a single Midwestern board-certified oral and maxillofacial surgeon. The files of intravenous sedation cases from December 1994 through November 2001 were organized retrospectively. A total of 2,889 sedations were performed by the surgeon during the 7-year period. There were 1,743 (about 60.33%) patients in ASA Class I, 1,139 (about 39.43%) in ASA Class II, and 7 (about 0.24%) in ASA Class III. There were a total of 70 patients who had 77 adverse events. Less than 3% of the sedation patients experienced complications. There were no deaths and no patients required emergency transport to a hospital. The administration of intravenous sedation by the operating surgeon for outpatient oral surgery procedures is safe and results in a low incidence of adverse events. In this series, a number of previously undiagnosed medical problems were discovered. The diagnosis and referral for management of these medical problems improved patient health.


Physician-Assisted Suicide and Other Forms of Euthanasia in Islamic Spiritual Care.
The muteness in the Qur'an about suicide due to intolerable pain and a firm opposition to suicide in the hadith literature formed a strong opinion among Muslims that neither repentance nor the suffering of the person can remove the sin of suicide or mercy 'killing' (al-qatl al-rahim), even if these acts are committed with the purpose of relieving suffering and pain. Some interpretations of the Islamic sources even give advantage to murderers as opposed to people who commit suicide because the murderers, at least, may have opportunity to repent for their sin. However, people who commit suicide are 'labeled' for losing faith in the afterlife without a chance to repent for their act. This paper claims that Islamic spiritual care can help people make decisions that may impact patients, family members, health care givers and the whole community by responding to questions such as 'What is the Islamic view on death?', 'What is the Islamic response to physician-assisted suicide and other forms of euthanasia?', 'What are the religious and moral underpinnings of these responses in Islam?'


Periodontitis and tooth loss: comparing diabetics with the general population.
People with diabetes may be at increased risk for periodontal disease. This study compared the periodontal health of diabetic and employed adults. While tooth loss and gingival attachment was similar for both groups, diabetics had a greater prevalence and extent of periodontal pockets. Diabetics with poor metabolic control and calculus also had more periodontitis.


Matrix-assisted pulsed laser evaporation of β-glucosidase from a dopa/quinone target.
β-glucosidase (BG) plays a key role in determining the efficiency of the enzymatic complex cellulase for the degradation of cellulose into sugars. It hydrolyses the cellobiose, an inhibitor of the enzymatic complex. Therefore, the immobilization of BG is a great challenge for the industrial application of cellulases. Cellulases usually contains a BG amount insufficient to avoid inhibition by cellobiose. Here the BG was immobilized by matrix assisted pulsed laser evaporation (MAPLE) technique. The frozen matrix was composed of water, water/m-DOPA and water/m-DOPA/quinone. The effect of the excipients on the final conformation of the enzyme after the MAPLE processing was determined. The enzyme secondary structure was studied by FTIR analysis. The catalytic performances of the deposited films were tested in the cellobiose hydrolysis reaction. The results demonstrate that the presence of the oxidized form of m-DOPA, the O-quinone form, can protect the protein native structure, with the laser inducing little or no damage. In fact, only the samples deposited from this target preserved the secondary structure of the polypeptide chain and allowed a complete hydrolysis of cellobiose for four consecutive runs, showing a high operational stability of the biocatalyst.


Nerve sheath tumor in the forearm of a common marmoset (Callithrix jacchus).
Tumors of the skin and subcutaneous tissues are uncommon in marmosets. In this report, we describe the gross, histopathology, and immunohistochemical findings of a nerve sheath tumor that arose in the left forearm of an adult female marmoset (Callthrix jacchus).


Late postoperative tamponade following coronary artery bypass grafting in patients on antiplatelet therapy.
Myocardial revascularization was performed in 1,361 patients over a 66-month period (February, 1978 to August, 1983) without a single occurrence of late cardiac tamponade. During a subsequent 4-month-period, aspirin and dipyridamole were administered routinely to all coronary bypass patients. The incidence of late cardiac tamponade rose significantly (p less than 0.001) to 3 of 85 patients (3.5%). Routine perioperative administration of aspirin and dipyridamole to patients undergoing myocardial revascularization may be associated with an increased incidence of delayed cardiac tamponade.


Evaluation of next generation sequencing for the analysis of Eimeria communities in wildlife.
Next-generation sequencing (NGS) techniques are well-established for studying bacterial communities but not yet for microbial eukaryotes. Parasite communities remain poorly studied, due in part to the lack of reliable and accessible molecular methods to analyse eukaryotic communities. We aimed to develop and evaluate a methodology to analyse communities of the protozoan parasite Eimeria from populations of the Australian marsupial Petrogale penicillata (brush-tailed rock-wallaby) using NGS. An oocyst purification method for small sample sizes and polymerase chain reaction (PCR) protocol for the 18S rRNA locus targeting Eimeria was developed and optimised prior to sequencing on the Illumina MiSeq platform. A data analysis approach was developed by modifying methods from bacterial metagenomics and utilising existing Eimeria sequences in GenBank. Operational taxonomic unit (OTU) assignment at a high similarity threshold (97%) was more accurate at assigning Eimeria contigs into Eimeria OTUs but at a lower threshold (95%) there was greater resolution between OTU consensus sequences. The assessment of two amplification PCR methods prior to Illumina MiSeq, single and nested PCR, determined that single PCR was more sensitive to Eimeria as more Eimeria OTUs were detected in single amplicons. We have developed a simple and cost-effective approach to a data analysis pipeline for community analysis of eukaryotic organisms using Eimeria communities as a model. The pipeline provides a basis for evaluation using other eukaryotic organisms and potential for diverse community analysis studies.


The effectiveness of N-acetyl-L-cysteine (L-NAC) in the prevention of severe noise-induced hearing loss.
Three groups of chinchillas were exposed to a nonGaussian continuous broadband noise at an Leq=10 5dB SPL, 8h/d for 5d. One group (N=6) received only the noise. A second group (N=6) received the noise and was additionally treated with L-NAC (325 mg/kg, i.p.). Treatment was administered twice daily for 2d prior to exposure and for 2d following the exposure. During exposure the animals received the L-NAC just prior to and immediately after each daily exposure. The third group (N=4) was exposed to the noise and received saline injections on the same schedule as the L-NAC treated animals. Auditory evoked potential recordings from the inferior colliculus were used to estimate pure tone thresholds and surface preparations of the organ of Corti quantified the sensory cell population. In all three groups PTS exceeded 50 dB at 2.0k Hz and above with severe sensory cell loss in the basal half of the cochlea. There was no statistically significant difference among the three groups in all measures of noise-induced trauma. Treatment with L-NAC did not reduce the trauma produced by a high-level, long duration, broadband noise exposure.


Oncolytic intralesional therapy for metastatic melanoma.
In-transit metastasis (ITM) develop in approximately 1 in 10 patients with melanoma and the disease course can vary widely. Surgical resection is the gold-standard treatment; however, ITM are often surgically unresectable due to size, distribution, and/or anatomic involvement. Oncolytic viral therapies are one category of non-surgical treatment options available for ITM. They induce tumor cell lysis and systemic anti-tumor activity through selective infection of tumor cells by naturally occurring or genetically modified factors. While there are numerous oncolytic viral therapies in various stages of development for the treatment of ITM, this discussion focuses on the mechanism and available literature for the two most established herpes virus-based therapies.


Multiple abscesses caused by Gardnerella vaginalis in an immunocompetent man.
Gardnerella vaginalis causing significant infection in men is rare. We report a case of sepsis in a previously well man, who developed a perinephric abscess and empyema. G. vaginalis was isolated after prolonged culture of samples from both sites. The microbiological features of the case are discussed.


Antibiotic-loaded Bone Cement in the Management of Neosternal Osteomyelitis.
Antibiotic-loaded bone cement is an alternative treatment option that can be used in the surgical management of osteomyelitis requiring bone resection and reconstruction. Current literature provides a focus on its use within the orthopedic patient group with scarce literature surrounding the cardiothoracic patient demographic. We hereby demonstrate the use of an antibiotic-loaded bone cement in the definitive management of neosternal osteomyelitis and nonunion, avoiding the need for further complex autografting and internal fixation.


Laboratory diagnosis of factitious disorder: a systematic review of tools useful in the diagnosis of Munchausen's syndrome.
To assist clinicians in the diagnosis of factitious disorder. This is a systematic review of the role of laboratory, radiologic, procedural, and pathological modalities to assist in the diagnosis of factitious disorder (Munchausen's syndrome). The review evaluated 3104 article titles and abstracts that were identified from MEDLINE as of January 2010. We found 190 articles that demonstrated techniques that will assist clinicians in recognizing fabricated manifestations of disease. The results are divided into 13 areas of clinical medicine for easy reference. They are further sub-divided by the diseases or conditions that patients have been reported to simulate and the diagnostic techniques suggested by the literature in each case. Factitious disorder is difficult to diagnose and may present as a wide array of fabricated conditions, but there are a range of laboratory and technical means available to assist clinicians in the 21st Century.


Relationship between boldness and exploratory behavior in adult zebrafish.
Behavioral responses vary between individuals and may be repeated in different contexts over time. When a behavioral response set is linked and present regardless of the context, it characterizes a behavioral syndrome. By evaluating how bold and shy (profiles related to risk-taking) individuals perform about exploration and anxiety, we can predict relationships of behavioral syndromes and better understand how different axis of personality is formed. Here we classified the profiles by risk-taking and evaluated their exploration behavior in the open field test. In this context, the two groups showed significant differences in thigmotaxis behavior: bold individuals habituate faster and show decreased thigmotaxis (less anxiety), while shy ones are less prone to leave the security of the side areas of the open tank and present higher anxiety. We emphasized the importance of further investigating the behavior of these profiles in other contexts and the importance of each one for the evolution and fitness of the species, in addition to a better understanding of which behaviors are involved in the behavioral syndromes in zebrafish.


[The role of hormones from the mucosa of the gastric antrum in regulating gastric secretion].
Removal of antral mucosa obviously reduced the sensitivity of glandulocytes to pentagastrin in dogs with Basov-Pavlov fistulae. Activation of the endocrinal cells of the antral mucosa after fundal and antral parts separation exerted an opposite effect. The data obtained suggest that, along with gastrin, there is another hormonal factor facilitating the action of gastrin in the antral mucosa.


Stress radiography for clinical evaluation of anterior shoulder instability.
The purpose of this study was to examine the validity of stress radiography using the Telos GA-IIE as a clinical methodology to evaluate shoulder instability. On 36 anterior shoulder dislocators and 23 uninjured volunteers, 4 types of stress radiographs were captured while applying 15 daN of force anteriorly (AER0 and AER60) and posteriorly (PER0 and PER60) at 2 different positions: (1) 90° of abduction combined with 0° external rotation and (2) 90° of abduction combined with 60° external rotation. The results of the anterior drawer test and of the same test under anesthesia were correlated. AER0 and AER60 from the affected shoulder revealed significantly larger displacement than on the normal side (P < .05), and all 4 radiographs from the affected joints demonstrated significantly larger displacement (P < .05) than in the volunteers. Among the 4 types of radiographs, AER0 and AER60 showed significantly higher displacement in the patients (P < .001), whereas there were no differences in the volunteers (P = .167). The results of the anterior drawer test positively correlated to AER60 (Pearson correlation coefficient [PCC] = 0.453; P = .005) and AER0 (PCC = 0.529; P = .001), and those of examination under anesthesia weakly correlated to AER60 (PCC = 0.287; P = .264) but highly correlated to AER0 (PCC = 0.695; P = .002). Stress radiographs on the affected shoulder frequently correlated with physical examinations, and the displacement of >3 mm on AER0 suggests anterior instability.


Habitat use, survival, and migration of a little-known East Asian endemic, the yellow-throated bunting Emberiza elegans.
Basic information on the ecology of species is key for their conservation. Here we study the ecology of the little-known yellow-throated bunting Emberiza elegans based on a multi-year study on its breeding grounds in the Russian Far East. For the first time in this species, we quantified breeding habitat parameters, calculated sex-specific apparent survival, and determined individual nonbreeding locations using light-level geolocation. We found that the habitat around song posts of male yellow-throated buntings is characterized by tree and shrub layers on richly littered moist ground. Habitat use overlaps with co-occurring Tristram's Buntings Emberiza tristrami and Black-faced Buntings E. spodocephala, but territories differ especially in tree cover and litter cover. Based on 4 years of color-ringing data of 72 individuals, we calculated an apparent survival rate of 36%, with higher survival estimates for male than for female yellow-throated buntings. We found no effect of carrying a geolocator on survival. We retrieved six geolocators from males. All birds migrated south-westward during autumn and spent the nonbreeding season at locations in China 700-1700 km away from their breeding sites. At least two individuals spent the boreal winter outside of the known range in northern or central China. Birds left the breeding area between early October and early November and returned between mid-March and mid-April. Our data on habitat use, survival rate, and migratory connectivity will help to assess threats to the populations of this enigmatic species, which might include habitat loss due to forest fires on the breeding grounds, and unsustainable harvest for consumption during the nonbreeding season.


Diagnostic assays for myeloperoxidase deficiency.
Polymorphonuclear neutrophils (PMN) represent the dominant cell in the acute response to microbial infection. Effective antimicrobial activity reflects the combined action of soluble agents in plasma with PMN-derived reactive oxygen species and granule proteins, including the azurophilic granule protein myeloperoxidase (MPO). The inhibition or absence of the MPO-H2O2-halide system results in marked reduction in PMN killing of a variety of microbes, implicating its relative prominence in the hierarchy of PMN antimicrobial systems. Although the most profound clinical defects are manifested in patients lacking the capacity to generate reactive oxygen species, as seen in chronic granulomatous disease, an inherited deficiency of MPO can also increase the frequency or severity of clinical infections. As a first step in evaluating the MPO-dependent system, determination of peroxidase activity of isolated leukocytes enriched for PMN coupled with histochemical staining of leukocytes allows assessment of functional MPO within PMN. Immunoblotting of the isolated leukocytes for MPO provides additional information, supplying insight into the molecular basis of the observed absence of functional enzyme.


Time-resolved measurements of an ion channel conformational change driven by a membrane phase transition.
Using temperature-jump infrared spectroscopy, we are able to trigger a gel-to-fluid phase transition in lipid vesicles and monitor in real time how a membrane protein responds to structural changes in the membrane. The melting of lipid domains in 1,2-dimyristoyl-sn-glycero-3-phosphocholine vesicles is observed to occur in as fast as 50 ns, with a temperature dependence characteristic of critical slowing. Gramicidin D (gD) added to the membrane responds primarily to the change in thickness of the membrane on a timescale coincident with the membrane melting. Using structure-based spectral modeling, we assign the conformational changes to compression and rotation of a partially dissociated gD dimer. Free energy calculations indicate that the high rate is a result of near-barrierless diffusion on a protein energy landscape that is radically reshaped by membrane thinning. The structural changes associated with the phase transition are similar to the fluctuation modes of fluid phase membranes, highlighting the importance of understanding the dynamic nature of the membrane environment around proteins.


Decreasing the Nursing Documentation Burden During the Covid-19 Surge.
During the Covid-19 pandemic, nurses requested a clean, streamlined, and intuitive view of the adult nursing assessment(s) within the electronic medical record (EMR). We created a more efficient method during a national disaster to reduce duplicative efforts and allow additional time with patients. This project was added as part of the clinically led EMR optimization strategy to eliminate unnecessary EMR assessment data elements in the adult medical, surgical, and critical care areas. This was completed in a 5-month period and decreased 20% of the data points entered by nursing. A total of 433 data points were excluded or relocated to achieve the desired result.


Assessment of technologies for disposing explosive waste.
The environmental impact and safety aspects are assessed for six different techniques for disposing decommissioned ammunition. These are open burning and open detonation (OD), closed detonation (CD), fluidised bed combustion (FBC), rotary kiln (RK) Incineration, and Mobile furnace (MF) Incineration. The assessment is performed in the form of a multi-criteria decision analysis (MCDA). Objectives for minimising environmental impact and risk are defined to enable selection of the "best" technology. A framework for comparing emissions of different air pollutants is proposed. Environmental impacts are described, especially air pollutants. The environmental impacts of traditional OB and OD can be drastically reduced using controlled incineration techniques in combination with high-pressure water washout. This enables the explosive contents to be separated from the casing, and simultaneously the explosive is transformed to a desensitised water-based slurry.


Association of genetic variants for FABP3 gene with back fat thickness and intramuscular fat content in pig.
The swine fatty acid binding protein gene (FABP3) has been screened with 4 primer sets for 270 purebred Yorkshire pigs from National Institute of Animal Science. The selection of primers was based on the swine cDNA sequence (AJ416019), and primer sets (FABP3-2 and FABP3-3) amplified target segments in real time PCR to analyze expression levels at growth stages, producing 235 and 224 bp of fragments, respectively. Relative expression of the swine FABP3 gene for back and intramuscular fat was continuously increased from day 0 to 150, and decreased at day 210, showing the highest expression levels at day 150 compared with day 0. The results may be caused by requirements of high physiological activities with more gene expressions for growth around day 150. Nucleotide variations were observed at nucleotide positions 80 (A/G), 167 (A/G), 260 (A/G), 295 (A/G), 394 (T/C), and 440 (A/G), showing substitutions of amino acids at positions 80 (S to G), 167 (T to A), and 260 (S to G). FABP3 genotypes at positioned nt167 have been associated with carcass back fat thickness (BFT), and dominance genetic effects were observed for BFT with nt167 and intramuscular fat (IMF) contents with nt80. Our results concluded that the FABP3 polymorphisms can be used as genetic markers in breeding programs for IMF content as well as carcass BFT.


Secondary hypospadias repair in two stages.
Following failed primary reconstruction, various single-stage reconstructive techniques have been proposed for secondary hypospadias repair. Unfortunately, these frequently fail to achieve a satisfactory cosmetic and functional outcome. We review a single surgeon's experience of two-staged reconstruction in this scenario. Of 104 patients with hypospadias treated in two stages, between July 1998 and June 2003, 42 were secondary reconstructions. The site of the meatus after initial failed repair was glanular (5), subcoronal (11), distal shaft (12), mid-shaft (6) or peno-scrotal (8). Factors associated with the choice of two-stage reconstruction included moderate/severe chordee (14), excessive scarring (15), shallow/no groove or poor glans (8), and balanitis xerotica obliterans (4). The grafts used were post-auricular skin (PAWG, 29) buccal mucosa (BMG, 6), inner prepuce (IP, 6) and one composite graft. The mean age of our patients was 131 months and the average follow up after the second stage was 26.3 months. In 40 of the 42 cases the graft took well. In one patient a PAWG developed keloid scarring which was excised and later successfully replaced with a BMG. In another, severe shrinkage of a BMG led to revision with a PAWG. Following the second stage, complications were experienced in five: the repair broke down in two BMG patients and was successfully reconstructed with a PAWG in both, and three developed fistulae that were repaired (1 PAWG, 1 BMG, 1 IP). The two-staged reconstruction is a versatile and technically straightforward secondary procedure for this difficult patient cohort. Excellent cosmetic and functional results can be achieved with only a small risk of a revision operation. Four of our six BMG patients experienced problems and PAWG appears more satisfactory with superior results.


Molecular investigations of a novel iduronate-2-sulfatase mutant in a Chinese patient.
Molecular investigations of iduronate-2-sulfatase (IDS) mutants for the X-linked lysosomal storage disease mucopolysaccharidosis type II (MPS II, Hunter disease), commonly depends on transient expression studies to verify a single nucleotide change to be pathogenic. In 2 severely affected patients, IDS missense mutations, c.1016T>C (novel) and c.1016T>G (known) were identified predicting the substitution of an ambivalent cyclic proline and a hydrophilic arginine respectively for the hydrophobic leucine at residue 339. We hypothesized that residue Leu339 may be functionally critical. We performed a study for the 2 mutations by in-situ mutagenesis, in vitro expression, and functional analysis. Transient expression revealed that both the missense variants had stable mRNA but their residual enzyme activities remained <2.5% of normal level. The effect of the missense mutations on protein expression was detected by Western blot analysis. Both the missense mutations synthesized the precursor form but had reduced mature form of IDS. The novel mutation p.L339P is a disease-causing mutation affecting maturation of the protein.


Multiloculated omental cystic tumor hiding an angioleiomyoma: case report of a rare and atypical presentation and literature review.
Angioleiomyoma is a rare benign tumor arising from vascular smooth muscle and generally located in the subcutaneous tissue of the extremities. We reported a rare case of an intra-abdominal localization originating from the small omentum in which progressive growth detected on radiological follow-up indicated surgical excision. Histology documented a cavernous angioleiomuscular tumor with uncertain potential for malignancy. Although angioleiomyoma is described as a benign tumor, the uncertain behavior for malignancy of this case could have led to neoplastic degeneration. Early diagnosis followed by surgical excision of the neoplasia is crucial.


Molecular and serological characterization of group a rotavirus isolates obtained from hospitalized children in Goiânia, Brazil, 1998-2000.
Fecal samples positive for rotavirus group A ( n=120) were analyzed by enzyme immunoassay-monoclonal antibody (EIA-MAb) serotyping and/or reverse transcription/multiplex polymerase chain reaction (PCR) amplification to determine the prevalence of the [P] and G genotypes. The most prevalent G genotype/serotype detected was G1 (76.7%), followed by G2 (5.0%). Six samples were characterized as G9 by multiplex PCR, and one sample was characterized as G3 by EIA-MAb. The combinations of [P] and G genotypes found were P[8] and G1 (20.8%), P[6] and G1 (10.8%), P[6] and G9 (4.2%), P[8] and G2 (1.7%), and P[6] and G2 (0.8%). The diversity of rotavirus group A [P] and G genotypes/serotypes reinforces the need for continuous characterization of rotaviruses circulating in populations in Brazil.


Separation of the valence intermediates of human haemoglobin by high-performance chromatofocusing.
Investigations into the properties of haemoglobin often require the isolation of the valence intermediates (alpha o2 beta+)2 and (alpha+ beta o2)2. Chromatofocusing with an anion-exchange gel (Mono PTM; Pharmacia, particle size 10 micron) in an HR5/20 column at various temperatures (10-25 degrees C) provides an excellent method for this task. A linearly decreasing pH gradient (8 to 7, generated by Polybuffer 96, Pharmacia) eluted sequentially the species methaemoglobin, (alpha o2 beta+)2, (alpha+ beta o2)2 and oxygenated haemoglobin. Calibration graphs help in quantitative analyses. This method is simpler and less time consuming and provides a similar or even better resolution than the traditional ion-exchange or isoelectric focusing methods.


Conformity and Group Performance.
This research provides evidence regarding the causal effect of group conformity on task performance in stable and variable environments. Drawing on studies in cultural evolution, social learning, and social psychology, we experimentally tested the hypotheses that conformity improves group performance in a stable environment (H1) and decreases performance (by hindering adaptability) in a temporally variable environment (H2). We compare the performance of individuals, low conformity groups, and high conformity groups in a four-arm randomized lab experiment (N = 240). High conformity was manipulated by rewarding agreement with the group's majority and imposing a cost on disagreement. The monetary implications of conformity impaired performance in a variable environment but did not have a significant effect on performance in the stable environment. Intragroup individual-level analyses provide insights into the mechanisms that account for the group-level results by showing that lower conformity in groups facilitates efficient adaptability in the use of social information.


Photocatalytic, self-cleaning and antibacterial properties of Cu(II) doped TiO2.
In the study, sol-gel based TiO2 nanoparticles (NPs) were doped by Cu(II), and the surface of cotton fabric was coated with Cu-doped TiO2 NPs to develop self-cleaning and antibacterial properties. Coffee stains were introduced on the modified cotton fabric and under suntest illumination; a decrease in the color of coffee stain was followed over time via K/S value to determine self-cleaning performance. The photocurrent in a photoelectrocatalytic reactor was measured to evaluate the photocatalytic effect of Cu(II) doping. TiO2 NPs showed self-cleaning and antibacterial effects under UV-illuminated conditions. However, no effects were observed under dark (non-illuminated) conditions. The modified textiles with Cu(II) doped TiO2 NPs showed antibacterial activity against E. coli under light and dark conditions. Under the 2 h illumination period, fluctuating color changes were observed on the raw cotton fabric, and stains remained on the fabric while 78% and 100% color removals were achieved in the cotton fabrics coated by Cu doped TiO2 NPs in 1 h and 2 h, respectively.


Working memory capacity predicts effects of methylphenidate on reversal learning.
Increased use of stimulant medication, such as methylphenidate, by healthy college students has raised questions about its cognitive-enhancing effects. Methylphenidate acts by increasing extracellular catecholamine levels and is generally accepted to remediate cognitive and reward deficits in patients with attention deficit hyperactivity disorder. However, the cognitive-enhancing effects of such 'smart drugs' in the healthy population are still unclear. Here, we investigated effects of methylphenidate (Ritalin, 20 mg) on reward and punishment learning in healthy students (N=19) in a within-subject, double-blind, placebo-controlled cross-over design. Results revealed that methylphenidate effects varied both as a function of task demands and as a function of baseline working memory capacity. Specifically, methylphenidate improved reward vs punishment learning in high-working memory subjects, whereas it impaired reward vs punishment learning in low-working memory subjects. These results contribute to our understanding of individual differences in the cognitive-enhancing effects of methylphenidate in the healthy population. Moreover, they highlight the importance of taking into account both inter- and intra-individual differences in dopaminergic drug research.


The Eye Phone Study: reliability and accuracy of assessing Snellen visual acuity using smartphone technology.
Smartphone-based Snellen visual acuity charts has become popularized; however, their accuracy has not been established. This study aimed to evaluate the equivalence of a smartphone-based visual acuity chart with a standard 6-m Snellen visual acuity (6SVA) chart. First, a review of available Snellen chart applications on iPhone was performed to determine the most accurate application based on optotype size. Subsequently, a prospective comparative study was performed by measuring conventional 6SVA and then iPhone visual acuity using the 'Snellen' application on an Apple iPhone 4. Eleven applications were identified, with accuracy of optotype size ranging from 4.4-39.9%. Eighty-eight patients from general medical and surgical wards in a tertiary hospital took part in the second part of the study. The mean difference in logMAR visual acuity between the two charts was 0.02 logMAR (95% limit of agreement -0.332, 0.372 logMAR). The largest mean difference in logMAR acuity was noted in the subgroup of patients with 6SVA worse than 6/18 (n=5), who had a mean difference of two Snellen visual acuity lines between the charts (0.276 logMAR). We did not identify a Snellen visual acuity app at the time of study, which could predict a patients standard Snellen visual acuity within one line. There was considerable variability in the optotype accuracy of apps. Further validation is required for assessment of acuity in patients with severe vision impairment.


RNA Function Prediction.
Recent studies have shown that a considerable proportion of eukaryotic genomes are transcribed as noncoding RNA (ncRNA), and regulatory ncRNAs have attracted much attention from researchers in many fields, especially of microRNA (miRNA) and long noncoding RNA (lncRNA). However, most ncRNAs are functionally uncharacterized due to the difficulty to accurately identify their targets. In this chapter, we first summarize the most recent advances in ncRNA research and their primary function. We then discuss the current state-of-the-art computational methods for predicting RNA functions, which comprise three different categories: miRNA function prediction approaches using target genes, lncRNA function prediction based on the guilt-by-association principle, and RNA function prediction approaches based on competing endogenous RNA partners. We consider that the application of these techniques can provide valuable functional and mechanistic insights into ncRNAs, and that they are crucial steps in future functional studies.


Immunomodifying and neuroprotective effects of noscapine: Implications for multiple sclerosis, neurodegenerative, and psychiatric disorders.
Noscapine is a phthalide isoquinoline alkaloid with antitussive activity. Noscapine protects oligodendroglia from ischemic and chemical injury, binds to bitter taste receptors, antagonizes the bradykinin and histaminergic systems, which may be of benefit in treatment of multiple sclerosis. Noscapine normalizes axonal transport and exerts significant therapeutic efficacy in animal models of Parkinson's Disease and Amyotrophic Lateral Sclerosis. Noscapine exerts neuroprotective effects on oxygen- and glucose-deprived fetal cortical neuronal cells and reduces ischemic brain damage in neonatal rat pups. Pilot clinical studies indicated some beneficial effects of noscapine in stroke. Noscapine harbours anxiolytic activity and methyl-noscapine blocks small conductance SK channels, which is beneficial in alleviating anxiety and depression. Noscapine exerts anticholinesterase activity and acts inhibitory on the inflammatory transcription factor NF-κB, which may be harnessed in treatment of Alzheimer's Disease. With its blood-brain barrier traversing features and versatile actions, noscapine may be a promising agent in the armamentarium against neurodegenerative and psychiatric diseases.


Roadside vegetation barrier designs to mitigate near-road air pollution impacts.
With increasing evidence that exposures to air pollution near large roadways increases risks of a number of adverse human health effects, identifying methods to reduce these exposures has become a public health priority. Roadside vegetation barriers have shown the potential to reduce near-road air pollution concentrations; however, the characteristics of these barriers needed to ensure pollution reductions are not well understood. Designing vegetation barriers to mitigate near-road air pollution requires a mechanistic understanding of how barrier configurations affect the transport of traffic-related air pollutants. We first evaluated the performance of the Comprehensive Turbulent Aerosol Dynamics and Gas Chemistry (CTAG) model with Large Eddy Simulation (LES) to capture the effects of vegetation barriers on near-road air quality, compared against field data. Next, CTAG with LES was employed to explore the effects of six conceptual roadside vegetation/solid barrier configurations on near-road size-resolved particle concentrations, governed by dispersion and deposition. Two potentially viable design options are revealed: a) a wide vegetation barrier with high Leaf Area Density (LAD), and b) vegetation-solid barrier combinations, i.e., planting trees next to a solid barrier. Both designs reduce downwind particle concentrations significantly. The findings presented in the study will assist urban planning and forestry organizations with evaluating different green infrastructure design options.


Identifying Programmatic Factors that Increase Likelihood of Health Facility Delivery: Results from a Community Health Worker Program in Zanzibar.
Community health worker (CHW) interventions have been utilized to address barriers that prevent pregnant women from delivering in health facilities in low- and middle-income countries (LMICs). The objective of this research was to assess the programmatic factors that increase the likelihood of health facility delivery within a large digital health-supported CHW program in Zanzibar, Tanzania. This study included 36,693 women who were enrolled in the Safer Deliveries program with a live birth between January 1, 2017 and July 31, 2019. We assessed whether long-term enrollment, recency of CHW pregnancy visit prior to delivery, and number of routine home pregnancy visits were associated with an increased likelihood of health facility delivery compared to home delivery. We used Chi-squared tests to assess bivariate relationships and performed logistic regression analyses to assess the association between each programmatic variable and health facility delivery, adjusting for relevant confounders. We found that long-term enrollment was significantly associated with increased likelihood of health facility delivery, with the strongest relationship among women with a previous home delivery (OR = 1.4, 95%CI [1.0,1.7]). Among first-time mothers, two or more pregnancy visits by a CHW was positively associated with health facility delivery (OR = 1.8, 95%CI [1.2, 2.7]). Recent pregnancy visit by a CHW was positively associated with health facility delivery, but was not significant at the α = 0.05 level. In this program, we found evidence that at least two routine home pregnancy visits, longer length of enrollment in the program, and recency of home visit to the delivery date were strategies to increase health facility delivery rates among enrolled mothers. Maternal and child health programs should undertake similar evaluations to improve program delivery.


Prognostic factors on periapical surgery: A systematic review.
Analyze the most important prognostic factors when performing periapical surgery and compare the success rates of distinct authors. Periapical surgery is an approach to treat non-healing periapical lesions and it should be viewed as an extension of endodontic treatment and not as a separate entity. A search of articles published in Cochrane, PubMed (MEDLINE) and Scopus was conducted with the key words "prognostic factors", "prognosis", "periapical surgery", "endodontic surgery" and "surgical endodontic treatment". The inclusion criteria were articles including at least 10 patients, published in English, for the last 10 years. The exclusion criteria were nonhuman studies and case reports. 33 articles were selected from 321 initially found. Ten articles from 33 were excluded and finally the systematic review included 23 articles: 1 metaanalysis, 1 systematic review, 2 randomized clinical trials, 6 reviews, 12 prospective studies and 1 retrospective study. They were stratified according to their level of scientific evidence using the SORT criteria. Factors associated with a better outcome of periapical surgery are patients ≤45 years old, upper anterior or premolar teeth, ≤10 sized lesions, non cystic lesions, absence of preoperative signs and symptoms, lesions without periodontal involvement, teeth with an adequate root-filling length, MTA as root-end filling material, uniradicular teeth, absence of perforating lesions, apical resection < 3 mm, teeth not associated to an oroantral fistula and teeth with only one periapical surgery.


Regulatory mechanism of body temperature in the central nervous system during the maintenance phase of hibernation in Syrian hamsters: involvement of β-endorphin.
We have shown previously that intracerebroventricular (icv) injection of naloxone (a non-selective opioid receptor antagonist) or naloxonazine (a selective μ1-opioid receptor antagonist) at the maintenance phase of hibernation arouses Syrian hamsters from hibernation. This study was designed to clarify the role of β-endorphin (an endogenous μ-opioid receptor ligand) on regulation of body temperature (T(b)) during the maintenance phase of hibernation. The number of c-Fos-positive cells and β-endorphin-like immunoreactivity increased in the arcuate nucleus (ARC) after hibernation onset. In contrast, endomorphin-1 (an endogenous μ-opioid receptor ligand)-like immunoreactivity observed on the anterior hypothalamus decreased after hibernation onset. In addition, hibernation was interrupted by icv injection of anti-β-endorphin antiserum at the maintenance phase of hibernation. The mRNA expression level of proopiomelanocortin (a precursor of β-endorphin) on ARC did not change throughout the hibernation phase. However, the mRNA expression level of prohormone convertase-1 increased after hibernation onset. [D-Ala2,N-MePhe4,Gly-ol5] enkephalin (DAMGO, a selective μ-opioid receptor agonist) microinjection into the dorsomedial hypothalamus (DMH) elicited the most marked T(b) decrease than other sites such as the preoptic area (PO), anterior hypothalamus (AH), lateral hypothalamus (LH), ventromedial hypothalamus and posterior hypothalamus (PH). However, microinjected DAMGO into the medial septum indicated negligible changes in T(b). These results suggest that β-endorphin which synthesizes in ARC neurons regulates T(b) during the maintenance phase of hibernation by activating μ-opioid receptors in PO, AH, VMH, DMH and PH.


Implementation of a bimorph-based aperture tapping-SNOM with an incubator to study the evolution of cultured living cells.
We present the implementation of a tapping-mode aperture scanning near-field optical microscope (Tapping-SNOM) to a Binder CB incubator (Istituto di Struttura della Materia, Rome, Italy). The microscope operates in the intermittent contact mode using a nonbent optical fibre allowing to reduce the perturbation exerted on the sample, while the incubator maintains a constant temperature, humidity and CO(2) level. This instrument can maintain and analyse in a controlled environment different samples, both organic and nonorganic. In particular, the Tapping-SNOM can study different cell lines at nanometric resolution and in physiological buffer, following the evolution of the living cells almost indefinitely. We will present several examples of the capabilities of the tapping scanning near-field optical microscope in the study of different lines of living cells, showing corresponding topographical, optical or phase-lag images of the live samples, evidencing the excellent stability, versatility and resolution of the system.


The IL-33/ST2 Axis Promotes Primary Sjögren's Syndrome by Enhancing Salivary Epithelial Cell Activation and Type 1 Immune Response.
The molecular mechanisms of primary Sjögren's syndrome (pSS) are poorly understood. In this study, we explored the role of the IL-33/ST2 axis in the development of pSS. In the mouse model of experimental Sjögren's syndrome, we found that the saliva flow rate at weeks 4 and 30 was preserved in IL-33-/- and ST2-/- mice, compared with that of wild-type mice. At week 30 of experimental Sjögren's syndrome induction, the histological score, anti-nuclear Ab levels, and numbers of Th1 and B cells in draining lymph nodes of the salivary gland were lower in the IL-33-/- and ST2-/- mice, whereas Th17 cells and regulatory T cells were not changed. Primary salivary gland epithelial cells expressed the IL-33 receptor ST2. After stimulation with rIL-33, salivary gland epithelial cells increased the transcriptional levels of CD86 and CCL2, accompanied by the activation of the NF-κB inflammatory pathway. There was a synergistic effect between rIL-33 and rIL-12 in augmenting the production of IFN-γ in CD4+ T cells. In the pSS patients, the expression of IL-33 was elevated in the labial salivary gland, with the number of IL-33+ cells positively correlated with the score of the EULAR (European Alliance of Associations for Rheumatology) Sjögren's syndrome disease activity index (ESSDAI). ST2 was highly expressed in the cytoplasm of ductal epithelial cells, with low levels of expression in lymphatic infiltration sites. Our data suggest that the IL-33/ST2 axis may promote the development of pSS by enhancing salivary epithelial cell activation and the type 1 immune response.


Tsg101: HIV-1's ticket to ride.
Recent studies implicate the vacuolar protein-sorting pathway in the transport of the retroviral structural precursor (Gag) protein to its budding site on the plasma membrane of infected cells. This exploitation of the cellular endocytic trafficking machinery to release viral particles could lead to the identification of virus-specific modulators and provide opportunities to design new targeted anti-viral agents.


Evaluation of the effect of levator ani muscle contraction on post-prostatectomy urinary incontinence using cine MRI.
Post-prostatectomy urinary incontinence (PPI) is the greatest concern for urologists after radical prostatectomy (RP). It is thought that PPI is composed of multiple factors including static and dynamic components. The purpose of this study is to show visually levator ani muscle (LAM) contraction during pelvic floor muscle contraction and to evaluate the dynamic differences in its contraction between men with and without PPI. This study was a case-control study of the urinary continent or incontinent men. It investigated whether LAM contraction was involved in urinary leakage based on examination of LAM contraction by cine magnetic resonance imaging. The LAM contracted from the coccyx to the pubis in the same manner before and after surgery. The degree of contraction of the LAM in post-prostatectomy groups was smaller than that in the healthy adult group. The contraction distances of each part of the pelvic floor were decreased by 50%-70% in the incontinence group compared to those in the continence group. The bladder neck moved 2.5-fold further in the continence group and the direction of movement was more vertical than in the incontinence group. Urethral compression was attenuated by about 40% in the incontinence group compared to that in the continence group. RP can cause damage to the LAM. LAM contraction is reduced after RP compared with that in healthy adult men. In men with PPI, the reduced muscle contraction might not compress the urethra sufficiently when abdominal pressure is raised. Pelvic floor muscle training might provide a meaningful method for the recovery of LAM contraction in patients with PPI.


Selective CO Production by Photoelectrochemical CO2 Reduction in an Aqueous Solution with Cobalt-Based Molecular Redox Catalysts.
Light-driven CO2 reduction was performed in a two-electrode photoelectrochemical cell (PEC) composed of a Co4O4 cubane complex-modified BiVO4 photoanode and a cobalt phthalocyanine complex-modified carbon cloth (cc) cathode. The hybrid electrodes assembled by the simple physical absorption of hydrophobic molecular catalysts exhibit long-term stability in an aqueous solution. Under 1 sun AM 1.5 G illumination, simultaneous oxygen and CO evolution at an approximately 2:1 ratio were achieved in a CO2-saturated NaHCO3 aqueous solution with high faradic efficiency up to 87% for CO production. Control experiments revealed a crucial role of immobilized molecular catalysts in promoting the activity and selectivity for both half-reactions. A solar-to-CO conversion efficiency of 0.44% was realized at a cell potential of 0.8 V, which is the highest efficiency for CO2 to CO conversion in PEC devices based on noble-metal-free materials.


Impact of pharmacological interventions on insulin resistance in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.
Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterized by insulin resistance and is a major risk factor for type 2 diabetes mellitus (T2DM). The objective was to review the literature on the effect of different pharmacological interventions on insulin resistance in women with PCOS. We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science in April 2020 and updated in March 2021. The study follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-ana. Reviwers extracted data and assessed the risk of bias using the Cochrane risk of bias tool. In 58 randomized controlled trials there were significant reductions in the fasting blood glucose (FBG) with metformin versus placebo (standardized mean difference [SMD]: -0.23; 95% confidence interval [CI]: -0.40, -0.06; I² = 0%, low-grade evidence), and acarbose versus metformin (mean difference [MD]: -10.50 mg/dl; 95% CI: -15.76, -5.24; I² = 0%, low-grade evidence). Significant reductions in fasting insulin (FI) with pioglitazone versus placebo (SMD: -0.55; 95% CI: -1.03, -0.07; I² = 37%; p = .02, very-low-grade evidence). A significant reduction in homoeostatic model assessment of insulin resistance (HOMA-IR) was seen with exenatide versus metformin (MD: -0.34; 95% CI: -0.65, -0.03; I² = 0%, low-grade evidence). No effect on homoeostatic model assessment of beta cells (HOMA-B) was observed. Pharmacological interventions, including metformin, acarbose, pioglitazone and exenatide have significant effects on FBG, FI, HOMA-IR but not on HOMA-B.


Horizontal ECG in acute anterolateral myocardial infarction.
The present study aims to compare the amount of ST segment changes recorded by horizontal electrocardiography (hECG) with standard ECG (sECG) in patients with acute anterior and/or lateral ST segment elevation myocardial infarction (STEMI). Consecutive eligible patients (n = 58) who were diagnosed with acute anterior and/or lateral STEMI were included in the study. After recording simultaneous sECG and hECG by placing precordial leads (V3-6) horizontally on the left 4th intercostal space, ST segment changes were compared. The mean ST segment changes (mV) on hECG were significantly higher than sECG in V4 (0.27 ± 0.2 vs. 0.21 ± 0.21, p = 0.001), V5 (0.21 ± 0.17 vs. 0.12 ± 0.16, p < 0.001) and V6 (0.09 ± 0.1 vs. 0.04 ± 0.12, p < 0.001), respectively. When hECG and sECG were compared in patients with BMI < 30 kg/m(2), mean ST segment changes (mV) on hECG were significantly higher than sECG in V4 (0.29 ± 0.21 vs. 0.21 ± 0.24, p = 0.004), V5 (0.22 ± 0.19 vs. 0.13 ± 0.17, p < 0.001) and V6 (0.11 ± 0.11 vs. 0.04 ± 0.11, p < 0.001), respectively. Mean ST segment changes in patients with anterior and/or lateral STEMI were significantly higher and easily detectable on hECG compared with sECG. We suggest that hECG be used in conjunction with sECG to diagnose anterior and lateral wall STEMI in cases of diagnostic doubt.


Symptomatic osteonecrosis as a treatment complication in Hodgkin lymphoma: an analysis of the German Hodgkin Study Group (GHSG).
The majority of patients with Hodgkin Lymphoma (HL) can be cured with stage and risk adapted treatment today. Therefore, current research focuses on reducing long-term sequelae of treatment. Osteonecrosis (ON) is a severe long-term complication of HL treatment which has so far not been systematically evaluated. Hence, we investigated incidence, risk factors and timing of symptomatic ON in HL patients. Further endpoints included localization, intervention and outcome of ON. We included all qualified HL patients of the randomized German Hodgkin Study Group trials HD10-15 and HD18, recruited between 05/1998 and 07/2014 and aged from 16 to 60 years. Among 11 330 patients, 66 developed symptomatic ON after first-line treatment, 83.3% within three years. The incidence of symptomatic ON was 0.2% in early-stage HL and 1.0% in advanced-stage HL. Logistic regression revealed the total cumulative corticosteroid dose to be a strong risk factor interacting with younger age. Male sex additionally increased the risk of symptomatic ON. The prognostic value of the corresponding logistic regression model was rather high (AUC = 0.78). Other tested potential risk factors including obesity, IPS and radiotherapy did not further increase the risk of ON. Further development of current treatment protocols should aim to reduce the cumulative corticosteroid dose.


Beta2-glycoprotein I inhibits vascular endothelial growth factor and basic fibroblast growth factor induced angiogenesis through its amino terminal domain.
Beta-2 glycoprotein I (beta(2)GPI) is a plasma glycoprotein which interacts with various proteins of the coagulation and fibrinolysis system. beta(2)GPI has recently been shown to have anti-angiogenic properties. We undertook this study to investigate the specific domain of beta(2)GPI involved in the anti-angiogenic function and its effect on downstream signaling of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Various preparations of beta(2)GPI were used on human umbilical vein endothelial cells (HUVECs) in the absence or presence of VEGF and bFGF. The effect on HUVECs' proliferation, migration and tubule formation in Matrigel matrix was investigated. The effect of beta(2)GPI on the mRNA expression of VEGF receptors and phosphorylation of signaling molecules was also studied. beta(2)GPI is shown in this study to be an anti-angiogenic molecule in vitro by inhibiting VEGF and bFGF-induced proliferation, migration and papillary-like tubule formation of HUVECs. This inhibition was achieved by native, proteolytically clipped and domain deletion mutants, domain I-IV (DI-IV) but not domain II-V (DII-V) of beta(2)GPI. Native beta(2)GPI was found to downregulate the expression of the VEGF receptor KDR/Flk-1 on endothelial cells and to block the phosphorylation of VEGF's downstream effector molecules in the MAPK/ERK and PI3K/Akt/GSK3beta pathways. These results indicate that beta(2)GPI has anti-angiogenic functions which depend on the presence of domain I. This anti-angiogenic activity may have important implications for the therapeutic manipulation of angiogenesis in various disease states.


Measles immunity gaps in an era of high vaccination coverage: A serology study from Taiwan.
Routine vaccination for children drastically reduces measles cases. Nonetheless, the global resurgence of measles since 2018 highlights the need for evaluating vaccine-induced immunity in an era of high vaccination coverage, especially in international travelers. This study aims to identify high-risk persons via analyzing the impact of age and different vaccination schedules on seroprevalence of measles in a country with high vaccination coverage, attempting to provide suggestions regarding pre-travel measles vaccination in highly immunized countries. We retrospectively collected serological results of measles from Taiwanese travelers during 2008-2017 and middle-aged subjects from community during 2007-2009. Participants were classified by age groups and cohort based on the national immunization program: cohort I (pre-mass vaccination), cohort II (suboptimal measles vaccination), and cohort III (2-dose MMR in childhood). The effects of age group on seropositivity was shown by odds ratio (OR) with 95% confidence interval (CI) in a logistic regression model. The overall measles seroprevalence was 74.5% (N = 1096, mean age = 31.7 ± 12.3 years), with adolescents having the lowest seropositivity (65.9%) and participants ≥50 years having the highest (89.4%). Seropositivity was significantly higher in cohort I (pre-mass vaccination) compared with the other 2 cohorts (P < 0.0001). The effect of aging on seropositivity was only significant in cohort II (OR = 1.84, 95% CI = 1.13-2.99, P = 0.014 for 30-39 years vs. 20-29 years). Waning immunity to measles in adolescents and young adults is a dominant issue in highly vaccinated cohorts. Enhancing pre-travel vaccination against measles can effectively fill the immunity gaps in highly immunized countries.


Susceptibility to 1,2-dimethylhydrazine-induced colonic tumors and epithelial cell proliferation characteristics of F1, F2, and reciprocal backcrosses derived from SWR/J and AKR/J parental mouse strains.
Hybrid crosses were performed between SWR/J, a strain highly sensitive to 1,2-dimethylhydrazine (DMH), and AKR/J, a strain highly resistant to the carcinogen. F1 and F2 and reciprocal backcrosses were tested to determine if proliferative characteristics such as high activity, wide compartment (PC), and a large S-phase population in the middle third of crypts were linked to susceptibility and inherited as a dominant autosomal trait as was reported for DMH tumor response. A blend of resistant and sensitive tumor and proliferative characteristics was observed in the F1 and F2 crosses. A tumor incidence of 43.7% in the F1 and 52% in the F2 was obtained rather than the respective 100% and 75% expected frequencies. One week after the sixth injection of DMH, the incidence of focal areas of atypism (FAA) in the backcross to resistance (BCR) and the backcross to sensitivity (BCS) was the same (4.1 per FAA-bearing animal). This suggested that the response to the carcinogen was similar in both groups up to this point. Yet 20 weeks later, the BCR had a 7.3% tumor incidence, far lower than the 50% incidence expected. The BCS had an incidence of 98.6%, not unlike SWR frequencies and close to the expected 100% tumor incidence. Proliferative characteristics in the backcrosses, however, did not revert to parental levels. Instead, the labeling index (LI) or percentage of S-phase cells to total cells scored was significantly higher in the BCR than in the BCS (10.2% +/- 3.2% versus 8.1% +/- 2.2%, P less than 0.02). This study has shown that in crosses between these two strains (SWR/J and AKR/J), susceptibility to DMH-induced tumor is not inherited as a dominant trait. Neither are the proliferative characteristics of the colonic mucosa inherited in a simple Mendelian manner nor are the kinetic properties of the epithelial cells linked to DMH tumor susceptibility. It is suggested that the parental AKR/J strain may contribute a protective or resistant factor, that is, a repressor gene, which impedes the progression of carcinogen-induced foci of dysplasia to colonic neoplasia.


[Undesired side effects of tapentadol in comparison to oxycodone. A meta-analysis of randomized controlled comparative studies].
Tapentadol is a new centrally acting analgesic with a dual mode of action as an agonist of the µ-opioid receptor and as a norepinephrine reuptake inhibitor. The aim of the present study was to evaluate the results from randomized controlled trials investigating the relative amount of adverse effects using tapentadol or oxycodone for the treatment of pain. A quantitative systematic review was carried out according to the PRISMA recommendations on randomized controlled trials comparing tapentadol and oxycodone in pain treatment. The incidences of typical adverse side effects of opioid-based analgesic therapy (e.g. nausea, vomiting, obstipation or pruritus) were extracted and the pooled relative risks (RR) with corresponding 95% confidence intervals (CI) were calculated. A total of 9 trials involving 7,948 patients were included and of these 2,810 patients were treated with oxycodone and 5,138 were treated with tapentadol in equivalent analgesic dosages as documented by an equivalent analgesic effect. The risk of typical opioid-based adverse effects, such as nausea (RR 0.61; 95% CI 0.57-0.66), vomiting (RR 0.50, 95% CI: 0.41-0.60), obstipation (RR 0.47, 95%-CI 0.40-0.56), dizziness (RR 0.86, 95% CI 0.78-0.95), somnolence (RR 0.76, 95% CI 0.67-0.86) and pruritus (RR 0.46, 95% CI 0.37-0.58) was reduced when tapentadol was used for analgesic treatment. These adverse effects were investigated in all nine trials. The risk for dryness of the mouth (6 trials, 6,218 patients, RR 1.79, 95% CI 1.40-2.29) and dyspepsia (1 trial, 646 patients, RR 2.75, 95% CI 1.09-6.94) was increased when tapentadol was used instead of oxycodone. There were no significant differences in the relative risk for any other investigated adverse effect such as dysentery, headache or fatigue. The results show that using tapentadol significantly reduces the risk of the typical opioid-based adverse effects compared with oxycodone while providing equivalent analgesic treatment.


Imaging of lipid droplets using coumarin fluorophores in live cells and C. elegans.
Fluorescent probes offer incredibly effective tools for visualizing the dynamic morphology of lipid droplets (LDs) and investigating their physiological interactions. In this work, we have utilized solvatochromic coumarin probes bearing nitrile and ester substituents for live-cell imaging. The fluorescence probes are characterized by a donor (diethylamino) and acceptor (nitrile and/or ester) substituents and a rotatable double bond. The designed architecture allows investigation of environmental sensitivity apart from providing excellent ability to target sub-cellular organelles. The synthesized fluorophores showed low cytotoxicity and excellent localization within the lipid droplets. Further, the fluorophores were also utilized to study viscosity changes within the LDs induced by Nystatin. More importantly, we also demonstrate imaging of LDs in multi-cellular animal models such as C. elegans.


Herd-level risk factors associated with chronic wasting disease-positive herd status in Minnesota, Pennsylvania, and Wisconsin cervid herds.
The objective of this study was to evaluate risks related to introduction of Chronic Wasting Disease (CWD) to farmed cervid herds in Minnesota (MN), Pennsylvania (PA), and Wisconsin (WI). This was the first study to evaluate risk factors related to multiple pathways of CWD transmission to farmed cervid herds. Participating herds in this case-control study included 22 case and 49 control herds identified through participation in the respective mandatory State CWD herd program. Data was voluntarily collected from white-tailed deer (WTD) study herds using a questionnaire and state animal health agency databases. Univariable analyses identified associations between CWD-positive herds and variables representing different transmission pathways, including direct contact with infected farmed cervids (imported from a herd that later tested positive for CWD) odds ratio (OR):7.16, 95 % confidence intervals (CI):1.64-31.21 and indirect contact with infected wild cervids (access of domestic cats to pens or feed storage area) OR:4.07, 95 % CI:1.35-12.26, observed evidence of mammalian scavengers inside or outside of fenceline in the previous 12 months OR:6.55, 95 % CI:1.37-31.32, ≤ 5 km distance to nearest detected CWD-positive wild cervid OR:3.08, 95 % CI:1.01-9.39, forested area crosses the perimeter fenceline OR:3.54, 95 % CI:1.13-11.11, ≤ 0.3 m distance of water source to fenceline OR:4.71, 95 % CI:1.60-13.83, and water source shared with wild cervids (running or standing water) OR:4.17, 95 % CI:1.34-12.92. Three variables from univariable analyses that represented different biological transmission pathways were placed in a Firth's penalized maximum likelihood multivariable logistic regression to evaluate associations between transmission pathway and CWD herd infection status. For the issue of low sample size and overfitting, 95 % CIs for estimated coefficients for the three variables were computed via bootstrapping of 10,000 independent bootstrap samples. The three biological variables were significantly associated with herd CWD infection status: imported cervids from a herd that later tested positive for CWD (OR:5.63; 95 % CI:1.1-28.2), ≤ 0.3 m distance of cervid water source to perimeter fenceline (OR:4.83; 95 % CI:1.5-16.1), and ≤ 5 km distance to nearest detected CWD-positive wild cervid (OR:4.10; 95 % CI:1.1-15.2). The risk factors associated with CWD herd status identified in this study indicated the importance of transmission through direct contact pathways with infected cervid herds (introduction of cervids from herds later identified as CWD-infected) and indirect contact pathways with infected wild cervids that could be related to other animals through the perimeter fence. Further studies are needed to confirm and clarify understanding of indirect pathways to allow development of improved biosecurity practices to prevent CWD introduction to cervid herds.


Novel methylene modified cyclohexyl ethylenediamine-N,N'-diacetate ligands and their platinum(IV) complexes. Influence on biological activity.
This paper focuses on the synthesis, characterization and biological activity of new N,N'-methylene modified cyclohexyl ethylenediamine-N,N'-diacetate (edda)-type ligands and their Pt(IV) complexes. Both the ligands and complexes were characterized by infrared, UV-vis, ESI-MS, 1D ((1)H, (13)C, (195)Pt) and 2D (COSY, HSQC, HMBC) NMR spectroscopy and elemental analysis. The possible correlation between the reduction potentials and the cytotoxicity of the complexes was examined. The potential antitumoral activity of all compounds was tested in vitro on human melanoma A375, human glioblastoma U251, human prostate cancer PC3, human colon cancer HCT116, mouse melanoma B16 and mouse colon cancer CT26CL25 cells, as well as primary fibroblasts and keratinocytes. The results obtained revealed strong antitumor potential of the newly synthesized drugs with preserved efficacy against cisplatin resistant lines and less toxicity towards nonmalignant counterparts. The mechanism found to be responsible for the observed tumoricidal action of each synthesized compound was induction of apoptosis generally accompanied with caspase activation. Taken together, the effective response to the treatment of a wide range of different cell lines, including cisplatin resistant subclones, as well as induction of apoptosis, as the mechanism suggested to be the most desirable way of eliminating malignant cells, represents a great advantage of this novel group of drugs in comparison to other members in this metallo-drug family.


Novel pathogenic variants underlie SLC26A4-related hearing loss in a multiethnic cohort.
The genetics of sensorineural hearing loss is characterized by a high degree of heterogeneity. Despite this heterogeneity, DNA variants found within SLC26A4 have been reported to be the second most common contributor after those of GJB2 in many populations. Whole exome sequencing and/or Sanger sequencing of SLC26A4 in 117 individuals with sensorineural hearing loss with or without inner ear anomalies but not with goiter from Turkey, Iran, and Mexico were performed. We identified 27 unique SLC26A4 variants in 31 probands. The variants c.1673A > G (p.N558S), c.1708-1G > A, c.1952C > T (p.P651L), and c.2090-1G > A have not been previously reported. The p.N558S variant was detected in two unrelated Mexican families. A range of SLC26A4 variants without a common recurrent mutation underlies SLC26A4-related hearing loss in Turkey, Iran, and Mexico.


Serum pseudocholinesterase in psychiatric patients.
Serum pseudocholinesterase activity was measured in 123 subjects: 16 agitated depressives, 12 retarded depressives, 7 acute schizophrenics, 14 residual schizophrenics, 16 healthy individuals, 45 surgical patients, and 13 first-degree relatives of 4 agitated depressive patients. The agitated depressive and acute schizophrenic patients had significantly higher pseudocholinesterase serum activity than their retarded inmates. As first-degree relatives of agitated depressive patients showed high levels similar to their ill relatives, a genetic component might play a crucial role. The level of pseudocholinesterase activity in serum of the surgical patients was significantly lower than that of all the psychiatric patients and the controls. The implications of this observation are still obscure.


Dysbaric osteonecrosis of the shoulder in a sport scuba diver.
The previously unreported occurrence of dysbaric osteonecrosis in an amateur sport scuba diver who had no other identified cause of avascular bone necrosis is described.


Use of ACE inhibitors and risk of community-acquired pneumonia: a review.
The administration of angiotensin-converting enzyme (ACE) inhibitors has been suggested as an alternative strategy for lowering the risk of community-acquired pneumonia (CAP) in the elderly, especially in patients with neurological and cerebrovascular comorbidity. We critically examined the relevant data from studies regarding the impact of ACE inhibitors in lowering the risk of CAP and/or mortality due to CAP in the elderly. We searched PubMed, Cochrane Database, and references of initially retrieved articles, and http://clinicaltrials.gov for ongoing trials. We identified 285 evaluable studies. Fourteen studies met the inclusion criteria and were evaluated further, of which seven were prospective studies, two randomized controlled trials, and five retrospective studies. Eight of ten studies including patients of Asian origin demonstrated a statistical significance in favor of ACE inhibitors. On the contrary, only one of five studies including patients of non-Asian origin demonstrated results in favor of ACE inhibitors. The available data suggest that ACE inhibitors may contribute to the reduction of the risk of CAP. Nevertheless, clinical data are scarce and mainly comprise studies including patients of Asian origin. As there seem to be differences regarding the genetic polymorphism of ACE among patients of different origins, future studies are needed that incorporate relevant genetics data that may help clarify the role, if any, of ACE inhibitors in preventing CAP.


Efficacy and safety of recombinant activated factor vii in major surgical procedures: systematic review and meta-analysis of randomized clinical trials.
To investigate the efficacy and safety of recombinant activated factor VII (rFVIIa) treatment in patients undergoing major surgical procedures. Relevant studies were searched in BioMedCentral, CENTRAL, PubMed, and PubMed Central. Only randomized controlled trials on humans undergoing major surgery were included. Efficacy was determined as the rate of patients receiving allogeneic packed red blood cells; safety was assessed in terms of thromboembolic complications and mortality rate. We followed the Cochrane Collaboration method for data extraction and internal validity procedures, as well as the Quality of Reporting of Meta-analyses statement. Seven randomized controlled trials met the inclusion criteria. Treatment with rFVIIa is associated with a reduced risk of receiving allogeneic packed red blood cells (odds ratio, 0.29; 95% confidence interval, 0.10-0.80). In a subgroup analysis, only patients receiving at least 50 mug/kg of rFVIIa had a significant benefit (odds ratio, 0.43; 95% confidence interval, 0.23-0.78). No differences in thromboembolic complications and mortality rates were observed. Treatment with rFVIIa is effective in reducing the rate of patients undergoing transfusion with allogeneic packed red blood cells. However, the cost-benefit ratio is favorable only in patients who need a huge number of packed red blood cell units. No safety concerns arise from the present study.


Classical dopamine agonists.
The pioneering work of Arvid Carlsson has laid the foundation for a number of innovative therapies for severe central nervous system (CNS) diseases. He was awarded the Nobel Price for the discovery of the crucial role of dopamine (DA) as a neurotransmitter in the CNS, thereby forming the basis for the symptomatic therapy of Parkinson's disease (PD) with L-DOPA and subsequently dopaminergic drugs. Parenteral apomorphine has a short lasting effect in PD, bromocriptine can be administered orally and has a long-lasting effects but is poorly tolerated. Lisuride on the other hand has a high affinity to DA receptors and can be administered orally, parenterally or via the transdermal route of administration. Last but not least Carlsson developed the concepts of presynaptic effects of DA agonists as well as DA partial agonism potentially innovative mechanisms for treatment of PD and schizophrenia.


Effects of a bioscaffold on collagen fibrillogenesis in healing medial collateral ligament in rabbits.
Bioscaffolds have been successfully used to improve the healing of ligaments and tendons. In a rabbit model, the application of porcine small intestine submucosa (SIS) to the healing medial collateral ligament (MCL) resulted in improved mechanical properties with the formation of larger collagen fibrils. Thus, the objective of the study was to find out whether the SIS bioscaffold could improve the gene expressions of fibrillogenesis-related molecules, specifically, collagen types I, III, V, and small leucine-rich proteoglycans including decorin, biglycan, lumican, and fibromodulin, as well as collagen fibril morphology and organization, in the healing rabbit MCL at an early time point (6 weeks postinjury). Twenty skeletally mature rabbits were equally divided into two groups. In the SIS-treated group, a 6-mm gap was surgically created and a layer of SIS was sutured to cover the gap, whereas the gap was left open in the nontreated group. At 6 weeks postinjury, Masson's trichrome staining showed that the SIS-treated group had more regularly aligned collagen fibers and cells. Transmission electron microscopy revealed that the SIS-treated group had larger collagen fibrils with a diameter distribution from 24 to 120 nm, whereas the nontreated group had only small collagen fibrils (ranging from 26 to 87 nm, p < 0.05). Finally, the quantitative real-time PCR showed that the mRNAs of collagen type V, decorin, biglycan, and lumican in the SIS-treated group were 41, 58, 51, and 43% lower than those in the nontreated group, respectively (p < 0.05). Such significant reduction in the gene expressions are closely related to the improved morphological characteristics, which are known to be coupled with better mechanical properties, as previously reported in longer term studies.


Seeking Pain Relief With Fewer Side Effects.
For the one in five adults who suffer from chronic pain, treatment largely relies on pharmaceuticals, which can come with serious downsides [1]. "They mitigate pain, but in the long term lead to such significant side effects and consequences that the burden from the treatment many times starts to exceed the burden from disease, and it attacks the person's quality of life," says Padma Gulur, M.D., professor of anesthesiology and head of the Pain Relief and Opioid Mitigation Innovation Science (PROMIS) Laboratory, Duke University (Figure 1).


Electron-beam CT angiography with three-dimensional reconstruction in the evaluation of coronary artery bypass grafts.
The authors evaluated the use of electron-beam computed tomographic (CT) angiography and three-dimensional (3D) reconstruction for evaluation of coronary artery bypass grafts (CABGs). Sixty patients (53 men and seven women; mean age, 56 years +/- 8) with 152 CABGs (29 internal mammary artery and 123 saphenous vein grafts) underwent electron-beam CT with 3D reconstruction. The time from bypass surgery to CT scanning was 7 days to 120 months (mean, 17 months +/- 28). Enhanced single-section and flow mode studies were performed in all cases. The results were correlated with CABG operation records, and patency was determined with time-attenuation curves. All patients were successfully examined. On the basis of time-attenuation curve criteria, 124 (81.6%) of 152 grafts were patent. The patency rate for the internal mammary artery subgroup was 93% (27 of 29 grafts); for the saphenous vein graft subgroup, 78.9% (97 of 123 grafts). Used in contrast-enhanced, single-section mode and flow studies with time-attenuation curves, electron-beam CT angiography with 3D reconstruction can provide quantitative data for evaluation of CABG patency.


The role of hereditary KCNQ1 mutations in water-related death.
Drowning remains one of the major causes of death in most developed countries despite the fact that many of the victims are known to be at least moderate swimmers as well as healthy directly before the event. Here, fatal arrhythmias and especially the long QT syndrome (LQTS) have been proposed as the underlying mechanism which may be connected to mutations in one of the associated genes. The KCNQ1 gene is involved in the occurrence of LQT1 which may be triggered by swimming. Therefore, 176 cases of drowning were screened for mutations in the exons 3, 5, 6, 7, and 8 of the KCNQ1 gene which have been shown to harbor major mutation clusters. No variation to the published sequence could be found in the exonic DNA in any of the cases clearly disproving an involvement of these mutation clusters in cases of drowning.


Pleiotropic mechanisms of virus survival and persistence.
Viruses are enormously efficient infectious agents that have been implicated in causing human disease for centuries. Transmission of these pathogens continues to be from one life form to another in the form of isolated cases, epidemics, and pandemics. Each infection requires entry into a susceptible host, replication, and evasion of the immune system. Viruses are successful pathogens because they target specific cells for their attack, exploit the cellular machinery, and are efficient in circumventing and/or inhibiting key cellular events required of survival. This article reviews some of the advances that have taken place in human virology in the past 50 years, emphasizing mechanisms that contribute to, and are involved with, virus survival and persistence.


Discovery of 1,2,4-triazine-based derivatives as novel neddylation inhibitors and anticancer activity studies against gastric cancer MGC-803 cells.
Neddylation modification is often over-expressed in a variety of human tumor cells. Therefore, targeting neddylation pathway may represent a potential approach to the treatment of human tumors. Herein, we describe the discovery of a hit scaffold from our in-house library and further structure-based optimizations. In this work, compound V11 could block the neddylation and inhibit the activity of NAE (with an EC50 value of 3.56 µM), and a dose-dependent reduction of the Ubc12-NEDD8 conjugations was also observed. Molecular docking results suggest compound V11 could bind tightly to NAE via hydrogen bonds and hydrophobic interactions. Compound V11 showed the best antiproliferative ability with an IC50 value of 8.22 μM against gastric cancer MGC-803 cells. Further anticancer activity studies suggested that compound V11 inhibited MGC-803 cell growth, caused a cell cycle arrestment at G2/M phase and induced apoptosis via extrinsic and intrinsic apoptosis pathways. All the findings suggest that 1,2,4-triazine scaffold might provide a novel scaffold for the further development of neddylation inhibitors and compound V11 might be a potential neddylation inhibitor with anticancer activity.


Oxygen therapy and massive pulmonary haemorrhage in newborn infants.
A significant rise in the frequency of neonatal pulmonary haemorrhage was observed in the year when intensive oxygen therapy by CPAP and IPPV ventilation was started. To clarify the role of oxygen therapy the neonatal deaths occurring in two periods of different oxygen treatment were analysed and compared in respect of all clinical features which may be involved in the pathogenesis of pulmonary haemorrhage. In conclusion it is suggested that the local effect of oxygen is probably an additional but significant pathogenetic factor in the condition.


Two cases of Kerstersia gyiorum isolated from sites of chronic infection.
Kerstersia gyiorum is infrequently associated with human infection. We report the isolation of Kerstersia gyiorum from two patients: the first, a patient with chronic ear infections, and the second, a patient with a chronic leg wound. Both isolates were resistant to ciprofloxacin, which has not been previously reported.


Striato-cortical tracts predict 12-h abstinence-induced lapse in smokers.
Striatal circuit dysfunction is implicated in smoking behaviors and lapses during abstinence attempts. However, little is known about whether the structural connectivity of striatal tracts can be used to predict abstinence-induced craving and lapses. The tract strengths of striatal circuits were compared in 53 male nicotine-dependent cigarette smokers and 58 matched nonsmokers, using seed-based classification by diffusion tensor imaging (DTI) probabilistic tractography with 10 a priori target masks. A 12-h abstinence procedure was then employed, after which 31 individuals abstained and 22 lapsed. Linear regression and binary logistic regression was conducted to test whether the tract strength of frontostriatal circuits was associated with craving changes in abstainers and predicted lapse in smokers. Compared with nonsmokers, in the left hemisphere, smokers showed weaker tract strength in striatum-medial orbitofrontal cortex (mOFC), striatum-ventral lateral prefrontal cortex (vlPFC), striatum-inferior frontal gyrus (IFG) and striatum-posterior cingulate cortex (PCC) (Bonferroni corrected, p < 0.05/20 = 0.0025). In abstainers, the abstinence-induced increases in craving were associated with the tract strength of the left striatum-mOFC and striatum-vlPFC. The tract strength of left striatum-dorsolateral PFC (dlPFC) predicted lapse in smokers with an accuracy of 68.3%. These results provide system-level insights into the weaker tract strength of frontostriatal circuits in male smokers and their potential roles as neuroimaging markers for abstinence-induced craving and risk of lapse. Future studies in female smokers are needed to determine if this generalizes across genders.


Finite-time complete periodic synchronization of memristive neural networks with mixed delays.
In this paper we study the oscillatory behavior of a new class of memristor based neural networks with mixed delays and we prove the existence and uniqueness of the periodic solution of the system based on the concept of Filippov solutions of the differential equation with discontinuous right-hand side. In addition, some assumptions are determined to guarantee the globally exponentially stability of the solution. Then, we study the adaptive finite-time complete periodic synchronization problem and by applying Lyapunov-Krasovskii functional approach, a new adaptive controller and adaptive update rule have been developed. A useful finite-time complete synchronization condition is established in terms of linear matrix inequalities. Finally, an illustrative simulation is given to substantiate the main results.


Post-contrast T1-weighted sequences in pediatric abdominal imaging: comparative analysis of three different sequences and imaging approach.
Post-contrast T1-weighted imaging is an essential component of a comprehensive pediatric abdominopelvic MR examination. However, consistent good image quality is challenging, as respiratory motion in sedated children can substantially degrade the image quality. To compare the image quality of three different post-contrast T1-weighted imaging techniques-standard three-dimensional gradient-echo (3-D-GRE), magnetization-prepared gradient-recall echo (MP-GRE) and 3-D-GRE with radial data sampling (radial 3-D-GRE)-acquired in pediatric patients younger than 5 years of age. Sixty consecutive exams performed in 51 patients (23 females, 28 males; mean age 2.5 ± 1.4 years) constituted the final study population. Thirty-nine scans were performed at 3 T and 21 scans were performed at 1.5 T. Two different reviewers independently and blindly qualitatively evaluated all sequences to determine image quality and extent of artifacts. MP-GRE and radial 3-D-GRE sequences had the least respiratory motion (P < 0.0001). Standard 3-D-GRE sequences displayed the lowest average score ratings in hepatic and pancreatic edge definition, hepatic vessel clarity and overall image quality. Radial 3-D-GRE sequences showed the highest scores ratings in overall image quality. Our preliminary results support the preference of fat-suppressed radial 3-D-GRE as the best post-contrast T1-weighted imaging approach for patients under the age of 5 years, when dynamic imaging is not essential.


The influence of ethanol treatment of cytogenetic effects in bone marrow cells of Chinese hamsters by cyclophosphamide, aflatoxin B1 and patulin.
Chromosomes were investigated from the bone marrow of Chinese hamsters which received 10% (v/v) ethanol as the only liquid supply for a period of 9 weeks. At the end of the ethanol drinking period 1 group of animals received 2 oral doses of 80 mg/kg cyclophosphamide (CP), a second group received 2 oral doses of 25 mg/kg aflatoxin B1 (AFB1), a third group 2 oral doses of 20 mg/kg patulin (PA). The 2 applications were separated by 24 h. The intake of ethanol had no effect on the bone marrow chromosomes, and had no potentiating effect on CP induced aberrations. 9 weeks consumption of 10% (v/v) ethanol revealed likewise no influence on the frequencies of chromosomal aberrations induced by the indirect mutagen AFB1. However, the rate of chromosomal aberrations induced by the direct mutagen PA was clearly suppressed in ethanol drinking animals.


Inkjet dispensing technology: applications in drug discovery.
The past year has seen significant advances in the reduction to practice of inkjet dispensing technology in drug discovery applications. Although much of the work in this area has been done by relatively few 'early innovators', broader acceptance of the feasibility of the use of inkjet dispensing is on the rise. Of the three main areas of drug discovery - genomics, high-throughput screening, and combinatorial chemistry - high-throughput screening has had the most applications to date. The burgeoning field of genomics has seen rapid incorporation of technologies that enable miniaturization of gene expression experiments. Inkjet dispensing has a clear role in this effort. Finally, as the miniaturization needs of combinatorial chemistry become more clear, inkjet dispensing technology will potentially play a role.


Some characteristics of a retrovirus isolated from transformed bovine cells.
A novel retrovirus has been isolated from bovine cells transformed after cocultivation with leukocytes from an animal suffering from sheep-associated bovine malignant catarrhal fever. Morphologically and in its morphogenesis the virus resembles the type D Mason-Pfizer monkey virus (MPMV) as well as the ovine jaagsiekte retrovirus (JSRV). It is also serologically related to these two viruses, whereas a relationship to other known bovine retroviruses was not detected. However, its density of 1.16 g/ml in sucrose and the preference of its reverse transcriptase for manganese ions are closer to the characteristics of type C retroviruses. Unsuccessful attempts at transmission suggest that the virus may be defective in some function affecting its infectivity.


Combined effects of cyclooxygenase-1 and cyclooxygenase-2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice.
As with cyclooxygenase (COX)-2, genetic disruption of COX-1 gene or pharmacologic inhibition of its activity has been shown to decrease the number of intestinal polyps in Apc gene-deficient mice. The present study was designed to investigate the combined effects of COX-1 and COX-2 selective inhibitors on spontaneous polyp formation in APC1309 female mice. The animals were treated with 300 or 600 ppm mofezolac (a COX-1 selective inhibitor) alone, 200 or 400 ppm nimesulide (a COX-2 selective inhibitor) alone, 300 ppm mofezolac plus 200 ppm nimesulide, 600 ppm mofezolac plus 400 ppm nimesulide, or 10 ppm indomethacin (a dual-COX inhibitor) in the diet from 7 weeks of age for 4 weeks. Percentage inhibition of polyp area in the intestine was 17% with 600 ppm mofezolac alone and 25% with 400 ppm nimesulide alone, their sum of 42% being almost equal to the 37% observed for the combination treatment. Administration of 300 ppm mofezolac plus 200 ppm nimesulide also significantly decreased polyp area in the intestine by 30%. Moreover, the numbers of polyps more than 2.5 mm in diameter were markedly decreased by combined treatment of both COX inhibitors. With 10 ppm indomethacin, the dual inhibitor, polyp area was also clearly reduced by 46%. Our results indicate that COX-1 and COX-2 may to some extent contribute to polyp formation independently and inhibitor combination treatment thus has particular potential for chemoprevention of colon carcinogenesis.


γ-Aminobutyric Acid (GABA) Accumulation in Tea (Camellia sinensis L.) through the GABA Shunt and Polyamine Degradation Pathways under Anoxia.
γ-Aminobutyric acid (GABA) is an important bioactive component of tea (Camellia sinensis) providing various health benefits. We studied GABA accumulation via the GABA shunt and polyamine degradation pathways under anoxia in tea leaves. Anoxia caused a ∼20-fold increment in GABA concentration, relative to fresh tea leaves. This increment was due to the increase of glutamate decarboxylase and diamine oxidase activities. Genes involved in GABA formation, such as CsGAD1 and CsGAD2, were significantly up-regulated by anoxia. The concentrations of putrescine and spermine, two substrates for GABA production, were also increased by anoxia. Treating tea leaves with aminoguanidine completely inhibited diamine oxidase activity during anoxia, but the concentration of GABA decreased by only ∼25%. We infer that about one-fourth of GABA formed in tea leaves under anoxia comes from the polyamine degradation pathway, opening the possibility of producing GABA tea based through the regulation of metabolism.


Further expanding the clinical phenotype in Bainbridge-Ropers syndrome and dissecting genotype-phenotype correlation in the ASXL3 mutational cluster regions.
Bainbridge-Ropers syndrome (BRPS) [OMIM#615485] is a neurodevelopmental disorder, characterized by delayed psychomotor development with generalized hypotonia, intellectual disability with poor or absent speech, feeding difficulties, growth failure, specific craniofacial and minor skeletal features. It was firstly reported in 2013 by Bainbridge et al., who observed a group of individuals sharing overlapping features with Bohring-Opitz syndrome which were caused by pathogenic variant in ASXL1, who indeed carried truncating mutations in ASXL3. To date, 33 cases were described in the literature. BRPS is caused by loss-of-function mutations in ASXL3 which are mostly located in two mutational cluster regions (MCR). The exact molecular mechanism of these mutations resulting in the disease phenotype is still uncertain due to the observation of LOF mutations in healthy population. Here, we report four individuals with BRPS carrying de novo LOF mutations in ASXL3, comparing and summarizing the clinical phenotype of all BRPS reported so far. Furthermore, we try to dissect the genotype-phenotype correlation among the two well reported MCRs in all BRPS from the literature.


Designing spike protein (S-Protein) based multi-epitope peptide vaccine against SARS COVID-19 by immunoinformatics.
The outbreak of COVID-19 was originated from China, responsible for Several Acute Respiratory Syndrome (SARS). Scientists are forced to develop vaccine and effective drugs to control COVID-19 infection. To develop effective vaccine for SARS - COVID 19, immunoinformatics and computational approaches could helps to design successful vaccine against this biggest danger for humanity. Here we used various in - silico approaches to designed vaccine against COVID-19. To develop vaccine, we target S- protein, expressed on the virus surface plays important role in COVID-19 infection. We identified 12 B-cell, 9 T-helper and 20 Cytotoxic T-cell epitope based on criteria of selection. The predicted epitopes were link simultaneously with GPGPG & AAY linkers. The β-defensin was used as adjuvant, linked with selected epitope by using EAAAK linker. For vaccine construct justification we analysed its immunogenicity, allergenicity and physiochemical properties. Our study revealed that vaccine was non toxic, immunogenic and antigenic in nature and covers 98.6% of world population, important for vaccine effectively. In- silico cloning was used to analyse its expression in vector. Molecular docking was performed to study the interaction of construct with TLR (TLR3, TLR4, and TLR9) molecules. The immune simulation was conducted and conformed that our vaccine constructs can induces both acquired and humoral immunity effectively against COVID-19 at very low concentration, but along with bioinformatics study we need to conduct experiment in laboratory to validate its safety and effectiveness.


Alleviation of cadmium accumulation in maize (Zea mays L.) by foliar spray of zinc oxide nanoparticles and biochar to contaminated soil.
Due to the increase in area of cadmium (Cd)-contaminated soils worldwide, effective measures are necessary to minimize the Cd accumulation in cereals including maize (Zea mays L.) plant. A study was therefore performed to explore the effectiveness of foliar spray of zinc oxide (ZnO) nanoparticle (NPs) alone (0, 50, 75, 100 mg/L) or combined with soil application of biochar (1.0% w/w) on biomass, antioxidant enzyme activity and Cd concentrations in maize plants grown on a Cd-contaminated soil. The results depicted that ZnO NPs alone or in combination with biochar improved the height of maize plants, number of leaves, shoot and roots dry biomass, chlorophyll concentrations and gas exchange attributes. All the amendments reduced the electrolyte leakage, malondialdehyde, and hydrogen peroxide contents while improved the activities of antioxidant enzymes in leaf and roots of maize over the control. The application of 50, 75 and 100 mg/L ZnO NPs reduced the Cd contents in shoots by about 12%, 23, and 61%, and in roots by 18%, 33%, and 53%, respectively, over the control. The Cd concentrations in shoot decreased by 15%, 28%, and 68% and in roots by 14%, 35, and 55% after biochar combined with foliar spray of 50, 75 and 100 mg/L ZnO NPs, respectively. All the amendments improved the Zn concentrations in maize shoots and roots whereas reduced the soil bioavailable Cd. Overall, biochar combined with foliar spray of ZnO NPs could be recommended for safely growing the crops on Cd-contaminated soils.


Classification-based deep neural network vs mixture density network models for insulin sensitivity prediction problem.
Model-based glycemic control (GC) protocols are used to treat stress-induced hyperglycaemia in intensive care units (ICUs). The STAR (Stochastic-TARgeted) glycemic control protocol - used in clinical practice in several ICUs in New Zealand, Hungary, Belgium, and Malaysia - is a model-based GC protocol using a patient-specific, model-based insulin sensitivity to describe the patient's actual state. Two neural network based methods are defined in this study to predict the patient's insulin sensitivity parameter: a classification deep neural network and a Mixture Density Network based method. Treatment data from three different patient cohorts are used to train the network models. Accuracy of neural network predictions are compared with the current model- based predictions used to guide care. The prediction accuracy was found to be the same or better than the reference. The authors suggest that these methods may be a promising alternative in model-based clinical treatment for patient state prediction. Still, more research is needed to validate these findings, including in-silico simulations and clinical validation trials.


Nonlethal Levels of Zeaxanthin Inhibit Cell Migration, Invasion, and Secretion of MMP-2 via NF-κB Pathway in Cultured Human Uveal Melanoma Cells.
Zeaxanthin at nonlethal dosages (3-10 μM) significantly inhibited the cell migration of cultured uveal melanoma cells (C918 cell line) as determined by wound healing assay and Boyden chamber assay. Matrigel invasion assay showed that cell invasion of uveal melanoma cells could be significantly inhibited by zeaxanthin. Secretion of MMP-2 by melanoma cells was significantly inhibited by zeaxanthin in a dose-dependent manner as measured by ELISA kit. Zeaxanthin also significantly inhibited the NF-κB levels in nuclear extracts of the UM cells, which is the upstream of the MMP-2 secretion. These results suggest that zeaxanthin might be a potentially therapeutic approach in the prevention of metastasis in uveal melanoma.


Association of sustained cardiovascular recovery with epinephrine in the delayed lipid-based resuscitation from cardiac arrest induced by bupivacaine overdose in rats.
The role of epinephrine combined with lipid emulsion in rescuing cardiovascular collapse induced by local anaesthetic overdose remains unclear. The objective of this study was to explore the effect of epinephrine on delayed lipid-based treatment for bupivacaine-induced cardiac arrest in rats. Thirty-two rats were subjected to bupivacaine to induce asystole. Basic life support was performed for 10 min before the rats received saline, epinephrine alone, or 20% lipid emulsion bolus with or without epinephrine pretreatment. ECG and invasive arterial pressure were monitored continuously. Arterial blood gas was analysed at 25 min; the right lungs and hearts of rats were harvested for measurement of dry-to-wet lung weight ratio and myocardial bupivacaine content, respectively. In the rats treated with epinephrine plus lipid emulsion, there was a marked improvement in haemodynamic parameters at 25 min compared with rats treated with lipid alone, P<0.05. The coronary perfusion pressure immediately after lipid rescue was higher in the epinephrine/lipid-treated rats when compared with rats given lipid only (70 and 24 mm Hg, respectively, P<0.05). The myocardial bupivacaine content was lower (8.34 nM g(-1)) in the epinephrine/lipid group relative to other groups (P<0.05). However, the rats treated with lipid alone which survived had higher PO(2), less severe acidosis, and better hypoxaemia relative to surviving rats given epinephrine plus lipid. Late intervention with epinephrine plus lipid emulsion contributed to sustained improvement in haemodynamic profile, but failed to alleviate deterioration of hypoxaemia and acidaemia in rats.