Studies on the poisonous skin secretion of individual red bellied toads, Melanophryniscus montevidensis (Anura, Bufonidae), from Uruguay.
Toads belonging to the genus Melanophryniscus contain toxic alkaloids in their skin. From six locations in south-eastern Uruguay 81 specimens of Melanophryniscusmontevidensis were collected. In whole animal methanolic extracts of individual specimens, alkaloids of the pumiliotoxin (PTX) group and indolizidines were identified by gas chromatography/mass spectrometry; the predominant component PTX 251D was assayed quantitatively. The PTX-content of the various toad populations was found to be highly variable among individual specimens as well as among the populations. Very high levels of PTX 251D were detected in toads of the western part of the collection area, whereas very low levels of this alkaloid were assayed in toads near the Brazilian border. Remarkably high concentrations of the non-alkaloid hydroquinone were found to be present in all toads. The analysis of extracts from 125 arthropod samples (Arachnida and Insecta, including termites, ants and beetles), which may represent a potential food source, revealed no alkaloids of the PTX group.


Potential surface alteration effects of laser-assisted periodontal surgery on existing dental restorations.
Laser-assisted gingivectomies are performed in proximity to teeth, existing restorations, and implants. In case of accidental exposures, a detrimental surface defect may cause failure. Surface interactions should be evaluated for safety margin determination of certain laser-material combinations. The purpose of this in vitro study was to assess the microscopic and visible effects of CO2, Nd:YAG, and 810-nm diode laser irradiations on various dental materials and tooth tissue. Study samples were fabricated (10 x 7.5 mm irradiation surface area, 1 mm thickness) from eight material groups (amalgam, base metal, gold, palladium-silver, composite, ceramic, titanium, and extracted tooth slices). Laser irradiations were performed with CO2, Nd:YAG, and 810-nm diode lasers using the manufacturer's recommended settings for gingivectomy at a 45-degree angle for 30 seconds. Irradiated surfaces were evaluated under SEM at 200x and 1,000x magnifications. Standardized photographs were obtained using a camera mount system (10x high-definition macro lens). The SEM images and photographs were correlated to determine surface interactions. Nd:YAG detrimentally affected all metallic materials and tooth structures. CO2 altered amalgam, gold, and palladium-silver slightly, whereas composite, ceramic, and tooth surfaces were detrimentally altered. The 810-nm diode altered amalgam, gold, titanium, palladium-silver, and composite but only gold and palladium-silver surfaces were barely traceable. Within the limitations of this in vitro study, surface effects were all instant; therefore, even a short accidental exposure may be destructive in some laser-material combinations. During gingivectomies, CO2 near tooth-colored restorations and Nd:YAG near metallic restorations and implants should be used carefully. The 810-nm diode was found to be safer due to its reversible alterations in only some materials. Further in vivo studies are necessary to clinically apply the outcomes of this study.


Validity of the telematic Fugl Meyer assessment scale - upper extremity (TFMA-UE) Spanish version.
Telematic assistance has become indispensable in recent years. The increased prevalence of Acquired brain injury and the sequels it causes, requires long-lasting multidisciplinary treatments. Validated tools to assess the evolution of the disabilities and limitations of this pathology are essential to individualize and prescribe adapted treatments. The aim has been to create the telematic version of the Fugl Meyer Assessment-Upper Extremity Motor Function (TFMA-UE) Spanish scale and its adaptation to the remote assessment of neurologic patients. An adapted scale was designed based on the Fugl Meyer Assessment scale-telematic version (FMA-TV): TFMA-UE. This scale is composed by 21 items which evaluate the upper extremity motor function. Physiotherapists trained in this tool, evaluate the results obtained from applying the two versions (on-site and telematic) to compare the results. TFMA-UE was administered to 30 patients with acquired brain injury. It was applied on site and through the web platform selected by the patients in two different days. Patients completed all the scale in an easily way without help. The exploratory and confirmatory factor analysis confirmed a factorial structure with a factor (76.08% of the variance). The Cronbach's internal consistency index obtained was 0.98 and the weight kappa index used to measure agreement between the two versions was 0.78 which represents substantial agreement. The Telematic Fugl Meyer Assessment-Upper Extremity Motor Function (TFMA-UE) scale is a viable, useful and easy to apply tool that allows the upper extremity motor function assessment of Acquired Brain Injury patients.


Majority of alpha2,6-sialylated glycans in the adult mouse brain exist in O-glycans: SALSA-MS analysis for knockout mice of alpha2,6-sialyltransferase genes.
Sialic acids are unique sugars with negative charge and exert various biological functions such as regulation of immune systems, maintenance of nerve tissues and expression of malignant properties of cancers. Alpha 2,6 sialylated N-glycans, one of representative sialylation forms, are synthesized by St6gal1 or St6gal2 gene products in humans and mice. Previously, it has been reported that St6gal1 gene is ubiquitously expressed in almost all tissues. On the other hand, St6gal2 gene is expressed mainly in the embryonic and perinatal stages of brain tissues. However, roles of St6gal2 gene have not been clarified. Expression profiles of N-glycans with terminal α2,6 sialic acid generated by St6gal gene products in the brain have never been directly studied. Using conventional lectin blotting and novel sialic acid linkage-specific alkylamidationmass spectrometry method (SALSA-MS), we investigated the function and expression of St6gal genes and profiles of their products in the adult mouse brain by establishing KO mice lacking St6gal1 gene, St6gal2 gene, or both of them (double knockout). Consequently, α2,6-sialylated N-glycans were scarcely detected in adult mouse brain tissues, and a majority of α2,6-sialylated glycans found in the mouse brain were O-linked glycans. The majority of these α2,6-sialylated O-glycans were shown to be disialyl-T antigen and sialyl-(6)T antigen by mass spectrometry analysis. Moreover, it was revealed that a few α2,6-sialylated N-glycans were produced by the action of St6gal1 gene, despite both St6gal1 and St6gal2 genes being expressed in the adult mouse brain. In the future, where and how sialylated O-linked glycoproteins function in the brain tissue remains to be clarified.


Body mass index of healthy men compared with healthy women in the United States.
To compare the distributions of body mass index (BMI) in relatively healthy nonsmoking men and women in the United States. Cross-sectional national survey data from the Third National Health and Nutrition Examination Survey (NHANES III). I n total, 11,404 nonsmoking men (n = 4894) and women (n = 6510), ages 20 years and above, drawn from a representative population sample. Increasingly stringent definitions of 'health' were applied, based on self-reported health, medical history, measurements of blood pressure, blood lipids, serum glucose, glycosylated hemoglobin, and behavioral factors including smoking and physical activity. Main outcome measures were mean and median BMI by health level, 5th and 95th percentiles of BMI, and the prevalence of overweight and obesity. For both men and women, the distribution of BMI became less skewed at better health levels. The range of BMI values that included 90% of healthy men and women was approximately 19.5-30 kg/m2 for men and 18-30 kg/m2 for women, with median values of approximately 24.5 kg/m2 for men and 21.5 kg/m2 for women. The prevalence of overweight declined sharply with increasing health level for women but varied little for men; the prevalence of obesity declined at higher health levels for both men and women. Only about 5% of healthy younger men or women would be classified as obese by BMI levels. However, the distribution of BMI differs between healthy men and healthy women. Relative to the distribution of BMI values for healthy men, the distribution of BMI values for healthy women is shifted to the left and is more skewed.


Non-bacterial thrombotic endocarditis and stroke.
Two cases of non-bacterial thrombotic endocarditis are described associated with stroke. This is followed by discussion of the pathophysiology of the disorder.


Zygomatic and mandibular augmentation with proplast and porous hydroxyapatite in rhesus monkeys.
Using an extraoral approach, subperiosteal pockets were created bilaterally over the zygomatic and mandibular regions in six Rhesus monkeys. One side of each animal received a Proplast I (Vitek Inc, Houston) implant and the contralateral side received an equivalent sized block of porous hydroxyapatite (HA). The animals were followed clinically and radiographically. Two animals were killed postoperatively at 3, 6, and 12 months, respectively. The implants were retrieved en bloc and halved. Half of each specimen was decalcified, embedded in paraffin, and stained. The other half was embedded in plastic, and sections were stained or carbon-coated for histometry scanning under electron microscopy. Clinical evaluation revealed that porous HA implants were more stable than Proplast implants. The Proplast implants showed complete encapsulation by infiltration with fibrovascular connective tissue, and progressive fragmentation with giant cell reactions. The porous HA implants were united to the underlying cortex by bony ingrowth. The volume of implants sampled within 2.5 mm of the underlying cortex contained 42.5% HA matrix and 23.8% bony ingrowth, and the surface area of the HA matrix (9.7 mm2/mm3) was 47.8% covered by bony ingrowth. No giant cell response, fragmentation, or biodegradation was observed or measured in the porous HA implants. The data from this primate model further substantiate previous canine studies and permit more reliable estimation of clinical performance. These results provide comparative data that can contribute to the decision-making process in selecting clinical implants.


An end to anxiety treating speech problems with rhetoritherapy.
The controversy over the connection between anxiety and nonproductive speech behavior can be resolved by taking note that alteration in behavior usually alters anxiety level. While many theorists recommend that treatment of anxiety will be beneficial, there is little contention that modification of anxiety alone alters skillful behavior. Rhetoritherapy is a mode of changing communication behavior through application of heuristics of problem solving and behavior change. Research studies tend to indicate a high level of success and selected case histories illustrate the process.


Measurement of serum bactericidal activity and use of vancomycin for treatment of nutritionally variant streptococcal bacteremia.
Nutritionally variant streptococci appear more resistant to antimicrobial treatment that other viridans streptococci. We describe a patient with nutritionally variant streptococcal bacteremia who responded to treatment with vancomycin. Results of serum bactericidal tests did not vary in six different media and correlated minimally with the serum concentration of vancomycin.


Sensitive and simple liquid chromatographic method with ultraviolet detection for the determination of nifedipine in canine plasma.
An isocratic high-performance liquid chromatographic method with detection at 240 nm was developed, optimized and validated for the determination of nifedipine in canine plasma. Liquid-liquid extraction was used as the sample preparation technique. Carbamazepine was used as internal standard. A Hypersil BDS RP-C18 column (250 mm x 4.6 mm, 5 microm) was equilibrated with a mobile phase composed of water and methanol, 45:55 (v/v). Its flow rate was 1 ml min(-1). The elution time for nifedipine and carbamazepine was approximately 12 and 8 min, respectively. Calibration curves of nifedipine in plasma were linear in the concentration range of 1-200 ng ml(-1). Limits of detection and quantification in plasma were 0.5 and 1.5 ng ml(-1), respectively. Recovery was greater than 98%. Intra- and inter-day relative standard deviation for nifedipine in plasma was less than 8.5 and 10%, respectively. This method was applied to the determination of nifedipine plasma levels after administration of commercially available soft gelatine capsules to dogs.


Titanium trisulfide (TiS3): a 2D semiconductor with quasi-1D optical and electronic properties.
We present characterizations of few-layer titanium trisulfide (TiS3) flakes which, due to their reduced in-plane structural symmetry, display strong anisotropy in their electrical and optical properties. Exfoliated few-layer flakes show marked anisotropy of their in-plane mobilities reaching ratios as high as 7.6 at low temperatures. Based on the preferential growth axis of TiS3 nanoribbons, we develop a simple method to identify the in-plane crystalline axes of exfoliated few-layer flakes through angle resolved polarization Raman spectroscopy. Optical transmission measurements show that TiS3 flakes display strong linear dichroism with a magnitude (transmission ratios up to 30) much greater than that observed for other anisotropic two-dimensional (2D) materials. Finally, we calculate the absorption and transmittance spectra of TiS3 in the random-phase-approximation (RPA) and find that the calculations are in qualitative agreement with the observed experimental optical transmittance.


One-shot lactate chemiluminescent biosensor.
A new chemiluminescence-based one-shot biosensor for lactate is described. The lactate recognition system is based on lactate oxidase (LOx) and the transduction system consists of luminol, peroxidase from Arthromyces ramosus (ARP) and metallic aluminum, all immobilized in a polyion complex membrane. The measurement of the chemiluminescence in a luminometer when 1 mL of sample is injected into a conventional cell containing the disposable sensing membrane makes it possible to determine lactate. The compositions of the membrane and reaction conditions have been optimized to obtain adequate sensitivity. The one-shot biosensor responds to lactate rapidly, with the typical CL acquisition time being 2 min, with a linearized logarithmic dependence whose dynamic range was from 5 x 10(-5) to 4 x 10(-3) with a detection limit of 9.2 x 10(-6)M and a sensor-to-sensor reproducibility (relative standard deviation, R.S.D.) of 5.5% at the medium level of the range. The performance of the chemiluminescent one-shot biosensor was tested for the analysis of lactate in yoghurt, validating the results against an enzymatic reference procedure. The proposed method is quick, inexpensive and sensitive and uses conventional CL instrumentation.


The impact of STRICTA and CONSORT on reporting of randomised control trials of acupuncture: a systematic methodological evaluation.
Clear and unambiguous reporting is essential for researchers and clinicians to be able to assess the quality of research. To enhance the quality of reporting, consensus-based reporting guidelines are commonly used. To update and extend previous research by evaluating the more recent impact of STRICTA (STandards for Reporting Interventions in Controlled Trials of Acupuncture) and CONSORT (CONsolidated Standards Of Reporting Trials) guidelines on the quality of reporting of acupuncture trials. By random sampling, approximately 45 trials from each of five 2-year time periods between 1994 and 2015 were included in the study. Using scoring sheets based on the STRICTA and CONSORT checklist items (range 0 to 7 and 0 to 5, respectively), the distribution of items reported over time was investigated, with changes shown using scatterplots. The primary analysis used a before-and-after t-test to compare time periods. A meta-analysis investigated whether or not trials published in journals that endorsed STRICTA were associated with better reporting. The study included 207 trials. Improved reporting of items over time was observed, as represented by changes in the scatterplot slope and intercept. The mean STRICTA score increased from 4.27 in the 1994-1995 period to 5.53 in 2014-2015, an 18% improvement. The mean CONSORT score rose from 1.01 in the 1994-1995 period to 3.32 in 2014-2015, an increment of 46%. There was proportionately lower reporting for items related to practitioner background (STRICTA) and for randomisation implementation and allocation concealment (CONSORT). Trials published in journals that endorsed STRICTA had statistically significantly superior reporting of both STRICTA and CONSORT items overall. This study has provided evidence of an improvement in reporting of STRICTA and CONSORT items over the time period from 1994 to 2015. Journals that endorse STRICTA have a better record in terms of reporting quality. Some evidence suggests that the publication of STRICTA has had a positive impact on reporting quality.


The oral microbiome of implant-abutment screw holes compared with the peri-implant sulcus and natural supragingival plaque in healthy individuals.
An implant-supported prosthesis consists of an implant fixture, an abutment, an internal screw that connects the abutment to the implant fixture, and the upper prosthesis. Numerous studies have investigated the microorganisms present on the implant surface, surrounding tissues, and the subgingival microflora associated with peri-implantitis. However, there is limited information regarding the microbiome within the internal screw space. In this study, microbial samples were collected from the supragingival surfaces of natural teeth, the peri-implant sulcus, and the implant-abutment screw hole, in order to characterize the microbiome of the internal screw space in healthy subjects. Samples were obtained from the supragingival region of natural teeth, the peri-implant sulcus, and the implant screw hole in 20 healthy subjects. DNA was extracted, and the V3-V4 region of the 16S ribosomal RNA was sequenced for microbiome analysis. Alpha diversity, beta diversity, linear discriminant analysis effect size (LEfSe), and network analysis were employed to compare the characteristics of the microbiomes. We observed significant differences in beta diversity among the samples. Upon analyzing the significant taxa using LEfSe, the microbial composition of the implant-abutment screw hole's microbiome was found to be similar to that of the other sampling sites' microbiomes. Moreover, the microbiome network analysis revealed a unique network complexity in samples obtained from the implant screw hole compared to those from the other sampling sites. The bacterial composition of the biofilm collected from the implant-abutment screw hole exhibited significant differences compared to the supra-structure of the implant. Therefore, long-term monitoring and management of not only the peri-implant tissue but also the implant screw are necessary.


Genome-scale genetic engineering in Escherichia coli.
Genome engineering has been developed to create useful strains for biological studies and industrial uses. However, a continuous challenge remained in the field: technical limitations in high-throughput screening and precise manipulation of strains. Today, technical improvements have made genome engineering more rapid and efficient. This review introduces recent advances in genome engineering technologies applied to Escherichia coli as well as multiplex automated genome engineering (MAGE), a recent technique proposed as a powerful toolkit due to its straightforward process, rapid experimental procedures, and highly efficient properties.


Optimal choice of word length when comparing two Markov sequences using a χ 2-statistic.
Alignment-free sequence comparison using counts of word patterns (grams, k-tuples) has become an active research topic due to the large amount of sequence data from the new sequencing technologies. Genome sequences are frequently modelled by Markov chains and the likelihood ratio test or the corresponding approximate χ 2-statistic has been suggested to compare two sequences. However, it is not known how to best choose the word length k in such studies. We develop an optimal strategy to choose k by maximizing the statistical power of detecting differences between two sequences. Let the orders of the Markov chains for the two sequences be r 1 and r 2, respectively. We show through both simulations and theoretical studies that the optimal k= max(r 1,r 2)+1 for both long sequences and next generation sequencing (NGS) read data. The orders of the Markov chains may be unknown and several methods have been developed to estimate the orders of Markov chains based on both long sequences and NGS reads. We study the power loss of the statistics when the estimated orders are used. It is shown that the power loss is minimal for some of the estimators of the orders of Markov chains. Our studies provide guidelines on choosing the optimal word length for the comparison of Markov sequences.


The Solution Structure of the Lantibiotic Immunity Protein NisI and Its Interactions with Nisin.
Many Gram-positive bacteria produce lantibiotics, genetically encoded and posttranslationally modified peptide antibiotics, which inhibit the growth of other Gram-positive bacteria. To protect themselves against their own lantibiotics these bacteria express a variety of immunity proteins including the LanI lipoproteins. The structural and mechanistic basis for LanI-mediated lantibiotic immunity is not yet understood. Lactococcus lactis produces the lantibiotic nisin, which is widely used as a food preservative. Its LanI protein NisI provides immunity against nisin but not against structurally very similar lantibiotics from other species such as subtilin from Bacillus subtilis. To understand the structural basis for LanI-mediated immunity and their specificity we investigated the structure of NisI. We found that NisI is a two-domain protein. Surprisingly, each of the two NisI domains has the same structure as the LanI protein from B. subtilis, SpaI, despite the lack of significant sequence homology. The two NisI domains and SpaI differ strongly in their surface properties and function. Additionally, SpaI-mediated lantibiotic immunity depends on the presence of a basic unstructured N-terminal region that tethers SpaI to the membrane. Such a region is absent from NisI. Instead, the N-terminal domain of NisI interacts with membranes but not with nisin. In contrast, the C-terminal domain specifically binds nisin and modulates the membrane affinity of the N-terminal domain. Thus, our results reveal an unexpected structural relationship between NisI and SpaI and shed light on the structural basis for LanI mediated lantibiotic immunity.


Brief intervention for daily marijuana users identified by screening in primary care: A subgroup analysis of the ASPIRE randomized clinical trial.
The use of brief intervention for decreasing frequent marijuana use holds potential, but its efficacy in primary care is not known. To assess the impact of 2 brief interventions on marijuana use among daily/or almost daily marijuana users. Subgroup analysis of a 3-arm randomized clinical trial of 2 brief counseling interventions compared with no brief intervention on daily marijuana use in a primary care setting (ASPIRE). ASPIRE study participants who both reported 21-30 days of marijuana use during the past month and identified marijuana as their drug of most concern. (1) brief negotiated interview (BNI), a 10-15-minute structured interview, and (2) an adaptation of motivational interviewing (MOTIV), a 30-45-minute intervention. Control group participants received only a list of substance use treatment resources. The primary outcome was number of days of marijuana use in the past 30 days at the 6-month follow-up. Secondary outcomes were (1) number of days of marijuana use at 6-week follow-up and (2) drug problems (Short Inventory of Problems-Drugs, SIP-D) at 6-week and 6-month follow-ups. Differences between intervention groups were analyzed using negative binomial regression models. Among the 167 eligible participants, we did not find any significant impact of either of the 2 interventions on past 30 days of marijuana use at 6 months (adjusted incidence rate ratio [aIRR]: 0.95, 95% confidence interval [CI]: 0.75-1.15, P = .82 for BNI vs. control; aIRR: 1.02, 95% CI: 0.85-1.23, P = .82 for MOTIV vs. control). There was no significant impact on drug-related problems at 6-month follow-up (aIRR: 1.12, 95% CI: 0.69-1.82, P = .66 and aIRR: 1.46, 95% CI: 0.89-2.38, P = .27 for BNI vs. control and MOTIV vs. control, respectively). Results were similar at 6 weeks. Brief intervention has no apparent impact on marijuana use or drug-related problems among primary care patients with frequent marijuana use identified by screening.


Drug-induced calcium release from heavy sarcoplasmic reticulum of skeletal muscle.
Calcium release from isolated heavy sarcoplasmic reticulum of rabbit skeletal muscle by several calmodulin antagonistic drugs was measured spectrophotometrically with arsenazo III and compared with the properties of the caffeine-induced calcium release. Trifluoperazine and W7 (about 500 microM) released all actively accumulated calcium (half-maximum release at 129 microM and 98 microM, respectively) in the presence 0.5 mM MgCl2 and 1 mg/ml sarcoplasmic reticulum protein; calmidazolium (100 microM) and compound 48/80 (70 micrograms/ml) released maximally 30-40% calcium, whilst bepridil (100 microM) and felodipin (50 microM) with calmodulin antagonistic strength similar to trifluoperazine (determined by inhibition of the calcium, calmodulin-dependent protein kinase of cardiac sarcoplasmic reticulum) did not cause a detectable calcium release, indicating that this drug-induced calcium release is not due to the calmodulin antagonistic properties of the tested drugs. Calcium release of trifluoperazine, W7 and compound 48/80 and that of caffeine was inhibited by similar concentrations of magnesium (half-inhibition 1.4-4.2 mM compared with 0.97 mM for caffeine) and ruthenium red (half-inhibition for trifluoperazine, W7 and compound 48/80 was 0.22 microM, 0.08 microM and 0.63 micrograms/ml, respectively, compared with 0.13 microM for caffeine), suggesting that this drug-induced calcium release occurs via the calcium-gated calcium channel of sarcoplasmic reticulum stimulated by caffeine or channels with similar properties.


Decline in intracellular free Mg2+ is associated with irreversible tissue injury after brain trauma.
Much of the tissue damage resulting from trauma to the central nervous system appears to result from secondary, delayed biochemical changes that follow primary mechanical injury. However, the early biochemical events remain to be elucidated. In the present studies, we have used phosphorus (31P) magnetic resonance spectroscopy (MRS) to examine in vivo, the temporal changes in brain intracellular free Mg2+ concentration following fluid percussion head injury in rats. We report that injury caused a profound and rapid decrease in intracellular free Mg2+ which was significantly correlated with the severity of injury. At high levels of injury, the decrease in intracellular free Mg2+ concentration was associated with a decrease in total Mg2+ concentration as determined by atomic absorption spectrophotometry. Prophylactic treatment with MgSO4 prevented the post-traumatic decrease in intracellular free Mg2+ and resulted in a significant improvement in acute neurological outcome. Because magnesium is essential for a number of critical enzyme reactions, including those of glycolysis, oxidative and substrate level phosphorylation, protein synthesis, and phospholipid synthesis, changes in free Mg2+ after brain trauma may represent a critical early factor leading to irreversible tissue damage.


Assessment of Dilute Epinephrine and Mechanical Pressure for Prevention of Feline Postoperative Scrotal Hematoma: A Randomized Controlled Trial.
To determine whether two immediately postoperative preventive procedures, dilute epinephrine (1:400,000) as a scrotal wash or application of controlled mechanical pressure to the scrotum, reduce the risk or severity of scrotal hematoma following routine castration. Male cats with two descended testicles presenting to Midwestern University's Trap Neuter Return program were eligible for inclusion. Cats were assigned via block randomization to control, dilute epinephrine wash, or controlled mechanical pressure groups. For the epinephrine group, 0.2 ml (0.008 mg) of epinephrine diluted with sterile saline was instilled inside the scrotum. In the case of mechanical pressure, a broad-based clip generating less than 0.5 kg of pressure was applied for 10 minutes. Cats were evaluated for scrotal hematoma and the need for treatment by a veterinarian blinded to treatment group. Multivariable logistic regression was used to determine if the incidence of scrotal hematoma or scrotal hematoma requiring treatment was different between groups while controlling for other variables. There were 276 cats with a median age of 30 months (IQR 12,48) and a mean weight of 3.5 kg (SD 1.2). Scrotal hematomas were noted in 15 of the 92 (16%) control cats, as compared with 12 of the 92 (13%) epinephrine and nine of the 92 (10%) pressure cats. Treatment was required for 10 (67%) control, six (50%) epinephrine, and three (33%) pressure hematomas. Regression demonstrated a decreased risk of scrotal hematoma requiring treatment for cats in the pressure group (OR = 0.2, P = .044) controlling for weight (OR = 2.2, P = .006) and surgical duration (OR = 1.1, P = .026). Weight was the only significant variable for the presence of scrotal hematoma (OR = 2.2, P < .0001). Controlled mechanical pressure applied immediately after routine castration can help decrease the proportion of scrotal hematomas that require treatment.


Recurrent Listeria monocytogenes bacteraemia in a liver transplant patient.
We report a case of a recurrent Listeria monocytogenes bacteraemia in a 46 year-old liver transplant patient. Serotyping revealed that the two episodes of bacteraemia were caused by different strains. The possibility of a recrudescence of a persisting infection was rejected. We concluded that the recurrent bacteraemia in this predisposed patient was due to re-infection, and that antibiotic treatment (amoxicillin plus an aminoglycoside) resulted in a complete eradication of the infective microorganism. Therefore long-term suppressive antibiotic treatment was not indicated. The source of these L. monocytogenes infections was not found.


Mid-treatment 18F-FDG PET imaging changes in parotid gland correlates to radiation-induced xerostomia.
The aim of this study was to measure functional changes in parotid glands using mid-treatment FDG-PET/CT and correlate early imaging changes to subsequent xerostomia in mucosal head and neck squamous cell carcinoma patients undergoing radiotherapy. 56 patients from two prospective imaging biomarker studies underwent FDG-PET/CT at baseline and during radiotherapy (week 3). Both parotid glands were volumetrically delineated at each time point. PET parameter SUVmedian were calculated for ipsilateral and contralateral parotid glands. Absolute and relative change (Δ) in SUVmedian were correlated to moderate-severe xerostomia (CTCAE grade ≥ 2) at 6 months. Four predictive models were subsequently created using multivariate logistic regression using clinical and radiotherapy planning parameters. Model performance was calculated using ROC analysis and compared using Akaike information criterion (AIC) RESULTS: 29 patients (51.8%) developed grade ≥ 2 xerostomia. Compared to baseline, there was an increase in SUVmedian at week 3 in ipsilateral (8.4%) and contralateral (5.5%) parotid glands. Increase in ipsilateral parotid Δ SUVmedian (p = 0.04) and contralateral mean parotid dose (p = 0.04) were correlated to xerostomia. The reference 'clinical' model correlated to xerostomia (AUC 0.667, AIC 70.9). Addition of ipsilateral parotid Δ SUVmedian to the clinical model resulted in the highest correlation to xerostomia (AUC 0.777, AIC 65.4). Our study shows functional changes occurring in the parotid gland early during radiotherapy. We demonstrate that integration of baseline and mid-treatment FDG-PET/CT changes in the parotid gland with clinical factors has the potential to improve xerostomia risk prediction which could be utilised for personalised head and neck radiotherapy.


Amino acid ionic liquid-based facilitated transport membranes for CO2 separation.
Supported liquid membranes incorporating amino acid ionic liquids remarkably facilitate CO(2) permeation under dry and low humid conditions.


The effect of repeated episodes of dietary restriction and refeeding on systolic blood pressure and food intake in exercise-trained normotensive rats.
To explore the effects of weight cycling and exercise on blood pressure and macronutrient intake in Sprague-Dawley rats. Female Sprague-Dawley rats (n = 62; 5 months old) were assigned to an ad libitum (Con) or weight-cycled (Cyc) group. They were either sedentary (Con-Sed and Cyc-Sed) or exercise-trained (Con-Ex and Cyc-Ex) on a motorized treadmill (20 m/minute; 60 minutes/day; 6 days/week). The Cyc groups underwent 2 cycles of 3 weeks of 60% food restriction followed by 5 weeks of ad libitum refeeding using a macronutrient self-selection diet. Body mass and food intake were analyzed weekly. Systolic blood pressure (SBP) was measured at baseline and during the first and fifth weeks of each refeeding. For both cycling periods, SBP was elevated in Cyc vs. Con groups at Week 1 of refeeding, but was similar among groups by Week 5 of refeeding. Both Con groups had greater total energy intake than the Cyc groups for both cycling periods (Cycle 1: 2882.2 +/- 75.1, Con-Sed; 2916.1 +/- 67.1, Con-Ex; 2692.2 +/- 58.7, Cyc-Sed; and 2780.5 +/- 52.4 kcal, Cyc-Ex) (Cycle 2: 2815.8 +/- 75.1, Con-Sed; 2938.8 +/- 49.4, Con-Ex; 2577.1 +/- 60.5, Cyc-Sed; and 2643.5 +/- 65.9 kcal, Cyc-Ex). Relative fat intake (percentage of total kcal/week) was significantly less for Con-Ex and Cyc-Ex than Con-Sed and Cyc-Sed throughout both refeeding periods. Weight cycling failed to produce significant sustained effects on SBP, body mass, or food intake. Exercise training, irrespective of diet, lowered dietary fat intake.


Ectomycorrhizae of Tuber huidongense and T. liyuanum with Castanea mollissima and Pinus armandii.
Tuber huidongense and T. liyuanum are common commercial white truffles in China that belong to the Rufum and Puberulum groups of the genus Tuber, respectively. Their mycorrhizae were successfully synthesized with two native trees--Castanea mollissima and Pinus armandii--under greenhouse conditions. The identities of the mycorrhizae were confirmed through internal transcribed spacer (ITS) sequence analyses, and their morphological characteristics were described. All of the obtained mycorrhizae have an interlocking pseudoparenchymatous mantle, which is a typical feature of truffle mycorrhizae. The mycorrhizae of T. huidongense on the two trees have hyaline branched emanating hyphae, similar to the documented mycorrhizae of the Rufum group. The unramified, spiky, and hyaline cystidia on the mycorrhizae of T. liyuanum with both C. mollissima and P. armandii further confirmed that this characteristic is constant for the mycorrhizae of the Puberulum group. The successful mycorrhizal syntheses on the two nut-producing trees will be of economic importance in the cultivation of the two truffles.


Rapid 18 F- and 19 F-Difluoromethylation through Desulfurative Fluorination of Transient N-, O-, and C-Linked Dithioles.
The difluoromethyl group plays an important role in modern medicinal and agrochemistry. While several difluoromethylation reagents have been reported, these typically rely on difluoromethyl carbenes or anions, or target specific processes. Here, we describe a conceptually unique and general process for O-H, N-H and C-H difluoromethylation that involves the formation of a transient dithiole followed by facile desulfurative fluorination using silver(I) fluoride. We also introduce the 5,6-dimethoxy-1,3-benzodithiole (DMBDT) function, which undergoes sufficiently rapid desulfurative fluorination to additionally support 18 F-difluoromethylation. This new process is compatible with the wide range of functional groups typically encountered in medicinal chemistry campaigns, and the use of Ag18 F is demonstrated in the production of 18 F-labeled derivatives of testosterone, perphenazine, and melatonin, 58.0±2.2, 20.4±0.3 and 32.2±3.6 MBq μmol-1 , respectively. We expect that the DMBDT group and this 18 F/19 F-difluoromethylation process will inspire and support new efforts in medicinal chemistry, agrochemistry and radiotracer production.


Sustained Type I Interferon Reinforces NK Cell-Mediated Cancer Immunosurveillance during Chronic Virus Infection.
The importance of natural killer (NK) cells in the early immune response to viral or bacterial infection is well known. However, the phenotype, function, and physiologic role of NK cells during the late stage of persistent viral infection have not been extensively studied. Here, we characterized NK cells in mice persistently infected with lymphocytic choriomeningitis virus clone 13 and showed that in contrast to NK cells from acutely infected or uninfected mice, NK cells from chronically infected mice expressed a terminally differentiated phenotype, stronger cytotoxicity, and reduced inhibitory receptor expression. In an in vivo tumor model, chronically infected mice exhibited significantly delayed tumor progression in an NK cell-dependent manner. NK cells from chronically infected mice also expressed high STAT1, and blocking the type I interferon (IFN) receptor revealed that type I IFN signaling directly regulated NK cell cytotoxicity. Our findings indicate that sustained type I IFN signaling during chronic viral infection potentiates the cytolytic function of NK cells and contributes to NK cell-dependent host immune surveillance.


Mandibular bone grafts for reconstruction of alveolar clefts.
This study evaluated the effect of mandibular bone grafts for reconstruction of alveolar clefts. The study included 25 patients with cleft lip and alveolar process only and three patients with unilateral cleft lip and palate, with a median postoperative follow-up of 8 months (range, 6 to 17 months). The bone grafts were obtained from below the mandibular incisors and canines through an intraoral approach. The marginal bone level achieved was satisfactory in all cases evaluated by occlusal radiographs; the radiographs also demonstrated that the bone grafts were totally integrated after 6 months in all cases. The morphology of the reconstructed alveolar process was satisfactory in all cases evaluated and no periodontal complications were seen. The donor site appeared healed radiologically in all cases 6 months after surgery. The advantages gained by using a mandibular bone graft as compared to an iliac crest graft include reduced morbidity, reduced hospitalization time, reduced operating time, and avoidance of scarring at the donor site. The results of the present study demonstrate that the mandibular symphysis can be used as donor site for reconstruction of small alveolar clefts.


16α-OHE1, a novel oestrogen metabolite, attenuates dysfunction of left ventricle contractility via regulation of autophagy after myocardial ischemia and reperfusion.
Myocardial ischemia-reperfusion (MI/R) can exacerbate the initial cardiac damage in the myocardial functional changes, including dysfunction of left ventricular contractility. Oestrogen has been proven to protect the cardiovascular system. However, whether the oestrogen or its metabolites play the main role in attenuating dysfunction of left ventricular contractility is unknown. This study used the LC-MS/MS to detect oestrogen and its metabolites in clinical serum samples (n = 62) with heart diseases. After correlation analysis with markers of myocardial injury including cTnI (P < 0.01), CK-MB (P < 0.05), and D-Dimer (P < 0.001), 16α-OHE1 was identified. The result from LC-MS/MS in female and ovariectomised (OVX) rat serum samples (n = 5) matched the findings in patients. In MI/R model of animal, the recovery of left ventricular developed pressure (LVDP), rate pressure product (RPP), dp/dtmax and dp/dtmin after MI/R in OVX or male group were worsened than those in female group. Also, the infarction area of OVX or male group was larger than that in females (n = 5, p < 0.01). Furthermore, LC3 II in the left ventricle of OVX and male group was lower than that in females (n = 5, p < 0.01) by immunofluorescence. In H9C2 cells, after the application of 16α-OHE1, the number of autophagosomes was further increased and other organelles improved in MI/R. Simultaneously, LC3 II, Beclin1, ATG5, and p-AMPK/AMPK were increased, and p-mTOR/mTOR was decreased (n = 3, p < 0.01) by Simple Western. 16α-OHE1 could attenuate left ventricle contractility dysfunction via autophagy regulation after MI/R, which also offered fresh perspectives on therapeutical treatment for attenuating MI/R injury.


Ranitidine-induced black tongue: A case report.
Black tongue is a rare, benign, self-limiting disorder caused by certain conditions and some medications. We report the first case of a child diagnosed with black tongue associated with ranitidine use. We report our case to emphasize the rare side effect of this frequently used drug. Health care professionals should be aware of the likelihood of ranitidine-induced black tongue in clinical practice.


Noise improves the association between effects of local stimulation and structural degree of brain networks.
Stimulation to local areas remarkably affects brain activity patterns, which can be exploited to investigate neural bases of cognitive function and modify pathological brain statuses. There has been growing interest in exploring the fundamental action mechanisms of local stimulation. Nevertheless, how noise amplitude, an essential element in neural dynamics, influences stimulation-induced brain states remains unknown. Here, we systematically examine the effects of local stimulation by using a large-scale biophysical model under different combinations of noise amplitudes and stimulation sites. We demonstrate that noise amplitude nonlinearly and heterogeneously tunes the stimulation effects from both regional and network perspectives. Furthermore, by incorporating the role of the anatomical network, we show that the peak frequencies of unstimulated areas at different stimulation sites averaged across noise amplitudes are highly positively related to structural connectivity. Crucially, the association between the overall changes in functional connectivity as well as the alterations in the constraints imposed by structural connectivity with the structural degree of stimulation sites is nonmonotonically influenced by the noise amplitude, with the association increasing in specific noise amplitude ranges. Moreover, the impacts of local stimulation of cognitive systems depend on the complex interplay between the noise amplitude and average structural degree. Overall, this work provides theoretical insights into how noise amplitude and network structure jointly modulate brain dynamics during stimulation and introduces possibilities for better predicting and controlling stimulation outcomes.


Detection of serum tumor markers in multiple myeloma using the CLINPROT system.
The discovery of biomarkers unique to multiple myeloma (MM) is of great importance to clinical practice. This study was designed to identify serum tumor marker candidates of MM in the mass range of 700-10000 Da. Serum samples from 48 MM patients and 74 healthy controls were collected and classified into a training dataset (MM/controls: 26/26) and a testing dataset (MM/controls: 22/48). Weak cation exchange magnetic beads, MALDI-TOF MS and analytic software in the CLINPROT system were used to do serum sample pre-fractionation, data acquisition and data analysis. Peak statistics were performed using Welch's t test. Mass spectra from the two model generation cohorts in the training dataset were analyzed by the Supervised Neural Network Algorithm (SNNA) in ClinProTools((TM)) to identify the mass peaks with the highest separation power. The resulting diagnostic model was subsequently validated in the testing dataset. A total of 89 discriminating mass peaks were detected by ClinProTools((TM)) in the range of 700-10000 Da using a signal to noise threshold of 3.0. Of these, 49 peaks had statistical significance (P < 0.0001) and four peaks with the highest separation power were picked up by SNNA to form a diagnostic model. This model achieved high sensitivity (86.36 %) and specificity (87.5 %) in the validation in the testing dataset. Using CLINPROT system and MB-WCX we found four novel biomarker candidates. The diagnostic model built by the four peaks achieved high sensitivity and specificity in validation. CLINPROT system is a powerful and reliable tool for clinical proteomic research.


Effect of hypoxia on the expression of procaspase-9 and procaspase-3 in neuronal nuclear, mitochondrial and cytosolic fractions of the cerebral cortex of newborn piglets.
Previous studies have shown that cerebral hypoxia results in increased activity of caspase-9, a key initiator of programmed cell death, in the cytosolic fractions of the cerebral cortex of newborn piglets. The present study tests the hypothesis that hypoxia results in increased expression of procaspase-9 and procaspase-3 in neuronal nuclear, mitochondrial and cytosolic fractions of the cerebral cortex of newborn piglets. To test this hypothesis, expression of procaspase-9 and procaspase-3 was determined in 10 newborn piglets divided into two groups: normoxic (Nx, n=5) and hypoxic (Hx, n=5). The hypoxic piglets were exposed to an FiO(2) of 0.06 for 1h. Tissue hypoxia was documented by ATP and phosphocreatinine (PCr) levels. Neuronal nuclear, mitochondrial and cytosolic fractions were isolated and the expression of procaspase-9 and procaspase-3 was determined by immunoblotting using specific anti-procaspase-9 and anti-procaspase-3 antibodies. ATP levels (micromol/g brain) were 4.34+/-0.36 in the Nx and 1.43+/-0.28 in the Hx (p<0.001 vs. Nx) groups. PCr levels (micromol/g brain) were 3.75+/-0.27 in the Nx and 0.69+/-0.26 in the Hx (p<0.001 vs. Nx) group. Cytosolic procaspase-9 density (ODxmm(2)) was 88.82+/-17.55 in the Nx and 215.54+/-22.77 in the Hx (p<0.001 vs. Nx). Mitochondrial procaspase-9 density (ODxmm(2)) was 104.67+/-12.75 in the Nx and 183.44+/-16.69 in the Hx (p<0.001 vs. Nx). Nuclear procaspase-9 density (ODxmm(2)) was 135.56+/-15.36 in the Nx and 190.66+/-29.35 in the Hx (p<0.001 vs. Nx). Cytosolic procaspase-3 density (ODxmm(2)) was 23.72+/-3.71 in the Nx and 92.44+/-8.46 in the Hx (p<0.001 vs. Nx). Mitochondrial procaspase-3 density (ODxmm(2)) was 22.12+/-2.97 in the Nx and 51.22+/-10.67 in the Hx (p<0.001 vs. Nx). Nuclear procaspase-3 density (ODxmm(2)) was 53.80+/-7.18 in the Nx and 84.67+/-5.63 in the Hx (p<0.001 vs. Nx). We conclude that procaspase-9 and procaspase-3 proteins increased in all cell compartments including cytosolic, mitochondrial and nuclear during hypoxia, indicating increased expression of procaspase-9 during hypoxia. We propose that following increased expression of procaspase-9 and procaspase-3, these molecules traffic among the various cell compartments and become available for their activation resulting in increased caspase-9 and caspase-3 activity.


Performance of electrospun poly(ε-caprolactone) fiber meshes used with mineral trioxide aggregates in a pulp capping procedure.
Living dental pulp tissue exposed to the oral environment should be protected with an appropriate pulp capping material to support the dentinogenesis potential of the pulp cells. Mineral trioxide aggregate (MTA) is the material of choice for the treatment of pulp. However, due to cytotoxicity during the initial setting phase of MTA, a new material is required that can act as a barrier to direct contact but facilitate the favorable effect of MTA. This study examined the feasibility of using electrospun poly(ε-caprolactone) fiber (PCL-F) meshes in the MTA-based pulp capping procedures. An experimental pulp capping was performed on the premolars of beagle dogs, and the efficacy of the PCL-F meshes was evaluated after 8 weeks. PCL-F/MTA formed a dentin bridge that was approximately fourfold thicker than that formed by the MTA. Columnar polarized odontoblast-like cells with long processes and tubular dentin-like matrices were observed beneath the dentin bridge in the PCL-F/MTA. The cells were also intensely immunostained for dentin sialoprotein. In cell cultures, PCL-F/MTA reduced cell death to ~8% of that in the MTA group. The proliferation of the cells cultured on PCL-F/MTA was much greater than that of cells cultured on MTA. Furthermore, PCL-F/MTA promoted the differentiation of MDPC23 cells to odontoblast-like cells and biomineralization, as confirmed by the expression of alkaline phosphatase and dentin sialophosphoprotein, and by the deposition of calcium. Based on these histologic findings and the cell responses observed in this study, PCL-F may be used efficiently in the MTA-based dental pulp therapy.


The femoral condyle as an alternative source of cancellous bone for grafting of maxillofacial defects.
A technique for obtaining cancellous bone from the distal femoral condyle had been presented. This had been an effective source for grafting selected maxillofacial defects. The method involves an uncomplicated surgical approach and has low morbidity.


Effectiveness of Clinpro Tooth Crème in comparison with MI Varnish with RECALDENT™ for treatment of white spot lesions: a randomized controlled trial.
Unsightly opaque white impaired enamel may ruin a great aesthetic orthodontic outcome. This study aims to evaluate effectiveness of Clinpro Tooth Crème (0.21% w/w NaF anti-caries dentifrice with 950 ppm fluoride and f-TCP) and MI Varnish with RECALDENT™ (CPP-ACP) for treatment of white spot lesions (WSLs). This was a randomized (1:1:1), single-blind, 3-armed, active-controlled, parallel-group trial. The study comprised three groups of 35 patients randomly assigned in blocks of 3 or 6 to one of the three following arms of the study- Group I: Clinpro™ Tooth Crème 0.21% Sodium Fluoride Anti-Cavity Paste with functional-Tri Calcium Phosphate(f-TCP) group. Group II: Fluoride varnish group (MI Varnish with RECALDENT™). Group III: Home-care group (control). For the subjective assessment, a blinded panel of 4 dental experts rated the improvement in WSLs over the eight weeks using a visual analog scale (VAS). In total, 240 WSLs were identified, with maxillary lateral incisors and canines showing the highest incidence. Group I achieved the highest success rate of 67.61 (%) followed by group II (60.59%). There were no significant differences between the success rates of treatment in groups I and II. A minimum decline in WSLs was found in the control group, with a success rate of only 32.43%, significantly less than the first two groups (P < .001). Both the test agents in consideration were comparable in their remineralization potential. Clinpro Tooth Crème provides additional protection against decalcification of enamel compared to MI Varnish with RECALDENT™ (CPP-ACP). TRIAL/PROJECT REGISTRATION NO. 4857/2017 on 21 June 2017.


Influence of Ultrasound Settings on Laboratory Vertical Artifacts.
The aim of the work described here was to analyze the relationship between the change in ultrasound (US) settings and the vertical artifacts' number, visual rating and signal intensity METHODS: An in vitro phantom consisting of a damp sponge and gelatin mix was created to simulate vertical artifacts. Furthermore, several US parameters were changed sequentially (i.e., frequency, dynamic range, line density, gain, power and image enhancement) and after image acquisition. Five US experts rated the artifacts for number and quality. In addition, a vertical artifact visual score was created to determine the higher artifact rating ("optimal") and the lower artifact rating ("suboptimal"). Comparisons were made between the tested US parameters and baseline recordings. The expert intraclass correlation coefficient for the number of vertical artifacts was 0.694. The parameters had little effect on the "optimal" vertical artifacts but changed their number. Dynamic range increased the number of discernible vertical artifacts to 3 from 36 to 102 dB. The intensity did not correlate with the visual rating score. Most of the available US parameters did not influence vertical artifacts.


Studies on isoprenaline-induced myocardial lesions. 1. Quantitative evaluation by mercurascan uptake.
For the quantitative evaluation of myocardial damage induced by isoprenaline (ISO) a method based on the uptake of 203Hg-labelled Mercurascan (MSC) in the heart was used. The increase of myocardial uptake of MSC in ISO-treated rats over control values was very rapid and might be directly proportional to the number of damaged myocardial cells actually present in the heart. MSC-uptake method of myocardial damage evaluation was more sensitive and precise than other methods tested (macroscopic evaluation according to Rona, increase of heart weight). Different modifications of MSC-uptake test may be selected in relation to experimental conditions. MSC test is especially useful for evaluation of early myocardial lesions induced by small doses of ISO (0.01 mg/kg).


An Unexpected Cause of Catastrophic Bleeding During Juvenile Nasopahryngeal Angiofibroma Excision.
We describe the first case of juvenile nasopharyngeal angiofibroma receiving blood supply from caroticotympanic artery which resulted in catastrophic bleeding intraoperatively. The patient was an 12-year-old boy with a Radkowski stage 3B JNA. We utilized preoperative embolization of feeders from external carotid artery though the surgeon failed to excise the tumor completely due to uncontrollable bleeding from the tumor. On retrospective analysis of angiography only the culprit feeder found. Tumor was excised in the second surgery conducted a week later. Although selective embolization of ICA branches are described in literature the data are sparse and so is the management of such cases.


Short-term air pollution exposure and exacerbation events in mild to moderate COPD: a case-crossover study within the CanCOLD cohort.
Infections are considered as leading causes of acute exacerbations of chronic obstructive pulmonary disease (COPD). Non-infectious risk factors such as short-term air pollution exposure may play a clinically important role. We sought to estimate the relationship between short-term air pollutant exposure and exacerbations in Canadian adults living with mild to moderate COPD. In this case-crossover study, exacerbations ('symptom based': ≥48 hours of dyspnoea/sputum volume/purulence; 'event based': 'symptom based' plus requiring antibiotics/corticosteroids or healthcare use) were collected prospectively from 449 participants with spirometry-confirmed COPD within the Canadian Cohort Obstructive Lung Disease. Daily nitrogen dioxide (NO2), fine particulate matter (PM2.5), ground-level ozone (O3), composite of NO2 and O3 (Ox), mean temperature and relative humidity estimates were obtained from national databases. Time-stratified sampling of hazard and control periods on day '0' (day-of-event) and Lags ('-1' to '-6') were compared by fitting generalised estimating equation models. All data were dichotomised into 'warm' (May-October) and 'cool' (November-April) seasons. ORs and 95% CIs were estimated per IQR increase in pollutant concentrations. Increased warm season ambient concentration of NO2 was associated with symptom-based exacerbations on Lag-3 (1.14 (1.01 to 1.29), per IQR), and increased cool season ambient PM2.5 was associated with symptom-based exacerbations on Lag-1 (1.11 (1.03 to 1.20), per IQR). There was a negative association between warm season ambient O3 and symptom-based events on Lag-3 (0.73 (0.52 to 1.00), per IQR). Short-term ambient NO2 and PM2.5 exposure were associated with increased odds of exacerbations in Canadians with mild to moderate COPD, further heightening the awareness of non-infectious triggers of COPD exacerbations.


The cumulative impacts of repeated heavy rainfall, flooding and altered water quality on the high-latitude coral reefs of Hervey Bay, Queensland, Australia.
Terrestrial runoff and flooding have resulted in major impacts on coral communities worldwide, but we lack detailed understanding of flood plume conditions and their ecological effects. Over the course of repeated flooding between 2010 and 2013, we measured coral cover and water quality on the high-latitude coral reefs of Hervey Bay, Queensland, Australia. In 2013, salinity, total suspended solids, total nitrogen and total phosphorus were altered for up to six months post-flooding. Submarine groundwater caused hypo-saline conditions for a further four months. Despite the greater magnitude of flooding in 2013, declines in coral abundance (∼28%) from these floods were lower than the 2011 flood (∼40%), which occurred immediately after a decade of severe drought. There was an overall cumulative decrease of coral by ∼56% from 2010 to 2013. Our study highlights the need for local scale monitoring and research to facilitate informed management and conservation of catchments and marine environments.


Molecular characterization of Mycobacterium bovis in slaughtered cattle in North-Central Nigeria and the public health implications.
The molecular biological techniques of polymerase chain reaction (PCR) are accurate and rapid diagnostic methods in the epidemiology of Mycobacterium species in humans and animals, especially in developing countries. In this study, positive cultures from suspected tuberculous lesions of slaughtered cattle from two abattoirs in north-central Nigeria were subjected to a two-step multiplex PCR technique, based on genus typing and genomic regions of difference (RD). Out of 50 suspected tuberculous lesions cultured, 40 isolates were obtained. Based on genus typing, 32 of the isolates were identified as Mycobacterium tuberculosis complex (MTC), one as non-tuberculous Mycobacterium (NTM) and the remaining seven were unclassified. Using genomic RD multiplex PCR, all the 32 isolates initially identified as MTC were further characterized as M. bovis. Our findings show that 80% of positive cultures from suspected tuberculous lesions were identified as M. bovis; hence, re-confirming M. bovis as the main cause of bovine tuberculosis in Nigeria. These results give further credence to the use of PCR-based molecular techniques as excellent complementary epidemiological tools in the tracking of bovine tuberculosis, a zoonotic disease of major public health importance in Nigeria.


Geological alteration of Precambrian steroids mimics early animal signatures.
The absence of unambiguous animal body fossils in rocks older than the late Ediacaran has rendered fossil lipids the most promising tracers of early organismic complexity. Yet much debate surrounds the various potential biological sources of putative metazoan steroids found in Precambrian rocks. Here we show that 26-methylated steranes-hydrocarbon structures currently attributed to the earliest animals-can form via geological alteration of common algal sterols, which carries important implications for palaeo-ecological interpretations and inhibits the use of such unconventional 'sponge' steranes for reconstructing early animal evolution.


Refined induction of anesthesia with remifentanil after bolus propofol administration in Landrace/Large White swine.
The authors report a prospective randomized blind study in which they used a refined anesthetic technique in male Landrace/Large White swine (n = 125 pigs, 19 ± 2 kg, 10-15 weeks old). The animals were first premedicated with ketamine, midazolam and atropine and then given a dose of 1, 2, 3, 4 or 5 μg remifentanil per kg body weight (dose amounts were randomly assigned) after a bolus dose of propofol. The authors assessed the intubation conditions (e.g., jaw relaxation and other parameters) 20 min after premedication and then 5 min after anesthesia induction. All animals that received each of the different remifentanil dose amounts were successfully intubated in less than 30 s. No animal developed apnea during intubation or experienced substantial reductions in heart rate or blood pressure (> 25%) between the two time points (20 min after premedication and 5 min after anesthesia induction). Overall intubation conditions were significantly better in animals that received 5 μg remifentanil per kg body weight than in animals that received other dose amounts (P < 0.001). The average time to intubation was significantly shorter for animals that received 5 μg remifentanil per kg body weight than for animals that received any of the other dose amounts (P < 0.001). The authors concluded that for this study, 5 μg remifentanil per kg body weight resulted in excellent intubating conditions in this swine breed.


Chemical constituents of the rhizomes of Coeloglossum viride var. bracteatum.
Seven new compounds, named coelovirins A-G (1-7), along with fourteen known constituents were isolated from the rhizomes of Coeloglossom viride var. bracteatum (Orchidaceae). On the basis of chemical and spectroscopic methods, including 2D-NMR techniques, the structures of new compounds were elucidated as 1-(4-beta-D-glucopyranosyloxybenzyl)-(2R,3S)-2-isobutyltartrate (1), 4-(4-beta-glucopyranosyloxybenzyl)-(2R,3S)-2-isobutyltartrate (2), 1-(4-beta-D-glucopyranosyloxybenzyl)-(2R,3S)-2-beta-D-glucopyranosyl-2-isobutyltartrate (3), 4-(4-beta-D-glucopyranosyloxybenzyl)-(2R,3S)-2-beta-D-glucopyranosyl-2-isobutyltartrate (4), (2R,3S)-2-beta-D-glucopyranosyl-2-isobutyltartaric acid (5), bis(4-beta-D-glucopyranosyloxybenzyl)-(2R,3S)-2-[beta-D-glucopyranosyl-(1 --> 4)-beta-D-glucopyranosyl]-2-isobutyltartrate (6) and bis(4-beta-D-glucopyranosyloxybenzyl)-(2R)-2-[beta-D-glucopyranosyl-(1 --> 4)-beta-D-glucopyranosyl]-2-isobutylmalate (7). The known compounds are 4-hydroxybenzaldehyde, 4-hydroxybenzyl alcohol, 4,4'-dihydroxydibenzyl ether, 4,4'-dihydroxydiphenylmethane, 4-(4-hydroxybenzyloxy)benzyl alcohol, gastrodin, quercetin-3,7-diglucoside, thymidine, loroglossin, militarine, dactylorhin A, dactylorhin B, beta-sitosterol and daucosterol.


Transmission efficiency of the plague pathogen (Y. pestis) by the flea, Xenopsylla skrjabini, to mice and great gerbils.
Plague, a zoonotic disease caused by Yersinia pestis, is characterized by its ability to persist in the plague natural foci. Junggar Basin plague focus was recently identified in China, with Rhombomys opimus (great gerbils) and Xenopsylla skrjabini as the main reservoir and vector for plague. No transmission efficiency data of X. skrjabini for Y. pestis is available till now. In this study, we estimated the median infectious dose (ID50) and the blockage rates of X. skrjabini with Y. pestis, by using artificial feeders. We then evaluated the flea transmission ability of Y. pestis to the mice and great gerbils via artificial bloodmeal feeding. Finally, we investigated the transmission of Y. pestis to mice with fleas fed by infected great gerbils. ID50 of Y. pestis to X. skrjabini was estimated as 2.04 × 10(5) CFU (95% CI, 1.45 × 10(5) - 3.18 × 10(5) CFU), around 40 times higher than that of X. cheopis. Although fleas fed by higher bacteremia bloodmeal had higher infection rates for Y. pestis, they lived significantly shorter than their counterparts. X. skrjabini could get fully blocked as early as day 3 post of infection (7.1%, 3/42 fleas), and the overall blockage rate of X. cheopis was estimated as 14.9% (82/550 fleas) during the 14 days of investigation. For the fleas infected by artificial feeders, they seemed to transmit plague more efficiently to great gerbils than mice. Our single flea transmission experiments also revealed that, the transmission capacity of naturally infected fleas (fed by infected great gerbils) was significantly higher than that of artificially infected ones (fed by artificial feeders). Our results indicated that ID50 of Y. pestis to X. skrjabini was higher than other fleas like X. cheopis, and its transmission efficiency to mice might be lower than other flea vectors in the artificial feeding modes. We also found different transmission potentials in the artificially infected fleas and the naturally infected ones. Further studies are needed to figure out the role of X. skrjabini in the plague epidemiological cycles in Junggar Basin plague focus.


Body fat distribution in women with polycystic ovary syndrome.
To investigate body fat distribution in women with polycystic ovary syndrome (PCOS). Body weight, body mass index (BMI), and six indices of body fat measured by dual-energy x-ray absorptiometry were compared in 40 women with PCOS and 97 age-matched controls. The possible correlations between the body fat characteristics and serum androgen levels were evaluated in the 40 PCOS women. Body fat distribution was classified into upper- (N = 24) and lower-half body type (N = 16), and androgen levels and the incidence of hirsutism were compared in the two types. The BMI, body fat ratio, upper-half body fat ratio, and upper-half/lower-half body fat ratio were significantly higher in PCOS women than in controls. After adjustment for age, height, and body weight, the upper-half/lower-half body fat ratio was still significant (P < .001). The PCOS subjects exhibited a significant positive correlation between the upper-half/lower-half body fat ratio and dehydroepiandrosterone-sulfate (DHEA-S) levels (r = 0.607, P < .01) as well as testosterone levels (r = 0.585, P < .05). Dehydroepiandrosterone-sulfate and testosterone levels were significantly higher in those with the upper-half body type than in those with the lower-half body type (P < .001). After adjustment for confounding variables, only DHEA-S was still significantly higher in this body type (P < .05). Serum DHEA-S levels seem to be associated with upper-half body fat distribution in women with PCOS, irrespective of body weight.


Benzimidazole derivatives as arginine mimetics in 1,4-benzodiazepine nonpeptide vitronectin receptor (alpha v beta 3) antagonists.
In a 3-oxo-1,4-benzodiazepine-2-acetic acid series of vitronectin receptor (alpha v beta 3) antagonists containing a benzimidazole as a novel arginine mimetic, we examined the effects of benzimidazole modifications and amide substitutions on both activity and pharmacokinetics.


Evaluating contributions of urbanization and global climate change to urban land surface temperature change: a case study in Lagos, Nigeria.
This study develops a general method to evaluate the contributions of localized urbanization and global climate change to long-term urban land surface temperature (ULST) change. The method is based on the understanding that long-term annual ULST is controlled by three factors: (1) localized urbanization, (2) global climate change, and (3) interannual climate variation. Then the method removes the interannual climate fluctuations on long-term observed LST time series via linear regression and separates the contributions of urbanization and climate change to the impacts on long-term ULST via urban-rural comparison. The method is applied to Lagos, a fast-growing metropolis in the tropical West Africa, as an example for reference. Combined time-series daily daytime and nighttime MODIS Land Surface Temperature (LST) data over the years of 2003-2021 are used as the representation of land surface temperature. To avoid the potentioal interannual data biase due to uneven availability of data in the rainy seasons over years, only MODIS LST data from dry seasons are used in the study. The results are summarized as follows for Lagos: (1) long-term annual ULST is confirmed to be controlled by the three factors; (2) the proposed method can separate the contribution of the three factors to the ULST; (2) both localized urbanization and global warming are verified to contribute to the ULST increase with positive trends; (3) daytime ULST increased the most in the afternoon time at a mean rate of 1.429 °C per decade, with 0.985 °C (10 year)-1 contributed by urbanization and 0.444 °C (10 year)-1 contributed by climate warming; (4) nighttime ULST in Lagos increased the most after midnight at a rate of 0.563 °C (10 year)-1, with 0.56 °C (10 year)-1 contributed by urbanization and 0.003 °C (10 year)-1 contributed by climate warming; and (5) urbanization is generally responsible for around 60.97% of the urban warming in Lagos. Therefore, the increasing urbaniztion-induced urban heat island effect is the major cause for more heat-related health risks and climate extremes that many urban residents are suffering. The results of this study are of useful reference for both urbanization and climate change related issues in the geo-science field.


Telomere dysfunction and the initiation of genome instability.
Tumour growth is an evolutionary process that is characterized by the selection of clonal populations of cells that acquire distinct genetic changes. Many cancer therapies aim to exploit the specific changes that occur in cancer cells, but understanding the underlying mechanisms of genomic instability that cause these mutations could lead to more effective therapies. If common mechanisms exist for initiating genomic instability in tumours, selection could explain the differences in specific gene mutations that accumulate in different tumour types. The cause of genomic instability in human tumours is unclear, although there is evidence to indicate that telomere dysfunction could make an important contribution.


Early changes of pulmonary arterial hemodynamics in patients with systemic sclerosis: flow pattern, WSS, and OSI analysis with 4D flow MRI.
To study the pulmonary artery (PA) hemodynamics in patients with systemic sclerosis (SSc) using 4D flow MRI (4D-flow). Twenty-three patients with SSc (M/F: 2/21, 57 ± 15 years, 3 manifest PA hypertension (PAH) by right heart catheterization) and 10 control subjects (M/F: 1/9, 55 ± 17 years) underwent 4D-flow for the in vivo measurement of 3D blood flow velocities in the PA. Data analysis included area-averaged flow quantification at the main PA, 3D wall shear stress (WSS), oscillatory shear index (OSI) calculation along the PA surface, and Reynolds number. The composite outcome of all-cause death and major adverse cardiac events was also investigated. The maximum PA flow at the systole did not differ, but the minimum flow at the diastole was significantly greater in patients with SSc compared with that in control subjects (7.7 ± 16.0 ml/s vs. ‑ 13.0 ± 17.3 ml/s, p < 0.01). The maximum WSS at the peak systole was significantly lower and OSI was significantly greater in patients with SSc compared with those in control subjects (maximum WSS: 1.04 ± 0.20 Pa vs. 1.33 ± 0.34 Pa, p < 0.01, OSI: 0.139 ± 0.031 vs. 0.101 ± 0.037, p < 0.01). The cumulative event-free rate for the composite event was significantly lower in patients with minimum flow in main PA ≤ 9.22 ml/s (p = 0.012) and in patients with Reynolds number ≤ 2560 (p < 0.001). 4D-flow has the potential to detect changes of PA hemodynamics noninvasively and predict the outcome in patients with SSc at the stage before manifest PAH. • The WSS at the peak systolic phase was significantly lower (p < 0.05), whereas OSI was greater (p < 0.01) in patients with SSc without manifest PAH than in controls. • The hemodynamic change detected by 4D-flow may help patient management even at the stage before manifest PAH in SSc. • The minimum PA flow and Reynolds number by 4D-flow will serve as a predictive marker for SSc.


Herpesviruses in brains in Alzheimer's and Parkinson's diseases.
We evaluated the association of HSV-1, HHV-6, and VZV with Alzheimer's disease (AD) and Parkinson's disease (PD). Brain specimens for viral DNA polymerase chain reaction represented 34 patients with AD, 40 with PD, and 40 controls. One AD patient (2.9%) was positive for HSV-1 DNA, 88.2% for HHV-6 DNA, and 26.5% for VZV DNA; 17.5% of PD patients were HSV-1 DNA-positive and 75% HHV-6-positive, whereas 40% had VZV DNA. Twenty-five percent of the controls were positive for HSV-1 DNA, 87.5% for HHV-6, and 27.5% for VZV. HSV-1, VZV, or HHV-6 DNA in brains was no additional risk factor for AD.


The role of adolescent lifestyle habits in biological aging: A prospective twin study.
Adolescence is a stage of fast growth and development. Exposures during puberty can have long-term effects on health in later life. This study aims to investigate the role of adolescent lifestyle in biological aging. The study participants originated from the longitudinal FinnTwin12 study (n = 5114). Adolescent lifestyle-related factors, including body mass index (BMI), leisure-time physical activity, smoking, and alcohol use, were based on self-reports and measured at ages 12, 14, and 17 years. For a subsample, blood-based DNA methylation (DNAm) was used to assess biological aging with six epigenetic aging measures in young adulthood (21-25 years, n = 824). A latent class analysis was conducted to identify patterns of lifestyle behaviors in adolescence, and differences between the subgroups in later biological aging were studied. Genetic and environmental influences on biological aging shared with lifestyle behavior patterns were estimated using quantitative genetic modeling. We identified five subgroups of participants with different adolescent lifestyle behavior patterns. When DNAm GrimAge, DunedinPoAm, and DunedinPACE estimators were used, the class with the unhealthiest lifestyle and the class of participants with high BMI were biologically older than the classes with healthier lifestyle habits. The differences in lifestyle-related factors were maintained into young adulthood. Most of the variation in biological aging shared with adolescent lifestyle was explained by common genetic factors. These findings suggest that an unhealthy lifestyle during pubertal years is associated with accelerated biological aging in young adulthood. Genetic pleiotropy may largely explain the observed associations. This work was supported by the Academy of Finland (213506, 265240, 263278, 312073 to J.K., 297908 to M.O. and 341750, 346509 to E.S.), EC FP5 GenomEUtwin (J.K.), National Institutes of Health/National Heart, Lung, and Blood Institute (grant HL104125), EC MC ITN Project EPITRAIN (J.K. and M.O.), the University of Helsinki Research Funds (M.O.), Sigrid Juselius Foundation (J.K. and M.O.), Yrjö Jahnsson Foundation (6868), Juho Vainio Foundation (E.S.) and Päivikki and Sakari Sohlberg foundation (E.S.).


Antecedents of open source software adoption in health care organizations: a qualitative survey of experts in Canada.
Open source software (OSS) adoption and use in health care organizations (HCOs) is relatively low in developed countries, but several contextual factors have recently encouraged the consideration of the possible role of OSS in information technology (IT) application portfolios. This article aims at developing a research model for investigating the antecedents of OSS adoption decisions in HCOs. Based on a conceptual framework derived from a synthesis of the literature on IT adoption in organizations, we conducted 18 semi-structured interviews with IT experts from all levels of the Province of Quebec's health and social services sector in Canada. We also interviewed 10 IT suppliers in the province. A qualitative data analysis of the interviews was performed to identify major antecedents of OSS adoption decisions in HCOs. Eight factors associated with three distinct theoretical perspectives influence OSS adoption. More specifically, they are associated with the classical diffusion of innovations theory, the theory of resources, as well as institutional theory and its spin-off, the organizing vision theory. The factors fall under three categories: the characteristics of OSS as an innovation, the characteristics of the HCO with respect to its ability to absorb OSS, and the characteristics of the external environment with respect to institutional pressures and public discourse surrounding OSS. We shed light on two novel factors that closely interact with each other: (1) interest of the health care community in the public discourse surrounding OSS, and (2) clarity, consistency and richness of this discourse, whether found in magazines or other media. OSS still raises many questions and presents several challenges for HCOs. It is crucial that the different factors that explain an HCO's decision on OSS adoption be considered simultaneously. Doing so allows a better understanding of HCOs' rationale when deciding to adopt, or not to adopt, OSS.


[Antihypertensives always evenings-absolutely not or sensible?]
The Spanish Hygia study has led to considerable irritation due to the general recommendation to prescribe antihypertensives preferably to be taken in the evening, especially since the lay press as well as medical media made enthusiastic comments. The discussion about the optimal time to take antihypertensive drugs shows once again how dangerous the uncritical handling of study data can be. No possible risks were pointed out. The Hygia study compared 19,084 patients with morning and evening intake of antihypertensive drugs under the control of a 48‑h blood pressure measurement (!). There was a significantly better reduction in blood pressure and the rate of cardiovascular and cerebrovascular events with evening intake. The data are scientifically valuable; however, the conclusions are incomprehensible based on the data, contradict many other studies and are dangerous for certain patient groups. There are also methodological shortcomings. Therefore, a general evening intake is not justified and nonsensical due to the diverse, individually very different pathophysiological findings of the nocturnal blood pressure behavior. Basically, the outpatient 24‑h blood pressure measurement (ABPM) enables a better assessment of the individual cardiovascular and cerebrovascular risks and prevents an incorrect assessment of the blood pressure and thus unnecessary or sufficient treatment. Instead of a general recommendation, the ABPM offers the option of an individually tailored treatment. Taking antihypertensive drugs in the evening should always be preceded by an ABDM in the case of prognostically unfavorable nocturnal hypertension in order to avoid the risk of nocturnal ischemic risks due to excessive drops in blood pressure.


Analysis of biogenic amines and their metabolites in biological tissues and fluids by gas chromatography-negative ion chemical ionization mass spectrometry (GC-NICIMS).
GC-NICIMS has been employed in the analysis of biogenic amines and their metabolites in human urine and human, bovine and porcine aqueous and vitreous humour. Several new chemical derivatization procedures have been developed in order to analyse these compounds. Concentrations of octopamines and synephrines were determined in urine from treated and untreated hypertensive subjects and normotensive individuals; there were no significant differences in concentrations of these metabolites between these groups. Human urine contained several dihydroxy-phenylethylamines which have not been reported as natural metabolites before and also 5- and 6-hydroxydopamine in relatively large amounts. Aqueous and vitreous humour contained very low quantities of noradrenaline, tyramine and dopamine but measurements were inconsistent because sometimes the levels were below the limits of detection. Metabolites of a number of biogenic amines were readily detected in aqueous and vitreous humour.


Longitudinal Analysis of Bidirectional Relationships between Nocturia and Depressive Symptoms: The Nagahama Study.
Although the association between nocturia and depressive symptoms has been demonstrated, the causal direction remains unclear. We investigated the directional association between nocturia and depressive symptoms using longitudinal data from the general population. This longitudinal analysis was conducted as part of the Nagahama Cohort Project, a population based cohort study, with baseline and 5-year followup investigations. Nocturnal voiding frequency and mental health were measured with self-report questionnaires, the International Prostate Symptom Score and the 5-item Mental Health Inventory. Logistic regression analyses and a cross-lagged panel analysis were performed to analyze the bidirectional association between nocturia and depressive symptoms. With 9,764 participants at baseline, data from 8,285 were used in this analysis. Median age at baseline was 57.3 years and the proportion of men was 32.0%. New onset depressive symptoms and nocturia were observed among 369 and 793 participants, respectively. In adjusted logistic regression analyses we observed a clear dose-relationship between baseline nocturnal voiding frequency and new onset depressive symptoms (p for trend <0.001) and a weak association between baseline 5-item Mental Health Inventory and new onset nocturia (p for trend=0.0087). In a cross-lagged panel analysis the path coefficient from nocturnal voiding frequency to 5-item Mental Health Inventory (β=-0.06, p <0.001) was stronger than that from 5-item Mental Health Inventory to nocturnal voiding frequency (β=-0.02, p=0.047). This longitudinal study demonstrated a bidirectional association between nocturia and depressive symptoms. The cross-lagged path coefficient suggested that nocturia could more likely be a cause than a result of depressive symptoms.


A novel 33.3 kb deletion (- -KOL) in the alpha-globin gene cluster: a brief report on deletional alpha-thalassaemia in the heterogeneous eastern Indian population.
We have detected, in three unrelated eastern Indian individuals, a hitherto unreported alpha zero deletion, - -KOL, in the heterozygous state, encompassing the embryonic zeta2-globin and the duplicated alpha-globin genes extending from c. 1150 bp upstream of the zeta2 globin gene to c. 960 bp downstream of the theta1 gene. Other deletions present in 120 unrelated, eastern Indian, putative alpha-thalassaemia patients are -3.7 kb (16.25%), -4.2 kb (5%) and - -SEA (3.33%).


Invasive fungal sinusitis due to Bipolaris hawaiiensis.
A phaeohyphomycotic sinusitis due to Bipolaris hawaiiensis, observed in an immunologically competent patient, is reported and a review of data from the literature is given. The patient was successfully treated by surgical drainage and amphotericin B.


Alpha(1)-adrenergic and alpha(2)-adrenergic balance in the dorsal pons and gross behavioral activity of mice in a novel environment.
Central alpha(1)- and alpha(2)-adrenoceptors in a number of different brain regions are known to have opposing actions on gross behavioral activity, with the former stimulating and the latter inhibiting activity. Therefore, blockade of alpha(1)-receptors may induce inactivity by leading to unopposed alpha(2) activity. The aim of this study was to test if central blockade of alpha(2)-receptor function restores behavioral activity in alpha(1)-receptor-blocked mice. Dose-response studies were undertaken on the effects of alpha(1)- and alpha(2)-agonists and antagonists microinjected into the dorsal pons on gross behavioral activity in a novel cage test. The behavioral inactivity resulting from blockade of alpha(1)-receptors in the pons with the antagonist, terazosin, was reversed by either a low dose of an alpha(2)-antagonist, atipamezole, or a low dose of an alpha(2)-agonist, dexmedetomidine, but was exacerbated by a high dose of the alpha(2)-agonist. The results support the hypothesis that blockade of alpha(1)-receptors in the dorsal pons of mice produces inactivity by causing unopposed activity of alpha(2)-receptors. This condition may be relevant to inactive states seen after stress or during depressive illness.


Neuronal types in the lateral geniculate nucleus of man. A Golgi-pigment study.
Nerve cell types of the lateral geniculate body of man were investigated with the use of a transparent Golgi technique that allows study of not only the cell processes but also the pigment deposits. Three types of neurons have been distinguished: Type-I neurons are medium- to large-sized multipolar nerve cells with radiating dendrites. Dendritic excrescences can often be encountered close to the main branching points. Type-I neurons comprise a variety of forms and have a wide range of dendritic features. Since all intermediate forms can be encountered as well, it appears inadequate to subdivide this neuronal type. One pole of the cell body contains numerous large vacuolated lipofuscin granules, which stain weakly with aldehyde fuchsin. Type-II and type-III neurons are small cells with few, sparsely branching and extended dendrites devoid of spines. In Golgi preparations they cannot be distinguished from each other. Pigment preparations reveal that the majority of these cells contains small and intensely stained lipofuscin granules within their cell bodies (type II), whereas a small number of them remains devoid of any pigment (type III). Intermediate forms do not occur.


Mutations of the iduronate-2-sulfatase (IDS) gene in patients with Hunter syndrome (mucopolysaccharidosis II).
Genomic DNA and cDNA from fibroblasts from nine unrelated German patients with X-linked iduronate-2-sulfatase (IDS) deficiency showing variable clinical manifestation were screened for point mutations and small structural aberrations. Direct sequencing revealed a splice mutation skipping exon A, one nonsense mutation, and five missense mutations concerning the exons B, F and I of the IDS gene. Several novel missense mutations were found: A68E, S426X, I485R, Q293H, and D478G. One of the point mutations eliminating a recognition site for the restriction enzyme MspI was used as a direct marker for a prenatal diagnosis. A relationship between type of mutation and clinical picture could not be recognized.


Sentinel node mapping identifies vaccine-draining lymph nodes with tumor-specific immunological activity.
Adoptive immunotherapy (AIT) with 4T07-IL2 vaccine-draining lymph node (DLN) cells induced regression of established 4T07 mammary carcinomas, but contralateral non-DLN were inactive. These experiments were performed to determine whether mapping with isosulfan blue (IB), as described for identification of sentinel nodes, would identify vaccine-DLN with antitumor activity. Ten days after vaccination with 4T07-IL-2, .1 ml of 1% IB was injected into the vaccination site (footpads or flanks). After 3 minutes, mice were euthanized, and the blue-stained nodes were collected. With flank vaccination, IB identified both an inguinal and an axillary node. We also collected DLNs blindly in mice not receiving IB dye. DLN cell suspensions were then activated with bryostatin 1, ionomycin, and IL-2, expanded in culture, and adoptively transferred to mice bearing established 4T07 flank tumors. Complete tumor regression occurred in nearly all mice treated with popliteal or inguinal DLNs collected with or without IB. IB-stained axillary DLNs cured 100% of tumor-bearing mice, whereas none of the mice treated with blindly collected axillary DLNs were cured. We have shown that IB identifies immunologically active DLNs, does not interfere with expansion of lymphocytes in vitro, and, more importantly, has no detrimental effect on the ability of lymphocytes to induce tumor regression in vivo. For axillary DLNs, use of IB mapping identified immunologically active lymph nodes that could not otherwise be found.


Separation of the integral membrane glycoproteins E1 and E2 of Semliki Forest virus by affinity chromatography on concanavalin A-Sepharose.
The membrane glycoproteins E1 and E2 of Semliki Forest virus are of about equal size but can be separated from each other by affinity chromatography on a concanavalin A-Sepharose column in the presence of sodium dodecyl sulfate. The E1 protein eluted like glycopeptides containing two peripheral sugar branches composed of N-acetylglucosamine, mannose, galactose and sialic acid. The E2 eluted like glycopeptides containing only N-acetylglucosamine and mannose.


Unlocking the Potential of Bio-Based Nitrogen-Rich Furanic Platforms as Biomass Synthons.
The demand for new biomass-derived fine and commodity chemicals propels the discovery of new methodologies and synthons. Whereas furfural and 5-hydroxymethylfurfural are cornerstones of sustainable chemistry, 3-acetamido-5-acetyl furan (3A5AF), an N-rich furan obtained from chitin biomass, remains unexplored, due to the poor reactivity of the acetyl group relative to previous furanic aldehydes. Here we developed a reactive 3-acetamido-5-furfuryl aldehyde (3A5F) and demonstrated the utility of this synthon as a source of bio-derived nitrogen-rich heteroaromatics, carbocycles, and as a bioconjugation reagent.


Virtual health education: Scaling practice to transform student learning: Using virtual reality learning environments in healthcare education to bridge the theory/practice gap and improve patient safety.
The advancements in and affordability of technologies offer increasing opportunities to modernise healthcare education into packages developed to meet the expectations and requirements of the digital generation. Purposefully designed and tested Virtual Reality Learning Environments (VRLE) can offer healthcare students the means to access and revisit learning materials in ways that enhance education and meet a range of needs; including those with specific learning differences and those who have traditionally been disenfranchised. Furthermore, this will make healthcare education much more readily available to those who have been previously marginalised by distance. This paper argues that Virtual Reality (VR) has the unique potential to transform healthcare education and suggests that more providers should consider collaborating with developers and investing in the technology.


Comparison of an ELISA system for the quantification of hepatitis B antibody with an automated and a semi-automated system.
In order to manage the increased workload resulting from post vaccination hepatitis antibody testing of health care workers, the anti-hepatitis B ELISA assay ETI-AB-AUK (Sorin Biomedica), adapted for quantification using standards available as an addition to the qualitative kit assay (ABAU-STD-SET, (Sorin Biomedica)) and a sample pre-dilution step, was compared with a fully automated microparticle enzyme immunoassay IMX AUSAB (Abbott Laboratories), and a semi-automated enhanced luminescence system (Amerlite Amersham, now Kodak). Seventy-eight samples were concurrently tested and analysed statistically using a Regression Coefficient computer package (Apple Mackintosh Cricket). Good quantitative agreement was observed with ELISA vs IMX giving a linear correlation coefficient (r = 0.96). The linear correlation coefficient for ELISA vs Amerlite was r = 0.77. This study validates the use of the automated IMX system and allows the comparison of IMX results with previous 'semi-quantitative' ELISA results when longitudinally assessing patients response to a recombinant hepatitis B vaccine.


Practice Patterns of Physicians Using Adjunct Therapies with Botulinum Toxin Injection for Spasticity: A Canadian Multicenter Cross-Sectional Survey.
Adjunct therapies are nonpharmacological treatments used with botulinum toxin (BoNT) injection that may improve spasticity outcomes. It has been suggested that physicians consider adjunct therapies as a part of comprehensive spasticity management. It is unclear which adjunct therapies are used by physicians in clinical practice. To determine physician practice patterns and perceptions of use of adjunct therapies following BoNT injection for limb spasticity. Cross-sectional national survey of current clinical practice using a 22-item questionnaire developed by the authors. Not applicable. Survey respondents were physicians actively administering BoNT injections for limb spasticity management across Canada (N = 48). Not applicable. Types of adjunct therapies used by physicians; physician opinions on barriers to adjunct therapy use, patient preferences, and future research priorities. Most physicians prescribe home stretching programs, home active exercise programs, and splinting; however, many physicians perceive that these same adjunct therapies are unwanted by patients. A minority of physicians prescribe electrical stimulation (ES), transcutaneous electrical nerve stimulation (TENS), casting, and extracorporeal shockwave therapy; financial limitations and perceived lack of evidence were identified as barriers to their use. Significantly more physicians practicing in academic settings compared with nonacademic, community, and private practice settings used functional ES (59% vs 11%) and TENS (41% vs 0%) as adjunct therapies (P < .05). Research priorities included determining the effectiveness of immediate postinjection application of adjunct therapies (eg, injected muscle activation with ES or stretching) and nutraceuticals. Canadian physicians frequently use adjunct therapies in combination with BoNT injection to treat spasticity. Financial and time constraints are identified as barriers to implementation of adjunct therapies that are currently supported by research, and patient preferences may also affect compliance. Future research should focus on adjunct therapies that overcome these barriers.


Pluripotent stem cell-based disease modeling: current hurdles and future promise.
Human induced pluripotent stem cells (hiPSCs) can yield unlimited numbers of patient-specific cells of any type and may be an important tool in efforts to overcome current shortcomings in biomedical research. In vitro disease models based on the use of hiPSCs have been proposed for various applications. Those include drug discovery and validation, efficacy, safety and toxicity assays, the elucidation of previously unknown disease mechanisms, the enhancement of animal based assays, the promise of conducting clinical trials in the dish and the identification of cell types and stages suitable for cell replacement therapies. Here, we provide an overview of the current state of hiPSC-based disease modeling and discuss recent progress and remaining challenges on the road to realizing the full potential of this novel technology.


Enumeration of Megasphaera elsdenii in rumen contents by real-time Taq nuclease assay.
To develop a real-time Taq nuclease assay (TNA) to enable the in vivo enumeration of Megasphaera elsdenii. Megasphaera elsdenii YE34 was phenotypically characteristic of the species and had 16S rDNA sequence similarity of 98% to previously described isolates. Calibration of the number of cells of M. elsdenii against the cycle threshold of fluorescent dye release gave a straight-line relationship with a correlation coefficient approximating unity. The specificity of the assay for M. elsdenii was confirmed by performing it against a panel of 24 heterogeneous, mainly ruminal bacteria. Megasphaera elsdenii was not detected in ruminal contents from a pasture-fed steer but was readily detected 2 and 50 h after the probiotic introduction of the bacterium into the rumen. Real-time TNA has provided a sensitive and specific means of enumerating the M. elsdenii population in rumen contents. Megasphaera elsdenii is an important lactate-degrading ruminal bacterium that has been selected for probiotic use to prevent acidosis and enhance starch utilization in grain-fed cattle. The assay developed in this study provides a tool for determining the ability of probiotically-introduced M. elsdenii to establish useful populations in the rumen.


A novel acridine derivative, LS-1-10 inhibits autophagic degradation and triggers apoptosis in colon cancer cells.
Autophagy promotes cancer cell survival and drug resistance by degrading harmful cellular components and maintaining cellular energy levels. Disruption of autophagy may be a promising approach to sensitize cancer cells to anticancer drugs. The combination of autophagic inhibitors, such as chloroquine (CQ) and lucanthone with conventional cancer therapeutics has been investigated in clinical trials, but adverse drug-drug interactions are a high possibility. Here we designed and synthesized a novel, small-molecule library based on an acridine skeleton and the CQ structure with various modifications and substitutions and screened the compounds for effective autophagy inhibition. We found that 9-chloro-2-(3-(dimethylamino)propyl)pyrrolo[2,3,4-kl]acridin-1(2H)-one (LS-1-10) was the most effective from our library at inhibiting autophagic-mediated degradation and could decrease the viability of multiple colon cancer cells. In addition, LS-1-10 induced DNA damage and caspase 8-mediated apoptosis. Overall, this small molecule was more efficient at reducing the viability of cancer cells than other conventional chemotherapeutic agents, such as CQ and amsacrine. The anticancer and autophagy-inhibiting activities of LS-1-10 were confirmed in vivo in a xenograft mouse model. Collectively, this study has identified a new and efficient single compound with both autophagy-inhibiting and anticancer activity, which may provide a novel approach for cancer therapy.


The blood supply of colorectal liver metastases.
Post-mortem studies suggest that liver metastases obtain the majority of their nutrition from the hepatic artery; however, cytotoxic arterial perfusion with or without hepatic-artery ligation has not proved entirely successful as a therapeutic regime. In this study we have measured blood flow into colorectal liver metastases using xenon-133 (133Xe) clearance in patients undergoing surgery for colorectal cancer. Pre-operative measurements after direct parenchymal injection gave a mean flow of 41.5 +/- 22.5 ml/min/100 g which after hepatic arterial occlusion perfusion, was reduced to a mean of 5% of the pre-occlusion value. Dynamic blood-flow studies using the gamma camera were performed in the post-operative period by administration of 133Xe into both hepatic arterial and portal venous catheters. The initial distribution images indicated a predominant arterial perfusion to the metastases, but after hepatic-artery ligation, portal-vein perfusion to the metastases was statistically significantly increased. Hence, a compensatory haemodynamic mechanism exists which may account for the poor results of hepatic-artery ligation and perfusion alone.