The hot rim sign on hepatobiliary scintigraphy (HIDA) with CT correlation.
An older male with multiple medical comorbidities presented to the emergency room after 3 days of worsening right upper quadrant pain. The patient had an elevated white blood cell count and mildly elevated liver functions. Initial ultrasound was equivocal and further imaging with CT scan was obtained. The CT scan was read as suggestive of cholecystitis, however a hepatobiliary scintigraphy (HIDA) scan was ordered for confirmation, as the patient was a poor operative candidate. The HIDA demonstrated no bile duct or small bowel activity on initial images or delays, however a classic 'hot rim' sign was present, confirming acute cholecystitis. The patient ultimately underwent percutaneous cholecystostomy with drainage for treatment where acute cholecystitis was confirmed. Upon retrospective review, the CT demonstrated hyperaemia surrounding the gallbladder fossa, which is the CT scan equivalent of a scintigraphic 'hot rim' sign. This is an uncommon example of a radiologic sign correlation between multiple imaging modalities.


Novel bluetongue virus in goats, Corsica, France, 2014.
During 2000-2013, 4 genotypes of bluetongue virus (BTV) were detected in Corsica, France. At the end of 2013, a compulsory BTV-1 vaccination campaign was initiated among domestic ruminants; biological samples from goats were tested as part of a corresponding monitoring program. A BTV strain with nucleotide sequences suggestive of a novel serotype was detected.


Endovascular treatment of distal thoracic aortic transection associated with severe thoracolumbar spinal fracture.
Endovascular repair has become the first line of treatment in most patients with blunt aortic injury. The most common mechanism is deceleration injury affecting the aortic isthmus distal to the origin of the left subclavian artery. Injuries of the distal thoracic aorta are uncommon. We report the case of a 25-year-old male patient who presented with paraplegia and distal thoracic aortic pseudoaneurysm associated with severe thoracolumbar vertebral fracture and displacement after a motocross accident. Endovascular repair was performed using total percutaneous technique and conformable C-TAG thoracic stent-graft (WL Gore, Flagstaff, AZ). Following stent-graft placement and angiographic confirmation of absence of endoleak, thoracolumbar spinal fixation was performed in the same operative procedure. This case illustrates a multispecialty approach to complex aortic and vertebral injury and the high conformability of newer thoracic stent-grafts to adapt to tortuous anatomy.


Systematic Review of Risk and Protective Factors for Revictimization After Child Sexual Abuse.
Child sexual abuse (CSA) is a widespread public health problem in the United States. It has been associated with multiple long-term deleterious outcomes including revictimization in adulthood. This systematic review of 25 studies synthesizes research examining possible risk and protective factors that might explain the established link between CSA and future victimizations. Specific risk factors identified included co-occurring maltreatment in the home, risky sexual behavior (particularly in adolescence), post-traumatic stress disorder, emotion dysregulation, and other maladaptive coping strategies. Only one protective factor was identified: perceived parental care. The review also revealed considerable variability in definitions and measurement of both CSA and adult victimization, particularly in terms of how researchers conceptualized age. Many of the studies were limited in generalizability by including only college-age women. These findings have clinical and research implications. Public health interventions working to prevent revictimization among CSA survivors can utilize these findings when designing programs. For researchers, the results highlight the need for standardized definitions of both CSA and revictimization, for well-validated and consistent measurement, and for inclusion of additional population groups in future research.


Audit of waste collected over one week from ten dental practices. A pilot study.
An audit of the waste practices of ten general dental surgeries identified problems that have occurred due to the lack of specific dental guidelines or codes of practice in this area. Occupational health and safety requirements for types and locations of sharps containers, and lack of consensus on what constitutes a sharp, were identified as areas needing attention. Cross-infection control items, such as gloves, masks, single-use cups, and protective coverings, were found to constitute up to 91 per cent of total waste. When infectious waste was reclassified by the audit team as 'that waste which was visibly blood stained,' a reduction in waste in this category was made, during the audit, at each practice. The practice of disposing of radiographic fixer and developer into the sewerage system occurred in three out of the ten practices, even though the Australian Dental Association Inc. has discouraged this practice.


[Systolic blood pressures are not comparable when home blood pressure is measured with a wrist or an arm validated monitor].
To compare home blood pressure values obtained with two validated OMRON (wrist or arm) monitors used sequentially in the same subject. In 265 hypertensive subjects referred to hypertension specialists, a self measurement of blood pressure was performed sequentially with an OMRON M4-I (arm cuff, A/A, BHS validation) or OMRON RX-I (wrist cuff, B/B, BHS validation). Each patient recorded home blood pressure during two periods of 4 days with 3 measures in the morning and 3 in the evening. Order for use of each monitor was randomised. With wrist devices, subjects were advised to keep the arm at heart level during measurements. BP values were reported on a standardized document. Patients were asked by a questionnaire about the tolerance and feasibility of the 2 methods. In this population, aged 59 +/- 14 years, with 60% of men and a mean blood pressure of 152 +/- 21 / 86 +/- 14 mmHg, the home blood pressure values were 143 +/- 20/81 +/- 11 mmHg with the arm monitor and 135 +/- 10 / 80 +/- 11 mmHg with the wrist monitor. Mean SBP adjusted on age, initial blood pressure level and period order was significantly lower when home blood pressure monitoring has been recorded with a wrist monitor as compared to an arm monitor (p < 0.001). Self measurement of blood pressure was felt as easy in 92% with the arm monitor and in 96% with the wrist monitor (p < 0.05). Self measurement of blood pressure was felt as constraining in 14% with the arm monitor and in 7% with the wrist monitor (p < 0.01). The feasibility between the two devices was good with none of the value missing in 86% with the arm monitor and in 85% with the wrist monitor. The missing values were in 56% the fourth day. Despite the use of two validated monitors, mean SBP is significantly lower when home blood pressure monitoring is recorded with a wrist monitor as compared to an arm monitor. Uncertainty in the arm position with the use of wrist device could explain these results. When advising home blood pressure monitoring, care should be taken to recommend only the use of validated devices and to prefer the use of arm devices in order to avoid the uncertainty of an inadequate utilisation.


Allelic variants of human calcitonin receptor: distribution and association with bone mass in postmenopausal Italian women.
Bone mass could be under control of several polymorphic genes which can modulate bone turnover via reciprocal interactions. One of the genes that can be involved in this process is the calcitonin receptor (CTR) gene. Evidence from cDNA cloning has shown that CTRs have seven potential transmembrane domains and they are known to be expressed in several tissues. In a Japanese population was discovered a novel Restriction Fragment Length Polymorphism (RFLP) at the CTR gene by Alu I restriction enzyme at the 1377th nucleotide expressing either proline (CC genotype) or leucine (TT genotype) as the 463rd amino acid. The heterozygote genotypes were indicated as TC. In the present study we analyzed the presence of this CTR gene RFLP in 307 postmenopausal Italian women. We observed that TC and TT genotypes represented the most frequent CTR genotypes in Italian women. In addition, Duncan's test used to compare the genotypes showed that TT genotype has significant lower lumbar BMD in comparison with CC genotype.


Lipopolysaccharide-Induced Systemic Inflammation in the Neonatal Period Increases Microglial Density and Oxidative Stress in the Cerebellum of Adult Rats.
Inflammatory processes occurring in the perinatal period may affect different brain regions, resulting in neurologic sequelae. Injection of lipopolysaccharide (LPS) at different neurodevelopmental stages produces long-term consequences in several brain structures, but there is scarce evidence regarding alterations in the cerebellum. The aim of this study was to evaluate the long-term consequences on the cerebellum of a systemic inflammatory process induced by neonatal LPS injection. For this, neonatal rats were randomly assigned to three different groups: naïve, sham, and LPS. Saline (sham group) or LPS solution (1 mg/kg) was intraperitoneally injected on alternate postnatal days (PN) PN1, PN3, PN5, and PN7. Spontaneous activity was evaluated with the open field test in adulthood. The cerebellum was evaluated for different parameters: microglial and Purkinje cell densities, oxidative stress levels, and tumor necrosis factor alpha (TNF-α) mRNA expression. Our results show that administration of LPS did not result in altered spontaneous activity in adult animals. Our data also indicate increased oxidative stress in the cerebellum, as evidenced by an increase in superoxide fluorescence by dihydroethidium (DHE) indicator. Stereological analyses indicated increased microglial density in the cerebellum that was not accompanied by Purkinje cell loss or altered TNF-α expression in adult animals. Interestingly, Purkinje cells ectopically positioned in the granular and molecular layers of the cerebellum were observed in animals of the LPS group. Our data suggest that neonatal LPS exposure causes persistent cellular and molecular changes to the cerebellum, indicating the susceptibility of this region to systemic inflammatory insults in infancy. Further investigation of the consequences of these changes and the development of strategies to avoid those should be subject of future studies.


Morphological Convolutional Neural Network Architecture for Digit Recognition.
Deep neural networks have proved promising results in many applications and fields, but they are still assimilated to a black box. Thus, it is very useful to introduce interpretability aspects to prevent the blind application of deep networks. This paper proposed an interpretable morphological convolutional neural network called Morph-CNN for pattern recognition, where morphological operations were incorporated using counter-harmonic mean into the convolutional layer in order to generate enhanced feature maps. Morph-CNN was extensively evaluated on MNIST and SVHN benchmarks for digit recognition. The different tested configurations showed that Morph-CNN outperforms the existing methods.


Tardive seizure and antibiotics: case reports and review of the literature.
Tardive seizure is a serious adverse reaction of electroconvulsive therapy (ECT). However, it was rarely reported in ECT sessions for psychiatric patients who needed concurrent antibiotic treatments. We present 2 cases of patients with schizophrenia who manifested a catatonic syndrome and were indicated for ECT, along with antibiotic therapies for infectious diseases with piperacillin and cefotiam, respectively. The beta-lactam antibiotics are reported to induce convulsions caused by the suppression of inhibitory GABAergic functions. In addition, there is a report on prolonged ECT seizure related to ciprofloxacin, which has an epileptogenic property with a similar action to beta-lactam antibiotics. Thus, tardive seizures in our cases are thought to be related to piperacillin and cefotiam.


Validity of the FACT Hepatobiliary (FACT-Hep) questionnaire for assessing disease-related symptoms and health-related quality of life in patients with metastatic pancreatic cancer.
Evaluate reliability and validity of the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire and its derivative FACT Hepatobiliary Symptom Indexes (FHSI-18 and FHSI-8) in people with metastatic pancreatic cancer. Self-reported questionnaire data from a randomized controlled Phase II study evaluating the efficacy and safety of conatumumab (AMG 655), ganitumab (AMG 479) or placebo combined with gemcitabine were evaluated. The following were assessed: internal consistency, using Cronbach's α; discriminant validity, comparing baseline patient-reported outcomes (PRO) scores across Eastern Cooperative Oncology Group (ECOG) performance status (PS) levels; and ability to detect change, comparing change from baseline PRO score at each cycle across PS and tumour response groups. The analysis included 96 patients. All scale scores demonstrated good internal consistency (Cronbach's α > 0.7) and discriminant validity. Baseline scores were significantly poorer among patients with PS = 1 versus patients with PS = 0 (e.g. difference in FACT-Hep total score -17.27; p < 0.001). Ability to detect change was established for Cycles 2/3 versus baseline; PRO scores reduced in the PS-worsened group versus the PS-stable group (e.g. difference in FACT-Hep total score -24.29; p < 0.001). All PRO scale scores showed significant decline for progressive disease versus stable disease (e.g. difference in FACT-Hep total score -12.58; p = 0.004). Changes on the FHSI-18 and FHSI-8 scales were similar in magnitude whether ECOG improved or worsened. FACT-Hep detects change and is a reliable and valid instrument for measuring health-related quality of life in patients with metastatic pancreatic cancer.


Long-Term Mortality Rates in Acute De Novo Versus Acute-on-Chronic Heart Failure: From the Heart Function Assessment Registry Trial in Saudi Arabia.
The heart function assessment registry trial in Saudi Arabia (HEARTS) is a national multicenter project that compared de novo versus acute-on-chronic heart failure (ACHF). This is a prospective registry in 18 hospitals in Saudi Arabia between October 2009 and December 2010. The study enrolled 2610 patients: 940 (36%) de novo and 1670 (64%) ACHF. Patients with ACHF were significantly older (62.2 vs 60 years), less likely to be males (64% vs 69%) or smokers (31.6% vs 36.7%), and more likely to have history of diabetes mellitus (65.7% vs 61.3%), hypertension (74% vs 65%), and severe left ventricular dysfunction (52% vs 40%). The ACHF group had a higher adjusted 3-year mortality rate (hazard ratio, 1.6; 95% confidence interval [CI] 1.3-2.0; P < .001). Patients with ACHF had significantly higher long-term mortality rates than those with de novo acute heart failure (HF). Multidisciplinary HF disease management programs are highly needed for such high-risk populations.


[Methadone maintenance: adoption of a new harm reduction approach in Hungary].
Methadone with its favourable physiological effects in comparison to heroin has been the most well-known and widely used tool of substitution treatment in heroinism. Research on efficiency has produced evidence of the fact that methadone maintenance as a model method of harm reduction is an efficient treatment of heroin dependent patients if used in the appropriate dose and indication. Due to its addictive effects, there has been some resistance against its worldwide spreading, especially in Central Eastern Europe. Methadone maintenance became a legal medical method in Hungary during the last ten years with approved classified protocol and manual owing to the consistent efforts of addiction-professionals, who were convinced of the treatment's efficacy. The process involved numerous conflicts, police provisions and media scandals. Professional legitimacy of methadone maintenance may hopefully be proved by research on efficiency in the near future.


The mouse as a model of cardiovascular adaptations to microgravity.
There are a multitude of physiological adaptations to microgravity, involving the cardiovascular, neuromuscular, and neuroendocrine systems. Some of these adaptations lead to cardiovascular deconditioning on return to normal gravity, posing a threat to human functional integrity after long-term spaceflight. Animal models of microgravity, e.g., tail suspension in rats, have yielded important information regarding the mechanism of these adaptations and have been useful in the design of countermeasures. The mouse could potentially be a useful experimental model, given its small size (smaller and lighter payload) and the powerful tools of experimental mouse genetics, which allow us to dissect mechanisms on a gene-specific basis. We show that the mouse demonstrates a wide range of cardiovascular responses to simulated microgravity, including alterations in heart rate, exercise capacity, peripheral arterial vasodilatory responsiveness, and baroreflex response. These responses are qualitatively similar to many of those demonstrated in humans during spaceflight and in rats using tail suspension, although there are some important differences. Thus the mouse has value as a model for studies of cardiovascular changes during microgravity; however, investigators must maintain an appreciation of important species differences.


The development of the anterior cruciate ligament in the paediatric population.
The aim of this study was to retrospectively compile normative data on the anterior cruciate ligament (ACL) in the paediatric population with magnetic resonance imaging, emphasizing the differences between men and women. In this retrospective study, musculoskeletal radiologists evaluated length, area, coronal and sagittal inclination of the ACL and inclination of the intercondylar notch. A total of 253 MR examinations (130 males and 123 females between 6 and 18 years of age) were included. The association between measurements, sex and age was considered. Linear and fractional polynomial regression models were used to evaluate the relationships between measurements. ACL length showed significant progressive growth (p < 0.001) with age in men and women, without characterization of growth peaks. ACL area in women showed more pronounced growth up to 11 years, stabilized from 11 to 14 years and then sustained a slight reduction. In men, ACL area showed more pronounced growth up to 12 years, stabilized from 12 to 15 years and then sustained slight reduction. Coronal and sagittal inclination of the ACL showed a significant progressive increase (p < 0.001) with age in both sexes, progressively verticalizing. The intercondylar roof inclination angle showed significant progressive reduction (p < 0.001) with age in both sexes. The area of the ACL does not accompany skeletal maturation, interrupting its growth around 11-12 years. Progressive verticalization of the ACL as well as of the intercondylar notch roof in the evaluated ages was also observed. The clinical relevance of this study is that the ACL presents different angular and morphologic changes during growth in the paediatric population. Since ACL repair is now being performed on younger children, recognition of the normal developmental changes of the ACL is of utmost importance for successful ACL graft placement. III.


Biofilm formation by Bacillus subtilis requires an endoribonuclease-containing multisubunit complex that controls mRNA levels for the matrix gene repressor SinR.
Biofilm formation by Bacillus subtilis is largely governed by a circuit in which the response regulator Spo0A turns on the gene for the anti-repressor SinI. SinI, in turn, binds to and inactivates SinR, a dedicated repressor of genes for matrix production. Mutants of the genes ylbF, ymcA and yaaT are blocked in biofilm formation, but the mechanism by which they act has been mysterious. A recent report attributed their role in biofilm formation to stimulating Spo0A activity. However, we detect no measurable effect on the transcription of sinI. Instead, we find that the block in biofilm formation is caused by an increase in the levels of SinR and of its mRNA. Evidence is presented that YlbF, YmcA and YaaT interact with, and control the activity of, RNase Y, which is known to destabilize sinR mRNA. We also show that the processing of another target of RNase Y, cggR-gapA mRNA, similarly depends on YlbF and YmcA. Our work suggests that sinR mRNA stability is an additional posttranscriptional control mechanism governing the switch to multicellularity and raises the possibility that YlbF, YmcA and YaaT broadly regulate mRNA stability as part of an RNase Y-containing, multi-subunit complex.


Rain-Free and Residue Hand-in-Hand: A Progressive Coupled Network for Real-Time Image Deraining.
Rainy weather is a challenge for many vision-oriented tasks (e.g., object detection and segmentation), which causes performance degradation. Image deraining is an effective solution to avoid performance drop of downstream vision tasks. However, most existing deraining methods either fail to produce satisfactory restoration results or cost too much computation. In this work, considering both effectiveness and efficiency of image deraining, we propose a progressive coupled network (PCNet) to well separate rain streaks while preserving rain-free details. To this end, we investigate the blending correlations between them and particularly devise a novel coupled representation module (CRM) to learn the joint features and the blending correlations. By cascading multiple CRMs, PCNet extracts the hierarchical features of multi-scale rain streaks, and separates the rain-free content and rain streaks progressively. To promote computation efficiency, we employ depth-wise separable convolutions and a U-shaped structure, and construct CRM in an asymmetric architecture to reduce model parameters and memory footprint. Extensive experiments are conducted to evaluate the efficacy of the proposed PCNet in two aspects: (1) image deraining on several synthetic and real-world rain datasets and (2) joint image deraining and downstream vision tasks (e.g., object detection and segmentation). Furthermore, we show that the proposed CRM can be easily adopted to similar image restoration tasks including image dehazing and low-light enhancement with competitive performance. The source code is available at https://github.com/kuijiang0802/PCNet.


The use of stable isotope labeling and liquid chromatography-tandem mass spectrometry techniques to simultaneously determine the oral and ophthalmic bioavailability of timolol in dogs.
Assays have been established for the quantitation of timolol and its 13C3- and 2H9-stable-isotope-labeled analogs in plasma and urine using liquid chromatography with atmospheric-pressure chemical-ionization tandem mass spectrometry. For the analysis of urine, underivatized timolol and its labeled analogs are monitored while timolol in plasma is assayed down to concentrations of 0.2 ng/mL after derivatization with phosgene. The great power of this technique is illustrated by simultaneously assaying three different species of timolol in plasma and urine obtained from dogs receiving simultaneous ophthalmic, oral, and intravenous doses of unlabeled and [2H9]- and [13C3]-labeled timolol. Thus, the ophthalmic and oral bioavailabilities of timolol are measured in a single experiment rather than as a three-phase crossover experiment. This approach yields accurate and precise analytical data, obviates intrasubject variability, and saves both analytical and animal resources.


Reassessment of recommended imipenem doses in febrile neutropenic patients with hematological malignancies.
Imipenem plasma concentrations were analyzed in 57 febrile neutropenic patients using the NONMEM program. The recommended 2-g/day regimen achieved coverage of the most common bacteria (MIC(90) = 1 mg/liter) during the whole dosing interval in only 53% of patients. This goal was achieved in 90% of patients with 3 g/day.


Studying Upper-Limb Kinematics Using Inertial Sensors Embedded in Mobile Phones.
In recent years, there has been a great interest in analyzing upper-limb kinematics. Inertial measurement with mobile phones is a convenient and portable analysis method for studying humerus kinematics in terms of angular mobility and linear acceleration. The aim of this analysis was to study upper-limb kinematics via mobile phones through six physical properties that correspond to angular mobility and acceleration in the three axes of space. This cross-sectional study recruited healthy young adult subjects. Humerus kinematics was studied in 10 young adults with the iPhone4. They performed flexion and abduction analytical tasks. Mobility angle and lineal acceleration in each of its axes (yaw, pitch, and roll) were obtained with the iPhone4. This device was placed on the right half of the body of each subject, in the middle third of the humerus, slightly posterior. Descriptive statistics were calculated. Descriptive graphics of analytical tasks performed were obtained. The biggest range of motion was found in pitch angle, and the biggest acceleration was found in the y-axis in both analytical tasks. Focusing on tridimensional kinematics, bigger range of motion and acceleration was found in abduction (209.69 degrees and 23.31 degrees per second respectively). Also, very strong correlation was found between angular mobility and linear acceleration in abduction (r=.845) and flexion (r=.860). The use of an iPhone for humerus tridimensional kinematics is feasible. This supports use of the mobile phone as a device to analyze upper-limb kinematics and to facilitate the evaluation of the patient.


An enzyme-linked immunosorbent assay (ELISA) specific for antibodies to TNP-LPS detects alterations in serum immunoglobulins and isotype switching in C57BL/6 and DBA/2 mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.
An enzyme-linked immunosorbent assay (ELISA) was developed to detect IgM and IgG antibodies specific for trinitrophenyl-lipopolysaccharide (TNP-LPS). Treatment of C57BL/6 and DBA/2 mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon (Ah) receptor agonists followed by immunization with TNP-LPS resulted in a dose-dependent decrease in serum IgM which paralleled the decrease in the splenic PFC response. The ED50 values for the IgM and splenic PFCs in C57BL/6 mice for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (pentaCB) and 3,3',4,4',5,5'-hexaCB were 2.8 and 1.6, 11 and 14, and 25 and 20 micrograms/kg, respectively; in the less Ah-responsive DBA/2 mice, the ED50 values were 8.5 and 10, 61 and 69, and 73 and 71 micrograms/kg, respectively. In addition, treatment of C57BL/6 mice with TCDD resulted in alterations of serum IgG relative to IgM and a delay of isotype switching was observed after immunization and boosting with TNP-LPS. This ELISA may prove to be a useful tool in monitoring immune function during long-term exposure of mice to TCDD and related compounds and exploring the mechanism of Ah receptor-mediated immunosuppression.


CD4+CD25+Foxp3+ T regulatory cells are not involved in oral desensitization.
Oral tolerance has been related to generation of T regulatory cells (Treg) or clonal anergy/deletion, respectively by administering low and high doses of fed antigens. CD4+CD25+ regulatory T cell clones can be induced by the antigen in Peyers patches of animal models. We selected ten subjects (mean age: 89.4 +/- 36.21 months; group A) with severe cows milk allergy. They underwent oral desensitization (OD) according to the current protocols. In six months they reached a tolerance of 50 ml of cows milk. CD4+CD25+Foxp3+ T(reg) blood levels were measured at the beginning of OD (A) and after 6 months (A), but almost the same values were obtained: A = 0.36 +/- 0.11 percent; A prime= 0.59 +/- 0.15 percent. These results were compared with a control group (C) of non-atopic children. Naturally outgrowing cows milk allergy can be related to high blood levels of CD4+CD25+Foxp3+ T(reg), as previously reported in children. On the other hand, a forced oral desensitization through a progressive intake of the antigenic food seems not to be related to an enhancement of CD4+CD25+Foxp3+ T(reg) levels in peripheral blood, making the role of long-lasting systemic immunologic changes unlikely.


Development of an FTP-LAMP assay based on TaqMan real-time PCR and LAMP for the specific detection of Xylella fastidiosa De Donno and mulberry strains in both plants and insect vectors.
We developed two real-time detection assays, TaqMan real-time PCR and LAMP, using primers and probe designed based on a sequence annotated to code for a Haemagglutinin-related protein (Hg) of Xylella fastidiosa (Xf), a gene uniquely present in the Italian olive (De Donno of olive) and American mulberry strains, for specific detection of the target Xf strains. These assays were validated with DNA samples extracted from Xf-infected plant samples and from two species of insect vectors (Philaenus spumarius, Ps; and Neophilaenus campestris, Nc). Both techniques were proven to be highly sensitive (100 fg of Xf-genomic DNA) and specific to the Italian De Donno and American mulberry strains of Xf. When our LAMP was utilized in a duplex manner by combining with previously published universal primers and probe for detection of all Xf-subspecies and strains, the duplex LAMP showed high versatility in the simultaneous detection and differentiation of the Italian De Donno and American mulberry stains form other subspecies/strains. Furthermore, the Hg gene-specific LAMP primers and TaqMan probe were exploited to develop a new approach; henceforth referred to as the Fluorescence of TaqMan Probe upon Dequenching - Loop mediated Isothermal Amplification (FTP-LAMP). In the FTP-LAMP, the Xf-Hg specific fluorophore-quenched probe was added to a standard LAMP reaction and fluoresces only when bound to its target, allowing for a sequence-specific detection of the Xf-Italian De Donno and American mulberry strains in a LAMP context. Our FTP-LAMP assay showed to be highly sensitive detecting down to 100 fg genomic DNA of Xf, when tested on Xf-genomic DNA extracted from infected plants, DAS-ELISA-crude saps and insect vectors. Furthermore, the assay showed high specificity (98.7% vs 89% for LAMP) when applied on DNA templates from insect vectors. With the addition of an extra target sequence-specific probe acting as a direct Xf-specific dye, the FTP-LAMP has gained more specificity and reduced one of the main problems of the LAMP assay (false positives) when used for detecting of Xf in insect vectors. To the best of our knowledge, this study reports the development of the first LAMP assay and the first novel FTP-LAMP method for specific detection of the Italian De Donno and the American mulberry strains of Xf. Together with the Xf universal LAMP primers in a duplex approach, the FTP-LAMP could represent a useful tool not only for the specific detection of the olive-associated strain in Italy, but also to differentiate the De Donno strain from other strains of Xf already reported in Italy and Europe (Germany, France, Spain and Portugal).


The glutamine commute: take the N line and transfer to the A.
The transfer of glutamine between cells contributes to signaling as well as to metabolism. The recent identification and characterization of the system N and A family of transporters has begun to suggest mechanisms for the directional transfer of glutamine, and should provide ways to test its physiological significance in diverse processes from nitrogen to neurotransmitter release.


Not all secretory granules are created equal: Partitioning of soluble content proteins.
Secretory granules carrying fluorescent cargo proteins are widely used to study granule biogenesis, maturation, and regulated exocytosis. We fused the soluble secretory protein peptidylglycine alpha-hydroxylating monooxygenase (PHM) to green fluorescent protein (GFP) to study granule formation. When expressed in AtT-20 or GH3 cells, the PHM-GFP fusion protein partitioned from endogenous hormone (adrenocorticotropic hormone, growth hormone) into separate secretory granule pools. Both exogenous and endogenous granule proteins were stored and released in response to secretagogue. Importantly, we found that segregation of content proteins is not an artifact of overexpression nor peculiar to GFP-tagged proteins. Neither luminal acidification nor cholesterol-rich membrane microdomains play essential roles in soluble content protein segregation. Our data suggest that intrinsic biophysical properties of cargo proteins govern their differential sorting, with segregation occurring during the process of granule maturation. Proteins that can self-aggregate are likely to partition into separate granules, which can accommodate only a few thousand copies of any content protein; proteins that lack tertiary structure are more likely to distribute homogeneously into secretory granules. Therefore, a simple "self-aggregation default" theory may explain the little acknowledged, but commonly observed, tendency for both naturally occurring and exogenous content proteins to segregate from each other into distinct secretory granules.


Biofilm microenvironment induces a widespread adaptive amino-acid fermentation pathway conferring strong fitness advantage in Escherichia coli.
Bacterial metabolism has been studied primarily in liquid cultures, and exploration of other natural growth conditions may reveal new aspects of bacterial biology. Here, we investigate metabolic changes occurring when Escherichia coli grows as surface-attached biofilms, a common but still poorly characterized bacterial lifestyle. We show that E. coli adapts to hypoxic conditions prevailing within biofilms by reducing the amino acid threonine into 1-propanol, an important industrial commodity not known to be naturally produced by Enterobacteriaceae. We demonstrate that threonine degradation corresponds to a fermentation process maintaining cellular redox balance, which confers a strong fitness advantage during anaerobic and biofilm growth but not in aerobic conditions. Whereas our study identifies a fermentation pathway known in Clostridia but previously undocumented in Enterobacteriaceae, it also provides novel insight into how growth in anaerobic biofilm microenvironments can trigger adaptive metabolic pathways edging out competition with in mixed bacterial communities.


Spherical CNN for Medical Imaging Applications: Importance of Equivariance in image reconstruction and denoising.
This work highlights the significance of equivariant networks as efficient and high-performance approaches for tomography applications. Our study builds upon the limitations of conventional Convolutional Neural Networks (CNNs), which have shown promise in post-processing various medical imaging systems. However, the efficiency of conventional CNNs heavily relies on an undiminished and proper training set. To tackle this issue, in this study, we introduce an equivariant network, aiming to reduce CNN's dependency on specific training sets. We evaluate the efficacy of equivariant spherical CNNs (SCNNs) for 2- and 3-dimensional medical imaging problems. Our results demonstrate superior quality and computational efficiency of SCNNs in denoising and reconstructing benchmark problems. Furthermore, we propose a novel approach to employ SCNNs as a complement to conventional image reconstruction tools, enhancing the outcomes while reducing reliance on the training set. Across all cases, we observe a significant decrease in computational costs while maintaining the same or higher quality of image processing using SCNNs compared to CNNs. Additionally, we explore the potential of this network for broader tomography applications, particularly those requiring omnidirectional representation.


Effects of thiopental, ketamine, diazepam, xylazine, and nitrous oxide on EEG spike activity and convulsive behavior during enflurane anesthesia in spontaneously breathing atropinized cats. Effect at surgical depth.
The effects of thiopental, ketamine, diazepam, xylazine and nitrous oxide, and combinations of thiopental-nitrous oxide and ketamine-nitrous oxide on electroencephalographic (EEG) spike activity and convulsive behaviors in atropinized cats at surgical depth of enflurane anesthesia were assessed quantitatively for 60 minutes during spontaneous ventilation. Mean inspired enflurane concentrations (MIEC) were reduced 16% to 29% by pretreatment with thiopental, ketamine, diazepam, and xylazine, and were reduced 19% by 66% nitrous oxide. The MIEC of cats anesthetized with thiopental-nitrous oxide-enflurane and ketamine-nitrous oxide-enflurane were 35% to 38% lower than that with nitrous oxide-enflurane. Pretreatment with thiopental, ketamine, diazepam, and xylazine did not reduce the EEG spike frequency during anesthesia but did markedly reduce the spike amplitude. The addition of 66% nitrous oxide did not alter the spike frequency during anesthesia but tended to reduce the spike amplitude. Combinations of thiopental-nitrous oxide and ketamine-nitrous oxide almost abolished the spike activity. The addition of 66% nitrous oxide prevented convulsive responses elicited by photic and auditory stimulation during enflurane anesthesia. Treatment with thiopental, ketamine, diazepam and xylazine, and combinations of thiopental-nitrous oxide and ketamine-nitrous oxide, completely prevented convulsive responses during enflurane anesthesia.


Cytotoxicity of a series of mono- and di-substituted thiourea in freshly isolated rat hepatocytes: a preliminary structure-toxicity relationship study.
The cytotoxicity of a series of 12 mono- and 4 di-substituted thiourea containing compounds in freshly isolated rat hepatocytes was investigated. It was found that thiourea toxicity, as evidenced by an increase in LDH-leakage from the cells, was accompanied by a depletion of intracellular glutathione (GSH). No increase in lipid peroxidation was observed with any of the thiourea. Burimamide and thioperamide, thiourea-containing histamine receptor ligands, were also found to deplete intracellular GSH. A clear structure-toxicity relationship was uncovered among a homologous series of N-phenylalkylthiourea. N-benzylthiourea (BTU) and N-phenylethylthiourea (PETU) were found to be non-toxic at a concentration of 1 mM, while N-phenylpropylthiourea (PPTU) and N-phenylbutylthiourea (PBTU) were found to cause significant LDH-leakage from the cells, accompanied by a depletion of intracellular GSH. This structure-toxicity relationship was further investigated using hepatocytes of differentially induced rats, however, no significantly different results were obtained when using hepatocytes of rats induced with phenobarbital (PB) or beta-naphthoflavone (BNF). Oxidation of the thiourea moiety is thought to be the first step in the bioactivation of thiourea containing compounds. The oxidation of thiocholine sulfenic acids, produced by FMO-mediated oxidation of the thiourea moiety, was used to determine whether the compounds examined are substrates for the FMO enzymes in rat liver. No clear relationship was found between cytotoxicity of the mono-substituted thiourea and lipophilicity of the N-substituent, nor with the FMO-mediated oxidation of the thionosulfur atom of the mono-substituted thiourea. It is concluded from this study, that thiourea toxicity in rat hepatocytes is structure-dependent and manifests itself as LDH-leakage and as a depletion of intracellular non-protein sulfhydryls, notably GSH, most likely followed by alkylation of vital macromolecular structures.


Cancer immunology and melanoma immunotherapy.
The stimulation of the immune system, in order to generate an attack against cancer cells, similarly to that which occurs in infectious disease, has long been matter of interest in oncology; however, only limited success has been achieved, with different treatment strategies tested in recent years. The development of new immune checkpoint inhibitors is currently changing this scenario, and immunotherapy is becoming a real choice among traditional cytotoxic treatments to fight cancer. Recent reports have shown efficacy and safety with the use of pembrolizumab, nivolumab, and ipilimumab for the treatment of different neoplasms, especially melanoma. In this article, we propose a review of the mechanisms of action involved in cancer immunology, the response evaluation of immunotherapies, and its toxicity profile, as well as a summary of the main clinical trials that led to the adoption of these new drugs for melanoma treatment.


Be on alert for pediatric AKI.
Acute kidney injury in children is associated with adverse outcomes, although much of our current understanding originates from studies in intensive care units. Holmes et al. used an automated acute kidney injury detection method to obtain epidemiologic data on pediatric acute kidney injury at a national level in outpatient, inpatient, and intensive care unit settings. We discuss the impact of these important results and the considerations needed with this approach.


Systems pharmacology and multi-scale mechanism of Enicostema axillare bioactives in treating Alzheimer disease.
As a progressive neurological disease with increased morbidity and mortality, Alzheimer Disease (AD) is characterized by neuron damage that controls memory and mental functions. Enicostema axillare (EA), an herb with a history of combativeness and effectiveness in treating Rheumatoid Arthritis, Cancer, and Diabetes, is used in Indian folk medicine from a holistic point of view. Though the herb is used for many illnesses, the molecular mechanism of its bioactive on AD has not been deciphered by intricate research. A unique pharmacology approach based on ADME drug screening and targeting, pathway enrichment (GO and KEGG), and network pharmacology, was established to explore the molecular mechanisms of E. axillare (EA) bioactive compounds for the treatment of AD. In brief, we bring to light the three active compounds of EA and seven potential molecular targets of AD, which are mainly implicated in four signaling pathways, i.e., MAPK, Apoptosis, neurodegeneration, and the TNF pathway. Moreover, the network analysis of the active compounds, molecular targets, and their pathways reveals the pharmacological nature of the compounds. Further, molecular docking studies were carried out to explore the interactions between the EA bioactive compounds and the targets and examine the binding affinity. The outcome of the work reflects the potential therapeutic effects of the compounds for treating AD through the modulation of the key proteins, which further corroborates the reliability of our network pharmacology analysis. This study not only helps in understanding the molecular mechanism of the drugs but also helps in finding and sorting new drugs for the treatment of AD, and other complex diseases through modern medicine.


Impact of Jaw Position Accuracy on Dose Variation in Volumetric Modulated Arc Therapy Using Jaw Tracking.
The technique of jaw tracking can be used in volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT). In this technique, jaw tracks apertures of the multi leaf collimator (MLC) during irradiation. It is reported that dose variation is occurred by the changing accuracy of MLC position in VMAT and IMRT. Though jaw moves dynamically in the irradiation by using this technique, the influence of the jaw position accuracy on dose variation is not examined. The purpose of this study is to verify the influence of jaw position accuracy on dose variation in VMAT using jaw tracking. We appended intentional errors on jaw position in digital image communication in medicine-radiation therapy (DICOM-RT) plans created using jaw tracking technique. These plans were irradiated on the phantom that was inserted ion chamber, and we measured dose variation by changing the intentional error. The dose variation in planning target volume (PTV) was enlarged by increasing the error, and agreed with the variation of a collimator scatter factor within 0.03%. In clinical case of oropharyngeal cancer, the maximum dose variations in parotid gland were 0.179% and 1.23% when the errors were 1 mm and 10 mm, respectively. Dose variation in parotid gland was larger than the variation in PTV and spinal cord because of increasing MLC transmission. The dose variation caused by jaw position error was smaller than it caused by MLC position error. So, we can keep the dose error slightly that is related to jaw position error in VMAT by maintaining jaw position accuracy correctly.


IL-4 and IL-13: their pathological roles in allergic diseases and their potential in developing new therapies.
The incidence of allergic diseases has dramatically increased in recent decades, and it is socially and medically important to establish more useful strategies to overcome allergic disorders. Various kinds of drugs are utilized for allergic patients; however, some cases are unresponsive to these drugs and in others there are undesired adverse effects. On the other hand, a substantial body of evidence has accumulated pointing to the pivotal role of Th2-cytokines, interleukin (IL)-4, and IL-13, in the pathogenesis of bronchial asthma. The evidence is categorized as (1) expression of these cytokines in the bronchial lesions, (2) genetic association of the signaling molecules of these cytokines, (3) analyses of mouse models. In addition, the molecular mechanism of the signal transduction of these cytokines has also been well characterized. Based on such information, IL-4 and IL-13 have emerged as promising means of improving allergic states, and several IL-4/IL-13 antagonists have been developed, among which soluble IL-4 receptor is now in human trials. Identifying the structure of the IL-13 variant and of the IL-4/IL-13-inducing genes would be of great use. It is expected that in the near future, several drugs will emerge based on these strategies, which will give us wider choice in treating patients, depending on the pathogenesis of the diseases.


MR Imaging Scoring System for White Matter Injury after Deep Medullary Vein Thrombosis and Infarction in Neonates.
Advanced imaging techniques have allowed earlier and more accurate detection of cerebral deep medullary vein thrombosis and infarction. Our objective was to develop an MR imaging scoring system to evaluate the severity of white matter injury in neonates with deep medullary vein thrombosis and infarction. This was a retrospective study of infants born ≥32 weeks' gestation (2000-2016) diagnosed with deep medullary vein thrombosis and infarction on neuroimaging in the first 30 days of life. A 102-point deep medullary vein white matter injury global severity score was developed. MR images were scored by 2 pediatric radiologists. Subject clinical data and regional and global severity scores were recorded. Fifty-one patients (mean gestational age, 37.3 ± 2.2 weeks; mean birth weight, 3182 ± 720 g) were included with a mean age at diagnosis via MR imaging of postnatal day 10.1 ± 6.1. Global severity scores ranged from 1 to 53, with a median score of 11 (interquartile range, 5-25). Lesions were more common in the frontal and parietal regions and less common in the occipital and temporal regions. Fifty-five percent of the group had neonatal seizures. No difference in perinatal risk factors (gestational age, birthweight, 5-minute Apgar score, chorioamnionitis, delivery room resuscitation, ventilator, or inotrope requirement) was observed among severity score quartiles. An MR imaging scoring system provides a comprehensive and objective classification of WM injury after deep medullary vein thrombosis and infarction in late preterm and term neonates. The global severity score is independent of gestational age and other antenatal risk factors, consistent with presentation in previously healthy-appearing neonates.


Chiral triazole fungicide difenoconazole: absolute stereochemistry, stereoselective bioactivity, aquatic toxicity, and environmental behavior in vegetables and soil.
In this study, the systemic assessments of the stereoisomers of triazole fungicide difenoconazole are reported for the first time, including absolute stereochemistry, stereoselective bioactivity toward pathogens (Alternaria sonali, Fulvia fulva, Botrytis cinerea, and Rhizoctonia solani), and toxicity toward aquatic organisms (Scenedesmus obliquus, Daphnia magna, and Danio rerio). Moreover, the stereoselective degradation of difenoconazole in vegetables (cucumber, Cucumis sativus and tomato, Lycopersicon esculentum) under field conditions and in soil under laboratory-controlled conditions (aerobic and anaerobic) was investigated. There were 1.33-24.2-fold and 1.04-6.78-fold differences in bioactivity and toxicity, respectively. Investigations on the stereoselective degradation of difenoconazole in vegetables showed that the highest-toxic and lowest-bioactive (2S,4S)-stereoisomer displays a different enrichment behavior in different plant species. Under aerobic or anaerobic conditions, (2R,4R)- and (2R,4S)-difenoconazole were preferentially degraded in the soil. Moreover, difenoconazole was configurationally stable in the test soil matrices. On the basis of biological activity, ecotoxicity, and environmental behavior, it is likely that the use of pure (2R,4S)-difenoconazole instead of the commercial stereoisomer mix may help to increase the bioactivity and reduce environmental pollution.


Forebrain-Specific Loss of BMPRII in Mice Reduces Anxiety and Increases Object Exploration.
To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII) in learning, memory, and exploratory behavior in mice, a tissue-specific knockout of BMPRII in the post-natal hippocampus and forebrain was generated. We found that BMPRII mutant mice had normal spatial learning and memory in the Morris water maze, but showed significantly reduced swimming speeds with increased floating behavior. Further analysis using the Porsolt Swim Test to investigate behavioral despair did not reveal any differences in immobility between mutants and controls. In the Elevated Plus Maze, BMPRII mutants and Smad4 mutants showed reduced anxiety, while in exploratory tests, BMPRII mutants showed more interest in object exploration. These results suggest that loss of BMPRII in the mouse hippocampus and forebrain does not disrupt spatial learning and memory encoding, but instead impacts exploratory and anxiety-related behaviors.


The legacy of the F344 rat as a cancer bioassay model (a retrospective summary of three common F344 rat neoplasms).
The Fischer 344 (F344) rat was used by the National Toxicology Program (NTP) for over 5 decades for toxicity and carcinogenicity studies. However, in 2006, the NTP decided to switch to a different rat stock due largely to high background control incidences of Leydig cell tumors (LCTs) and mononuclear cell leukemia (MNCL), also known as large granular lymphocytic (LGL) leukemia. In the current review, we aim (1) to provide a summary of NTP bioassays with treatment-associated effects involving MNCL and LCTs in addition to male F344-specific tunica vaginalis mesothelioma (TVM); (2) to describe important pathobiological differences between these F344 rat tumor responses and similar target tissue-tumor response in humans; and (3) to present the NTP reasons for switching away from the F344 rat. We show that due to the highly variable background incidence of F344 MNCL, more reliance on historical control data than is usual for most tumor responses is warranted to evaluate potential effect of any chemical treatment in this rat strain. The high spontaneous incidence of LCTs in the testes of male F344 rats has made this tumor endpoint of little practical use in identifying potential testicular carcinogenic responses. TVM responses in F344 rats have a biological plausible relationship to LCTs unlike TVM in humans. Given their high spontaneous background incidence and species-specific biology, we contend that MNCL and LCT, along with TVM responses, in F344 rat carcinogenicity studies are inappropriate tumor types for human health risk assessment and lack relevance in predicting human carcinogenicity.


Carcinogenicity in mice of a mutagenic compound, 2-amino-3-methylimidazo[4,5-f]quinoline, from broiled sardine, cooked beef and beef extract.
A potent mutagenic compound, 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ), isolated from broiled sardines, cooked beef and beef extract was tested for carcinogenicity in CDF1 mice of both sexes. Mice were given diet containing 0.03% IQ or control diet for up to 675 days. Tumors were observed mainly in the liver, forestomach and lung. In the mice given IQ, the incidences of these tumors were as follows: liver tumors - 41% in males and 75% in females; tumors of the forestomach - 41% in males and 31% in females; lung tumors - 69% in males and 42% in females. In the control mice, incidences of these tumors were as follows: liver tumors - 9% in males and 8% in females; tumors of the forestomach - 3% in males and 0% in females; lung tumors - 21% in males and 18% in females. The incidences of tumors in the liver, forestomach and lung were significantly higher in mice given IQ than in control mice.


Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study.
In developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM) children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children. In this retrospective case-control study SAM children aged 0-59 months, admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50) with those without severe sepsis (controls = 354). Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline. The case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons). We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case fatality in such children.


Repeated transurethral resection of recurrent superficial bladder tumors--does it affect the spread and stage of the tumor?
This prospective study was done to demonstrate the effect of repeated resection of superficial bladder tumors (TURT) on deep malignant cell infiltration in bladder wall. Thirty-six patients underwent radical cystectomy for invasive bladder cancer, 16 patients originally had superficial cancer that became invasive after repeated TURT (group I) and the other 20 patients (group II) presented with invasive bladder cancer from the start. Each cystectomy specimen was subjected to a thorough histopathological study. There was a statistically significant difference in pattern of local spread of malignant cells between the two groups. Isolated clusters of malignant cells in-between normal bladder muscle fibers, isolated subserosal malignant deposits as well as cells reaching the adjacent cervix uteri were found only in group I. Intravesical pressure was measured in another 10 patients during TURT and was found to be high reaching up to 80 cm H2O. We conclude that some malignant cells penetrate through the denuded urothelium during TURT by the effect of high intravesical pressure. This may be responsible, among other factors, for tumor recurrence with deeper stages.


Plasma position measurements by O-mode and X-mode reflectometry systems in tokamak plasmas.
Plasma Position Reflectometry (PPR) is planned to provide plasma position and shape information for plasma operation in future fusion reactors. Its primary function is to calibrate the drift of the magnetic signals due to the integral nature of magnetic measurement. Here, we attempt to measure plasma position using ordinary mode (O-mode) and extraordinary mode (X-mode) reflectometry systems on two tokamaks. A new physical model based on the phase shift is proposed to deduce the relative movement of the cut-off layer without density inversion. We demonstrate the plasma position measurements by absolute measurement from density profile inversion and relative measurement from phase shift. The combination of X-mode and O-mode reflectometers can minimize the limitations of single polarization reflectometry and further increase the accuracy of plasma position measurement. These results could provide an important technical basis for the further development of a real-time control system based on PPR.


Prevalence of porcine cysticercosis in the Lake Kyoga Basin, Uganda.
Taenia solium is a zoonotic helminth with the potential to cause life threatening epilepsy in people through the aberrant larval infection of the brain called Neurocysticercosis (NCC). The pig is the intermediate host for T. solium where the larval form, cysticercus cellulosae, normally develops after the pig eats eggs of the parasite. Humans are the definitive host where the adult tapeworm develops and are infected through the consumption of poorly cooked, infected meat. T. solium has been acknowledged by the World Health Organization (WHO), Food and Agriculture Organization (FAO) and UK Department for International Development (DFID) as being a neglected zoonotic disease, and was recently included in the WHO roadmap for control of neglected tropical diseases. This neglect encompasses a lack of epidemiological data and a lack of validated, effective control strategies being adopted. Understanding the epidemiology of this parasite in the intermediate host is the first step towards designing suitable intervention strategies for the improvement of public health. This study was undertaken to provide an accurate and up-to-date estimate for the prevalence of porcine cysticercosis in the Lake Kyoga basin. Sera from 378 pigs were analysed with the HP10 Antigen Enzyme Linked Immunosorbant Assay (ELISA) and the prevalence was found to be 25.7% (95% confidence interval 21.0% to 30.0%). Previous sero- surveillance in this region, using the B158/B60 Ag Elisa had indicated a prevalence of 8.6% in 2005 indicating a dramatic increase in prevalence (J. Parasitol Res, Article ID 375493, 2009) within a 6 year period. This increasing prevalence in the disease indicates to us that there is currently no effective control of this parasite and that in this region of Uganda at least; cysticercosis remains a neglected zoonotic disease.


Histological changes in the endometrial arterioles during postpartum offthe Chinese hamster (Cricetulus griceus).
The morphology of the uterine wall in the postpartum Chinese hamster (Cricetulus griceus) was studied with particular reference to the changes in the arterioles in the mesometrial endometrium. At day 0 postpartum, the endometrial arterioles were characterized by the appearance of trophoblastic giant cells plugging ruptured arterioles. On days 1 to 3 postpartum, the giant cells were replaced by epitheloid cells. On days 4 to 5 postpartum, the epitheloid cell mass was invaded by fibroblasts to occlude the arterial lumens. On days 6 to 7 postpartum, endometrial regeneration was completed. The giant cell might play a role in hemostasis immediately after parturition.


Blood viscoelasticity measurement using steady and transient flow controls of blood in a microfluidic analogue of Wheastone-bridge channel.
Accurate measurement of blood viscoelasticity including viscosity and elasticity is essential in estimating blood flows in arteries, arterials, and capillaries and in investigating sub-lethal damage of RBCs. Furthermore, the blood viscoelasticity could be clinically used as key indices in monitoring patients with cardiovascular diseases. In this study, we propose a new method to simultaneously measure the viscosity and elasticity of blood by simply controlling the steady and transient blood flows in a microfluidic analogue of Wheastone-bridge channel, without fully integrated sensors and labelling operations. The microfluidic device is designed to have two inlets and outlets, two side channels, and one bridge channel connecting the two side channels. Blood and PBS solution are simultaneously delivered into the microfluidic device as test fluid and reference fluid, respectively. Using a fluidic-circuit model for the microfluidic device, the analytical formula is derived by applying the linear viscoelasticity model for rheological representation of blood. First, in the steady blood flow, the relationship between the viscosity of blood and that of PBS solution (μBlood /μPBS ) is obtained by monitoring the reverse flows in the bridge channel at a specific flow-rate rate (QPBS (SS) /QBlood (L) ). Next, in the transient blood flow, a sudden increase in the blood flow-rate induces the transient behaviors of the blood flow in the bridge channel. Here, the elasticity (or characteristic time) of blood can be quantitatively measured by analyzing the dynamic movement of blood in the bridge channel. The regression formula (ABlood (t) = A α + A β exp [-(t - t 0 )/λBlood ]) is selected based on the pressure difference (ΔP = PA - PB ) at each junction (A, B) of both side channels. The characteristic time of blood (λBlood ) is measured by analyzing the area (ABlood ) filled with blood in the bridge channel by selecting an appropriate detection window in the microscopic images captured by a high-speed camera (frame rate = 200 Hz, total measurement time = 7 s). The elasticity of blood (GBlood ) is identified using the relationship between the characteristic time and the viscosity of blood. For practical demonstrations, the proposed method is successfully applied to evaluate the variations in viscosity and elasticity of various blood samples: (a) various hematocrits form 20% to 50%, (b) thermal-induced treatment (50 °C for 30 min), (c) flow-induced shear stress (53 ± 0.5 mL/h for 120 min), and (d) normal rat versus spontaneously hypertensive rat. Based on these experimental demonstrations, the proposed method can be effectively used to monitor variations in viscosity and elasticity of bloods, even with the absence of fully integrated sensors, tedious labeling and calibrations.


Myocardial performance index by tissue Doppler echocardiography predicts adverse events in patients with atrial fibrillation.
The prognostic value of myocardial performance index (MPI) has not yet been assessed in patients with atrial fibrillation (AF). The aim of this study was to evaluate the prognostic value of MPI by tissue Doppler imaging (TDI) M-mode in AF patients. Echocardiograms from 210 patients with AF during examination were analysed offline. Patients with known heart failure (HF) were excluded. Time intervals were measured using an M-mode line through the mitral valve leaflets to provide a colour diagram of the mitral leaflet movement so all time intervals could be measured from one cardiac cycle. MPI was calculated as the sum of isovolumic relaxation time and isovolumic contraction time divided by the ejection time [(IVRT+IVCT)/ET]. During a median follow-up of 2.4 years, 84 patients (40%) reached the combined endpoint of major adverse cardiovascular events (MACE), being all-cause mortality, HF, myocardial infarction, or stroke. Increasing MPI was significantly associated with an increased risk of MACE, and the risk increased with 20% per 0.1 increase in MPI [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.10-1.32; P < 0.001]. Increasing MPI was also significantly associated with a lower left ventricular ejection fraction (LVEF) (P < 0.001). Nevertheless, MPI remained an independent predictor even after adjustment for age, sex, diabetes mellitus, left atrial volume, and LVEF (HR 1.12, 95% CI 1.01-1.25; P = 0.038). Increasing MPI was significantly associated with increased risk of MACE and remained an independent predictor after multivariable adjustment. This demonstrates that the MPI obtained by TDI M-mode might be useful in assessing cardiac function in AF patients with ongoing arrhythmia during examination.


[Literature of so-called "clinical research": structure and trends, 1991-2010].
The authors studied trends and patterns in the literature of research labeled as clinical (i.e., having the word "clinical" in their title) in the period between 1991 and 2010. The main findings are: 1. The growth of the literature under study was somewhat stronger than that of the overall medical literature. 2. The dominance of the USA is strong but is challenged by some of the most rapidly developing countries (particularly in the Far-East region: China, Korea) in total production, and by the developed European countries in highly cited publications. The eminence of Italy is remarkable. 3. In comparing the medical fields, the most striking tendencies are the increase of oncology and the attenuation of internal medicine. Surgery is steadily growing in size but decreasing in its citation influence. 4. Word frequency studies support the ever growing weight of oncology and also of genetics. 5. Beyond the thematic changes, word frequency studies also reveal a substantial change in attitude: in the period under study more and more effort was made on emphasizing the usefulness, efficiency and risks of the results in contrast with the more descriptive, investigative approach of the past. The role of therapy is growing, the role of diagnostics is decreasing. The knowledge of these trends and patterns may orient health and science policy makers to cope appropriately with the ever changing world of clinical research.


Precision of Classification of Odorant Value by the Power of Olfactory Bulb Oscillations Is Altered by Optogenetic Silencing of Local Adrenergic Innervation.
Neuromodulators such as noradrenaline appear to play a crucial role in learning and memory. The goal of this study was to determine the role of norepinephrine in representation of odorant identity and value by olfactory bulb oscillations in an olfactory learning task. We wanted to determine whether the different bandwidths of olfactory bulb oscillations encode information involved in associating the odor with the value, and whether norepinephrine is involved in modulating this association. To this end mice expressing halorhodopsin under the dopamine-beta-hydrolase (DBH) promoter received an optetrode implant targeted to the olfactory bulb. Mice learned to differentiate odorants in a go-no-go task. A receiver operating characteristic (ROC) analysis showed that there was development of a broadband differential rewarded vs. unrewarded odorant-induced change in the power of local field potential oscillations as the mice became proficient in discriminating between two odorants. In addition, the change in power reflected the value of the odorant rather than the identity. Furthermore, optogenetic silencing of local noradrenergic axons in the olfactory bulb altered the differential oscillatory power response to the odorants for the theta, beta, and gamma bandwidths.


Getting it right first time: national survey of surgical site infection 2019.
Surgical site infections (SSIs) are associated with increased morbidity and mortality. Deep SSI, or prosthetic joint infection (PJI), is associated with revision surgery involving longer operative times with higher infection rates, longer length of stay (LoS) and high costs in addition to the catastrophic effect on the patient. The surveillance of SSI is important for patient decision making, identification of outliers for support and maximising focussed improvement. This paper reports the findings of the second Getting it Right First Time (GIRFT) national SSI survey for orthopaedic and spinal surgery. Data were submitted prospectively by 67 orthopaedic units and 22 spinal units between 1 May 2019 and 31 October 2019. For a patient to be included, they had to present with SSI within the study period and within 1 year of the index procedure. A total of 309 SSIs were reported from primary and revision, total hip, knee, shoulder, elbow and ankle replacements, and 58 SSIs were reported from lumbar spine single level discectomy or decompression, lumbar spine single-level instrumented posterior fusion, posterior cervical spine decompression and instrumented fusion and posterior correction of adolescent idiopathic scoliosis. SSIs rates have remained low compared with the 2017 survey. There were variations in SSI rates by procedure, with primary shoulder replacement reporting the lowest (0.4%) and revision shoulder replacement the highest (2.5%) rates. The authors recommend that the elective surgical restart following the COVID-19 pandemic provides a unique opportunity for all units to implement a full SSI prevention bundle to minimise the risk of infection and improve patient outcomes.


Novel 2-benzylthio-5-(1,3,4-oxadiazol-2-yl)benzenesulfonamides with anticancer activity: Synthesis, QSAR study, and metabolic stability.
A series of novel 2-benzylthio-4-chloro-5-(5-substituted 1,3,4-oxadiazol-2-yl)benzenesulfonamides (4-27) have been synthesized as potential anticancer agents. MTT assay was carried out to determine the cytotoxic activity against three human cancer cell lines: colon cancer HCT-116, breast cancer MCF-7 and cervical cancer HeLa as well as to determine the influence on human keratinocyte cell line HaCaT. Relatively high (IC50: 7-17 μM) cytostatic activity and selectivity against HeLa cell line was found for compounds 6, 7, 9-11 and 16. While compounds 23-27 bearing styryl moieties attached to a 1,3,4-oxadiazole ring at position 5, exhibited significant activity against two and/or three cancer cell lines with IC50: 11-29 μM. Further quantitative structure-activity relationships based on molecular descriptors calculated by DRAGON software, were investigated by Orthogonal Projections to Latent Structures (OPLS) technique and Variable Influence on Projection (VIP) analysis. Considering molecular descriptors with the highest influence on projection (highest VIP values) lipophilicity of tested compounds was pointed as main factor affecting activity towards HCT-116 cell line, while structural parameters associated with presence of styryl substituent in position 5 of 1,3,4-oxadiazole ring were identified as essential for activity towards MCF-7 breast cancer. In vitro tests for metabolic stability in the presences of pooled human liver microsomes and NADPH showed that some of the most active compounds 26 and 27 presented favorable metabolic stability with t1/2 in the range of 28.1-36.0 min.


Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis.
GPR109A agonists have been used for the treatment of obesity however, the role of GPR109A in regulating aging-associated alterations in lipid metabolism is unknown. In this study we used Gpr109a-/- mice to investigate the effect of aging in the regulation of lipid accumulation. We observed that in mouse and human livers, in addition to Kupffer cells, GPR109A is expressed in hepatocytes. Over 12 months, compared to wild type (WT), Gpr109a-/- mice gained significantly more weight. Food intake and levels of serum lipids were similar among both groups. Compared to age-matched WT mice, 12-months old Gpr109a-/- mice had significantly increased liver weight, hepatic steatosis and serum markers of liver injury. The fatty liver phenotype in Gpr109a-/- mice was associated with increased hepatic expression of lipogenesis genes and decreased expression of lipolysis genes. Gpr109a-/- mice had significantly increased fat tissues, which was associated with significant increase in adipocyte diameter and surface area. Adipose tissue from Gpr109a-/- mice had increased expression of lipogenesis genes; however, expression of lipolytic genes was similar in both groups. Collectively, these results indicate that during aging, GPR109A modulates de novo lipid accumulation in liver and adipose tissue, and its dysregulation can lead to age-associated obesity and hepatic steatosis.


Revision of the ant genus Melophorus (Hymenoptera, Formicidae).
The fauna of the purely Australian formicine ant genus Melophorus (Hymenoptera: Formicidae) is revised. This project involved integrated morphological and molecular taxonomy using one mitochondrial gene (COI) and four nuclear genes (AA, H3, LR and Wg). Seven major clades were identified and are here designated as the M. aeneovirens, M. anderseni, M. biroi, M. fulvihirtus, M. ludius, M. majeri and M. potteri species-groups. Within these clades, smaller complexes of similar species were also identified and designated species-complexes. The M. ludius species-group was identified purely on molecular grounds, as the morphology of its members is indistinguishable from typical members of the M. biroi species-complex within the M. biroi species-group. Most species-complexes sampled were also found to be monophyletic. Sequencing generally supported monophyly in taxa sampled but some species of the M. fieldi complex and M. biroi were not monophyletic and the implications arising from this are discussed in this monograph. Based on morphology, ninety-three species are recognized, 73 described as new. A further new species (here called 'Species K' [TERC Collection]) is noted in the taxonomic list, but is not described in this work. One species is removed from Melophorus: M. scipio Forel is here placed provisionally in Prolasius. Six species and five subspecies pass into synonymy. Of the full species, M. constans Santschi, M. iridescens (Emery) and M. insularis Wheeler are synonymized under M. aeneovirens (Lowne), M. pillipes Santschi is synonymized under M. turneri Forel, M. marius Forel is synonymized under M. biroi Forel, and M. omniparens Forel is synonymized under M. wheeleri Forel. Of the subspecies, M. iridescens fraudatrix and M. iridescens froggatti Forel are synonymized under M. aeneovirens (Lowne), M. turneri aesopus Forel and M. turneri candidus Santschi are synonymized under M. turneri Forel and M. fieldi propinqua Viehmeyer is synonymized under M. biroi. Camponotus cowlei Froggatt is reinstated as a junior synonym of Melophorus bagoti Lubbock. In addition, the subspecies M. fieldi major Forel, M. ludius sulla Forel and M. turneri perthensis Forel are raised to species. A key to workers of the genus is supplied. A lectotype is designated for M. curtus Forel, M. sulla, and M. turneri.


Optical Coherence Tomography Features Preceding the Onset of Advanced Age-Related Macular Degeneration.
Age-related macular degeneration (AMD) is a progressive disease with multifactorial etiology. There is a need to identify clinical features that are harbingers of advanced disease. We evaluated morphologic features of the retina and choroid on optical coherence tomography (OCT) to determine if they predict progression to advanced disease. Progressors transitioned from early or intermediate AMD to advanced disease (n = 40 eyes), and were matched on baseline AMD grade and follow-up interval to nonprogressors who did not develop advanced AMD (n = 40 eyes). Features of the neurosensory retina, photoreceptors, retinal pigment epithelium (RPE), and choroid were evaluated. Logistic regression was used to evaluate univariate associations between features and progression to overall advanced AMD, geographic atrophy (GA), and neovascular disease (NV). Multivariate associations based on stepwise regression models were also assessed. Ellipsoid zone disruption was associated with progression to overall advanced AMD and NV (odds ratios [ORs]: 17.9 and 30.6; P < 0.001), with a similar trend observed for GA. Drusenoid RPE detachment, RPE thickening, and retinal pigmentary hyperreflective material were significantly associated with higher risk of progression to advanced AMD (ORs: 5.0-8.5) and NV (ORs: 10.8-17.2). Pigmentary hyperreflective material was associated with progression to GA (OR: 7.5, P = 0.009). Total retinal thickness, pigmentary hyperreflective material, nascent GA features, and choroidal vessel abnormalities were independently associated with progression to advanced AMD in a multivariate stepwise model. Abnormalities in the photoreceptors, retinal thickness, RPE, and choroid were associated with higher risk of developing advanced AMD. These findings provide insights into disease progression, and may be helpful to identify earlier endpoints for clinical studies.


Superluminal propagation through 500 m optical fiber via stimulated Brillouin scattering.
We have experimentally demonstrated superluminal propagation through a 500 m optical fiber using stimulated Brillouin scattering (SBS), which is the longest superluminal propagating distance reported so far, to the best of our knowledge. Brillouin-induced loss resonance for fast light generation of pump signals is achieved in a single frequency Brillouin lasing oscillator with a highly nonlinear fiber as the SBS medium. The single frequency operation is realized by embedding the saturable absorber fiber loop with an unpumped erbium-doped fiber. Consequently, signals with a pulse width of 710 ns experience a maximum advancement of 1330 ns. Furthermore, the effects of pulse width and the duty cycle of pump signals are also investigated.


Water quality and the effects of different pastoral animals.
Water quality in agricultural catchments tends to be worse than in forested (native or exotic) catchments. Reduced water quality tends to have significant effects on the ecosystem of streams, including increased nuisance algal and plant growth (eutrophication) associated with nutrient input, toxicity to aquatic life due to ammonia, faecal contamination, and loss of habitat or spawning areas due to sedimentation. An analysis of catchment contaminant loads from 38 studies conducted since 1975 was carried out to determine if there were differences in loads between land uses under different livestock (dairy, sheep, sheep-and-beef (mixed), deer) and non-agricultural. Significantly more N was lost from dairy catchments than catchments with other land uses, and more sediment lost from deer catchments than other catchments. Median loads of N were greatest from dairy > deer = mixed > sheep > non-agricultural; while loads of P were greatest for deer = mixed > dairy > sheep > non-agricultural; and for sediment, deer > sheep > mixed > dairy > non-agricultural. This information should be considered in catchments of mixed stock types to target the most pertinent mitigation practice for improving water quality. For example, if a stream in a catchment with deer and sheep present is choked with algae and limited by inputs of P, mitigation should focus on deer rather than sheep.


Early operation on patients with a hip fracture improved the ability to return to independent living. A prospective study of 850 patients.
The outcome for many patients with a hip fracture remains poor. The aim of the present study was to investigate whether the timing of surgery in such patients could influence the short-term clinical outcome. We included 850 consecutive patients with a hip fracture who were admitted to the hospital during one year in a prospective study. Three cutoff limits for a comparison of early and late operation were defined. The outcome (the ability to return to independent living, risk for the development of pressure ulcers, length of the hospital stay, and mortality rate) for patients who had an operation within twenty-four, thirty-six, and forty-eight hours was compared with the outcome for those who had an operation at a later time. Patients who had the operation more than thirty-six and forty-eight hours after admission were less likely to return to independent living within four months (odds ratio, 0.44 and 0.33, respectively), whereas there was no significant difference with use of the twenty-four-hour cutoff limit. The incidence of pressure ulcers in the groups that had the operation later was increased at all three cutoff limits (a delay of more than twenty-four hours, more than thirty-six hours, and more than forty-eight hours) (odds ratio, 2.19, 3.42, and 4.34, respectively). The length of hospitalization was also increased in the groups that had the later operation (median, fourteen compared with eighteen days, fifteen compared with nineteen days, and fifteen compared with twenty-one days, respectively) (p < 0.001 for all comparisons). The importance of surgical timing remained significant after adjusting for several possible confounders (p < 0.05). Early compared with late operative treatment of patients with a hip fracture is associated with an improved ability to return to independent living, a reduced risk for the development of pressure ulcers, and a shortened hospital stay.


Introduction to focus issue: rhythms and dynamic transitions in neurological disease: modeling, computation, and experiment.
Rhythmic neuronal oscillations across a broad range of frequencies, as well as spatiotemporal phenomena, such as waves and bumps, have been observed in various areas of the brain and proposed as critical to brain function. While there is a long and distinguished history of studying rhythms in nerve cells and neuronal networks in healthy organisms, the association and analysis of rhythms to diseases are more recent developments. Indeed, it is now thought that certain aspects of diseases of the nervous system, such as epilepsy, schizophrenia, Parkinson's, and sleep disorders, are associated with transitions or disruptions of neurological rhythms. This focus issue brings together articles presenting modeling, computational, analytical, and experimental perspectives about rhythms and dynamic transitions between them that are associated to various diseases.


Vitellogenin genes are transcribed in Culex quinquefasciatus ovary.
Culex quinquefasciatus, a cosmopolitan, domestic, and highly anthropophilic mosquito, is a vector of pathogenic arboviruses such as West Nile virus and Rift Valley virus, as well as lymphatic filariasis. The current knowledge on its reproductive physiology regarding vitellogenin expression in different tissues is still limited. In this study, we analysed the transcriptional profiles of vitellogenin genes in the fat body and ovaries of C. quinquefasciatus females during the first gonotrophic cycle. C. quinquefasciatus ovaries and/or fat bodies were dissected in different times during the first gonotrophic cycle and total RNA was extracted and used for reverse transcription polymerase chain reaction, quantitative real time-PCR, and in situ hybridisation. We confirmed the classical descriptions of the vitellogenic process in mosquitoes by verifying that vitellogenin genes are transcribed in the fat bodies of C. quinquefasciatus females. Using RNA in situ hybridisation approach, we showed that vitellogenin genes are also transcribed in developing ovaries, specifically by the follicle cells. This is the first time that vitellogenin transcripts are observed in mosquito ovaries. Studies to determine if Vg transcripts are translated into proteins and their contribution to the reproductive success of the mosquito need to be further investigated.


H3N2v and other influenza epidemic risk based on age-specific estimates of sero-protection and contact network interactions.
Cases of a novel swine-origin influenza A(H3N2) variant (H3N2v) have recently been identified in the US, primarily among children. We estimated potential epidemic attack rates (ARs) based on age-specific estimates of sero-susceptibility and social interactions. A contact network model previously established for the Greater Vancouver Area (GVA), Canada was used to estimate average epidemic (infection) ARs for the emerging H3N2v and comparator viruses (H1N1pdm09 and an extinguished H3N2 seasonal strain) based on typical influenza characteristics, basic reproduction number (R(0)), and effective contacts taking into account age-specific sero-protection rates (SPRs). SPRs were assessed in sera collected from the GVA in 2009 or earlier (pre-H1N1pdm09) and fall 2010 (post-H1N1pdm09, seasonal A/Brisbane/10/2007(H3N2), and H3N2v) by hemagglutination inhibition (HI) assay. SPR was assigned per convention based on proportion with HI antibody titre ≥40 (SPR40). Recognizing that the HI titre ≥40 was established as the 50%sero-protective threshold we also explored for ½SPR40, SPR80 and a blended gradient defined as: ¼SPR20, ½SPR40, ¾SPR80, SPR160. Base case analysis assumed R(0) = 1.40, but we also explored R(0) as high as 1.80. With R(0) = 1.40 and SPR40, simulated ARs were well aligned with field observations for H1N1pdm09 incidence (AR: 32%), sporadic detections without a third epidemic wave post-H1N1pdm09 (negligible AR<0.1%) as well as A/Brisbane/10/2007(H3N2) seasonal strain extinction and antigenic drift replacement (negligible AR<0.1%). Simulated AR for the novel swine-origin H3N2v was 6%, highest in children 6-11years (16%). However, with modification to SPR thresholds per above, H3N2v AR ≥20% became possible. At SPR40, H3N2v AR ≥10%, ≥15% or ≥30%, occur if R(0)≥1.48, ≥1.56 or ≥1.86, respectively. Based on conventional assumptions, the novel swine-origin H3N2v does not currently pose a substantial pandemic threat. If H3N2v epidemics do occur, overall community ARs are unlikely to exceed typical seasonal influenza experience. However risk assessment may change with time and depends crucially upon the validation of epidemiological features of influenza, notably the serologic correlate of protection and R(0).


The effects of ketamine on conduction velocity and maximum rate of rise of action potential upstroke in guinea pig papillary muscles: comparison with quinidine.
Using standard microelectrode techniques, the effects of ketamine on the maximum rate of rise of action potential upstroke (Vmax) and the conduction velocity were examined and compared with the effects of quinidine, a sodium channel blocker, in isolated guinea pig papillary muscles. Both ketamine and quinidine decreased Vmax and the square of the conduction velocity in a concentration-dependent manner. The conduction slowing paralleled the decreases in Vmax, suggesting that the sodium current inhibition produced by these drugs is responsible for the conduction slowing. In the presence of quinidine, a train of stimulation after a quiescent period produced an exponential decline in Vmax, and the decrease in Vmax was enhanced by increasing stimulation frequency (i.e., use-dependent block). Ketamine significantly depressed Vmax of the first action potential after a long quiescent period (tonic block), and failed to produce a further decrease in Vmax during the subsequent train of stimulation. The decrease in Vmax was enhanced by simultaneous administration of ketamine and quinidine. Thus, ketamine decreases conduction velocity by inhibiting the sodium current. The mode of action on cardiac conduction is similar to that of quinidine, but different from that of volatile anesthetics which produce conduction slowing by impairing cell-to-cell coupling. However, ketamine produces a tonic block of the sodium channel while quinidine produces a use-dependent block. We conclude that ketamine should be administered with caution to patients receiving Class I antiarrhythmic drugs.


New triterpene constituents, foliasalacins A(1)-A(4), B(1)-B(3), and C, from the leaves of Salacia chinensis.
Four dammarane-type, three lupane-type, and an oleanane-type triterpenes named foliasalacins A(1) (1), A(2) (2), A(3) (3), A(4) (4), B(1) (5), B(2) (6), B(3) (7), and C (8) were isolated from the leaves of Salacia chinensis LINN. collected in Thailand. The structures of new triterpene constituents (1-8) were characterized on the basis of chemical and physiochemical evidence.


Oxidative modification and electrochemical inactivation of Escherichia coli upon cold atmospheric pressure plasma exposure.
Cold atmospheric pressure plasmas (CAPPs) are known to have bactericidal effects but the mechanism of their interaction with microorganisms remains poorly understood. In this study the bacteria Escherichia coli were used as a model and were exposed to CAPPs. Different gas compositions, helium with or without adjunctions of nitrogen or oxygen, were used. Our results indicated that CAPP induced bacterial death at decontamination levels depend on the duration, post-treatment storage and the gas mixture composition used for the treatment. The plasma containing O2 in the feeding gas was the most aggressive and showed faster bactericidal effects. Structural modifications of treated bacteria were observed, especially significant was membrane leakage and morphological changes. Oxidative stress caused by plasma treatment led to significant damage of E. coli. Biochemical analyses of bacterial macromolecules indicated massive intracellular protein oxidation. However, reactive oxygen and nitrogen species (RONS) are not the only actors involved in E. coli's death, electrical field and charged particles could play a significant role especially for He-O2 CAPP.


Individual risk attitudes arise from noise in neurocognitive magnitude representations.
Humans are generally risk averse, preferring smaller certain over larger uncertain outcomes. Economic theories usually explain this by assuming concave utility functions. Here, we provide evidence that risk aversion can also arise from relative underestimation of larger monetary payoffs, a perceptual bias rooted in the noisy logarithmic coding of numerical magnitudes. We confirmed this with psychophysics and functional magnetic resonance imaging, by measuring behavioural and neural acuity of magnitude representations during a magnitude perception task and relating these measures to risk attitudes during separate risky financial decisions. Computational modelling indicated that participants use similar mental magnitude representations in both tasks, with correlated precision across perceptual and risky choices. Participants with more precise magnitude representations in parietal cortex showed less variable behaviour and less risk aversion. Our results highlight that at least some individual characteristics of economic behaviour can reflect capacity limitations in perceptual processing rather than processes that assign subjective values to monetary outcomes.


Kinetic Study of the Aroxyl-Radical-Scavenging Activity of Five Fatty Acid Esters and Six Carotenoids in Toluene Solution: Structure-Activity Relationship for the Hydrogen Abstraction Reaction.
A kinetic study of the reaction between an aroxyl radical (ArO•) and fatty acid esters (LHs 1-5, ethyl stearate 1, ethyl oleate 2, ethyl linoleate 3, ethyl linolenate 4, and ethyl arachidonate 5) has been undertaken. The second-order rate constants (ks) for the reaction of ArO• with LHs 1-5 in toluene at 25.0 °C have been determined spectrophotometrically. The ks values obtained increased in the order of LH 1 < 2 < 3 < 4 < 5, that is, with increasing the number of double bonds included in LHs 1-5. The ks value for LH 5 was 2.93 × 10-3 M-1 s-1. From the result, it has been clarified that the reaction of ArO• with LHs 1-5 was explained by an allylic hydrogen abstraction reaction. A similar kinetic study was performed for the reaction of ArO• with six carotenoids (Car-Hs 1-6, astaxanthin 1, β-carotene 2, lycopene 3, capsanthin 4, zeaxanthin 5, and lutein 6). The ks values obtained increased in the order of Car-H 1 < 2 < 3 < 4 < 5 < 6. The ks value for Car-H 6 was 8.4 × 10-4 M-1 s-1. The ks values obtained for Car-Hs 1-6 are in the same order as that of the values for LHs 1-5. The results of detailed analyses of the ks values for the above reaction indicated that the reaction was also explained by an allylic hydrogen abstraction reaction. Furthermore, the structure-activity relationship for the reaction was discussed by taking the result of density functional theory calculation reported by Martinez and Barbosa into account.


How the Whole School, Whole Community, Whole Child model works: creating greater alignment, integration, and collaboration between health and education.
The Whole School, Whole Community, Whole Child (WSCC) model calls for greater collaboration across the community, school, and health sectors to meet the needs and support the full potential of each child. This article reports on how 3 states and 2 local school districts have implemented aspects of the WSCC model through collaboration, leadership and policy creation, alignment, and implementation. We searched state health and education department websites, local school district websites, state legislative databases, and sources of peer-reviewed and gray literature to identify materials demonstrating adoption and implementation of coordinated school health, the WSCC model, and associated policies and practices in identified states and districts. We conducted informal interviews in each state and district to reinforce the document review. States and local school districts have been able to strategically increase collaboration, integration, and alignment of health and education through the adoption and implementation of policy and practice supporting the WSCC model. Successful utilization of the WSCC model has led to substantial positive changes in school health environments, policies, and practices. Collaboration among health and education sectors to integrate and align services may lead to improved efficiencies and better health and education outcomes for students.


Quantifying the degradation of degradable implants and bone formation in the femoral condyle using micro-CT 3D reconstruction.
Degradation limits the application of magnesium alloys, and evaluation methods for non-traumatic in vivo quantification of implant degradation and bone formation are imperfect. In the present study, a micro-arc-oxidized AZ31 magnesium alloy was used to evaluate the degradation of implants and new bone formation in 60 male New Zealand white rabbits. Degradation was monitored by weighing the implants prior to and following implantation, and by performing micro-computed tomography (CT) scans and histological analysis after 1, 4, 12, 24, 36, and 48 weeks of implantation. The results indicated that the implants underwent slow degradation in the first 4 weeks, with negligible degradation in the first week, followed by significantly increased degradation during weeks 12-24 (P<0.05), and continued degradation until the end of the 48-week experimental period. The magnesium content decreased as the implant degraded (P<0.05); however, the density of the material exhibited almost no change. Micro-CT results also demonstrated that pin volume, pin mineral density, mean 'pin thickness', bone surface/bone volume and trabecular separation decreased over time (P<0.05), and that the pin surface area/pin volume, bone volume fraction, trabecular thickness, trabecular number and tissue mineral density increased over time (P<0.05), indicating that the number of bones and density of new bone increased as magnesium degraded. These results support the positive effect of magnesium on osteogenesis. However, from the maximum inner diameter of the new bone loop and diameter of the pin in the same position, the magnesium alloy was not capable of creating sufficient bridges between the bones and biomaterials when there were preexisting gaps. Histological analyses indicated that there were no inflammatory responses around the implants. The results of the present study indicate that a micro-arc-oxidized AZ31 magnesium alloy is safe in vivo and efficiently degraded. Furthermore, the novel bone formation increased as the implant degraded. The findings concluded that micro-CT, which is useful for providing non-traumatic, in vivo, quantitative and precise data, has great value for exploring the degradation of implants and novel bone formation.


The postadoption experience of surrendering parents.
In order to ascertain the effects on subsequent life adjustment of having relinquished a child for adoption, a survey was conducted among 334 individuals, most of whom are members of Concerned United Birthparents. Findings indicate that having surrendered a child is perceived by these respondents as having a protracted negative influence on their lives in the areas of marriage, fertility, and parenting. Implications for adoption work and policy are discussed.


Distance Metric Learning via Iterated Support Vector Machines.
Distance metric learning aims to learn from the given training data a valid distance metric, with which the similarity between data samples can be more effectively evaluated for classification. Metric learning is often formulated as a convex or nonconvex optimization problem, while most existing methods are based on customized optimizers and become inefficient for large scale problems. In this paper, we formulate metric learning as a kernel classification problem with the positive semi-definite constraint, and solve it by iterated training of support vector machines (SVMs). The new formulation is easy to implement and efficient in training with the off-the-shelf SVM solvers. Two novel metric learning models, namely positive-semidefinite constrained metric learning (PCML) and nonnegative-coefficient constrained metric learning (NCML), are developed. Both PCML and NCML can guarantee the global optimality of their solutions. Experiments are conducted on general classification, face verification, and person re-identification to evaluate our methods. Compared with the state-of-the-art approaches, our methods can achieve comparable classification accuracy and are efficient in training.