Putting diabetes on the map: what does population health really look like at the local level?
Population health data are used to profile local conditions, call attention to areas of need, and evaluate health-related programs. Demand for data to inform health care decision making has spurred development of data sources and online systems, but these are often poorly integrated or limited in scope. Our objective was to identify existing data about diabetes mellitus-related conditions in Minnesota, build an online data resource, and identify what data are currently missing that, if available, would better inform assessment of health conditions in the state. A Web site was developed and populated with existing data and data not available elsewhere. It features functionality identified as most important by users, such as maps and county profiles. The site could serve as a flexible tool for stakeholder engagement, but issues were identified during development, including concerns about interpreting map data and open questions about sustainability, that need to be addressed.


CNS-induced natriuresis and renal hemodynamics in conscious rats.
Sodium excretion was studied following experimental elevation of cerebrospinal fluid (CSF) sodium in heterozygous and homozygous (DI) Brattleboro rats given exogeneous antidiuretic hormone. Sodium excretion increased 4.5-fold in heterozygous and 3.5-fold in DI rats. The natriuresis in both groups was rapid in onset and occurred with a simultaneous kaliuresis. Blood pressure increased approximately 10 mmHg in the heterozygous but not in the DI rats. Accordingly, increased blood pressure may contribute to the natriuresis but is not the sole mechanism. Plasma renin concentration did not change in the DI rats during high Na CSF infusion, and chronic bilateral renal denervation did not abolish the natriuresis. Glomerular filtration rate increased during the high Na period in both the intact and renally denervated rats. These data provide evidence that a natriuretic mechanism exists that is not mediated by changes in antidiuretic hormone, renal nerve activity, mean arterial pressure, aldosterone, or angiotensin II, and thus may be due to another circulating substance or natriuretic hormone. This hormone may act totally or in part by increasing glomerular filtration rate.


Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms.
Neurological-related disorders are diseases that affect the body's neurons or peripheral nerve tissue, such as Parkinson's disease (PD) and Alzheimer's disease (AD). The development of neurological disorders can cause serious harm to the quality of life and functioning of the patient. The use of traditional therapeutic agents such as dopamine-promoting drugs, anticholinergic drugs, cholinesterase inhibitors, and NMDA receptor antagonists is often accompanied by a series of side effects such as drug resistance, cardiac arrhythmia, liver function abnormalities, and blurred vision. Therefore, there is an urgent need to find a therapeutic drug with a high safety profile and few side effects. Herbal medicines are rich in active ingredients that are natural macromolecules. Ginsenoside is the main active ingredient of ginseng, which has a variety of pharmacological effects and is considered to have potential value in the treatment of human diseases. Modern pharmacological studies have shown that ginsenosides Rg2 and Rh1 have strong pharmacological activities in the nervous system, with protective effects on nerve cells, improved resistance to neuronal injury, modulation of neural activity, resistance to cerebral ischemia/reperfusion injury, improvement of brain damage after eclampsia hemorrhage, improvement of memory and cognitive deficits, treatment of AD and vascular dementia, alleviation of anxiety, pain, and inhibition of ionic-like behavior. In this article, we searched the pharmacological research literature of Rg2 and Rh1 in the field of neurological diseases, summarized the latest research progress of the two ginsenosides, and reviewed the pharmacological effects and mechanisms of Rg2 and Rh1, which provided a new way of thinking for the research of the active ingredients in ginseng anti-neurological diseases and the development of new drugs.


Ethical Frameworks in Public Health Decision-Making: Defending a Value-Based and Pluralist Approach.
A number of ethical frameworks have been proposed to support decision-making in public health and the evaluation of public health policy and practice. This is encouraging, since ethical considerations are of paramount importance in health policy. However, these frameworks have various deficiencies, in part because they incorporate substantial ethical positions. In this article, we discuss and criticise a framework developed by James Childress and Ruth Bernheim, which we consider to be the state of the art in the field. Their framework distinguishes aims, such as the promotion of public health, from constraints on the pursuit of those aims, such as the requirement to avoid limitations to liberty, or the requirement to be impartial. We show how this structure creates both theoretical and practical problems. We then go on to present and defend a more practical framework, one that is neutral in avoiding precommitment to particular values and how they ought to be weighted. We believe ethics is at the very heart of such weightings and our framework is developed to reflect this belief. It is therefore both pluralist and value-based. We compare our new framework to Childress and Bernheim's and outline its advantages. It is justified by its impetus to consider a wide range of alternatives and its tendency to direct decisions towards the best alternatives, as well as by the information provided by the ranking of alternatives and transparent explication of the judgements that motivate this ranking. The new framework presented should be useful to decision-makers in public health, as well as being a means to stimulate further reflection on the role of ethics in public health.


Clinical and imaging surveillance following breast cancer diagnosis.
Breast cancer is the most common malignancy affecting women worldwide. Women have a 1 in 8 lifetime risk of breast cancer. Breast conservation therapy (BCT) is the most common method of definitive treatment. Patients who previously have had to undergo mastectomy may be now eligible for BCT or a multitude of options for reconstruction, either immediate or delayed. Surveillance imaging after a breast cancer diagnosis is important because there is an increased risk of recurrence developing in patients, and early detection has been shown to improve survival. There is currently no consensus on a protocol for imaging the postoperative breast. In patients who have undergone mastectomy, detection of recurrence has mostly been via clinical symptoms and physical exam, often at a later stage. New imaging modalities, such as magnetic resonance imaging (MRI), ultrasound (US), and positron emission mammography (PEM) are changing the way we image the postsurgical breast. MRI, coupled with physical exam and mammography, approaches 100% sensitivity and high specificity for the identification of recurrent disease. We present a review of major academic institutions' imaging protocols and discuss the advantages of including MRI in traditional mammographic and clinical exams.


Tissue-specific utilization of menaquinone-4 results in the prevention of arterial calcification in warfarin-treated rats.
The effects of vitamin K (phylloquinone: K1 and menaquinone-4: MK-4) on vascular calcification and their utilization in the arterial vessel wall were compared in the warfarin-treated rat model for arterial calcification. Warfarin-treated rats were fed diets containing K1, MK-4, or both. Both K1 and MK-4 are cofactors for the endoplasmic reticulum enzyme gamma-glutamyl carboxylase but have a structurally different aliphatic side chain. Despite their similar in vitro cofactor activity we show that MK-4 and not K1 inhibits warfarin-induced arterial calcification. The total hepatic K1 accumulation was threefold higher than that of MK-4, whereas aortic MK-4 was three times that of K1. The utilization of K1 and MK-4 in various tissues was estimated by calculating the ratios between accumulated quinone and epoxide species. K1 and MK-4 were both equally utilized in the liver, but the aorta showed a more efficient utilization of MK-4. Therefore, the observed differences between K1 and MK-4 with respect to inhibition of arterial calcification may be explained by both differences in their tissue bioavailability and cofactor utilization in the reductase/carboxylase reaction. An alternative explanation may come from an as yet hypothetical function of the geranylgeranyl side chain of MK-4, which is a structural analogue of geranylgeranyl pyrophosphate and could interfere with a critical step in the mevalonate pathway.


Development of a Symmetry Score for Infantile Postural and Movement Asymmetries: Preliminary Results of a Pilot Study.
The purpose of this study was to develop and verify a quantifiable symmetry score for infantile postural and movement asymmetries. Three studies were conducted. For reliability, 6 test items examining postural and movement asymmetries, which came under consideration, were investigated in 24 infants with postural abnormality (range: 14-24 weeks). The inter-rater reliability was chosen as the primary endpoint. Furthermore, intrarater reliability and test-retest reliability were determined. Analysis and weighting of the items were performed by calculating the intraclass correlation coefficient. The validity was reviewed by expert opinion and by using a study with 26 infants (range: 12-28 weeks) of a cross-section population. The pilot study involved 38 infants, aged 14 to 24 weeks, who were examined using video. Their autonomic symptoms were recorded, and subsequently, they were treated once by means of manual medicine. The parents were instructed to a daily home program that focused on "tummy time." The reliability tests led to a 4-item symmetry score with a point value between 4 points (very symmetrical) and 17 points (very asymmetrical). The chosen items achieved an intraclass correlation coefficient >0.8 and Cohen's κ >0.6, respectively. The experts' opinions matched mainly to a majority agreement (>50%). Furthermore, a comparison between the outcome of clinical testing and the symmetry score applied to 26 children without diagnosed abnormalities displayed an agreement of 84.6%. The pilot study showed a good reduction of the postural and movement abnormalities because 63% of the manual treated children were assessed as being symmetric afterward. The reliable and valid 4-item symmetry score served for the diagnosis, evaluation, and follow-up of infants aged 3 to 6 months with infantile postural and movement asymmetries. The results of a pilot study showed the positive effect of a single manual medical treatment session along with a home program focusing on "tummy time."


Two dimensional diffusion-controlled triplet-triplet annihilation kinetics.
Diffusion controlled chemical reactions are usually observed in three dimensional media. In contrast, planar bimolecular reactions taking place between reagents adsorbed at a soft interface are two-dimensional and therefore cannot be studied within the same formalism. Indeed, soft interfaces allow the adsorbed species to freely diffuse in a liquid-like manner. Here, we present the first experimental observation of a diffusion-controlled reaction in an environment that is planar at the ångström scale. By means of time-resolved surface second harmonic generation, an inherently surface sensitive technique, we observed that the kinetics of the diffusion of the reagents in the plane decreases as the surface concentration of adsorbed species increases. This is of course not the case for bulk reactions where the rates always increase with the reactant concentration. Such changes in the kinetics regime were rationalised as the evolution from a regular 2D free diffusion regime to a geometry-controlled scheme.


Two types of alpha satellite DNA in distinct chromosomal locations in Azara's owl monkey.
Alpha satellite DNA is a repetitive sequence known to be a major DNA component of centromeres in primates (order Primates). New World monkeys form one major taxon (parvorder Platyrrhini) of primates, and their alpha satellite DNA is known to comprise repeat units of around 340 bp. In one species (Azara's owl monkey Aotus azarae) of this taxon, we identified two types of alpha satellite DNA consisting of 185- and 344-bp repeat units that we designated as OwlAlp1 and OwlAlp2, respectively. OwlAlp2 exhibits similarity throughout its entire sequence to the alpha satellite DNA of other New World monkeys. The chromosomal locations of the two types of sequence are markedly distinct: OwlAlp1 was observed at the centromeric constrictions, whereas OwlAlp2 was found in the pericentric regions. From these results, we inferred that OwlAlp1 was derived from OwlAlp2 and rapidly replaced OwlAlp2 as the principal alpha satellite DNA on a short time scale at the speciation level. A less likely alternative explanation is also discussed.


Application of Antidromic Conduction Monitoring in Ganglion Radiofrequency Thermocoagulation for Locating Trigeminal Branches in Trigeminal Neuralgia.
The aim of this study was to investigate whether antidromic conduction monitoring (ACM) can be utilized to map the trigeminal system under sedation as a potential substitute for subjective paresthesia description (SPD) during percutaneous ganglion radiofrequency thermocoagulation (PGRT). Eighty-two patients with 152 pain divisions of trigeminal neuralgia (TN) were treated by computed tomography (CT)-guided PGRT. After the puncture needle entered the foramen ovale (FO), sensory and motor stimulation were applied to locate the pain division. And the corresponding voltage values were recorded by patients' SPD. In the following, the proper location was certified by ACM. The corresponding earliest waves and voltage values in the identified trigeminal branch were also recorded to outline a comparison between two methods. The correlation of ACM and patients' SPD with voltage at ≤ 0.5 V was statistically significant (P < 0.05, r = 0.159; Spearman's rank correlation analysis). Although ACM and SPD showed weak correlation, as their interclass correlation coefficient was significant (F = 1.868, P < 0.01) with coefficient of internal consistency. Moreover, the two methods had consistency. Kruskal-Wallis test showed that ophthalmic (V1), maxillary (V2), and mandibular (V3) divisions had significant differences for test sensitivity (H = 15.945, P < 0.01). For comparison of sensitivities with ACM, V3 was most sensitive followed by V2 and then V1. ACM could potentially substitute for SPD of the paresthesias intra-operatively, enabling greater specificity and eliminating the need to interrupt the administration of anesthetic. These improvements would increase patient satisfaction and practitioner efficiency and accuracy.


[Variations of vital signs and peripheral oxygen saturation in critically ill preterm newborn, after sponge bathing].
To determine the variability of the vital signs (temperature, heart rate and respiratory frequency), skin coloration and peripheral oxygen saturation in critically ill preterm newborns (CI PTNB) before, during and after sponge bathing as well as to determine the possible presence of secondary complications of this procedure. We performed a quasi-experimental study (experimental, prospective, comparative and clinical study with intervention) May to December 2008, in a Neonatal Intensive Care Unit. We included CI PTNB of 0 to 28 days of extrauterine life who have practiced in the routine sponge bathing. Area of significance was considered when p < 0.05. During or after the events in any of the patients presented any complications after 12 h of monitoring, but it was necessary to increase the inspired fraction of oxygen and temperature in the incubator or radiant heat cradle temporarily. We conclude that the sponge bath is not safe for a CI PTNB and this should be performed in the shortest time possible, and the medical must be very alert to the possibility that patients require more support than they had prior to sponge bathing, mainly in the temperature of the incubator or radiant heat cradle and inspired fraction of oxygen for the required time according to the evolution of these variables.


Synaptic mechanisms for auditory-vocal integration and the correction of vocal errors.
A central goal of neuroscience is to understand the cellular mechanisms enabling the cultural transmission of behaviors, such as speech and music. Birdsong is a rare non-human instance of a culturally transmitted vocal behavior. The songbird's brain provides a powerful system in which to study the cellular mechanisms underlying auditory-guided vocal learning. Identifying those mechanisms requires an analysis of synaptic function, because the synapse is the fundamental organizational unit of the neuronal networks that mediate behavior. Intracellular recordings provide a powerful method for simultaneously probing the activities of a single neuron and the synaptic networks in which that cell is embedded. This chapter details initial steps in the in vivo intracellular analysis of the synaptic connectivity of neurons important to singing and song learning. Our analysis is focused upon HVC and involves studies of interneurons as well as projection neurons of the two major output pathways of HVC. We test predictions derived from several models of how such learning may take place, including contributions from "comparator" and "corollary discharge" auditory feedback cancellation mechanisms. Our studies in anesthetized animals and brain slices provide insight into the synaptic properties of HVC that might be well suited for these mechanisms, although extrapolation to synaptic behavior in the awake, singing bird must be made with caution. We suggest that future work must extend the analysis of synaptic properties into the intact brain of the songbird, preferably as the bird learns to sing.


Muscle Activation in the Shoulder Girdle and Lumbopelvic-Hip Complex During Common Therapeutic Exercises.
Lumbopelvic-hip complex (LPHC) exercises are used to increase stabilization within the human body. Torso-elevated side support (TESS), foot-elevated side support (FESS), prone bridge plank (PBP), and V-sit are common LPHC exercises. To evaluate muscle activation in the shoulder girdle and LPHC during 4 LPHC exercises and evaluate the reasoning for termination. Cross-sectional study. Laboratory. Seventeen healthy participants (12 males and 5 females; age: 21.47 [3.16] y, height: 179.73 [8.92] cm, mass: 76.89 [11.17] kg). Participants completed 2 repetitions of the TESS, FESS, PBP, and V-sit until failure. Surface electromyography of the middle deltoid, latissimus dorsi, middle trapezius, rectus abdominis, erector spinae, external oblique, and gluteus medius were recorded and normalized to maximum voluntary isometric contraction (MVIC). The duration of exercise and subjective reasoning for termination of exercise was completed following the 4 tasks. The TESS and PBP had significantly greater middle deltoid muscle activation (TESS: 55.66% [24.45%] MVIC and PBP: 42.63% [18.25%] MVIC) compared with the FESS (10.10% [10.04%] MVIC) and V-sit (2.21% [1.94%] MVIC), P < .05. The TESS produced significantly greater external oblique activity (78.13% [32.32%] MVIC) than the PBP (54.99% [19.54%] MVIC), P < .05. Due to shoulder fatigue and pain, 41.1% and 17.0% of participants terminated the TESS, respectively. The PBP was terminated due to abdominal fatigue (41.1%) and upper-extremity fatigue (47.0%). The V-sit resulted in isolated activity of the abdominal portion of the LPHC. The FESS had increased global co-contraction of the LPHC compared with the TESS. The PBP and TESS had significant muscle activation in the upper-extremity.


Color adaptation induced from linguistic description of color.
Recent theories propose that language comprehension can influence perception at the low level of perceptual system. Here, we used an adaptation paradigm to test whether processing language caused color adaptation in the visual system. After prolonged exposure to a color linguistic context, which depicted red, green, or non-specific color scenes, participants immediately performed a color detection task, indicating whether they saw a green color square in the middle of a white screen or not. We found that participants were more likely to perceive the green color square after listening to discourses denoting red compared to discourses denoting green or conveying non-specific color information, revealing that language comprehension caused an adaptation aftereffect at the perceptual level. Therefore, semantic representation of color may have a common neural substrate with color perception. These results are in line with the simulation view of embodied language comprehension theory, which predicts that processing language reactivates the sensorimotor systems that are engaged during real experience.


A Study of Haemostatic Parameters in Patients of Chronic Myeloid Leukaemia.
Chronic Myeloid Leukaemia (CML) is characterized by derangement of various components of the haemostatic system resulting in thrombo-haemorrhagic complications. Although less common than other myeloproliferative neoplasms, derangement of various components of the haemostatic system is observed in CML. Haemostatic abnormalities have been described in relation to hyperleucostasis and drugs used to treat CML. However, the correlation between haemostatic derangements and phase of CML is unclear in the literature. The purpose of this cross-sectional study was to assay various haemostatic parameters in patients of CML receiving Imatinib and to determine any correlation between them and phases of disease as well as the status of remission. The study included 30 patients with CML (17 males, 13 females, mean age of 35.53 ± 8.92 years) receiving imatinib mesylate. Haemostatic parameters including platelet counts, Prothrombin Time (PT), activated Partial Thromboplastin Time (APTT), fibrinogen, D-dimers and Factor VIII levels were assayed for all patients using standard methods. Bcr-abl gene product (quantitative) was determined on the peripheral blood by reverse transcriptase polymerase chain reaction (RT-PCR). Patients were grouped into phases of disease (chronic, accelerated and blast) and their response to imatinib was determined in the form of remission (clinical, haematological and molecular). Correlations were drawn between them using spearman's coefficient. A significant positive correlation was found between PT (p=0.002), fibrinogen (p=0.011), D-dimers (p=0.050), Factor VIII levels (p=0.006) with the phase of CML and a significant negative correlation was observed between PT (p=0.003, 0.006), fibrinogen (p=0.010, 0.005), D-dimers (p=0.035, 0.017), Factor VIII levels (p=0.005, 0.001) and clinical and haematological remission respectively. No significant correlation of platelet counts and APTT was seen with the phase of CML or remission status. Haemostatic system is significantly disturbed in CML and correlate positively with the progression of the disease. Imatinib treatment leads to improvement in some of these parameters.


Best practices in PA development: Lessons from three countries.
As the PA profession moves into its 50th year and develops globally, its flexibility and underlying principles make it adaptable to a wide range of healthcare needs and governmental priorities. A key feature of effective PA development is adapting the profession to the needs of each country rather than adopting it exactly as it has developed in the United States. The successful adaptation of new PA models must assure that the new profession meets a societal need, such as increasing healthcare access for specific populations or geographic areas.


Conservation of the biochemical properties of IncA from Chlamydia trachomatis and Chlamydia caviae: oligomerization of IncA mediates interaction between facing membranes.
The developmental cycle of Chlamydiaceae occurs in a membrane compartment called an inclusion. IncA is a member of a family of proteins synthesized and secreted onto the inclusion membrane by bacteria. IncA proteins from different species of Chlamydiaceae show little sequence similarity. We report that the biochemical properties of Chlamydia trachomatis and Chlamydia caviae are conserved. Both proteins self-associate to form multimers. When artificially expressed by the host cell, they localize to the endoplasmic reticulum. Strikingly, heterologous expression of IncA in the endoplasmic reticulum completely inhibits concomitant inclusion development. Using truncated forms of IncA from C. caviae, we show that expression of the C-terminal cytoplasmic domain of the protein at the surface of the endoplasmic reticulum is sufficient to disrupt the bacterial developmental cycle. On the other hand, development of a C. trachomatis strain that does not express IncA is not inhibited by artificial IncA expression, showing that the disruptive effect observed with the wild-type strain requires direct interactions between IncA molecules at the inclusion and on the endoplasmic reticulum. Finally, we modeled IncA tetramers in parallel four helix bundles based on the structure of the SNARE complex, a conserved structure involved in membrane fusion in eukaryotic cells. Both C. trachomatis and C. caviae IncA tetramers were highly stable in this model. In conclusion, we show that the property of IncA proteins to assemble into multimeric structures is conserved between chlamydial species, and we propose that these proteins may have co-evolved with the SNARE machinery for a role in membrane fusion.


Extraction of nucleic acids from ancient formalin- and ethanol-preserved specimens of the tapeworm Bertiella studeri: which method works best?
In this study we show that intact DNA can be recovered from both alcohol- and formalin-preserved specimens of the parasitic tapeworm Bertiella studeri for >1 yr after the original fixation and can be successfully amplified and quantified using real-time polymerase chain reaction (RT-PCR). Three different DNA extraction techniques on formalin- and alcohol-fixed material were evaluated to determine which is best suited for obtaining DNA of sufficient yield and purity to be used in downstream applications such as RT-PCR. These techniques included a first organic extraction procedure with an extensive washing step based on a glycine-containing buffer, a second organic extraction procedure that omits the glycine-containing buffer and halves the number of washes in organic solvents, and a third procedure that involves the use of a silica-based DNA binding column from Qiagen(©). The quality of extracted DNA was first examined by agarose gel electrophoresis and ethidium bromide staining and the concentrations were evaluated by OD260. We then used an RT-PCR Applied Biosystems TaqMan® Fluorogenic 5' Nuclease Gene Expression Assay based on the detection of a universal eukaryotic 18S rRNA gene sequence to evaluate the efficiency of the 3 methods. Here we report that, first, the use of a silica column-based DNA extraction technique results in the maximum yield of DNA, on average 55% higher than for the organic extraction methods; second, the use of glycine as a formaldehyde-binding agent in the washing buffer does not necessarily result in a better DNA yield and; third, specimens preserved in ethanol result in significantly higher yields of amplifiable DNA than do specimens preserved in formalin. We, therefore, strongly recommend the use of ethanol as the appropriate fixative if specimens are to be used for molecular work. This is the first report of DNA extraction from preserved specimens of Bertiella studeri.


Effects of the extracorporeal shock wave therapy on the skin: an experimental study.
Extracorporeal shock wave therapy (ESWT) has been extensively studied for its multiple biological properties, and although it is widely applied in esthetical procedures, little is known about its effects on the epidermis and dermis. In this study, a histological and immunohistochemical study of the effects of ESWT was performed on rat skin. Forty-five female rats were treated with one or two sessions of ESWT and sacrificed on days 1, 7, 14, and 21 after treatment. The samples were histologically processed and then morphometric analyses were performed to assess the epidermis, dermis, and subcutaneous fat tissue thickness. Immunohistochemical reactions were also performed against the antibodies: basic fibroblastic growth factor (FGF2), its receptor (FGFR1), and α-smooth muscle actin. Slides were scanned and digitally assessed, to determine the microvessel density (MVD) and digital scoring of the immunohistochemical staining. The results showed that ESWT produced a significantly higher collagen content, MVD, and epidermis and dermis thickness than the control, non-treated group. Both in epidermis and dermis, FGF2 was overexpressed in the ESWT-treated groups, whereas FGFR1 was increased only in the group treated with two ESWT sessions at 21-days post-treatment. The ESWT-treated groups have also shown diminished thickness of subcutaneous fat tissue. In conclusion, ESWT induces neocollagenesis and neoangiogenesis, and upregulates the FGF2 expression, particularly in the groups treated with two sessions. Furthermore, it was demonstrated that overexpression of FGF2 on skins treated with ESWT seems to be a key role on its mechanism of action.


Use of a Bipolar Vessel-Sealing Device for Splenic Parenchymal Resection in Three Dogs and One Cat.
Based on splenic abnormalities noted during surgery, four client-owned animals (three dogs, one cat) undergoing exploratory laparotomy were identified as candidates for partial splenectomy. In three cases, small mass lesions of the spleen were identified on elective exploratory laparotomy. In one case, the patient was referred for emergency surgery for diaphragmatic hernia with entrapment of stomach and spleen. The discovery of avulsion of a significant portion of the splenic mesentery led to the decision to perform partial splenectomy in this case. All animals included in the study underwent partial splenectomy by one of two board-certified veterinary surgeons at a multispecialty hospital between 2014 and 2018. The same type of bipolar vessel-sealing device was used in each surgery, and three of four partial splenectomy cases recovered uneventfully. One patient went into cardiopulmonary arrest hours after surgery and died; however, this is not suspected to be due to the described partial splenectomy technique. The bipolar vessel-sealing device is suitable for use in resection of the splenic parenchyma in some canine and feline patients. This technique is designed to decrease surgical time, provide effective hemostasis, and preserve the important functions of the spleen that are lost when total splenectomy is undertaken.


[Neuroimaging of the penumbra in ischemic stroke].
Brain ischemia has been recently a central problem in basic and applied studies in angioneurology. The latest investigations that give an insight into a relationship between metabolic changes and cerebral blood flow and make it possible to study ischemia at the molecular level and its changes over time have promoted the accumulation of fundamentally new facts and some reappraisal of existing ideas. Ischemic semishadow or penumbra is one of the most important presently studied phenomena. Detection of penumbra signs suggests that it is expedient to evaluate cerebral blood flow and metabolism when planning treatment (thrombolysis or neuroprotective therapy) and that it is important to predict the severity of ischemic stroke. Positron emission tomography (PET) is the reference method for detecting the penumbra; however, its application is limited in clinical practice. Computed tomography (CT) perfusion and perfusion MRI, a combination of diffusion-weighted and perfusion MRI, single-photon emission CT, and xenon-enhanced CT are most frequently used to evaluate a cerebral ischemia area and its blood flow. However, there are no standardized approaches to quantifying the thresholds for cerebral blood flow or unified algorithms for penumbra verification, which calls for further investigations.


Shelter-based homeless youth. Health and access to care.
To compare the self-reported risk-taking behaviors, health status, and access to care issues of 2 samples of shelter-based homeless youth who had previously been street youth (youth on streets or doubling-up with friends or lovers) and systems youth (youth involved in foster care) and to examine information on the etiology of homelessness, including parent or family of origin risk factors for both samples. The study population consisted of 109 shelter-based homeless youth: 41 street youth and 68 systems youth. A chart audit was completed on all youth, noting documentation of past health problems, reasons for shelter placement, and parental risk factors. Adolescents from both samples completed a health history questionnaire followed by a physical examination. Differences between the 2 samples for behaviors and disease diagnoses were examined using chi 2 and 2-tailed t tests. The street youth exhibited greater risk-taking behaviors and suffered from poorer health status and access to care than did systems youth. The main differences were in substance using and high-risk sexual behaviors. The street youth were more likely to report previous exposure to violence and having been victims of forced sex. Self-reported risk behaviors, including sexual activity and substance abuse were corroborated by more objective information on these items from medical record information. The street youth were more likely to be medically uninsured, to have used an emergency department in the past year, and to have used an emergency department for their last care. There are important variations in health needs between samples of homeless youth, often overlooked in health planning for this population. Knowledge of parent or family of origin risk factors and causes of homelessness provides important contextual information for understanding the risk behaviors and health states of homeless youth.


Confidence-based progress-driven self-generated goals for skill acquisition in developmental robots.
A reinforcement learning agent that autonomously explores its environment can utilize a curiosity drive to enable continual learning of skills, in the absence of any external rewards. We formulate curiosity-driven exploration, and eventual skill acquisition, as a selective sampling problem. Each environment setting provides the agent with a stream of instances. An instance is a sensory observation that, when queried, causes an outcome that the agent is trying to predict. After an instance is observed, a query condition, derived herein, tells whether its outcome is statistically known or unknown to the agent, based on the confidence interval of an online linear classifier. Upon encountering the first unknown instance, the agent "queries" the environment to observe the outcome, which is expected to improve its confidence in the corresponding predictor. If the environment is in a setting where all instances are known, the agent generates a plan of actions to reach a new setting, where an unknown instance is likely to be encountered. The desired setting is a self-generated goal, and the plan of action, essentially a program to solve a problem, is a skill. The success of the plan depends on the quality of the agent's predictors, which are improved as mentioned above. For validation, this method is applied to both a simulated and real Katana robot arm in its "blocks-world" environment. Results show that the proposed method generates sample-efficient curious exploration behavior, which exhibits developmental stages, continual learning, and skill acquisition, in an intrinsically-motivated playful agent.


Partially deficient glutamate dehydrogenase activity and attenuated oscillatory potentials in patients with spinocerebellar degeneration.
Glutamate dehydrogenase (GDH, EC 220.127.116.11) catalyzes the synthesis and degradation of glutamate, an excitatory neurotransmitter in the retina. Recently, two forms of GDH, a soluble heat-stable form and a particulate heat-labile form, have been demonstrated to be deficient in some types of spinocerebellar degeneration (SCD). We measured these forms of GDH activity in leukocyte homogenate from patients with SCD (n = 22) and normal subjects (n = 20) who were examined ophthalmoscopically and electrophysiologically. Seven patients with SCD showed attenuated oscillatory potentials (OPs) on electroretinography. The heat-labile GDH activity in these seven patients (78 +/- 51 nmol/mg protein/h) was significantly lower than that of 15 patients with normal OPs (367 +/- 189) and the normal subjects (397 +/- 1720 (P less than 0.001). Our results indicated that patients with SCD could be separated into two groups electrophysiologically, one with normal OPs and one with attenuated OPs. Also indicated was that a deficiency of heat-labile GDH might affect some functions of neural elements in the retina that are responsible for the generation of OPs.


COMMUNITY READINESS AS A MULTIDIMENSIONAL CONSTRUCT.
Both the organizational studies literature and the community psychology literature discuss the importance of readiness when implementing change. Although each area emphasizes different characteristics, several common themes are present within the literature. The current study integrates and applies organizational and community psychology literature in evaluating community readiness in the context of a school-community-university collaborative prevention model. Results demonstrate (a) that there is substantial agreement between members of community prevention teams on the level of readiness of a community; (b) that readiness is a cohesive, but multidimensional, construct related to hypothesized community and individual characteristics; and (c) that there is small to moderate agreement between members of prevention teams and their "agency directors." These results support the notion that clear "theories of change" need to be formulated before deciding how to assess community readiness, as assessments will vary due to several factors: the type of respondent, the level in which analyses are conducted, and the specific community domain (i.e., school, workplace collaboration, collaboration experience) investigated.


[Women boxing athletes' EMG of upper limbs and lumbar muscles in the training of air striking of straight punch].
To study training effect of upper limbs and lumbar muscles in the proceed of air striking of straight punch by analyzing boxing athletes' changes of electromyogram (EMG). We measured EMG of ten women boxing athletes' upper arm biceps (contractor muscle), upper arm triceps (antagonistic muscle), forearm flexor muscle (contractor muscle), forearm extensor muscle (antagonistic muscle), and lumbar muscles by ME6000 (Mega Electronics Ltd.). The stipulated exercise was to do air striking of straight punch with loads of 2.5 kg of dumbbell in the hand until exhausted. In the proceed of exercise-induce exhausted, the descend magnitude and speed of median frequency (MF) in upper limb antagonistic muscle exceeded to contracting muscle, moreover, the work percentage showed that contractor have done a larger percentage of work than antagonistic muscle. Compared with world champion's EMG, the majority of ordinary athletes' lumbar muscles MF revealed non-drop tendency, and the work percentage showed that lumbar muscles had a very little percentage of work. After comparing the EMG test index in upper limb and lumbar muscle of average boxing athletes with that of the world champion, we find the testees lack of the training of upper limb antagonistic muscle and lumbar muscle, and more trainings aimed at these muscles need to be taken.


Q fever 1985-1998. Clinical and epidemiologic features of 1,383 infections.
In order to describe the clinical features and the epidemiologic findings of 1,383 patients hospitalized in France for acute or chronic Q fever, we conducted a retrospective analysis based on 74,702 sera tested in our diagnostic center, National Reference Center and World Health Organization Collaborative Center for Rickettsial Diseases. The physicians in charge of all patients with evidence of acute Q fever (seroconversion and/or presence of IgM) or chronic Q fever (prolonged disease and/or IgG antibody titer to phase I of Coxiella burnetii > or = 800) were asked to complete a questionnaire, which was computerized. A total of 1,070 cases of acute Q fever was recorded. Males were more frequently diagnosed, and most cases were identified in the spring. Cases were observed more frequently in patients between the ages of 30 and 69 years. We classified patients according to the different clinical forms of acute Q fever, hepatitis (40%), pneumonia and hepatitis (20%), pneumonia (17%), isolated fever (17%), meningoencephalitis (1%), myocarditis (1%), pericarditis (1%), and meningitis (0.7%). We showed for the first time, to our knowledge, that different clinical forms of acute Q fever are associated with significantly different patient status. Hepatitis occurred in younger patients, pneumonia in older and more immunocompromised patients, and isolated fever was more common in female patients. Risk factors were not specifically associated with a clinical form except meningoencephalitis and contact with animals. The prognosis was usually good except for those with myocarditis or meningoencephalitis as 13 patients died who were significantly older than others. For chronic Q fever, antibody titers to C. burnetii phase I above 800 and IgA above 50 were predictive in 94% of cases. Among 313 patients with chronic Q fever, 259 had endocarditis, mainly patients with previous valvulopathy; 25 had an infection of vascular aneurysm or prosthesis. Patients with endocarditis or vascular infection were more frequently immunocompromised and older than those with acute Q fever. Fifteen women were infected during pregnancy; they were significantly more exposed to animals and gave birth to only 5 babies, only 2 with a normal birth weight. More rare manifestations observed were chronic hepatitis (8 cases), osteoarticular infection (7 cases), and chronic pericarditis (3 cases). Nineteen patients were observed who experienced first a documented acute infection, then, due to underlying conditions, a chronic infection. To our knowledge, we report the largest series of Q fever to date. Our results indicate that Q fever is a protean disease, grossly underestimated, with some of the clinical manifestations being only recently reported, such as Q fever during pregnancy, chronic vascular infection, osteomyelitis, pericarditis, and myocarditis. Our data confirm that chronic Q fever is mainly determined by host factors and demonstrate for the first time that host factors may also play a role in the clinical expression of acute Q fever.


Aroma formation by immobilized yeast cells in fermentation processes.
Immobilized cell technology has shown a significant promotional effect on the fermentation of alcoholic beverages such as beer, wine and cider. However, genetic, morphological and physiological alterations occurring in immobilized yeast cells impact on aroma formation during fermentation processes. The focus of this review is exploitation of existing knowledge on the biochemistry and the biological role of flavour production in yeast for the biotechnological production of aroma compounds of industrial importance, by means of immobilized yeast. Various types of carrier materials and immobilization methods proposed for application in beer, wine, fruit wine, cider and mead production are presented. Engineering aspects with special emphasis on immobilized cell bioreactor design, operation and scale-up potential are also discussed. Ultimately, examples of products with improved quality properties within the alcoholic beverages are addressed, together with identification and description of the future perspectives and scope for cell immobilization in fermentation processes.


A structure for adaptive order statistics filtering.
In applications such as smoothing and enhancement of images, adaptive filtering techniques offer the flexibility needed for good performance with non-stationary observations. Many adaptive schemes can be based on the idea of determining the local statistics of the signal through appropriate tests on the data, to aid in the selection of a filtering procedure that is suited to the data. In the paper, the authors consider decision-directed or data-dependent adaptive filtering schemes that are based on order statistics. A general formulation for such a class of adaptive order statistics filters is presented. Approximate statistical performance analysis, especially in the presence of edges, may be carried out for this entire class of filters. The authors give examples of some existing filters that fit into this framework. The formulation also accommodates filters that employ multiple windows in their operation. To illustrate the potential of this class of multiple window (MW) filters, they construct and analyze simple filters, like the triple window median (TW-MED) and the triple window median of means (TW-MOM) filters, that are shown to yield useful performance. The class of mean-median hybrid (MMH) filters is also presented as a simple example which may be extended to give interesting performance.


What factors are associated with health-related quality of life among patients with chronic musculoskeletal pain? A cross-sectional study in primary health care.
Chronic musculoskeletal pain (CMP) affects daily life function and is the most prevalent disorder in primary health care. The primary objective was to examine demographic factors and pain characteristics associated with reduced health-related quality of life (HRQoL) among patients in primary care reporting CMP. Our secondary objective was to compare HRQoL in patients with and without CMP. This cross-sectional study was conducted in Trondheim, Norway. Twenty randomly selected GPs, and their listed patients aged 21-58 were invited to participate. Self-reported CMP data was collected using online questionnaires. HRQoL was measured by the 15D questionnaire, total score of 0.9 was used as cut-off for clinical reduced HRQoL. A total of 969 patients (650 females) were recruited from six GPs' patient lists, mean age 45.6 (SD 10.1). CMP was reported by 517 (53%). Factors significantly associated with reduced HRQoL were gender (OR 2.0, 95% CI 1.2, 3.4), disability pension (OR 26.6, 95% CI 3.1, 228.0), mood (OR 1.3, 95% CI 1.1, 1.6), relations with other people (OR 0.8, 95% CI 0.6, 0.9), sleep (OR 1.2, 95% CI 1.0, 1.3) and enjoyment (OR 1.2, 95% CI 1.0). CMP patients had significantly lower total HRQoL score compared to patients without CMP (Between group difference 0.08, 95% CI 0.07-0.09). Half of the CMP patients reported a HRQoL score < 0.9 compared to 14% in the no CMP group. Being female, receiving disability pension, and several psychosocial factors were found highly associated with reduced HRQoL in CMP patients, whereas pain characteristics were not. Patients with CMP reported statistically and clinically significant lower HRQoL than patients without CMP. Due to low response rate the conclusions must be handled with caution. Clinicaltrials.gov (NCT02020772).


Ultrasensitive femtosecond two-photon detector with resonantly enhanced nonlinear absorption.
We report on two-photon detection based on nonlinear absorption between subbands in quantum wells. Resonantly enhanced nonlinear absorption, 6 orders of magnitude higher than that of typical bulk semiconductors, leads to a threshold power density for quadratic detection as low as 0.1 W/cm2 and to femtosecond time resolution. The approach facilitates dynamic characterization of the optical light field of infrared emitters with unprecedented sensitivity. We also present a new method for determining the intersubband and intrasubband scattering times by means of autocorrelation measurements.


Varicella-zoster virus glycoprotein I is essential for spread in dorsal root ganglia and facilitates axonal localization of structural virion components in neuronal cultures.
Neurons of the sensory ganglia are the major site of varicella-zoster virus (VZV) latency and may undergo productive infection during reactivation. Although the VZV glycoprotein E/glycoprotein I (gE/gI) complex is known to be critical for neurovirulence, few studies have assessed the roles of these proteins during infection of dorsal root ganglia (DRG) due to the high human specificity of the virus. Here, we show that the VZV glycoprotein I gene is an important neurotropic gene responsible for mediating the spread of virus in neuronal cultures and explanted DRG. Inoculation of differentiated SH-SY5Y neuronal cell cultures with a VZV gI gene deletion strain (VZV rOkaΔgI) showed a large reduction in the percentage of cells infected and significantly smaller plaque sizes in a comparison with cultures infected with the parental strain (VZV rOka). In contrast, VZV rOkaΔgI was not significantly attenuated in fibroblast cultures, demonstrating a cell type-specific role for VZV gI. Analysis of rOkaΔgI protein localization by immunofluorescent staining revealed aberrant localization of viral glycoprotein and capsid proteins, with little or no staining present in the axons of differentiated SH-SY5Y cells infected with rOkaΔgI, yet axonal vesicle trafficking was not impaired. Further studies utilizing explanted human DRG indicated that VZV gI is required for the spread of virus within DRG. These data demonstrate a role for VZV gI in the cell-to-cell spread of virus during productive replication in neuronal cells and a role in facilitating the access of virion components to axons.


[Gardnerella vaginalis in reports of cervico-vaginal cytology].
Gardnerella vaginalis is a microorganism of great importance because of its participation in some gynecological diseases. Data contained in 3421 cervicovaginal cytology reports obtained from the Profamilia Clinic, Cartagena, Colombia between June 1993 and February 1994 were analyzed retrospectively and analytically. Cells suggestive of Gardnerella vaginalis were found in 723 reports, the greatest proportion being in the 25-29, 30-34, 35-39 year-old age groups (without statistical significance). There is a high frequency of Gardnerella vaginalis as related to healthy cervix and flux. Among the population with Gardnerella vaginalis a low percentage of neoplasia and non-classified atypical cell were found inflammatory reaction was reported in more than half of the cases. In 95% of the reports, Gardnerella vaginalis was the only agent found, the remaining 5% had associated HVP, fungus and trichomonas. Because of the medical staff responsible for taking the samples, cervico-vaginal cytology is an effective method for studying the state of the vagina and cervix.


Outcomes of removal of peritoneal dialysis catheter at the time of renal transplant.
There is no consensus regarding timing of peritoneal dialysis (PD) catheter removal following kidney transplant. We hypothesize that early removal of PD catheter reduces the risk of peritonitis. We conducted a prospective closed-loop audit to review existing practice in our department and determine whether a better strategy could be implemented. Simple descriptive and inferential statistics were used to generate results. Categorical data were described using frequency and percentage. Continuous values were reported as mean ± standard deviation. Between November 2016 and April 2017, forty patients had renal transplant with PD in situ. On average time to removal of PD catheter, posttransplant was 84 days. Four patients (10%) developed exit-site infection. Following departmental consultation, practice was changed to remove all PD catheters at the time of transplant. Between May 2017 and January 2018, twenty patients had renal transplant and 19 had PD catheter removed at the time of transplant. Of these, one required re-insertion. In the patient where PD catheter was left in situ, peritonitis was a complication. We continue to recommend PD catheter removal at the time of transplant.


beta-Lactamase inhibitory activity of iodopenicillanate and bromopenicillanate.
Iodopenicillanate and bromopenicillanate were shown to be effective inhibitors of a variety of beta-lactamases. Staphylococcus aureus isolates were synergistically inhibited by iodopenicillanate and bromopenicillanate combined with ampicillin. Methicillin-resistant S. aureus was not synergistically inhibited. Escherichia coli which possessed TEM beta-lactamase activity had a reduction in ampicillin minimal inhibitory concentration, but an E. coli isolate which had chromosomal beta-lactamase and a low ampicillin minimal inhibitory concentration showed no reduction in ampicillin minimal inhibitory concentration with either iodopenicillanate or bromopenicillanate. Of the Klebsiella isolates tested, 80% were synergistically inhibited by both iodopenicillanate and bromopenicillanate. Most Morganella isolates were synergistically inhibited by either iodopenicillanate or bromopenicillanate combined with ampicillin, as were many Salmonella, Shigella, Citrobacter diversus, and Citrobacter freundii isolates. No Pseudomonas aeruginosa isolates were synergistically inhibited by iodopenicillanate or bromopenicillanate. Preincubation did not improve the inhibitory activity of iodopenicillanate or bromopenicillanate.


Gastrointestinal symptomatic outcomes of laparoscopic and open gastrectomy.
To compare the laparoscopic and the open gastrectomy approaches for short term morbidity, length of hospital stay and also long term gastrointestinal symptoms. Patients who have undergone gastrectomy had their medical records reviewed for demographic data, type of gastrectomy, short term morbidity, and length of hospital stay. Patients were contacted and asked to complete the Gastrointestinal Symptom Rating Scale (GSRS). The GSRS measures three domains of GI symptoms: Dyspepsia Syndrome (DS) for the foregut (best score 0, worse score 15), indigestion syndrome (IS) for the midgut (best score 0, worse score 12), and bowel dysfunction syndrome (BDS) for the hindgut (best score 0, worse score 16). Statistical analysis was done using the Mann-Whitney U-test. We had complete data on 32 patients: 7 laparoscopic and 25 open. Of these, 25 had a gastroenteric anastomosis and 6 did not. The table shows the results as medians with interquartile range. Laparoscopic gastrectomy had a better score than open gastrectomy in the DS domain (0 vs 1, P = 0.02), while gastrectomy without anastomosis had a better score than gastrectomy with anastomosis in the IS domain (0 vs 1, P = 0.05). Patients have little adverse gastrointestinal symptoms and preserve good gastrointestinal function after undergoing any type of gastrectomy. Laparoscopic approach had better dyspepsia and foregut symptoms. Performing an anastomosis led to mild adverse midgut and indigestion effects.


Investigation and Application of Bacillus licheniformis Volatile Compounds for the Biological Control of Toxigenic Aspergillus and Penicillium spp.
The present study was designed to investigate the antagonistic activity of Bacillus licheniformis BL350-2 against mycotoxigenic strains of Aspergillus and Penicillium. In vitro coincubation for 5 days indicated Aspergillus westerdijkiae BA1 as the most sensitive strain, with a growth inhibition of 62%, followed by A. carbonarius MG7 (60%), Penicillium verrucosum MC12 (53%), A. niger MC05 (50%), A. flavus CM5 (49%), A. parasiticus SB01 (47%), and A. ochraceus MD1 (44%). Likewise, the majority of the tested strains on exposure to bacterial volatiles showed complete inhibition of mycotoxin synthesis. In vivo assays on maize ears resulted in 88% reduction in A. flavus CM5 growth and complete inhibition of fungal sporulation and aflatoxin accumulation. The GC-MS-based volatile profile showed 3-methyl-1-butanol as the most abundant compound. The findings of the present study advocate that B. licheniformis BL350-2 is suitable as a biocontrol agent against mycotoxigenic fungi, at least during storage of cereal grains.


Hippocampal activity during recognition memory co-varies with the accuracy and confidence of source memory judgments.
It has been proposed that the hippocampus selectively supports retrieval of contextual associations, but an alternative view holds that the hippocampus supports strong memories regardless of whether they contain contextual information. We employed a memory test that combined the 'Remember/Know' and source memory procedures, which allowed test items to be segregated both by memory strength (recognition accuracy) and, separately, by the quality of the contextual information that could be retrieved (indexed by the accuracy/confidence of a source memory judgment). As measured by fMRI, retrieval-related hippocampal activity tracked the quality of retrieved contextual information and not memory strength. These findings are consistent with the proposal that the hippocampus supports contextual recollection rather than recognition memory more generally.


Female age, serum antimüllerian hormone level, and number of oocytes affect the rate and number of euploid blastocysts in in vitro fertilization/intracytoplasmic sperm injection cycles.
To study the relative role of female age and ovarian reserve, measured through serum antimüllerian hormone (AMH) in determining the rate and number of euploid blastocysts in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Retrospective analysis of cycles performed in 2014-2015. Tertiary referral IVF center. A total of 578 infertile couples undergoing IVF/ICSI and preimplantation genetic screening (PGS) analysis. All embryos were cultured and biopsied at the blastocyst stage. The method involved whole-genome amplification followed by array comparative genome hybridization. Serum AMH was measured by means of the modified Beckman Coulter AMH Gen II assay. The rate and number of euploid blastocysts and their correlation with ovarian reserve and response to stimulation. The mean (±SD) age of patients was 37.6 ± 4.1 years, and the mean number of blastocysts per patient was 3.1 ± 2. The total number of blastocysts available to the analysis was 1,814, and 36% of them were euploid after PGS. Age and serum AMH were significantly and independently related to the rate of euploid blastocysts available for patients. As an effect of the cohort size, the number of mature oocytes positively affected the total number of euploid blastocysts per patient. A strong positive age-independent relationship between AMH level and the rate of euploid blastocysts was found. This confirms that the measurement of ovarian reserve by means of AMH has high relevance when counseling infertile patients.


Hypergammaglobulinemia is a marker of extraintestinal manifestations in pediatric inflammatory bowel disease.
The significance of hypergammaglobulinemia as a phenotypic feature of inflammatory bowel disease is unknown. Thus, we aimed to analyze the magnitude and significance of hypergammaglobulinemia in newly diagnosed pediatric inflammatory bowel disease patients. The medical records of 296 pediatric onset inflammatory bowel disease patients who were evaluated from 2002 to 2015 were retrospectively reviewed. Patients with recorded immunoglobulin G (IgG) levels were categorized as either normal or high IgG levels at diagnosis. Baseline characteristics included age at onset, sex, severity indices, laboratory data, extraintestinal manifestations, endoscopic findings, and anthropometric measurements. Of 184 subjects [mean age, 13.2±2.8 years; 105 (60%) males] with recorded IgG levels, 129 (70%) had Crohn disease, 46 (25%) had ulcerative colitis, and 9 (5%) had unclassified inflammatory bowel disease. Overall, 46 patients (25%) had hypergammaglobulinemia, including 30 (23%) with Crohn disease, 14 (30%) with ulcerative colitis, and 2 (22%) with unclassified disease. Hypergammaglobulinemia was associated with the female sex (55% vs. 35%; p=0.03) and extraintestinal manifestations (70% vs. 10%; p<0.0001), including arthritis, skin disorders, and primary sclerosing cholangitis but not with arthralgia. It was also associated with corticosteroid induction (68% vs. 45%; p=0.02) and maintenance with an immunomodulator (61% vs. 21%; p=0.0001) after diagnosis. In ulcerative colitis patients, hypergammaglobulinemia was associated with a high pancolitis prevalence (p=0.002). Hypergammaglobulinemia is a marker of extraintestinal manifestations in pediatric inflammatory bowel disease and may assist in distinguishing arthritis from arthralgia.


Further studies of the kinetics of oxygenation of arachidonic acid by soybean lipoxygenase.
A kinetic model for soybean lipoxygenase (EC 126.96.36.199) has been examined by comparing results from extensive experimental data with theoretical data generated from a computer program. Kinetic constants have been established by closely fitting experimental and computer-generated data with both product formation versus time, and the more complex accelerative and decelerative relationships of velocity changes with time. It has been confirmed that activation of lipoxygenase by its hydroperoxide product is necessary for activity, and product removal gives inhibition in a manner quantitatively predicted by the model. The earliest accurate measurement of velocity (at 9 s) is a convenient index of the amount of product-activator present in reaction mixtures, and can be used to assay quantitatively the amount of product-activator. The results confirm that soybean lipoxygenase catalyzes a product-activated, substrate-inhibited oxygenation accompanied by a self-catalyzed destruction of its activity.


Genetic diversity and domestication origin of tea plant Camellia taliensis (Theaceae) as revealed by microsatellite markers.
Tea is one of the most popular beverages in the world. Many species in the Thea section of the Camellia genus can be processed for drinking and have been domesticated. However, few investigations have focused on the genetic consequence of domestication and geographic origin of landraces on tea plants using credible wild and planted populations of a single species. Here, C. taliensis provides us with a unique opportunity to explore these issues. Fourteen nuclear microsatellite loci were employed to determine the genetic diversity and domestication origin of C. taliensis, which were represented by 587 individuals from 25 wild, planted and recently domesticated populations. C. taliensis showed a moderate high level of overall genetic diversity. The greater reduction of genetic diversity and stronger genetic drift were detected in the wild group than in the recently domesticated group, indicating the loss of genetic diversity of wild populations due to overexploitation and habitat fragmentation. Instead of the endangered wild trees, recently domesticated individuals were used to compare with the planted trees for detecting the genetic consequence of domestication. A little and non-significant reduction in genetic diversity was found during domestication. The long life cycle, selection for leaf traits and gene flow between populations will delay the emergence of bottleneck in planted trees. Both phylogenetic and assignment analyses suggested that planted trees may have been domesticated from the adjacent central forest of western Yunnan and dispersed artificially to distant places. This study contributes to the knowledge about levels and distribution of genetic diversity of C. taliensis and provides new insights into genetic consequence of domestication and geographic origin of planted trees of this species. As an endemic tea source plant, wild, planted and recently domesticated C. taliensis trees should all be protected for their unique genetic characteristics, which are valuable for tea breeding.


Strain-dependent cellular immune responses in cattle following Escherichia coli O157:H7 colonization.
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic diarrhea and potentially fatal renal failure in humans. Ruminants are considered to be the primary reservoir for human infection. Vaccines that reduce shedding in cattle are only partially protective, and their underlying protective mechanisms are unknown. Studies investigating the response of cattle to colonization generally focus on humoral immunity, leaving the role of cellular immunity unclear. To inform future vaccine development, we studied the cellular immune responses of cattle during EHEC O157:H7 colonization. Calves were challenged either with a phage type 21/28 (PT21/28) strain possessing the Shiga toxin 2a (Stx2a) and Stx2c genes or with a PT32 strain possessing the Stx2c gene only. T-helper cell-associated transcripts at the terminal rectum were analyzed by reverse transcription-quantitative PCR (RT-qPCR). Induction of gamma interferon (IFN-γ) and T-bet was observed with peak expression of both genes at 7 days in PT32-challenged calves, while upregulation was delayed, peaking at 21 days, in PT21/28-challenged calves. Cells isolated from gastrointestinal lymph nodes demonstrated antigen-specific proliferation and IFN-γ release in response to type III secreted proteins (T3SPs); however, responsiveness was suppressed in cells isolated from PT32-challenged calves. Lymph node cells showed increased expression of the proliferation marker Ki67 in CD4(+) T cells from PT21/28-challenged calves, NK cells from PT32-challenged calves, and CD8(+) and γδ T cells from both PT21/28- and PT32-challenged calves following ex vivo restimulation with T3SPs. This study demonstrates that cattle mount cellular immune responses during colonization with EHEC O157:H7, the temporality of which is strain dependent, with further evidence of strain-specific immunomodulation.


Studying aggression in Drosophila (fruit flies).
Aggression is an innate behavior that evolved in the framework of defending or obtaining resources. This complex social behavior is influenced by genetic, hormonal and environmental factors. In many organisms, aggression is critical to survival but controlling and suppressing aggression in distinct contexts also has become increasingly important. In recent years, invertebrates have become increasingly useful as model systems for investigating the genetic and systems biological basis of complex social behavior. This is in part due to the diverse repertoire of behaviors exhibited by these organisms. In the accompanying video, we outline a method for analyzing aggression in Drosophila whose design encompasses important eco-ethological constraints. Details include steps for: making a fighting chamber; isolating and painting flies; adding flies to the fight chamber; and video taping fights. This approach is currently being used to identify candidate genes important in aggression and in elaborating the neuronal circuitry that underlies the output of aggression and other social behaviors.


Meaning in Life Moderates Relations between Personality and Temperament and Nonsuicidal Self-Injury in Hospitalized Adolescents.
Previous research indicates that sensation seeking, emotion dysregulation, and impulsivity are predictive of non-suicidal self-injury (NSSI). A body of research supports that meaning in life predicts improved mental health and well-being, including fewer suicidal thoughts and attempts, yet no research has examined the moderating effects of meaning in life on the relations between personality and temperament and NSSI. Given the growing incidence rates of NSSI among adolescents and the potential lifelong consequences of NSSI, it is imperative to better understand the factors that reduce the rates at which adolescents in a clinical sample engage in NSSI. The present study investigates if the protective factors of meaning in life moderate the relation between personality and temperament variables and NSSI among 126 adolescents (71% female, Mage = 16.1, SD = 1.1, range 13-18, 80% White) residing in an inpatient psychiatric hospital who endorsed NSSI in the last 12 months. Results from hurdle modeling indicate that two subtypes of meaning in life, presence of meaning in life and search for meaning of life, may serve as robust protective factors against engagement in NSSI among a clinical sample of adolescents. Additionally, results suggest that search for meaning, but not presence of meaning in life, variables moderate the relations between personality and temperament and NSSI. Results provide evidence that meaning in life is an understudied variable of importance in understanding how to prevent or treat NSSI. It also underscores the need to develop, refine, and test meaning-making interventions.


Regional variation in brain white matter diffusion index changes following chemoradiotherapy: a prospective study using tract-based spatial statistics.
There is little known about how brain white matter structures differ in their response to radiation, which may have implications for radiation-induced neurocognitive impairment. We used diffusion tensor imaging (DTI) to examine regional variation in white matter changes following chemoradiotherapy. Fourteen patients receiving two or three weeks of whole-brain radiation therapy (RT) ± chemotherapy underwent DTI pre-RT, at end-RT, and one month post-RT. Three diffusion indices were measured: fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). We determined significant individual voxel changes of diffusion indices using tract-based spatial statistics, and mean changes of the indices within fourteen white matter structures of interest. Voxels of significant FA decreases and RD increases were seen in all structures (p<0.05), with the largest changes (20-50%) in the fornix, cingula, and corpus callosum. There were highly significant between-structure differences in pre-RT to end-RT mean FA changes (p<0.001). The inferior cingula had a mean FA decrease from pre-RT to end-RT significantly greater than 11 of the 13 other structures (p<0.00385). Brain white matter structures varied greatly in their response to chemoradiotherapy as measured by DTI changes. Changes in FA and RD related to white matter demyelination were prominent in the cingula and fornix, structures relevant to radiation-induced neurocognitive impairment. Future research should evaluate DTI as a predictive biomarker of brain chemoradiotherapy adverse effects.


Artifacts and Technical Considerations at Contrast-enhanced US.
Contrast-enhanced US (CEUS), similar to other radiologic modalities, requires specific technical considerations and is subject to image artifacts. These artifacts may affect examination quality, negatively impact diagnostic accuracy, and decrease user comfort when using this emerging technique. Some artifacts are related to commonly known gray-scale US artifacts that can also appear on the contrast-only image (tissue-subtracted image obtained with the linear responses from background tissues nulled). These may include acoustic shadowing and enhancement; reverberation, refraction, and reflection; and poor penetration. Other artifacts are exclusive to CEUS owing to the techniques used for contrast mode image generation and the unique properties of the microbubbles that constitute ultrasound-specific contrast agents (UCAs). UCA-related artifacts may appear on the contrast-only image, the gray-scale image, or various Doppler mode images. Artifacts related to CEUS may include nonlinear artifacts and unintentional microbubble destruction resulting in pseudowashout. The microbubbles themselves may result in specific artifacts such as pseudoenhancement, signal saturation, and attenuation and shadowing and can confound the use of color and spectral Doppler US. Identifying and understanding these artifacts and knowing how to mitigate them may improve the quality of the imaging study, increase user confidence, and improve patient care. The authors review the principles of UCAs and the sound-microbubble interaction, as well as the technical aspects of image generation. Technical considerations, including patient positioning, depth, acoustic window, and contrast agent dose, also are discussed. Specific artifacts are described, with tips on how to identify and, if necessary, apply corrective measures, with the goal of improving examination quality. © RSNA, 2022 Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.


Biomechanical effects of harvesting bone graft with the Reamer/Irrigator/Aspirator on the adult femur: a cadaver study.
Test the biomechanical properties of femurs that have undergone reaming with the Reamer Irrigator Aspirator (RIA) device with an aim to prove no difference in torsional strength between matched pairs. Intact femurs were harvested from embalmed cadavers, representing 19 matched pairs. One femur from each pair was randomly selected to undergo reaming using the RIA to 15 mm. The bones were then cut and potted using a uniform jig for testing. Each specimen was tested in torsion and torsional stiffness was calculated for each pair. Samples were loaded until fracture or 11 3 N·m of torque. Nine of the reamed specimens and 13 of the unreamed samples remained intact until the machine limit of 113 N·m was reached, representing approximately four times the peak torque of 30N·m seen with stair climbing [Garino J, Beredjiklian P. Core Knowledge in Orthopaedics: Adult Reconstruction and Arthroplasty. Chapter 1, page 33. Mosby, 2007]. Mean torsional stiffness for the reamed group was 532.1 N·m/rad (SD = 208.2), and the unreamed was 546.2 N·m/rad (SD=206). Torsional load capacity was calculated for all specimens and compared in groups in which both reamed and unreamed specimens failed. In these five groups, mean load capacity was 80.6 Nm (SD = 9.5) for the reamed group, and 85 Nm (SD = 16.1) for the unreamed group. 17 of our reamed specimens and all of our unreamed specimens withstood normal physiologic load seen with stair climbing. In addition, 16 of 19 reamed specimens remained intact at twice this load. The specimen in the reamed group with the lowest torsional load capacity was eccentrically reamed in the distal anterior cortex highlighting potential complications. Given these findings, reaming the cortex of the femur with the RIA device for the purpose of harvesting bone graft does not appear to dramatically diminish the mechanical properties of the cortex or require postoperative weight bearing restrictions. However, careful attention must be paid to technique as eccentric reaming either proximally or distally may result in catastrophic failure. Careful attention must be paid to the use of irrigating fluid and post operative blood loss, and a thorough discussion of risk factors including postoperative fracture should be covered when obtaining informed consent.


A new compound, jolynamine, from marine brown alga Jolyna laminarioides.
A new compound, jolynamine (1), was isolated from the marine brown alga Jolyna laminarioides collected from the coast of Karachi, Pakistan. In addition, four known compounds, namely saringosterol (2), loliolide (3), methyl-4-hydroxybenzoate (4) and propyl-4-hydroxybenzoate (5), were isolated for the first time from the marine brown alga Iyengaria stellata, and two known compounds, namely 3,4,5-trimethylaniline (6) and harmine (7), were isolated for the first time from the marine brown alga Melanothamnus afaqhusainii. Compound 6 is synthetically known but was isolated for the first time from a natural source. The structures of these compounds were elucidated with the help of powerful spectroscopic techniques. Furthermore, the methanolic extracts of both algae showed anti-microbial activities against various bacteria and fungi.


Restriction of the hours of sale of alcohol in a small community: a beneficial impact.
The population of Halls Creek, a small town in the remote Kimberley region of Western Australia, is predominantly Aboriginal. After many years of high alcohol consumption, a number of measures were taken in an effort to redress its negative influence on the community. Key among these was a restriction on the trading hours when 'take-away' alcohol was available. The effects of this intervention were monitored by examining longitudinal patterns of alcohol consumption, incidence of crime and outpatient data at the local hospital. The data were compared with equivalent periods prior to the restricted trading hours. A decrease in alcohol consumption was observed for each of the two years following the intervention. Overall, incidence of crime declined. Alcohol-related presentations to the hospital and presentations resulting from domestic violence decreased relative to the equivalent quarterly period prior to the intervention. There were short-term fluctuations observed, particularly with domestic violence, where presentations (of lesser severity) became more frequent during several quarters. Emergency evacuations as a result of injury showed a marked decrease. The consistency of trends across a variety of health and social data show a positive effect after the implementation of restricted trading hours. While a direct effect is likely, a multitude of concurrent programs which promote health in the community place limitations on this conclusion. The process in achieving change, supported by statutory measures, has, however, been successful in curbing the morbidity and mortality experienced by the community.


Inorganic Polysulfide Chemistries for Better Energy Storage Systems.
ConspectusSulfur-based cathode materials have become a research hot spot as one of the most promising candidates for next-generation, high-energy lithium batteries. However, the insulating nature of elemental sulfur or organosulfides has become the biggest challenge that leads to dramatic degradation and hinders their practical application. The disadvantage is more obvious for all-solid-state battery systems, which require both high electronic and ionic migration at the same sites to realize a complete electrochemical reaction. In addition to adding conductive components into the cathode composites, another effective way to realize high-reversibility sulfur-based cathodes is by optimizing the inherent nature of sulfur-based materials to make them "conductive". Inorganic polysulfide materials including polysulfide molecules, selenium-sulfur solid solutions, and (lithium) metal polysulfides are promising, as they have different structures that can make them intrinsically conductive or becoming conductive during lithiation. They all contain at least one -S-S- bridged bond, which is the intrinsic structural characteristic and the source of the chemical properties of these polysulfide compounds. For example, by balancing the conductivity and reversible capacity, researchers in the US National Aeronautics and Space Administration (NASA) have shown that 500 Wh/kg solid-state Li-Se/S batteries can power cars and even electric aircraft.We have long been focusing on the inorganic polysulfide component, reported the selenium-sulfur solid solutions, the first sulfur-rich phosphorus polysulfide molecules, and followed the research of metal polysulfide components. The proposed Account summarizes our current knowledge of the fundamental aspects of inorganic polysulfides in energy storage systems based on state-of-the-art publications on this topic. Both fast electron and ion migrations within the electrode materials are vital to achieving high-energy batteries. We begin by illustrating effective approaches to enhance the electronic/ionic conductivity of sulfur-based electrode materials. We then present some basic observations and properties (especially the intrinsic high conductivities) of the inorganic polysulfide electrode materials. The key chemical and structural factors dictating their conductive and electrochemical behaviors will be discussed. Finally, we show the advantages and broad applications of inorganic polysulfides in energy storage areas. The proposed Account will provide an insightful perspective on the current knowledge of inorganic polysulfide materials, as well as their future research directions and development potential, serving as a keynote reference for researchers in the field of energy storage.


Predicting the Local Response of Metastatic Brain Tumor to Gamma Knife Radiosurgery by Radiomics With a Machine Learning Method.
The current study proposed a model to predict the response of brain metastases (BMs) treated by Gamma knife radiosurgery (GKRS) using a machine learning (ML) method with radiomics features. The model can be used as a decision tool by clinicians for the most desirable treatment outcome. Using MR image data taken by a FLASH (3D fast, low-angle shot) scanning protocol with gadolinium (Gd) contrast-enhanced T1-weighting, the local response (LR) of 157 metastatic brain tumors was categorized into two groups (Group I: responder and Group II: non-responder). We performed a radiomics analysis of those tumors, resulting in more than 700 features. To build a machine learning model, first, we used the least absolute shrinkage and selection operator (LASSO) regression to reduce the number of radiomics features to the minimum number of features useful for the prediction. Then, a prediction model was constructed by using a neural network (NN) classifier with 10 hidden layers and rectified linear unit activation. The training model was evaluated with five-fold cross-validation. For the final evaluation, the NN model was applied to a set of data not used for model creation. The accuracy and sensitivity and the area under the receiver operating characteristic curve (AUC) of the prediction model of LR were analyzed. The performance of the ML model was compared with a visual evaluation method, for which the LR of tumors was predicted by examining the image enhancement pattern of the tumor on MR images. By the LASSO analysis of the training data, we found seven radiomics features useful for the classification. The accuracy and sensitivity of the visual evaluation method were 44 and 54%. On the other hand, the accuracy and sensitivity of the proposed NN model were 78 and 87%, and the AUC was 0.87. The proposed NN model using the radiomics features can help physicians to gain a more realistic expectation of the treatment outcome than the traditional method.


Recanalisation therapies for wake-up stroke.
About one in five strokes occur during sleep (wake-up stroke). People with wake-up strokes have traditionally been considered ineligible for thrombolytic treatment because the time of stroke onset is unknown. However, some studies suggest that these people may benefit from recanalisation therapies. To assess the effects of intravenous thrombolysis and other recanalisation therapies versus control in people with acute ischaemic stroke presenting on awakening. We searched the Cochrane Stroke Group Trials Register (last search: 9 January 2018). In addition, we searched the following electronic databases in December 2017: Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11) in the Cochrane Library, MEDLINE, Embase, US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the ISRCTN registry, and Stroke Trials Registry. We also screened references lists of relevant trials, contacted trialists, undertook forward tracking of relevant references, and contacted manufacturers of relevant devices and equipment. Randomised controlled trials of intravenous thrombolytic drugs or intra-arterial therapies in people with acute ischaemic stroke presenting upon awakening. Two review authors applied the inclusion criteria, extracted data, and assessed trial quality and risk of bias using the GRADE approach. We obtained both published and unpublished data. We included one pilot trial with nine participants. The trial was a feasibility trial that included participants with an unknown onset of stroke and signs on perfusion computed tomography of ischaemic tissue at risk of infarction, who were randomised to alteplase (0.9 mg/kg) or placebo. One trial was prematurely terminated due to signs of efficacy of the intervention arm; we did not include this trial because we were not able to obtain data for the portion of the participants with wake-up stroke after requesting this information from the trial authors. We identified six ongoing trials. There is insufficient evidence from randomised controlled trials for recommendations concerning recanalisation therapies for wake-up stroke. Results from ongoing trials will hopefully establish the efficacy and safety of such therapies.


Metabolic and additional vascular effects of thiazolidinediones.
Several cardiovascular risk factors (dyslipidaemia, hypertension, glucose intolerance, hypercoagulability, obesity, hyperinsulinaemia and low-grade inflammation) cluster in the insulin resistance syndrome. Treatment of these individual risk factors reduces cardiovascular complications. However, targeting the underlying pathophysiological mechanisms of the insulin resistance syndrome is a more rational treatment strategy to further improve cardiovascular outcome. Our understanding of the so-called cardiovascular dysmetabolic syndrome has been improved by the discovery of nuclear peroxisome proliferator-activated receptors (PPARs). PPARs are ligand-activated transcription factors belonging to the nuclear receptor superfamily. As transcription factors, PPARs regulate the expression of numerous genes and affect glycaemic control, lipid metabolism, vascular tone and inflammation. Activation of the subtype PPAR-gamma improves insulin sensitivity. Expression of PPAR-gamma is present in several cell types involved in the process of atherosclerosis. Thus, modulation of PPAR-gamma activity is an interesting therapeutic approach to reduce cardiovascular events. Thiazolidinediones are PPAR-gamma agonists and constitute a new class of pharmacological agents for the treatment of type 2 (non-insulin-dependent) diabetes mellitus. Two such compounds are currently available for clinical use: rosiglitazone and pioglitazone. Thiazolidinediones improve insulin sensitivity and glycaemic control in patients with type 2 diabetes. In addition, improvement in endothelial function, a decrease in inflammatory conditions, a decrease in plasma levels of free fatty acids and lower blood pressure have been observed, which may have important beneficial effects on the vasculature. Several questions remain to be answered about PPAR-gamma agonists, particularly with respect to the role of PPAR-gamma in vascular pathophysiology. More needs to be known about the adverse effects of thiazolidinediones, such as hepatotoxicity, increased low-density lipoprotein cholesterol levels and increased oedema. The paradox of adipocyte differentiation with weight gain concurring with the insulin-sensitising effect of thiazolidinediones is not completely understood. The decrease in blood pressure induced by thiazolidinedione treatment seems incompatible with an increase in the plasma volume, and the discrepancy between the stimulation of the expression of CD36 and the antiatherogenic effects of the thiazolidinediones also needs further explanation. Long-term clinical trials of thiazolidinediones with cardiovascular endpoints are currently in progress. In conclusion, studying the effects of thiazolidinediones may shed more light on the mechanisms involved in the insulin resistance syndrome. Furthermore, thiazolidinediones could have specific, direct effects on processes involved in the development of vascular abnormalities.


Integration of in vitro data from three dimensionally cultured HepaRG cells and physiologically based pharmacokinetic modeling for assessment of acetaminophen hepatotoxicity.
Selection of appropriate fit-for-purpose in vitro and in silico models is critical for non-animal safety assessment of chemical-induced hepatoxicity. The present study evaluated the feasibility of integrating in vitro data from three-dimensionally (3D)-cultured HepaRG cells and physiologically based pharmacokinetic (PBPK) modeling to predict chemical-induced liver toxicity. A 3D organoid culture system was established using an ultralow attachment method. HepaRG cells cultured in a two-dimensional (2D) monolayer and under 3D conditions were exposed to acetaminophen (APAP) at concentrations of 0.16-20 mM. The results showed that the viability of both 3D- and 2D cultured cells was significantly decreased by APAP in a concentration-dependent manner. Furthermore, 3D cultures were more sensitive to APAP-induced mitochondrial damage than 2D cultures were, based on measurements of mitochondrial superoxide accumulation and mitochondrial membrane potential loss. PBPK simulations using nominal in vitro concentrations showed that the APAP concentration eliciting mitochondrial damage was closer to the predicted peak liver concentration in humans in 3D cultures than it was in 2D cultures. In summary, our results suggest that combining in vitro data from 3D HepaRG cultures and PBPK modeling provides a promising tool for assessment of liver injury.


Poly(β-amino ester) nanoparticle delivery of TP53 has activity against small cell lung cancer in vitro and in vivo.
Small cell lung cancer (SCLC) is an aggressive disease with one of the highest case-fatality rates among cancer. The recommended therapy for SCLCs has not changed significantly over the past 30 years; new therapeutic approaches are a critical need. TP53 is mutated in the majority of SCLC cases and its loss is required in transgenic mouse models of the disease. We synthesized an array of biodegradable poly(β-amino ester) (PBAE) polymers that self-assemble with DNA and assayed for transfection efficiency in the p53-mutant H446 SCLC cell line using high-throughput methodologies. Two of the top candidates were selected for further characterization and TP53 delivery in vitro and in vivo. Nanoparticle delivery of TP53 resulted in expression of exogenous p53, induction of p21, induction of apoptosis, and accumulation of cells in sub-G1 consistent with functional p53 activity. Intratumoral injection of subcutaneous H446 xenografts with polymers carrying TP53 caused marked tumor growth inhibition. This is the first demonstration of TP53 gene therapy in SCLC using nonviral polymeric nanoparticles. This technology may have general applicability as a novel anticancer strategy based on restoration of tumor suppressor gene function.


[Yield of soybean genotypes under infestation of the velvetbean caterpillar and stink bugs].
Three soybean experiments, one for each maturation group (early, semi-early, and medium), were installed in the field in Assis, State of São Paulo, during the 2003/2004 growing season to evaluate damage caused by Anticarsia gemmatalis (Hubn.) and by the soybean stink bug complex, Euschistus heros (F.), Piezodorus guildinii (West.), and Nezara viridula (L.). The experiments were installed again in 2004/2005, with the exception of the early cycle group. Defoliation caused by A. gemmatalis was evaluated by the percentage estimate of leaf area cut in the first year only, due to low caterpillar infestations in 2004/2005. All three stink bug species were present in both growing seasons. In 2003/2004, E. heros was predominant over the other two; in the following year, all three species occurred in similar numbers. The productivity criterion was adopted to evaluate stink bug damage. Based on both growing seasons and mainly considering productivity, a few lines could be selected within each maturation group for new field studies or for hybridizations in breeding programs. Among the early germplasm varieties, lines IAC 98-4540, IAC 98-4576, and IAC 98-3123 can be highlighted as promising; the latter also showed little defoliation by A. gemmatalis; in the semi-early group, IAC 98-4017, IAC 98-2663, and IAC 98-4250 were prominent, with steady productivity in both years; in the medium group, IAC 98-4136, the most productive, as well as IAC 98-4140 and IAC 98-4133, all with little defoliation, can be pointed out as promising.


Identification of FOXP1 and SNX2 as novel ABL1 fusion partners in acute lymphoblastic leukaemia.
We have identified two novel ABL1 fusion genes in two patients with B-cell acute lymphoblastic leukaemia (ALL) associated with a t(3;9)(p12;q34) and a t(5;9)(q23;q34), respectively. Molecular analysis revealed a FOXP1-ABL1 fusion for the t(3;9) and a SNX2-ABL1 fusion for the t(5;9). The fusions were confirmed by specific amplification of the genomic breakpoints using reverse transcription polymerase chain reaction. The identification of ALL with rare ABL1 fusion partners is important because the leukaemia may respond to tyrosine kinase inhibitors in the same way as ALL patients with a classical BCR-ABL1 fusion gene.


Insulin-loaded hydroxyapatite combined with macrophage activity to deliver insulin for diabetes mellitus.
We aimed to develop a diabetes mellitus (DM) treatment that could be administered by intramuscular (IM) injection and it lasted for more than 3 days. The objective was to load insulin into the lattice space of hydroxyapatite (HAP) to prevent its release based on a concentration gradient or detachment from the surface, with insulin release being aided by cellular activity. To avoid insulin denaturation during the synthesis of insulin-loaded HAP (insHAP), we developed a single-step insHAP synthesis method by the hydrolysis of brushite. X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) results suggested that insulin could be loaded into the HAP crystal lattice. After IM administration in rats with DM, the synthesized insHAP is thought to be engulfed by macrophages, escape from lysosome/endosome hybrids following disruption by osmotic pressure, and pumped into the extracellular space before entering the blood stream by diffusion. In rats with DM, the normal blood glucose level was maintained for 4 days after a single IM injection of the synthesized insHAP particles. Thus, insHAP may provide a breakthrough in insulin delivery for DM treatment, and may also be used to deliver fluorescent proteins, antibodies, and anticancer drugs.


Dynamic patterns of histone methylation are associated with ontogenic expression of the Cyp3a genes during mouse liver maturation.
Human cytochrome P450 3A (CYP3A) members are major drug-metabolizing enzymes in the liver. Two genes, CYP3A4 and CYP3A7, exhibit a developmental switch in gene expression during liver maturation. CYP3A4 is mainly expressed in adults, whereas CYP3A7 is dominantly expressed during the fetal and neonatal stages. Their ontogenic expression results in developmentally related changes in the capacity to metabolize endogenous and exogenous compounds. Thus, it is desirable to understand the mechanisms controlling the developmental switch. Mice also exhibit a developmental switch between Cyp3a16 (neonatal isoform) and Cyp3a11 (adult isoform) and may serve as a model to study the mechanisms controlling the developmental switch. Because the epigenetic code (e.g., DNA methylation and histone modifications) is implicated in regulating gene expression and cellular differentiation during development, the current study determined the status of DNA methylation, histone-3-lysine-4 dimethylation (H3K4me2) and histone-3-lysine-27 trimethylation (H3K27me3) around the mouse Cyp3a locus at various developmental ages from prenatal, through neonatal, to young adult. DNA was not hypermethylated in the Cyp3a locus at any age. However, increases in Cyp3a16 expression in neonatal livers and Cyp3a11 in adult livers were associated with increases of H3K4me2. Suppression of Cyp3a16 expression in adult livers coincided with decreases of H3K4me2 and increases of H3K27me3 around Cyp3a16. In conclusion, histone modifications of H3K4me2 and H3K27me3 are dynamically changed in a locus-specific manner along the Cyp3a locus. Developmental switch between Cyp3a11 and Cyp3a16 gene expression seems to be due to dynamic changes of histone modifications during postnatal liver maturation.


Hypercholesterolemia and hypertriglyceridemia as biochemical markers of disease in companion rabbits.
Inflammation has important effects on lipid metabolism, but the relationship between hyperlipidemia, inflammation, and disease remains unknown in rabbits. While rabbits are sensitive to dietary hypercholesterolemia, the etiology of hyperlipidemia when fed non-atherogenic diets is uncertain. This study aimed to determine the association between hypercholesterolemia and patient characteristics, diseases, and select CBC and biochemistry analytes in rabbits, and to measure plasma lipoprotein lipid fractions in rabbits with inflammatory and other diseases. Complete blood count and plasma biochemistry data, including total cholesterol concentrations, were evaluated in 531 companion rabbits. Lipoprotein cholesterol fractions (non-high-density lipoprotein cholesterol [non-HDLc] and high-density lipoprotein [HDLc]) and triglycerides were measured using a colorimetric enzymatic assay in archived plasma from a subset of 267 rabbits. Rabbits were categorized by age, sex, spay/neuter status, breed, diet status (fed atherogenic dietary components or not), the organ system affected by disease, and the pathologic process. Cholesterol was associated with fibrinogen (P = 0.01), globulins (P < 0.01), and heterophil (P < 0.01) concentrations. Adjusting for diet, rabbits with severe infection or sepsis (odds ratio [OR] = 13.25, 95% CI = 5.83-30.12), renal failure (OR = 14.42, 95% CI = 5.69-36.54), and hepatopathy (OR = 8.55, 95% CI = 3.55-20.62) had increased risks of hypercholesterolemia. Increased non-HDLc and triglyceride concentrations were also associated with these three disease states (P < 0.05). Hyperlipidemia is associated with biochemical and CBC markers of inflammation, and with severe infection or sepsis, renal failure, and hepatopathy. Independent of diet, increased cholesterol, non-HDLc, and triglycerides are indicators of disease in companion rabbits.